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FINAL AGENDA

april 28 - 29, 2012 The Boston Park Plaza Hotel & Towers | Boston, MA Biologics PHARMA-BIO partnering forum PARTNERING FORUMS Emerging &

Focusing on the Right Partners

REASONS TO ATTEND: Network and foster business with the companies that are going drive biologics growth over the next decade, as well those interested in funding its expansion In-Depth Presentations focused on promising technology platforms and innovative approaches in antibody therapies and Leading Early-Stage Companies hand-picked to present by top biologics experts from our Program Advisory Board TOP INDUSTRY EXECUTIVES, BIG PHARMA & INVESTORS in attendance, open to further business collaborations

COVERAGE includes: • In Vivo Transgenic Antibody Platforms • Fusion • In Vitro Antibody Development Platforms • Protein Diversity • Antibody Tools • Human-Derived • Novel Antibody Products in Development • Novel Protein Scaffolds • Bi-Specific and Multi-Specific Antibody • Screening and Platforms Technologies for Protein Engineering

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the essential protein engineering summit

Organized by Cambridge Healthtech Institute PEGSummit.com/Antibody-Engineering-Partnering1 Program Advisory Board includes: Brian Atwood, M.B.A., Managing Director, Versant Robert Kastelein, Ph.D., Vice President, Biologics Hilde Revets, Ph.D., Senior Research Fellow, Ventures Strategy, Merck Research Labs Technology, Ablynx Sharon Cload, Ph.D., Vice President, Adnexus, Reid Leonard, Ph.D., Executive Director, Licensing, Barry Springer, Ph.D., Head of External Research Bristol Myers Squibb Merck Research Labs and Innovation, Biologics Research, Johnson & Jon Ellis, Ph.D., Vice President, Business Luke Li, M.D., Executive Director, Head of Global Johnson Development, Biopharmaceutical R&D BioTherapeutic Technologies, Pfizer Charles Wilson, Ph.D., Vice President, Global and Platform Technology & Science, GlaxoSmithKline Thomas Li, Ph.D., Senior Director, Technology, Roche Head of Strategic Alliances, Novartis Institutes for Richard Harkins, Ph.D., Principal Scientist, Global Diagnostics Biomedical Research Drug Discovery, Bayer Kia Motesharei, Ph.D., Vice President, Business Gordon Wong, Ph.D., Vice President, Business Healthcare Pharmaceuticals Development & Alliance Management, Dyax Corp. Development, Biogen-IDEC Margaret Karow, Ph.D., Executive Director, Protein Sciences, Amgen

BIOLOGICS PARTNERING FORUM PRESENTERS: Dustin Armstrong, Ph.D., Vice President of Research, 4S3 Lee Henderson, Ph.D., Chief Executive Officer, Vybion, Inc. Andrew Rakestraw, Ph.D., Head of Technical Operations, Bioscience Paul Kang, Chief Scientific Officer, Innovative Targeting Protein Engineering, Celexion LLC Tom Barnes, Ph.D., Vice President, Discovery, Eleven Solutions, Inc. Mike Romanos, Ph.D., Chief Executive Officer, Crescendo Biotherapeutics, Inc. David King, Ph.D., Chief Scientific Officer, AnaptysBio Biologics Ltd. Julian Bertschinger, Ph.D., Chief Executive Officer, Marie Kosco-Vilbois, Ph.D., Chief Scientific Officer, Joseph Rucker, Ph.D., Director of R&D, Integral Molecular Covagen NovImmune SA Inc. Roland Buelow, Ph.D., Chief Executive Officer, Open Allen Krantz, Ph.D., President and Chief Executive Officer, Sushma Shivaswamy, Ph.D., Director of Research & Monoclonal Technology, Inc. Advanced Proteome Therapeutics, Inc. Development, XBiotech Robert Burns, Ph.D., Chief Executive Officer, 4-Antibody Titus Kretzschmar, Ph.D., CSO Delenex Therapeutics AG Lesley Stolz, Ph.D., Vice President, Business Development, AG Sutro Biopharma, Inc. Volker Lang, Ph.D., Managing Director, AbCheck s.r.o. Bassil Dahiyat, Ph.D., Chief Executive Officer, Xencor, Inc. Kristine Swiderek, Ph.D., CSO & VP of Research, Casey Logan, M.B.A., Senior Vice President, Business Theraclone Sciences James R. Dasch, Ph.D., Chief Scientific Officer and Co- Development, Anaphone, Inc. Founder, Abazyme LLC Ali Tehrani, Ph.D., Chief Executive Officer, Zymeworks Nico Mertens, Ph.D., Director of Antibody Engineering, Davis Farmer, Chairman, Executive, MSM Protein Biotecnol, Inc. Mark Throsby, Ph.D., Chief Scientific Officer, Merus BV Technologies Sean McCarthy, Ph.D., M.B.A., Chief Executive Officer, Chris Ullman, Ph.D., Chief Scientific Officer, Isogenica Ltd. Barbara Fox, Ph.D., Chief Executive Officer, Avaxia CytomX Therapeutics, Inc. Mark Vaeck, Ph.D., Chief Executive Officer, Complix NV Biologics, Inc. Dinesh Patel, Ph.D., Chief Executive Officer, Protagonist Richard Wagner, Ph.D., Founder and Chief Scientific Katherine Griffiths, Ph.D.,Senior Scientist, Biochemistry, Therapeutics Officer, X-BODY BioSciences AdAlta / LaTrobe University David Rabuka, Ph.D., Chief Scientific Officer, Redwood Jin-San Yoo, Ph.D., Chief Executive Officer & President, Ulrich Haupts, Ph.D., Chief Scientific Officer, Bioscience, Inc. PharmAbcine, Inc. Technology, Scil Proteins GmbH

