THE PREMIER GATHERING for PROTEIN SCIENCE RESEARCHERS - Where Research Is Shared, Knowledge Is Gained, Connections Are Made, and Innovation Shapes the Future

Cover

Sponsors

Event-at-a-Glance

CORPORATE SPONSORS

By Cambridge Healthtech Institute

SHORT COURSES CORPORATE SUPPORT SPONSORS Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 3 FINAL WEEKS TO REGISTER Present Your Research Poster at PepTalk! Cover Cambridge Healthtech Institute encourages Sponsors attendees to gain further exposure by Event-at-a-Glance presenting their work in the poster sessions. Reasons you should present your research poster at this conference: • Your poster will be seen by our international delegation, representing leaders from top pharmaceutical, biotech, academic and government institutions. 2018 STUDENT • Receive $50 off your registration. FELLOWSHIP PROGRAM • Your poster abstract will be published in our Full-time graduate students and Ph.D. candidates are encouraged conference materials. to apply for the PepTalk: The Protein Science Week Student • You will automatically be entered into our Fellowship. Applications are due by October 13, 2017. poster competition. To secure a poster board and inclusion in the conference materials, your abstract must be • Interested students must complete the online application for the submitted, approved and your registration 2018 Student Fellowship. paid in full by November 10, 2017. • Fellows are required to present a scientific poster. A poster title and Register online, or by phone, fax or mail. Please indicate that abstract are due at the time of the application. you would like to present a poster. • All applications will be reviewed by the scientific review committee and the Once your registration has been fully processed, we will send accepted students will be notified if they are accepted. an email with a unique link and instructions for submitting your abstract using our online abstract submission tool. • Accepted Student Fellows will receive a discounted conference registration rate of $295*, which must be paid in full by November 10, 2017. (Payment is requested at the time of the application but will not be charged until the application is approved.) POSTER PAVILION • This fellowship is limited to 20 students and provides access to all conferences (January 8-12, 2018). Excludes Short Courses and Training Seminars. • Accepted Fellows will be asked to help promote the event onsite, at their By Cambridge Healthtech Institute FRIDAY, JANUARY 12, 10:35 AM college, and throughout their social media networks. PepTalk is proud to support and recognize • Students not accepted for the 2018 Student Fellowship can register at a SHORT COURSES the protein scientists of tomorrow during the discounted rate of $595*, and will not be required to present a poster. Poster Pavilion. This time has been set aside • Student Fellows will be entered into the conference’s Poster Competition to view the Student Fellowship posters and featuring cash prizes. All poster presenters are eligible to win. interact with presenters one on one. Sponsorship Opportunities • ADDED BONUS! POSTER PAVILION - In addition to the main poster This opportunity gives job seekers the viewing times, there will be a special FELLOW ONLY POSTER VIEWING Hotel/Additional Information chance to share their expertise with future/ on Friday morning. Registration & Pricing potential employers or develop contacts to * This discounted Fellow rate cannot be combined with any other discounts for this event. Your further their research. discounted registration does not grant access to any of the Short Courses or Training Seminars. It also does not include hotel, travel or meals. CHI-PepTalk.com CHI-PepTalk.com | 4 FINAL TUESDAY, JANUARY 9 WEEKS TO REGISTER DINNER SHORT COURSES*

Cover

Sponsors SC4: An Evening with Envoys of Eclectic Expression Experiences Event-at-a-Glance TUESDAY, JANUARY 9 | 5:45 - 8:45 pm There is no “universal” recombinant protein production system to satiate the —SC1: Introduction to CAR-T Engineering for Protein Scientists ever-expanding, complex needs of protein expression laboratories. Fortunately, This course presents advances in CAR design with an eye toward clinical a variety of mature protein production systems exist that can be combined to development. Topics include 1) screening and selection of active binding create an expression toolbox to address these protein production challenges. This domains, 2) additional design steps needed to confer activity, 3) roles of linker course features panelists with expertise in different expression systems (E. coli, and structural domain in CAR activity, 4) role of tumor-expressed cellular targets Baculovirus, Yeast, Plant, and Mammalian) discussing the applications, advantages, in regulating activity, 5) combining binding domains to create multi-targeting and challenges of their respective systems in an interactive, roundtable environment CARs that may prevent disease escape, and 6) novel structural domains that appropriate for expression scientists of all experience levels. regulate association of binding to signaling domains to confer therapeutic Moderator: Richard Altman, MS, Scientist, Protein Technologies, Amgen control of CAR activity. Panelists: Henry C. Chiou, Ph.D., Associate Director, Cell Biology, Life Science Instructor: Rimas J. Orentas, Ph.D., Scientific Director, Lentigen Technology, Inc. Solutions, Thermo Fisher Scientific Dominic Esposito, Ph.D., Director, Protein Expression Laboratory, Frederick SC2: Selection, Screening and Engineering for Affinity Reagents National Laboratory for Cancer Research Biologics such as recombinant antibodies and alternative binding scaffolds are Feras Hatahet, Ph.D., Scientist, Protein Technologies, Amgen routinely used in various applications. This success has led to the development of numerous selection, screening and engineering technologies for these Roland Weis, Ph.D., Head, Operations, VTU Technology GmbH molecules. This course gives a comprehensive overview on different display Additional Panelist to be Announced technologies and screening approaches for the selection of specific binders, engineering strategies including affinity maturation, and how to implement these SC5: Optimizing Cell Line Development and Engineering strategies. Classical antibodies and antibody fragments and alternative binding Recent achievements driven by the application of novel approaches and tools scaffolds such as DARPins will be covered. have caused significant savings in time and money for cell line selection and development. This course outlines the latest developments in cell and molecular Instructors: Julia Neugebauer, Ph.D., Associate Director, Lead Discovery Programs biology, cell line development technologies, applications of automated tools, R&D, MorphoSys AG “-omics” technologies, CRISPR/Cas9, and engineering strategies to help you Jonas V. Schaefer, Ph.D., Head, High-Throughput Binder Selection Facility, understand and improve the stability, quality, and workability of your cell lines to Biochemistry, University of Zurich optimize upstream processing. SC3: Protein Aggregation: Mechanism, Characterization and Instructor: Osama O. Ibrahim, Ph.D., Consultant, Bio Innovation USA Consequences SC6: Creating a Next-Generation Vaccine Facility Protein aggregation is recognized by regulatory agencies and the This course will focus on a new holistic approach that integrates tested biopharmaceutical industry as a key quality attribute of biotherapeutics. Various strategies for cost-efficient manufacturing of vaccines, linking innovations in cell aggregates hold the potential for adversely impacting production and patients culture strategies, bioreactor design, membrane chromatography and flexible in a variety of ways. This in-depth course reviews the origins and consequences facility design for a 500-fold increase in overall productivity. This next-generation of aggregation in biotherapeutics, and then examines strategies for predicting facility merging high-productivity technologies to achieve simplified process and quantifying aggregation in biopharmaceuticals. It benefits scientists architecture, increased robustness and augmented yield can be replicated engaged in development, production, analytical characterization and approval By Cambridge Healthtech Institute anywhere to make production in developing countries in need of vaccines a of biotherapeutics and who require a good working knowledge of protein reality. aggregation. Instructors: Renaud Jacquemart, Ph.D., Author, BioProcess International Instructors: Thomas Laue, Ph.D., Professor Emeritus, Molecular, Cellular and SHORT COURSES Biomedical Sciences, University of New Hampshire Alfred Luitjens, Director, Cell Technology, Batavia Biosciences Kevin Mattison, Principal Scientist, Bioscience, Malvern PANalytical Benjamin Damien, Business Developer, Univercells James G. Stout, Ph.D., Vice President, Process Sciences, Natrix Separations

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

* Separate registration required. Please visit our website for more details. CHI-PepTalk.com CHI-PepTalk.com | 5 FINAL Please visit CHI-PepTalk.com to view WEEKS detailed agendas for each Training Seminar TO REGISTER

Cover

Sponsors SUNDAY, JANUARY 7 PRE-REGISTRATION 4:00 - 6:00 PM TUESDAY, JANUARY 9 - WEDNESDAY, JANUARY 10 Event-at-a-Glance — MONDAY, JANUARY 8 - TUESDAY, JANUARY 9 —DAY 1 - 2:00 - 5:30 PM | DAY 2 - 8:30 AM - 5:30 PM —DAY 1 - 9:00 AM - 6:00 PM | DAY 2 - 8:30 AM - 12:30 PM TS3B: Next-Generation Approaches to Antibody Screening and TS8A: Introduction to Bioprocessing Discovery CHI’s Introduction to Bioprocessing training seminar offers a comprehensive Over the space of a few years, a series of technologies have improved greatly survey of the steps needed to produce today’s complex biopharmaceuticals, from in both capability and affordability, and have been adapted to enhance the early development through commercial. The seminar steps through the stages of discovery and development of antibodies and other immunotherapies. Among bioprocessing, beginning with cell line development and ending at scaling up for these technologies, DNA sequencing and data analysis, DNA synthesis, single- commercial production. The seminar also explores emerging process technologies, cell isolation, and genome engineering using CRISPR/Cas9 combine to give facility design considerations and the regulatory and quality standards that govern significant advances in how we can engineer antibodies and cell lines. This our industry throughout development. The important roles of analytical methods training seminar will evaluate these new developments and their applications in and formulation development are also examined. The class is directed to attendees antibody and immunotherapy discovery and development. working in any aspect of industry, including scientific, technical, business, marketing Instructor: or support functions, who would benefit from a detailed overview of this field. Instructors: David Bramhill, Ph.D., Founder, Bramhill Biological Frank J. Riske, Ph.D., Sheila G. Magil, Ph.D., Consulting, LLC Senior Consultant, Senior Consultant, BioProcess Technology BioProcess Technology Consultants, Inc. Consultants, Inc. TS9A: Introduction to Antibody Engineering TS10B: Introduction to Biologics Formulation Development In this training seminar, students will learn about antibody basics, including structure, CHI’s Introduction to Biologics Formulation Development training seminar genetics and the generation of diversity, as well as the generation of potential focuses on strategies to plan and execute preformulation and formulation therapeutic antibodies. This latter part will include antibody humanization, affinity and development studies for biologics. The seminar begins with an overview of specificity maturation, display technologies, creation of naïve libraries and antibody biophysical and biochemical properties of proteins and protein structure, setting characterization. The seminar will be fully interactive, with students provided ample the stage for the concepts and goals at the core of protein formulation. The opportunities to discuss technology with instructors. seminar then continues with an exploration into the theory and application of the Instructors: James D. Marks, M.D., Ph.D., relevant analytical and biophysical techniques that support preformulation and Andrew M. Bradbury, Ph.D., Chief of Staff, Chief of formulation development studies. The seminar provides an in-depth discussion MB, CSO, Specifica, Inc. Anesthesia, San Francisco of typical formulation development workflows, including statistical analysis and General Hospital; Professor & use of DoE, and an examination of real-world case studies. Vice Chairman of Anesthesia, Instructor: University of California, San Francisco Donald E. Kerkow, Ph.D., TS10A: Introduction to Cell Culture Associate Director, The seminar will describe the basic requirements for establishing and maintaining Biopharmaceutical Development, By Cambridge Healthtech Institute mammalian cell cultures both in the laboratory and in large-scale operations. The KBI Biopharma, Inc. objective of the seminar is to provide detailed information of the scientific principles behind the use of mammalian cell culture techniques at either a laboratory scale or SHORT COURSES at a large scale for the production of biopharmaceuticals, which include monoclonal antibodies, recombinant proteins, viral vaccines as well as cell-based therapies. Some attention will also be given to the quality of the increasing list of biopharmaceuticals that have been licensed and are in large-scale manufacture. Sponsorship Opportunities Instructor: Michael Butler, Ph.D., CSO, Hotel/Additional Information National Institute of Bioprocessing Research & Registration & Pricing Training (NIBRT), Ireland

CHI-PepTalk.com CHI-PepTalk.com | 6 FINAL Please visit CHI-PepTalk.com to view WEEKS detailed agendas for each Training Seminar TO REGISTER

Cover

Sponsors TUESDAY, JANUARY 9 - WEDNESDAY, JANUARY 10 THURSDAY, JANUARY 11 - FRIDAY, JANUARY 12 Event-at-a-Glance —DAY 1 - 2:00 - 5:30 PM | DAY 2 - 8:30 AM - 5:30 PM —DAY 1 - 8:15 AM - 5:45 PM | DAY 2 - 8:00 AM - 12:45 PM TS11B: Introduction to Biologics Analytical Development TS3C: Introduction to Immunogenicity and Characterization All protein drugs generate an immunogenic response. This 1.5-day training seminar provides This training seminar will review analytical method development and a practical, comprehensive overview of immunogenicity – the causes, how to assess, validation in the context of IND regulatory filing of therapeutic proteins, predict and prevent, and what to do if you observe immunogenicity during preclinical, including monoclonal antibodies and recombinant proteins. The curriculum clinical and post-market approval. The seminar begins by detailing the science behind will provide a broad overview of biologics analytical and characterization immunogenicity, the latest international Guidances, followed by assay and bioanalytical and is beneficial to individuals involved in biologics drug development, assessment strategies for traditional and emerging biologics. Other topics include predictive analytical development, quality control, quality assurance, regulatory affairs, models and how to report immunogenicity incidents both internally and externally. project management, process development, formulation development Instructor: or related functional areas. Attendees will learn the practical aspects of Arno Kromminga, Ph.D., Member, commonly used analytical panel not only for DS/DP release and stability European Immunogenicity Platform, but also for monitoring manufacturing process and facilitating formulation Senior Vice President and European development: product purity and impurity analysis, product strength and CSO, BioAgilytix potency, plus matrix verification of the most common process-related impurities. The characterization panel specifically emphasizes structure TS9C: Basic Technologies in a Protein Production Lab elucidation by mass spectroscopy, posttranslational modification, This seminar introduces basic technologies, strategies and considerations in recombinant biophysical characterization of higher order structure (HOS), and protein protein expression and purification inE. coli, insect and mammalian cells for multiple aggregates. Real-world case studies and common pitfalls will be presented. research and development applications. It supplies a basic toolbox for management Instructor: of multiple and diverse projects. It also addresses common problems when translating Kevin Zen, Ph.D., Senior academic ideas and IP to biotech startup companies, how to avoid those problems, and Director, Analytical how to better facilitate this translation, focusing on protein production processes. Development, CMC Instructors: Biologics, AnaptysBio, Inc. Tsafi Danieli, Ph.D., Director, Mario Lebendiker, Ph.D., Head, BioGiv Excubator & Head, Protein Purification Facility, Protein Expression Facility, Wolfson Centre for Applied Wolfson Centre for Applied Structural Biology, Alexander TRAINING SEMINAR INFORMATION Structural Biology, Alexander Silberman Silberman Institute of Life Sciences, The Each CHI Training Seminar offers 1.5 days of instruction with start Institute of Life Sciences, The Hebrew Hebrew University of Jerusalem and stop times for each day shown above and on the Event-at-a- University of Jerusalem Glance published in the onsite Program & Event Guide. Training Seminars will include morning and afternoon refreshment breaks, as TS10C: Managing Risks Associated with Manufacture, Storage and applicable, and lunch will be provided to all registered attendees on Delivery of Traditional and Novel Biotherapeutics the full day of the class. This training seminar will provide a background on the sensitivities of various modalities By Cambridge Healthtech Institute Each person registered specifically for the training seminar will be such as therapeutic proteins, stem cells and gene therapies in conjunction with the provided with a hard copy handbook for the seminar in which they are materials used in the manufacture, storage and delivery to patients. There are performance registered. A limited number of additional handbooks will be available expectations for systems in contact with biologics and each component should be SHORT COURSES for other delegates who wish to attend the seminar, but after these considered based on the unique characteristics of diverse modalities and intended use. At have been distributed, no additional books will be available. this seminar, you will learn about identification and evaluation of risks related to particulates, Though CHI encourages track hopping between conference container closure integrity, functional performance and leachables/extractables. This programs, we ask that Training Seminars not be disturbed once they knowledge will put the current regulations into perspective and provide a basis for applying Sponsorship Opportunities have begun. In the interest of maintaining the highest quality learning science and risk-based approaches into the biologic development cycle. environment for Training Seminar attendees, and because Seminars Instructors: Hotel/Additional Information are conducted differently than conference programming, we ask that Diane Paskiet, MS, Director of Fran DeGrazio, Vice President, attendees commit to attending the entire program, and not engage in Scientific Affairs, Scientific Global Scientific Affairs and Registration & Pricing track hopping, as to not disturb the hands-on style instruction being Affairs and Technical Services, Technical Services, West offered to the other participants. West Pharmaceutical Services Pharmaceutical Services

CHI-PepTalk.com CHI-PepTalk.com | 7 FINAL WEEKS TO REGISTER

Cover

Sponsors Event-at-a-Glance PROTEIN ENGINEERING & DEVELOPMENT

JANUARY 8-9 AGENDA Recombinant Protein Therapeutics

JANUARY 9-10 AGENDA Enhancing Antibody Binding and Specificity

JANUARY 11-12 AGENDA Emerging Technologies for Antibody Discovery

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 8 FINAL WEEKS JANUARY 8-9 | 14TH ANNUAL PROTEIN ENGINEERING TO REGISTER Recombinant Protein Therapeutics & DEVELOPMENT Fusion Proteins & Beyond Cover

Sponsors Cambridge Healthtech Institute’s Fourteenth Annual Recombinant Protein Therapeutics conference profiles the varying designs of therapeutic fusion proteins in Event-at-a-Glance differing stages of development, and investigates the challenges and benefits associated with these promising therapies. By combining modular building blocks that can reach targets not accessible to antibodies, fusion protein therapeutics possess advantages over antibody-based therapies; their customizable functionality translates into lower patient dosing, reduced production costs, and improved product homogeneity. This conference will disclose how these molecules are being engineered to form more efficacious therapeutics that offer specificity with enhanced stability and longer half-life.

SUNDAY, JANUARY 7 9:50 Making Proteins “Druggable”: Fc Fusion the commonly used (G4S)n linkers recently Proteins as a Therapeutic Class found to carry heterogeneous xylose-containing 4:00 - 6:00 pm Pre-Conference Registration Steven Chamow, Ph.D., Principal Consultant, Chamow O-glycosylation. Using high-resolution mass & Associates, Inc. spectrometry (HR-MS) and MSn, we demonstrated the presence of an unexpected hydroxylation of Immunoglobulin G has substantial in vivo stability MONDAY, JANUARY 8 a prolyl residue (Hyp) in a (G4P) linker. Further due to its binding to the neonatal Fc receptor (FcRn) efforts in determining whether the modification is which is responsible for IgG recycling. By creating an 7:00 am Registration and Morning Coffee 3-hydroxyproline (3-Hyp) or 4-hydroxyproline (4-Hyp) Fc fusion, a protein with a short in vivo half-life can will be discussed. CREATING EFFICACIOUS PROTEIN be transformed into a stable therapeutic product. THERAPEUTICS This technology has been applied broadly and 11:45 Turning Affibody Molecules into there are now 6 FDA approved products from this Efficient Peptide Binders by Dimerization 9:00 Welcome by Conference Organizer therapeutic class. Their structures and properties will be reviewed. John Löfblom, Ph.D., Associate Professor, Protein Mary Ruberry, Senior Conference Director, Cambridge Technology, Biotechnology, KTH Royal Institute of Healthtech Institute 10:20 Networking Coffee Break Technology Affibody molecules are small three-helical affinity 9:05 Chairperson’s Opening Remarks NEXT-GEN ENGINEERING proteins. Generating binders for the amyloid ß peptide Stefan Schmidt, Ph.D., MBA, CSO, Development and yielded variants with 300-pM affinity, and with unique Innovation, Rentschler Biotechnology 10:45 Generating Ion Channel Blocking mode of binding, sequestering the peptide in a tunnel- Antibodies by Fusing Cysteine-Knot like cavity. Similar binders for other peptides have KEYNOTE PRESENTATION Miniproteins into Peripheral CDR Loops been engineered, involving structural rearrangements of both affibody and peptide upon binding, indicating John McCafferty, Ph.D., CEO, Antibody Engineering, 9:10 Fusion Proteins: An Intro to the Field that it is well suited for such molecular recognitions. IONTAS, Ltd. and Selected Case Studies from Roche’s This presentation will include unpublished preclinical Research & Early Development Pipeline Cysteine-knot miniproteins (knottins) have potential data for the Aß binder. as therapeutic agents to block proteases and ion Stefan Weigand, Ph.D., Head, Large Molecule channels involved in cancer, autoimmunity and ® Sponsored by Research, Roche Innovation Center, Roche 12:15 pm Veltis Engineered pain, but suffer from manufacturing difficulties, Albumins and Their Potential for Pharma Research & Early Development (pRED) short half-lives, and a lack of specificity. Using Improved Therapeutic Performance This talk will introduce the concept of fusion X-ray crystallography and biochemical assays, we proteins, provide an overview on which have demonstrated that functional knottins can be Helen Rawsthorne, Ph.D., Senior Research Scientist, By Cambridge Healthtech Institute fusion proteins are on the market, how they inserted into peripheral antibody CDRs via short Molecular Biology and Fermentation, Albumedix compare to classical antibodies in the same linkers. Thus, the resulting “KnotbodyTM” retains The natural properties of albumin have ensured its field, and look at general trends for fusion the advantage of blocking activity from the knottin use for decades in enhancing the pharmacokinetic SHORT COURSES proteins from development pipelines of while enjoying the extended half-life and additional and pharmacodynamic properties of drug biotech and big pharma. In the second part, I specificity conferred by the antibody molecule. candidates. We have designed rationally engineered will provide examples from Roche’s pipeline albumins to enhance these properties. A half-life how to discover, design, develop, and deliver 11:15 High-Resolution Mass Spectrometry of more than double that seen for native sequence differentiated, multi-functional therapeutics Confirms the Presence of a Hydroxyproline albumin is obtainable for therapeutic candidates Sponsorship Opportunities ® that allow for tailored solutions for the (Hyp) Post-Translational Modification in the associated with Veltis albumins engineered for Hotel/Additional Information biological problem at hand. GGGGP Linker of an Fc-Fusion Protein increased FcRn binding affinity. Newly developed thio-engineered albumins with additional free thiol Chris Spahr, Senior Scientist, Therapeutic Discovery, groups allow further options for multi-valent site- Registration & Pricing Discovery Attribute Sciences, Amgen, Inc. specific drug loading. (G4P)n protein linkers were proposed to replace CHI-PepTalk.com CHI-PepTalk.com | 9 FINAL WEEKS JANUARY 8-9 | 14TH ANNUAL PROTEIN ENGINEERING TO REGISTER Recombinant Protein Therapeutics & DEVELOPMENT Fusion Proteins & Beyond Cover

Sponsors 12:45 Session Break and rFIX(R338L) Fc-XTEN fusion proteins will be Event-at-a-Glance 3:15 BuzZ Sessions with Refreshments presented, as well as antibody screening methods 1:00 Luncheon Presentation (Sponsorship Join your peers and colleagues for used to generate a true FVIIIa mimetic bispecific Opportunity Available) or Enjoy Lunch on Your interactive roundtable discussions. (FIXa/FX) antibody. Own Please see page 78 for additional 5:30 Designed Ankyrin Repeat Protein as information. IMPROVING THERAPEUTIC Inhibitors of Clostridium Difficile Toxin B PROPERTIES AND MANUFACTURING Zhilei Chen, Ph.D., Associate Professor, Microbial 2:00 Chairperson’s Remarks FIGHTING DISEASE WITH FUSION Pathogenesis and Immunology, Texas A&M College of Medicine John McCafferty, Ph.D., CEO, Antibody Engineering, PROTEIN THERAPEUTICS Using phage-panning combined with high- IONTAS, Ltd. 4:30 SELECTED POSTER PRESENTATION: throughput in vitro functional screening, we recently 2:05 Design, Structure and Manufacturability: Computational Driven Protein Engineering engineered several designed ankyrin repeat protein (DARPin) with picomolar neutralization potency Lessons Learned from Fusion Proteins Platform Enables the Discovery and Development of Next-Gen Antibacterial against C. difficile TcdB, which is 100-1000-fold Stefan Schmidt, Ph.D., MBA, CSO, Development and Therapeutics more potent than bezlotoxumab. These anti- Innovation, Rentschler Biotechnology toxin DARPins were found to effectively protect Yongliang Fang, Ph.D., Scientist, Thayer School of Next-generation therapeutic proteins are typically mice against TcdB-associated mortality. Cryo- Engineering, Dartmouth College human designed molecules with no counterpart in electromicroscopy studies revealed that binding living organisms. As they have not been selected in Conventional small-molecule antibiotics only inhibit of one of these DARPins induced significant a natural evolution process, they can suffer from low the growth of MRSA and are known to rapidly induce conformational change of TcdB, likely rendering it expression, mis-assembly and mis-folding, disulfide new resistance once they are applied in the clinic. unable to associate with the target receptor. scrambling, a tendency to aggregate, and sensitivity Therefore, there is a critical need for an alternative to protease degradation. In this presentation, I will approach to combat this threat to public health. 6:00 - 7:15 Welcome Reception Sponsored by show examples from our portfolio and the literature Lysostaphin is an antibacterial enzyme which has in the Exhibit Hall with Poster demonstrating how to avoid these product-related drawn the attention of researchers, pharmaceutical Viewing impurities by smart fusion protein design and companies, and the medical community because strategies to eliminate these impurities in efficient of its extraordinary potency against MRSA both 7:15 Close of Day bioprocesses. in vitro and in vivo. The success of our methods for deimmunization of lysostaphin demonstrates 2:35 Advanced Bi- and Multi-Specific the potential impact of computationally-driven TUESDAY, JANUARY 9 Antibody Derivatives and Fusion Proteins for engineering throughout the biotherapeutic pipeline. 8:00 am Registration and Morning Coffee Targeted Therapy: From Molecular Design to In addition, the computational algorithms will also Therapeutic Application allow us to develop various types of therapeutic proteins with lower immunogenicities and may FIGHTING CANCER Ulrich Brinkmann, Ph.D., Expert Scientist, Scientific ultimately aid the rising tide of biologics that are 8:30 Chairperson’s Remarks Director, Roche Pharma Research & Early currently entering the R&D pipeline. By Cambridge Healthtech Institute Development, Roche Innovation Center Munich Robert Peters, Ph.D., Senior Vice President, Research, ‘Success needs Diversity - Diversity breeds 5:00 Protein Engineering to Further Improve Bioverativ, Inc. Success’: Roche develops bi & multifunctional Clotting Factor-Fc Fusions and Create Novel 8:35 Combinatorial Protein Engineering antibody derivatives in diverse compositions and FVIIIa Mimetic Bispecific Antibodies SHORT COURSES formats (as opposed to ‘one-size/format-fits- of Proteolytically Resistant Mesotrypsin Robert Peters, Ph.D., Senior Vice President, Research, all’ approaches). The presentation will highlight Inhibitors as Candidates for Cancer Therapy Bioverativ, Inc. examples of the variety of multifunctional antibody Niv Papo, Ph.D., Group Leader and Assistant Professor, Further protein engineering was performed on formats, covering examples of diverse molecules in Biotechnology Engineering, Ben-Gurion University clotting factor-Fc fusions with a goal to further Sponsorship Opportunities clinical development as well as novel approaches in Our study describes a rapid methodology for improve protection from bleeds provided by a preclinical evaluation. identifying mutations that convert the human prophylaxis regimen, and to potentially enable Hotel/Additional Information amyloid precursor protein Kunitz protease inhibitor subcutaneous administration, while preserving the 3:05 Transition to BuzZ Sessions domain (APPI), a natural substrate of the oncogenic biology of the coagulation system. Considerations Registration & Pricing protease mesotrypsin, into a proteolytically and the path to creation of rFVIIIFc-VWF-XTEN

CHI-PepTalk.com CHI-PepTalk.com | 10 FINAL WEEKS JANUARY 8-9 | 14TH ANNUAL PROTEIN ENGINEERING TO REGISTER Recombinant Protein Therapeutics & DEVELOPMENT Fusion Proteins & Beyond Cover

Sponsors stable high affinity inhibitor of mesotrypsin. We TNFR-SF Agonists for Cancer Immunotherapy of the protein to the immune system. Event-at-a-Glance demonstrated that APPIM17G/I18F/F34V acts Oliver Hill, Ph.D., Vice President, Molecular Biology/ as a functional inhibitor in cell-based models of Protein Engineering, Apogenix AG 12:00 pm Sponsored Presentation mesotrypsin-dependent prostate cancer cellular The HERA technology platform developed by (Opportunity Available) invasiveness. Additionally, by solving the crystal Apogenix is based on trivalent but single-chain 12:30 Session Break structure of the complex, we uncovered new molecular mimics of the TNF-SF receptor binding insights into the structural and mechanistic basis for domains (scTNFSF-RBDs) fused to a dimerization improved binding and proteolytic resistance. 12:45 Luncheon Presentation (Sponsorship scaffold. These hexavalent fusion proteins are true Opportunity Available) or Enjoy Lunch on 9:05 Redefinition of ErbB2/3 Tumor Targeting: agonists and their biological activity is, in contrast to Your Own agonistic anti-TNFR-SF antibodies, independent of Novel Platform for Development of Truly secondary Fc-receptor based crosslinking events. We 1:15 Close of Recombinant Protein Efficient Anti-ErbB Bispecific and Biparatopic will present the molecular engineering concept and Therapeutics Conference Agents report on in vitro and in vivo activities of HERA-CD40L, Rastislav Tamaskovic, Ph.D., Senior Scientist, HERA-CD27L, HERA-GITRL and HERA-CD137L. Biochemistry, University of Zurich We built a new platform for RTK fingerprinting of 11:30 Improving Enzyme-Based Therapy of tumors under therapy, for identification of points Acute Lymphoblastic Leukemia: Molecular of fragility in oncogene-addicted tumors with the Design of Human L-Asparaginases developed acquired resistance, and for the design of Manfred Konrad, Ph.D., Research Director, Enzyme prospective therapeutic leads in a variety of bispecific Biochemistry, Max Planck Institute for Biophysical formats. This novel approach heralds the next Chemistry generation of ErbB targeting vehicles with beneficial Acute lymphoblastic leukemia (ALL), the most properties owing to maximization of drug potency common cancer in children, is a genetically and minimization of the risk of side and off-target heterogenous disease. We designed and engineered effects associated with the current drug formats. human enzyme homologues displaying the clinically established enzyme drug L-asparaginase 9:35 Sponsored Presentation (Opportunity (L-ASNase) activity with the aim of identifying Available) catalytically efficient variants to substitute for the bacterial enzymes. Furthermore, to increase 9:50 Coffee Break in the Exhibit Hall with the serum half-life of the enzymes, we generated Poster Viewing biocompatible microcapsules as carriers, thus 11:00 HERA: Engineering Next Generation enhancing serum stability and preventing exposure

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 11 FINAL WEEKS JANUARY 9-10 | 5TH ANNUAL PROTEIN ENGINEERING TO REGISTER Enhancing Antibody Binding and Specificity & DEVELOPMENT Scientific Strategies for Engineering Biotherapeutic Binding and Cover Specificity for Next-Generation Antibody Therapeutics

Sponsors As the industry expands its repertoire of antibody drug products into new therapeutic areas, product formats and protein constructs, the control of antibody/antigen targeting, binding and specificity will take on a new level of importance for researchers in this field. The second meeting in the PepTalk Protein Engineering & Event-at-a-Glance Development pipeline, Cambridge Healthtech Institute’s Fifth Annual Enhancing Antibody Binding and Specificity conference, presents innovative approaches to the modulation of binding activity for traditional antibodies, new product formats and difficult targets such as transmembrane proteins.

TUESDAY, JANUARY 9 tissue and showed that a low affinity Her2 CAR had mutants with small molecules has been extremely a higher therapeutic index compared to its high challenging. In this talk, I will introduce the 1:00 pm Registration affinity counterpart. development of cytosol-penetrating antibody that internalizes into the cytosol of living cells and 1:30 Refreshment Break in the Exhibit Hall 3:15 Featured Poster Presentation: An selectively binds to the activated form of oncogenic with Poster Viewing Integrated Nanofluidic and Optoelectronic Ras mutants to block the interactions with effector Platform to Screen Engineered Antibody proteins, thereby exerting in vivo anti-tumor activity ADVANCES IN TARGETING AND Panels in mouse models after systemic administration. SIGNALING Fen-Fen Lin, Senior Scientist, Amgen 5:30 Close of Day We explored an innovative nanofluidic cell culture 2:00 Chairperson’s Opening Remarks 5:30 - 5:45 Short Course Registration Madhu Natarajan, Ph.D., Preclinical Therapeutic Area platform from Berkeley Lights, the BeaconTM, to Head, Ophthalmology & Complement Biology, Shire screen engineered antibody panels for the early stages of therapeutic antibody selection. We 5:45 - 8:45 Dinner Short Courses* developed on-chip assays for both IgG secretion See page 5 for details KEYNOTE PRESENTATION from mammalian cells and antigen binding and * Separate registration required demonstrated correlation with standard assays. 2:05 Integrated Computational Design The Beacon™ platform could potentially compress and Experimental Selection Leads to timelines, increase capacity, and reduce resources Custom Targeted Biologics required for our workflow. WEDNESDAY, JANUARY 10 Philip M. Kim, Ph.D., Associate Professor, 3:45 Refreshment Break in the Exhibit Hall Computational and Integrative Biology, with Poster Viewing 8:00 am Registration and Morning Coffee University of Toronto, Canada I will present our technology platform on 4:30 Engineering a Therapeutic Antibody for ANALYTICAL METHODS integrating a number of different computational Long-Acting Delivery to the Eye 8:30 Chairperson’s Remarks protein strategies (including classic protein Devin Tesar, Ph.D., Scientist, Drug Delivery, Genentech Tilman Schlothauer, Ph.D., Principal Scientist, design, thermodynamic integration and Ocular delivery of protein therapeutics often Biochemical and Analytical Research, Large Molecule machine learning) with high-throughput requires favorable viscosity properties to support Research, Roche Innovation Center Munich selection strategies (including phage display, high-concentration formulations. Using structure- 8:35 Robust Determination of Antibody yeast-2-hybrid and phenotypic selections in based design we generated high-affinity mutants mammalian cell culture) to obtain custom of a backup Fab which exhibited superior viscosity Affinity to Cells Using Flow Cytometry targeted biologics. properties but inferior target binding and inhibition Timothy Fenn, Ph.D., Associate Director, Prevail

By Cambridge Healthtech Institute as compared to the lead candidate. Two of these Therapeutics 2:45 Affinity-Tuned CARs Can Reduce On- mutants, FM1 and FM2, exhibit binding and target Determining the affinity of a protein-cell interaction Target Off-Tumor CAR T Cell Cytotoxicity inhibition equal or superior to that of the lead is often performed using Scatchard-like analyses. molecule, while retaining the superior viscosity Here, we show the limitations and pitfalls of Mauro Castellarin, Ph.D., Postdoctoral Researcher, SHORT COURSES profile. such an approach and present a novel method Center for Cellular Immunotherapies, University of 5:00 Cytosol-Penetrating Antibody of data analysis and fitting that provides a robust Pennsylvania School of Medicine determination of affinity, even in the case of a CAR T cells can effectively kill malignant cells but Technology for Targeting Oncogenic Ras bivalent ligand such as an antibody. We also Sponsorship Opportunities autoimmune toxicity can occur when normal cells Mutants compare the results with other methods such as express the same targets. This type of on-target off- Yong-Sung Kim, Ph.D., Professor, Molecular Science SPR for affinity determination. Hotel/Additional Information tumor toxicity can be lessened using affinity-tuned and Technology, Ajou University, Korea CARs. We developed an in vivo mouse model that Oncogenic Ras mutants are high-priority anticancer Registration & Pricing expresses human tumor antigens in normal mouse drug targets. However, direct inhibition of Ras

CHI-PepTalk.com CHI-PepTalk.com | 12 FINAL WEEKS JANUARY 9-10 | 5TH ANNUAL PROTEIN ENGINEERING TO REGISTER Enhancing Antibody Binding and Specificity & DEVELOPMENT Scientific Strategies for Engineering Biotherapeutic Binding and Cover Specificity for Next-Generation Antibody Therapeutics

Sponsors 9:05 Modeling Protein-Protein Complexes. 11:20 Utilities of Biosensor Platforms in 2:05 Engineering Antibodies to Modulate Event-at-a-Glance The Good, the Bad and the Ugly Antibody Discovery Their Spatiotemporal Behavior Enrico Purisima, Ph.D., Team Leader, Molecular Danlin Yang, Ph.D., Scientist, Biophysics, E. Sally Ward, Ph.D., Professor, Molecular and Cellular Modeling, National Research Council Canada Biotherapeutics Discovery, Boehringer Ingelheim Medicine, Texas A&M Health Science Center The talk will examine the challenges of protein- Pharmaceuticals The role of FcRn as a global regulator of antibody protein docking with a particular emphasis on Label-free optical biosensors are powerful tools and albumin levels and transport in the body is well antibody-antigen complexes. A major complication in drug discovery for the characterization of established. Recent studies using a combination is accounting for the conformational changes that biomolecular interactions. Here, we compare the of antibody engineering, microscopy and in vivo can occur between the bound and free states of the strengths and weaknesses of four routinely used studies have led to strategies to modulate antibody docking partners. We will highlight recent progress biosensor platforms by assessing their ability to levels for use in diagnostic imaging and therapy. in the field and describe specific efforts in our own provide quality kinetic data on high affinity antibody- Developments in these and other FcRn-related areas lab. An assessment of what we can realistically antigen interactions. Applications including the will be presented. expect from current methods will be given. classification of antibody binding epitopes via epitope binning studies and the profiling of the 2:35 Altering Antibody Specificities for Better 9:35 Featured Poster Presentation: quality of antigen-induced polyclonal immune Clearance Discovering Antibody Binding Signatures responses in immune sera are demonstrated. Madhu Natarajan, Ph.D., Preclinical Therapeutic Area in Age-Related Macular Degeneration for Head, Ophthalmology & Complement Biology, Shire Diagnostic Development 11:50 Human IgG Subtype Cross-Species In recent years, the clearance of antibodies Joel Bozekowski, Ph.D. Candidate, Chemical Reactivity to Mouse and Cynomolgus Monkey through antigen-mediated processes has re- Engineering, University of California, Santa Barbara FcƔReceptors emerged as a topic of interest, with the implication Signatures in the antibody repertoire can indicate Mehabaw G. Derebe, Ph.D., Scientist, Biologics that engineering the affinities of therapeutic the onset and presence of various diseases. Here, Engineering, Janssen BioTherapeutics antibodies for antigens in a context-dependent we utilized random peptide library screening to manner can yield dramatic improvements in both analyze the collection of peptides that bind serum Animal models are routinely used to assess pharmacokinetic and pharmacodynamic effects. antibodies from subjects at various stages of age- pharmacodynamics, toxicity, efficacy and other related macular degeneration (AMD). Bioinformatics properties of candidate therapeutic antibodies. The We have systematically explored the biology analysis of the peptide sequences enabled the interaction of human IgG molecules to endogenous and interdependencies of these mechanisms to characterization of binding specificities present in FcƔ receptors of animal models can be different understand and inform the rational engineering AMD samples and absent from controls which could from their interaction to human FcƔ receptors. This of novel therapeutic antibodies for improved be utilized for early diagnostic development. study confirms the binding characteristics of human pharmacodynamic and pharmacokinetic properties. IgG subtypes IgG1, IgG2 & IgG4 as well as their silent 10:05 Coffee Break in the Exhibit Hall with versions to human, mouse and cynomolgus monkey 3:05 Refreshment Break in the Exhibit Hall Poster Viewing FcƔ receptors. To control interactions between Fab with Poster Viewing and Fc domains, the test articles all have the same ENGINEERING BINDING AFFINITY variable regions. 4:00 Highly Efficient Recovery of GPCR- 10:50 Conditional Fc Receptor Interactions – Specific Antibodies Coupling Yeast Library What Effector Cells Are Interested In 12:20 pm Sponsored Presentation Selection and Next-Generation Sequencing By Cambridge Healthtech Institute Tilman Schlothauer, Ph.D., Principal Scientist, (Opportunity Available) Robert Pejchal, Ph.D., Scientist, Antibody Engineering, Biochemical and Analytical Research, Large Molecule Adimab LLC 12:50 Session Break Research, Roche Innovation Center Munich Discovery of antibodies specific to GPCRs, and SHORT COURSES An assay platform has been established to assess 1:00 Luncheon Presentation (Sponsorship other challenging multi-spanning membrane protein targets, has been a long-standing challenge for antibody-Fc-receptor interaction. This platform, Opportunity Available) or Enjoy Lunch on Your drug development. Adimab’s platform utilizes comprised of a broad panel of reagent tools Own and assay formats, is utilized for mechanistic whole mammalian cells over-expressing the target Sponsorship Opportunities studies towards the deeper understanding of Fc membrane protein for selection and couples next functionality. Besides the comparison of wildtype OPTIMIZING ANTIGEN generation sequencing (NGS) to identify antibodies Hotel/Additional Information IgG1 antibodies, antibody variants with reduced or SPECIFICITY with desired specificities. Methodologies and enhanced Fc-functionality can also be investigated outcomes for discovery and optimization efforts on Registration & Pricing by this comprehensive set of cell-free and cell-based 2:00 Chairperson’s Remarks GPCR and tetra-spanning targets will be reviewed. in vitro functional assays. Timothy Fenn, Ph.D., Principal Scientist, Boehringer Ingelheim CHI-PepTalk.com CHI-PepTalk.com | 13 FINAL WEEKS JANUARY 9-10 | 5TH ANNUAL PROTEIN ENGINEERING TO REGISTER Enhancing Antibody Binding and Specificity & DEVELOPMENT Scientific Strategies for Engineering Biotherapeutic Binding and Cover Specificity for Next-Generation Antibody Therapeutics

Sponsors 4:30 ProTIA – Bispecific T Cell Engagers Event-at-a-Glance Designed for Local Activation in the Tumor Environment Volker Schellenberger, Ph.D., President and CEO, Amunix Amunix is developing ProTIA (Protease Triggered Immune Activator) therapeutics based on our proprietary XTEN™ protein polymer platform. ProTIAs are administered as inactive prodrugs that are activated in the tumor environment by release of their blocking XTEN polymer. AMX-168 is a ProTIA molecule targeting EpCAM, which is overexpressed in the majority of solid malignancies. AMX-168 has shown excellent efficacy and selectivity in a range of in vivo models.

