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Attachement B Summary
Summary - Paediatric Strategy Forum Medicinal Product Development for Acute Myeloid Leukaemia in Children and Adolescents 24-6-19 Paediatric Strategy Forum for Medicinal Product Development for Acute Myeloid Leukaemia in Children and Adolescents ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration 11-12 April 2019 Summary Context: The fourth multi-stakeholder Paediatric Strategy Forum, organised by ACCELERATE in collaboration with the European Medicines Agency (EMA) with participation of the Food and Drug Administration (FDA) was held at Erasmus University, Rotterdam and focused on acute myeloid leukaemia (AML) in children and adolescents. Paediatric Strategy Forums are multi-stakeholder (clinicians, academics, patient advocates, pharmaceutical companies and regulators) scientific meetings on specific topics regarding paediatric oncology. The Forums aim to share information and advance learning, which may inform subsequent strategic and regulatory decisions on the development of medicines for children with cancer. The goal of this meeting was to facilitate development of innovative medicines for the treatment of children and adolescents with AML, and ultimately, by extension, introduce these medicines into the standard-of-care for children. The 5-year overall survival (OS) for paediatric AML currently is approximately 75%; however, the standard of care for frontline therapy for many decades has been daunorubicin and cytarabine. Furthermore, cardiotoxicity, due to anthracyclines, is an important long-term sequelae in a substantial proportion of survivors. AML is more frequent under the age of 3 years and its incidence initially declines and subsequently increases throughout young adulthood and is most frequent in the elderly. The occurrence of specific genetic alterations differs in AML in children compared to adults and the elderly. -
Predictive QSAR Tools to Aid in Early Process Development of Monoclonal Antibodies
Predictive QSAR tools to aid in early process development of monoclonal antibodies John Micael Andreas Karlberg Published work submitted to Newcastle University for the degree of Doctor of Philosophy in the School of Engineering November 2019 Abstract Monoclonal antibodies (mAbs) have become one of the fastest growing markets for diagnostic and therapeutic treatments over the last 30 years with a global sales revenue around $89 billion reported in 2017. A popular framework widely used in pharmaceutical industries for designing manufacturing processes for mAbs is Quality by Design (QbD) due to providing a structured and systematic approach in investigation and screening process parameters that might influence the product quality. However, due to the large number of product quality attributes (CQAs) and process parameters that exist in an mAb process platform, extensive investigation is needed to characterise their impact on the product quality which makes the process development costly and time consuming. There is thus an urgent need for methods and tools that can be used for early risk-based selection of critical product properties and process factors to reduce the number of potential factors that have to be investigated, thereby aiding in speeding up the process development and reduce costs. In this study, a framework for predictive model development based on Quantitative Structure- Activity Relationship (QSAR) modelling was developed to link structural features and properties of mAbs to Hydrophobic Interaction Chromatography (HIC) retention times and expressed mAb yield from HEK cells. Model development was based on a structured approach for incremental model refinement and evaluation that aided in increasing model performance until becoming acceptable in accordance to the OECD guidelines for QSAR models. -
Comparative Safety and Efficacy of Anti-PD-1 Monotherapy, Chemotherapy