Reserve your hotel room and SAVE $100 off your conference registration* *You must book your reservation under the Cambridge Healthtech/PEGS room block for a minimum of four nights Partner Direct is a networking tool designed to facilitatecollaboration amongst at The Boston Park Plaza Hotel & Towers. emerging companies and potential strategic partners. It is only available to The $100 discount is per room. registered attendees of the Bio-Pharma Partnering Forums. CHI employs partnering software so the audience will have the opportunity to sign up for one- *See page 7 for hotel and travel details* on-one meetings ahead of time with company presenters during the conference. For more information on CHI’s Partnering Forums please visit PharmaBioPartnering.com stay connected

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“The great thing about the PEGS meetings is not only the superb science, but the great networking and opportunities.” - Premus

2 | the essential protein engineering summit PEGSummit.com biologics partnering forum Emerging Antibody & Protein Engineering Particularly efficient for promoting discussion of partnerships, Cambridge Healthtech Insititute’s Biologics Partnering Forum is designed for both the emerging companies with promising technology platforms and innovative approaches, as well as more established companies looking to collaborate as a way to gain access to novel technology and competitive products. Because of the focused and review process for selecting presenting companies, essentially every attendee will have significant shared interests with every other participant. SATURDAY, APRIL 28 been designed to reject molecules with less desirable drug characteristics as early as possible in the discovery process, and to deliver lead molecules 8:00am Registration and Morning Coffee for pre-clinical characterization which can be viewed as ‘development 9:00 Chairperson’s Opening Remarks ready’ early in discovery with a resulting enhanced likelihood of eventual biological and physiological success. In addition to partnering its 9:10 Panel Discussion: New Platforms for Antibody Discovery technology platform with corporate pharma, 4-Antibody is now applying its Retrocyte Display® technology in an R&D collaboration with the NOVEL TRANSGENIC DEVELOPMENT PLATFORMS Ludwig Institute for Research & the Memorial Sloan Kettering 9:40 MeMo® - A Transgenic Mouse for the Discovery of Cancer Center in New York to develop therapeutic antibodies directed to Innovative Human Antibody Therapeutics a series of molecular targets with key roles in the suppression of immune Mark Throsby, Ph.D., Chief Scientific Officer, Merus BV (www.merus.nl) responses in cancer patients. MeMo® is a transgenic mouse that produces human antibodies upon 10:40 Diversity Trap: Generating Monospecific Antibodies and immunization and that is engineered for ease of antibody lead selection Bispecific Kappa/Lambda-Bodies by Capturing Natural CDR3 and development. All MeMo® -derived antibodies are encoded by a single light chain V region. Antibodies derived from MeMo® are suitable for Diversity direct insertion into Merus’s proprietary bispecific IgG1 format or more Marie Kosco-Vilbois, Ph.D., Chief Scientific Officer, NovImmune SA (www. complex proprietary combinatorial formats. Merus is developing a pipeline novimmune.com) of innovative human antibody therapeutics based on these technologies in The generation of diverse and functional antibody repertoires is key for the areas of oncology, and infectious disease. any in vitro selection technology for antibody discovery. The Diversity Trap approach that we have developed allows for the retrieval and capture 9:55 Development of a Unique Transgenic Mouse Platform to of CDRH3 or CDRL3 sequences from humans or other species, into Produce Human Single-Domain VH Antibody Fragments human antibody frameworks. This approach enables the generation of Mike Romanos, Ph.D., Chief Executive Officer, Crescendo Biologics Ltd. human antibody repertoires with a high of functionality as well (www.crescendobiologics.com) as the creation of libraries biased against predefined targets. Diversity Crescendo is developing a transgenic mouse platform to generate high- Trap libraries support the development of both classical monospecific affinity human heavy chain antibodies, which readily yieldin vivo matured antibodies as well as NovImmune’s proprietary bispecific kappa/Lambda- single domain VH fragments requiring no humanisation. VH fragments are body, a format undistinguishable from a standard human IgG. Furthermore, the smallest portions of immunoglobulin that retain target specificity and as diversification is focused on the center of the antibody combining potency and, compared to whole antibodies, have properties more akin site, the approach is fully compatible with next generation sequencing to small molecules, making them highly attractive therapeutic agents. A technologies for accelerated discovery and deep mining of potential summary of platform development and timelines will be described, with candidates. outline plans for a pipeline of novel medicines and a limited number of 10:55 Networking Coffee Break strategic partnering relationships. 11:15 Shark Antibodies and NCAMs as Novel Therapeutics 10:10 A New Human Platform based on Katherine Griffiths, Ph.D., Senior Scientist, Biochemistry, AdAlta / LaTrobe Transgenic Rats University (www.adalta.com.au) Roland Buelow, Ph.D., Chief Executive Officer, Open Monoclonal AdAlta’s libraries are two structural homologues: a single Technology, Inc. (www.omtinc.com) immunoglobulin (Ig) variable domain (VNAR) from the shark new Open Monoclonal Technology, Inc. (“OMT”) is a private, California-based receptor (IgNAR) and the Ig1 domain from human neural cell adhesion company, which developed a fully human monoclonal molecule (NCAM). These small scaffolds are excellent alternative antibody (mAb) platform based on transgenic rats. This new technology therapeutic and diagnostic candidates. They have a rigid core which is the result of breakthroughs in the understanding of B-cell development confers high physicochemical and proteolytic stability, and their small and a novel approach to the inactivation of endogenous antibody size (14 kDa) and solubility may benefit tissue penetration and uptake. expression. OMT’s antibody platform has broad freedom to operate and The scaffolds have exposed binding loops which are readily amenable to uses technology protected by a new patent application. modification and can mediate penetration into clefts and active sites, thereby accessing regions of proteins that have been difficult to NOVEL IN VITRO DEVELOPMENT PLATFORMS target by conventional monoclonal antibody approaches. 10:25 Retrocyte Display® - in vitro High-Throughout Antibody 11:30 Beyond the Mouse: HuTARG—the Next Generation Discovery Utilizing Nature’s own Display Platform - the B cell Fully Human Antibody Technology Robert Burns, Ph.D., Chief Executive Officer, 4-Antibody AG (www.4- Paul Kang, Chief Scientific Officer, Innovative Targeting Solutions, Inc. antibody.com) (www.innovativetargeting.com) With many different antibody discovery technologies now available to Innovative Targeting Solutions Inc. has developed a novel technology to corporate pharma, 4-Antibody has differentiated its technology offering generate fully human antibody repertoires in vitro. The HuTARG technology by utilizing a B-cell display approach which combines the fidelity of utilizes a mammalian cell line capable of V(D)J recombination to generate mammalian B-cell expression with the efficiency of anin vitro high- novel antibody repertoires de novo. These repertoires are not subject to in throughput display process to rapidly discover molecules with favorable vivo tolerance (i.e. are preimmune) and offer other technological advantages. performance characteristics as development leads. Retrocyte Display® is a high-throughput in vitro discovery process utilizing cellular expression 11:45 Mammalian Cell Display Coupled with Somatic libraries encoding full length human antibodies in B-lineage cells, thus Hypermutation: A Powerful Approach for Generation of mimicking nature’s own antibody generation process. This approach has Therapeutic Antibodies

