3月31日
7:30 am Registration and Morning Coffee
8:50 Chairperson's Opening Remarks
Dimiter Dimitrov, Ph.D., Senior Investigator, NCI, National Institutes of Health
抗体结合、特异性、类药特性的强化
9:00 Antibody Engineering for Better in vivo Efficacy
Weidong Jiang, Ph.D., CSO, Henlius Biopharmaceuticals, Inc.
Antibody engineering is a great tool for improving antibody functions in vivo. We have routinely engineered therapeutic antibodies for better in vivo efficacies via affinity maturation, specifically by improving on-rate of the antibody binding affinities. One particular case will be reported here for better functions in vivo as well as other functions such as immunogenicity improvement.
9:30 In vitro and in vivo Study of pH-Dependent Antigen Binding Antibody with Increased FcgammaRIIB Binding
Yuji Hori, Ph.D., Research Scientist, Chugai Pharmaceutical, Japan
Sweeping antibody with enhanced FcR mediated cellular uptake of antibody-antigen complex and pH-dependent endosomal antigen dissociation enables antigen elimination from plasma, providing enhanced efficacy and novel mode of action for antibody therapeutics. This talk will present an in vivo profile of sweeping antibody and its in vitro confocal microscopic study to address the intracellular trafficking of the soluble antigen.
10:00 Design and Develop Next-Generation Bispecific Antibodies with Good Drug Like Properties (DLP)
Jinming Gu, Ph.D., Senior Scientist, Global Biologics, Abbvie, Inc.
Bispecific antibodies have emerged as the next generation of antibody-based therapeutics. So far, there have been more than 50 different bispecific antibody platforms published in the literature. However, it continues to be a major challenge to identify bispecific antibodies with good drug like properties which functions preclinically. This presentation will discuss different approaches we are utilizing to design and develop bispecific antibodies with good drug like properties.
10:30 Coffee Break
新蛋白质与替代支架
11:00 Anticalins: Versatile Binding Proteins based on a Flexible Natural Scaffold
Arne Skerra, Ph.D., Professor, Technische Universität München; Founder, Pieris AG, Germany
Anticalins are derived from human lipocalins, whose four structurally hypervariable loops form a binding site that can be tailored against medically relevant targets. However, anticalins are much smaller and comprise a single polypeptide chain, offering facile production in microbial hosts and flexible formatting: multiple specificities, attachment of payloads and extended plasma half-life via PEGylation or PASylation. Two anticalins have reached clinical stage for therapeutic applications.
11:30 ADAPT - A Novel Scaffold Protein for Radionuclide Molecular Imaging
Johan Nilvebrant, Ph.D., Postdoctoral Researcher, The Donnelly Centre, Center for Cellular and Biomolecular Research, University of Toronto, Canada
ADAPTs (ABD-derived affinity proteins) are a novel class of scaffold-based affinity proteins, which are derived from the albumin-binding domain (ABD) of streptococcal protein G. They have been generated in a bispecific format to target various antigens. These radiolabeled ADAPTs were recently used to provide high contrast PET-images of HER2 positive tumor xenografts shortly after injection and show promise as a new class of imaging agents.
12:00 pm Sponsored Presentation (Opportunity Available)
12:30 Networking Luncheon
1:45 Chairperson's Remarks
Dimiter Dimitrov, Ph.D., Senior Investigator, NCI, National Institutes of Health
新蛋白质与替代支架（续）
1:50 Exceptionally Potent and Broad Inhibitors of HIV-1 based on Antibody Domains and One Domain Soluble CD4 Multivalent Fusion Proteins
Dimiter Dimitrov, Ph.D., Senior Investigator, NCI, National Institutes of Health
We generated bispecific multivalent fusion proteins of an engineered cavity-altered single-domain CD4 with another potent HIV-1 inhibitor - an antibody domain targeting the coreceptor-binding site on gp120. The fusion proteins neutralized all HIV-1 isolates tested with potency about 10-, 50-, and 200-fold higher than that of VRC01, T20, and sCD4-Fc fusion protein CD4-Ig, respectively. These fusion proteins could be potentially useful for HIV-1 therapy including eradication of the virus.