Lv et al. Journal for ImmunoTherapy of Cancer (2019) 7:159 https://doi.org/10.1186/s40425-019-0636-7 COMMENTARY Open Access Comparative safety and efficacy of anti-PD- 1 monotherapy, chemotherapy alone, and their combination therapy in advanced nasopharyngeal carcinoma: findings from recent advances in landmark trials Jia-Wei Lv1†, Jun-Yan Li1†, Lin-Na Luo2†, Zi-Xian Wang2* and Yu-Pei Chen1* Abstract Recent phase 1–2 trials reported manageable safety profiles and promising antitumor activities of anti-PD-1 drugs (pembrolizumab, nivolumab, camrelizumab and JS001) with/without chemotherapy in recurrent/metastatic nasopharyngeal carcinoma (RM-NPC), however head-to-head comparison among these regimens is lacking. We aimed to comprehensively compare the efficacy and safety of different anti-PD-1 drugs, standard chemotherapy, and their combination therapy in RM-NPC. Adverse event (AE) and objective response rate (ORR) were assessed. The pooled incidence rates of grade 1–5/3–5 AEs were 74.1%/29.6, 54.2%/17.4, 92.3%/24.5, 96.8%/16.1, 91.2%/42.8, and 100%/87.9% for pembrolizumab, nivolumab, JS001, camrelizumab, chemotherapy and camrelizumab+chemotherapy, respectively, which suggested that nivolumab and pembrolizumab exhibited the optimal safety regarding grade 1–5 AEs whereas camrelizumab and nivolumab regarding grade 3–5 AEs. As second- or later-line therapy, ORR was higher with camrelizumab (34.1%), followed by pembrolizumab (26.3%), JS001 (23.3%), and nivolumab (19.0%); whereas ORR with first-line nivolumab reached 40%. Additionally, first-line camrelizumab+chemotherapy achieved a dramatically higher ORR than that with chemotherapy alone (90.9% vs. -
2015 Post-ASH Report
Datamonitor Healthcare Trialtrove Biomedtracker Pharma intelligence | Pharma intelligence | Pharma intelligence | 2015 Post-ASH Report RACHEL MEIGHAN-MANTHA Principal Analyst, Citeline JOSEPH HEDDEN Senior Analyst, Datamonitor Healthcare Summary Profiled themes at the 57th Annual Meeting and Exposition of the American Society of Hematology (ASH), held December 5-8, 2015, in Orlando, Florida, included Genomic Profiling and Chemical Biology, Genome Editing and Gene Therapy, Epigenetic Mechanisms, Immunologic Treatments, Stem Cell Biology and Regenerative Medicine and Preventing Venous Thromboembolic Disease. This report will mainly focus on the theme of Immunologic Treatments because of the importance and popularity of immunotherapies for many different hematological cancers. Also covered in this report are the results from pivotal trials presented at ASH, as well as highlights from other drugs/therapies of interest. In addition, we felt it was important to cover first-in-human trials since (hopefully) some of these drugs/therapies will be in pivotal trials in a few years. At the end of the report, we’ve included a section showcasing drugs that had top- line results presented at ASH, followed by a list of other data presentations supplied by BioMedTracker (BMT). Accompanying links to BioMedTracker events along with changes to the drugs’ likelihood of approval (LOA) are also provided throughout the report. Finally, additional supplemental material related to ASH is listed in the Appendix. 2 Datamonitor Healthcare Trialtrove Biomedtracker -
Tanibirumab (CUI C3490677) Add to Cart
5/17/2018 NCI Metathesaurus Contains Exact Match Begins With Name Code Property Relationship Source ALL Advanced Search NCIm Version: 201706 Version 2.8 (using LexEVS 6.5) Home | NCIt Hierarchy | Sources | Help Suggest changes to this concept Tanibirumab (CUI C3490677) Add to Cart Table of Contents Terms & Properties Synonym Details Relationships By Source Terms & Properties Concept Unique Identifier (CUI): C3490677 NCI Thesaurus Code: C102877 (see NCI Thesaurus info) Semantic Type: Immunologic Factor Semantic Type: Amino Acid, Peptide, or Protein Semantic Type: Pharmacologic Substance NCIt Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor tyrosine kinase expressed by endothelial cells, while VEGF is overexpressed in many tumors and is correlated to tumor progression. PDQ Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor -
Engineered Technologies and Bioanalysis of Multispecific Antibody Formats