PEGSummit.com the essential protein engineering summit | 3 David King, Ph.D., Chief Scientific Officer, AnaptysBio (www.anaptysbio.com) A new scaffold for a bispecific IgG is presented that solves the long-standing Mammalian cell display of full-length IgG has been coupled with somatic problems of producing in high yield and easily purifying to homogeneity, in hypermutation, the natural mechanism of antibody maturation, in a powerful addition to an easily resolved analytical profile. Using protein engineering of in vitro system for selection and optimization of antibodies. Antibodies can be the Fc domain, we have created a format that is generally applicable and have directly selected for functional properties, as well as high expression levels demonstrated expression, superior purification, andin vitro and in vivo activity in mammalian cells and good biophysical properties, ensuring that antibodies for a variety of molecules. Further, we can freely combine this format with selected are suitable for development as therapeutics. The technology will be the wide array of Fc variants for extending half-life, increasing cytotoxicity and illustrated with a series of examples including the isolation of potentially best- immune modulation. in-class antibodies to IL-17 and NGF. HUMAN DERIVED ANTIBODY APPROACHES 12:00pm Combining Strength of Phage and Yeast Display for Discovering and Optimizing of Drugable IgG and Bispecific 3:10 True Human™ Antibodies: A Path to Safe and Effective Antibody Constructs Antibody Therapy Volker Lang, Ph.D., Managing Director, AbCheck s.r.o. (www.abcheck.com) Sushma Shivaswamy, Ph.D., Director of Research & Development, Antibody specifications beyond affinity are addressed by combining the XBiotech (www.xbiotech.com) strength of highly validated phage display libraries with the advanced Efforts to better humanize therapeutic antibodies have been challenging. possibilities of yeast display. Thereby the key features high expression yields Even so called fully human antibodies still use in vitro modifications to and stability of antibody drug candidates are addressed as early as possible improve target affinities.In vitro modifications bypass crucialin vivo selection in the discovery process. The combination is used for the optimization of full processes and likely result in creating an immunogenic footprint for products. length antibodies and novel/bispecific antibody constructs. Here we summarize a novel approach to generating True Human™ antibodies: from discovery of protein sequences from human blood, to cloning, to 12:15 Antibody Selection from Immunoglobulin Gene therapeutic antibody development. Finally, we will briefly present data on the Libraries Expressed in Mammalian Cells safety, tolerability, and efficacy of a True Human™ antibody. Ernest Smith, Ph.D., Senior Vice President of Research and Chief Scientific 3:25 Turning the Repertoire’s Most Potent Antibodies into Officer,Vaccinex, Inc. (www.vaccinex.com) Superior Therapeutics Utilizing a vaccinia virus based library technology we have developed an Kristine Swiderek, Ph.D., CSO & Vice President of Research, Theraclone antibody discovery technology that enables efficient selection of fully Sciences (www.theraclone.com) functional IgG antibodies from highly diverse immunoglobulin gene libraries Theraclone Sciences utilizes a therapeutic antibody rescue platform expressed in mammalian cells. This technology can be used either for de novo technology (I-STAR) to effectively discover and develop fully human antibody selection or for the robust conversion of a non-human antibody into monoclonal antibody therapeutics. The technology enables us to a panel of fully human antibodies with similar or even improved affinity and comprehensively interrogate the entire human B-cell repertoire from sero- functional activity. This technology has a number of advantages, including a positive donor samples, and through the application of high throughput built in selection for full length IgG antibodies that are efficiently expressed in screening technologies to rapidly identify the few rare antibodies that have mammalian cells. This technology has proven to be very effective at enabling evolved in the human immune system to successfully ward off disease in the discovery of therapeutic quality human antibodies. In addition, details of indications of infectious diseases and cancer. The company’s most advanced some of the new, path changing strategies that we are developing in the area lead projects are TCN-032 for treatment of Influenza, currently in Phase of antibody discovery will be discussed. 1, and pre-clinical candidate TCN-202 for treatment of HCMV infections, 12:30 Networking Lunch, Discussion with Company commencement of a Phase 1 clinical trial is anticipated in H1 of 2012. Presenters 3:40 Networking Refreshment Break 1:45 Chairperson’s Remarks ANTIBODY TOOLS 1:55 Panel Discussion: New Antibody Features or Capabilities Wish List 4:00 Lipoparticle Technology as an Innovative Approach for Antibody Discovery against Targets MULTI-SPECIFIC ANTIBODY TECHNOLOGIES Joseph Rucker, Ph.D., Director of R&D, Integral Molecular Inc. 2:25 Next Generation Biologics: Multi-Valent Antibody Integral Molecular has developed a technology, the ‘Lipoparticle’ Therapeutics with Tailored Effector Function and Optimized for deriving valuable antibodies against membrane protein targets. Lipoparticles present high concentrations (10-100 fold greater than cells Serum Half-life or membrane preparations) of properly folded and oriented membrane Ali Tehrani, Ph.D., Chief Executive Officer, Zymeworks (www.zymeworks. proteins on their surface. Membrane proteins of all classes, including com) GPCRs, ion channels, and transporters can be incorporated into Antibody therapeutics are hot, and bi-specific (multi-valent) antibodies are Lipoparticles, used as immunogens to elicit antibody responses, and used the hottest need in that market because they enable the development as a tool for screening resulting hybridomas. For example, we have used of novel drugs based on novel mechanisms of action and biologies. Lipoparticles to derive target-specific, highly-reactive sera against the Currently, there are no established leaders in the field of multi-valent therapeutic target CXCR4 by mouse immunization, and to screen a panel antibody therapeutics. There is a race with a few in the lead, one of which of >900 hybridoma clones. The use of Lipoparticles enabled the discovery is Zymeworks with its Azymetric platform. In Sep of this year Zymeworks of CXCR4-specific, conformation-sensitive monoclonal antibodies (MAbs), press released a collaboration with Merck to develop bi-specific antibody and can be used in antibody discovery against numerous other high-value therapeutics using Zymeworks’ Azymetric platform. membrane protein targets. 2:40 Pre-Clinical Development of Multispecific Antibodies: 4:15 A Rapid and Reliable Approach for Generating Functional The Tribody Approach Antibodies to Cell Membrane Proteins Nico Mertens, Ph.D., Director of Antibody Engineering, Biotecnol, Inc. Davis Farmer, Chairman, Executive, MSM Protein Technologies (www.biotecnol.com) Cell membrane proteins represent a major class of drug targets in man. To Bispecifc antibodies are in the focus of R&D and development. Beyond that date few have been able to raise antibodies that modulate cell function by multi-specific targeting seems to provide synergistic effects. The technology targeting these proteins. We have established methods that have generated for development of Tribodies and examples of the activity of such products multiple functional antibodies to GPCRs and combined these with other will be described. Tribodies allow for easy development of stable, multi- technologies to shorten the discovery and optimization process dramatically. specific reagents for therapeutic development. 4:30 Predicting Antibody Binding Properties by Interrogation 2:55 A Readily Expressed and Purified Bispecific IgG Format of Fully Human Libraries with Deep Sequencing Bassil Dahiyat, Ph.D., Chief Executive Officer, Xencor, Inc. (www.xencor.com) Richard Wagner, Ph.D., Founder and Chief Scientific Officer, X-BODY