5:00 A Pre-Targeting Strategy for Enhancing Reactivity of Antibody Therapeutics Jonathan Wall, Ph.D., Professor and Director, Amyloidosis and Cancer Theranostics Program, University of Tennessee Medical Center Passive immunotherapy is an efficient method for mediating antibody-dependent cell-mediated cytotoxicity or phagocytosis. Pre-targeting can be used to enhance and expand the utility of antibody therapeutics. We have developed a bifunctional polypeptide that combines a specific amyloid- targeting peptide moiety with a high-affinity linear epitope sequence for a known antibody. Using this “peptope” reagent we have successfully targeted antibodies to a pathology which would otherwise not be recognized.

5:30 - 6:45 Networking Reception in the Exhibit Hall with Poster Viewing

By Cambridge Healthtech Institute 6:45 Close of Enhancing Antibody Binding and Specificity Conference

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 14 FINAL WEEKS JANUARY 11-12 | 3RD ANNUAL PROTEIN ENGINEERING TO REGISTER Emerging Technologies for Antibody Discovery & DEVELOPMENT Exploring the Intersection of Display Technologies, Next-Generation Sequencing Cover and Informatics for the Discovery of Next-Generation Biotherapeutics

Sponsors As large pharma continues its integration of biologic drugs into its product portfolios and discovery operations, it is imperative that industry companies identify Event-at-a-Glance truly novel drug targets for unmet medical needs – and that the biotherapeutics against these are selected and engineered to minimize development risk. For 2018, Cambridge Healthtech Institute’s Third Annual Emerging Technologies for Antibody Discovery conference considers the intersection of traditional display based screening and selection approaches with next-generation tools such as immune repertoire sequencing, in silico modeling and high-resolution imaging.

THURSDAY, JANUARY 11 9:30 Phage-Displayed Ubiquitin Variant (UbV) mistakes novices make, and present our practices to Libraries to Rapidly Identify Potent and Highly ensure the correctness of every amino acid. 7:45 am Registration and Morning Coffee Selective Protein-Based Inhibitors Targeting 12:00 pm Session Break E3 Ligases and Deubiquitinases 8:15 Chairperson’s Opening Remarks Wei Zhang, Ph.D., Mitacs Elevate Fellow, University of 12:15 Luncheon Presentation I: Sponsored by Andrew Bradbury, Ph.D., CSCO, Specifica, Inc. Toronto, Canada Next-Generation Capillary E3 ligases and deubiquitinases regulate diverse Electrophoresis Technology for KEYNOTE PRESENTATION cellular processes and are implicated in numerous Protein Analysis human diseases. However, targeting these enzymes Wei-Chiang Chen, Ph.D., Scientist, Analytical 8:20 Remodeling of Cell Surfaceomes in potently and specifically remains a big challenge. Development, Biogen Cancer We thus devised a screening platform to develop Recombinant adeno-associated virus (AAV) is a protein-based modulators for ubiquitin proteasome James A. Wells, Ph.D., Professor, promising platform in human gene therapy. AAV system components. I will report how we design the Pharmaceutical Chemistry, University of vectors contain a protein outer shell called capsid, ubiquitin variant (UbV) library to generate inhibitors California, San Francisco which is comprised of 60 subunits containing three and activators for E3 ligases (RING and HECT The cell surface proteome (surfaceome) is viral proteins. To confirm the purity of the AAV family) and deubiquitinases (viral and human origin). the primary hub for cells to communicate with capsids, we developed a CE-SDS method on the the outside world. My lab studies how the 10:00 Coffee Break in the Exhibit Hall with Maurice platform, which automates analysis of 96 surfaceome is remodeled in cancer. We find Poster Viewing samples in one batch. This assay demonstrates the new set of proteins promote enhanced good separation of viral proteins (LOQ at 5e11 vg/ cell growth and detachment from native 11:00 Efficient B Cell Cloning and Antibody ml), and comparable results with SDS-PAGE gels. tissues allowing metastasis. Our primary goal Engineering Platform for Rare Ab Generation is to systematically understand how cancer 12:45 Presentationto be Announced Feng Shu, Ph.D., Senior Researcher, Chugai cells remodel their membrane proteomes Pharmabody Research, Singapore (surfaceomes) during cancer transformation and 1:15 Ice Cream Break in the Exhibit Hall with develop antibodies to detect and attack them. Here we describe a high throughput antibody Poster Viewing identification system by single B cell cloning, which can generate and evaluate a large number ADVANCES IN DISPLAY FUNCTIONAL SCREENING of antibodies with high diversity to identify the rare antibodies with required properties such as pH TECHNOLOGIES AND LIBRARY 9:00 Combining Screening with Phenotypic dependency. A robust antibody engineering system DESIGN Selection in Antibody Phage Display is also introduced, where thousands of antibodies By Cambridge Healthtech Institute 2:00 Chairperson’s Remarks Marcin Paduch, Ph.D., Pipeline Director, Recombinant with designed mutations can be generated and Nicolas Fischer, Ph.D., Head, Research, Novimmune Antibody Network, University of Chicago evaluated in 2 weeks’ time to further accelerate the antibody discovery process. SA, Switzerland State-of-the-art methods for generating recombinant SHORT COURSES Sponsored by antibodies do not necessarily allow for targeting the 11:30 Antibody Protein 2:05 Enhancing the Chemical Versatility of particular cellular phenotype posing a fundamental Yeast Display challenge. A set of next generation high-throughput Sequencing with Mass James Van Deventer, Ph.D., Assistant Professor, technologies that allow for phenotypic selection has Spectrometry Chemical and Biological Engineering, Tufts University Sponsorship Opportunities to be developed. Intimate knowledge of conformation Mingjie Xie, MSc, MBA, CEO, Rapid Novor Inc We have established a version of yeast display that states and biochemistry of antigens can be exploited Many applications in antibody engineering require the supports the integration of chemical groups into Hotel/Additional Information to mimic native-like environments and create the direct sequencing of antibody proteins. At Rapid Novor displayed proteins using noncanonical amino acid possibility of trapping physiologically-relevant states (rapidnovor.com) we have developed a robust workflow incorporation. We are currently investigating strategies Registration & Pricing otherwise not accessible by current methods. and routinely sequenced antibody proteins. Here we share the success experiences, examine common for positioning chemical groups within antibodies in CHI-PepTalk.com CHI-PepTalk.com | 15 FINAL WEEKS JANUARY 11-12 | 3RD ANNUAL PROTEIN ENGINEERING TO REGISTER Emerging Technologies for Antibody Discovery & DEVELOPMENT Exploring the Intersection of Display Technologies, Next-Generation Sequencing Cover and Informatics for the Discovery of Next-Generation Biotherapeutics

Sponsors order to enhance and change the molecular recognition the development of bispecific antibodies. To achieve stakeholders working across the stages of protein Event-at-a-Glance capabilities of these proteins. This talk will highlight that goal, we have developed methodologies science R&D. Join experts representing this PepTalk our recent progress in constructing, evaluating, and that allow ‘in format’ phage display selection and pipeline, peers, and colleagues for an interactive screening “hybrid” structures with potential applications screening of candidates early in discovery. roundtable discussion. Topics include highlights in the tumor microenvironment. from the week’s presentations, new technologies 4:45 Synthetic Human Antibody Fragment and strategies, challenges, and future trends. 2:35 How Big Are Antibody Libraries Really? Libraries for CAR T Cell Therapy Table Moderator: James Van Deventer, Ph.D., And Are We Accessing the Full Diversity? Thomas J. Van Blarcom, Ph.D., Associate Research Assistant Professor, Chemical and Biological Andrew Bradbury, Ph.D., CSO, Specifica, Inc. Fellow, Rinat Laboratories, Oncology Research and Engineering, Tufts University In vitro antibody libraries have been used to generate Development, Pfizer, Inc. Table Moderator: Marcin Paduch, Ph.D., Pipeline Director, antibodies against many different therapeutic lead Unlike most therapeutic antibodies, CAR T cells Recombinant Antibody Network, University of Chicago targets. Analyses indicate that one would expect to are typically generated with single chain variable select 1-3 antibodies from a 1e7 library. However, fragment (scFv) antibodies. In this study, we present this does not appear to scale to larger libraries with a human synthetic scFv antibody library that we use INTEGRATED DISCOVERY diversities estimated to be >1 billion, suggesting to simplify the generation and testing of large panels PLATFORMS that libraries are less diverse than thought or of antibodies for use as CAR T cells. The CAR T selection methods do not tap the full diversity. This cells generated from these antibodies had desirable 9:00 Chairperson’s Remarks talk discusses the use of NGS to explore these phenotypes and demonstrated robust and specific Sagar Kathuria, Ph.D., Senior Scientist, Protein issues and the application of NGS to the creation of cytotoxic activity in vitro. Engineering, Sanofi Genzyme improved antibody libraries. 5:15 Highly Multiplexed Cell Surfaceomics 9:05 Generation of Mono and Bispecific 3:05 Featured Poster Presentation: Mapping Using Genetically Barcoded Antibody-Phage Antibodies from Immunized Transgenic Rodents the Antibody Response to Vaccines Directly Samuel Pollock, Researcher, Pharmaceutical and the Potential to Engineer Multi-Specific from Patient Serum Chemistry, University of California, San Francisco Entities Using Common Light Chain Paratopes Michael Szardenings, Ph.D., Vice Head Department Cells express thousands of different surface Simon Krah, Ph.D., Senior Scientist, Protein Engineering of Immunology, Fraunhofer Institute for Cell Therapy proteins that can be used for their classification. and Antibody Technologies, Merck KGaA, Germany and Immunology, Germany We present a surface proteomic method using We demonstrate that by using Yeast Surface A novel phage display-based platform provides genetically barcoded antibodies called Phage- Display (YSD), a more effective coverage of the a promising alternative technology to determine antibody Next Generation Sequencing. We use antibody diversity generated during the course of epitopes of vaccines. Antibody epitope variations PhaNGS to reveal changes in surface protein an immunization can be realized in comparison were studied over 6 years in the serum of a single abundance in the contexts of drug resistance, to classical hybridoma technology. Moreover, we patient (influenza, Hepatitis B vaccines and traces adaptation to oncogenes, and on the single-cell show that bispecific antibodies can also be readily of other infections). Information about the natural level. Linking selective, genetically encoded binders engineered via such YSD approaches in combination antibodies’ epitopes may help to design vaccines to NGS enables direct, multiplexed protein detection, with the application of common light chains. In and to clone or design antibodies for multiple comparable to RNAseq for mRNA. addition, we established a methodology which therapeutic and diagnostic applications. facilitates the tedious and time-consuming process By Cambridge Healthtech Institute 5:45 Close of Day of YSD library generation. 3:35 Refreshment Break in the Exhibit Hall with Poster Viewing FRIDAY, JANUARY 12 9:35 Discovery Platform for Antibody Generation and Screening for Different Applications SHORT COURSES 4:15 Dual Display Technology for “In Format” 8:00 am Registration Anne Marcil, Team Lead, Monoclonal Antibodies, Selection and Screening of Bispecific Antibodies National Research Council, Canada Nicolas Fischer, Ph.D., Head, Research, Novimmune The National Research Council of Canada has SA, Switzerland 8:00 BuzZ Sessions with Continental Sponsorship Opportunities a strong history in target discovery, antibody The desired biological activity of bispecific Breakfast generation and characterization, resulting in the Hotel/Additional Information antibodies is often dependent on the adequate Protein therapeutics is a fast-growing production of new antibodies against hundreds geometry of the two antibody binding sites, thus global market. As the science improves, of targets. An overview of our antibody discovery Registration & Pricing requiring extensive combinatorial testing of isolated so does the complexity of the R&D pipeline which includes bioinformatics and MS antibodies. Being able to evaluate candidates ‘in organization. Ensuring product quality analysis for target discovery, monoclonal, single- format’ as early as possible would greatly facilitate plus speed to market requires insights from CHI-PepTalk.com CHI-PepTalk.com | 16 FINAL WEEKS JANUARY 11-12 | 3RD ANNUAL PROTEIN ENGINEERING TO REGISTER Emerging Technologies for Antibody Discovery & DEVELOPMENT Exploring the Intersection of Display Technologies, Next-Generation Sequencing Cover and Informatics for the Discovery of Next-Generation Biotherapeutics

Sponsors domain and antibody library screening, in vitro make use of several high-throughput biophysical Event-at-a-Glance screening for function (ADCs, Blood-brain barrier and biochemical tools for antibody characterization crossers, electrophysiology, etc.) and in vivo towards achieving this goal. Results from some test screening will be presented. cases will be discussed.

10:05 A Patient-Centric Function F.I.R.S.T™ 11:45 High Content Confocal for Antibody Approach to Cancer Immunotherapy Selection and Potency Screening Discovery Tianyi Wang, Ph.D., Scientist, R&D, Sorrento Björn Frendéus, Ph.D., CSO, Bioinvent, Sweden Therapeutics We have developed a patient-centric phenotypic This talk outlines applications of high content discovery approach (F.I.R.S.T) that utilizes primary confocal and cell-by-cell metrics for selection and cancer patients’ cells from the initial steps of isolating potency of antibodies with applications toward antibodies from a naïve human antibody library intracellular targets. 3D spheroids and high content through POC studies and subsequent identification confocal in vitro system are used to screen the of targeted receptors. A lead candidate which blocks phenotypic effects of selected intracellular-targeting FcgRIIB internalization and acts in synergy with antibodies. 3D spheroids, by mimicking tumor rituximab to boost responses and help overcome microenvironment, are a better predictor of clinical resistance in the background of emerging targeted potential of antibody therapeutics. Our method therapies as well as conventional chemotherapy in proposes multiparametric analyses of spheroids to vivo, is now in clinical phase testing. elucidate mechanism of action.

10:35 Coffee Break with a Poster Pavilion 12:15 pm Conference Wrap-Up See page 4 for details Tilman Schlothauer, Ph.D., Principal Scientist, 11:15 Tool and Platform Development for Biochemical and Analytical Research, Large Molecule Antibody Developability Assessment and Research, Roche Innovation Center Munich Mitigation Sagar Kathuria, Ph.D., Senior Scientist, Protein 12:45 Close of Conference Engineering, Sanofi Genzyme Antibodies have emerged as very successful biological drugs in the recent past. The growth of this industry has highlighted a need for a comprehensive set of non-redundant assays and corresponding threshold values to identify likely candidates early during research and prioritize their development. We

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 17 FINAL WEEKS TO REGISTER

Cover

Sponsors Event-at-a-Glance ANTIBODY THERAPEUTICS

JANUARY 8-9 AGENDA Engineering Next-Generation Cancer Immunotherapies

JANUARY 9-10 AGENDA Antibody-Drug Conjugates

JANUARY 11-12 AGENDA Bispecific Antibody Therapeutics

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 18 FINAL WEEKS JANUARY 8-9 | 4TH ANNUAL ANTIBODY TO REGISTER Engineering Next-Generation Cancer Immunotherapies THERAPEUTICS New Protein Engineering Science and Technology to Support the Development Cover of Novel Immunotherapeutics and Treatment Combinations Sponsors A succession of strong clinical successes with antibodies against checkpoint targets has spawned a surge of interest from across the industry in the development of Event-at-a-Glance antibody immunotherapeutics and treatment combinations. The major challenges facing those now entering the field include establishing clinical proof of concept, product and target differentiation, selection of patient responders and the rational design of effective immunotherapy combinations. CHI’s Fourth Annual Engineering Next-Generation Cancer Immunotherapies conference offers protein engineering strategies to improve the efficacy of immunotherapeutics and drive the progress of more personalized treatments in this space.

SUNDAY, JANUARY 7 9:50 Optimization of Immune Regulatory response against the tumor, and then isolated and Antibodies for Depletion of Regulatory T Cells expressed DNA sequences from the relevant single 4:00 - 6:00 pm Pre-Conference Registration Frederick Arce-Vargas, M.D., Ph.D., Research B cells. A recombinant antibody was produced, Associate, University College London Cancer and showed anti-tumor activity. This strategy Institute, United Kingdom represents an alternative paradigm in anti-cancer MONDAY, JANUARY 8 drug discovery. Modulation of the anti-tumor immune response with 7:00 am Registration and Morning Coffee antibodies targeting co-inhibitory and co-stimulatory 11:45 Manipulation of Affinity Maturation and molecules is a promising strategy in cancer therapy. B Cell Subsets in vivo ANTIBODY ENGINEERING In some cases, the effectiveness of these antibodies is not limited to receptor activation or blockade and Ali Zarrin, Ph.D., Senior Scientist, Immunology and CHALLENGES FOR also relies on depletion of Tregs. Characterizing the Antibody Engineering, Genentech IMMUNOTHERAPEUTICS expression density of these targets in different T B cells diversify their immunoglobulin genes to cell compartments and the myeloid cells involved in produce high affinity antibodies. Antigen specific B 9:00 Welcome by Conference Organizer Treg depletion is paramount for the design of next cells are selectively differentiated in the germinal Kent Simmons, Senior Conference Director, generation immune-modulatory antibodies. centers to seed short- or long- lived plasma cells, a Cambridge Healthtech Institute process known as affinity maturation. It is not clear 10:20 Networking Coffee Break how B cells commit to short or long-lived plasma 9:05 Chairperson’s Opening Remarks cell fate. Our study provides insights on how this Dimiter S. Dimitrov, Ph.D., Senior Investigator, Protein 10:45 The Impact of mAb Format in Targeting decision might be made during immune response Interactions Section, Cancer and Inflammation the Tumor Microenvironment and autoimmunity. Program, National Cancer Institute, NIH Stephen Beers, Ph.D., Associate Professor, Cancer 12:15 pm Antigen Epitope Immunology and Immunotherapy, University of Southampton, United Kingdom Analysis and De-Immunogenicity of Antibody/ KEYNOTE PRESENTATION Protein Drugs Monoclonal antibodies (mAb) are transforming 9:10 Evolution and Advancements in cancer therapy. Although the number of mAb Le Sun, Ph.D., CEO, AbMax Biotechnology Cancer Immunotherapy reaching the clinic continues to rise rapidly, 1) prediction of immunogenicity based on a.a. Partha Chowdhury, Ph.D., Senior Director and successful targets are scarce and new ones sequence using B-cell epitope analysis, 2) strong Head, Antibody Discovery, Sanofi Genzyme frequently fail. Understanding why promising correlations of ADA data between animal studies Cancer is an immunological disease pre-clinical candidates do not translate to humans and human clinic trials, 3) Case study with de- characterized by hijacking and evasion of the is a critical question. Here we show how mAb immunogenicity of Humira showed that ADA titers in By Cambridge Healthtech Institute natural immune response of the host. Although format can be key to efficacy and that this could mouse reduced by 90%. the idea to exploit the host’s immune response be particularly relevant when seeking new mAb to to fight against cancer is decades old, clinical target the tumor microenvironment. 12:45 Session Break SHORT COURSES success of immunotherapy is a relatively new 1:00 Luncheon Presentation (Sponsorship achievement. This talk will focus on the various 11:15 Novel Therapeutic Antibodies for Opportunity Available) or Enjoy Lunch on Your strategies used to manipulate a multitude Cancer Isolated from Single Human B Cells Own of factors that underlies the phenomenon Edward F. Patz, Jr., M.D., Professor, Radiology, Sponsorship Opportunities of immunotherapy, including recent Pharmacology and Cancer Biology Duke University advancements on new targets and approaches Medical Center Hotel/Additional Information to enhance the therapeutic efficacy of novel In an effort to develop novel therapeutic antibodies, biological drugs. we took cues from the native immune response Registration & Pricing in “exceptional outcomes” patients. We identified relevant tumor antigens by exploring the humoral CHI-PepTalk.com CHI-PepTalk.com | 19 FINAL WEEKS JANUARY 8-9 | 4TH ANNUAL ANTIBODY TO REGISTER Engineering Next-Generation Cancer Immunotherapies THERAPEUTICS New Protein Engineering Science and Technology to Support the Development Cover of Novel Immunotherapeutics and Treatment Combinations Sponsors IMMUNOTHERAPY COMBINATIONS Interactions for OX40 Agonists and Their TUESDAY, JANUARY 9 Event-at-a-Glance Ability to Drive Tumor Ag-Specific T Cell 2:00 Chairperson’s Remarks Expansion 8:00 am Registration and Morning Coffee Stephen Beers, Ph.D., Associate Professor, Cancer Andrew Weinberg, Ph.D., Judy Ann Hartmann Immunology and Immunotherapy, University of Endowed Chair for Cancer Immunology Research, NOVEL IMMUNOTHERAPIES Southampton, United Kingdom Robert W. Franz Cancer Research Center 8:30 Chairperson’s Remarks 2:05 Update on Clinical Progress of OX40 agonists have been shown to increase T cell effector function, proliferation and survival. G. Jonah Rainey, Ph.D., Executive Director, Research, Immunotherapy Combinations These T cell stimulating properties are important to MabVax Therapeutics Holdings, Inc. Gregory Daniels, M.D., Ph.D., Professor, Medicine, enhance anti-tumor therapeutic efficacy. We have 8:35 Efficacy of CAR-T Cells and Other Moores Cancer Center, University of California, San found that Fc receptor interactions are important Diego for the agonist properties of these OX40 targeting Immunotherapies Tumors development occurs in the context of a Abs, which appear to be completely independent of Dimiter S. Dimitrov, Ph.D., Senior Investigator, Protein functioning immune system with intrinsic and Treg depletion. Recently we have found that OX40 Interactions Section, Cancer and Inflammation extrinsic growth pathways dynamically shaping agonists can expand tumor reactive T cells within Program, National Cancer Institute, NIH a pro-tumor microenvironment. Tumor response the cancer microenvironment. Parameters that could affect efficacy of CAR-T cells to current therapies depend upon the quantitate and other immunotherapies including affinity, epitope and qualitative presence of the natural immune 5:30 Targeted Mass Spectrometry for Cancer location, surface expression and concentration response. I will discuss examples of combination Antigen Discovery of target cell surface associated antigen will be immune therapy in solid tumors that overcome the Paul Armistead, M.D., Ph.D., Associate Professor, discussed as well as possible underlying mechanisms. barriers in generating an anti-tumor response. Medicine, Lineberger Comprehensive Cancer Center, Specific examples will be presented including an University of North Carolina, Chapel Hill update on the high efficacy of the anti-CD22 CARs 2:35 Rational Combination of Oncolytic Virus Mass spectrometry based identification of based on the scFv m971 as well as newly developed and Checkpoint Therapy HLA-bound, cancer antigens is essential for BiKEs targeting the HIV-1 envelope glycoprotein. Jason DeVoss, Ph.D., Senior Scientist, Oncology, many immunotherapeutic strategies; however, 9:05 Neo-Antigen Targeting and Biomarkers Amgen standard non-targeted methods are insensitive in Cancer Immunotherapy and inadequate for the discovery of previously 3:05 Transition to BuzZ Sessions Laszlo Radvanyi, Ph.D., Senior Vice President, Senior undefined peptides (e.g., neoantigens). These Scientific Advisor, Immunology, Immuno-Oncology, problems can be overcome, however, by optimizing EMD Serono R&D Institute (a business of Merck mass spectrometers for the targeted detection 3:15 BuzZ Sessions with Refreshments KGaA, Darmstadt, Germany) of specific antigens. Targeting approaches that Join your peers and colleagues for we have adopted involve differential ion mobility This talk will discuss the emerging field of neo- interactive roundtable discussions. spectrometry for target enrichment and parallel antigen (mutanome) targeting. I will summarize Please see page 78 for additional reaction monitoring for target confirmation. current approaches used to deduce cancer neo- information. antigen epitopes and provide examples of how neo- 6:00 - 7:15 Welcome Reception Sponsored by antigens are being targeted in cancer immunotherapy By Cambridge Healthtech Institute in the Exhibit Hall with Poster clinical trials and the application of mutanome Viewing evaluation as a predictive biomarker. The talk also EMERGING PATHWAYS AND describes some conceptual obstacles being faced in TARGETS FOR CANCER SHORT COURSES 7:15 Close of Day the field and comment on the strategic position and IMMUNOTHERAPY future impact of neo-antigen targeting in the overall cancer immunotherapy landscape. 4:30 Epigenomic Mapping to Discover Novel Immunotherapy Targets 9:35 Featured Poster Presentation: Sponsorship Opportunities Pandurangan Vijayanand, M.D., Ph.D., Associate Identification of Breast Cancer Subtypes by Phenotypic Antibody Selection Hotel/Additional Information Professor, Vaccine Discovery, La Jolla Institute for Allergy and Immunology Kristine Kim, PhD, Professor, Department of Systems Registration & Pricing Immunology, College of Biomedical Science, 5:00 The Importance of Fc Receptor Kangwon National University, Korea

CHI-PepTalk.com CHI-PepTalk.com | 20 FINAL WEEKS JANUARY 8-9 | 4TH ANNUAL ANTIBODY TO REGISTER Engineering Next-Generation Cancer Immunotherapies THERAPEUTICS New Protein Engineering Science and Technology to Support the Development Cover of Novel Immunotherapeutics and Treatment Combinations Sponsors 9:50 Coffee Break in the Exhibt Hall with Engineering Adenosine Deaminase 2 for Event-at-a-Glance Poster Viewing Cancer Immunotherapy Development Lin Wang, Ph.D., Principal Scientist, Halozyme 11:00 A New Immunomodulatory Strategy of Therapeutics, Inc. Releasing Immunosuppression in the Tumor Adenosine is an endogenous immunosuppressant Microenvironment that binds to adenosine receptor checkpoints. Li Peng, Ph.D., Vice President, Antibody Engineering Abnormally high level of adenosine contributes to a and Protein Sciences, Palleon Pharmaceuticals highly immunosuppressive tumor microenvironment Cancer therapy has been revolutionized by inhibiting (TME). We hypothesized that adenosine deaminase immune-checkpoints to harness the power of 2 (ADA2), a human enzyme that catalyzes the the immune system in fighting cancer. Immune- deamination of adenosine, could be administered checkpoint inhibitors have proved to achieve a at therapeutic levels to deplete high level of TME durable response in a subset of cancer patients. adenosine and stimulate anti-tumor immune However, most patients are still resistant to activity. This talk will present data that supports our these first generation I/O drugs. Enormous effort hypothesis. is pursued to identify new immunomodulatory strategies. We describe a novel approach of 12:30 Session Break blocking an immunosuppression pathway involved Sponsored by in innate and adaptive response. 12:45 Luncheon Presentation: Identification of Novel Receptor 11:30 Achieving Broad Tumor Coverage by Targets and Specificity Screening Targeting Cancer Carbohydrate Antigens: of Biotherapeutics Lessons from the Clinic Accelerate Alex Kelly, Business Development Manager, Development of Additional Targets Retrogenix Limited G. Jonah Rainey, Ph.D., Executive Director, Research, Human cell microarray screening enables the MabVax Therapeutics Holdings, Inc. discovery of primary cell surface receptors and Glycans are promising therapeutic targets present off-targets for a variety of biotherapeutic molecules, on broad tumor types. We are clinically developing including peptides, antibodies and proteins, as well an anti-sialyl Lewis A (sLea) naked antibody (MVT- as CAR T and other cell therapies. Case studies 5873), immunoPET imaging agent (MVT-2163), will demonstrate the utility of the technology in and radioimmunoconjugate (MVT-1075). Here we identifying novel immunotherapy targets as well describe a fully human antibody against another as in specificity screening for biotherapeutics to cancer glycan, Tn (GalNAc alpha-O-Ser/Thr), aid safety assessment and provide critical data to which shows minimal overlap with sLea by tumor support IND submissions. microarray. We compare translational learnings from anti-sLea programs and describe how they have 1:15 Close of Engineering Next-Generation By Cambridge Healthtech Institute guided development of our anti-Tn effort. Cancer Immunotherapies Conference

12:00 pm Featured Poster Presentation: SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 21 FINAL WEEKS JANUARY 9-10 | 5TH ANNUAL ANTIBODY TO REGISTER Antibody-Drug Conjugates THERAPEUTICS Engineering for Clinical Success Cover

Sponsors The Fifth Annual Antibody-Drug Conjugates conference reveals the engineering that has brought about today’s ADC revolution, and examines how to design safe and Event-at-a-Glance effective therapeutics. Exploring options for selecting new targets and ensuring potency will be discussed, along with strategies for advancing ADCs to the clinic. A special focus on fighting cancer will be highlighted including tumor penetration. Analyzing ADCs to explore conjugation, stability, and payloads will also be addressed in this leading ADC event.

TUESDAY, JANUARY 9 3:15 Computational Exploration Sponsored by 5:30 Close of Day of Mechanistic Determinants of 5:30 - 5:45 Short Course Registration 1:00 pm Registration ADC Pharmacokinetics Using QSP Modeling Strategies 1:30 Refreshment Break in the Exhibit Hall John Burke, Ph.D., Co-Founder, President, CEO, 5:45 - 8:45 Dinner Short Courses* with Poster Viewing Applied BioMath, LLC See page 5 for details The pharmacokinetics of ADC therapeutics * Separate registration required IMPROVING THERAPEUTIC INDEX typically show a discrepancy between PK of total 2:00 Chairperson’s Opening Remarks antibody and of conjugated antibody, carrying one or more payload molecules. This discrepancy is Ian Schwartz, MS, CMC Expert, Antibody Drug often attributed to deconjugation, however recent WEDNESDAY, JANUARY 10 Conjugate and Upstream/Downstream Process evidence suggests that underlying mechanisms Development, Tech Transfer, and Manufacturing Ops, may be more complex. This presentation will 8:00 am Registration and Morning Coffee Sartorius Stedim Biotech demonstrate a computational approach to understand the impact of DAR and resulting FIGHTING CANCER WITH ADCs KEYNOTE PRESENTATION changes in molecular properties on overall PK and relative payload disposition as observed in 8:30 Chairperson’s Remarks 2:05 Case Study: Translational Safety of preclinical and clinical studies. Floris Van Delft, Ph.D., Founder & CSO, SynAffix BV Antibody Drug Conjugates -- Opportunities to Mitigate Clinical Toxicities and Improve 3:45 Refreshment Break in the Exhibit Hall Therapeutic Index (TI) with Poster Viewing FEATURED PRESENTATION Rakesh Dixit, Ph.D., DABT, Vice President, R&D, 8:35 Targeted Protein Therapeutic Drug MedImmune/AstraZeneca NEXT-GEN ADC STRATEGIES Design in Oncology I discuss preclinical toxicity models of 4:30 From Cells to ADCs: Jeannick Cizeau, Ph.D., Director, Research, Viventia safety assessment, translational safety and A Magnetic Bead-Based Workflow Bio, Inc. therapeutic index, and clinical development of ADCs using precision medicine approaches. for Antibody Capture and Conjugation Targeted protein therapeutics, or TPTs, are Paul Gianella, Ph.D., Postdoctoral Research Fellow, recombinant proteins composed of targeting Amgen, Inc. moieties genetically fused via a short peptidic linker 2:45 Improved Therapeutic Window with to cytotoxic protein payloads. A fit-for-purpose Antibody Linked Pyrrolobenzodiazepine 5:00 Exploring Higher Order Structure of design approach is utilized to overcome specific By Cambridge Healthtech Institute Dimers That Is Enhanced by PARP Inhibitor in ADCs with Biophysical Characterization challenges inherent to antibody drug conjugates BCA Mutant Tumors Techniques currently in use for the treatment of solid cancers. An overview of drug design for both local and Haihong (Helen) Zhong, Ph.D., Senior Scientist, David Chiu, Ph.D., Scientist, Analytical Sciences, systemically deliverable TPTs will be presented. SHORT COURSES Oncology Research, MedImmune, Inc. Seattle Genetics One of the major challenges to ADCs is how to Conformational changes to a biotherapeutic can impact product stability, safety, and efficacy, making improve therapeutic index. PBDs are DNA-damaging 9:05 Targeting Solid Tumors with Antibody- agents that have potent cytotoxicity against a broad higher order structure (HOS) characterization Sponsorship Opportunities spectrum of tumors. In preclinical efficacy and fundamentally important. Multiple biophysical Drug Conjugates: An Update safety studies including a “mouse PDX trial”, PBD- techniques, each with their own capabilities and Dimiter S. Dimitrov, Ph.D., Senior Investigator, Center Hotel/Additional Information based ADC as a single agent or in combination with limitations, are required to elucidate HOS. ADCs can for Cancer Research, NCI/NIH PARPi demonstrated enhanced anti-tumor acitivity in present unique biophysical analytical challenges, Therapy of solid tumors continues to be a major Registration & Pricing BRCA mutant tumors. Furthermore, the combination and as a case study, the biophysical characterization challenge. We have been developing several was better tolerated than monotherapy, indicating an of a cysteine-conjugated ADC with a drug-to- antibody-drug conjugates (ADCs) to solid tumors improved therapeutic index. antibody ratio of 8 will be presented. CHI-PepTalk.com CHI-PepTalk.com | 22 FINAL WEEKS JANUARY 9-10 | 5TH ANNUAL ANTIBODY TO REGISTER Antibody-Drug Conjugates THERAPEUTICS Engineering for Clinical Success Cover

Sponsors including lung, colon and breast cancer, and Carolin Sellmann, Ph.D., Scientist, Protein Engineering glucocorticoid (GC) conjugates selectively delivered Event-at-a-Glance neuroblastoma. The ADCs were generated by and Antibody Technologies, Merck KGaA GCs to Ag+ cells with > 500-fold selectivity over site-specific conjugation through glycans and Therapies targeting EGFR often suffer from toxicities non-target cells in vitro, and demonstrated excellent conjugated to PBD dimers. They were tested in due to basal EGFR expression in normal tissue and stability in vivo. Specifically delivering GCs to disease- vitro and in mouse models and showed promise for may face limited efficacy through c-MET activation. affected cells via an ADC could potentially reduce the further evaluation in humans. Potential problems Hence, we aim to construct bispecific EGFR x c-MET systemic side effects of non-targeted GC therapy. related to toxicity and efficacy will be discussed. antibodies employing affinity-optimized binding moieties to balance both high selectivity and anti- 2:35 HydraSpace Technology: A Versatile 9:35 Accelerate Development of tumor efficacy and to evaluate their potential for an Ionic Spacer to Further Empower Glycan- Bioconjugates innovative antibody-drug conjugate approach. Conjugated (GlycoConnect) Antibody-Drug Tyler Gable, Ph.D., Technology and Application Conjugates Consultant, Bio and Reaction Engineering, METTLER 11:50 Development and Optimization of Floris Van Delft, Ph.D., Founder & CSO, SynAffix BV TOLEDO AUTOCHEM Antibody-Drug Conjugates Armed with DNA Conjugation and spacer technology constitute key Rapid, reproducible, and data-rich process Damaging Payloads components of antibody-drug conjugates (ADCs). understanding Design of Experiment (DoE) can Julia Gavrilyuk, Ph.D., Principal Research Scientist, We here demonstrate that manufacturability and achieve accelerated process development of Chemistry Lead, Discovery Chemistry, Abbvie stability of our “GlycoConnect” technology, based antibody and protein-conjugates. Gain confidence in StemcentRx, Inc. on site-specific conjugation of payload through the the precise control of drug substance process with Highly potent DNA damaging payloads present native glycan, is further enhanced by a novel spacer repeatable reactions under reproducible conditions. unique challenges in prediction of corresponding technology (“HydraSpace”). Moreover, head-to- Examine two recent industry case studies utilizing ADCs in vivo efficacy and toxicological profile head in vivo assessment versus all main-stream automated bioconjugate workstations to eliminate based on limited in vitro evaluation. Unexpected conjugation technologies, including based on process induced aggregates, improve product experimental findings in the course of cysteine engineering, indicate a major improvement distribution and monomeric drug substance development and optimization of calicheamicin in pharmacokinetics, efficacy and safety, hence composition, optimize raw material consumption, and pyrrolobenzodiazepine based ADCs will be significantly enhanced therapeutic index. efficiency and reduce overall process time. presented. 3:05 Refreshment Break in the Exhibit Hall 10:05 Coffee Break in the Exhibit Hall with 12:20 pm Sponsored Presentation with Poster Viewing Poster Viewing (Opportunity Available) OVERCOMING PRODUCTION INNOVATING LINKER & PAYLOAD 12:50 Session Break CHALLENGES TECHNOLOGIES 1:00 Luncheon Presentation (Sponsorship 4:00 Early and Late-Stage Development and 10:50 Understanding Stability of ADCs Opportunity Available) or Enjoy Lunch on Your Own Manufacturing Challenges for ADCs Utilizing Deconjugation of Small Molecule Robert Herbst, Ph.D., Director, Process Development Drugs and Engineering, ImmunoGen, Inc. Colin Medley, Ph.D., Senior Scientist, Small Molecule SITE-SPECIFIC CONJUGATION By Cambridge Healthtech Institute Pharmaceutical Sciences, Genentech, Inc. 2:00 Chairperson’s Remarks 4:30 Strategy to Advance ARX788 ADC from Development to Clinical Manufacturing This presentation will highlight our recent efforts Julia Gavrilyuk, Ph.D., Principal Research Scientist, to use deconjugation of the payload of ADCs to Chemistry Lead, Discovery Chemistry, Abbvie Yun Bai, Ph.D., Director, Ambrx, Inc. SHORT COURSES better understand the stability and degradation StemcentRx, Inc. ADC technology transfer and manufacturing can be pathways for the linker drug portion of ADCs. We very challenging, especially for CMOs in a different have developed methods of enzymatic and chemical 2:05 Optimized Site-Specific Antibody- country with different cGMP and clinical filing deconjugation that have proved effective for Glucocorticoid Conjugation for Targeted regulations. This presentation will focus on various analyzing ADCs comprised of different linker drugs Sponsorship Opportunities Delivery of Novel Glucocorticoids to Ag+ Cells strategies used in ARX788 ADC technology transfer and different antibodies. Amy Han, Ph.D., Director, Chemistry, Regeneron project for multi-country clinical filing. Hotel/Additional Information 11:20 Balancing Selectivity and Efficacy of Pharmaceuticals Bispecific EGFR x c-MET Antibodies and We optimized transglutaminase-mediated site- Registration & Pricing Antibody-Drug Conjugates specific conjugations, and our site-specific antibody

CHI-PepTalk.com CHI-PepTalk.com | 23 FINAL WEEKS JANUARY 9-10 | 5TH ANNUAL ANTIBODY TO REGISTER Antibody-Drug Conjugates THERAPEUTICS Engineering for Clinical Success Cover

Sponsors 5:00 Blocking Salt Release with Precision Event-at-a-Glance James R. Prudent, Ph.D., President & CEO, Centrose LLC Extracellular drug conjugates (EDCs) act at the cell surface, do not internalize and do not release free drug. This talk will describe anti-cancer EDCs that induce irreversible cell swelling. Swelling is a highly evolved system that induces stress, disrupts gradients, and activates the immune system. This talk will discuss how triggered irreversible swelling can be induced in a cancer specific manner and why this is important.

5:30 - 6:45 Networking Reception in the Exhibit Hall with Poster Viewing 6:45 Close of Antibody-Drug Conjugates Conference

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 24 FINAL WEEKS JANUARY 11-12 | 7TH ANNUAL ANTIBODY TO REGISTER Bispecific Antibody Therapeutics THERAPEUTICS Engineering Multi-Specificity Cover

Sponsors The Seventh Annual Bispecific Antibody Therapeutics conference explores the challenges of engineering multi-specificity to achieve more effective therapies that Event-at-a-Glance bind to at least two molecular targets simultaneously. These next-generation antibody formats are showing efficacy in the efforts to conquer cancer and other diseases. Case studies will highlight novel engineering approaches that address safety, stability, enhanced targeting, and manufacturability, as well as breakthrough development technologies and strategies.