Journal of Applied Bioanalysis openaccess http://dx.doi.org/10.17145/jab.20.005 REVIEW Engineered Technologies and Bioanalysis of multispecific Antibody Formats Marta Amaral, Soraya Hölper, Christian Lange, Jennifer Jung, Hanno Sjuts, Sandra Weil, Melanie Fischer, Katarina Rado�evi�, Ercole Rao* Sanofi R&D, Biologics Research. *Correspondence: Sanofi-Aventis Deutschland GmbH, R&D, Biologics Research, Industriepark Höchst, H812, 65926 Frankfurt am Main, Germany. Phone: +49 6930515147. Email: [email protected] Citation: Amaral M, Hölper S, Lange C, Jung J, Sjuts H, Weil S, Fischer M, Rado�evic K, Rao E. Engineered Technologies and Bioanalysis of multispecific ABSTRACT antibody formats. J Appl Bioanal 6(1), The idea of designing multispecific antibodies capable of simultaneously 26-51 (2020). engaging two or more epitopes on the same or different antigens was developed more than 50 years ago. However, the molecular complexity of such Editor: molecules may pose significant challenges for their development and clinical Dr. Lin-zhi Chen, Boehringer use. Particularly challenging is to obtain the correctly assembled combination of Ingelheim Pharmaceuticals Inc., different polypeptide chains, which places significant demand on downstream Ridgefield, CT 06877, USA. process development, analytical characterization and control strategy. Here, we review the progress made in protein engineering to force the correct assembly of Received: July 29, 2019. different heavy and light chains, as well as upstream and downstream processes Revised: September 13, 2019. currently applied to control generation of unwanted byproduct species. We Accepted: September 16, 2019. cover in-depth the analytical methods available to characterize such complex molecules, focusing on mispairing analysis and functional characterization. -
2017 Immuno-Oncology Medicines in Development
2017 Immuno-Oncology Medicines in Development Adoptive Cell Therapies Drug Name Organization Indication Development Phase ACTR087 + rituximab Unum Therapeutics B-cell lymphoma Phase I (antibody-coupled T-cell receptor Cambridge, MA www.unumrx.com immunotherapy + rituximab) AFP TCR Adaptimmune liver Phase I (T-cell receptor cell therapy) Philadelphia, PA www.adaptimmune.com anti-BCMA CAR-T cell therapy Juno Therapeutics multiple myeloma Phase I Seattle, WA www.junotherapeutics.com Memorial Sloan Kettering New York, NY anti-CD19 "armored" CAR-T Juno Therapeutics recurrent/relapsed chronic Phase I cell therapy Seattle, WA lymphocytic leukemia (CLL) www.junotherapeutics.com Memorial Sloan Kettering New York, NY anti-CD19 CAR-T cell therapy Intrexon B-cell malignancies Phase I Germantown, MD www.dna.com ZIOPHARM Oncology www.ziopharm.com Boston, MA anti-CD19 CAR-T cell therapy Kite Pharma hematological malignancies Phase I (second generation) Santa Monica, CA www.kitepharma.com National Cancer Institute Bethesda, MD Medicines in Development: Immuno-Oncology 1 Adoptive Cell Therapies Drug Name Organization Indication Development Phase anti-CEA CAR-T therapy Sorrento Therapeutics liver metastases Phase I San Diego, CA www.sorrentotherapeutics.com TNK Therapeutics San Diego, CA anti-PSMA CAR-T cell therapy TNK Therapeutics cancer Phase I San Diego, CA www.sorrentotherapeutics.com Sorrento Therapeutics San Diego, CA ATA520 Atara Biotherapeutics multiple myeloma, Phase I (WT1-specific T lymphocyte South San Francisco, CA plasma cell leukemia www.atarabio.com -
Looking for Therapeutic Antibodies in Next Generation Sequencing Repositories
bioRxiv preprint doi: https://doi.org/10.1101/572958; this version posted March 10, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Title: Looking for Therapeutic Antibodies in Next Generation Sequencing Repositories. Authors: Konrad Krawczyk1*, Matthew Raybould2, Aleksandr Kovaltsuk2, Charlotte M. Deane2 1 NaturalAntibody, Hamburg, Germany 2 Oxford University Department of Statistics, Oxford, UK *Correspondence to [email protected] Abstract: Recently it has become possible to query the great diversity of natural antibody repertoires using Next Generation Sequencing (NGS). These methods are capable of producing millions