4 | the essential protein engineering summit PEGSummit.com BioSciences (www.x-bodybioscience.com) Delenex’ proprietary PENTRA® antibody format has proven its drug-like We employ X-BODY’s Protein Chain Reaction™ method for rapid cell-free characteristics (affinity, manufacturability, safety), and adds the unique generation of hMABs under mammalian folding conditions. Our human combination of a short half-life and excellent tissue penetration. On this VH and VL libraries capture the natural antibody repertoire and can be basis, Delenex will be running three PoM and PoC clinical trials in 2012, screened for binding to targets on living cells. We present data showing that addressing the areas of dermatology, gastro-intestinal disease and acute sequencing of thousands of hits can provide an early read on the function inflammation. and specificity of lead candidates. 10:25 Oral Antibody Therapeutics with Local Activity in the 4:45 Getting Away from Hybridomas: Research Antibodies GI Tract Go Molecular with ACE™ Barbara Fox, Ph.D., Chief Executive Officer, Avaxia Biologics, Inc. (www. James R. Dasch, Ph.D., Chief Scientific Officer and Co-Founder, Abazyme avaxiabiologics.com) LLC (www.abazyme.com) Avaxia is developing orally delivered antibody therapeutics designed to work Getting commercially available monoclonal antibodies to work in specific locally in the GI tract. The antibodies are bovine polyclonal antibodies isolated assays is the bane of many life science researchers. Whole research from the early milk (colostrum) of immunized cows. These antibodies are projects have crumbled for lack of good antibodies. Abazyme has a safe for oral administration and inherently stable to gastric digestion, making new proprietary cloning platform, ACEtm, which enables us to deliver them ideally suited to oral delivery. recombinant antibodies, which can be readily optimized to our client’s TM assays through antibody engineering. We can do this in less time that it 10:40 Development of Probodies -Proteolytically-active typically takes others to produce stable hybridomas.Why should important Antibodies for Therapy immunoassays rely on >30 year old technology? Abazyme is bringing Debanjan Ray, Senior Director, Head of Business Development, CytomX the advances in antibody engineering, formerly used only for therapeutic Therapeutics, Inc. (www.cytomx.com) antibodies, to the research marketplace. CytmoX is developing masked antibodies, called Probodies™, that are proteolytically activated. Probodies™ are inert until they are localized 5:00 Intrabodies: Applications to Drug Development and to the site of disease at which point they are activated into traditional Target Validation antibodies. Since upregulation and disregulation of proteases is a Lee Henderson, Ph.D., Chief Executive Officer, Vybion, Inc. common feature of most diseased tissue and tumors, Probodies™ have (www.vybion.com) several potential applications, including significant increase in therapeutic ProCode is an platform that uniquely selects for functional index versus a given parental antibody, improved biodistribution, and Intrabodies which are also fully capable of performing as traditional development of drugs against targets that are deemed intractable antibodies. This display technology in bacteria has been used against because they are too widely dispersed. CytomX has recently generated multiple targets of which our Huntington’s drug is the most advanced in vivo tumor model data with our platform that demonstrates Probodies program. By adjusting dose and affinity, Intrabodies can provide are being activated site specifically and mimic the activity of parenteral pharmacologically relevant information for signaling networks when antibodies at the site of disease, but are inert in circulation and other coupled to arrays and biochemical readouts. healthy tissue. 5:15 Networking Session, Discussion with Company Presenters 10:55 Networking Coffee Break 6:00 End of Day One 11:15 One Molecule – Six Binding Sites: A New Class of TRAIL-receptor Agonists for the Treatment of Solid Tumors SUNDAY, APRIL 29 Oliver Hill, Ph.D., Vice President, , Apogenix GmbH Apogenix has designed a new class of modular TRAIL-receptor agonists 9:00am Chairperson’s Opening Remarks suitable for biopharmaceutical development. The main feature of these 9:10 Panel Discussion: Clinical Development of Antibodies second generation pro-apoptotic receptor agonists (PARAs) is an Apo2L/ and Antibody-Like Proteins TRAIL mimic combining three Apo2L/TRAIL protomer sub-sequences in one polypeptide chain, termed single-chain-TRAIL-receptor-binding-domain ANTIBODY PRODUCTS IN DEVELOPMENT (scTRAIL-RBD). The scTRAIL-RBD exposes, like its natural counterpart, three binding sites for the interaction with death inducing TRAIL-receptors 9:40 Clinical Development of Tanibirumab and its Next- (TRAIL-R1, TRAIL-R2). By fusing the hinge and the CH2-CH3 segment of Generation Dual Specific Antibodies, DIG-KT and PIG-KM human IgG1 to the C-terminus of the scTRAIL-RBD module, a dimeric Jin-San Yoo, Ph.D., Chief Executive Officer & President, PharmAbcine, Inc. fusion protein comprising six binding sites per molecule (scTRAIL-RBD- (www.pharmabcine.com) Fc) with an overall antibody like shape and volume was generated. The Novel anti-KDR neutralizing fully human IgG with cross-species prototype of this engineering concept, APG350, distinguishes itself crossreactivity, Tanibirumab is in Phase I and will be completed in this from current agonistic anti-TRAIL-R1 or TRAIL-R2 antibodies in clinical fall. DIG-KT is one of the leading pipeline from DIG-Body platform and development by its ability to form “super-clusters” on target cells. In vivo, it neutralize both VEGF-KDR and ANG-Tie2 pathways and performed APG350 and its muteins with reduced or depleted Fc-gamma-Receptor synergistic value like overcome Avastin resistance issue. PIG-KM from binding ability showed similar anti-tumor efficacy in the Colo205 human PIG-Body neutralizes both VEGF-KDR and HGF-cMET pathways and also colon xenograft tumor model. potential value. PROTEIN ENGINEERING-FUSION PROTEINS 9:55 Chemoenzymatic Site-Specific Antibody-Drug Conjugate Generation 11:30 Intracellular Delivery of Fusion Proteins to Muscle David Rabuka, Ph.D., Chief Scientific Officer, Redwood Bioscience, Inc. based on a Cell Penetrating Antibody Fragment (www.redwoodbioscience.com) Dustin Armstrong, Ph.D., Vice President of Research, 4S3 Bioscience We have developed a technology platform that enables the chemical (www.4S3bioscience.com) modification of proteins in a controlled, site-specific manner. Using this 11:45 Bispecific Fynomer-Antibody Fusions technology we are able to generate panels of modified recombinant IgGs Julian Bertschinger, Ph.D., Chief Executive Officer, Covagen (www. that are site-specifically modified and are easy to chemically elaborate covagen.com) with toxic payloads. The resulting homogenous ADCs are loaded with a Covagen is a pioneer in the development and commercialization defined amount of drug placed at defined locations on the proteins. of Fynomers as next generation protein drugs for the treatment of 10:10 Delenex: Changing the Game in Immuno-Inflammation inflammatory diseases and cancer. Fynomers are small binding proteins Titus Kretzschmar, Ph.D., CSO Delenex Therapeutics AG derived from a fully human and have excellent biophysical (www.delenex.com) properties. Fynomers can be used for the construction of multivalent and