2:20 Cross-Neutralizing Single-Domain Antibodies to Pandemic Influenza
Simon E. Hufton, Ph.D., Principal Scientist, Biotherapeutics, National Institute for Biological Standards and Control (NIBSC)
The response to the 2009 A(H1N1) influenza pandemic has highlighted the need for additional strategies for intervention which preclude the prior availability of the influenza strain. We have isolated single domain antibodies with broad neutralisation activity from immunised alpaca's and used yeast display technology to investigate antibody/antigen interactions to assist in the understanding of their mechanism of action. These single domain antibodies are attractive candidates for diagnostics and immunotherapy of pandemic influenza.
2:50 Meditopes: Development of Noncovalent Peptide-Fab Interaction to Rapidly and Specifically Add Functionality to mAbs
John C. Williams, Ph.D., Associate Professor, Molecular Medicine, Beckman Research Institute at City of Hope
MAbs require chemical conjugation and/or extensive re-engineering to deliver toxins, imaging agents and other functionalities to diseased tissues. Herein, we present the discovery of a novel cyclic peptide (aka a meditope) that binds to the cavity of cetuximab Fab. While this binding site is unique to cetuximab, it can be grafted on to mAbs. Studies will be presented highlighting the rapid and efficient functionalization of mAbs.
3:20 Sponsored Presentation (Opportunity Available)
3:50 Refreshment Break
4:35 Keynote Introductions
Weidong Jiang, Ph.D., CSO, Henlius Biopharmaceuticals, Inc.
4:40 Antibody Development Strategies in Today's China
Chengbin WuChengbin Wu, Ph.D., President, R&D and CSO, Shanghai C.P. Guojian Pharamceutical Co. Ltd., PR China
In the past 10 years, commercial manufacturing of antibodies at GMP standard has become possible in China, leading to successful commercialization of several antibody-based therapeutics, with many more in various stages of development. This talk will provide a brief overview of antibody development in China, with a case study discussing key aspects of developing an anti-Her2 antibody that has completed Phase III clinical trials in China.
5:10 Designing and Engineering Novel Bispecific/Bifunctional Antibodies and Fusion Proteins for Enhanced Antitumor Activity
Zhenping ZhuZhenping Zhu, Ph.D., Executive Vice President, Global Biopharmaceuticals, Kadmon Corporation
Major obstacles in the successful development of BsAb (bispecific antibodies) have been the difficulties of designing and constructing a druggable molecule and producing sufficient materials for development and commercialization. The technological challenge is to construct a recombinant molecule with good pharmaceutical properties. Developing highly effective BsAb and bifunctional proteins will require clear elucidation and understanding of the molecular details in the aberrant signaling pathways that lead to various diseases to guide the selection of the target pairs for co-targeting.
4月1日
全体专题研讨会
2:00 pm Chairperson's Opening Remarks
Robb KahnRobb Kahn, M.D., Senior Safety Science Leader, Global Pediatric Oncology Drug Development, Genentech, a member of the Roche Group
2:05 ADCs: Is It Time to Rethink Some Preconceptions?
Jaume Pons, Ph.D., Senior Vice President and CSO, Rinat-PfizerJaume Pons
In this presentation, we will discuss how site-specific conjugation technologies have allowed a deeper understanding of ADC properties.
2:35 Whose Problem is Post-Translational Modifications? Discovery, Cell Culture, Chromatography or Formulation?
Chandrashekar Ganesa, Ph.D., Senior Director, Analytical Development, Global Biotherapeutics, Sanofi
Recombinant protein post-translational modifications (PTMs) are important to monitor and control during the manufacture of biologics. However, the diversity, identification and understanding the relevance of PTMs during the product development cycle can be challenging. This presentation will examine current analytical technologies and discuss how to effectively use them in characterizing the different types of PTMs. It will also discuss various strategies to manage PTMs during various stages of therapeutic protein development.