of sequences in a single experiment. Here we compare Clinical Stage Therapeutic antibodies to the ~1b sequences from 60 independent sequencing studies in the Observed Antibody Space Database. Of the 242 post Phase I antibodies, we find 16 with sequence identity matches of 95% or better for both heavy and light chains. There are also 54 perfect matches to therapeutic CDR-H3 regions in the NGS outputs, suggesting a nontrivial amount of convergence between naturally observed sequences and those developed artificially. This has potential implications for both the discovery of antibody therapeutics and the legal protection of commercial antibodies. Introduction Antibodies are proteins in jawed vertebrates that recognize noxious molecules (antigens) for elimination. An organism expresses millions of diverse antibodies to increase the chances that some of them will be able to bind the foreign antigen, initiating the adaptive immune response. -
Antibodies to Watch in 2021 Hélène Kaplona and Janice M
MABS 2021, VOL. 13, NO. 1, e1860476 (34 pages) https://doi.org/10.1080/19420862.2020.1860476 PERSPECTIVE Antibodies to watch in 2021 Hélène Kaplona and Janice M. Reichert b aInstitut De Recherches Internationales Servier, Translational Medicine Department, Suresnes, France; bThe Antibody Society, Inc., Framingham, MA, USA ABSTRACT ARTICLE HISTORY In this 12th annual installment of the Antibodies to Watch article series, we discuss key events in antibody Received 1 December 2020 therapeutics development that occurred in 2020 and forecast events that might occur in 2021. The Accepted 1 December 2020 coronavirus disease 2019 (COVID-19) pandemic posed an array of challenges and opportunities to the KEYWORDS healthcare system in 2020, and it will continue to do so in 2021. Remarkably, by late November 2020, two Antibody therapeutics; anti-SARS-CoV antibody products, bamlanivimab and the casirivimab and imdevimab cocktail, were cancer; COVID-19; Food and authorized for emergency use by the US Food and Drug Administration (FDA) and the repurposed Drug Administration; antibodies levilimab and itolizumab had been registered for emergency use as treatments for COVID-19 European Medicines Agency; in Russia and India, respectively. Despite the pandemic, 10 antibody therapeutics had been granted the immune-mediated disorders; first approval in the US or EU in 2020, as of November, and 2 more (tanezumab and margetuximab) may Sars-CoV-2 be granted approvals in December 2020.* In addition, prolgolimab and olokizumab had been granted first approvals in Russia and cetuximab saratolacan sodium was first approved in Japan. The number of approvals in 2021 may set a record, as marketing applications for 16 investigational antibody therapeutics are already undergoing regulatory review by either the FDA or the European Medicines Agency. -
W W W .Bio Visio N .Co M
Biosimilar Monoclonal Antibodies Human IgG based monoclonal antibodies (mAbs) are the fastest-growing category of therapeutics for cancer therapy. Several mechanisms of tumor cell killing by antibodies (mAbs) can be summarized as: direct action through receptor blockade or induction of apoptosis; immune-mediated cell killing by complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) or regulation of T cell function. Several monoclonal antibodies have received FDA approval for the treatment of a variety of solid tumors and hematological malignancies. BioVision is pleased to offer research grade biosimilars in human IgG format for your research needs. Our monoclonal antibodies are manufactured using recombinant technology with variable regions from the therapeutic antibody to achieve similar safety and efficacy. These antibodies can be used as controls for preclinical lead identification and potency assays for the development of novel therapeutics. Antibody Name Cat. No. Trade Name Isotype Size Anti-alpha 5 beta 1 Integrin (Volociximab), Human IgG4 Ab A1092 - IgG4 200 µg Anti-Beta-galactosidase, Human IgG1 Ab A1104 - IgG1 200 µg Anti-C5 (Eculizumab), Humanized Ab A2138 - IgG2/4 100 μg Anti-Carcinoembryonic antigen (Arcitumomab), Human IgG1 Ab A1096 - IgG1 200 µg Anti-CCR4 (Mogamulizumab), Human IgG1, kappa Ab A2005 - IgG1 200 μg Anti-CD11a (Efalizumab), Human IgG1 Ab A1089 Raptiva IgG1 200 µg Anti-CD20 (Rituximab), Chimeric Ab A1049 Mabthera IgG1 100 µg Anti-CD22 (Epratuzumab), Human IgG1 Ab A1445 LymphoCide IgG1 200 µg Anti-CD3 epsilon (Muromonab), Mouse IgG2a, kappa Ab A2008 - IgG2a 200 μg Anti-CD33 (Gemtuzumab), Human IgG4 Ab A1443 Mylotarg IgG4 200 µg Anti-CD38 (Daratumumab), Human IgG1 Ab A2151 Darzalex IgG1 100 μg www.biovision.com 155 S. -