PEGSummit.com the essential protein engineering summit | 5 multispecific therapeutic proteins with a novel mode of action. Of particular scaffold. is a small and highly stable human protein whose interest are bispecific Fynomer-antibody fusion proteins, as Fynomers sequence is fully conserved across all mammalian species, simplifying pre- can be genetically fused to antibodies to enhance their potency and clinical development. Examples of engineered to picomolar affinity functionality without compromising their beneficial drug-like properties. and high specificity, fusions with effector molecules or dimeric constructs Fynomer-antibody fusions represent a new generation of bispecific protein and applications will be presented. therapeutics which are based on clinically well validated antibodies. Data obtained from in vitro and in vivo characterization of a bispecific TNF/IL-17A 2:55 A Technology Platform for Rapid Discovery of Oral and inhibitor will be presented. Injectable Therapeutics Dinesh Patel, Ph.D., Chief Executive Officer, Protagonist Therapeutics 12:00pm Site-Specific Crosslinking of Proteins Using Swift (www.protagonist-inc.com) Linkage Multivalent Technology Rich (DRPs) offer better stability & potency compared Allen Krantz, Ph.D., President and Chief Executive Officer, Advanced to conventional peptides. Protagonist’s technology platform integrates Proteome Therapeutics, Inc. (www.advancedproteome.com) computational, phage, and med chem drug discovery tools to discover The trifecta of fusion proteins, antibody drug-conjugates, and polymer well differentiated and superior DRPs against those targets and diseases therapeutics comprise the bulk of the burgeoning protein therapeutics wherein conventional and antibody approaches do not offer market. For each of these therapeutic types it is necessary to connect a satisfactory solution. Examples of application of DRP technology platform two or more entities to achieve viable drugs. Whereas antibody drug- will be provided. conjugates, and polymer therapeutics require chemical methods to forge a bond between entities, the production of fusion proteins by 3:10 Accessing Extracellular and Intracellular Targets with the recombinant methods has become an integral part of the repertoire of Next-Generation of Protein Therapeutics: ™ protein therapeutics. A major limitation in the production of homogeneous Mark Vaeck, Ph.D., Chief Executive Officer, Complix NV (www.complix.be) protein drugs of all types has been the lack of site-specific chemical Complix has demonstrated it can successfully discover Alphabodies™ methods designed to connect two entities at a single site on each of their against a variety of target classes – both extra-cellular and intracellular surfaces. In fact, to date essentially no practical chemical methods have targets. Alphabodies™ can act on therapeutic targets that are difficult been developed for producing protein multimers to rival fusion proteins and or impossible to address with other therapeutic classes (antibodies or expand the range of chemical functionalities beyond peptides. Advanced small chemicals). This is due to their special structure and exceptional Proteome Therapeutics has introduced advanced chemical modification properties. In addition, Complix is presenting a new paradigm in protein techniques to enable the linking of entities to diverse positions along drug discovery: Its break-through ™ discovery engine is based the protein framework with crosslinks of variable chemical functionality. on i) the identification of a key functional epitope on the target structure, ii) Advanced Proteome Therapeutics has developed Swift Linkage Multivalent the design of initial Alphabody™ hits through 3-D computer modeling, iii) Technology (SLMT) to rapidly link proteins, peptides and organic chemical the creation of optimized leads through “dedicated” library selection and pharmacophores to a target protein, site specifically. Using SLMT, protein iv) the iterative process of structure activity relation analysis resulting in the dimers can be prepared within 24 hours, site-specifically, biologically active, final product. Our process eliminates the “black box” of random selection and in good yield. from phage libraries or unpredictable outcome of animal immunizations. 