THURSDAY, JANUARY 11 on how the development processes were adapted constructs can provide significant advantages for to deliver these new format molecules in the best use in cancer immunotherapy. However, as highly 7:45 am Registration and Morning Coffee quality and quantity for clinical studies. engineered molecules they pose new design, engineering, cloning, expression, purification, and CREATING NEXT-GENERATION 9:30 Engineering IgM CH2 Domain as a analytics challenges. Genedata Biologics enables Versatile Building Block for the Construction the automated design, screening, production, THERAPIES of Various Multi-Specific Antibodies and testing of large panels of these candidate therapeutic molecules and includes built-in tools for 8:15 Chairperson’s Opening Remarks Jijie Gu, Ph.D., Research Fellow and Function Head, Immunology Discovery, AbbVie Bioresearch Center developability and manufacturability assessments. David E. Szymkowski, Ph.D., Vice President, Cell Biology, Xencor, Inc. Multi-specific antibodies hold great promise as one 12:00 pm Session Break of the approaches for developing next generation antibody-based therapeutics. We engineered IgM2 12:15 Luncheon Presentation (Sponsorship KEYNOTE PRESENTATION CH2 domain from a homodimeric domain to a CH1/ Opportunity Available) or Enjoy Lunch on Your CK like heterodimeric domain. Engineered IgM CH2 8:20 The Rise of Bispecific Antibodies as Own domain can be used as a versatile building block for Drugs the construction of various multi-specific antibody 1:15 Ice Cream Break in the Exhibit Hall with Paul J. Carter, Ph.D., Staff Scientist and Senior formats to enable various novel therapeutic concepts. Poster Viewing Director, Antibody Engineering, Genentech, Inc. 10:00 Coffee Break in the Exhibit Hall with Bispecific antibodies are emerging as FIGHTING CANCER drugs with two such molecules approved Poster Viewing for human therapy and over 50 more in 11:00 Tailoring Processing of Amyloid 2:00 Chairperson’s Remarks clinical development. We developed a robust Precursor Protein as a Therapeutic for Eric Smith, Ph.D., Director, Bispecific Antibdies, method for production of bispecific IgG in Regeneron Pharmaceuticals, Inc. single mammalian host cells to support Alzheimer’s Disease the clinical development of these complex Michael Sierks, Ph.D., Professor, Chemical hetero-tetrameric molecules. Additionally, we Engineering, Arizona State University FEATURED PRESENTATION established high-resolution mass spectrometry Generation of beta-amyloid from the amyloid methods to facilitate the characterization and precursor protein is a key step in the progression of 2:05 Non-Engineered Multi-Specific quantitation of bispecific antibodies and other Alzheimer’s disease. We have designed a bispecific Antibodies complex biologics. antibody that inhibits toxic amyloidogenic processing Marie Kosco-Vilbois, Ph.D., CSO, NovImmune SA of the amyloid precursor protein while simultaneously By Cambridge Healthtech Institute catalyzing formation of a neuroprotective fragment. The κλ body continues to embody an innovative 9:00 Examples of Development Strategies for We show that the bispecific antibody provides design to incorporate multi-specificity into a human Next-Generation Therapeutics excellent therapeutic benefit in a mouse model of AD. framework devoid of any mutation, foreign sequences or linkers. κλ bodies exploit light chain diversity, SHORT COURSES Nicola Beaucamp, Ph.D., Head, Process Research, 11:30 Design and Evaluation of Next- conferring different specificities into >1500 targeting Pharma Research and Early Development, Roche arms directed against >15 targets. The format’s Innovation Center Munich, Roche Diagnostics GmbH Generation Biologics for Cancer Immunotherapy simplicity makes manufacturing from research to A number of novel antibody formats have been clinical easily scalable and ensures high purity and Sponsorship Opportunities advanced into the clinic by Roche pRED. In order Christopher Smith, Ph.D., Senior Scientific Consultant, stability. The first κλ bodies are designed to exploit to discover and develop differentiated monoclonal Biologics, Genedata the innate immune checkpoint, CD47, safely yet Hotel/Additional Information antibodies, Roche’s strategy is based on engineering Bi- and multi-specific antibodies, Ab-cytokine fusion effectively, by targeting phagocytosis of cancer cells technologies which bear several challenges for proteins, non-Ig scaffolds, chimeric antigen receptors specifically to B cell malignancies and solid tumors. Registration & Pricing technical development. Examples will be presented (CARs), engineered TCRs and TCR-based bispecific

CHI-PepTalk.com CHI-PepTalk.com | 25 FINAL WEEKS JANUARY 11-12 | 7TH ANNUAL ANTIBODY TO REGISTER Bispecific Antibody Therapeutics THERAPEUTICS Engineering Multi-Specificity Cover

Sponsors 2:35 Bispecific Antibodies for Dual Immune 5:15 The Benefits of Bispecific mAb2 ENGINEERING IMPROVED Event-at-a-Glance Checkpoint Blockade Antibodies Targeting EGFR and HGF PROPERTIES WITH NEXT-GEN David E. Szymkowski, Ph.D., Vice President, Cell Kin-Mei Leung, Ph.D., Principal Scientist, Drug Biology, Xencor, Inc. Discovery, F-star Biotechnology, Ltd. TECHNOLOGIES TM Combinations of checkpoint-blocking antibodies are F-star’s Modular Antibody Technology platform 9:00 Chairperson’s Remarks more efficacious then single inhibitors, but generate was utilized to generate bispecific molecules that Marie Kosco-Vilbois, Ph.D., CSO, NovImmune SA greater immune-related toxicities. We reasoned that bind to Epidermal Growth Factor Receptor (EGFR) a bispecific antibody could achieve dual blockade and Hepatocyte Growth Factor (HGF). The EGFR/ 9:05 Identification and Quantitation of 2 to selectively target tumor-reactive lymphocytes, HGF mAb inhibit cell proliferation in vitro and show DuoBody Bispecific IgG1 Using Mass improving safety and efficacy. We generated anti-tumor activity in patient-derived xenograft (PDX) Spectrometry and Automated Data multiple dual-checkpoint inhibitors including models in vivo. The mAb2 molecules show superior XmAb20717 (anti-PD1 x anti-CTLA4) that display inhibition of tumor growth compared to combination Processing and Analysis Workflow compelling in vivo activity relative to combinations treatments in tumors with specific molecular profiles Ewald Van den Bremer, Ph.D., Senior Scientist, of monospecific antibodies, suggesting that suggesting novel biology of the bispecific. Genmab A/S checkpoint bispecifics may have clinical advantages The characterization of bispecific antibodies for the treatment of cancer. 5:45 Close of Day (BsAbs) by mass spectrometry (MS) offers several advantages over traditional chromatographic 3:05 Sponsored Presentation (Opportunity FRIDAY, JANUARY 12 techniques (e.g. HIC, CEX). MS provides Available) unambiguous identification and relevant quantitative 8:00 am Registration information, and combined with automated data 3:35 Refreshment Break in the Exhibit Hall processing and analysis, it can be employed in a with Poster Viewing high-throughput environment. We present a software 8:00 BuzZ Sessions with Continental solution and the related workflows that enabled us 4:15 Development of T Cell Redirecting Fully Breakfast to accelerate BsAb research batch characterization Human Bispecific Antibodies and release, achieving high quality results and Eric Smith, Ph.D., Director, Bispecific Antibodies, Protein therapeutics is a fast-growing significant time and cost savings. Regeneron Pharmaceuticals, Inc. global market. As the science improves, so does the complexity of the R&D This presentation will describe Regeneron’s 9:35 bisFabs: Tools for Rapidly Screening organization. Ensuring product quality bispecific platform and present preclinical data on Hybridoma IgGs for Their Activities as plus speed to market requires insights from T cell redirecting bispecifics being developed for Bispecific Antibodies stakeholders working across the stages of protein solid tumor indications. In addition, a brief update science R&D. Join experts representing this PepTalk Bushra Husain, Ph.D., Senior Scientific Researcher, on the status of REGN1979, Regeneron’s CD20xCD3 pipeline, peers, and colleagues for an interactive Genentech, Inc. bispecific in Phase I clinical trials, will be presented. roundtable discussion. Topics include highlights Bispecific antibodies enable therapeutics with novel mechanisms of actions. To expedite the screening 4:45 Co-Stimulation of Immune Cells in the from the week’s presentations, new technologies and strategies, challenges, and future trends. of hybridoma clones for their potential as bispecific Tumor Microenvironment via Bispecific DART antibodies, we developed procedures to chemically Table Moderator: Nicola Beaucamp, Ph.D., Head, By Cambridge Healthtech Institute and TRIDENT Molecules crosslink Fabs obtained from hybridomas with Process Research, Pharma Research and Early Gundo Diedrich, Ph.D., Associate Director, Antibody different isotypes. The resulting crosslinked F(ab’)2s Development, Roche Innovation Center Munich, Engineering, MacroGenics, Inc. (bisFabs) were compared for their biological Roche Diagnostics GmbH SHORT COURSES Targeting costimulatory receptors on immune cells activities to the counterpart molecules reformatted with agonistic antibodies is a promising strategy into the full-length IgG. Results showed bisFabs and in cancer therapy. To limit the immune activity to full-length IgGs had comparable activities, validating tumors, while sparing effects on normal tissue, we the predictive value of bisFabs. generated bispecific DART and TRIDENT molecules Sponsorship Opportunities targeting several tumor antigens together with the costimulatory receptor, CD137. T cell agonistic Hotel/Additional Information activity by these molecules was strictly dependent on the expression of the tumor antigens. Preclinical Registration & Pricing development of these proteins will be addressed.

CHI-PepTalk.com CHI-PepTalk.com | 26 FINAL WEEKS JANUARY 11-12 | 7TH ANNUAL ANTIBODY TO REGISTER Bispecific Antibody Therapeutics THERAPEUTICS Engineering Multi-Specificity Cover

Sponsors 10:05 From the Bench to the Clinic: better than corresponding IgG’s. Moreover, it shows T Event-at-a-Glance Developing Next-Generation ADAPTIR cell dependent cytotoxicity even on cells with very low Molecules cell surface expression of CD20 (Namalwa). David Bienvenue, Senior Director, Protein Sciences, 11:45 A Novel Trifunctional Antibody Aptevo Therapeutics Combining PD-1/PD-L1 Blockade and The presentation will highlight the activity, stability Targeting of a Tumor-Specific Carbohydrate and manufacturability of ADAPTIR bispecifics and will include recent data for a lead preclinical Antigen candidate, APVO436, which targets CD123 and CD3. Christoph Goletz, Associate Director, APVO436 has shown potent biological activity in Immunomodulation, Glycotope GmbH preclinical studies and is rapidly advancing towards We developed a trifunctional antibody combining first-in-human clinical trials. PD-1/PD-L1 blocking and highly tumor-specific targeting via the novel protein/carbohydrate mixed 10:35 Coffee Break with a Poster Pavilion epitope TA-MUC1 with a functional Fc part in one See page 4 for details molecule. By focusing the checkpoint blockade to the tumor and combining multiple modes of action, that 11:15 An IgM-Based Bispecific Platform for antibody has the potential to increase efficacy and Enhanced T Cell and Complement Dependent broaden the patient coverage giving additional benefit Cytotoxicity on Low Antigen Expressing Cells compared to the respective monospecific antibody. Ramesh Baliga, Ph.D., Vice President, Discovery Biology, IGM Biosciences 12:15 pm Conference Wrap-Up IGM Biosciences has built a unique bispecific Nicola Beaucamp, Ph.D., Head, Process Research, platform based on a CD3 epsilon binding single chain Pharma Research and Early Development, Roche Fv domain fused to the IgM joining chain. Our CD20 Innovation Center Munich, Roche Diagnostics GmbH targeted IgM bispecific antibody IGM-2323 binds CD20 antigen greater than 1000X better, and shows functional effects such as CDC greater than 100X 12:45 Close of Conference

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 27 FINAL WEEKS TO REGISTER

Cover

Sponsors Event-at-a-Glance INNOVATIONS IN DISCOVERY & DEVELOPMENT

JANUARY 8-9 AGENDA Advancing CNS Biotherapeutics and Crossing the Blood-Brain Barrier

JANUARY 9-10 AGENDA Next-Generation Approaches to Antibody Screening and Discovery TRAINING SEMINAR

JANUARY 11-12 AGENDA Emerging Technologies for Antibody Discovery

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 28 INNOVATIONS IN FINAL WEEKS JANUARY 8-9 | INAUGURAL DISCOVERY & TO REGISTER Advancing CNS Biotherapeutics and Crossing the DEVELOPMENT Blood-Brain Barrier Innovation, New Targets, Tools, Delivery and New Research Updates Cover

Sponsors CHI’s Inaugural Advancing CNS Biotherapeutics and Crossing the Blood-Brain Barrier conference strives to bring you the hottest topics and biggest opportunities in discovering and developing highly efficacious therapeutic agents against CNS disorders and innovative strategies for delivering therapies across the blood- Event-at-a-Glance brain barrier (BBB). This new meeting will brainstorm ideas and share new research on topics such as the biologics for CNS targets and biomarkers, brain cancer, neurodegeneration, neuroinflammation, neuroimmunology, alteration of CNS/BBB barriers due to injury or disease, preclinical models, neuroimaging, tools for prediction of brain penetration, and updates from the industry.

SUNDAY, JANUARY 7 notable advance in vascular tissue engineering by 11:45 PANEL DISCUSSION: Challenges and generating the first functional 3- dimensioinal model of Opportunities in Discovery and Development 4:00 - 6:00 pm Pre-Conference Registration CAA in bioengineered human vessels. We show that of New CNS and BBB Therapies lipoproteins including brain (apoE) and circulating (high- Moderator: density lipoprotein) synergize to facilitate Aβ transport MONDAY, JANUARY 8 Lois A. Lampson, Ph.D., Emeritus Associate across bioengineered human cerebral vessels. These Professor of Neurosurgery, Brigham & Women’s lipoproteins facilitate Aβ42 transport more efficiently 7:00 am Registration and Morning Coffee Hospital/Harvard Medical School than Aβ40, consistent with Aβ40 being the primary species that accumulates in CAA. Moreover, apoE4 is Panelists: CONSIDERATIONS FOR DISCOVERY less effective than apoE2 in promoting Aβ transport, Per-Ola Freskgard, Ph.D., Vice Director and Senior AND DEVELOPMENT FOR CNS AND also consistent with the well-established role of apoE4 Leader, Neuroscience, Roche Innovation Center Basel, BBB THERAPIES in Aβ deposition in AD. F. Hoffmann-La Roche Ltd. Robert D. Bell, Ph.D., Senior Principal Scientist, 9:00 Welcome by Conference Organizer 10:20 Networking Coffee Break Neurovascular Biology Lab Head, Pfizer, Inc. Nandini Kashyap, Conference Director, Cambridge 10:45 Biologics That Already Benefit the Servio Ramirez, Ph.D., Associate Professor, Pathology Healthtech Institute Brain: Lessons, Mysteries, Surprises and Laboratory Medicine, Lewis Katz School of Medicine, Temple University 9:05 Chairperson’s Opening Remarks Lois A. Lampson, Ph.D., Emeritus Associate Per-Ola Freskgard, Ph.D., Vice Director and Senior Professor of Neurosurgery, Brigham & Women’s 12:15 pm Sponsored Presentation Leader, Neuroscience, Roche Innovation Center Basel, Hospital/Harvard Medical School (Opportunity Available) F. Hoffmann-La Roche Ltd. Biologics that already benefit the brain include 12:45 Session Break monoclonal antibodies for MS, brain metastases, and models of AD and other tauopathies. Lessons 1:00 Luncheon Presentation (Sponsorship KEYNOTE PRESENTATION include the value of indirect effects, often involving Opportunity Available) or Enjoy Lunch on Your Own 9:10 Efficient and Safe Biologics for migratory cells, with the antibody itself not crossing Diseases of CNS the BBB. Mysteries include the final effector DRUG DELIVERY AND MOLECULAR Per-Ola Freskgard, Ph.D., Vice Director and mechanism, and the state and role of the BBB. TRANSPORT ACROSS BBB Senior Leader, Neuroscience, Roche Innovation Surprises include unorthodox specificities, such as Center Basel, F. Hoffmann-La Roche Ltd. anti-tumor antibodies that also attack normal cells. 2:00 Chairperson’s Remarks 11:15 New Targets and Biomarkers for CNS Torben Moos, M.D., Ph.D., DMSc, Professor, Medicine and Health Technology, Aalborg University 9:50 Clearance of Beta-amyloid is Facilitated Disorders and Diseases By Cambridge Healthtech Institute by Apolipoprotein E and Circulating High- Servio Ramirez, Ph.D., Associate Professor, Pathology 2:05 Brain Penetrating IgG Fusion Proteins: density Lipoproteins in Bioengineered Human and Laboratory Medicine, Lewis Katz School of From Genetic Engineering to Clinical Trials in Medicine, Temple University Vessels Lysosomal Storage Disorders Extracellular microvesicles (EVs) have emerged as Ruben Boado, Ph.D., Vice President, Research & Jerome Robert, PhD, Pathology and Laboratory SHORT COURSES a novel biological phenomenon, released by virtually Development/Co-Founder, ArmaGen, Inc. Medicine, Djavad Mowafaghian Centre for Brain every cell type in the body. We have identified that Lysosomal enzymes, such as iduronase (IDUA) and Health, University of British Columbia brain endothelial derived EVs contain key constituents sulfatases, are large molecule drugs that do not cross Amyloid plaques, consisting of deposited beta- of the BBB. Our recent discoveries suggest that BBB the blood-brain barrier (BBB). The BBB-penetration of Sponsorship Opportunities amyloid (Aβ), are a neuropathological hallmark of de-stabilization during neuroinflammation triggers enzyme therapeutics is enabled by re-engineering the Alzheimer’s Disease (AD). Cerebral vessels play a brain endothelial EV release which facilitates BBB recombinant enzyme as bi-functional IgG fusion proteins, Hotel/Additional Information major role in AD, as Aβ is cleared from the brain by breach. Thus, I will introduce concepts that could help wherein the IgG domain targets a specific endogenous pathways involving the cerebrovasculature, most us understand EV significance in vascular remodeling receptor-mediated transporter system within the BBB, Registration & Pricing AD patients have cerebrovascular amyloid (cerebral and utility as biomarkers. such as the human insulin receptor (HIR). The enzyme amyloid angiopathy (CAA), and cardiovascular risk factors increase dementia risk. Here we present a CHI-PepTalk.com CHI-PepTalk.com | 29 INNOVATIONS IN FINAL WEEKS JANUARY 8-9 | INAUGURAL DISCOVERY & TO REGISTER Advancing CNS Biotherapeutics and Crossing the DEVELOPMENT Blood-Brain Barrier Innovation, New Targets, Tools, Delivery and New Research Updates Cover

Sponsors therapeutic domain of the fusion protein exerts the 5:00 Development of Highly Efficient BBB TUESDAY, JANUARY 9 Event-at-a-Glance pharmacological effect in brain once across the BBB. Transport of Antibodies to the CNS Using in Several brain penetrating IgG-LSD fusion proteins have vivo Phage Display with Single Domain VNAR 8:00 am Registration and Morning Coffee been engineered and validated. First in human proof of to the Transferrin Receptor concept Phase II clinical trial in LSD is in progress. IMAGING, PRECLINICAL TOOLS, Frank S. Walsh, Ph.D., CEO, Ossianix 2:35 Deliverable Biologics at the Blood-Brain Antibody-based molecules do not cross the BBB in MODELS AND TRANSLATIONS Barrier amounts required for therapeutic efficacy. Receptor- STRATEGIES Torben Moos, M.D., Ph.D., DMSc, Professor, Medicine mediated transporters in the luminal membrane 8:30 Chairperson’s Remarks and Health Technology, Aalborg University of brain capillary endothelium offer an approach Miroslaw Janowski, M.D., Ph.D., Associate Professor, for the delivery of therapeutics to the brain. Using My presentation will cover the concepts of the blood- Radiology, Johns Hopkins University brain barrier (BBB) with emphasis on macromolecular a combination of in vitro and in vivo phage display transport. I will cover the restraints and probable technology, we isolated a panel of cross species 8:35 Extremely Fast Clinical MRI for avenues for transport of biologics through the BBB. I will binders to the transferrin receptor 1 (TfR1) from Predicting and Real-Time Monitoring of Intra- place emphasis on transport of proteins with therapeutic synthetic single domain VNAR libraries. At therapeutic Arterial Opening of the Blood-Brain Barrier potential. This will include targeted uptake at the BBB, (2 mg/kg) doses delivered by tail vein injection, high Miroslaw Janowski, M.D., Ph.D., Associate Professor, the potential of induced gene therapy to the BBB, and levels (>5% brain/plasma ratio) of the bispecific Radiology, Johns Hopkins University antibodies were found in the brain after 18 hours. hypotheses on further release of biologics into the brain. MRI guidance enables opening of the blood-brain barrier (BBB) using intra-arterial route in a predicted and precise 3:05 Transition to BuzZ Sessions 5:30 Blood-Brain Barrier Penetrating Dual Specific Binding Proteins for Treating Brain fashion. However, the monitoring of the process of BBB and Neurological Diseases opening was difficult, as the real-time EPI MRI pulse sequence was not capable of visualizing the marker of 3:15 BuzZ Sessions with Refreshments Kangwen Deng, Ph.D., Senior Scientist, Biologics, AbbVie BBB permeability. Here, we show that extreme speed Join your peers and colleagues for Blood-brain barrier (BBB), which consists mainly of MRI reconstruction using the new GPU set-up allows interactive roundtable discussions. of specialized brain capillary endothelial cells, is a turning other pulse sequences into real-time mode and Please see page 78 for additional information. physical and physiological barrier that controls very visualize the process of BBB opening. efficiently and selectively the entry of compounds from blood into the CNS, and protects nervous tissue from 4:30 Delivery across the BBB, Utilizing Single- 9:05 Nanobodies to Cross the Blood-Brain harmful substances and infectious agents present in Barrier Domain Antibodies and a New Receptor- circulating blood. While naturally protective, the BBB Mediated Transcytosis Pathway Yessica Wouters, Researcher, VIB & KU Leuven Center provides a challenge for drug development as most of for Brain & Disease Research Kristin Kemmerich, Ph.D., Head, Antibody Generation the small organic molecule drugs and nearly all biologic Section, National Research Council Canada therapeutics do not cross the BBB to therapeutically 9:35 Sponsored Presentation (Opportunity The blood-brain barrier (BBB) regulates brain relevant concentrations. Here, we will describe the Available) homeostasis and provides protection against generation and expression of DVD-Ig proteins which pathogens and other molecules, but it also restricts are capable of binding specific disease targets in the 9:50 Coffee Break in the Exhibit Hall with brain. The levels and localization of DVD-Ig proteins, Poster Viewing By Cambridge Healthtech Institute the effective delivery of biotherapeutics into the CNS. Here we characterize an unexplored receptor-mediated which were injected systemically, were assessed by transcytosis pathway to deliver biologics to the brain. two orthogonal methods. Results showing the uptake, We developed specific single-domain antibodies that retention as well as the elevated functional activity of SHORT COURSES can carry payload across the BBB and assessed these DVD-Ig proteins in the brain will be demonstrated. in vitro and in vivo to allow for PK/PD modeling. 6:00 - 7:15 Welcome Reception Sponsored by in the Exhibit Hall with Poster Sponsorship Opportunities Viewing 7:15 Close of Day Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 30 INNOVATIONS IN FINAL WEEKS JANUARY 8-9 | INAUGURAL DISCOVERY & TO REGISTER Advancing CNS Biotherapeutics and Crossing the DEVELOPMENT Blood-Brain Barrier Innovation, New Targets, Tools, Delivery and New Research Updates Cover

Sponsors 11:00 The Blood Meningeal Barrier Event-at-a-Glance (BMB) Orchestrates the Development of Neuroinflammatory Responses Jorge Iván Alvarez, Ph.D., Assistant Professor, Department of Pathobiology, University of Pennsylvania To address how CNS endothelium drives neuroinflammation, we established a novel human model of the BMB and BBB. We found that the BMB immunological fingerprint induces a proinflammatory phenotype on migrating lymphocytes and promotes B cell aggregates that mirror their distribution within the meningeal compartment during multiple sclerosis. Our findings highlight the heterogeneity of the CNS vascular beds, how they regulate leukocyte function and demonstrate that the BMB niche is more conducive to promote neuroinflammation. 11:30 Intranasal Administration as a Method to Target Therapeutics to the CNS Jeffrey Lochhead, Ph.D., Research Assistant Professor, Department of Pharmacology, University of Arizona 12:00 pm Sponsored Presentation (Opportunity Available) 12:30 Session Break 12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own 1:15 Close of Advancing CNS Biotherapeutics and Crossing the Blood-Brain Barrier Conference

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 31 FINAL INNOVATIONS IN WEEKS JANUARY 9-10 | INAUGURAL DISCOVERY & TO REGISTER Next-Generation Approaches to Antibody DEVELOPMENT Screening and Discovery TRAINING SEMINAR Cover

Sponsors

Event-at-a-Glance TUESDAY, JANUARY 9 - WEDNESDAY, JANUARY 10 By Cambridge Healthtech Institute —DAY 1 - 2:00 - 5:30 PM | DAY 2 - 8:30 AM - 5:30 PM

Instructor: David Bramhill, Ph.D., Founder, Bramhill Biological Consulting, LLC

Over the space of a few years, a series of technologies have improved greatly in both capability and affordability, and have been adapted to enhance the discovery and development of antibodies and other immunotherapies. Among these technologies, DNA sequencing and data analysis, DNA synthesis, single-cell isolation, and genome engineering using CRISPR/Cas9 combine to give significant advances in how we can engineer antibodies and cell lines. This training seminar will evaluate these new developments and their applications in antibody and immunotherapy discovery and development.

Attendees will learn about: • “Next-Generation Sequencing” of DNA - new capabilities, torrents and pores • DNA sequencing applied to single cells and entire immune responses • Data analysis of whole population responses to immunogen/vaccine • Cell sorting and other direct isolation-selection of B cells • Protein level antibody sequencing capabilities • Application of new insights to humanization and engineering of IgG • CRISPR/Cas9 applied to engineer libraries and cell lines

INSTRUCTOR BIOGRAPHY

By Cambridge Healthtech Institute David Bramhill, Ph.D., Founder, Bramhill Biological Consulting, LLC Dr. Bramhill has over 20 years’ experience in biologics, both in large biopharma and startup biotech companies. He has experience in isolating and improving antibodies using phage display and is SHORT COURSES an inventor of library design techniques for small scaffolds. He also has experience in diverse expression systems for producing antibodies, antibody fragments and different scaffolds. He has taught numerous technical courses for over 10 years at international conferences. Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 32 FINAL INNOVATIONS IN WEEKS JANUARY 11-12 | 3RD ANNUAL DISCOVERY & TO REGISTER Emerging Technologies for Antibody Discovery DEVELOPMENT Exploring the Intersection of Display Technologies, Next-Generation Sequencing and Informatics Cover for the Discovery of Next-Generation Biotherapeutics

THURSDAY, JANUARY 11 9:30 Phage-Displayed Ubiquitin Variant (UbV) share the success experiences, examine common Libraries to Rapidly Identify Potent and Highly mistakes novices make, and present our practices to 7:45 am Registration and Morning Coffee Selective Protein-Based Inhibitors Targeting ensure the correctness of every amino acid. E3 Ligases and Deubiquitinases 8:15 Chairperson’s Opening Remarks 12:00 pm Session Break Wei Zhang, Ph.D., Mitacs Elevate Fellow, University of Andrew Bradbury, Ph.D., CSCO, Specifica, Inc. Sponsored by Toronto, Canada 12:15 Luncheon Presentation I: E3 ligases and deubiquitinases regulate diverse Next-Generation Capillary KEYNOTE PRESENTATION cellular processes and are implicated in numerous Electrophoresis Technology for 8:20 Remodeling of Cell Surfaceomes in human diseases. However, targeting these enzymes Protein Analysis potently and specifically remains a big challenge. Cancer Wei-Chiang Chen, Ph.D., Scientist, Analytical We thus devised a screening platform to develop Development, Biogen James A. Wells, Ph.D., Professor, protein-based modulators for ubiquitin proteasome Recombinant adeno-associated virus (AAV) is a Pharmaceutical Chemistry, University of system components. I will report how we design the promising platform in human gene therapy. AAV California, San Francisco ubiquitin variant (UbV) library to generate inhibitors vectors contain a protein outer shell called capsid, The cell surface proteome (surfaceome) is and activators for E3 ligases (RING and HECT which is comprised of 60 subunits containing three the primary hub for cells to communicate with family) and deubiquitinases (viral and human origin). viral proteins. To confirm the purity of the AAV the outside world. My lab studies how the capsids, we developed a CE-SDS method on the surfaceome is remodeled in cancer. We find 10:00 Coffee Break in the Exhibit Hall with Maurice platform, which automates analysis of 96 the new set of proteins promote enhanced Poster Viewing samples in one batch. This assay demonstrates cell growth and detachment from native 11:00 Efficient B Cell Cloning and Antibody good separation of viral proteins (LOQ at 5e11 vg/ tissues allowing metastasis. Our primary goal Engineering Platform for Rare Ab Generation ml), and comparable results with SDS-PAGE gels. is to systematically understand how cancer cells remodel their membrane proteomes Feng Shu, Ph.D., Senior Researcher, Chugai 12:45 Presentation to be Announced (surfaceomes) during cancer transformation and Pharmabody Research, Singapore develop antibodies to detect and attack them. Here we describe a high throughput antibody 1:15 Ice Cream Break in the Exhibit Hall with identification system by single B cell cloning, Poster Viewing which can generate and evaluate a large number FUNCTIONAL SCREENING of antibodies with high diversity to identify the rare ADVANCES IN DISPLAY antibodies with required properties such as pH 9:00 Combining Screening with Phenotypic dependency. A robust antibody engineering system TECHNOLOGIES AND LIBRARY By Cambridge Healthtech Institute Selection in Antibody Phage Display is also introduced, where thousands of antibodies DESIGN with designed mutations can be generated and Marcin Paduch, Ph.D., Pipeline Director, Recombinant 2:00 Chairperson’s Remarks Antibody Network, University of Chicago evaluated in 2 weeks’ time to further accelerate the Nicolas Fischer, Ph.D., Head, Research, Novimmune State-of-the-art methods for generating recombinant antibody discovery process. SHORT COURSES Sponsored by SA, Switzerland antibodies do not necessarily allow for targeting the 11:30 Antibody Protein particular cellular phenotype posing a fundamental Sequencing with Mass 2:05 Enhancing the Chemical Versatility of challenge. A set of next generation high-throughput Spectrometry Yeast Display technologies that allow for phenotypic selection has Sponsorship Opportunities Mingjie Xie, MSc, MBA, CEO, Rapid Novor Inc James Van Deventer, Ph.D., Assistant Professor, to be developed. Intimate knowledge of conformation Chemical and Biological Engineering, Tufts University states and biochemistry of antigens can be exploited Hotel/Additional Information Many applications in antibody engineering require the We have established a version of yeast display to mimic native-like environments and create the direct sequencing of antibody proteins. At Rapid Novor that supports the integration of chemical groups possibility of trapping physiologically-relevant states Registration & Pricing (rapidnovor.com) we have developed a robust workflow into displayed proteins using noncanonical amino otherwise not accessible by current methods. and routinely sequenced antibody proteins. Here we acid incorporation. We are currently investigating CHI-PepTalk.com CHI-PepTalk.com | 33 FINAL INNOVATIONS IN WEEKS JANUARY 11-12 | 3RD ANNUAL DISCOVERY & TO REGISTER Emerging Technologies for Antibody Discovery DEVELOPMENT Exploring the Intersection of Display Technologies, Next-Generation Sequencing and Informatics Cover for the Discovery of Next-Generation Biotherapeutics

Sponsors strategies for positioning chemical groups within are typically generated with single chain variable Director, Recombinant Antibody Network, University Event-at-a-Glance antibodies in order to enhance and change the fragment (scFv) antibodies. In this study, we present of Chicago molecular recognition capabilities of these proteins. a human synthetic scFv antibody library that we use This talk will highlight our recent progress in to simplify the generation and testing of large panels constructing, evaluating, and screening “hybrid” of antibodies for use as CAR T cells. The CAR T structures with potential applications in the tumor cells generated from these antibodies had desirable INTEGRATED DISCOVERY microenvironment. phenotypes and demonstrated robust and specific PLATFORMS cytotoxic activity in vitro. 2:35 How Big Are Antibody Libraries Really? 9:00 Chairperson’s Remarks And Are We Accessing the Full Diversity? 5:15 Highly Multiplexed Cell Surfaceomics Sagar Kathuria, Ph.D., Senior Scientist, Protein Andrew Bradbury, Ph.D., CSO, Specifica, Inc. Using Genetically Barcoded Antibody-Phage Engineering, Sanofi Genzyme Samuel Pollock, Researcher, Pharmaceutical In vitro antibody libraries have been used to generate 9:05 Generation of Mono and Bispecific antibodies against many different therapeutic lead Chemistry, University of California, San Francisco Antibodies from Immunized Transgenic targets. Analyses indicate that one would expect to Cells express thousands of different surface select 1-3 antibodies from a 1e7 library. However, proteins that can be used for their classification. Rodents and the Potential to Engineer Multi- this does not appear to scale to larger libraries with We present a surface proteomic method using Specific Entities Using Common Light Chain diversities estimated to be >1 billion, suggesting genetically barcoded antibodies called Phage- Paratopes that libraries are less diverse than thought or antibody Next Generation Sequencing. We use Simon Krah, Ph.D., Senior Scientist, Protein Engineering selection methods do not tap the full diversity. This PhaNGS to reveal changes in surface protein and Antibody Technologies, Merck KGaA, Germany talk discusses the use of NGS to explore these abundance in the contexts of drug resistance, We demonstrate that by using Yeast Surface issues and the application of NGS to the creation of adaptation to oncogenes, and on the single-cell Display (YSD), a more effective coverage of the improved antibody libraries. level. Linking selective, genetically encoded binders antibody diversity generated during the course of to NGS enables direct, multiplexed protein detection, 3:05 Sponsored Presentation (Opportunity an immunization can be realized in comparison comparable to RNAseq for mRNA. to classical hybridoma technology. Moreover, we Available) show that bispecific antibodies can also be readily 5:45 Close of Day 3:35 Refreshment Break in the Exhibit Hall engineered via such YSD approaches in combination with the application of common light chains. In with Poster Viewing FRIDAY, JANUARY 12 addition, we established a methodology which 4:15 Dual Display Technology for “In Format” facilitates the tedious and time-consuming process Selection and Screening of Bispecific Antibodies 8:00 am Registration of YSD library generation. Nicolas Fischer, Ph.D., Head, Research, Novimmune 9:35 Discovery Platform for Antibody SA, Switzerland 8:00 BuzZ Sessions with Continental Generation and Screening for Different The desired biological activity of bispecific Breakfast Applications antibodies is often dependent on the adequate geometry of the two antibody binding sites, thus Protein therapeutics is a fast-growing Anne Marcil, Team Lead, Monoclonal Antibodies, requiring extensive combinatorial testing of isolated global market. As the science improves, National Research Council, Canada By Cambridge Healthtech Institute antibodies. Being able to evaluate candidates ‘in so does the complexity of the R&D The National Research Council of Canada has format’ as early as possible would greatly facilitate organization. Ensuring product quality a strong history in target discovery, antibody the development of bispecific antibodies. To achieve plus speed to market requires insights from generation and characterization, resulting in the SHORT COURSES that goal, we have developed methodologies stakeholders working across the stages of protein production of new antibodies against hundreds that allow ‘in format’ phage display selection and science R&D. Join experts representing this PepTalk of targets. An overview of our antibody discovery screening of candidates early in discovery. pipeline, peers, and colleagues for an interactive pipeline which includes bioinformatics and MS roundtable discussion. Topics include highlights analysis for target discovery, monoclonal, single- 4:45 Synthetic Human Antibody Fragment from the week’s presentations, new technologies domain and antibody library screening, in vitro Sponsorship Opportunities Libraries for CAR T Cell Therapy and strategies, challenges, and future trends. screening for function (ADCs, Blood-brain barrier crossers, electrophysiology, etc.) and in vivo Hotel/Additional Information Thomas J. Van Blarcom, Ph.D., Associate Research Table Moderator: James Van Deventer, Ph.D., Fellow, Rinat Laboratories, Oncology Research and Assistant Professor, Chemical and Biological screening will be presented. Registration & Pricing Development, Pfizer, Inc. Engineering, Tufts University Unlike most therapeutic antibodies, CAR T cells Table Moderator: Marcin Paduch, Ph.D., Pipeline

CHI-PepTalk.com CHI-PepTalk.com | 34 FINAL INNOVATIONS IN WEEKS JANUARY 11-12 | 3RD ANNUAL DISCOVERY & TO REGISTER Emerging Technologies for Antibody Discovery DEVELOPMENT Exploring the Intersection of Display Technologies, Next-Generation Sequencing and Informatics Cover for the Discovery of Next-Generation Biotherapeutics

Sponsors 10:05 A Patient-Centric Function F.I.R.S.T™ Selection and Potency Screening Event-at-a-Glance Approach to Cancer Immunotherapy Discovery Tianyi Wang, Ph.D., Scientist, R&D, Sorrento Björn Frendéus, Ph.D., CSO, Bioinvent, Sweden Therapeutics We have developed a patient-centric phenotypic This talk outlines applications of high content discovery approach (F.I.R.S.T) that utilizes primary confocal and cell-by-cell metrics for selection and cancer patients’ cells from the initial steps of isolating potency of antibodies with applications toward antibodies from a naïve human antibody library intracellular targets. 3D spheroids and high content through POC studies and subsequent identification confocal in vitro system are used to screen the of targeted receptors. A lead candidate which blocks phenotypic effects of selected intracellular-targeting FcgRIIB internalization and acts in synergy with antibodies. 3D spheroids, by mimicking tumor rituximab to boost responses and help overcome microenvironment, are a better predictor of clinical resistance in the background of emerging targeted potential of antibody therapeutics. Our method therapies as well as conventional chemotherapy in proposes multiparametric analyses of spheroids to vivo, is now in clinical phase testing. elucidate mechanism of action.

11:45 High Content Confocal for Antibody By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 35 FINAL WEEKS TO REGISTER

Cover

Sponsors Event-at-a-Glance FORMULATION & STABILITY

JANUARY 8-9 AGENDA Optimizing Biologics Formulation Development

JANUARY 9-10 AGENDA Lyophilization and Emerging Drying Technologies

JANUARY 11-12 AGENDA Protein Aggregation and Emerging Analytical Tools

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 36 FINAL JANUARY 8-9 | 10TH ANNUAL FORMULATION & WEEKS STABILITY TO REGISTER Optimizing Biologics Formulation Development A Best Practices Exchange for Resolving the Challenges of Formulating Cover Novel Biologic Drug Products

Sponsors Cambridge Healthtech Institute’s Tenth Annual Optimizing Biologics Formulation Development conference is an essential international gathering of analytical Event-at-a-Glance and formulation scientists from leading industry companies, offering an exchange of scientific developments and emerging technologies in an environment that encourages discussion with colleagues. For 2018, the conference focuses on a set of best practices for resolving key formulation development challenges. Each talk in the program will be presented by a different industry or academic group to ensure the widest possible range of perspectives.