Flotetuzumab: CD123 × CD3 DART Molecule
® Breakthrough Biologics, Life-changing Medicines Corporate Update January 6, 2019 Legal Notices The information in this slide deck is current as of January 6, 2019, unless otherwise noted. The information in this slide deck is qualified in its entirety by reference to MacroGenics’ Annual, Quarterly and Current Reports filed with the SEC. MacroGenics undertakes no obligation to update any of the information herein. Cautionary Note on Forward-Looking Statements Any statements in these materials about future expectations, plans and prospects for MacroGenics (“Company”), including statements about the Company’s strategy, future operations, clinical development of the Company’s therapeutic candidates, milestone or opt-in payments from the Company’s collaborators, the Company’s anticipated milestones and future expectations and plans and prospects for the Company and other statements containing the words “subject to”, "believe", “anticipate”, “plan”, “expect”, “intend”, “estimate”, “project”, “may”, “will”, “should”, “would”, “could”, “can”, the negatives thereof, variations thereon and similar expressions, or by discussions of strategy constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation and enrollment of future clinical trials, expectations of expanding ongoing clinical trials, availability and timing of data from ongoing clinical trials, expectations for regulatory approvals, other matters that could affect the availability or commercial potential of the Company's product candidates and other risks described in the Company’s filings with the Securities and Exchange Commission. -
Immune Checkpoint Blockade Therapies for HCC: Current Status and Future Implications
Shrestha et al. Hepatoma Res 2019;5:32 Hepatoma Research DOI: 10.20517/2394-5079.2019.24 Review Open Access Immune checkpoint blockade therapies for HCC: current status and future implications Ritu Shrestha1,2, Kim R. Bridle1,2, Darrell H. G. Crawford1,2, Aparna Jayachandran1,2 1The University of Queensland, Faculty of Medicine, Brisbane, Queensland 4120, Australia. 2Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, Queensland 4120, Australia. Correspondence to: Dr. Aparna Jayachandran, The University of Queensland, Faculty of Medicine, Lower Lobby Level, Administration Building, Greenslopes Private Hospital, Greenslopes, Queensland 4120, Australia. E-mail: [email protected] How to cite this article: Shrestha R, Bridle KR, Crawford DHG, Jayachandran A. Immune checkpoint blockade therapies for HCC: current status and future implications. Hepatoma Res 2019;5:32. http://dx.doi.org/10.20517/2394-5079.2019.24 Received: 27 Jun 2019 First Decision: 11 Jul 2019 Revised: 6 Aug 2019 Accepted: 9 Aug 2019 Published: 3 Sep 2019 Science Editors: Jia Fan, Ying-Hong Shi Copy Editor: Jia-Jia Meng Production Editor: Jing Yu Abstract Received: First Decision: Revised: Accepted: Published: Hepatocellular carcinoma (HCC) is the most lethal and common type of liver cancer with limited treatment options Science Editor: Copy Editor: Production Editor: Jing Yu at the advanced stage. The use of immune checkpoint inhibitor (ICI) based immunotherapy is exponentially increasing in the treatment of patients with advanced solid tumors. The expression of immune checkpoints on tumor cells leading to lower activity of T-cells is one of the major mechanisms of immune escape. Checkpoint blockade immunotherapies with antibodies against PD-1, PD-L1 or CTLA-4 are being investigated in clinical trials in HCC patients.