12:15 Networking Lunch, Discussion with Company Presenters 3:25 Networking Refreshment Break 1:30 Chairperson’s Remarks 3:45 Better by Design: Creating Differentiated Protein 1:40 Panel Discussion “Design and Selection of Improved Products by Engineering Protein Therapeutics” Tom Barnes, Ph.D., Vice President, Discovery, Eleven Biotherapeutics, Inc. (www.elevenbio.com) PROTEIN DIVERSITY Eleven Biotherapeutics is a biopharmaceutical company focused on engineering and developing innovative protein-based therapeutics 2:10 Peptide and Protein Engineering Using CIS Display to improve human health and treat disease. By integrating a unique Chris Ullman, Ph.D., Chief Scientific Officer, Isogenica Ltd. (www. molecular-level understanding and structure-based design capabilities, isogenica.com) Eleven Biotherapeutics has built a protein design product engine to create CIS display is a cell-free display technology that is capable of displaying and develop best in class protein-based therapies. Our lead product in very large libraries (>10e13) of polypeptides. The technology uses DNA development, EBI-005, is a chimera of IL-1Ra and IL-1beta which combines rather than RNA and is therefore different to phage, yeast and ribosome the ideal properties of both, for the treatment of dry eye disease. IL-1 display. Through iterative rounds of selection, CIS display has yielded highly blockade has been recently shown to be a promising mechanism in dry eye specific -binding peptides, protein scaffolds and antibody fragments therapy. We will describe the discovery, pre-clinical validation and process to a wide range of targets, such as kinases, growth factors, GPCRs and development of EBI-005, and preview salient aspects of Eleven’s pipeline. proteases. In this presentation, an overview of the technology will be provided including applications and examples. 4:00 Celexion’s Protein Engineering Platforms for the Discovery and Optimization of Therapeutics 2:25 Open Cell-Free Protein Synthesis as a Viable Route Andrew Rakestraw, Ph.D., Head of Technical Operations, Protein for Rapid Design and Manufacturing of Novel Engineered Engineering, Celexion LLC (www.celexionbio.com) Therapeutic Proteins Celexion is a biotechnology company focused on creating next-generation Lesley Stolz, Ph.D., Vice President, Business Development, Sutro protein engineering tools to empower partners to push the boundaries Biopharma, Inc. (www.sutrobio.com) of human therapeutics. Celexion’s team of scientists has developed Sutro has developed a scalable cell–free protein synthesis platform for customizable platforms that enable partners to construct, discover, the efficient production of complex or difficult to express therapeutic optimize and refine next-generation antibody and protein scaffolds (full- proteins, including full length IgGs and ADCs, bispecific antibodies, and length IgG, tandem scFv, bi-specifics, non-antibody scaffolds, therapeutic other complex eukaryotic proteins. The system allows for a 1-2 week proteins, etc.) for applications in de novo discovery, , make test cycle that can produce hundreds of variants rapidly for activity protein expression improvement, and enzyme engineering. The platforms and specificity testing. Because of its scalable nature, it is a rapid route to are comprised of the SECANT® yeast display system for library selections, manufacturing once discovery has been finished. Sutro has a GMP facility a fully-human, naïve, full-length IgG library for de novo discovery of that is capable of producing materials up through Phase I clinical trials. fully human antibodies, novel linker libraries for multi-domain scaffold construction, and tremendous know-how from helping partners achieve 2:40 Affilin: The Ubiquitin-Based Therapeutic Drug Platform human therapeutic goals for a number of diseases. Celexion uses a flexible Ulrich Haupts, Ph.D., Chief Scientific Officer, Affilin Technology, Scil Proteins business model to make these technologies available to our partners GmbH (www scilproteins.com.) through outlicensing and service arrangements. Scil Proteins develops biotherapeutics based on Ubiquitin as a new