SUNDAY, JANUARY 7 9:50 Present and Future Trends in treatment outcomes, and increase patient Biotherapeutic Device-Mediated Delivery convenience and compliance is receiving increased 4:00 - 6:00 pm Pre-Conference Registration Technologies scientific interest. This talk will provide a CMC outlook on challenges when formulating mAb Didier Pertuy, Vice President, Global Drug Device combinations. Case studies of challenges during Integrated Development & Device Strategy, Sanofi, MONDAY, JANUARY 8 in-use stability, development of formulation and France presentations, analytical characterization, and fill/ 7:00 am Registration and Morning Coffee Biotherapeutic device-mediated delivery is finish processes will be discussed. dominated by self-injectable devices like prefilled A PRODUCT-CENTRIC VIEW OF syringes, pens and auto-injectors. Next incremental 11:45 Case Study: Clinical In-Use Stability step should be Large Volume Devices driven by FORMULATION DEVELOPMENT Evaluation: Co-Administration of Two dosing frequency reduction and low device-ability Antibody Therapeutics 9:00 Welcome by Conference Organizer profile of new formats. In parallel, emerging mHealth-enabling technology is bringing new Zhen Wu, Ph.D., Senior Scientist, AbbVie Kent Simmons, Senior Conference Director, opportunities for smarter devices and integrated Concomitant IV administration of drugs, if clinically Cambridge Healthtech Institute care solutions. Even though longer-term evolution feasible, is a convenient approach for the patients and may offer competitive advantage. In this presentation, 9:05 Chairperson’s Opening Remarks stays difficult to predict some potential trends could be considered. co-administration of two antibody therapeutics will be Tarik Khan, Ph.D., Group Leader, Late-Stage presented as an example. Both drugs were diluted in an Pharmaceutical and Processing Development, F. 10:20 Networking Coffee Break IV bag and an in-use study was performed to evaluate Hoffmann-La Roche Ltd., Switzerland dose solution stability. The approach taken to adapt CO-FORMULATION AND the analytical methods and overcome the analytical challenges will be discussed. KEYNOTE PRESENTATION CO-ADMINISTRATION Sponsored by 12:15 pm See Stability in Hi-Def 9:10 An End to End Approach 10:45 The Challenges and Considerations of with Hunky to Formulation Development: Protein and Peptide Coformulations Greg Manley, Ph.D., Senior Considerations from Cell Line to Drug Rebecca Davis-Harrison, Ph.D., Research Scientist, Applications Specialist, Unchained Labs Product Process Development BioTechnology Discovery Research, Eli Lilly and Kapil Gupta, Ph.D., Associate Director, Protein Company Developing biologics requires identifying ideal constructs and assessing a wide range Pharmaceutical Development, Biogen The coformulation of two therapeutic peptides and/ of formulation space to ensure stability and Development of high concentration stable or proteins into a single dose is an emerging area minimize aggregation. Assessing ΔG is a powerful formulations requires an end to end approach. of biological therapeutics and brings additional By Cambridge Healthtech Institute approach for the quantitative assessment of Product heterogeneity and process impurities complexity to the already complex field of protein conformational stability and aggregation. Unchained generated from upstream process can impact formulations. Preserving the physiochemical Labs automates the tedious and manual task of drug product stability and might not be solved integrity of each molecule often requires that determining ΔG, allowing for quantitative stability SHORT COURSES by formulation optimization. An integrated formulation conditions needed for one be applied and aggregation assessment throughout biologic development approach is needed by balancing simultaneously to the other. Analytical methods development. We'll discuss how automated bioreactor productivity, yield, quality attributes must also be able to detect changes in either chemical denaturation can be used with more and drug product stability to ensure success. molecule in this more complex environment. traditional approaches to assess stability. Sponsorship Opportunities This talk will highlight this concept using some recent case studies. 11:15 Challenges in mAb Combination Drug 12:45 Session Break Hotel/Additional Information Products: A CMC Overview Jiali Du, Ph.D., Scientist, Formulation Sciences, 1:00 Luncheon Presentation (Sponsorship Registration & Pricing MedImmune Opportunity Available) or Enjoy Lunch on Your The use of two mAbs in combination to improve Own CHI-PepTalk.com CHI-PepTalk.com | 37 FINAL JANUARY 8-9 | 10TH ANNUAL FORMULATION & WEEKS STABILITY TO REGISTER Optimizing Biologics Formulation Development A Best Practices Exchange for Resolving the Challenges of Formulating Cover Novel Biologic Drug Products

Sponsors CELL AND GENE THERAPIES PROTEIN FORMULATION 5:30 Characterization and Control of Event-at-a-Glance CHALLENGES Interfacial Antibody Adsorption and 2:00 Chairperson’s Remarks Aggregation Arun Alphonse Ignatius, Ph.D., Principal Scientist, 4:30 Formulation Challenges for Low and Ian Shieh, Ph.D., Scientist, Genentech Pfizer High Concentration Proteins Exposure to interfaces can accelerate aggregation 2:05 Formulation Development for AAV-Based Shiang Gwee, Scientist, Drug Product Sciences, of antibody therapeutics during manufacture, transportation, and administration. Controlling Gene Therapy Products MacroGenics, Inc. DART® molecules are bi-specific antibody- interfacial antibody adsorption is critical to limiting Arun Alphonse Ignatius, Ph.D., Principal Scientist, based proteins developed for immuno-oncology aggregation. A panel of mAbs was characterized by Pfizer indications. These molecules are manufactured multiple surface-sensitive techniques to predict their Over the past few years, adeno-associated viruses using conventional antibody platforms, and risk of interfacially mediated aggregation. We also (AAV) have evolved significantly with few products demonstrate comparable product quality and measured and visualized antibody coadsorption with moving into late stage clinical development, and stability to conventional antibodies. Increased surfactant at the air-water interface to understand many others in early trials showing significant potency and lower dose requirement of certain the protective mechanisms of the surfactants promise in the clinic. However, there are significant bi-specific molecules present challenges included in antibody formulations. challenges that remain primarily due to the rapid for intravenous administration in early stage transition into industry. This presentation will use Sponsored by development. Case studies will be presented of 6:00 - 7:15 Welcome Reception case studies to showcase some of the challenges approaches for IV administration of low/high in the Exhibit Hall with Poster and considerations in the formulation development concentration protein formulations that highlight Viewing for AAVs. these challenges. 7:15 Close of Day 2:35 Biophysical Characterization of mRNA 5:00 Pulse Proteolysis: A Novel High- Loaded Lipid Nanoparticles Formulations Throughput Tool for Formulation Screening Flaviu Gruia, Ph.D., Principal Scientist, Drug Product Lavanya Iyer, Ph.D., Research Investigator, Bristol- Analytical Development, Moderna Therapeutics Myers Squibb Developing a delivery vehicle capable of Biologics formulation selection is typically based transporting the mRNA cargo to its intended on shelf-life stability data obtained over months. In target is a key challenge that should be addressed this work, a novel analytical method called Pulse during development of mRNA-based products. Proteolysis was used to rank-order formulations, Lipid nanoparticles represent a class of non-viral based on resistance to proteolysis. The results delivery systems that show potential in this space. demonstrate that formulations could be rank- The presentation will review some analytical ordered based on T-zero stability, as measured by development aspects, with specific examples pulse proteolysis. The high correlation with storage of techniques that are valuable for biophysical stability indicates that pulse proteolysis could prove characterization of nanoparticle formulations. to be a useful tool for formulation screening. Selected case studies will be included. By Cambridge Healthtech Institute 3:05 Transition to BuzZ Sessions

SHORT COURSES 3:15 BuzZ Sessions with Refreshments Join your peers and colleagues for interactive roundtable discussions. Please see page 78 for additional Sponsorship Opportunities information.

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 38 FINAL JANUARY 8-9 | 10TH ANNUAL FORMULATION & WEEKS STABILITY TO REGISTER Optimizing Biologics Formulation Development A Best Practices Exchange for Resolving the Challenges of Formulating Cover Novel Biologic Drug Products

Sponsors Sponsored by TUESDAY, JANUARY 9 9:35 Molecular Knowledge and 12:00 pm Formulation of Hard-to- Sponsored by Event-at-a-Glance Experience as the Driving Forces Stabilize Biopharmaceuticals 8:00 am Registration and Morning Coffee Behind Successful Protein Phil Morton, Ph.D., Science Director, Formulation Development Bioprocess Characterisation, Albumedix PREFORMULATION STUDIES Modern biopharmaceuticals are changing. Katherine Bowers, Ph.D., Principal Scientist, Group Increasingly, the industry is shifting towards Leader, Analytical and Formulation Development, 8:30 Chairperson’s Remarks more complex biological molecules intensifying FUJIFILM Diosynth Biotechnologies Rebecca Davis-Harrison, Ph.D., Research Scientist, formulation challenges requiring more advanced BioTechnology Discovery Research, Eli Lilly and 9:50 Coffee Break in the Exhibit Hall with excipients. Human albumin is well known to Company Poster Viewing stabilize proteins through a variety of roles, therefore recombinant human albumin is a promising stabilizer 8:35 Think Big, Go Small: A Screening 11:00 Poloxamer 188 as an Alternative for hard-to-formulate biopharmaceuticals. We present Approach Utilizing Small Volumes to Optimize data on the use of Albumedix® Recombumin® as a Formulation Selection to Provide Scale Down Surfactant stabilizing agent across several different stress tests Models to Support Manufacturing Tarik Khan, Ph.D., Group Leader, Late-Stage showing its versatility as an advanced excipient. William Callahan, Senior Scientist, Amgen Pharmaceutical and Processing Development, F. Hoffmann-La Roche Ltd., Switzerland There is a vital need in the biopharmaceutical industry 12:30 Session Break Polysorbates have long been the workhorse to perform formulation development expeditiously 12:45 Luncheon Presentation (Sponsorship and with relatively small amounts of material. In this surfactant for stabilizing biologics. However, due Opportunity Available) or Enjoy Lunch on Your presentation, an approach is shown which utilizes to their susceptibility to degradation there is a small volumes, requiring less material and resources, clear desire to identify alternative surfactants. Own Poloxamer 188 (P188) is one such stable yet sampling a larger design space. Further, this 1:15 Close of Optimizing Biologics small volume approach can be extended to include surfactant that has been successfully utilized in the manufacturing support and anticipate scale-up formulation of biologics. This talk will highlight real Formulation Development Conference issues. A case study will be presented illustrating formulation/stability data as well as mechanistic these concepts on the development of an antibody characterization of how P188 stabilizes biologics by formulation. interfacial activity and solution behavior. 11:30 Prospects for the Identification and SURFACTANTS AND EXCIPIENTS Application of Excipient Mixtures and Novel 9:05 Challenges and Solutions in Polysorbate Excipients Degradation Miko Schleinitz, PhD Student, Biochemical and Steven LaBrenz, Ph.D., Scientific Director, Cell and Chemical Engineering, Technical University, Developability Sciences, PDMS, Janssen R&D Dortmund, Germany Polysorbate degradation events in biopharmaceuticals Classically, novel excipients and excipient mixtures are identified based on heuristic approaches By Cambridge Healthtech Institute are becoming more understood, moving beyond the original autooxidation work of Donbrow. often neglecting synergetic effects and hindering Understanding degradation processes, relating that transferability of the results to novel formulations. knowledge to actual conditions of use and controlling It is thus desired, to develop a physically-sound SHORT COURSES degradation events involving polysorbate are essential method to identify excipient mixtures and novel to developing a stable protein formulation. When excipients based on modeling/predicting the controlling for external effectors that lead to issues intermolecular interactions in solution. This allows in a protein formulation, degradation events involving for considering the mutual influence of multi- excipient systems and to determine the optimal Sponsorship Opportunities polysorbate can be controlled. excipient mixture circumventing cost-intensive screening methods. Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 39 FINAL JANUARY 9-10 | 11TH ANNUAL FORMULATION & WEEKS STABILITY TO REGISTER Lyophilization and Emerging Drying Technologies Formulation and Process Optimization, Models, QbD, Delivery and Devices Cover

Sponsors The popular Eleventh Annual Lyophilization and Emerging Drying Technologies conference covers latest trends and challenges in lyophilization and emerging drying technologies. This conference will feature in-depth case studies, new and unpublished data and discussions on developing scientifically sound freeze dried Event-at-a-Glance formulation, process optimization for biologics and vaccines. It will also present cutting edge research and case studies on freeze/thaw and formulation challenges, drying in cartridges, storage stability, QbD and PAT approaches and strategies for scale-up from R&D scale to full production level, and selection of container closure systems.

TUESDAY, JANUARY 9 matrix, and that the buffer maintains the optimized Superior Técnico, University of Lisbon solid-state ionization (i.e., pH equivalent). We Reactions that can compromise stability and 1:00 pm Registration have been using solid-state NMR spectroscopy quality of the freeze dried products happen within to show that the stability of the protein, especially the ice structure. However, it’s difficult to correlate 1:30 Refreshment Break in the Exhibit Hall against aggregation, requires that the protein parameters with results, because of the complexity with Poster Viewing and cryoprotectant remain intimately mixed and and intricate relation between thermodynamic relatively immobile. and kinetic variables leading to cryoconcentration, PREDICTION OF STABILITY IN 3:15 Roles for Antifreeze Polypeptides in cold-denaturation, precipitation or aggregation. FREEZE DRIED PRODUCTS: NEW Experimental and modeling approaches were Optimizing Lyophilization Formulations and TOOLS AND STRATEGIES developed to understand and anticipate some Protecting Stability of Proteins of these mechanisms, which can assist the 2:00 Chairperson’s Opening Remarks Xin Wen, Ph.D., Professor, Department of Chemistry development of more rational formulations and Elizabeth M. Topp, Ph.D., Dane O. Kildsig Chair and and Biochemistry, California State University, Los optimized freeze drying procedures. Department Head, Department of Industrial and Angeles Physical Pharmacy, Purdue University In this talk, we will discuss the potential use of 5:30 Close of Day antifreeze polypeptides (AFPs) in optimizing 5:30 - 5:45 Short Course Registration lyophilized formulations and protecting stability KEYNOTE PRESENTATION proteins. Naturally produced by many cold-adapted 5:45 - 8:45 Dinner Short Courses* organisms including fish, insects, and plants, AFPs 2:05 Hydrogen Deuterium Exchange are known for their ability to inhibit ice growth and See page 5 for details in Lyophilized Solids: Correlation with recrystallization efficiently. We have demonstrated * Separate registration required Protein Stability that AFPs can also control the crystallization of Elizabeth M. Topp, Ph.D., Dane O. Kildsig Chair carbohydrates and nucleosides and protect proteins and Department Head, Department of Industrial under extreme temperatures. WEDNESDAY, JANUARY 10 and Physical Pharmacy, Purdue University 8:00 am Registration and Morning Coffee Solid-state hydrogen deuterium exchange with 3:45 Refreshment Break in the Exhibit Hall mass spectrometric analysis (ssHDX-MS) with Poster Viewing MODELS AND TOOLS FOR provides high resolution structural information 4:30 Predicting Stability of Freeze Dried PROCESS DESIGN, SCALE-UP AND for proteins in lyophilized solids. Recent studies Proteins Using Materials Dynamics with a lyophilized monoclonal antibody (mAb) TECHNOLOGY TRANSFER Marcus T. Cicerone, Ph.D., Biomaterials Group, show that deuterium incorporation is highly 8:30 Chairperson’s Remarks correlated with chemical and physical stability National Institute of Standards and Technology By Cambridge Healthtech Institute Xiaofeng Lu, Ph.D., Principal Research Scientist, on storage, and will be presented here. I will describe efforts in our lab towards understanding the fundamental connection Pharmaceutical Development, AbbVie, Inc. between picosecond timescale, molecular length 8:35 Optimizing the Vial Heat Transfer 2:45 Prediction of Protein Stability in SHORT COURSES scale motions and protein degradation processes Coefficient for Pharmaceutical Freeze Drying: Lyophilized Formulations: Miscibility, in lyophilized formulations. I will also discuss our A Case Study Illustrating a New Press-Blow Mobility, and Microenvironmental pH efforts in developing benchtop methods to rapidly Technique for the Manufacturing of Molded Eric J. Munson, Ph.D., Patrick DeLuca Endowed predict protein stability using this fundamental understanding. Vials Sponsorship Opportunities Professor, Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky Henning Gieseler, Ph.D., CSO, Pharmaceutical 5:00 New Tools for Prediction of Stability of Development, GILYOS GmbH Hotel/Additional Information The stabilization of proteins in lyophilized matrices Freeze Dried Products - A Cold Perspective requires that the protein and cryoprotectant, such The vial heat transfer coefficient (Kv) serves as a Miguel Ângelo Rodrigues, Ph.D., Researcher and key parameter to assess the total heat flow to a Registration & Pricing as sucrose or trehalose, be in intimate contact with each other and have reduced mobility in the Invited Professor, Chemical Engineering, Instituto vial during primary drying. The present case study

CHI-PepTalk.com CHI-PepTalk.com | 40 FINAL JANUARY 9-10 | 11TH ANNUAL FORMULATION & WEEKS STABILITY TO REGISTER Lyophilization and Emerging Drying Technologies Formulation and Process Optimization, Models, QbD, Delivery and Devices Cover

Sponsors discusses the heat transfer characteristics of a vial for lyophilizers of different scale and cleanroom ADVANCES IN ICE NUCLEATION, manufactured by a blow-blow and new press-blow environment using a typical protein formulation. Event-at-a-Glance VISUAL INSPECTION AND process, and subsequently discusses the impact of 11:20 Lyophilization Development of a such a design and manufacturing features on Kv. High Concentration Antibody Formulation: RECONSTITUTION CHALLENGES The results clearly suggest a significant impact of Technology Transfer from Lab to Pilot Plant 2:00 Chairperson’s Remarks the manufacturing technique on Kv. Akhilesh Bhambhani, Ph.D., Principal Scientist & Theodore W. Randolph, Ph.D., Kenneth and Genevieve 9:05 Freeze Drying of a Low Tg’ and High Group Leader, New Technologies-Vaccine Drug Gillespie Professor, Department of Chemical and Fill Protein Drug Product: The Critical Role Product Development, Merck & Co., Inc. Biological Engineering, University of Colorado, of Freezing on Primary Drying Process Recommendations for a successful scale-up of a Boulder Performance and Final Product Quality high concentration mAb will be shared with emphasis Attributes on a) formulation characterization, b) product and process design space, c) significance of engineering 2:05 Secondary Ice Nucleation as the True Xiaofeng Lu, Ph.D., Principal Research Scientist, runs and d) robust manufacturing process. Driver for Product Heterogeneity When Pharmaceutical Development, AbbVie, Inc. 11:50 Process Monitoring by Mass Controlling Ice Nucleation in Pharmaceutical Development of an efficient and robust freeze drying Freeze Drying cycle was challenging for low Tg’ and high fill protein Spectrometry during Freeze Drying drug product. A regular freezing protocol resulted in Jason Stewart, BS, Senior Associate Scientist, Tim Wenzel, Scientist, Ph.D. Candidate, University of a long primary drying process and undesired product Pharmaceutical Research and Development, Pfizer, Erlangen GILYOS GmbH appearance. In this presentation, the critical role Inc. The common ground for controlled ice nucleation of freezing conditions on primary drying process Mass spectrometry has emerged as a key technologies in freeze drying is that they can only performance and product quality attributes will be technology for the detection of trace levels of control primary nucleation. However, formation of demonstrated. An effective freezing protocol will be silicone oil in freeze drying chamber. With the the ice network throughout the product solution recommended to achieve an efficient primary drying capability of measuring low molecular mass gasses determines the overall drying performance and process and desired product quality attributes. such as water and nitrogen, mass spectrometry product quality. To obtain optimum homogeneity, secondary nucleation and ice crystal growth must 9:35 Emerging Drying Techniques for positions itself to be a powerful tool for monitoring the entire drying process. be controlled post primary nucleation. Impact Manufacturing of Pharmaceutical Biologics factors and appropriate process set-up for two Qi (Tony) Zhou, Ph.D., Assistant Professor, Industrial 12:20 pm Lyophilisation of High pressure-dependent nucleation technologies will be and Physical Pharmacy, Purdue University Concentration Protein Formulations: discussed. Traditional lyophilization is a batch and time- Excipient Selection and Challenges consuming process with low energy consumption 2:35 Methods to Reduce the Reconstitution Valeria Gervasi, PhD Candidate, School of efficiency. There are increasing interests to Time of High Concentration Lyophilized Pharmacy, Synthesis & Solid State Pharmaceutical develop emerging drying techniques that have Protein Therapeutics Centre,University College Cork higher processing efficiency and lower costs while Jacob Luoma, Engineer II, Pharmaceutical Processing maintain product quality. A few drying techniques The design of lyophilisation process for high and Technology Development, Genentech concentration protein formulations can be have been attempted such as spray drying and spray There is increasing interest in producing high challenging due to the necessity of employing freeze drying. This talk will discuss the advantages concentration lyophilized protein therapeutics. products with high total solute concentration, By Cambridge Healthtech Institute and disadvantages of these emerging drying Since reconstitution time increases as protein resulting in high cake resistance. Excipient techniques for the application of biologics. concentration increases, the product may become selection and modelling approaches, as well as inconvenient to use in the clinic if reconstitution the identification of critical parameters for the 10:05 Coffee Break in the Exhibit Hall with time is not addressed. This talk will review methods SHORT COURSES optimization of the lyophilisation process, can aid Poster Viewing that Genentech has evaluated for reducing the efficient manufacture of a stable product with 10:50 Use of Model in Process Design and reconstitution time. prolonged shelf-life. Scale-Up: A Case Study Using Lab, Pilot and 3:05 Refreshment Break in the Exhibit Hall GMP Equipment Sponsorship Opportunities 12:50 Session Break with Poster Viewing Alina Alexeenko, Ph.D., Professor, School of Aeronautics and Astronautics, Purdue University 1:00 Luncheon Presentation (Sponsorship Hotel/Additional Information In this presentation, we will discuss use of model Opportunity Available) or Enjoy Lunch on Your Registration & Pricing in process design and scale up. We will present Own a case study of freeze-drying cycle variations

CHI-PepTalk.com CHI-PepTalk.com | 41 FINAL JANUARY 9-10 | 11TH ANNUAL FORMULATION & WEEKS STABILITY TO REGISTER Lyophilization and Emerging Drying Technologies Formulation and Process Optimization, Models, QbD, Delivery and Devices Cover

Sponsors 5:00 Considerations for Assessment of FEATURED PRESENTATION Particles in Biologics Originating from Event-at-a-Glance Packaging and Standardization Initiatives 4:00 Visual Inspection and Reconstitution Diane Paskiet, MS, Director of Scientific Affairs, Challenges: Protein Aggregation and Scientific Affairs and Technical Services, West Nanobubbles Pharmaceutical Services Theodore W. Randolph, Ph.D., Kenneth and Genevieve It is critical to understand the types and sources Gillespie Professor, Department of Chemical and of particulates in biologic products and how their Biological Engineering, University of Colorado, presence may affect product quality and patient Boulder safety. The linkage between particles, biologic When glassy lyophilized disaccharide cakes are formulation and packaging development involves reconstituted, large numbers (billions per mL) of understanding contributions from all sources. This small (130-150 nm) bubbles may be formed. These presentation will provide insight into measurements nanobubbles are remarkably stable, lasting months of particles originating from packaging components, in suspension. When incubated with proteins, they comparison of data from various technologies and can induce aggregation, an effect that appears to be USP standardization initiatives. modulated by ions bound to the nanobubble surface. 5:30 - 6:45 Networking Reception in the Exhibit Hall with Poster Viewing 4:30 Characterization of Universal Stabilized 6:45 Close of Lyophilization and Emerging Stem Flu Vaccine Candidates Drying Technologies Conference Sashikanth Banappagari, Ph.D., Scientist II, Formulation Development, Vaccine Production Program/VRC/NIAID/NIH The purpose of this project is to elicit responses across multiple strains, looking towards a pandemic flu vaccine. This study describes advanced biophysical characterization of stabilized stem constructs of HA-Ferritin by CD, DSC, FTIR, Fluorescence and 2D UV-vis spectroscopy. These methods can contribute to understanding the basal physicochemical properties for optimal formulation development and monitoring vaccine quality that pertains to product comparability studies during development.

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 42 FINAL JANUARY 11-12 | 9TH ANNUAL FORMULATION & WEEKS STABILITY TO REGISTER Protein Aggregation and Emerging Analytical Tools Mechanism, Prediction, Screening, Immunogenicity and Formulation Challenges Cover

Sponsors The popular Protein Aggregation and Emerging Analytical Tools conference covers latest trends, challenges and solutions in understanding, characterization and Event-at-a-Glance mitigation of problems generated by protein aggregation in biopharmaceuticals. This conference will feature in-depth discussion on mechanisms of aggregation, new tools for detection and quantitation of aggregates. It will also discuss mechanistic understanding of protein aggregation and present case studies on prevention of particle formation by engineering and formulation approaches, aggregation in ADCs, bispecifics, impact of aggregation on production, aggregates as a factor for immunogenicity, and approaches for improvement of biophysical properties of protein solutions.

THURSDAY, JANUARY 11 For proteins to aggregate, they need to come into Measuring key stability parameters of a protein contact. The hydration/solvation shell around formulation is critical in the early stage development 7:45 am Registration and Morning Coffee proteins can block protein-protein contacts. This talk of biopharmaceutical products. At this early stage will focus on what factors impact the strength of the the quantity of drug substance available for testing MECHANISM, PREDICTION solvation shell. is limited, requiring these tests be performed on very small sample volumes. The Viscosizer TD AND OVERCOMING PROTEIN 9:30 Characterizing and Inhibiting Glucagon system is an automated platform to characterize AGGREGATION Fibrillation the stability of formulations. The system provides Elizabeth M. Topp, Ph.D., Dane O. Kildsig Chair and automated, low volume measurement of Viscosity, 8:15 Chairperson’s Opening Remarks Department Head, Department of Industrial and Hydrodynamic Size, Stokes Radius, and the Diffusion Thomas Laue, Ph.D., Professor Emeritus, Molecular, Physical Pharmacy, Purdue University Interaction Parameter (kD). Cellular and Biomedical Sciences, University of New Glucagon, a peptide hormone, is currently marketed Hampshire in lyophilized form for treating severe hypoglycemia. 12:00 pm Session Break The lyophilized form is necessary because glucagon 12:15 Luncheon Presentation (Sponsorship rapidly fibrillates in solution. This presentation Opportunity Available) or Enjoy Lunch on Your KEYNOTE PRESENTATION summarizes computational and experimental Own 8:20 Light-Induced Protein Disulfide studies of the mechanisms of glucagon fibrillation, Degradation: Product Characterization and presents novel glucagon derivatives that resist 1:15 Ice Cream Break in the Exhibit Hall with fibrillation. Christian Schoneich, Ph.D., Distinguished Poster Viewing Professor and Chair, Pharmaceutical Chemistry, 10:00 Coffee Break in the Exhibit Hall with University of Kansas Poster Viewing NEW TOOLS AND STRATEGIES FOR Protein biotherapeutics can degrade via a HTS SCREENING manifold of physical and chemical degradation 11:00 Design of Stable and Aggregation mechanisms. We will show here, that light Resistant Single-Domain Antibody 2:00 Chairperson’s Remarks exposure of therapeutic disulfide-containing Biotherapeutics Wayne F. Reed, Ph.D., Professor, Physics, Tulane University proteins can lead to > 60 different products, Jamshid Tanha, Ph.D., Senior Research Officer, generated via novel cross-linking and 2:05 Recent Progress in Light Scattering fragmentation mechanisms. Some of these Human Health Therapeutics Portfolio, National Research Council Canada Determination of Aggregation Rates with reactions may be catalyzed by metal impurities Small Samples in Parallel Format such as iron or tungstate, which can be present Various approaches for improving the stability of By Cambridge Healthtech Institute in pre-filled glass syringes. Mechanistically, VH and VL single-domain antibodies have been Wayne F. Reed, Ph.D., Professor, Physics, Tulane product formation can be rationalized by light- described. Here we zoom in on one particular University induced generation of radicals and reactive approach, namely disulfide engineering approach, Monitoring protein aggregation via simultaneous oxygen species. which improves the stability of VHs and VLs. The multiple sample light scattering in real time allows SHORT COURSES approach appears to be universally applicable rapid, parallel determination of aggregation rates across all VHs and VLs and may also apply to scFvs, (AR), which are directly related to protein stability for Fabs, mAbs and their derivatives. different formulations. Recent progress beyond AR 9:00 Protein Solvation: Preventing Sponsored by includes: interpretation of non-linear light scattering Sponsorship Opportunities Aggregation by Forming a Tighter ‘Shield’ 11:30 Automated, Low Volume signatures in terms of mechanisms, relationship of around a Protein Assessment of Stability AR to GPC data, distinguishing small populations Hotel/Additional Information Thomas Laue, Ph.D., Professor Emeritus, Molecular, Parameters in Protein Formulations of large aggregates from large populations of small Cellular and Biomedical Sciences, University of New Kevin Mattison, Principal Scientist, Bioscience, aggregates, and considerations of reproducibility Registration & Pricing Hampshire Malvern PANalytical and predictability of aggregation.

CHI-PepTalk.com CHI-PepTalk.com | 43 FINAL JANUARY 11-12 | 9TH ANNUAL FORMULATION & WEEKS STABILITY TO REGISTER Protein Aggregation and Emerging Analytical Tools Mechanism, Prediction, Screening, Immunogenicity and Formulation Challenges Cover

Sponsors Sponsored by 2:35 High Throughput, Low Volume FORMULATION, PROCESS AND 5:45 Close of Day Event-at-a-Glance Subvisible Particle Screening MANUFACTURING STRATEGIES TO Bernardo Cordovez, Ph.D., President, Halo Labs FRIDAY, JANUARY 12 Halo labs will present a subvisible particle screening OVERCOME AGGREGATION tool, the HORIZON, with detailed explanation 4:15 Formulation, Process and Manufacturing 8:00 am Registration of its Backgrounded Membrane Imaging (BMI) Strategies to Prevent and Overcome technology. A comparative analysis between HORIZON and flow imaging will be presented and Aggregation Challenges in Early and Late 8:00 BuzZ Sessions with Continental Breakfast key performance indicators including sample Stage Development Protein therapeutics is a fast-growing volume, throughput, dynamic range, instrument Sreedhara Alavattam, Ph.D., Principal Scientist and global market. As the science improves, repeatability will be evaluated. Senior Group Leader, Genentech so does the complexity of the R&D Aggregation remains a challenge during protein organization. Ensuring product quality 2:50 Protein (In)stability and Analytical Tools process development. Aggregation during plus speed to market requires insights from for Monitoring Aggregation production, purification and product handling can stakeholders working across the stages of protein Vasco Filipe, Ph.D., Lab Head, Pharmaceutical have potential impacts on immunogenicity. The talk science R&D. Join experts representing this PepTalk Development Biologics, Sanofi will cover various aspects of decreasing aggregates pipeline, peers, and colleagues for an interactive Drug product development of therapeutic proteins and potentially remediate the aggregation during roundtable discussion. Topics include highlights involves a complex selection and optimization handling of drug products in the clinical setting. from the week’s presentations, new technologies process aimed at making proteins manufacturable, and strategies, challenges, and future trends. stable and deliverable. Avoiding protein aggregation 4:45 Particulate Formation during Fill & Finish Table Moderator: Thomas Laue, Ph.D., Professor is one of the main concerns. Choosing the right Operations Emeritus, Molecular, Cellular and Biomedical formulation and setting up good strategies to Cheng Her, Ph.D., Postdoctoral Research Fellow, Sciences, University of New Hampshire monitor, predict and avoid protein aggregation Carpenter Lab, Pharmaceutical Sciences, University during the various steps of the process is crucial. of Colorado-Denver, Anschutz Medical Campus Formulation development considerations and As the final step before the drug product reaches the IMMUNOGENICITY, analytical tools used to monitor protein aggregation patient, it is vital that a fill & finish operation mitigate will be presented. both particulate formation and aggregation. It was the DEVELOPABILITY, EXCIPIENTS, Sponsored by aim of this study to have a more comprehensive look at AND STABILITY 3:05 Sifting through the particulate formation during fill & finish operations, from Noise-Utilizing Light Scattering for the tubing and pumps used, to the storage and handling 9:00 Chairperson’s Remarks Rapid Formulation Development of the drug product after fill & finish operations. Nathan H. Joh, Ph.D., Scientist, Attribute Sciences, Amgen Lynette Schroeter, Crystalomics, Group Lead, Formulations Development, Althea CMO 5:15 PANEL DISCUSSION: Preventive and 9:05 High Molecular Weight Species of a Delivering high concentration, low viscosity Analytical Approaches for Reduction and Therapeutic Antibody is Chemically Modified, biotherapeutics to patients is an attractive option Removal of Aggregates that Work Lacks Distinct Structure, and Shows No for innovator companies. Althea's Crystalomics® Moderator: Increased Risk of Immunogenicity in Model By Cambridge Healthtech Institute technology delivers formulated protein crystal Wayne F. Reed, Ph.D., Professor, Physics, Tulane Systems suspensions subcutaneously, whereby the crystals University Nathan H. Joh, Ph.D., Scientist, Attribute Sciences, dissolve readily with no adverse effect. Light Panelists: Amgen scattering analysis, particularly rapid screening SHORT COURSES Bernardo Cordovez, President, Halo Labs High-molecular-weight (HMW) species from utilizing the Wyatt Technology Dynapro® Plate Cheng Her, Ph.D., Postdoctoral Research Fellow, monoclonal antibody drug substance was Reader II, is critical to rapidly optimizing formulation investigated to elucidate structure, chemical conditions and characterizing the protein pre and Carpenter Lab, Pharmaceutical Sciences, University of Colorado-Denver, Anschutz Medical Campus modifications, and potential risk of immunogenicity. post crystallization. Higher levels of oxidized methionine and tryptophan Sponsorship Opportunities Sophia Kenrick, Ph.D., Senior Applications Scientist, were observed in HMW compared to monomer. Wyatt Technology Hotel/Additional Information 3:35 Refreshment Break in the Exhibit Hall HMW species lacked a well-defined molecular with Poster Viewing Sreedhara Alavattam, Ph.D., Principal Scientist and structure. Little to no risk of immunogenicity was Registration & Pricing Senior Group Leader, Genentech observed for HMW in multiple immune model Wei Qi, Ph.D., Scientist, Pre-Pivotal Drug Product, systems, including heterozygous transgenic mice, Amgen CHI-PepTalk.com CHI-PepTalk.com | 44 FINAL JANUARY 11-12 | 9TH ANNUAL FORMULATION & WEEKS STABILITY TO REGISTER Protein Aggregation and Emerging Analytical Tools Mechanism, Prediction, Screening, Immunogenicity and Formulation Challenges Cover

Sponsors human peripheral blood mononuclear cells, and 11:15 Excipients Affect Solvation and Event-at-a-Glance engineered immune cells. Interactions in High Protein Concentration mAb Solutions 9:35 Evaluation and Development Prasad Sarangapani, Ph.D., Staff Scientist, Protein of Screening Methods for Antibody Biochemistry, Regeneron Pharmaceuticals Developability Assessment In this presentation, we will discuss how excipients Nikolai Lorenzen, Ph.D., Large Protein Biophysics, influence intermolecular and hydrodynamic Novo Nordisk A/S interactions in high protein concentration mAb Biophysical screening is widely used in early phase solutions. development of monoclonal antibodies to guide selection of molecules with a high potential to reach 11:45 Understanding the Mechanism of clinical testing. Using the in silico solubility predictor Interaction between Leachates and Proteins CamSol we have designed a modelsystem of and Its Impact on Drug Product Quality antibody variants displaying a range of solubilities. I Heather Flores, BS, Scientist, Technical Development will present how selected biophysical measures as Scientist, Late Stage Pharmaceutical Development, e.g. AC-SINS, CIC, PEG precipitation and diffusion Genentech, Inc. interaction parameter predict for formulation Chemical impurities that leach from product relevant measures for this modelsystem. contacting material have long been assessed Sponsored by 10:05 Counting and Sizing Protein for potential toxicological effects. More recently, Aggregates Down to 0.15 um at however, several instances of interaction of leachables and/or impurities with the active High Concentrations by pharmaceutical ingredient or other formulation Focused-Beam SPOS components have been reported. Understanding David Nicoli, Ph.D., Vice-President R&D, Particle the mechanisms by which leachates interact with Sizing Systems LLC biomolecules is key in assessing the potential Protein aggregates as small as 0.15-um can be impact to drug product quality and associated safety counted/sized at concentrations 100-1000X higher and efficacy concerns. than is possible with light scattering sensors of conventional design, using a novel focused-beam 12:15 pm Conference Wrap-Up single-particle optical sizing (SPOS) technique. Adding a second sensor that combines light Thomas Laue, Ph.D., Professor Emeritus, Molecular, obscuration and scattering extends the upper Cellular and Biomedical Sciences, University of New particle size limit to 200 microns. Analysis can be Hampshire made on sub-mL samples, including those of high viscosity, and the sample is conserved following 12:45 Close of Conference analysis. By Cambridge Healthtech Institute 10:35 Coffee Break with a Poster Pavilion See page 4 for details SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 45 FINAL WEEKS TO REGISTER

Cover

Sponsors Event-at-a-Glance ANALYTICS & IMPURITIES

JANUARY 8-9 AGENDA Characterization of Biotherapeutics

JANUARY 9-10 AGENDA Detection and Characterization of Particulates and Impurities

JANUARY 11-12 AGENDA Bioprocess Analytics

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 46 FINAL ANALYTICS & WEEKS JANUARY 8-9 | 4TH ANNUAL IMPURITIES TO REGISTER Characterization of Biotherapeutics Improving Prediction, Screening and Characterization of New Biologics Cover New biotherapeutics formats are flooding the discovery and development pipelines and with this comes an increasing need for better and faster characterization tools and Sponsors strategies, and improved biomolecular and biophysical assays for the new biotherapeutics. The Fourth Annual Characterization of Biotherapeutics conference will present new tools, strategies and case studies on analytical development and characterization of mAbs, ADCs, and other novel protein formats, biosimilars, HOS, and developability. We invite you to Event-at-a-Glance present a poster and attend to join with colleagues in this discussion of the key challenges and solutions improving predication, screening and characterization of biologics.