3:05 Refreshment Break in the Exhibit Hall with Poster Viewing
3:45 Chairperson's Opening Remarks
Robb Kahn, M.D., Senior Safety Science Leader, Global Pediatric Oncology Drug Development, Genentech, a member of the Roche Group
前临床开发阶段以及临床开发阶段的ADC
Featured Presentation
3:50 Current Clinical Experience with Antibody-Drug Conjugates: A View through the Therapeutic Window
Robb Kahn, M.D., Senior Safety Science Leader, Global Pediatric Oncology Drug Development, Genentech, a member of the Roche Group
Numerous antibody-drug conjugates (ADCs) are in clinical development and several have entered the therapeutic market. The concept of an ADC is to improve the "therapeutic window" of cancer chemotherapy. This presentation will examine the therapeutic windows for representative ADCs in clinical development, allowing us to peer into the therapeutic window of specific ADCs through a discussion of their risk-benefit profiles.
4:20 Sponsored Presentation (Opportunity Available)
4:50 Superior Anti-Tumor Activity Compared to T-DM1 in Preclinical Studies of Targeted Therapies for Her2-positive Cancers by a Novel Her2-ADC
Sheldon Cao, Ph.D., CEO, Zova Biotherapeutics, Inc.
ZV02-1016 is a Her2-targeting ADC based on newly developed K-LockTM technology. Anti-Her2 Ab was conjugated with highly cytotoxic auristatin analogue through a non-cleavable linker to form ZV02-1016. ZV02-1016 is shown to be more potent than T-DM1 in vitro in Her2 expressing cancer cell lines and in vivo in Her2-positive cancer cell line xenografts. ZV02-1016 is currently under further evaluation as a candidate for clinical treatment of Her2-positive cancers in future.
5:20 Application of Translational PKPD in ADC Development
Kedan Lin, Ph.D., Senior Scientist, Therapeutic Area Lead for Oncology Large Molecules, Pharmacokinetics & Pharmacodynamics, Genentech, Inc.
5:50 Close of Day
4月2日
8:30 am Morning Coffee
8:50 Chairperson's Opening Remarks
Thomas Pillow, Ph.D., Scientist, Discovery Chemistry, Genentech, Inc.
9:00 ADCs based on RNA Polymerase II Inhibiting Toxins
Andreas Pahl, Ph.D., CSO, Heidelberg Pharma GmbH
Payloads of today's ADCs are exclusively based on compounds acting on microtubules or DNA and seem to suffer from various limitations. New generations of payloads enter the field including Heidelberg Pharma's amanitin, a highly effective inhibitor of the eukaryotic RNA Polymerase II. Due to its unique mode of action and its hydrophilic properties, this toxin differs from well-known payloads. This presentation will summarize the current status of this new toxin.
9:30 Cancer Stem Cell Targeting with Antibody-Drug Conjugate Payloads and Linker Technologies
Riley Ennis, MSc, Thiel Fellow, Cell and Molecular Biology, Dartmouth College
A challenge with current antibody-drug conjugates (ADCs) is to improve patient outcomes by circumventing drug resistance, disease recurrence, and cancer stem cells. We explore a novel cytotoxic payload, Azonafides, that can be integrated into ADC platforms. This cytotoxin is more stable in circulation, has unique mechanisms of action, and is derived from natural products. Azonafides create an exciting clinical opportunity to improve the therapeutic window, efficacy, and safety of ADCs.
10:00 New Linker Chemistries for Expanding the Utility of ADCs
Thomas Pillow, Ph.D., Scientist, Discovery Chemistry, Genentech, Inc.
This presentation will describe the use of potent anthracycline and PBD payloads for second generation HER2-targeted ADCs, and how different linkers to these payloads can be used to tune the therapeutic activity. A new linker that takes advantage of the site-specificity of THIOMABTM technology will be described. Additionally, the presentation will describe the application of ADCs to non-oncology indications.
10:30 Coffee Break in the Exhibit Hall with Poster Viewing
11:10 Engineering Homogeneous ADCs with Single or Combination Warheads
Aaron Sato, Ph.D., Vice President, Research, Sutro Biopharma, Inc.
Using Xpress CF+, hundreds of non-natural amino acid antibody variants are made within a day. Using fast, quantitative conjugation chemistries, antibodies are conjugated within hours with low molar excess of linker warhead. The best sites are selected based on expression, cell binding, conjugation efficiency (DAR), and cell killing. In vivo efficacy, PK/PD, and stability studies further winnow to our best ADC candidates. Multiple ADC examples will be provided.