6 | the essential protein engineering summit PEGSummit.com hotel & travel information

Conference Hotel: Cambridge Healthtech Institute conference attendee to receive The Boston Park Plaza Hotel & Towers the discounted room rate with the host hotel. Reservations 50 Park Plaza at Arlington Street made after the cut-off date or after the group room block Boston, MA 02116 has been filled (whichever comes first) will be accepted on a T: 617-426-2000 and rate-availability basis. Rooms are limited, so please book early. Discounted Room Rates are Available for this Conference Discounted Room Rate Cut-off Date: March 30, 2012 Travel Information For additional travel information and discounts, visit the hotel and Please visit our conference website to make your reservations travel page of the conference website. online or call the hotel directly to reserve your sleeping accommodations. You will need to identify yourself as a PEGS 2012 Sponsors & exhibitors

(As of March 8, 2012) Abcore Blue Sky BioServices GENEWIZ Inc. OriGene Technologies Schrodinger Abpro Brookhaven Instruments GenScript Corporation Pall Life Sciences SDIX Accelagen Bruker Optics Gyros Inc. Paragon Bioservices Selexis Accelrys Catalent Pharma Integral Molecular PerkinElmer SENSIQ Affinity Cell Signaling Technology IntelliCyt Pfenex SGS Life Science Services Agilent Technologies CEVEC Pharmaceuticals KBiosystems Limited Pharma Diagnostics Siloam Biosciences AllCells Chemical Computing Group Life Technologies Phynexus Soluble Therapeutics Analytical Technologies Group Cisbio LifeSensors PolyPlus Transfection STEMCELL Technologies, Inc. Anaphore CovalX Instruments Lonza Precision Antibody TA Instruments Applied Photophysics Discove Rx Corporation Lucigen Corporation Premas Biotech Tecan Aragen Bioscience DNA 2.0 Malvern Instruments ProteinSimple Teknova BAC BV EMD Millipore Corporation MaxCyte Proteos Inc. Thermo Scientific Biolin Scientific ExSAR Molecular Devices PX Therapeutics Thomson Instrument Co. Bioneer Fluid Imaging Technologies Nanosight Quanta BioDesign U.S. Pharmacopeia BiOptix ForteBio NanoTemper Technologies GmbH Rheosense Inc. Vivalis Bio-Rad Laboratories Fujifilm Diosynth New England Biolabs Sapidyne Instruments X-Body Biosciences BioTek Instruments Genedata Novozymes SAW Instruments