SUNDAY, JANUARY 7 simultaneously bind to two targets. These versatile Here we present a case study for the development of a molecules have the potential for improved efficacy robust reversed phase UPLC separation to accurately 4:00 - 6:00 pm Pre-Conference Registration and safety profile through enhanced selectivity and precisely quantify free drug related impurities and recruitment of specialized effector cells. This (FDRI) in an ADC using components of analytical QbD MONDAY, JANUARY 8 presentation will discuss analytical characterization including the use of an Analytical Target Profile (ATP), strategies using this novel class of molecules and prior knowledge, and Design of Experiment (DoE). 7:00 am Registration and Morning Coffee other antibody molecules as case studies. 12:15 pm Expanding the Role Sponsored by CHARACTERIZATION OF NEW 10:20 Networking Coffee Break of CD in Biotherapeutic BIOTHERAPEUTICS 10:45 Effects of Chemical Degradation on Characterization- Beyond α-helix and β-sheet Helen Wu, Ph.D., Senior Scientist, Boehringer 9:00 Welcome by Conference Organizer Higher Order Structure, Conformational Ingelheim Pharmaceuticals Inc Nandini Kashyap, Conference Director, Cambridge Stability, Physical Instabilities, and Biological Healthtech Institute Properties of an IgG1 mAb This presentation includes case studies highlighting Dinen Shah, Department of Pharmaceutical Sciences the role of CD in Higher Order Structure (HOS) 9:05 Chairperson’s Opening Remarks (Krishna Mallela Lab), University of Colorado Denver comparisons of potential biotherapeutics. Detection Alexey Rak, Ph.D., Head of Bio Structure and Health Sciences Center of even minor changes in secondary and tertiary Biophysics, Integrated Drug Discovery, Sanofi R&D Oxidation is a critical challenge during the life structure and generation statistically-validatable cycle of any therapeutic protein. In this study, we data for critical quality attributes contributes to KEYNOTE PRESENTATION probed the effect of oxidation on the structure, informed decision-making and strengthens totality 9:10 Novel Low-Protein Consuming High stability, aggregation, and function of a therapeutic of evidence in regulatory submissions. Throughput Biophysical Methods for IgG1 monoclonal antibody (mAb-8). In particular, 12:45 Session Break we examined whether the extent of protein mAbs, ADCs and Multi-Specific Biologics Sponsored by destabilization, aggregate formation, and loss of 1:00 Luncheon Presentation I: Characterization specific protein activity can be correlated with the Glycans before Lunch: Rapid Alexey Rak, Ph.D., Head of Bio Structure and site and extent of oxidation. N-Glycan Sample Preparation Biophysics, Integrated Drug Discovery, Sanofi R&D Workflows for Screening and Characterization Modern drug discovery operations require 11:15 Composition and Thermal Stability of of Biotherapeutics characterization of biomolecular interactions Adsorbed Vaccines Aled Jones, Senior Product and Applications to be both time- and cost-effective as well as Marina Kirkitadze, Ph.D., Deputy Director, Head of Manager, ProZyme Biophysics and Conformation Unit, Analytical R&D to be highly precise and reproducible. Here we The structure of N-linked glycans can play a critical role Biochemistry, Sanofi Pasteur, Canada report applications of novel biophysical methods in the pharmacology of therapeutic proteins, potentially nano-Diffrential Scanning Fluorimetry (nanoDSF), The focus of this presentation is a characterization affecting immunogenicity, pharmacokinetics and MicroScale Thermophoresis (MST) and kinetic of adsorbed vaccine consisting of several protein pharmacodynamics. This makes the characterization antigens and new adjuvant. The applicability of By Cambridge Healthtech Institute stability experiments that we are applying in our of N-glycans an essential part of the biotherapeutic biologics discovery and development for mAbs, several biophysical methods (FTIR, Raman, DSF) to development process. We present 3 rapid N-glycan ADCs and multi-specific biologics. The examples characterize vaccine components in the final drug sample preparation and analysis workflows: Gly-X of the demonstrated effectiveness of the novel product without desorption. SHORT COURSES with InstantPC or 2-AB Express labeling for glycan integrated biophysical methods will be presented 11:45 Analytical QbD Applied to the characterization by liquid chromatography, and Gly-Q and discussed. Development of a Robust Reversed Phase for rapid screening using an integrated system with capillary electrophoresis. 9:50 Analytical Characterization of Next- Separation Method to Monitor Free Drug 1:30 Luncheon Presentation II (Sponsorship Sponsorship Opportunities Generation Antibody-Based Therapeutics Related Impurities in an ADC Kevin Strozyk, Sr. Research Associate, Analytical Opportunity Available) Tasneem Bahrainwala, PhD, Analytical Sciences Mass Hotel/Additional Information Sciences, Seattle Genetics Spectrometry Group Leader, MacroGenics, Inc. Quality by Design (QbD) allows for a systematic DART® molecules are bispecific antibody-based Registration & Pricing approach to method development with predefined proteins developed for a variety of indications objectives while leveraging prior method understanding. including immune-oncology, and are designed to CHI-PepTalk.com CHI-PepTalk.com | 47 FINAL ANALYTICS & WEEKS JANUARY 8-9 | 4TH ANNUAL IMPURITIES TO REGISTER Characterization of Biotherapeutics Improving Prediction, Screening and Characterization of New Biologics Cover

Sponsors HIGH-THROUGHPUT SCREENING, BIOSIMILARS, COMPARABILITY, TUESDAY, JANUARY 9 Event-at-a-Glance IMMUNOASSAY AND HIGHER ORDER STRUCTURE & BIOCHEMICAL ASSAY BIOPHYSICAL CHARACTERIZATION 8:00 am Registration and Morning Coffee 2:00 Chairperson’s Remarks 4:30 Selection and Sensitivity of Biophysical DEVELOPABILITY ASSESSMENT AND Czeslaw Radziejewski, Ph.D., Senior Principal Techniques in Characterization of Higher ANALYTICAL CHARACTERIZATION Research Scientist, Biophysical Chemistry, AbbVie Order Structure of Proteins 8:30 Chairperson’s Remarks 2:05 In vitro Assays to Predict Immunogenicity Haripada Maity, Ph.D., Research Advisor, Formulation Development, CMC Development, Eli Lilly and Company Haripada Maity, Ph.D., Research Advisor, Formulation Risk Assessment of Protein Therapeutics Development, CMC Development, Eli Lilly and Company Shanmuuga T. Sundaram, Ph.D., Research Advisor, A strong correlation among higher order structure BioAnalytical Sciences, Bioproduct Research and (HOS), conformational stability, and functional 8:35 Developability Assessment to Support Development, Eli Lilly and Company properties is generally observed for proteins. Pre-Candidate Selection of Biotherapeutics Characterization of HOS is primarily performed by 2:35 Deciphering the Root-Causes for Jonathan S. Kingsbury, Ph.D., Principal Scientist, different biophysical techniques. The selection and Global Pharmaceutical Development Biologics, Sanofi Atypical PK of mAbs and Complex Biologics sensitivity of these techniques is very important, and Developability/deviceability is a critical pipeline by Protein Engineering may depend on protein to protein. This presentation support activity, the results of which are used to Thomas E. Kraft, Ph.D., Postdoctoral Scientist, Large will discuss the sensitivity and limitations of different techniques used in the characterization of proteins focus the field of potential candidate molecules. Molecule Research, Roche Diagnostics GmbH Such assessments can be conducted in diverse Therapeutic antibodies with nearly identical Fc of different sizes, and the number of intrinsic chromophores under a variety of stress conditions. ways, with different testing compositions and timing. domains show >10-fold differences in clearance. We The benefits of a multi-checkpoint strategy for systematically identified properties of the Fv domain 5:00 Biologics Characterization and candidate credentialing completed at different stages that can cause atypical pharmacokinetic behavior. Comparability throughout the early discovery/development timeline Using protein engineering, we created Fab mutants Yemin Xu, Ph.D., Senior Regulatory Scientist, will be discussed. In addition, the defining qualities with defined biophysical properties and tested them Regulatory Science, Regeneron of a comprehensive, process-relevant assessment in biochemical PK prediction assays and for in vivo strategy will be discussed and explained using Biologics development is the fastest growing clearance. Our results are highly relevant for predicting examples. The use of the resulting data to enable pharmaceutical market. Biologics development and improving in vivo PK based on biophysical decision making for pre-candidate selection using and licensing application require thorough properties and biochemical assay data. empirical benchmarks will be highlighted. physicochemical and biological characterization. 3:05 Transition to BuzZ Sessions Across development stages, analytical comparability 9:05 Case Study: Light-Induced Covalent exercises are commonly required when changes Histidine Adducts on A IgG1 Molecule: are implemented into the manufacturing process. Reaction Pathways and Influencing Factors 3:15 BuzZ Sessions with Refreshments Analytical comparability plays a crucial role to Join your peers and colleagues for demonstrate that pre- and post-change products are Ming Lei, Ph.D., Associate Scientist, Protein Analytical interactive roundtable discussions. comparable and have no adverse impact on safety, Chemistry, Genentech Please see page 78 for additional information. identity, purity, or efficacy of the product. Light is known to induce many reactions on protein residues such as tryptophan (Trp), cysteine (Cys) and By Cambridge Healthtech Institute 5:30 Biophysical Studies of Multivalent histidine (His). In this work, light-induced His-adducts Antibody-Antigen Complexes were found on a monoclonal antibody (mAb-1) Czeslaw Radziejewski, Ph.D., Senior Principal formulated in His-containing buffer. The reaction SHORT COURSES Research Scientist, Biophysical Chemistry, AbbVie pathways and influencing factors such as solvent accessibility and the concentrations of common This presentation will describe electron microscopy surfactants are thoroughly investigated. studies of various complexes that are formed when TNF alpha interacts with anti-TNF monoclonal antibodies. 9:35 Sponsored Presentation (Opportunity Sponsorship Opportunities 6:00 - 7:15 Welcome Reception Sponsored by Available) in the Exhibit Hall with Poster Hotel/Additional Information 9:50 Coffee Break in the Exhibit Hall with Viewing Poster Viewing Registration & Pricing 7:15 Close of Day

CHI-PepTalk.com CHI-PepTalk.com | 48 FINAL ANALYTICS & WEEKS JANUARY 8-9 | 4TH ANNUAL IMPURITIES TO REGISTER Characterization of Biotherapeutics Improving Prediction, Screening and Characterization of New Biologics Cover

Sponsors 11:00 Structural Characterization of SDS- 12:00 pm Rapid Development Sponsored by Event-at-a-Glance Solubilized Proteins by ESI-MS of Anti-Idiotypic Binders Using Cheng Zhao, Ph.D., Principal Scientist, Abbott a Novel Affinity Scaffold Laboratories Matt Johnson, Ph.D., CSO, Avacta Life Sciences The diversity and increasing complexity of new protein Affimer® proteins are next-generation affinity formats requires a change from former platform scaffolds, offering highly specific and stable approaches often applied for antibodies, to project binders, with great potential for the generation of specific strategies. The developability assessment novel biotherapeutics and renewable research and concept applied at Novartis combines information diagnostics tools. We produced highly-specific about early process development, aggregation anti-idiotypic Affimers, for Trastuzumab, anti-CTLA4, propensity, stability, solubility, physicochemical anti-CD20 and anti-TNFa antibodies, via a 12-week properties and immunogenicity of potential development process. The resulting Affimer® candidates. This integrated approach prior to lead binders can be used selection provides a thorough yet resource efficient approach. The presentation will provide an overview 12:30 Session Break about the concept and provide selected case studies. 12:45 Luncheon Presentation (Sponsorship 11:30 PANEL DISCUSSION: Application of Opportunity Available) or Enjoy Lunch on Your New Analytical Tools and Mass Spectroscopy Own for Characterization of Biologics 1:15 Close of Characterization of Moderator: Biotherapeutics Conference Haripada Maity, Ph.D., Research Advisor, Formulation Development, CMC Development, Eli Lilly and Company Panelists: Jonathan S. Kingsbury, Ph.D., Principal Scientist, Global Pharmaceutical Development Biologics, Sanofi Thorsten Lorenz, Ph.D., Global Head Developability Assessment, Integrated Biologics Profiling, Novartis Pharma AG Ming Lei, Ph.D., Senior Research Associate, Protein Analytical Chemistry, Genentech

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 49 FINAL ANALYTICS & WEEKS JANUARY 9-10 | 4TH ANNUAL IMPURITIES TO REGISTER Detection and Characterization of Particulates and Impurities Rapid Tools for Risk Assessment, Prediction and Characterization of Impurities Cover from Products, Excipients, Processes and Packaging

Sponsors Particles and impurities can arise from the products and/or during any stage of bioprocessing or from the delivery devices and primary packaging. These impurities have the potential to impact stability, safety and efficacy of the biomolecules and biologic products. Therefore, early understanding, detection and characterization of the Event-at-a-Glance impurities are critical to ensure safety and efficacy of the drug product for its intended duration of use. The Fourth Annual Detection and Characterization of Particulates and Impurities conference provides a platform to explore novel tools and strategies to detect, characterize and carry out risk assessment of particles and impurities such as subvisible particles, host cell proteins, extractables and leachables, impurities from excipients and raw materials, glass and other particles, etc.

TUESDAY, JANUARY 9 public health through standards for medicines and their ingredients. As biological science contributes to more 5:30 Close of Day advanced therapies, standards continue to play a critical 1:00 pm Registration 5:30 - 5:45 Short Course Registration role in drug development and manufacturing. This talk 1:30 Refreshment Break in the Exhibit Hall will highlight new quality standards for demonstration with Poster Viewing of method performance, as well as measurement and 5:45 - 8:45 Dinner Short Courses* characterization of impurities in peptides and biologics. See page 5 for details GUIDANCE, PARTICLES, 3:15 Talk Title to be Announced Sponsored by * Separate registration required AGGREGATES AND Eric Bishop, MBA, MSc, Vice President, IMMUNOGENICITY Research & Development, Cygnus Technologies 2:00 Chairperson’s Opening Remarks WEDNESDAY, JANUARY 10 Maura Kibbey, Ph.D., Director, Global Biologics, U.S. 3:45 Refreshment Break in the Exhibit Hall Pharmacopeia with Poster Viewing 8:00 am Registration and Morning Coffee 4:30 Assessment of Immunogenic Risk Posed HOST CELL PROTEIN AND KEYNOTE PRESENTATION by Biologic Aggregation PROCESS IMPURITIES 2:05 Anticipating Aggregation Michael Swanson, Ph.D., Senior Scientist, Merck Propensity of Proteins at Early Aggregated therapeutic antibodies have the potential 8:30 Chairperson’s Remarks Formulation Development Stage: How to induce an immune response. Elucidation of the Joël Richard, Ph.D., Vice President, Peptides, CMC & Engineering, Ipsen to Support a Data-Based Approach for mechanism of responses to aggregated antibodies could mitigate the immunogenic risk. Utilizing Immunogenicity Risk Assessment 8:35 Host Cell Proteins, What We Know, What cell-based in vitro models, we investigated the role Joël Richard, Ph.D., Vice President, Peptides, of different innate immune receptors in responses We Don’t and How to Control CMC & Engineering, Ipsen to aggregated antibody. By comparing the ability Judy Shimoni, Ph.D., Principal Scientist and Group In the perspective of accelerating early of aggregated antibody and natural ligands to Leader, Protein Analytical Chemistry, Genentech, Inc., stage protein formulation development, it activate different receptors, we were able to begin to a member of the Roche Group has become key to anticipate and predict determine the relative risk posed by aggregates. The presentation is intended to share some current formulation, storage and processing conditions thinking and to use case studies to demonstrate the that will lead to aggregation. To anticipate 5:00 PANEL DISCUSSION: Strategies and application of orthogonal methods complementing aggregation propensity and avoid associated Experience with Managing Regulatory HCP testing and supporting process development By Cambridge Healthtech Institute immunogenicity risks, it is proposed to Expectation for Particles and Impurities for and control strategy, and to illustrate the use of risk focus on the very early steps of aggregation, Early and Late Stage Submissions assessment for HCP identification and control with often involving higher order structure (HOS) Moderator: consideration of clinical information. SHORT COURSES alterations and loss of colloidal stability, using a Maura Kibbey, Ph.D., Director, Global Biologics, U.S. set of orthogonal characterization techniques. 9:05 Quantitation of Affinity Ligand Leachate Pharmacopeia in Processing Samples – Why Commercial Panelists: Kits Fail and What You Can Do About It 2:45 USP Standards to Monitor and Jonas Hoeg Thygesen, Ph.D., Area Specialist, R&D - Xiaohui Lu, Ph.D., Senior Scientist, BioPharma Sponsorship Opportunities Microanalysis Centre, Novo Nordisk Pharmatech Characterize Impurities in Biologics Development, Biogen Maura Kibbey, Ph.D., Director, Global Biologics, U.S. Judy Shimoni, Ph.D., Principal Scientist and Group Hotel/Additional Information Pharmacopeia Leader, Protein Analytical Chemistry, Genentech, Inc., The United States Pharmacopeial Convention (USP) a member of the Roche Group Registration & Pricing is an independent scientific organization that protects Joël Richard, Ph.D., Vice President, Peptides, CMC & Engineering, Ipsen CHI-PepTalk.com CHI-PepTalk.com | 50 FINAL ANALYTICS & WEEKS JANUARY 9-10 | 4TH ANNUAL IMPURITIES TO REGISTER Detection and Characterization of Particulates and Impurities Rapid Tools for Risk Assessment, Prediction and Characterization of Impurities Cover from Products, Excipients, Processes and Packaging

Sponsors 9:35 Identification and Sponsored by Regulatory agencies call for identification and demonstrate how to address challenges in particle characterization of any intrinsic, inherent or extrinsic analysis using state-of-the-art particle analysis. Event-at-a-Glance Quantification of HCPs in mAbs, particles present in pharmaceuticals. USP <1787> Recombinant Proteins and 2:35 Protein-Excipient Interactions Evaluated via Biosimilars by Mass Spectrometry outlines methods and strategies for particle identification and characterization. Scanning Electron Microscopy NMR Studies in Polysorbate-Based Multi-Dose Michael Schirm, Ph.D., Associate Director, R&D (SEM) and Energy Dispersive X-ray Spectroscopy (EDS) Protein Formulations: Influence on Antimicrobial Proteomics, CAPRION BIOSCIENCES INC. are two of the methods discussed in USP <1787>. This Efficacy and Potential Study Approach Gel-free, label-free mass spectrometry (MS) enables presentation will show how SEM and EDS in combination Riccardo Torosantucci, Ph.D., Head of Laboratory identification and quantitation of total and individual with multivariate statistics enable rapid identification of Formulation Development, Pharmaceutical Development HCP in biotherapeutic products, and represents both visible and subvisible steel particles. Biologics, Sanofi-Aventis Deutschland GmbH an orthogonal method to ELISA. Examples will be presented showing use of semi-quantitative HCP 11:50 New NMR Methods for Fast and Preservatives are excipients needed in discovery (LC-MS/MS) and absolute quantitation Efficient Analysis of Trace Leachables and biopharmaceutical multi-dose formulations to prevent of HCP (LC-MRM/MS), as applied to monitoring microbial growth. However, they are known to interact Impurities in Biologics with non-ionic surfactants like polysorbate and of process changes/improvements, scale-up, Ken Skidmore, Technical Development Scientist, potentially with the active pharmaceutical ingredient batch uniformity, clearance, and comparison of Protein Analytical Chemistry, Genentech (API). In the current study those interactions were Biosimilars vs Innovators. Caprion’s HCP platform Analyzing process pools and drug product for a features customizable organism/process-specific successfully quantified via NMR and correlated to the broad spectrum of impurities is challenging. We will stability and antimicrobial activity of the formulations. databases, highly controlled analytical processes discuss three key NMR techniques we use for process and reproducible robust detection (to ~1ppm). NMR represents therefore a powerful tool to support development and regulatory filings: suppression of formulation development of multi-dose formulations. 10:05 Coffee Break in the Exhibit Hall with protein drug signals, while leaving impurity signals Poster Viewing intact; quantitation by 2D NMR in complex matrices; 3:05 Refreshment Break in the Exhibit Hall and the use of CRAFT NMR, a powerful new technique with Poster Viewing FORMULATION, RAW MATERIALS, which resolves the signals of trace impurities from EXCIPIENTS AND E&L IMPURITIES those of protein and formulation components. 10:50 Understanding Mechanism of Interaction 12:20 pm Sponsored Presentation FEATURED PRESENTATION between E&L and Proteins to Minimize Risk on (Opportunity Available) 4:00 Visual Inspection and Reconstitution Product Safety and Quality Attributes 12:50 Session Break Challenges: Protein Aggregation and Nanobubbles Kim Li, Ph.D., DABT, MPH, Senior Manager, Environment, Health, Safety and Sustainability 1:00 Luncheon Presentation (Sponsorship Theodore W. Randolph, Ph.D., Kenneth and Genevieve Product Stewardship Toxicology, Amgen Opportunity Available) or Enjoy Lunch on Your Gillespie Professor, Department of Chemical and Biological Engineering, University of Colorado, Boulder Plastic components are commonly used in the Own manufacture of drug-device combination products. When glassy lyophilized disaccharide cakes are The identification of the extractable and leachable FORMULATION, RAW MATERIALS, reconstituted, large numbers (billions per mL) of (E&L) impurities from the device components form the EXCIPIENTS AND E&L IMPURITIES small (130-150 nm) bubbles may be formed. These basis for toxicology assessments. However, significant nanobubbles are remarkably stable, lasting months (CONT.) in suspension. When incubated with proteins, they By Cambridge Healthtech Institute challenges remain with the quality evaluation of the can induce aggregation, an effect that appears to be therapeutic proteins. E&L impurities may interact 2:00 Chairperson’s Remarks modulated by ions bound to the nanobubble surface. with certain biological products, thus compromising Kim Li, Ph.D., DABT, MPH, Senior Manager, the quality attributes (e.g. protein aggregates and Environment, Health, Safety and Sustainability SHORT COURSES structural modifications). This presentation will Product Stewardship Toxicology, Amgen 4:30 Characterization of Universal Stabilized attempt to show how safety and quality evaluations can be bridged through the principles of Cramer 2:05 Challenges in Subvisible Particle Stem Flu Vaccine Candidates classification in relation to adverse outcome pathway. Characterization Sashikanth Banappagari, Ph.D., Scientist II, Formulation Development, Vaccine Production Sponsorship Opportunities Miguel Saggu, Scientist, Late Stage Pharmaceutical 11:20 Identification of Micro Steel Particles Program/VRC/NIAID/NIH Development, Genentech Using Energy Dispersive X-ray Spectroscopy The purpose of this project is to elicit responses Hotel/Additional Information This presentation will address challenges in across multiple strains, looking towards a pandemic Coupled with Multivariate Statistics subvisible particle analysis in biopharmaceutical Jonas Hoeg Thygesen, Ph.D., Area Specialist, R&D - flu vaccine. This study describes advanced biophysical Registration & Pricing formulations. It will discuss case studies to Microanalysis Centre, Novo Nordisk Pharmatech characterization of stabilized stem constructs of CHI-PepTalk.com CHI-PepTalk.com | 51 FINAL ANALYTICS & WEEKS JANUARY 9-10 | 4TH ANNUAL IMPURITIES TO REGISTER Detection and Characterization of Particulates and Impurities Rapid Tools for Risk Assessment, Prediction and Characterization of Impurities Cover from Products, Excipients, Processes and Packaging

Sponsors HA-Ferritin by CD, DSC, FTIR, Fluorescence and 2D UV-vis spectroscopy. These methods can contribute to Event-at-a-Glance understanding the basal physicochemical properties for optimal formulation development and monitoring vaccine quality that pertains to product comparability studies during development.

5:00 Considerations for Assessment of Particles in Biologics Originating from Packaging and Standardization Initiatives Diane Paskiet, MS, Director of Scientific Affairs, Scientific Affairs and Technical Services, West Pharmaceutical Services It is critical to understand the types and sources of particulates in biologic products and how their presence may affect product quality and patient safety. The linkage between particles, biologic formulation and packaging development involves understanding contributions from all sources. This presentation will provide insight into measurements of particles originating from packaging components, comparison of data from various technologies and USP standardization initiatives.

5:30 - 6:45 Networking Reception in the Exhibit Hall with Poster Viewing 6:45 Close of Detection and Characterization of Particulates and Impurities Conference

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 52 FINAL ANALYTICS & WEEKS JANUARY 11-12 | 2ND ANNUAL IMPURITIES TO REGISTER Bioprocess Analytics Data Measurement, Monitoring and Modeling Allow Informed Control of Bioprocesses Cover

Sponsors The biopharmaceutical industry is meeting increasing demands and costs for biotherapeutics through process optimization. Advanced instrumentation with sampling techniques, new sensor technologies and analyzers have emerged to monitor both upstream and downstream processes. These analytical tools, however, Event-at-a-Glance result in large, complex datasets with multivariate interactions. The inherently complex nature of these datasets makes extraction of meaningful and relevant information a difficult task. Cambridge Healthtech Institute’s Second Annual Bioprocess Analytics conference addresses statistical analysis strategies including multivariate data analysis (MVDA), quality by design (QbD), process analytical technology (PAT) and multi-attribute method (MAM), allowing for optimized and informed control of bioprocessing.

THURSDAY, JANUARY 11 9:00 Speed to IND: Alignment and quantified by mass spectrometry. This dataset Acceleration of Critical Early Phase Activities of HCPs provides insights into determining the 7:45 am Registration and Morning Coffee Kyle Zingaro, Ph.D., Development Scientist II, Early appropriate target proteins to be removed during Stage Development, Alexion Pharmaceuticals both the cultures and purification steps for ensuring good therapeutic protein quality. PROCESS TO PRODUCT Speed to IND is the current battle cry across early 8:15 Chairperson’s Opening Remarks phase biologics development. Despite some 11:30 Using SUREscan™ to Survey Sponsored by Gyun Min Lee, Ph.D., Professor, Biological Sciences, KAIST risks, new technologies and workflow alignment Genetic Changes in Stable CHO can afford faster and better decisions during this crucial phase of new product development. This is Cell Lines KEYNOTE PRESENTATION especially true across the Discovery and Process Pierre-Alain Girod, CSO, Selexis Development handoff. We present new data and CHO cells are the most frequently applied host- 8:20 Integrating Cell Culture with approaches to improve that handoff and detail the cell system for industrial protein therapeutic Magnetic Protein A Bead-Trap impact on timelines and quality of molecules and manufacturing. Rapid generation of high-producing Technology Accelerates Antibody cell lines in early phase development. clones that don’t lose expression capability over Purification time has been a major industry focus. Using John K. Kawooya, Ph.D., Director, Biologics 9:30 "Lost in Translation": Bridging the Gap SUREscan™ with next-generation sequencing (NGS), Optimization, Discovery Research, Amgen between Academia and Biotech we can quickly analyze whole genomes of any cell line, improving traceability of Research Cell Banks Antibody engineering produces large Tsafi Danieli, Ph.D., Director, BioGiv Excubator & Head, (RCBs). In contrast to other CHO published data, we numbers of molecules (200-500 molecules Protein Expression Facility, Wolfson Centre for Applied will show that SUREtechnology Platform™ generates at 30-50ml each) which require purification, Structural Biology, Alexander Silberman Institute of RCBs with chromosomally stable lineages. analysis and screening for potency, binding, Life Sciences, The Hebrew University of Jerusalem pharmacodynamics, pharmacokinetics, One of the most difficult and frustrating aspects of 12:00 pm Session Break manufacturability, expression levels and basing a startup company on academic findings is Sponsored by stability in order to select leads. Ever since its translating and transferring academic findings to 12:15 Luncheon Presentation: inception over 30 years ago, the AKTA system biotech language. This procedure is often frustrating Get Your High Protein to both parties and requires psychological skills as combined with Protein A agarose columns Concentrations Right on the Money with Lunatic has remained the “workhorse” of antibody well as critical review of the research. Working in the purification from cell cultures. However, the interphase between academia and industry, there Thomas Martens, Principal Scientist, Unchained Labs inability of this system to process multiple are several preemptive strikes we can take to avoid Stop quantifying proteins one by one hoping that samples in parallel coupled with both its some of the major pitfalls. your old reader is getting the numbers right. Get rid By Cambridge Healthtech Institute limiting flow rates, its requirement for multiple of that dilution step you always need to measure 200 FTEs to remove cells and particulate from 10:00 Coffee Break in the Exhibit Hall with mg/ml IgG or even higher. Come learn about how each sample prior to loading together with Poster Viewing Lunatic gets rid of all dilutions, eliminates any risk SHORT COURSES the potential for sample swapping errors and of cross contamination and accurately measures cross contaminations – all impose major 11:00 Proteomic Analysis of Host Cell Protein protein concentration at high throughput and high bottlenecks in expediting large purified panels Dynamics in the Culture Supernatants of concentrations. We’ll talk about how lunatic: of molecules. In this presentation, I show how Therapeutic Protein-Producing CHO Cells • measures either 16 or 96 samples in one run • uses only 2 µL for each measurement Sponsorship Opportunities a single FTE with parallel Magnetic Protein A Gyun Min Lee, Ph.D., Professor, Biological Sciences, KAIST • needs only 5 minutes bead-trap technology accelerates delivery of Host cell proteins (HCPs) accumulate extracellularly • Requires no dilutions Hotel/Additional Information high-quality purified antibodies in high yield during the cultures of recombinant CHO (rCHO) directly from small (30ml-5liters) to large cells, potentially impairing product quality. HCPs Registration & Pricing (25-liter wave-bag) crude cell cultures without accumulated extracellularly in batch and fed-batch centrifugation or filtration. cultures of rCHO cell lines were identified and CHI-PepTalk.com CHI-PepTalk.com | 53 FINAL ANALYTICS & WEEKS JANUARY 11-12 | 2ND ANNUAL IMPURITIES TO REGISTER Bioprocess Analytics Data Measurement, Monitoring and Modeling Allow Informed Control of Bioprocesses Cover

Sponsors 1:15 Ice Cream Break in the Exhibit Hall with to the Cedex Bio HT Analyzer (Roche Diagnostics, FRIDAY, JANUARY 12 Germany) for an accurate sample processing Event-at-a-Glance Poster Viewing and sophisticated process analytics. Thereby, all 8:00 am Registration ANALYTICAL WORKFLOWS AND systems are integrated in our data acquisition, management and analysis system to ensure an 8:00 BuzZ Sessions with Continental Breakfast MODELING efficient data processing. Protein therapeutics is a fast-growing 2:00 Chairperson’s Remarks 3:35 Refreshment Break in the Exhibit Hall global market. As the science improves, Tsafi Danieli, Ph.D., Director, BioGiv Excubator & Head, with Poster Viewing so does the complexity of the R&D Protein Expression Facility, Wolfson Centre for Applied organization. Ensuring product quality Structural Biology, Alexander Silberman Institute of CELL LINE DEVELOPMENT plus speed to market requires insights from Life Sciences, The Hebrew University of Jerusalem stakeholders working across the stages of protein 4:15 Lost in Translation: On the Formation of science R&D. Join experts representing this PepTalk 2:05 Novel Hybrid Modeling Approaches for Protein Sequence Variants pipeline, peers, and colleagues for an interactive QbD: Getting More from the Combination Zhongqi Zhang, Ph.D., Scientific Director, Attribute roundtable discussion. Topics include highlights of Fundamental Knowledge and Statistical Sciences, Process Development, Amgen from the week’s presentations, new technologies Methods With modern mass spectrometry and appropriate and strategies, challenges, and future trends. Moritz von Stosch, Ph.D., Senior Manager, informatics tools, a large number of low-level Table Moderator: Diane Paskiet, MS, Director of Fermentation, Technical R&D, GSK Vaccines sequence variants in therapeutic proteins are Scientific Affairs, Scientific Affairs and Technical The combination of fundamental knowledge with detected and quantified. This large collection of Services, West Pharmaceutical Services statistical methods is referred to as hybrid modeling. information allows for a deeper understanding of the Table Moderator: Moritz von Stosch, Ph.D., Senior These models have been shown to 1) provide mechanism for the formation of sequence variants, Manager, Fermentation, Technical R&D, GSK Vaccines better extrapolation properties, 2) have lower data thereby facilitating optimization of cell line and cell requirements, and 3) are more efficient to develop culture process to minimize them. than models based on a single knowledge source. This talk introduces novel hybrid methods that work 4:45 The Stability of CHO Genome: Essential PRODUCT CHARACTERIZATION more coherently with small datasets and estimate for Cell Line Characterization or Not? AND ANALYTICS their own prediction quality, such being optimal for Noriko Yamano, Ph.D., Senior Scientist, 9:00 Chairperson’s Remarks the development of the process design space in the Manufacturing Technology Association of Biologics; Moritz von Stosch, Ph.D., Senior Manager, context of QbD. Guest Academic Staff, Graduate School of Fermentation, Technical R&D, GSK Vaccines Engineering, Osaka University 2:35 Phase-Appropriate Analytics The chromosomes in CHO cells frequently cause SiowFong Wee, Ph.D., Director, Formulation, 9:05 Characterization of mAbs Using Charge genomic variations, due to genetic instability. Analytical & Bioassay, Aptevo Therapeutics Variant Analysis Coupled to High Resolution Distribution and stability of chromosomes were Native Mass Spectrometry It can be a struggle to decide how much analytics is examined in CHO-DG44 cells, and two cell lines Jonathan Bones, Ph.D., Principal Investigator, considered sufficient for product quality evaluation and expressing different numbers of chromosomes Characterisation and Comparability Laboratory, characterization to support a project that is in the early were isolated from the original CHO-DG44 cell By Cambridge Healthtech Institute National Institute for Bioprocessing Research and development stage. Phase-appropriate analytics to line to investigate the effect of aneuploid cells on Training support ‘clone-to-clinic’ will be presented in this talk. recombinant protein production. In addition, gene expression profiles between cells with disparate Charge variant analysis (CVA) of biopharmaceuticals 3:05 Integration of ambr High-Throughput SHORT COURSES chromosome numbers have been compared by is required under ICH Q6B. Issues arise when a Bioreactor Systems into the USP mRNA-seq analysis. new peak is identified in the CVA profile. Here, the Development Workflow and into the Data development of high resolution charge variant Acquisition, Management and Analysis 5:15 High-Throughput Screening of analysis coupled directly to native high resolution System Transfection Efficiency of dTtaPS Reagent mass spectrometry is described that facilitates Sponsorship Opportunities the intact mass analysis of minor charge variants Timo Frensing, Ph.D., Senior Scientist, Cell Culture Library, and Its Application for Transient with high mass accuracy. Application to the Hotel/Additional Information Research, Roche Diagnostics GmbH Production of Proteins in Micro Bioreactors characterization of mAbs and other recombinant To enable a high-throughput USP development Harsh Jain, PhD, Visiting Associate, FDA proteins is described under normal conditions and Registration & Pricing we implemented a semi-automated workflow to during forced degradation studies. connect ambr® bioreactors (Sartorius, Germany) 5:45 Close of Day via a Fluent® pipetting robot (Tecan, Switzerland) CHI-PepTalk.com CHI-PepTalk.com | 54 FINAL ANALYTICS & WEEKS JANUARY 11-12 | 2ND ANNUAL IMPURITIES TO REGISTER Bioprocess Analytics Data Measurement, Monitoring and Modeling Allow Informed Control of Bioprocesses Cover

Sponsors 9:35 Utilizing High-Throughput Lab To optimize the efficiency of these processes, we have improved already existing and developed novel Event-at-a-Glance Automation and Analytics, Advanced Data Management and Multivariate Statistical methods to efficiently test candidates for their Analysis to Define the Formulation Design suitability, e.g., regarding their specificity. Space for Biotherapeutics 11:45 High-Throughput Characterization Michael Siedler, Ph.D., Head, NBE High-Throughput of Hydrolytic Enzymes in Low Volume and and Advanced Formulation Sciences, Drug Product Closed Systems Development, AbbVie Deutschland GmbH & Co. KG Nigel F. Reuel, Ph.D., Assistant Professor, Chemical We discuss adaption and miniaturization of and Biological Engineering, Iowa State University standard analytical methods to be used for 96 and Hydrolytic enzymes play a significant role in 384 well plates, transition to a data-centric strategy, biologic and synthetic processes. The ability to and implementation of advanced data management better characterize these enzymes would enable to effectively integrate and analyze screening data shorter development times and better products. (including metadata). We also discuss multivariate This talk will detail two recent developments for parameter analysis and statistical modeling to hydrolytic enzyme characterization: 1) a carbon calculate the formulation design space, hence nanotube-based optical sensor that allows for assuring safety and efficacy of new products. quantitative measurement in <20ul volumes and 2) a 10:05 The Use of Method Performance resonant antenna sensor that passively transmits its Monitoring as a Component of a response in the 1-100MHz range, enabling detection within closed, opaque systems. Comprehensive Product Control Strategy Juma Bridgewater, Ph.D., Senior Scientist, Analytical Sciences and Technology, Bristol-Myers Squibb 12:15 pm Conference Wrap-Up Method performance monitoring is a critical Richard Altman, MS, Scientist, Protein Technologies, component of a comprehensive pharmaceutical Amgen product control strategy. It comprises the real-time Haiyan Jiang, Ph.D., Principal Scientist, Biologics trending of sample-independent method metrics to Research, Janssen BioTherapeutics, Janssen R&D assess the performance of methods used to control Diane Paskiet, MS, Director of Scientific Affairs, process parameters, raw material, intermediate, DS Scientific Affairs and Technical Services, West and DP quality attributes. MPM detects deterioration Pharmaceutical Services in method performance and maintains consistent Bjørn Voldborg, Director, CHO Cell Line Development, quality of the data used for product control. The Novo Nordisk Foundation Center for 10:35 Coffee Break with a Poster Pavilion Biosustainability, Technical University of Denmark Moritz von Stosch, Ph.D., Senior Manager, See page 4 for details Fermentation, Technical R&D, GSK Vaccines By Cambridge Healthtech Institute HIGHER-THROUGHPUT SYSTEMS 12:45 Close of Conference 11:15 High-Throughput Automations and SHORT COURSES Optimizations for Improved Binder Generation and Validation Jonas Schaefer, Ph.D., Head, High-Throughput Binder Selection Facility, Biochemistry, University of Zurich Sponsorship Opportunities While recombinant binder selection pipelines by now work in rather high-throughput, the screening Hotel/Additional Information of suitable affinity reagents and especially the validation of their essential features for the final Registration & Pricing applications is still laborious and time-intensive.

CHI-PepTalk.com CHI-PepTalk.com | 55 FINAL WEEKS TO REGISTER

Cover

Sponsors Event-at-a-Glance PROCESS TECHNOLOGIES & PURIFICATION

JANUARY 8-9 AGENDA Single-Use Technologies and Continuous Processing

JANUARY 9-10 AGENDA Protein Purification and Recovery

JANUARY 11-12 AGENDA Higher-Throughput Protein Production and Characterization

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 56 FINAL PROCESS WEEKS JANUARY 8-9 | 5TH ANNUAL TECHNOLOGIES & TO REGISTER Single-Use Technologies and Continuous Processing PURIFICATION Advancing Bioprocessing through Technological Innovation Cover

Sponsors Cambridge Healthtech Institute’s Fifth Annual Single-Use Technologies and Continuous Processing conference will once again gather technology and equipment Event-at-a-Glance providers, end users, and regulators to discuss innovative approaches to current challenges, update companies on the trends in technology, share case studies on successful implementation, and ultimately identify how to derive as much value as possible from these technological advances.

SUNDAY, JANUARY 7 9:50 Challenges and Limitations of In the future, traditional cleanroom environments Continuous Processing and Use of and facilities will need to be more agile to adapt with 4:00 - 6:00 pm Pre-Conference Registration Disposables manufacturers’ product portfolio and throughput needs, and will require faster implementation in Berthold Boedeker, Ph.D., Chief Scientist, Global order to respond to new opportunities and demand MONDAY, JANUARY 8 Biologics Development, Bayer Pharma AG around the world. The discussion will focus on Continuous processing in combination with use 7:00 am Registration and Morning Coffee advancements in single-use technologies and of disposables has made significant advances in continuous manufacturing, future manufacturing and the past years. However, despite many advantages CONTINUOUS PROCESSING: facility needs, and innovative cleanroom and facility to standard processing, there are still many designs being developed to address these needs. CONSIDERATIONS, hurdles ahead of us, before these technologies IMPLEMENTATION AND ENABLING will be suitable for routine production. This talk 12:15 pm Sponsored Presentation will summarize several aspects of necessary (Opportunity Available) TECHNOLOGIES improvements as well as some risks associated with 9:00 Welcome by Conference Organizer these technologies, which are often underestimated 12:45 Session Break in their impact, such as process validation, process Kip Harry, Senior Conference Director, Cambridge characterization and scale-down models. 1:00 Luncheon Presentation (Sponsorship Healthtech Institute Opportunity Available) or Enjoy Lunch on Your 9:05 Chairperson’s Opening Remarks 10:20 Networking Coffee Break Own Dennis Powers, Director, Sales Engineering, G-CON 10:45 A Single-Use Strategy to Enable Manufacturing Manufacturing of Affordable Biologics ADVANCES IN SINGLE-USE Renaud Jacquemart, Ph.D., BioPharma Downstream TECHNOLOGIES Process Specialist, Natrix Separations KEYNOTE PRESENTATION 2:00 Chairperson’s Remarks Single-use technologies and continuous upstream 9:10 A Fully Automated Adam Goldstein, MSc, Principal Scientist, Global processes have proven to be cost-efficient options Technology, Roche/Genentech Biopharmaceutical Manufacturing Plant: to increase biomass production. This case study Process Design, Modeling, and Control summarizes how a single-use strategy including a 2:05 Technology Advances in Single-Use Richard D. Braatz, Ph.D., Edwin R. Gilliland holistic process approach, continuous operation, Technologies Professor of Chemical Engineering, full utilization of media life (up to 100 cycles per Massachusetts Institute of Technology batch) and high-throughput chromatography Adam Goldstein, MSc, Principal Scientist, Global This presentation describes the strategy used (residence time ≤6s and loads in kg/L media) can Technology, Roche/Genentech in the design of a fully automated small- overcome scale limitations and enable cost-efficient This presentation will focus on challenges single- By Cambridge Healthtech Institute footprint biopharmaceutical manufacturing manufacturing to support the growing demand for use applications currently have and may have in plant that produces multiple biologics. affordable biologics. the future of biomanufacturing. I will also discuss Dynamic models are constructed for the advances in single-use technologies, with particular 11:15 Integrated Continuous Manufacturing emphasis on bulk freeze applications. SHORT COURSES design of the equipment for the unit operations and their operations including the real-time Progress and the Life Sciences Industry “Fad 2:35 Challenges Faced by the End Users control of biologic drug production. An or Reality” during the Qualification of SUS opportunity is the use of a “virtual” plant for the Robert Dream, Ph.D., Managing Director, HDR dynamic operations of the entire end-to-end Company LLC Ben Jeyaretnam, E&L Analytical Lead, Sanofi Sponsorship Opportunities biomanufacturing process. The virtual plant Recently the pharmaceutical industry has been can guide the selection of a control strategy for 11:45 Flexible Facility Designs increasingly using single-use systems (SUS). Before Hotel/Additional Information each critical quality attribute (CQA), design of Complementing Continuous Processing a SUS can be used in the manufacturing process, startup and shutdown operations, and control it needs to be qualified for use by a predetermined Registration & Pricing Dennis Powers, Director, Sales Engineering, G-CON systems design. Manufacturing process. This presentation will discuss a variety

CHI-PepTalk.com CHI-PepTalk.com | 57 FINAL PROCESS WEEKS JANUARY 8-9 | 5TH ANNUAL TECHNOLOGIES & TO REGISTER Single-Use Technologies and Continuous Processing PURIFICATION Advancing Bioprocessing through Technological Innovation Cover

Sponsors of challenges that the end user faces during steel to a 1000 L single-use bioreactor for a monoclonal antibody Protein A capture using a twin- Event-at-a-Glance the qualification process. Complexity of SUS, continuous cell culture application will be discussed. column countercurrent CaptureSMB process and varying quality of vendor data, component change As a second part, a 10 mL down-scale system for polishing using a twin-column MCSGP process are management, changing regulatory expectations, perfusion cultivation in a single-use microbioreactor discussed in greater detail. E&L study execution, analytical challenges, and the will be introduced and its application for process potential impact of unexpected E&L study results development evaluated. 9:35 Sponsored Presentation (Opportunity will be presented. Available) 6:00 - 7:15 Welcome Reception Sponsored by 3:05 Transition to BuzZ Sessions in the Exhibit Hall with Poster 9:50 Coffee Break in the Exhibit Hall with Viewing Poster Viewing 3:15 BuzZ Sessions with Refreshments 7:15 Close of Day 11:00 Large-Scale Extractable and Leachable Join your peers and colleagues for Analysis of Single-Use Bioreactors for interactive roundtable discussions. TUESDAY, JANUARY 9 Biopharmaceutical Manufacture Please see page 78 for additional Jonathan Bones, Ph.D., Principal Investigator, information. 8:00 am Registration and Morning Coffee Characterisation and Comparability Laboratory, National Institute for Bioprocessing Research and BIOPROCESS ANALYTICS FOR Training 4:30 Selected Presentation SINGLE-USE SYSTEMS AND This presentation will describe the characterization of extractables and leachables from disposable 5:00 Plastic Components and Systems Used CONTINUOUS PROCESSING bioreactors within a public-private partnership. on the Manufacturing of a Drug Product: Current Compendial Perspectives 8:30 Chairperson’s Remarks 11:30 High-Throughput Cell Line Screening Desmond G. Hunt, Ph.D., Senior Scientific Liaison, Jonathan Bones, Ph.D., Principal Investigator, Specific for Perfusion Processes Standards Development, United States Pharmacopeia Characterisation and Comparability Laboratory, Jean-Marc Bielser, Research Scientist, Biopharma (USP) National Institute for Bioprocessing Research and Technology and Innovation, Global Manufacturing & Training USP General Chapter <661.3> contains tests, test Supply, Merck methods and specifications for characterizing 8:35 SU Sensors on FlexAct UD, a SU Platform 12:00 pm PANEL DISCUSSION: Advances in materials used to construct manufacturing for UF/DF: In-Process Testing and Evaluation components and for components used in Bioprocess Technologies and Analytics of Robustness manufacturing systems. In this presentation, the Moderator: philosophy behind the form and contents of <661.3> Nikhil Ramsubramaniam, Ph.D., Senior Scientist, Merck Jonathan Bones, Ph.D., Principal Investigator, is discussed, specifically focusing on similarities 9:05 Continuous Chromatography for the Characterisation and Comparability Laboratory, and differences between packaging (addressed in National Institute for Bioprocessing Research and Improvement of the Purification of Proteins <661.1> and <661.2>) and manufacturing. Training and Peptides Panelists: By Cambridge Healthtech Institute 5:30 Single-Use Considerations for the Thomas Müller-Späth, Ph.D., Senior Scientist, Institute Nikhil Ramsubramaniam, Ph.D., Senior Scientist, Merck High-Yield Production of Glyco-Optimized for Chemical and Bioengineering, ETH Zürich Thomas Müller-Späth, Ph.D., Senior Scientist, Institute Biopharmaceuticals with Human Cells in Continuous chromatography processes allow for Chemical and Bioengineering, ETH Zürich SHORT COURSES Perfusion Bioreactors a number of improvements in the downstream processing of biomolecules including increase in Steffen Kreye, Ph.D., Associate Director, USP, 12:30 Session Break Glycotope GmbH throughput, improved stationary phase utilization, improved yield and reduced buffer consumption. The GlycoExpress® (GEX®) technology displays 12:45 Luncheon Presentation (Sponsorship In this talk a brief overview of the different process a set of human cell lines for the production of Opportunity Available) or Enjoy Lunch on Your Sponsorship Opportunities concepts including CaptureSMB and MCSGP is glyco-optimized human biopharmaceuticals. Case presented and their strengths and weaknesses Own studies for GEX® processes will be highlighted with Hotel/Additional Information with respect to different applications is discussed. special focus on single-use applicability, continuous 1:15 Close of Single-Use Technologies and The concepts are also reviewed in the context processing and product quality. In a first section, Continuous Processing Conference Registration & Pricing of integration into continuous downstream data of a process transfer from a 200 L stainless manufacturing. The application examples of CHI-PepTalk.com CHI-PepTalk.com | 58 FINAL PROCESS WEEKS JANUARY 9-10 | 10TH ANNUAL TECHNOLOGIES & TO REGISTER Protein Purification and Recovery PURIFICATION Streamlining & Innovating Processes Cover

Sponsors The Tenth Annual Protein Purification and Recovery conference examines the strategies that efficiently lead to pure protein for research or therapeutic use. As the Event-at-a-Glance most costly and time-consuming process in the manufacture of protein-based therapies, purification poses continual challenges for streamlining steps and cutting costs. Challenges are multiplied when purifying complex molecules, such as membrane proteins or antibody-drug conjugates. This leading purification meeting explores how experts are optimizing processes to reach project goals in a timely way. Along with innovating ‘traditional’ technologies such as affinity tags, Protein A, and chromatography, leaders will also address alternatives and breakthroughs.