11:40 Bidentate Linkers for Site-Specific Conjugation and Improvement of Homogeneity and Other Druggabilities in ADC
Bruce Nianhe Han, Ph.D., CSO, Research & Development, NewBio Therapeutics, PR China
We have discovered new linkers, bis(maleimde)derivatives which can conjugate small molecule toxins to antibodies in site-specific manner. With this technology, no antibody engineering is required and we only need to use the interchain disulfide bonds of IgG to perform conjugation. The resulting final products have high percentage of ADC with defined antibody-drug ratios. These homogeneous ADCs have also shown improved in vitro and in vivo stability, and other related druggabilities.
12:10 pm Sponsored Presentation (Opportunity Available.
12:40 Networking Luncheon in the Exhibit Hall with Poster Viewing
2:00 Chairperson's Remarks
Thomas Pillow, Ph.D., Scientist, Discovery Chemistry, Genentech, Inc.
2:05 Site-Specific Conjugations for Well-Defined and Stable ADCs
Changshou Gao, Ph.D., Fellow, R&D, Department of Antibody Discovery & Protein Engineering, MedImmune, LLC.
Significant effort has been devoted recently to developing site-specific conjugations for producing homogenous ADCs with well-defined drug to antibody ratios. This presentation will discuss our approaches to generate ADCs with different conjugation chemistries that allow precise control of conjugation site and stoichiometry. Upon conjugation to a drug, the site-specific ADCs showed enhanced stability, increased in vivo anti-tumor efficacy, and decreased off-target toxicity.
2:35 Overcoming Challenges and Enhancing Production of Antibody for Site-Specific Antibody-Drug Conjugates
Marie Zhu, Ph.D., Director, Process Sciences, Agensys, Inc./Astellas, Inc.
ADCs have been emerging as a new class of anticancer therapeutics, in which monoclonal antibodies are designed to deliver a cytotoxic drug selectively to antigen expressing cells. The site-specific ADC technology we are using results in ADCs with a homogenous drug-antibody ratio. In this study, we investigate how the cell line development process impacts on antibody expression, and how feed media components and cell culture processes affect cell growth and antibody production.
3:05 Sponsored Presentation (Opportunity Available)
3:35 Refreshment Break
Characterizing ADCs for Better Developability
4:00 Chairperson's Remarks
Darshana Jani, Ph.D., Senior Manager, Clinical Assay Group, Global Innovation Pharma, Pfizer, Inc.
4:05 Analytical Strategies and Characterization of Antibody-Drug Conjugates
Gayathri Ratnaswamy, Ph.D., Director, Analytical & Formulation, Agensys, Inc.
This presentation will focus on the challenges of analytical method development and characterization for ADCs in comparison with that of mAbs using case studies. Strategies for the analytical development for early stage versus late stage will be presented.
4:35 Bioanalytical Support for the Clinical Development of Antibody-Drug Conjugate Program
Darshana Jani, Ph.D., Senior Manager, Clinical Assay Group, Global Innovation Pharma, Pfizer, Inc.
Antibody-Drug Conjugates (ADC) are a novel class of biotherapeutics, combining the targeted delivery capability of a monoclonal antibody with the potent cytotoxic activity of a small molecule. Due to the complex and heterogeneous nature of ADCs, a more robust bioanalytical testing strategy is required to assess the ADC pharmacokinetics (PK) and immunogenicity (anti-drug antibody (ADA) and neutralizing ADA). Challenges and solutions to ADC bioanalysis will be discussed.
5:05 ADCs: Biophysical Characteristics and Impact on Product and Process
Satish K. Singh, Ph.D., Research Fellow, Biotherapeutics Pharmaceutical Sciences, Pfizer, Inc.
The biophysical characteristics of ADCs are strongly impacted by the chemistry and associated linker-payload. A strong understanding of these characteristics is therefore important for robust product and process development. This talk will cover some examples illustrating these aspects for ADCs.
5:35 Close of Conference