For information on sponsorships and exhibits, please contact: Carol Dinerstein, Director, Business Development | T: 781-972-5471 | E: [email protected] pegs summit at-a-Glance For more information on PEGS programs and short courses, please visit PEGSummit.com

Saturday PHARMA-BIO Biologics Partnering Forum* PARTNERING FORUMS Sunday Focusing on the Right Partners Discovery Expression Analytical Antibodies Monday Phage & Yeast Difficult to Express Characterization of Antibodies for Cancer Display Proteins Biotherapeutics Therapy Tuesday Phage & Yeast Difficult to Express Characterization of Antibodies for Cancer Display Proteins Biotherapeutics Therapy Dinner Short Courses* Wednesday Engineering Optimizing Protein Protein Bispecific Antibodies Expression Aggregation Antibodies Thursday am Engineering Optimizing Protein Protein Bispecific Antibodies Expression Aggregation Antibodies Thursday pm Antibody Purifying Immunogenicity Antibody-Drug Optimization Antibodies Conjugates Dinner Short Courses* Friday Antibody Purifying Immunogenicity Antibody-Drug Optimization Antibodies Conjugates

* Separate Registration Required

PEGSummit.com the essential protein engineering summit | 7 april 28 - 29, 2012 The Boston Park Plaza Biologics Hotel & Towers PHARMA-BIO partnering forum PARTNERING FORUMS Emerging Antibody & Protein Engineering FocusingPrici onn theg Right & R Paegistratiortners n Information Conference Short Courses Tuesday, May 1 Thursday, May 3 Dinner Short Courses Dinner Short Courses PHARMA-BIO SC12 Asia-U.S. Biotech Alliances: Opening Up New SC14 Antibody Conjugate Therapeutics Challenges PARTNERING Opportunities for Pre-Clinical Development of Biologics SC15 Advances in Immunogenicity Assays FORUMS SC13 Light Scattering – Theory, Do’s & Don’ts, and Data Focusing on the Right Partners Interpretation Biologics Partnering Forum Choose 1 Short Course Choose 2 Short Courses Non-Attendee Rate...... $1395 Commercial...... $695 Commercial...... $995 Conference Attendee Rate...... $1045 Academic, Gov’t, Hospital Affiliated....$345 Academic, Gov’t, Hospital Affiliated....$595

Conference pricing CONFERENCE DISCOUNTS SPECIAL OFFER: Add the Partnering Forum to your conference registration and save $350 • Poster Discount ($50 Off) off the forum rate! • Hotel Discount ($100 Off) See page 2

Academic, Gov’t, • Alumni Discount (20% Off) Commercial Rate Hospital Affiliated For Poster Information, visit PEGSummit.com Deadline to submit is March 23, 2012. Advance Rate Regular Rate until March 23, 2012 after March 23, 2012 Alumni Discounts: Cambridge Healthtech Institute (CHI) Premium: appreciates your past participation at PEGS. As a result of the great Best Value $2,795 $2,945 loyalty you have shown us, we are pleased to extend to you the (Includes access to conference options I, II, III) $1,455 $1,595 exclusive opportunity to save an additional 20% off the registration rate. Please note: Our records must indicate you were an attendee of Standard: $2,375 $2,575 the PEGS Summit in the past in order to qualify. (Includes access to either conference options I & II, OR II & III) $1,195 $1,295 Register 3 ­- 4th is FREE: Individuals must register for the same conference or conference combination and submit completed Basic: $1,525 $1,695 registration form together for discount to apply. (Includes access to either conference option I, II, OR III) $775 $845 Group Discounts Available! Special rates are available for multiple attendees from the same organization. For more information on group discounts contact Conference Options David Cunningham at +1-781-972-5472 Based on your pricing package, please select the conferences you will most likely attend. NOTE: Choose one program per option Additional Registration Details I. April 30 - May 1 II. May 2 - 3 (am) III. May 3 - 4 (pm) Conference registration includes all conference sessions, posters and exhibits, food functions, and access to the conference proceedings link. • Phage & Yeast Display • Engineering Antibodies • Antibody Optimization To view our handicap information and our substitutions/cancellations policy, go to www.healthtech.com/regdetails. Video and/or audio • Difficult to Express Proteins • Optimizing Protein Expression • Purifying Antibodies recording of any kind is prohibited onsite at all CHI events.

• Characterization of Biotherapeutics • Protein Aggregation & Stability • Immunogenicity To purchase conference proceedings visit PEGSummit .com. • Antibodies for Cancer Therapy • Bispecific Antibodies • Antibody-Drug Conjugates

How to Register: PEGSummit.com Please use keycode PGP F when registering T: 781.972.5400 or Toll-free in the U.S. 888.999.6288 | [email protected]