TUESDAY, JANUARY 9 a very valuable new tool for antibody and Fc-fusion 5:00 Co-Elution of Host Cell Proteins (HCP) protein purification. The process of the development, with Monoclonal Antibodies and Their 1:00 pm Registration its function as well as the molecular explanation of Potential Immunogenicity Risk Assessment its behavior will be discussed. Qingchun Zhang, Ph.D., Senior Scientist, Process 1:30 Refreshment Break in the Exhibit Hall Development, Amgen, Inc. with Poster Viewing 3:15 SELECTED POSTER PRESENTATION: Designing a State-of-the-Art Sample Recent advances in mass spectrometry allow Management Facility to Empower Research the identification and quantification of individual ANTIBODY PURIFICATION HCPs. These advancements now make it possible Katharine Heeringa, Scientific Researcher, Protein to characterize HCPs in the presence of mAbs 2:00 Chairperson’s Opening Remarks Sciences, Genentech, Inc. and to collect data to perform a risk assessment Christopher H. Gray, Ph.D., Team Leader, Structural Biomolecular Resources Sample Management of individual HCP impurities. A comprehensive Biology, Drug Discovery Program, CRUK Beatson Institute (BMR-SM) at gRED is a state-of-the-art facility comparison of HCP subpopulations across supporting all of research at Genentech, acting as different mAbs was conducted and the potential both a nucleic acid and protein repository and a KEYNOTE PRESENTATION immunogenicity risk of commonly observed HCPs nucleic acid production facility. BMR-SM leverages was investigated using both in silico prediction and 2:05 Introduction of a Disruptive bioinformatics and automation to support multiple an in vitro PBMC-based assay. Technology into a Highly Regulated users and at multiple access points with a diverse Industry: A Brief History with Lessons range of products and comprehensive sample and 5:30 Close of Day process tracking. We seek to build a core biologic Learned molecule repository and nucleic acid production 5:30 - 5:45 Short Course Registration David Wood, Ph.D., Professor, Professor, group that can expand and adapt to an ever- Chemical & Biomolecular Engineering, The Ohio changing research environment. 5:45 - 8:45 Dinner Short Courses* State University See page 5 for details 3:45 Refreshment Break in the Exhibit Hall Over the past 20 years, we and others * Separate registration required have worked to develop a highly disruptive with Poster Viewing self-cleaving tag technology for the 4:30 An Introduction to HisMAB: An Antibody- biopharmaceutical industry. As we draw closer WEDNESDAY, JANUARY 10 to this goal, it is worthwhile to consider the Based Affinity Purification System for His larger picture of how we have adapted our goals Tagged Proteins and approaches to this highly regulated and Jiansheng Wu, Ph.D., Principle Scientific Manager, 8:00 am Registration and Morning Coffee

By Cambridge Healthtech Institute rapidly developing industry. This talk will cover Protein Chemistry, Genentech, Inc. the history and most recent developments of Ni based methods have been well established for INNOVATING PROCESSES this technology in this context. the purification of his tagged proteins for decades. 8:30 Chairperson’s Remarks They usually have high binding capacity at relatively Sophia Hober, Ph.D., Professor, Molecular SHORT COURSES low cost. However, due to the low selectivity of Ni 2:45 Optimization of an IgG-Binding, Protein Biotechnology, KTH Royal Institute of Technology resin, sometimes it is difficult to purify His tagged A-Based Purification Matrix proteins with poor expression. In my lab, we have Sophia Hober, Ph.D., Professor, Molecular developed a new antibody based affinity system for Sponsorship Opportunities Biotechnology, KTH Royal Institute of Technology the purification of His tagged proteins. The antibody Presented here is an engineered protein based on called HisMAB binds to his tagged proteins at high Hotel/Additional Information the Protein A-derived Z domain, to which a calcium- affinity. It has very high specificity toward his tagged binding EF-loop has been introduced. The new proteins. In this talk, we will share our experience Registration & Pricing protein domain, ZCa, is shown to have a calcium using the antibody. HisMAB is best suited for dependent binding to IgG and can be used to purify the purification of secreted his tagged proteins antibodies with elution by EDTA at pH 5.5, providing expressed by BEVS and mammalian systems. CHI-PepTalk.com CHI-PepTalk.com | 59 FINAL PROCESS WEEKS JANUARY 9-10 | 10TH ANNUAL TECHNOLOGIES & TO REGISTER Protein Purification and Recovery PURIFICATION Streamlining & Innovating Processes Cover

Sponsors time and expertise required to perform these in Native Separations of a Thiol-Linked Event-at-a-Glance FEATURED PRESENTATION techniques. We present a new platform that swiftly Antibody-Drug Conjugate identifies sample quality and relative functionality Andrew Holloway, Senior Research Associate, 8:35 Ten-Minute Purification and Rapid in minutes complementing and guiding purification Analytical Sciences, Seattle Genetics, Inc. Folding of Proteins by Vortex Fluidic Device and characterization workflows—making go/no go decisions easy and quick—saving time, effort and ® Sponsored by Gregory A. Weiss, Ph.D., Professor, Chemistry and 12:20 The Strep-tag Technology - cost downstream. Molecular Biology & Biochemistry, University of The Superior Tag System for the California, Irvine 10:05 Coffee Break in the Exhibit Hall with Entire Protein Production Recombinant proteins often require process intensive Poster Viewing Workflow purification and refolding steps. In collaboration with Dennis Niermeier, MSc, IBA Lifesciences Professor Colin Raston (U. Flinders, Australia), my NEXT-GEN CHROMATOGRAPHY lab applies a vortex fluidic device for continuous flow 12:50 Session Break purification and refolding of proteins. Cell lysates 10:50 SELECTED POSTER PRESENTATION: 1:00 Luncheon Presentation (Sponsorship can be directly processed without chromatography Tricks to Enhance Bispecific Antibody Opportunity Available) or Enjoy Lunch on Your or centrifugation steps. Furthermore, the proteins Purification by Using Protein L remain bioconjugated to the surface of the flow Own Chromatography reactor, allowing in-line bioprocessing by enzymes after their recovery from lysates. Yuichiro Shimizu, Ph.D., Research Manager, Chugai PURIFYING MEMBRANE PROTEINS Pharmabody Research PTE. LTD. In this study, we have established a system to 2:00 Chairperson’s Remarks 9:05 Bigger, Brighter, Faster: Accelerating efficiently separate 4-chain bispecific antibodies Dmitry G. Vassylyev, Ph.D., Professor, Biochemistry Protein Production by Enhancing Soluble (BiAb) as well as to remove certain type of by- and Molecular Genetics, University of Alabama at products by using protein L chromatography. Due Yield, Monitoring Expression and Birmingham to its simplicity and robustness, this method can Compressing Chromatography Strategies potentially be used broadly for BiAb purification with 2:05 Detergent-Free Purification of Christopher H. Gray, Ph.D., Team Leader, Structural minimum engineering of amino acid sequences. Membrane Proteins Using SMA Polymer Biology, Drug Discovery Program, CRUK Beatson Institute Alice Rothnie, D.Phil., Lecturer, Biochemistry, Life & We increased output using auto-cleaving MBP fusions, Health Sciences, Aston University elevating soluble expression while eliminating MBP 11:20 An Efficient, Ultra-High Affinity Purification of membrane proteins can be from purification. Additionally, we developed systems Chromatography in a One-Step Purification of challenging due to the need to remove them from for rapid monitoring of target expression during Complex Proteins the membrane. Traditionally, this is achieved using fermentation using a co-expressed GFP tracer. Finally, Dmitry G. Vassylyev, Ph.D., Professor, Biochemistry and detergents, which often cause instability and/ we developed multimodal style affinity chromatography Molecular Genetics, University of Alabama at Birmingham or loss of function. A new methodology for the for tandem tagged proteins giving high purity material Protein purification is the basis for numerous extraction and purification of membrane proteins in a single column without need for slow polishing biochemical and biomedical studies. It is particularly uses a styrene maleic acid co-polymer (SMA) which steps. The net result is reliability, higher yields and crucial and challenging for structural analysis inserts in the membrane and assembles into small accelerated delivery to downstream users. By Cambridge Healthtech Institute and industrial protein production, where it has discs of bilayer encircled by polymer, termed SMA 9:35 A Quick Check of Protein Sponsored by to meet the High-yield/High-purity/High-activity lipid particles (SMALPs). These particles are stable, Quality that Will Vastly Improve (HHH) requirement. The ultra-high affinity (CL7/ maintain the lipid environment of a protein and are amenable to structural and biophysical studies. all Protein Purification and Im7) purification system allows for one-step SHORT COURSES HHH-purification of a wide range of traditionally Characterization Workflows challenging proteins and might emerge as a 2:35 Small Affinity Tags for Efficient Peter Fung, Ph.D., Senior Manager, Product universal high-throughput purification tool to Purification and Recovery of Integral Marketing, NanoTemper Technologies advance biological studies and manufacturing of Membrane Receptors Sponsorship Opportunities Starting with material of questionable quality for therapeutic proteins. Alexei Yeliseev, Ph.D., Staff Scientist, LMBB, NIH/ NIAAA protein purification and characterization leads We expressed the recombinant cannabinoid Hotel/Additional Information to irreproducible or ambiguous results. Methods 11:50 Multidimensional Chromatography receptor CB2 expressed in E. coli cells as well as in such as chromatography while widely used, can Coupled with Mass Spectrometry expi CHO cells in milligram quantities. Protein was Registration & Pricing also derail experiments—due to the amount of Characterization of Species Observed purified by tandem affinity chromatography using

CHI-PepTalk.com CHI-PepTalk.com | 60 FINAL PROCESS WEEKS JANUARY 9-10 | 10TH ANNUAL TECHNOLOGIES & TO REGISTER Protein Purification and Recovery PURIFICATION Streamlining & Innovating Processes Cover

Sponsors either His tag/twin Strep-tag or His tag/EF1 tag consensus sequences reversibly precipitate with Event-at-a-Glance pairs. In this work, we compare the use of single calcium addition and we have developed this for affinity and tandem affinity purification strategies. non-chromatographic protein purification. We have The protocols developed in our laboratory can be also engineered a face of the beta roll domain to applied to expression and purification of other bind to a target protein and this enables a new membrane receptors for structural and functional calcium-dependent catch and release affinity studies. chromatography platform.

3:05 Refreshment Break in the Exhibit Hall 5:30 - 6:45 Networking Reception in the with Poster Viewing Exhibit Hall with Poster Viewing OVERCOMING PERSISTENT 6:45 Close of Protein Purification and CHALLENGES Recovery Conference 4:00 The Development of Optimised Silica Resins to Solve Complex Purification Challenges Søren Flygenring Basset, Ph.D., Director, R&D, Novo Nordisk Pharmatech A/S 4:30 Establishing Guiding Principles to Optimize Host Cell Protein Removal during Purification Process Development André C. Dumetz, Ph.D., Senior Scientific Investigator, Biopharm Downstream PD-3, R&D Platform Technology & Science, GlaxoSmithKline 5:00 Engineering the Beta Roll Domain for Bioseparations Applications Scott Banta, Ph.D., Professor, Chemical Engineering, Columbia University RTX peptide domains are intrinsically disordered and reversibly fold into the beta roll secondary structure domain specifically upon calcium addition. RTX domains created from concatenated

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 61 FINAL PROCESS WEEKS JANUARY 11-12 | 7TH ANNUAL TECHNOLOGIES & TO REGISTER Higher-Throughput Protein Production and Characterization PURIFICATION Innovating Processes Cover

Sponsors High-throughput processes have come of age by transforming the traditional protein-by-protein trial-and-error approach for testing criteria and scaling up. In this Event-at-a-Glance leading conference, HTP will be explored in the quest to develop methods that ensure quality and translate to large scale. Automation, robotics and liquid handlers will be discussed, along with developing small-scale models that shed light on bioproduction. Case studies will be presented that illustrate how leaders in the field are integrating HTP approaches to reduce the time and effort needed to successfully analyze proteins, fine tune processes, and achieve well-folded, pure protein.

THURSDAY, JANUARY 11 Tricks for Ultra-High Throughput Screening of 1:15 Ice Cream Break in the Exhibit Hall with Recombinant Protein Libraries Poster Viewing 7:45 am Registration and Morning Coffee Karl E. Griswold, Ph.D., Associate Professor, Thayer School of Engineering, Dartmouth College HTP PURIFICATION NEXT-GEN HTP TOOLS AND Flow cytometry (FC) is a powerful tool for TECHNOLOGIES screening recombinant protein libraries via cell 2:00 Chairperson’s Remarks surface display. However, functional screening of Nigel F. Reuel, Ph.D., Assistant Professor, Chemical 8:15 Chairperson’s Opening Remarks soluble, secreted proteins that act in-trans upon and Biological Engineering, Iowa State University heterologous target cells is more challenging, since Allan Matte, Ph.D., Senior Research Officer, 2:05 Integrated High-Throughput Purification Downstream Processing & Analytics, Human Health the genotype-phenotype link is inherently lost for Platforms for Bio-Therapeutics R&D Therapeutics, National Research Council Canada such trans-interactions. Here, we describe integrated (NRC-CNRC) gel microdroplet-FC (GMD-FC) screens in which Allan Matte, Ph.D., Senior Research Officer, recombinant expression hosts are co-encapsulated Downstream Processing & Analytics, Human Health with heterologous target cells in micron scale Therapeutics, National Research Council Canada KEYNOTE PRESENTATION hydrogel droplets, thereby re-establishing the (NRC-CNRC) genotype-phenotype link and enabling FC screening Early-stage screening campaigns for therapeutic 8:20 High-Throughput de novo of soluble, secreted protein libraries. antibody development involve the purification of Computational Protein Design and Its hundreds of antibody samples, often produced in Applications 10:00 Coffee Break in the Exhibit Hall with CHO or HEK transient expression systems with a Gabriel Rocklin, Ph.D., Senior Fellow, Poster Viewing range of titers and volumes. To meet this challenge, Biochemistry & Bioengineering, University of we have implemented a number of high-throughput Washington 11:00 High-Throughput Protein Production purification platforms capable of rapidly generating Advances in computational protein design within the Swedish Human Protein Atlas sub-milligram to hundreds of milligrams of purified and DNA synthesis technology have made it Project products. Redundancies in purification platforms possible to design and recombinantly express Hanna Tegel, Ph.D., Scientist and Group Leader, and integration with in-process analytics is required tens of thousands of small designer proteins Biotechnology, Proteomics and Nanobiotechnology, to achieve this outcome. (40-80 amino acids) at once, each with a novel KTH Royal Institute of Technology 2:35 Development of an Automated Mid- de novo fold and unique functional possibilities. Within the Swedish Human Protein Atlas project, These proteins can be engineered to bind to an antibody-based proteomics effort with focus on Scale Parallel Protein Purification System targets and to resist thermal denaturation and protein profiling in human tissues and cells, a protein for Antibody Purification and Affinity aggregation, and we can iteratively improve By Cambridge Healthtech Institute production pipeline has been set up to handle Chromatography these properties through cycles of large- hundreds of proteins per week. The challenges we Brian Hall, Ph.D., Principal Scientist, Biologics, Merck scale design and efficient, massively parallel met when setting up this pipeline and the solutions & Co. experimental testing. we have chosen will be discussed and presented. To address the need for higher throughput affinity SHORT COURSES purification of samples 20ml-100ml we modified 9:00 Mitigating Developability Risks by 11:30 Sponsored Presentation (Opportunity a 4 channel SPE system with switching valves and Application of Affinity-Capture Self- Available) holding loops to perform affinity purification using Interaction Nanoparticle Spectroscopy (AC- commercially available columns and micro-titer Sponsorship Opportunities 12:00 pm Session Break deep well blocks. The system has the capacity SINS) 12:15 Luncheon Presentation (Sponsorship to purify 24 samples using a single-step affinity Hotel/Additional Information Craig D. Dickinson, Ph.D., Senior Research Advisor, purification protocol or a two-step protocol Opportunity Available) or Enjoy Lunch on Your AME, Eli Lilly and Company consisting of affinity chromatography followed by Registration & Pricing Own 9:30 Flow Cytometry – An Old Dog with New desalting/buffer exchange.

CHI-PepTalk.com CHI-PepTalk.com | 62 FINAL PROCESS WEEKS JANUARY 11-12 | 7TH ANNUAL TECHNOLOGIES & TO REGISTER Higher-Throughput Protein Production and Characterization PURIFICATION Innovating Processes Cover

Sponsors 3:05 SELECTED POSTER PRESENTATION: through Affinity and Specificity Engineering Modular Cloning to Automated Deconvolution Event-at-a-Glance Automated Procedures for Large-Scale Yongku Cho, Ph.D., Assistant Professor, Chemical and of Variant Libraries Purification of Human GTPase KRas and Raf1 Biomolecular Engineering, University of Connecticut Joerg Birkenfeld, Ph.D., Section Head, High Cystine Rich Domain (CRD) Developing high affinity and specificity antibodies Throughput Biologics, R&D Biologics Research/ Simon Messing, Ph.D., Scientist II, Leidos Biomedical targeting protein post-translational modification Protein Therapeutics, Sanofi-Aventis Deutschland Research/RAS initiative sites remains a challenge. Using human tau as a GmbH Here, we show a fully automated protein purification model protein, we show that antibodies engineered The success rate to identify a multi-specific lead strategy for the large-scale production of the for high affinity alone often lose their specificity. molecule with favorable drug-like properties G domain of KRas, and one of its effectors, the Using a novel approach to screen for improved increases with the number of variants tested. cysteine rich domain of RAF1. This strategy includes specificity, we engineered picomolar affinity clones We report here the establishment of a novel, five purification steps, which includes TEV protease- with no detectable off target binding. The new automated platform process for the fast generation mediated affinity tag cleavage, Ni2+ affinity, ion methods developed may be useful for setting a of large panels of multi-specific variants (up to exchange, and size exclusion chromatography. This quantitative standard for characterizing antibody 10,000). Our high-throughput process integrates automated approach provides distinct advantages specificity. emerging cloning technologies with state-of-the-art to previous manual workflows, by reducing typical automation and workflow supporting bioinformatics 5:45 Close of Day large-scale purification from 3-4 days down to based on Genedata Biologics Database. 1.5 days. This saving in run time and workload significantly reduces protein production as a rate- FRIDAY, JANUARY 12 9:35 High-Throughput Methods for Protein limiting step in the processes of drug discovery. Stability Prediction and Formulation 8:00 am Registration Challenges Identification 3:35 Refreshment Break in the Exhibit Hall Smita Raghava, Ph.D., Senior Scientist, Sterile with Poster Viewing Formulation Sciences, Merck & Co. 8:00 BuzZ Sessions with Continental Breakfast Successful development of biologics requires HTP ANTIBODY PRODUCTION Protein therapeutics is a fast-growing development of orthogonal tools to meet the global market. As the science improves, challenge of rapidly and accurately assessing 4:15 Medium-Scale Higher Throughput so does the complexity of the R&D protein solution stability using limited material. Purification and Characterization of Antibody organization. Ensuring product quality This presentation will focus on combination of Therapeutics and Bispecific Antibodies plus speed to market requires insights from high-throughput technologies and assays for Haiyan Jiang, Ph.D., Principal Scientist, Biologics stakeholders working across the stages of protein formulation and drug product development of Research, Janssen BioTherapeutics, Janssen R&D science R&D. Join experts representing this PepTalk biologics, such as monoclonal antibodies (mAbs) pipeline, peers, and colleagues for an interactive and mAb-based modalities. The overview of 4:45 High-Throughput Production of roundtable discussion. Topics include highlights tools, their novel implementation, and relationship Antibodies Using Yeast and Mammalian Cells from the week’s presentations, new technologies to commonly conducted “stability studies” will Juergen Nett, Ph.D., Director, High Throughput and strategies, challenges, and future trends. be further discussed using examples of high- Expression, Adimab, LLC Table Moderator: Haiyan Jiang, Ph.D., Principal throughput workflows, pre-formulation screening, Scientist, Biologics Research, Janssen and formulation development/optimization. By Cambridge Healthtech Institute High-throughput, small-scale production of antibodies is an essential part of a discovery BioTherapeutics, Janssen R&D 10:05 HTP Method for Affinity Determination workflow. After isolation from a large yeast-based antibody library, Adimab directly expresses large in Complex Matrices by Solution Equilibrium SHORT COURSES panels of full-length IgGs in 96-well and 24-well ASSESSING AND ENSURING Analysis Using Meso Scale Discovery format. Protein purification is accomplished in a Technology plate-based format using liquid handling platforms. DEVELOPABILITY Eilyn R. Lacy, Ph.D., Principal Scientist, Janssen The same semi-automated process is also 9:00 Chairperson’s Remarks BioTherapeutics (JBIO), Janssen Research & Sponsorship Opportunities compatible with IgGs expressed in mammalian Development, LLC Gabriel Rocklin, Ph.D., Senior Fellow, Biochemistry & hosts. Process setup, attributes, and output will be Bioengineering, University of Washington The determination of antigen-antibody affinity is Hotel/Additional Information reviewed. essential in the development of biotherapeutics 9:05 Platformization of Multi-Specific Protein and high throughput methods for affinity analysis in Registration & Pricing 5:15 High-Quality Antibodies Targeting Engineering I: From in silico Design and Bulk physiologically relevant and complex matrices are Protein Post-Translational Modification Sites CHI-PepTalk.com CHI-PepTalk.com | 63 FINAL PROCESS WEEKS JANUARY 11-12 | 7TH ANNUAL TECHNOLOGIES & TO REGISTER Higher-Throughput Protein Production and Characterization PURIFICATION Innovating Processes Cover

Sponsors needed. We developed a high throughput method Diane Paskiet, MS, Director of Scientific Affairs, Event-at-a-Glance for affinity determination in neat serum by solution Scientific Affairs and Technical Services, West equilibrium analysis using Meso Scale Discovery Pharmaceutical Services technology (MSD-SEA). The results highlight the Bjørn Voldborg, Director, CHO Cell Line Development, potential of the MSD-technology for HTP analysis The Novo Nordisk Foundation Center for of high affinity therapeutic candidates using Biosustainability, Technical University of Denmark physiologically relevant matrices. Moritz von Stosch, Ph.D., Senior Manager, Fermentation, Technical R&D, GSK Vaccines 10:35 Coffee Break with a Poster Pavilion See page 4 for details 12:45 Close of Conference 11:15 High-Throughput Automations and Optimizations for Improved Binder Generation and Validation Jonas Schaefer, Ph.D., Head, High-Throughput Binder Selection Facility, Biochemistry, University of Zurich While recombinant binder selection pipelines by now work in rather high-throughput, the screening of suitable affinity reagents and especially the validation of their essential features for the final applications is still laborious and time-intensive. To optimize the efficiency of these processes, we have improved already existing and developed novel methods to efficiently test candidates for their suitability, e.g., regarding their specificity.

11:45 High-Throughput Characterization of Hydrolytic Enzymes in Low Volume and Closed Systems Nigel F. Reuel, Ph.D., Assistant Professor, Chemical and Biological Engineering, Iowa State University Hydrolytic enzymes play a significant role in biologic and synthetic processes. The ability to better characterize these enzymes would enable shorter development times and better products. This talk will detail two recent developments for By Cambridge Healthtech Institute hydrolytic enzyme characterization: 1) a carbon nanotube-based optical sensor that allows for quantitative measurement in <20ul volumes and 2) a SHORT COURSES resonant antenna sensor that passively transmits its response in the 1-100MHz range, enabling detection within closed, opaque systems.

Sponsorship Opportunities 12:15 pm Conference Wrap-Up

Hotel/Additional Information Richard Altman, MS, Scientist, Protein Technologies, Amgen Registration & Pricing Haiyan Jiang, Ph.D., Principal Scientist, Biologics Research, Janssen BioTherapeutics, Janssen R&D

CHI-PepTalk.com CHI-PepTalk.com | 64 FINAL WEEKS TO REGISTER

Cover

Sponsors Event-at-a-Glance BIOTHERAPEUTIC EXPRESSION & PRODUCTION

JANUARY 8-9 AGENDA Engineering Genes and Hosts

JANUARY 9-10 AGENDA Recombinant Protein Expression and Production

JANUARY 10-11 AGENDA CHO Cell Lines

JANUARY 11-12 AGENDA Optimizing Expression Platforms

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 65 FINAL BIOTHERAPEUTIC WEEKS JANUARY 8-9 | 10TH ANNUAL EXPRESSION & TO REGISTER Engineering Genes and Hosts PRODUCTION Exploring Strategies in Systems Engineering and Synthetic Biology Cover

Sponsors The mandate of “faster, better, less expensive” resonates with recombinant protein expression and production researchers. Thus, protein expression scientists are Event-at-a-Glance exploring new engineering tools including synthetic biology and systems engineering. However, many variables still must be considered during the engineering process, including verification and sequence analysis of the gene or protein of interest, codon optimization, vector construction and clone/host selection. Ultimately, as with any new system, these tools must be weighed against traditional expression and production strategies to achieve the desired quantity and quality. Cambridge Healthtech Institute’s Tenth Annual Engineering Genes and Hosts conference continues the tradition of applying effective engineering strategies for protein expression and production research leading to functional protein products. Learn from seasoned, savvy researchers as they share their real-world experiences, applications and results.

SUNDAY, JANUARY 7 interactions rather than H-bonding. More recently, 11:45 Data-Driven Approaches for Rapid we have engineered E. coli to import the requisite Scale-Up of Bioproducts 4:00 - 6:00 pm Pre-Conference Registration unnatural triphosphates and shown that DNA Derek Abbott, Ph.D., Director, Analytics, Amyris, Inc. containing the unnatural base pair is efficiently Optimization of microbial production of any product replicated, transcribed, and translated within the cell, requires repeated iterations of the design-build- MONDAY, JANUARY 8 resulting in the first semi-synthetic organism that test-analyze engineering cycle to achieve economic stores and retrieves increased information. 7:00 am Registration and Morning Coffee viability. The presentation covers details of the automated platforms that enable Amyris scientists to rapidly cycle through a data-driven strain SYNTHETIC BIOLOGY 10:20 Networking Coffee Break improvement process. Additionally, we present 9:00 Welcome by Conference Organizer 10:45 Codon and Codon Context Optimization our vision for how the industry can leverage these Mary Ann Brown, Executive Director, Conferences, in Synthetic Gene and Gene Library Design platforms to positively impact the bioeconomy by dramatically reducing the cost and time to market Cambridge Healthtech Institute Dimitris Papamichail, Ph.D., Assistant Professor, for a variety of molecules. Computer Science, The College of New Jersey 9:05 Chairperson’s Opening Remarks Advances in de novo synthesis of DNA and Mark Welch, Ph.D., Vice President, Research and 12:15 pm SELECTED POSTER computational gene design methods make possible Development, ATUM (formerly DNA2.0) PRESENTATION: A High Throughput the customization of genes and gene libraries by Approach to Construct Generation and direct manipulation of features such as codon Expression Screening for Recombinant KEYNOTE PRESENTATION and codon context bias. I present computational methods to design genes with desired codon and Protein Production 9:10 Forward Genome Engineering codon context content, and low-cost gene variant Christine Kugel, Scientific Researcher, Biomolecular Ryan T. Gill, Ph.D., Slade Professor, Chemical libraries for high-throughput experimentation. Resources, Genentech, Inc. and Biological Engineering, University of 12:45 Session Break Colorado 11:15 Synthetic Biology for Natural Product I discuss new technologies and approaches Biosynthesis 1:00 Luncheon Presentation I: Sponsored by that are enabling the engineering of biological Christopher Boddy, Ph.D., Professor & Director, A Systematic Approach to Biochemistry Program, University of Ottawa systems at scales of 100,000s of designer Address Development and By Cambridge Healthtech Institute mutations in parallel. Synthetic biology approaches are dramatically Production Challenges for Complex Biologics impacting the scientific community’s ability to heterologous express complex natural product Claes Gustafsson, Ph.D., CCO & Founder, ATUM biosynthetic pathways, revolutionizing the discovery (formerly DNA2.0) SHORT COURSES By using design of experiment (DoE) methodologies FEATURED PRESENTATION and characterization of these pathways as well as the development the natural products they coupled with machine learning, transient transfection has been optimized to yield milligram 9:50 A Semi-Synthetic Organism that Stores encode. In this presentation we will highlight new strategies for heterologous expression of bacterial levels of purified proteins in just a few days. Stable Sponsorship Opportunities and Retrieves Increased Genetic Information biosynthetic pathways, focusing on the violacein cell lines can be created in weeks to generate Floyd Romesberg, Ph.D., Professor, Chemistry, The biosynthetic pathway, and examine methods to proteins at the gram scale. Case studies showing Hotel/Additional Information Scripps Research Institute harness biosynthetic pathways for overproduction how these methods have been applied to multiple We have examined numerous unnatural nucleotides of natural products, using nonulosonic acid targets including soluble secreted proteins and Registration & Pricing bearing mainly hydrophobic nucleobase analogs biosynthetic pathways. integral membrane proteins will be presented. that pair based on packing and hydrophobic CHI-PepTalk.com CHI-PepTalk.com | 66 FINAL BIOTHERAPEUTIC WEEKS JANUARY 8-9 | 10TH ANNUAL EXPRESSION & TO REGISTER Engineering Genes and Hosts PRODUCTION Exploring Strategies in Systems Engineering and Synthetic Biology Cover

Sponsors 1:30 Luncheon Presentation II (Sponsorship 5:30 PANEL DISCUSSION: CRISPR/Cas 3:15 BuzZ Sessions with Refreshments Event-at-a-Glance Opportunity Available) Genome Editing for Protein Expression Join your peers and colleagues for CRISPR/Cas has emerged as a powerful tool for GENOME ENGINEERING interactive roundtable discussions. engineering the genome in diverse organisms. Please see page 78 for additional However, there are also financial and legal 2:00 Chairperson’s Remarks information. considerations in using this tool. Hear this panel of Bjørn Voldborg, Director, CHO Cell Line Development, experts discuss the pros and cons of CRISPR/Cas The Novo Nordisk Foundation Center for genome editing and its role in enhancing desired Biosustainability, Technical University of Denmark 4:30 Mammalian Display: Antibody Discovery, protein expression. Affinity Maturation and Developability Moderator: 2:05 CRISPR/Cas Tools for Host Cell Screening in IgG Format Improvement in the Baculovirus-Insect Cell Bjørn Voldborg, Technical University of Denmark Mike Dyson, Ph.D., CTO, IONTAS, Ltd. System Panelists: Using directed integration of antibody genes Mike Dyson, Ph.D., IONTAS, Ltd. Donald L. Jarvis, Ph.D., Professor, Molecular Biology, by CRISPR/Cas9 and TALE nucleases, we have University of Wyoming Donald L. Jarvis, Ph.D., University of Wyoming constructed large libraries in mammalian cells Eric Kelsic, Ph.D., Harvard Medical School One of my group’s major efforts has focused on containing a single antibody gene/cell. This has Dongxin Zhao, Ph.D., University of California, San Diego engineering protein glycosylation pathways in the permitted construction of millions of monoclonal baculovirus-insect cell system (BICS) to create stable cell lines displaying IgG antibodies on their Sponsored by new systems capable of producing “humanized” 6:00 - 7:15 Welcome Reception surface from which antibodies have been selected in the Exhibit Hall with Poster recombinant glycoproteins. We report development by flow cytometry for specificity, binding affinity, Viewing of novel CRISPR/Cas9 tools for site-specific genome species cross-reactivity and expression level. editing in the BICS. We then describe the use of Expression in production cell lines also enables 7:15 Close of Day these new tools to enhance our glycoengineering high-throughput developability screening. efforts by targeting an endogenous Spodoptera frugiperda (Sf) glycogene, which antagonizes human- 5:00 RNA Structural Determinants of Optimal type glycan elongation. Codons Revealed by MAGE-Seq 2:35 New Strategies of CRISPR/Cas9-Based Eric Kelsic, Ph.D., Staff Scientist, George Church Laboratory, Wyss Institute, Harvard Medical School High-Throughput Functional Genomic To understand the determinants of codon choice Screening across a gene, we generated 12,726 in situ codon Dongxin Zhao, Ph.D., Postdoctoral Fellow, Prashant mutants in the Escherichia coli essential gene Mali Lab, Department of Bioengineering, University of infA and measured their fitness with MAGE-seq. California, San Diego Correlating predicted 5’ RNA structure with fitness Cancer is a complex disease of which targetable revealed that codons even far from the start of vulnerabilities are the consequence of the gene are deleterious if they disrupt the native reprogramming of genetic architecture driven by 5’ RNA conformation. Our results shed light on By Cambridge Healthtech Institute various genetic mutations. Dissection of genetic natural codon distributions and should improve interactions in a systematic way would provide engineering of gene expression for synthetic biology unprecedented insights in drug discovery. Applying applications. SHORT COURSES the new powerful CRISPR/Cas9 technology, we developed a combinatorial screening platform which allows for both high-throughput mapping of synthetic lethality and quantification of cancer cell type-specific interactions in metabolic circus. Sponsorship Opportunities 3:05 Transition to BuzZ Sessions Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 67 FINAL BIOTHERAPEUTIC WEEKS JANUARY 8-9 | 10TH ANNUAL EXPRESSION & TO REGISTER Engineering Genes and Hosts PRODUCTION Exploring Strategies in Systems Engineering and Synthetic Biology Cover

Sponsors TUESDAY, JANUARY 9 9:35 Engineering a CHO K1 Sponsored by 12:00 pm Unlock Pichia – Novel Sponsored by Event-at-a-Glance Toolbox for Reliable High Titer Strategies and Molecular Tools to 8:00 am Registration and Morning Coffee Protein Expression Enhance Protein Expression Jamie Freeman, Ph.D., Product Manager, Horizon Iskandar Dib, Ph.D., Principal Scientist DSP & CASE STUDIES IN ENHANCING Discovery Analytics, VTU Technology GmbH EXPRESSION SYSTEMS Aside from single gene knockouts to allow for Pichia pastoris is an established, safe and highly metabolic selection systems, the CHO host remains competitive expression host with strong and 8:30 Chairperson’s Remarks largely unchanged. I will present how we have used effective secretory capacities often resulting in Henry C. Chiou, Ph.D., Associate Director, Cell Biology, a combination of techniques including genome double-digit g/l levels of recombinant protein. Life Science Solutions, Thermo Fisher Scientific engineering approaches such as CRISPR and rAAV Recent research has brought about new exciting to improve the biomanufacturing capacity of our GS technologies increasing the potential of this already knockout CHO K1 cell line. powerful yeast production host. An extended FEATURED PRESENTATION molecular toolbox addresses challenges in protein 9:50 Coffee Break in the Exhibit Hall with folding and secretion and facilitates the expression 8:35 Engineering Cell Factories for Protein Poster Viewing of more complex proteins, thus maximizing yields without compromising product quality. Production 11:00 Development of a High-Yielding Bjørn Voldborg, Director, CHO Cell Line Development, Expression Platform for the Introduction of 12:30 Session Break The Novo Nordisk Foundation Center for Non-Natural Amino Acids Biosustainability, Technical University of Denmark 12:45 Luncheon Presentation (Sponsorship Gargi Roy, MSc, Scientist I, Antibody Discovery and We have engineered cell-based factories for protein Protein Engineering/Research, MedImmune LLC Opportunity Available) or Enjoy Lunch on Your production, using state-of-the-art technologies Own combined with high-throughput genome engineering, We developed an expression technology that in silico modeling, deep -omics analysis and big enables site-specific incorporation of non-natural 1:15 Close of Engineering Genes and Hosts amino acids (nnAA) in a protein sequence. Fully data analysis. Our main focus is CHO cells, where Conference we have generated a panel of CHO cell lines, with functional, high titered IgG, in a continuous perfusion optimized phenotypes generating tailormade PTMs, process, was produced in hosts stably expressing improved bioprocess and product quality, etc. an orthogonal tRNA synthetase/tRNA pair. This host platform holds promise to overcome the expression challenges that have encumbered the developability 9:05 SKIK Tag Increasing the Expression of of this technology for manufacturing of antibody- drug conjugates and other protein conjugates. Hard-to-Express Proteins and Its Application to Antibody Screening from Single B Cells 11:30 Establishing Protein Production without Teruyo Ojima-Kato, Ph.D., Researcher, Meijo Reinventing the Wheel: ProteinData.Cloud University Peter Nollert, Ph.D., Business Director, Research and A novel tag sequence SKIK can drastically increase Development, Bio Data Bridges By Cambridge Healthtech Institute the expression of hard-to-express proteins in Establishing viable paths for recombinant protein Eschericha coli in vivo and in vitro protein synthesis sample production is typically inefficient due to the systems without affecting its activity in most cases. commonly applied laborious trial-and-error approach. SHORT COURSES We used the peptide for a novel antibody production ProteinData.Cloud is a platform to access and share from single B cells by RT-PCR, PCR and cell-free otherwise invisible experimental recombinant protein protein synthesis, because the amount of protein production information. Researchers find engineered expressed can be highly improved and normalized vector sequences, positive and negative recombinant Sponsorship Opportunities for better evaluation of Fab synthesized. expression trials and purification detail, apply and improve recombinant protein production strategies to Hotel/Additional Information their own targets to improve protein production yield and purity. Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 68 FINAL BIOTHERAPEUTIC WEEKS JANUARY 9-10 | 20TH ANNUAL EXPRESSION & TO REGISTER Recombinant Protein Expression and Production PRODUCTION Achieving Quality and Quantity Cover

Sponsors Biopharmaceuticals currently represent the fastest-growing sector of the pharmaceutical industry, driven by a rapid expansion in the manufacture of recombinant Event-at-a-Glance protein-based drugs. Consequently, the efficient expression and production of these valuable biomolecules face challenges in improving their quantity and quality while minimizing time and cost. To meet these demands, an increasing variety of recombinant production platforms are being developed. Unfortunately, there is no “universal” production system which can guarantee high yields of recombinant protein, particularly as every biomolecule itself causes its own issues in terms of expression. To meet the demand, it is crucial to increase the throughput of expression, production and purification processes and systems. Cambridge Healthtech Institute’s Recombinant Protein Expression and Production conference explores the newest data and innovations relating to the best choices in hosts/systems, as well as ways to “rescue” existing systems and make them work more effectively to produce the quality and quantity of the desired biotherapeutic.

TUESDAY, JANUARY 9 Institute, University of California, Los Angeles recombinant bacterial microcompartment (BMC) Successful production of recombinant proteins systems in Escherichia coli to shield the toxicity 1:00 pm Registration requires an appropriate expression host and careful and enhance the expression of lysis protein E from consideration of protein expression conditions. bacteriophage ϕX174. Ultimately, our recombinant 1:30 Refreshment Break in the Exhibit Hall Important factors to consider are the origin of system achieved a ~7-fold improvement in protein with Poster Viewing the target protein, the context in which the target yield compared to prior reports. Ongoing efforts to protein natively exists, and additional factors (e.g., express antimicrobial peptides within encapsulin OPTIMIZING PRODUCTION chaperones) that may be required for proper folding microcompartments to enhance their recombinant expression will also be discussed. PLATFORMS of the target protein. Sponsored by 3:15 A Chemically-Defined 5:00 Development of Diatoms (Algae) as 2:00 Chairperson’s Opening Remarks Baculovirus-Based Expression Therapeutic Protein Expression Systems Mark Arbing, Ph.D., Core Facility Director, UCLA-DOE Mark Hildebrand, Ph.D., Research Scientist and Institute, University of California, Los Angeles System for Enhanced Protein Production in Sf9 Cells Director, Marine Biology Research Division, Scripps Jonathan Zmuda, Ph.D., Director, Cell Biology R&D, Institution of Oceanography, University of California, KEYNOTE PRESENTATION Thermo Fisher Scientific San Diego The Baculovirus Expression Vector System (BEVS) We have developed microalgae called diatoms as 2:05 Combining Biophysical Analytics protein expression systems, particularly for vaccine with NGS-Based Genetic Characterization is one of the major platforms for recombinant protein production. Unlike mammalian systems, production. We use a novel inducible promoter that and Gene Editing Technologies to insect systems rely on yeastolate-containing suppresses expression during growth (enabling Improve mAb Producing CHO Cell Lines media that can exhibit significant variability in cell expression of toxic proteins), and induces under Holger Thie, Ph.D., Associate Director, Molecular growth and protein expression. Here, we present nutrient-induced growth cessation – increasing Biology, Early Stage Bioprocess Development, the development of a novel Sf9-based Baculovirus yields by enabling channeling of energy and Boehringer Ingelheim Pharma GmbH & Co. KG expression system based on a high-density, metabolites into protein synthesis. Diatom silica cell This study demonstrates how state-of-the- chemically-defined medium, a high-expressing Sf9 walls are an effective adjuvant, and the system is art technologies foster the development of cell line and enhancers that allow for consistent an all-in-one package of adjuvant and slow-release production cell lines by gaining a more holistic protein production with improvements in titers particulate antigen. understanding of these cells to ensure high compared to traditional workflows. 5:30 Close of Day By Cambridge Healthtech Institute performance and product quality. Here, the process is shown from the detection of an 3:45 Refreshment Break in the Exhibit Hall 5:30 - 5:45 Short Course Registration unfavorable molecule property (remarkable with Poster Viewing differences in N-linked glycosylation between SHORT COURSES 4:30 Redirecting Bacterial Microcompartment two production clones derived from the same 5:45 - 8:45 Dinner Short Courses* Systems to Improve Expression of Toxic CHO cell line), the identification of the genetic See page 5 for details background by NGS and how this can be fixed Proteins * Separate registration required by applying gene editing technologies. Mimi Cho Yung, Ph.D., Biomedical Staff Scientist, Sponsorship Opportunities Biosciences and Biotechnology Division, Lawrence 2:45 Hosts, Partners, and Accessories: Keys Hotel/Additional Information Livermore National Laboratory to Productive Protein Production Recombinant expression of toxic peptides/proteins Registration & Pricing Mark Arbing, Ph.D., Core Facility Director, UCLA-DOE remains a challenging problem. We redirected

CHI-PepTalk.com CHI-PepTalk.com | 69 FINAL BIOTHERAPEUTIC WEEKS JANUARY 9-10 | 20TH ANNUAL EXPRESSION & TO REGISTER Recombinant Protein Expression and Production PRODUCTION Achieving Quality and Quantity Cover

Sponsors WEDNESDAY, JANUARY 10 10:05 Coffee Break in the Exhibit Hall with potentially suggested that precisely regulated fed- Event-at-a-Glance Poster Viewing batch fermentation is a promising way for secretory 8:00 am Registration and Morning Coffee production of target recombinant proteins. ANTIBODY PRODUCTION IN E. COLI CELL-FREE SYSTEMS 11:50 Soluble Expression of Antibody 10:50 Rapid Screening of Cyclotide-Based Fragments in the Cytoplasm of E. coli 8:30 Chairperson’s Remarks Libraries against Intracellular Protein-Protein Feras Hatahet, Ph.D., Scientist, Protein Technologies, Feras Hatahet, Ph.D., Scientist, Protein Technologies, Interactions Amgen Amgen Julio A. Camarero, Ph.D., Professor, Pharmacology E. coli is widely used for the production of proteins of and Pharmaceutical Sciences, School of Pharmacy, pharmaceutical importance. However, the production 8:35 Protein Production Platform for Rational University of Southern California of soluble functional proteins can be hampered Design Engineering We report novel methods for the biosynthesis of when disulfide bonds are required. We demonstrate Takanori Kigawa, Ph.D., Team Leader, Quantitative natively folded MCoTI-based cyclotides inside the feasibility of producing single chain variable Biology Center, RIKEN live E. coli cells using split protein splicing units. fragments (scFv) of antibodies and multi-chain We have established a protein production platform The cyclotide MCoTI-cylotides are potent trypsin peptides in the cytoplasm of genetically altered E. based on cell-free technologies, which can produce inhibitors recently isolated from the seeds of coli. This approach is potentially quite useful for milligram quantities of a hundred kinds of newly Momordica cochinchinensis, a plant member of the assessing the convertibility of antibodies into multi- generated mutant proteins within a day totally cucurbitaceae family. Biosynthesis of genetically specific antibody formats containing scFvs. without recombinant DNA technology. By using this encoded cyclotide-based libraries opens the 12:20 Enjoy Lunch on Your Own platform, time and labor consuming site-directed possibility of using single cells as microfactories mutagenesis and subsequent mutant protein where the biosynthesis and screening of a particular expression/purification are dramatically accelerated. inhibitor can take place in a single process within CHO CELL DEVELOPMENT FOR Therefore, this platform is highly useful for protein the same cellular cytoplasm. The cyclotide scaffold EFFICIENT PROTEIN PRODUCTION engineering with rational design approaches. has tremendous potential for the development of therapeutic leads based on its extraordinary 2:00 Chairperson’s Remarks 9:05 Membrane Protein Production stability and potential for grafting applications. We Bjørn Voldborg, Director, CHO Cell Line Development, and Characterization in Tailored Lipid show an example, where a large cyclotide-based The Novo Nordisk Foundation Center for Environments genetically encoded library was used to screen for Biosustainability, Technical University of Denmark Frank Bernhard, Ph.D., Lab Leader, Institute of low nanomolar antagonists for the Hdm2-HdmX Biophysical Chemistry, Goethe University Frankfurt RING-mediated E3 ligase activity. We also present 2:05 Optimizing Expression of Proteins in Using proprietary cell-free expression platforms, different strategies to improve the cellular uptake CHO through a Systems Biology Approach we synthesize membrane proteins directly into and pharmacokinetic profiles of bioactive cyclotides. Nathan E. Lewis, Ph.D., Assistant Professor, Department supplied preformed nanoparticles containing of Pediatrics, University of California, San Diego defined lipid compositions. The process has been 11:20 Super Secretory Production of In our lab, we are mapping out the cell pathways optimized for preparative scale production yielding Recombinant Antibody Fragments by Precisely controlling CHO cell growth, protein synthesis, and up to 100 µM concentrations of membrane protein Controlled Fed-Batch Culture of E. coli protein glycosylation. Here I discuss our work in By Cambridge Healthtech Institute containing nanoparticles in the reactions. We show Yoichi Kumada, Ph.D., Associate Professor, Department which we have developed computational models applications of GPCRs, ion channels, transporters of Functional Chemistry, Kyoto Institute of Technology to predict the cell costs for protein synthesis and as well as of large assemblies and demonstrate Large-scale production of single-chain Fv antibodies identify how to improve protein synthesis through SHORT COURSES the complete detergent-free structural analysis of by recombinant E. coli was investigated. Periplasmic media and genetic modifications. membrane proteins by crystallization and NMR. secretion signal, pel B reader was often effective Sponsored by for leaking proteins to supernatant, while most of 9:35 Oral Insulin: Significant them were aggregated as inclusion body in flask Sponsorship Opportunities COGs Reduction via Innovative culture. When the fed-batch culture was performed Process Development and by Jar fermenter with tightly regulated DO control Hotel/Additional Information Production for Late Stage Clinical Trials system, the scFvs expressed were highly secreted Prabuddha K Kundu, Ph.D., Cofounder, Executive to the culture supernatant. Consequently, final Registration & Pricing Director, Premas Biotech concentration of scFv reached at more than 4g/L, and solubility of scFv was approx. 50%. These results

CHI-PepTalk.com CHI-PepTalk.com | 70 FINAL BIOTHERAPEUTIC WEEKS JANUARY 9-10 | 20TH ANNUAL EXPRESSION & TO REGISTER Recombinant Protein Expression and Production PRODUCTION Achieving Quality and Quantity Cover

Sponsors 2:35 Optimizing Biologics by Cell-Based 4:30 Using GlycoExpress to Overcome Event-at-a-Glance Glycan Display Production Limitations for Difficult-to- Claus Kristensen, Ph.D., CEO, GlycoDisplay Aps Express Proteins Glycan structures are important for efficacy and Lars Stöckl, Ph.D., Director, Glycoprotein Development distribution of biologics. Optimization of glycans has and PTM Analytics, Glycotope GmbH been hampered by inefficient technologies for glyco- Even though productivity for CHO systems has engineering in mammalian cells. Now GlycoDisplay remarkedly improved over the last years, some offers technologies allowing development of novel biopharmaceuticals like bispecific constructs or glyco-optimized biologics. GlycoDisplay has applied complex glycoproteins remain very challenging. We targeted cell engineering to generate cell lines with present case study data from clone and upstream different glycosylation capacities. By expressing a perfusion development for the human GlycoExpress drug candidate protein in panels of glycoengineered cell line, which overcomes productivity limitations. cell lines, followed by screening novel glyco- optimized leads are identified. 5:00 Expression of Recombinant Blood Coagulation Factor VIII: Importance for 3:05 Refreshment Break in the Exhibit Hall Human Healthcare and Approaches to with Poster Viewing Improve the Protein’s Yield and Quality 4:00 Overexpression of Ebola Virus Envelope Andrey G. Sarafanov, Ph.D., Chemist, Principal GP1 Protein Investigator, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration (FDA) Zhongcheng Zou, Ph.D., Staff Scientist, Structural Immunology Section, Lab of Immunogenetics, NIAID/ Deficiency in factor VIII (FVIII) results in abnormal NIH bleeding (Hemophilia A), which is treated by infusions of FVIII. However, the FVIII production To elucidate the role of the mucin-like domain of is challenging as the protein is expressed at low GP1 in Ebola-host attachment and infection and levels both in plasma (0.3 nM) and heterologous to facilitate vaccine development, we constructed systems. The presentation overviews approaches to a GP1 expression vector containing the entire improve FVIII production, in particular, re-design of attachment region. Cysteine 53 of GP1 was the protein and its gene, optimization of the protein mutated to serine to avoid potential disulfide bond expression and purification, and selection of test mispairing. Stable expression clones using codon methods. optimized open reading frame were developed in human 293-H cells with yields reaching ~ 25 mg of 5:30 - 6:45 Networking Reception in the GP1 protein per liter of spent medium. Exhibit Hall with Poster Viewing 6:45 Close of Recombinant Protein Expression and Production Conference By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 71 FINAL BIOTHERAPEUTIC WEEKS JANUARY 10-11 | 4TH ANNUAL EXPRESSION & TO REGISTER CHO Cell Lines PRODUCTION Enhancing Expression, Performance & Process Cover

Sponsors CHO cells’ rapid rise in production prominence is due to their adaptability to various culture conditions, gene plasticity, and ability in proper folding, posttranslational modifications, and glycosylation of desired proteins. Thus, advances in CHO cell lines and culture continue to significantly improve biotherapeutic production. This Event-at-a-Glance achievement is due to progress in engineering stable and transient cell lines, enhancing cell culture conditions and performance, as well as optimizing process development. When all are accomplished, higher-production titers and better product quality result. The CHO Cell Lines conference gathers cell line engineers, cell culture specialists and bioprocess development managers to explore the latest data, tools and strategies for improving protein expression, production, and product quality.

WEDNESDAY, JANUARY 10 To elucidate the role of the mucin-like domain of THURSDAY, JANUARY 11 GP1 in Ebola-host attachment and infection and 1:00 pm Registration to facilitate vaccine development, we constructed 7:45 am Morning Coffee a GP1 expression vector containing the entire ENHANCING EXPRESSION attachment region. Cysteine 53 of GP1 was IMPROVING PRODUCT QUALITY THROUGH ENGINEERING mutated to serine to avoid potential disulfide bond THROUGH PROCESS mispairing. Stable expression clones using codon 2:00 Chairperson’s Opening Remarks optimized open reading frame were developed in 8:15 Chairperson’s Remarks Bjørn Voldborg, Director, CHO Cell Line Development, human 293-H cells with yields reaching ~ 25 mg of Gyun Min Lee, Ph.D., Professor, Biological Sciences, KAIST The Novo Nordisk Foundation Center for GP1 protein per liter of spent medium. Biosustainability, Technical University of Denmark 4:30 Using GlycoExpress to Overcome KEYNOTE PRESENTATION 2:05 Optimizing Expression of Proteins in Production Limitations for Difficult-to- 8:20 Integrating Cell Culture with CHO through a Systems Biology Approach Express Proteins Magnetic Protein A Bead-Trap Nathan E. Lewis, Ph.D., Assistant Professor, Department Lars Stöckl, Ph.D., Director, Glycoprotein Development Technology Accelerates Antibody of Pediatrics, University of California, San Diego and PTM Analytics, Glycotope GmbH Purification In our lab, we are mapping out the cell pathways Even though productivity for CHO systems has controlling CHO cell growth, protein synthesis, and John K. Kawooya, Ph.D., Director, Biologics remarkedly improved over the last years, some protein glycosylation. Here I discuss our work in Optimization, Discovery Research, Amgen biopharmaceuticals like bispecific constructs or which we have developed computational models Antibody engineering produces large complex glycoproteins remain very challenging. We to predict the cell costs for protein synthesis and numbers of molecules (200-500 molecules present case study data from clone and upstream identify how to improve protein synthesis through at 30-50ml each) which require purification, perfusion development for the human GlycoExpress media and genetic modifications. analysis and screening for potency, binding, cell line, which overcomes productivity limitations. pharmacodynamics, pharmacokinetics, 2:35 Optimizing Biologics by Cell-Based manufacturability, expression levels and 5:00 Expression of Recombinant Blood Glycan Display stability in order to select leads. Ever since its Coagulation Factor VIII: Importance for Claus Kristensen, Ph.D., CEO, GlycoDisplay Aps inception over 30 years ago, the AKTA system Human Healthcare and Approaches to combined with Protein A agarose columns Glycan structures are important for efficacy and Improve the Protein’s Yield and Quality has remained the “workhorse” of antibody distribution of biologics. Optimization of glycans has purification from cell cultures. However, the been hampered by inefficient technologies for glyco- Andrey G. Sarafanov, Ph.D., Chemist, Principal inability of this system to process multiple engineering in mammalian cells. Now GlycoDisplay Investigator, Center for Biologics Evaluation and samples in parallel coupled with both its offers technologies allowing development of novel Research, U.S. Food and Drug Administration (FDA) By Cambridge Healthtech Institute limiting flow rates, its requirement for multiple glyco-optimized biologics. GlycoDisplay has applied Deficiency in factor VIII (FVIII) results in abnormal FTEs to remove cells and particulate from targeted cell engineering to generate cell lines with bleeding (Hemophilia A), which is treated by infusions each sample prior to loading together with different glycosylation capacities. By expressing a of FVIII. However, the FVIII production is challenging the potential for sample swapping errors and SHORT COURSES drug candidate protein in panels of glycoengineered as the protein is expressed at low levels both in cross contaminations – all impose major cell lines, followed by screening novel glyco- plasma (0.3 nM) and heterologous systems. The bottlenecks in expediting large purified panels optimized leads are identified. presentation overviews approaches to improve FVIII production, in particular, re-design of the protein and of molecules. In this presentation, I show how 3:05 Refreshment Break in the Exhibit Hall its gene, optimization of the protein expression and a single FTE with parallel Magnetic Protein A Sponsorship Opportunities with Poster Viewing purification, and selection of test methods. bead-trap technology accelerates delivery of high-quality purified antibodies in high yield Hotel/Additional Information 4:00 Overexpression of Ebola Virus Envelope 5:30 - 6:45 Networking Reception in the directly from small (30ml-5liters) to large GP1 Protein (25-liter wave-bag) crude cell cultures without Registration & Pricing Exhibit Hall with Poster Viewing Zhongcheng Zou, Ph.D., Staff Scientist, Structural centrifugation or filtration. Immunology Section, Lab of Immunogenetics, NIAID/NIH 6:45 Close of Day CHI-PepTalk.com CHI-PepTalk.com | 72 FINAL BIOTHERAPEUTIC WEEKS JANUARY 10-11 | 4TH ANNUAL EXPRESSION & TO REGISTER CHO Cell Lines PRODUCTION Enhancing Expression, Performance & Process Cover

Sponsors 9:00 Speed to IND: Alignment and 11:30 Using SUREscan™ to Sponsored by Tadas Panavas, Ph.D., Associate Director, Discovery Research, Alexion Pharmaceuticals Event-at-a-Glance Acceleration of Critical Early Phase Activities Survey Genetic Changes in Kyle Zingaro, Ph.D., Development Scientist II, Early Stable CHO Cell Lines Chinese Hamster Ovary (CHO) cells are the principal Stage Development, Alexion Pharmaceuticals Pierre-Alain Girod, CSO, Selexis mammalian host used for stable cell line generation and biotherapeutic protein production. Until recently, Speed to IND is the current battle cry across early CHO cells are the most frequently applied host- production of milligrams to grams of protein in CHO phase biologics development. Despite some cell system for industrial protein therapeutic transient systems was challenging. To overcome risks, new technologies and workflow alignment manufacturing. Rapid generation of high-producing such challenges, we evaluated the ExpiCHO system, can afford faster and better decisions during this clones that don’t lose expression capability over a high-density CHO-S transient transfection system, crucial phase of new product development. This is time has been a major industry focus. Using and compared it to the Expi293 and FreeStyle MAX especially true across the Discovery and Process SUREscan™ with next-generation sequencing (NGS), CHO transient systems. Detailed analysis was Development handoff. We present new data and we can quickly analyze whole genomes of any cell performed on protein titer, monodispersity, enzyme approaches to improve that handoff and detail the line, improving traceability of Research Cell Banks activity, and posttranslational modifications. impact on timelines and quality of molecules and (RCBs). In contrast to other CHO published data, we cell lines in early phase development. will show that SUREtechnology Platform™ generates 2:35 Transient Protein Production: RCBs with chromosomally stable lineages. Harmonizing the Process from Construct 9:30 "Lost in Translation": Bridging the Gap Generation through Protein Characterization between Academia and Biotech 12:00 pm Session Break Richard Altman, MS, Scientist, Protein Technologies, Tsafi Danieli, Ph.D., Director, BioGiv Excubator & Sponsored by 12:15 Luncheon Presentation: Amgen Head, Protein Expression Facility, Wolfson Centre for Applied Structural Biology, Alexander Silberman Get Your High Protein A robust, flexible transient protein production Institute of Life Sciences, The Hebrew University of Concentrations Right on the facility provides critical support to drug discovery Jerusalem Money with Lunatic efforts. We review the ongoing evolution of our protein production endeavors focusing on two One of the most difficult and frustrating aspects of Thomas Martens, Principal Scientist, Unchained Labs critical components. The first is the strategic basing a startup company on academic findings is Stop quantifying proteins one by one hoping that assembly of mammalian expression “tools” that translating and transferring academic findings to your old reader is getting the numbers right. Get rid gives us a toolbox capable of expressing diverse biotech language. This procedure is often frustrating of that dilution step you always need to measure and challenging candidate proteins. The second is to both parties and requires psychological skills as 200 mg/ml IgG or even higher. Come learn about the harmonization of the entire protein production well as critical review of the research. Working in the how Lunatic gets rid of all dilutions, eliminates process thereby reducing turnaround times and interphase between academia and industry, there any risk of cross contamination and accurately increasing throughput. are several preemptive strikes we can take to avoid measures protein concentration at high throughput some of the major pitfalls. and high concentrations. We’ll talk about how 3:05 Sponsored Presentation (Opportunity lunatic: Available) 10:00 Coffee Break in the Exhibit Hall with • measures either 16 or 96 samples in one run Poster Viewing • uses only 2 µL for each measurement 3:35 Refreshment Break in the Exhibit Hall • needs only 5 minutes with Poster Viewing 11:00 Proteomic Analysis of Host Cell Protein • Requires no dilutions Dynamics in the Culture Supernatants of 4:15 Chairperson’s Remarks By Cambridge Healthtech Institute Therapeutic Protein-Producing CHO Cells 1:15 Ice Cream Break in the Exhibit Hall with Tsafi Danieli, Ph.D., Director, BioGiv Excubator & Gyun Min Lee, Ph.D., Professor, Biological Sciences, Poster Viewing Head, Protein Expression Facility, Wolfson Centre KAIST for Applied Structural Biology, Alexander Silberman SHORT COURSES Host cell proteins (HCPs) accumulate extracellularly PROTEIN PRODUCTION: Institute of Life Sciences, The Hebrew University of during the cultures of recombinant CHO (rCHO) TRANSIENT, STABLE OR BOTH? Jerusalem cells, potentially impairing product quality. HCPs 2:00 Chairperson’s Remarks 4:15 Lost in Translation: On the Formation of accumulated extracellularly in batch and fed-batch Saurabh Sen, Ph.D., Principal Scientist, Protein Sequence Variants Sponsorship Opportunities cultures of rCHO cell lines were identified and quantified by mass spectrometry. This dataset Biotherapeutics Discovery, Boehringer Ingelheim Zhongqi Zhang, Ph.D., Scientific Director, Attribute Sciences, Process Development, Amgen Hotel/Additional Information of HCPs provides insights into determining the 2:05 A High-Density CHO-S Transient With modern mass spectrometry and appropriate appropriate target proteins to be removed during Transfection System: Comparison of ExpiCHO both the cultures and purification steps for ensuring informatics tools, a large number of low-level Registration & Pricing and Expi293 good therapeutic protein quality. sequence variants in therapeutic proteins are

CHI-PepTalk.com CHI-PepTalk.com | 73 FINAL BIOTHERAPEUTIC WEEKS JANUARY 10-11 | 4TH ANNUAL EXPRESSION & TO REGISTER CHO Cell Lines PRODUCTION Enhancing Expression, Performance & Process Cover

Sponsors detected and quantified. This large collection of information allows for a deeper understanding of the Event-at-a-Glance mechanism for the formation of sequence variants, thereby facilitating optimization of cell line and cell culture process to minimize them. 4:45 The Stability of CHO Genome: Essential for Cell Line Characterization or Not? Noriko Yamano, Ph.D., Senior Scientist, Manufacturing Technology Association of Biologics; Guest Academic Staff, Graduate School of Engineering, Osaka University The chromosomes in CHO cells frequently cause genomic variations, due to genetic instability. Distribution and stability of chromosomes were examined in CHO-DG44 cells, and two cell lines expressing different numbers of chromosomes were isolated from the original CHO-DG44 cell line to investigate the effect of aneuploid cells on recombinant protein production. In addition, gene expression profiles between cells with disparate chromosome numbers have been compared by mRNA-seq analysis. 5:15 High-Throughput Screening of Transfection Efficiency of dTtaPS Reagent Library, and Its Application for Transient Production of Proteins in Micro Bioreactors Harsh Jain, PhD, Visiting Associate, FDA 5:45 Close of CHO Cell Lines Conference

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 74 FINAL BIOTHERAPEUTIC WEEKS JANUARY 11-12 | 5TH ANNUAL EXPRESSION & TO REGISTER Optimizing Expression Platforms PRODUCTION Tools for Effective Expression, Production & Purification Cover

Sponsors The utilization of engineered therapeutic proteins for basic research, clinical diagnostics and therapy continues to expand. Consequently, protein expression Event-at-a-Glance laboratory researchers face challenges in efficient expression, production, and purification even while improving quantity and quality and minimizing time and cost. Transient protein production (TPP) has the advantage of speed and limiting risk while stable transfection – the longer and more complex process – has the advantage of producing long-term expression of the biotherapeutic of interest. The rapidly increasing need for recombinant proteins necessitates further improvements in both technologies. Cambridge Healthtech Institute’s Fifth Annual Optimizing Expression Platforms conference convenes protein expression specialists who share their experiences of the differences, tradeoffs, and improvements in producing recombinant proteins in transient or stable production systems, and who investigate their advantages and disadvantages and when to use both.

THURSDAY, JANUARY 11 bead-trap technology accelerates delivery of 11:00 Fundamentals of Baculovirus high-quality purified antibodies in high yield Expression and Applications 7:45 am Registration and Morning Coffee directly from small (30ml-5liters) to large Christopher Kemp, Ph.D., President, Kempbio (25-liter wave-bag) crude cell cultures without The baculovirus expression vector system centrifugation or filtration. TRANSIENT PROTEIN (BEVS) is a major protein expression platform PRODUCTION for the production of research and therapeutic 9:00 Transient Antibody Production: How to grade proteins. BEVS supports the expression of 8:15 Chairperson’s Opening Remarks Generate Higher Titers proteins in both insect and mammalian cell hosts Richard Altman, MS, Scientist, Protein Technologies, Saurabh Sen, Ph.D., Principal Scientist, and the high efficiency and reproducibility of viral Amgen Biotherapeutics Discovery, Boehringer Ingelheim transduction allows the expression of difficult The presentation covers topics on optimizing proteins. This presentation focuses on applications of BEVS for the expression of proteins and protein KEYNOTE PRESENTATION efficient expression and production even while improving quantity and quality and minimizing time complexes in insect and mammalian cells. 8:20 Integrating Cell Culture with and cost. Our Transient Gene Expression (TGE) 11:30 Accelerated Protein Sponsored by Magnetic Protein A Bead-Trap technology for transient protein production (TPP) Technology Accelerates Antibody has significant advantages by using lesser amounts Production via Transient Cell Purification of coding DNA by 70-80% -- and using 50% less Engineering John K. Kawooya, Ph.D., Director, Biologics transfection reagent. For research purposes, we Enrique Miranda Rota, Ph.D., Research Associate, Optimization, Discovery Research, Amgen have an improved TGE protocol with significant MaxCyte, Inc., University College London Cancer Institute Antibody engineering produces large advantage of speed, higher yields and lower costs. Biotherapeutic protein development groups are numbers of molecules (200-500 molecules often faced with producing a wide variety of proteins at 30-50ml each) which require purification, 9:30 Advances and Challenges in Transient with varying and often complex requirements. analysis and screening for potency, binding, Plant-Based Therapeutic Protein Production Our presentation describes a fully scalable, cGMP pharmacodynamics, pharmacokinetics, Karen McDonald, Ph.D., Professor, Chemical compliant, transient cell engineering strategy manufacturability, expression levels and Engineering, University of California, Davis along with a streamlined purification process that stability in order to select leads. Ever since its Plants are an excellent host for transient production allows us to generate large quantities of purified inception over 30 years ago, the AKTA system biotherapeutic proteins quickly to satisfy the needs of By Cambridge Healthtech Institute of therapeutic proteins due to their high expression combined with Protein A agarose columns levels, rapid development timescales, short batch our collaborators without having to do labor and time has remained the “workhorse” of antibody production times, flexibility, robustness, scalability, intensive stable clone generation or produce large cell purification from cell cultures. However, the biosafety, and economics. A variety of transient collections. SHORT COURSES inability of this system to process multiple expression systems/platforms and glycoengineered samples in parallel coupled with both its plant host lines have been developed and 12:00 pm Session Break limiting flow rates, its requirement for multiple Sponsored by commercial-scale facilities have been built. 12:15 Luncheon Presentation I: FTEs to remove cells and particulate from Current work in the area of transient production New Tools for Screening & Sponsorship Opportunities each sample prior to loading together with of recombinant proteins in plant cell suspension the potential for sample swapping errors and cultures will be presented. Harvesting Solutions for CHO & HEK293 Cells, Hotel/Additional Information cross contaminations – all impose major for Both Transient and Stable Cell bottlenecks in expediting large purified panels 10:00 Coffee Break in the Exhibit Hall with Sam Ellis, Vice President, Thomson Instrument Registration & Pricing of molecules. In this presentation, I show how Poster Viewing Company a single FTE with parallel Magnetic Protein A Evaluation of different transfection tools, product CHI-PepTalk.com CHI-PepTalk.com | 75 FINAL BIOTHERAPEUTIC WEEKS JANUARY 11-12 | 5TH ANNUAL EXPRESSION & TO REGISTER Optimizing Expression Platforms PRODUCTION Tools for Effective Expression, Production & Purification Cover

Sponsors quality, and titer for both CHO and HEK293 cell We review the ongoing evolution of our protein 4:45 The Stability of CHO Genome: Essential Event-at-a-Glance lines. Data will be presented on techniques and production endeavors focusing on two critical for Cell Line Characterization or Not? technology that mimic large-scale bioreactors in components. The first is the strategic assembly of Noriko Yamano, Ph.D., Senior Scientist, non-controlled devices from 1mL-3L. Technologies mammalian expression “tools” that gives us a toolbox Manufacturing Technology Association of Biologics; presented include well plates and culture tube capable of expressing diverse and challenging Guest Academic Staff, Graduate School of systems with incorporated filtration methodology. candidate proteins. The second is the harmonization Engineering, Osaka University A new direct harvesting technique will also be of the entire protein production process thereby The chromosomes in CHO cells frequently cause introduced that eliminates centrifugation while reducing turnaround times and increasing throughput. genomic variations, due to genetic instability. maintaining 0.2um sterile filtration. All of these tools Distribution and stability of chromosomes were will be presented with case studies from scientists. 3:05 Difficult to Express Proteins: Sponsored by Novel Plasmid Technology to examined in CHO-DG44 cells, and two cell lines expressing different numbers of chromosomes 12:45 Luncheon Presentation II (Sponsorship Significantly Increase Product Opportunity Available) were isolated from the original CHO-DG44 cell Yield in CHO Cells line to investigate the effect of aneuploid cells on 1:15 Ice Cream Break in the Exhibit Hall with Marco Cacciuttolo, Ph.D., Head of Operations, Batavia recombinant protein production. In addition, gene Biosciences Poster Viewing expression profiles between cells with disparate Yield is still an area that requires significant chromosome numbers have been compared by improvement for many promising recombinant mRNA-seq analysis. CHO CELLS: proteins and antibodies. Novel vector technology TRANSIENT, STABLE OR BOTH? enables rapid generation of stable, CHO cell lines able 5:15 High-Throughput Screening of to provide at least 10-fold more product per cell. Transfection Efficiency of dTtaPS Reagent 2:00 Chairperson’s Remarks Library, and Its Application for Transient Saurabh Sen, Ph.D., Principal Scientist, 3:35 Refreshment Break in the Exhibit Hall Production of Proteins in Micro Bioreactors Biotherapeutics Discovery, Boehringer Ingelheim with Poster Viewing Harsh Jain, PhD, Visiting Associate, FDA 2:05 A High-Density CHO-S Transient 4:15 Chairperson’s Remarks 5:45 Close of Day Transfection System: Comparison of ExpiCHO Tsafi Danieli, Ph.D., Director, BioGiv Excubator & Head, and Expi293 Protein Expression Facility, Wolfson Centre for Applied Tadas Panavas, Ph.D., Associate Director, Discovery Structural Biology, Alexander Silberman Institute of Research, Alexion Pharmaceuticals Life Sciences, The Hebrew University of Jerusalem Chinese Hamster Ovary (CHO) cells are the principal mammalian host used for stable cell line generation 4:15 Lost in Translation: On the Formation of and biotherapeutic protein production. Until recently, Protein Sequence Variants production of milligrams to grams of protein in CHO Zhongqi Zhang, Ph.D., Scientific Director, Attribute transient systems was challenging. To overcome Sciences, Process Development, Amgen such challenges, we evaluated the ExpiCHO system, With modern mass spectrometry and appropriate a high-density CHO-S transient transfection system, informatics tools, a large number of low-level

By Cambridge Healthtech Institute and compared it to the Expi293 and FreeStyle MAX sequence variants in therapeutic proteins are CHO transient systems. Detailed analysis was detected and quantified. This large collection of performed on protein titer, monodispersity, enzyme information allows for a deeper understanding of the activity, and posttranslational modifications. mechanism for the formation of sequence variants, SHORT COURSES thereby facilitating optimization of cell line and cell 2:35 Transient Protein Production: culture process to minimize them. Harmonizing the Process from Construct Generation through Protein Characterization Sponsorship Opportunities Richard Altman, MS, Scientist, Protein Technologies, Amgen Hotel/Additional Information A robust, flexible transient protein production facility provides critical support to drug discovery efforts. Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 76 FINAL BIOTHERAPEUTIC WEEKS JANUARY 11-12 | 5TH ANNUAL EXPRESSION & TO REGISTER Optimizing Expression Platforms PRODUCTION Tools for Effective Expression, Production & Purification Cover

Sponsors FRIDAY, JANUARY 12 of large panels of multi-specific variants (up to have improved already existing and developed novel Event-at-a-Glance 10,000). Our high-throughput process integrates methods to efficiently test candidates for their 8:00 am Registration emerging cloning technologies with state-of-the-art suitability, e.g., regarding their specificity. automation and workflow supporting bioinformatics based on Genedata Biologics Database. 11:45 High-Throughput Characterization 8:00 BuzZ Sessions with Continental of Hydrolytic Enzymes in Low Volume and Breakfast 9:35 High-Throughput Methods for Protein Closed Systems Stability Prediction and Formulation Protein therapeutics is a fast-growing Nigel F. Reuel, Ph.D., Assistant Professor, Chemical global market. As the science improves, Challenges Identification and Biological Engineering, Iowa State University so does the complexity of the R&D Smita Raghava, Ph.D., Senior Scientist, Sterile Hydrolytic enzymes play a significant role in biologic organization. Ensuring product quality Formulation Sciences, Merck & Co. and synthetic processes. The ability to better plus speed to market requires insights from Successful development of biologics requires characterize these enzymes would enable shorter stakeholders working across the stages of protein development of orthogonal tools to meet the development times and better products. This talk science R&D. Join experts representing this PepTalk challenge of rapidly and accurately assessing will detail two recent developments for hydrolytic pipeline, peers, and colleagues for an interactive protein solution stability using limited material. enzyme characterization: 1) a carbon nanotube- roundtable discussion. Topics include highlights This presentation will focus on combination of based optical sensor that allows for quantitative from the week’s presentations, new technologies high-throughput technologies and assays for measurement in <20ul volumes, and 2) a resonant and strategies, challenges, and future trends. formulation and drug product development of antenna sensor that passively transmits its Table Moderator: Richard Altman, MS, Scientist, biologics, such as monoclonal antibodies (mAbs) response in the 1-100MHz range, enabling detection Protein Technologies, Amgen and mAb-based modalities. The overview of within closed, opaque systems. Table Moderator: Bjørn Voldborg, Director, CHO Cell tools, their novel implementation, and relationship to commonly conducted “stability studies” will Line Development, The Novo Nordisk Foundation 12:15 pm Conference Wrap-Up Center for Biosustainability, Technical University of be further discussed using examples of high- Denmark throughput workflows, pre-formulation screening, Richard Altman, MS, Scientist, Protein Technologies, and formulation development/optimization. Amgen Haiyan Jiang, Ph.D., Principal Scientist, Biologics 10:05 HTP Method for Affinity Determination Research, Janssen BioTherapeutics, Janssen R&D TECHNOLOGIES TO ESTABLISH in Complex Matrices by Solution Equilibrium Diane Paskiet, MS, Director of Scientific Affairs, EFFICIENT PRODUCTION & Analysis Using Meso Scale Discovery Scientific Affairs and Technical Services, West PURIFICATION Technology Pharmaceutical Services Eilyn R. Lacy, Ph.D., Principal Scientist, Janssen Bjørn Voldborg, Director, CHO Cell Line Development, 9:00 Chairperson’s Remarks BioTherapeutics (JBIO), Janssen Research & The Novo Nordisk Foundation Center for Gabriel Rocklin, Ph.D., Senior Fellow, Biochemistry & Development, LLC Biosustainability, Technical University of Denmark Bioengineering, University of Washington 10:35 Coffee Break with a Poster Pavilion Moritz von Stosch, Ph.D., Senior Manager, Fermentation, Technical R&D, GSK Vaccines 9:05 Platformization of Multi-Specific Protein See page 4 for details By Cambridge Healthtech Institute Engineering I: From in silico Design and Bulk 11:15 High-Throughput Automations and Modular Cloning to Automated Deconvolution 12:45 Close of Conference of Variant Libraries Optimizations for Improved Binder Generation SHORT COURSES Joerg Birkenfeld, Ph.D., Section Head, High and Validation Throughput Biologics, R&D Biologics Research/ Jonas Schaefer, Ph.D., Head, High-Throughput Binder Protein Therapeutics, Sanofi-Aventis Deutschland Selection Facility, Biochemistry, University of Zurich GmbH While recombinant binder selection pipelines by Sponsorship Opportunities The success rate to identify a multi-specific lead now work in rather high-throughput, the screening molecule with favorable drug-like properties of suitable affinity reagents and especially the Hotel/Additional Information increases with the number of variants tested. validation of their essential features for the final We report here the establishment of a novel, applications is still laborious and time-intensive. Registration & Pricing automated platform process for the fast generation To optimize the efficiency of these processes, we

CHI-PepTalk.com CHI-PepTalk.com | 77 FINAL WEEKS TO REGISTER

Cover

Sponsors Event-at-a-Glance ALTERNATIVE EXPRESSION & PRODUCTS

JANUARY 8-9 AGENDA Engineering Genes and Hosts

JANUARY 9-10 AGENDA Biocatalysis and Bio-Based Chemical Production

JANUARY 11-12 AGENDA Microbial Production

By Cambridge Healthtech Institute

SHORT COURSES

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 78 FINAL ALTERNATIVE WEEKS JANUARY 8-9 | 10TH ANNUAL EXPRESSION TO REGISTER Engineering Genes and Hosts & PRODUCTS Exploring Strategies in Systems Engineering and Synthetic Biology Cover

SUNDAY, JANUARY 7 bearing mainly hydrophobic nucleobase analogs of natural products, using nonulosonic acid that pair based on packing and hydrophobic biosynthetic pathways. 4:00 - 6:00 pm Pre-Conference Registration interactions rather than H-bonding. More recently, we have engineered E. coli to import the requisite 11:45 Data-Driven Approaches for Rapid unnatural triphosphates and shown that DNA Scale-Up of Bioproducts MONDAY, JANUARY 8 containing the unnatural base pair is efficiently Derek Abbott, Ph.D., Director, Analytics, Amyris, Inc. replicated, transcribed, and translated within the cell, Optimization of microbial production of any product 7:00 am Registration and Morning Coffee resulting in the first semi-synthetic organism that requires repeated iterations of the design-build- stores and retrieves increased information. test-analyze engineering cycle to achieve economic SYNTHETIC BIOLOGY viability. The presentation covers details of the 9:00 Welcome by Conference Organizer automated platforms that enable Amyris scientists 10:20 Networking Coffee Break to rapidly cycle through a data-driven strain Mary Ann Brown, Executive Director, Conferences, improvement process. Additionally, we present Cambridge Healthtech Institute 10:45 Codon and Codon Context Optimization our vision for how the industry can leverage these in Synthetic Gene and Gene Library Design 9:05 Chairperson’s Opening Remarks platforms to positively impact the bioeconomy by Dimitris Papamichail, Ph.D., Assistant Professor, dramatically reducing the cost and time to market Mark Welch, Ph.D., Vice President, Research and Computer Science, The College of New Jersey for a variety of molecules. Development, ATUM (formerly DNA2.0) Advances in de novo synthesis of DNA and computational gene design methods make possible 12:15 pm SELECTED POSTER KEYNOTE PRESENTATION the customization of genes and gene libraries by PRESENTATION: A High Throughput direct manipulation of features such as codon Approach to Construct Generation and 9:10 Forward Genome Engineering and codon context bias. I present computational Expression Screening for Recombinant Ryan T. Gill, Ph.D., Slade Professor, Chemical methods to design genes with desired codon and Protein Production and Biological Engineering, University of codon context content, and low-cost gene variant Christine Kugel, Scientific Researcher, Biomolecular Colorado libraries for high-throughput experimentation. Resources, Genentech, Inc. I discuss new technologies and approaches that are enabling the engineering of biological 11:15 Synthetic Biology for Natural Product 12:45 Session Break systems at scales of 100,000s of designer Biosynthesis By Cambridge Healthtech Institute mutations in parallel. Christopher Boddy, Ph.D., Professor & Director, 1:00 Luncheon Presentation I: Sponsored by Biochemistry Program, University of Ottawa A Systematic Approach to Synthetic biology approaches are dramatically Address Development and SHORT COURSES impacting the scientific community’s ability to Production Challenges for Complex Biologics heterologous express complex natural product FEATURED PRESENTATION Claes Gustafsson, Ph.D., CCO & Founder, ATUM biosynthetic pathways, revolutionizing the discovery (formerly DNA2.0) and characterization of these pathways as well By using design of experiment (DoE) methodologies 9:50 A Semi-Synthetic Organism that Stores as the development the natural products they Sponsorship Opportunities coupled with machine learning, transient and Retrieves Increased Genetic Information encode. In this presentation we will highlight new transfection has been optimized to yield milligram strategies for heterologous expression of bacterial Hotel/Additional Information Floyd Romesberg, Ph.D., Professor, Chemistry, The levels of purified proteins in just a few days. Stable biosynthetic pathways, focusing on the violacein Scripps Research Institute cell lines can be created in weeks to generate biosynthetic pathway, and examine methods to Registration & Pricing We have examined numerous unnatural nucleotides proteins at the gram scale. Case studies showing harness biosynthetic pathways for overproduction

CHI-PepTalk.com CHI-PepTalk.com | 79 FINAL ALTERNATIVE WEEKS JANUARY 8-9 | 10TH ANNUAL EXPRESSION TO REGISTER Engineering Genes and Hosts & PRODUCTS Exploring Strategies in Systems Engineering and Synthetic Biology Cover

Sponsors how these methods have been applied to multiple Panelists: Event-at-a-Glance targets including soluble secreted proteins and 3:15 BuzZ Sessions with Refreshments Mike Dyson, Ph.D., IONTAS, Ltd. integral membrane proteins will be presented. Join your peers and colleagues for Donald L. Jarvis, Ph.D., University of Wyoming interactive roundtable discussions. Eric Kelsic, Ph.D., Harvard Medical School 1:30 Luncheon Presentation II (Sponsorship Please see page 78 for additional Dongxin Zhao, Ph.D., University of California, San Diego Opportunity Available) information. 6:00 - 7:15 Welcome Reception Sponsored by GENOME ENGINEERING in the Exhibit Hall with Poster 4:30 Mammalian Display: Antibody Discovery, Viewing 2:00 Chairperson’s Remarks Affinity Maturation and Developability Bjørn Voldborg, Director, CHO Cell Line Development, Screening in IgG Format 7:15 Close of DayTUESDAY, JANUARY 9 The Novo Nordisk Foundation Center for Mike Dyson, Ph.D., CTO, IONTAS, Ltd. 8:00 am Registration and Morning Coffee Biosustainability, Technical University of Denmark Using directed integration of antibody genes 2:05 CRISPR/Cas Tools for Host Cell by CRISPR/Cas9 and TALE nucleases, we have CASE STUDIES IN ENHANCING constructed large libraries in mammalian cells Improvement in the Baculovirus-Insect Cell containing a single antibody gene/cell. This has EXPRESSION SYSTEMS System permitted construction of millions of monoclonal 8:30 Chairperson’s Remarks Donald L. Jarvis, Ph.D., Professor, Molecular Biology, stable cell lines displaying IgG antibodies on their Henry C. Chiou, Ph.D., Associate Director, Cell Biology, University of Wyoming surface from which antibodies have been selected Life Science Solutions, Thermo Fisher Scientific One of my group’s major efforts has focused on by flow cytometry for specificity, binding affinity, engineering protein glycosylation pathways in the species cross-reactivity and expression level. baculovirus-insect cell system (BICS) to create Expression in production cell lines also enables new systems capable of producing “humanized” high-throughput developability screening. FEATURED PRESENTATION recombinant glycoproteins. We report development of novel CRISPR/Cas9 tools for site-specific genome 5:00 RNA Structural Determinants of Optimal 8:35 Engineering Cell Factories for Protein editing in the BICS. We then describe the use of Codons Revealed by MAGE-Seq Production these new tools to enhance our glycoengineering Eric Kelsic, Ph.D., Staff Scientist, George Church Bjørn Voldborg, Director, CHO Cell Line Development, efforts by targeting an endogenous Spodoptera Laboratory, Wyss Institute, Harvard Medical School The Novo Nordisk Foundation Center for frugiperda (Sf) glycogene, which antagonizes To understand the determinants of codon choice Biosustainability, Technical University of Denmark human-type glycan elongation. across a gene, we generated 12,726 in situ codon We have engineered cell-based factories for protein mutants in the Escherichia coli essential gene production, using state-of-the-art technologies 2:35 New Strategies of CRISPR/Cas9-Based infA and measured their fitness with MAGE-seq. combined with high-throughput genome engineering, High-Throughput Functional Genomic Correlating predicted 5’ RNA structure with fitness in silico modeling, deep -omics analysis and big Screening revealed that codons even far from the start of the data analysis. Our main focus is CHO cells, where Dongxin Zhao, Ph.D., Postdoctoral Fellow, Prashant gene are deleterious if they disrupt the native 5’ RNA we have generated a panel of CHO cell lines, with Mali Lab, Department of Bioengineering, University of conformation. Our results shed light on natural codon optimized phenotypes generating tailormade PTMs, By Cambridge Healthtech Institute California, San Diego distributions and should improve engineering of gene improved bioprocess and product quality, etc. Cancer is a complex disease of which targetable expression for synthetic biology applications. vulnerabilities are the consequence of 5:30 PANEL DISCUSSION: CRISPR/Cas 9:05 SKIK Tag Increasing the Expression of SHORT COURSES reprogramming of genetic architecture driven by various genetic mutations. Dissection of genetic Genome Editing for Protein Expression Hard-to-Express Proteins and Its Application interactions in a systematic way would provide CRISPR/Cas has emerged as a powerful tool for to Antibody Screening from Single B Cells unprecedented insights in drug discovery. Applying engineering the genome in diverse organisms. Teruyo Ojima-Kato, Ph.D., Researcher, Meijo the new powerful CRISPR/Cas9 technology, we However, there are also financial and legal University Sponsorship Opportunities developed a combinatorial screening platform considerations in using this tool. Hear this panel of A novel tag sequence SKIK can drastically increase which allows for both high-throughput mapping of experts discuss the pros and cons of CRISPR/Cas the expression of hard-to-express proteins in Hotel/Additional Information synthetic lethality and quantification of cancer cell genome editing and its role in enhancing desired Eschericha coli in vivo and in vitro protein synthesis type-specific interactions in metabolic circus. protein expression. Registration & Pricing systems without affecting its activity in most cases. Moderator: We used the peptide for a novel antibody production 3:05 Transition to BuzZ Sessions Bjørn Voldborg, Technical University of Denmark CHI-PepTalk.com CHI-PepTalk.com | 80 FINAL ALTERNATIVE WEEKS JANUARY 8-9 | 10TH ANNUAL EXPRESSION TO REGISTER Engineering Genes and Hosts & PRODUCTS Exploring Strategies in Systems Engineering and Synthetic Biology Cover

Sponsors from single B cells by RT-PCR, PCR and cell-free sample production is typically inefficient due to Event-at-a-Glance protein synthesis, because the amount of protein the commonly applied laborious trial-and-error expressed can be highly improved and normalized approach. ProteinData.Cloud is a platform to for better evaluation of Fab synthesized. access and share otherwise invisible experimental recombinant protein production information. Sponsored by 9:35 Engineering a CHO K1 Researchers find engineered vector sequences, Toolbox for Reliable High Titer positive and negative recombinant expression Protein Expression trials and purification detail, apply and improve Jamie Freeman, Ph.D., Product Manager, Horizon recombinant protein production strategies to their Discovery own targets to improve protein production yield and purity. Aside from single gene knockouts to allow for metabolic selection systems, the CHO host remains 12:00 pm Unlock Pichia – Novel Sponsored by largely unchanged. I will present how we have used a combination of techniques including genome Strategies and Molecular Tools to engineering approaches such as CRISPR and rAAV Enhance Protein Expression to improve the biomanufacturing capacity of our GS Iskandar Dib, Ph.D., Principal Scientist DSP & knockout CHO K1 cell line. Analytics, VTU Technology GmbH Pichia pastoris is an established, safe and highly 9:50 Coffee Break in the Exhibit Hall with competitive expression host with strong and Poster Viewing effective secretory capacities often resulting in double-digit g/l levels of recombinant protein. 11:00 Development of a High-Yielding Recent research has brought about new exciting Expression Platform for the Introduction of technologies increasing the potential of this already Non-Natural Amino Acids powerful yeast production host. An extended Gargi Roy, MSc, Scientist I, Antibody Discovery and molecular toolbox addresses challenges in protein Protein Engineering/Research, MedImmune LLC folding and secretion and facilitates the expression We developed an expression technology that of more complex proteins, thus maximizing yields enables site-specific incorporation of non-natural without compromising product quality. amino acids (nnAA) in a protein sequence. Fully 12:30 Session Break functional, high titered IgG, in a continuous perfusion process, was produced in hosts stably expressing 12:45 Luncheon Presentation (Sponsorship an orthogonal tRNA synthetase/tRNA pair. This host Opportunity Available) or Enjoy Lunch on Your platform holds promise to overcome the expression challenges that have encumbered the developability Own of this technology for manufacturing of antibody- 1:15 Close of Engineering Genes and Hosts drug conjugates and other protein conjugates. By Cambridge Healthtech Institute Conference 11:30 Establishing Protein Production without Reinventing the Wheel: ProteinData.Cloud SHORT COURSES Peter Nollert, Ph.D., Business Director, Research and Development, Bio Data Bridges Establishing viable paths for recombinant protein

Sponsorship Opportunities

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 81 FINAL ALTERNATIVE WEEKS JANUARY 9-10 | 2ND ANNUAL EXPRESSION TO REGISTER Biocatalysis and Bio-Based Chemical Production & PRODUCTS Biocatalysis, Enzyme and Metabolic Engineering, and Synthetic Biology Cover

Sponsors Advances in protein engineering, the advent of new chemistries and custom-made biocatalysis are leading to broader industrial enzyme across a range of industries, Event-at-a-Glance including pharma, fine chemicals and agriculture. Coupled with advances in systems and synthetic biology, the opportunities to create sustainable, scalable and cost-effective chemical production are greater than ever. CHI’s Second Annual Biocatalysis and Bio-Based Chemical Production conference tackles the latest advances in biocatalysis, metabolic and enzyme engineering, and synthetic biology, with dedicated sessions on new chemistries, protein engineering and novel applications of enzymes across a range of industries.

TUESDAY, JANUARY 9 exploit natural enzyme latent catalytic promiscuity to rapidly design new catalysts. Successful 5:45 - 8:45 Dinner Short Courses* 1:00 pm Registration applications of this approach will be presented. See page 5 for details * Separate registration required 1:30 Refreshment Break in the Exhibit Hall 3:15 Sponsored Presentation (Opportunity with Poster Viewing Available) NEW ADVANCES IN BIOCATALYSIS 3:45 Refreshment Break in the Exhibit Hall WEDNESDAY, JANUARY 10 with Poster Viewing 2:00 Chairperson’s Opening Remarks 8:00 am Registration and Morning Coffee 4:30 Bioinformatics and Machine Learning David Rozzell, Ph.D., Senior Vice President, Biocatalysis, Provivi Methods to Accelerate Enzyme Engineering NEW ENZYME SCREENING, James Lalonde, Ph.D., Senior Vice President, R&D, Codexis DISCOVERY, DESIGN AND KEYNOTE PRESENTATION Enzyme engineering has benefited from DEVELOPMENT — CASE STUDIES technological advances in the design, testing, and 2:05 The Discovery of a New Enzyme analysis of variant libraries. Molecular modeling 8:30 Chairperson’s Remarks ‘Reductive Aminase’ methods inform library design, while automation David Weiner, Ph.D., Vice President, Technology & Nicholas Turner, Ph.D., Professor, Chemical (particularly for sequencing) accelerates testing, and Product Development, BASF Enzymes, LLC Biology, University of Manchester machine learning algorithms facilitate elucidation of 8:35 Accelerating the Application of The reductive aminase from Aspergillus complex structure-function relationships. Integration oryzae (AspRedAm) is an NADP(H)-dependent of such advances will be presented, along with case Biocatalysis for Drug Discovery and oxidoreductase that has been shown to studies highlighting efficient enzymatic synthesis of Development catalyse the enantioselective reductive active pharmaceutical ingredients. Douglas Fuerst, Ph.D., Director, GSK Fellow, Advanced coupling of a remarkably broad set of ketones Manufacturing Technologies, GlaxoSmithKline and aldehydes with different amines, ranging 5:00 Genomic Mining of Aldehyde Advances in biocatalysis and directed evolution from primary/secondary amines to ammonia, Deformylating Oxygenates Defines Structural are increasing the number of opportunities to apply in up to >98% conversion and with >98% Features that Enable Engineering of Function enzymes and cells in the synthesis of pharmaceutical enantiomeric excess. The AspRedAm wild- Justin Siegel, Ph.D., Assistant Professor, compounds. This presentation will describe the type biocatalyst has been applied to reductive Biochemistry & Molecular Medicine, UC Davis approach being advanced at GlaxoSmithKline across By Cambridge Healthtech Institute amination reactions on a preparative-scale, Genome Center both drug discovery and development highlighted displaying total turnover numbers up to 32,000. I will discuss the combination of genomic mining, with several relevant case studies. structural biology, and machine learning to 9:05 Biocatalysis: An Enabling Technology for 2:45 From Novel Enzymes to de novo determine the structural features that enable soluble SHORT COURSES Rapid Chemical Process Development Pathways and Designer Strains aldehyde deformylating oxygenase (ADO) activity. Jacob Janey, Ph.D., Associate Director, BMS Alexandre Zanghellini, Ph.D., CEO, Arzeda These features were then used to introduce ADO’s activity into the small subunit of ribonucleotide Biocatalysis has long been recognized as a Our ability to design cell factories to produce reducatase. key, green chemical technology in the design of valuable chemicals requires the “recombination” Sponsorship Opportunities robust, efficient manufacturing routes for active not only of existing but also designer enzymes into 5:30 Close of Day pharmaceutical ingredients. It also represents Hotel/Additional Information novel metabolic pathways to achieve entirely new an important tool for the rapid execution of metabolic function. To this end, Arzeda is developing 5:30 - 5:45 Short Course Registration “fit-for-purpose” campaigns to fund supplies of Registration & Pricing high-throughput computational methodologies to development compounds’ early clinical studies.

CHI-PepTalk.com CHI-PepTalk.com | 82 FINAL ALTERNATIVE WEEKS JANUARY 9-10 | 2ND ANNUAL EXPRESSION TO REGISTER Biocatalysis and Bio-Based Chemical Production & PRODUCTS Biocatalysis, Enzyme and Metabolic Engineering, and Synthetic Biology Cover

Sponsors This talk will focus on informative case studies promiscuity by novel efficient parallel expression engineering of the cofactor selectivity of this from BMS’s Chemical and Synthetics Development and purification strategies. They are efficient in the enzyme, including the introduction of an intrinsically Event-at-a-Glance organization where bespoke biocatalysts have synthesis of a wide range of halogenated nucleosides disordered peptide into the active site to tune served as a critical enabling technology for by one-pot transglycosylation reactions. Also, we cofactor selectivity by calcium addition. innovative synthetic route development. established an enzymatic phosphorylation cascade from nucleosides to nucleotides. These tools provide a 3:05 Refreshment Break in the Exhibit Hall 9:35 Sponsored Presentation (Opportunity solid basis for the efficient synthesis of a wide range of with Poster Viewing Available) novel substances. 4:00 Bringing Some Structure to Biocatalysis 10:05 Coffee Break in the Exhibit Hall with 12:20 pm Sponsored Presentation - Designing Genetically Programmable Poster Viewing (Opportunity Available) Biocatalytic Systems Stefan Lutz, Ph.D., Professor and Department Chair, 10:50 Towards a Synthetic Biology Platform 12:50 Session Break Department of Chemistry, Emory University for Natural Product Discovery 1:00 Luncheon Presentation (Sponsorship Protein-based nanocompartments represent Charles Moore, Ph.D., Research Investigator, Novartis Opportunity Available) or Enjoy Lunch on Your robust carrier matrices for the assembly of artificial The maturation of DNA sequencing technologies Own biocatalytic nanoreactors. Challenges related to coupled with the rapid emergence of synthetic biology ineffective permeability of metabolites due to small has turned (meta)genome mining into an attractive STRAIN, ENZYME AND METABOLIC pores in the protein shell and lacking exterior surface avenue to acquire novel chemical starting points functionality are addressed through protein engineering, to facilitate early lead discovery. We present our ENGINEERING enabling the creation of tailored carriers that can serve experiences from a multi-year effort to design and 2:00 Chairperson’s Remarks as highly versatile scaffold with excellent control over implement a natural product discovery pipeline based on spatial organization of (bio)catalysts. principles of synthetic biology. This effort has permitted Yoram Barak, Ph.D., Biosciences Innovation Manager, us to understand where bottlenecks reside and BASF Enzymes, LLC 4:30 Combining Genome-Scale Modeling and potentially how they could be addressed going forward. 2:05 Genome-Scale Engineering: A New Adaptive Laboratory Evolution to Optimize Enzymes and Whole Cells 11:20 Enzyme Engineering for Regioselective Frontier in Metabolic Engineering Adam Feist, Ph.D., Project Scientist, Systems Biology Hydroxylation in a Whole Cell Environment Huiman Zhao, Ph.D., Departments of Chemical and Biomolecular Engineering, Chemistry, and Research Group, University of California Toni Lee, Ph.D., Senior Scientist, Biocatalysis, Provivi Biochemistry, Bioengineering, Institute for Genomic Constraint-based modeling is a predictive approach Membrane-bound enzymes present unique challenges Biology, and Center for Biophysics and Computational which can be utilized to drive metabolic engineering to protein engineers. We are currently generating (Z)- Biology, University of Illinois through simulating strain designs and integrating 11-hexadecenol from the alkene using an oleaginous Advances in reading, writing and editing genomes have omics measurements. Adaptive laboratory evolution cell catalyst expressing membrane-anchored P450 greatly expanded our ability to reprogram biological is a powerful experimental technique that, unlike alkane or fatty acid hydroxylases. Using a medium- systems at the resolution of a single nucleotide and on rational engineering, is conducted without a priori throughput whole-cell screen, we detected hydroxylase the scale of a whole genome. In this talk, I will highlight knowledge on how beneficial traits would arise homologs or single point mutants with improved our recent work in the development of new molecular and therefore can result in unintuitive biological regioselectivity for hydroxylating the desired terminus parts and tools for genome-scale engineering and our mechanisms. These two technologies can be of the alkene. These findings have application to the By Cambridge Healthtech Institute attempt in automating the design, build and test cycle combined to predict and acquire strains with production of lepidopteran sex pheromones for use in for strain development. beneficial industrial biotechnology capabilities. agricultural pest control. 2:35 Engineering Cofactor Selectivity: Some 5:00 The Role of Synthetic Biology in Creating SHORT COURSES 11:50 The Potential of Biocatalysis for the New Ideas for an Old Problem New Pathways and Products Synthesis of Small Drugs: Exploiting the Scott Banta, Ph.D., Professor, Chemical Engineering, Srivatsan Raman, Ph.D., Assistant Professor, Promiscuity of Nucleoside and Nucleotide Columbia University Departments of Biochemistry & Bacteriology, University of Wisconsin-Madison Phosphorylases Engineering cofactor selectivity in dehydrogenases Sponsorship Opportunities Peter Neubauer, Ph.D., Professor, Department of has been an important engineering goal for more 5:30 - 6:45 Networking Reception in the Bioprocess Technology, Institute of Biotechnology, than 25 years. We have been engineering just about Hotel/Additional Information Exhibit Hall with Poster Viewing Technische Universität Berlin every aspect of the NAD(H)-dependent thermostable We develped a broad portfolio of recombinantly alcohol dehydrogenase D (AdhD) from Pyrococcus Registration & Pricing 6:45 Close of Biocatalysis and Bio-Based expressed thermophilic enzymes with wide substrate furiosus. I will discuss recent insights into the Chemical Production Conference CHI-PepTalk.com CHI-PepTalk.com | 83 FINAL ALTERNATIVE WEEKS JANUARY 11-12 | 2ND ANNUAL EXPRESSION TO REGISTER Microbial Production & PRODUCTS Optimizing the Expression and Production of Microbial Expressed Proteins Cover

Sponsors Microbial expression systems offer significant advantages over other hosts by providing faster development times, greater yields, and lower production costs. However, limitations around glycosylation and central metabolic pathways poses significant challenges. Event-at-a-Glance Cambridge Healthtech Institute’s Microbial Production conference covers the latest developments in microbial expression and production – from host strain development to metabolic engineering, assembly to scale-up, downstream processing to process characterization – with particular focus on the role of E. coli for biotherapeutics and novel products.

THURSDAY, JANUARY 11 E. coli expression platform to reliably and rapidly 12:00 pm Session Break achieve increased protein yields. This enables the Sponsored by 7:45 am Registration and Morning Coffee development of new production processes that are 12:15 Luncheon Presentation I: commercially viable from both a cost of goods and cGMP Biologics Production Using INCREASING YIELD AND capacity perspective. Case studies will be presented Corynex®: A Highly-Productive Gram-Positive in which the original process presented significant Microbial Protein Secretion System EXPRESSION challenges with respect to the cost of goods and the Yoshimi Kikuchi, Ph.D., Executive Professional and production capacity. 8:15 Chairperson’s Opening Remarks Group Manager, Recombinant Protein Research Georg Klima, Dipl. Ing., Executive Director, Process 10:00 Coffee Break in the Exhibit Hall with Group, Material Development & Application Labs, Ajinomoto Co., Inc. Science, Boehringer Ingelheim RCV GmbH & Co. KG Poster Viewing Corynex® is Ajinomoto’s highly-productive protein 11:00 Easy Intracellular Recombinant Protein expression system based on the fast-growing KEYNOTE PRESENTATION Expression in Yeast by Pichia pastoris Auto- gram-positive bacteria C. glutamicum. The powerful and easy-to-handle platform can secrete correctly- 8:20 Expression of Complex Proteins in Induction folded proteins directly into the media with high E. coli Jonas Lee, Ph.D., Scientist, Amgen purity and no endotoxins. These advantages allow Dorothea Reilly, Ph.D., Principle Scientist and Pichia pastoris is a highly successful recombinant users to avoid many manufacturing/quality pitfalls Associate Director, Early Stage Cell Culture, microbial protein expression system due to its and ultimately improve profitability and timelines. Genentech eukaryotic components while maintaining fast growth We recently demonstrated successful 1000L cGMP Genentech produces recombinant proteins time. Despite these advantages, protein expression biologics production using Corynex®. for therapeutic use employing both CHO methods in P. pastoris are still burdensome due to a cells and E. coli. We have developed E. coli need to swap entire growth media to induction media. 12:45 Luncheon Presentation II (Sponsorship processes that are optimized for the secretion Here we present a simple method to auto-induce P. Opportunity Available) of recombinant proteins into the periplasmic pastoris using the inhibitive properties of the AOX1 space where folding and assembly can occur. promoter by residual glycerol. 1:15 Ice Cream Break in the Exhibit Hall with This talk will describe how these approaches Poster Viewing have enabled the production of complex 11:30 Microbial Secretion by Sponsored by protein formats. ESETEC®: A Cost-Efficient HOST ENGINEERING AND STRAIN Alternative to Mammalian Cells for Non- DEVELOPMENT Glycosylated Proteins 9:00 Pfizer E. coli Expression Platform Part By Cambridge Healthtech Institute I: Development and Testing of an Integrated Sebastian Schuck, Ph.D., Head, Business 2:00 Chairperson’s Remarks Development, Wacker Biotech GmbH Cloning and Expression System Christoph Reese, Ph.D., Director, Microbial The microbial secretion technology ESETEC® Fermentation, Roche Diagnostics GmbH Kevin Rust, Ph.D., Principal Scientist, Bioprocess R&D, SHORT COURSES offers a cost- and time-efficient alternative for the BioTherapeutics Pharmaceutical Sciences, Pfizer, Inc. production of biologics. With straightforward strain 2:05 E. coli Periplasmic Expression of ® 9:30 Pfizer E. coli Expression Platform Part and process development, ESETEC combines Antibody Fab Fragments benefits of microbial and mammalian systems. II: Application of the Platform to Test Reliably Mark Ellis, Principal Scientist, Protein Expression and Applying cutting-edge process simulation tools, Purification, UCB Pharma Sponsorship Opportunities and Rapidly Achieve Increased Protein Yields ® we demonstrated that Cost-of-Goods for ESETEC Engineered variants of wild type E. coli strains Marie Caparon, Ph.D., Associate Research Fellow, manufacturing is up to 3 times lower than CHO. have been developed which significantly improved Hotel/Additional Information Bioprocess R&D, BioTherapeutics Pharmaceutical periplasmic Fab expression yields. Furthermore, Sciences, Pfizer, Inc. 11:45 Sponsored Presentation (Opportunity Registration & Pricing co-expression of E. coli host proteins, combined The presentation describes the application of an Available) with engineered strains and fermentation process

CHI-PepTalk.com CHI-PepTalk.com | 84 FINAL ALTERNATIVE WEEKS JANUARY 11-12 | 2ND ANNUAL EXPRESSION TO REGISTER Microbial Production & PRODUCTS Optimizing the Expression and Production of Microbial Expressed Proteins Cover

Sponsors refinements have enabled Fab yields over 5g/L. These Science, Boehringer Ingelheim RCV GmbH & Co. KG Associate Research Fellow, Cell Line Development, increases have been achieved without compromising Bioprocess R&D, Pfizer Event-at-a-Glance Novel biotherapeutic formats pose unique cell viability or the quality of the Fab produced. development challenges. Strategies for successful development need to holistically consider all 2:35 A Strategy for Production of Correctly aspects of biopharmaceutical processes such MICROBIAL BIOPROCESSING AND Folded Disulfide-Rich Peptides in the as expression strategies, novel unit operations, Periplasm of E. coli automated high-throughput process development, PROCESS CHARACTERIZATION Natalie Saez, Ph.D., Senior Research Officer, as well as scale up and transfer from bench to 9:00 Chairperson’s Remarks Institute for Molecular Bioscience, The University of large-scale manufacturing. We present our holistic Adekunle O. Onadipe, Ph.D., Associate Research Queensland approach based on a HTPD toolbox to lever the Fellow, Cell Line Development, Bioprocess R&D, Pfizer Disulfide bonds generally confer favorable complexity of manufacturing development for non- properties, such as high stability, to the native platform biotherapeutics. Integration of the whole peptides, but can pose considerable challenges process is also discussed. FEATURED PRESENTATION for recombinant production. Presented herein is a 5:15 High-Throughput Automated Protein method for recombinant expression of disulfide- 9:05 Microbial Process Development in View Folding and Quantitative Assessment rich peptides in the periplasm of Escherichia coli of Industry 4.0 Philip An, Scientist, Biologics, Amgen using a cleavable, solubility-enhancing fusion tag. Peter Neubauer, Ph.D., Prof. Dr., Chair of Bioprocess Examples of recombinant periplasmically-expressed Employing E. coli to recombinantly express a gene Engineering, Department of Biotechnology, disulfide-rich venom peptides of therapeutic and/or of interest can enable rapid and robust production; Technische Universität Berlin commercial interest are provided. however, the proteins are often located in inclusion In our lab-of-the-future concept we integrate bodies, necessitating a folding reaction to obtain Sponsored by and fully automate all wetlab techniques for the 3:05 Approaches and High their native state. To address this in a high- production of competent cells, DNA transformation, Through-Put Tools to Solve Strain throughput, quantitative manner, we developed a optimization of cultivation parameters with the dense folding matrix system that employs highly and Process Development analytical methods for medium components and integrated liquid-handling automation and a Challenges for Recombinant Proteins downstream operation to analyze product activity quantitative assessment system to swiftly identify Expressed in E. coli and other quality parameters. This allows us to apply effective folding conditions. Nigel Shipston, Ph.D., Head of Programme Design, a dynamic optimal design of experiments strategy FUJIFILM Diosynth Biotechnologies 5:45 Close of Day (ODoE) to create digital twins for each target protein process (mechanistic models) which can be applied 3:35 Refreshment Break in the Exhibit Hall for computation-based bioprocess development. with Poster Viewing FRIDAY, JANUARY 12 4:15 High-Yield, Mineral Medium, Antibiotics 8:00 am Registration 9:35 A S. Cerevisiae Process Characterization Free E. coli Expression System for Production of a Therapeutic Recombinant Protein Using a Multivariate Analysis Christoph Reese, Ph.D., Director, Microbial 8:00 BuzZ Sessions with Continental Fermentation, Roche Diagnostics GmbH Juan Aon, Ph.D., Senior Manager, MCCD, RD Breakfast Biopharm, R&D, GSK By Cambridge Healthtech Institute The development of a mineral medium based, Protein therapeutics is a fast-growing antibiotics free E. coli expression system will be 10:05 Microbial Expression and Production of presented. In a case study, we show the suitability global market. As the science improves, of the expression system for the manufacturing so does the complexity of the R&D Pasylated Proteins and Peptides: Biobetters SHORT COURSES of a recombinant enzyme in industrial scale in organization. Ensuring product quality with Extended Half-Life and Enhanced Action high yield. The system may also be utilized to plus speed to market requires insights from Uli Binde, Ph.D., CTO, XL-Protein express otherwise insoluble proteins. A comparison stakeholders working across the stages of protein PASylation comprises the genetic fusion of to antibiotics-based selection systems and science R&D. Join experts representing this PepTalk biologics with a natively disordered biosynthetic Sponsorship Opportunities hydrolysates-based growth media will be discussed. pipeline, peers, and colleagues for an interactive polymer made of Pro, Ala and/or Ser (PAS). Such roundtable discussion. Topics include highlights PAS sequences are highly soluble in physiological Hotel/Additional Information 4:45 Holistic Process Development Strategies from the week’s presentations, new technologies solution and stably adopt random coil conformation for Microbial Expression and strategies, challenges, and future trends. with an expanded hydrodynamic volume which leads Registration & Pricing Georg Klima, Dipl. Ing., Executive Director, Process Table Moderator: Adekunle O. Onadipe, Ph.D., to retarded kidney filtration and drastically prolonged

CHI-PepTalk.com CHI-PepTalk.com | 85 FINAL ALTERNATIVE WEEKS JANUARY 11-12 | 2ND ANNUAL EXPRESSION TO REGISTER Microbial Production & PRODUCTS Optimizing the Expression and Production of Microbial Expressed Proteins Cover

Sponsors pharmacokinetics in vivo. PASfusion proteins often 11:45 Recoded E. coli for Incorporation of Event-at-a-Glance show improved stability, and they can be produced Non-Natural Amino Acids and Also for the in a single step in microbial hosts, thus avoiding Purpose of Genetic Isolation costly chemical modification steps. Farren Isaacs, Ph.D., Assistant Professor, Molecular 10:35 Coffee Break with a Poster Pavilion Cellular and Development Biology, Yale University See page 4 for details Genetically modified organisms (GMOs) are increasingly used in research and industrial systems 11:15 Towards a New Generation of to produce high-value pharmaceuticals, fuels, and Glycoengineered Pneumococcal Bioconjugate chemicals. Here, we describe the construction of a Vaccines series of genomically recoded organisms (GROs), 11 whose growth is restricted by the expression Christian Harding, Ph.D., CSO, VaxNewMo of multiple essential genes that depend on Glyco-conjugate vaccines, consisting of a exogenously supplied synthetic amino acids (sAAs). polysaccharide attached to a carrier protein, are excellent immunogens manufactured using labor-intensive chemical crosslinking 12:15 pm Conference Wrap-Up steps. As an innovative alternative, VaxNewMo Adekunle O. Onadipe, Ph.D., Associate Research utilizes a glycoengineering strategy to generate Fellow, Cell Line Development, Bioprocess R&D, Pfizer “bioconjugates” in Escherichia coli. Key to this process is a conjugating enzyme, which attaches a polysaccharide to a protein. 12:45 Close of Conference

PepTalk’s BuzZ Sessions are focused, stimulating By Cambridge Healthtech Institute discussions in which delegates discuss important and interesting topics related to upstream protein expression SHORT COURSES and production through downstream scale-up and manufacturing. This is a moderated discussion with What’s the BuzZ about? brainstorming and interactive problem-solving between Sponsorship Opportunities scientists from diverse areas who share a common interest in the discussion topic. Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 86 FINAL WEEKS TO REGISTER SPONSORSHIP AND LEAD GENERATION OPPORTUNITIES Comprehensive sponsorship packages allow you to achieve your objectives before, during, and long after Cover the event. Signing on earlier will allow you to maximize exposure to hard-to-reach decision-makers. Sponsors Sponsored Presentations - Available within the Main Agenda! Additional Opportunities Available for Sponsorship Include: Event-at-a-Glance Showcase your solutions to a guaranteed, targeted audience • Hotel Room Keys • Literature Distribution through a 15- or 30-minute presentation during a specific conference • Focus Groups (Tote Bag Insert or Chair Drop) program, breakfast, lunch, or separate from the main agenda within • Footprint Trails • Badge Lanyards - SOLD a pre-conference workshop. Package includes exhibit space, on-site • Staircase Ads • Conference Notebook branding, and access to cooperative marketing efforts by CHI. For the • Conference Tote Bags • Program Guide Advertisement luncheon option, lunches are delivered to attendees who are already seated in the main session room. Presentations will sell out quickly, so Looking for Additional Ways to Drive Leads to Your Sales Team? sign on early to secure your talk! CHI’s Lead Generation Programs will help you to obtain more targeted, One-on-One Meetings quality leads throughout the year. We will mine our database of over 800,000 life science professionals to your specific needs. We Select your top prospects from the pre-conference registration list. guarantee a minimum of 100 leads per program! Opportunities include: CHI will reach out to your prospects and arrange the meeting for • White Papers • Webinars you. A minimum number of meetings will be guaranteed, depending on your marketing objectives and needs. A limited number of these • Custom Market Research Survey • Podcasts packages will be sold. Invitation-Only Dinner/Hospitality Suite For Sponsorship and Exhibit Information, Please Contact: Sponsors will select their top prospects from the conference COMPANIES A-K preregistration list for an evening of networking at the hotel or choice Jason Gerardi View current local venue. CHI will extend invitations, conduct follow-up and confirm Sr. Manager, Business Development Exhibitor List attendees. The evening will be customized to meet with your specific 781-972-5452 [email protected] and Floor Plan objectives. COMPANIES L-Z Exhibit Carol Dinerstein Exhibitors will enjoy facilitated networking opportunities with over Register as an Sr. Manager, Business Development 1,300 qualified delegates, making it the perfect platform to launch a Exhibitor Here 781-972-5471 [email protected] new product, collect feedback, and generate new leads from around the world. Exhibit space sells fast, so reserve yours today!

PEPTALK 2017 DEMOGRAPHICS Professor: 4% Other: 4% By Cambridge Healthtech Institute Manager: 9% Academic: 14% COMPANY TYPE SHORT COURSES DELEGATE TITLE Sales & Commercial Government: 2% Marketing: (Biotech + Services/Societies: 2% 15% Scientist/ Sponsorship Opportunities Pharma): Healthcare: 2% Technologist: 79% 39% Hotel/Additional Information Executive & Other: 1% Director: 27% Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 87 FINAL WEEKS TO REGISTER HOTEL & TRAVEL INFORMATION Cover

Sponsors Conference Venue and Hotel:

Event-at-a-Glance Hilton San Diego Bayfront One Park Boulevard San Diego, CA 92101 T: 619-564-3333 Reservations: Visit the travel page of CHI-PepTalk.com Discounted Room Rate: $262 s/d *Room rate includes wireless internet in your guestroom* Discounted Cut-off Date: December 12, 2017

Visit the travel page of CHI-PepTalk.com for additional information

2018 MEDIA SPONSORS

SPONSORING ORGANIZATIONS: SPONSORING PUBLICATIONS: WEB PARTNERS:

By Cambridge Healthtech Institute

OFFICIAL PUBLICATION: FierceBiotech SHORT COURSES THE BIOTECH INDUSTRY’S DAILY MONITOR

Sponsorship Opportunities LEAD SPONSORING PUBLICATIONS:

Hotel/Additional Information

Registration & Pricing

CHI-PepTalk.com CHI-PepTalk.com | 88 FINAL January 8-12, 2018 WEEKS San Diego, CA TO REGISTER

Cover How to Register: CHI-PepTalk.com [email protected] P: 781.972.5400 or Toll-free in the U.S. 888.999.6288 Sponsors Please use keycode PTK F when registering Event-at-a-Glance

CONFERENCE DISCOUNTS

Poster Submission - Discount ($50 Off): Poster abstracts are due by November 10. Once your PRICING & REGISTRATION INFORMATION registration has been fully processed, we will send an email containing a unique link allowing you to submit SHORT COURSE PRICING your poster abstract. If you do not receive your Commercial Academic, Government, link within 5 business days, please contact jring@ Hospital-affiliated healthtech.com. *CHI reserves the right to publish Short Course $699 $349 your poster title and abstract in various marketing materials and products. Tuesday, January 9 | 5:45-8:45 pm Sponsoring Organization Discounts: CHI is pleased to offer our partnering organization CONFERENCE AND TRAINING SEMINAR PRICING members a 20% discount to attend. Please see the online registration page for details and offers. PREMIUM PACKAGE - BEST VALUE! REGISTER 3 - 4th IS FREE: Individuals must (Includes access to all conferences and Training Seminars Monday-Friday. register for the same conference or conference Plus, attend a Dinner Short Course at a discounted rate.) combination and submit completed registration Advance Registration until November 17 $3199 $1699 form together for discount to apply. Registration after November 17 $3399 $1799 Alumni Discount: SAVE 20%: CHI appreciates your participation at our events. As a result of the great Plus, add a Dinner Short Course for only… $349 $199 loyalty you have shown us, we are pleased to STANDARD PACKAGE extend to you the exclusive opportunity to save an (Includes access to 2 conferences and/or Training Seminars. Excludes Short Courses.) additional 20% off the registration rate. Advance Registration until November 17 $2749 $1329 Group Discounts: Discounts are available for multiple attendees from the same organization. Registration after November 17 $2999 $1399 For more information on group rates contact David BASIC PACKAGE Cunningham at +1-781-972-5472. (Includes access to 1 conference or Training Seminar. Excludes Short Courses.) *Alumni, Antibody Society, Twitter, LinkedIN, Facebook or any other promotional discounts cannot be combined. Advance Registration until November 17 $1849 $929 Discounts not applicable on event Short Courses. Registration after November 17 $2079 $1079 By Cambridge Healthtech Institute If you are unable to attend but would like to purchase the PepTalk CD for $750 (plus shipping), please visit CHI-PepTalk.com. Massachusetts delivery will include sales tax. SHORT COURSES

Sponsorship Opportunities ADDITIONAL REGISTRATION DETAILS: Each registration includes all conference sessions, posters and exhibits, food functions, and access to the conference proceedings link. Handicapped Equal Access: In Hotel/Additional Information accordance with the ADA, Cambridge Healthtech Institute is pleased to arrange special accommodations for attendees with special needs. All requests for such assistance must be submitted in writing to CHI at least 30 days prior to the start of the meeting. Registration & Pricing To view our Substitutions/Cancellations Policy, go to www.healthtech.com/regdetails. Video and or audio recording of any kind is prohibited onsite at all CHI events. CHI-PepTalk.com