The field of bispecific antibodies is advancing rapidly with results demonstrating their effective use in immunotherapy and oncology, as well as applications that are emerging in ophthalmology, infectious disease, and inflammation. This conference will highlight novel engineering approaches to bispecific antibody constructs and reveal key elements for efficacy and drug-like properties. The latest improvements in manufacturing, purification, stability, enhanced targeting, modulating immune response, expression, characterization, humanization and clearance will be shared.

Scientific Advisory Board

Christian Klein, Ph.D., Discovery Oncology oDTA, Pharma Research and Early Development (pRED), Roche Glycart AG

Robert Mabry, Ph.D., Director, Protein Sciences and Antibody Technology, Jounce Therapeutics

G. Jonah Rainey, Ph.D., Senior Scientist, ADPE, MedImmune, LLC

Eric Smith, Ph.D., Associate Director, Bispecifics, Regeneron Pharmaceuticals

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Recommended Pre-Conference Short Course*

SC2: Bioanalytical Considerations of Multi-Domain Biotherapeutics: Preclinical and Clinical Development

*Separate registration required.


Novel Approaches to Engineering Bispecifics: Enhancing Function

12:35 pm Luncheon in the Exhibit Hall with Poster Viewing

1:40 Chairperson’s Remarks

G. Jonah Rainey, Ph.D., Senior Scientist, ADPE, MedImmune, LLC


Developing Dual-Specific and Bi-specific Antibodies for Cancer Treatment using Next Generation Maleimides (NGMs)

Kerry_ChesterKerry Chester, Ph.D., Professor, Molecular Medicine, University College London Cancer Institute

NGM conjugation technology can facilitate site specific labelling of the solvent accessible disulphide bonds in antibodies and their fragments. The versatility of this chemical approach also enables the construction of antibody fragment homo or hetero dimers and the incorporation of half-life extending technologies. The presentation will explore the potential of NGM technology to develop engineered antibodies for cancer therapy, both by site-specific attachment of warheads and as a flexible platform to create new bispecifics.

2:20 CrossMAb Vh-Vl and Fab

Jorg_RegulaJörg T. Regula, Ph.D., Head, Protein Analytics, Roche Diagnostics GmbH

The CrossMAb technology (Schäfer et al., 2011) can be used to generate a bispecific antibody from two independent parental antibodies by immunoglobulin domain exchange. The three different CrossMAb designs were named according to their exchanged domains: CH1-CL, Vh-Vl and Fab. The CrossMAb CH1-CL was used for the Ang2-VEGF CrossMAb (Kienast et al. 2013). The introduction of additional modifications renders the CrossMAb Vh-Vl and the CrossMAb Fab to suitable alternatives. The CrossMAb technology enables several bispecific molecules with 1+1, 2+1 or 2+2 binding sites.

2:50 Multimerization Strategy to Enhance Potency and Developability of Bispecific Antibodies

Mahiuddin_AhmedMahiuddin Ahmed, Ph.D., Assistant Attending for Immunotherapies, Pediatrics, Memorial Sloan Kettering Cancer Center

Bispecific antibodies have proven to be highly efficient at re-directing T cells for cancer immunotherapy. In order to enhance the anti-tumor potency and developability of tandem scFv bispecific antibodies (tsc-BsAbs or BITEs), we exploited the dimerization domain of the human transcription factor HNF1α to enhance the avidity of a tsc-BsAb to the tumor antigen disialoganglioside GD2 while maintaining functional monovalency to CD3 to limit potential toxicity.

3:20 Engineering Next-Generation Biotherapeutics: Developability & Manufacturability

Maria Wendt, Ph.D., Head , Science, Genedata

Next-gen biotherapeutics, specifically bi- and multi-specifics, alternative scaffolds and ADCs, provide significant advantages over traditional IgG-based molecules. As highly engineered molecules, they pose new design, cloning, expression, purification and analytics challenges. Our workflow platform automates the engineering, production, and testing of large panels of candidate therapeutic molecules. We demonstrate its capability to explore the huge combinatorial space of novel molecule-specific designs as well as its high-throughput capability and built-in tools for assessing developability and manufacturability.

3:50 Refreshment Break

4:20 Bispecific FynomAbs with Tailored Architecture and Novel Modes-of-Action

Simon_BrackSimon Brack, Ph.D., Director, Discovery Research, Covagen (one of the Janssen pharmaceutical companies of Johnson & Johnson)

Covagen develops bispecific FynomAbs by fusing its human Fynomer binding protein to antibodies, resulting in bispecific protein therapeutics with novel modes-of-action and enhanced efficacy for the treatment of inflammatory diseases and cancer. We will present an update on COVA322, a clinical-stage bispecific TNF/IL-17A inhibitor that has the potential to improve currently existing anti-inflammatory therapies. Furthermore, we will present case studies demonstrating that FynomAbs with tailored architecture overcome limitations encountered with other therapeutic protein formats, such as suboptimal efficacy or lack of tumor selectivity.

4:50 How to Minimalize Antibodies: The Success of Antibodies as Pharmaceuticals has Triggered Interest in Crafting Much Smaller Mimics

Patrick_McEnaneyPatrick J. McEnaney, Ph.D., Postdoctoral Researcher, Departments of Cancer Biology and Chemistry, The Scripps Research Institute Florida

In the past decade monoclonal antibodies have revolutionized the treatment of cancer. These antibodies possess excellent specificity and affinity for cell targets, and can perform their function through hijacking of native immune effector functions. However, the potential drawbacks are daunting, including immunogenicity, issues with scalability, storage and cost. This talk will look to leverage the specificity and efficacy seen with large biological agents through utilization of modular synthetic constructs, showing the development and optimization of a fully synthetic molecule capable of eliciting a targeted, specific immune response against prostate cancer.

5:20 End of Day

5:15 Registration for Dinner Short Courses*


SC11: Clinical Prospects of Cancer Immunotherapy

*Separate registration required.

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8:00 am Registration and Morning Coffee

Target Combinations for Immunotherapy

8:30 Chairperson’s Remarks

Robert Mabry, Ph.D., Director, Protein Sciences and Antibody Technology, Jounce Therapeutics

8:35 Arming of Effector T Cells or Tregs with BiTEs or CARs

Michael_BachmannMichael P. Bachmann, Ph.D., Professor, Helmholtz Zentrum Dresden Rossendorf (HZDR); Institute of Radiopharmaceutical Cancer Research, Radio-/Tumorimmunology

In parallel to conventional BiTEs and CARs we established a modular platform technology (UniTARG) for retargeting of T cells with complexes in either a BiTE (UniMAB) or CAR (UniCAR) format for simultaneous or subsequent application against different antigens, and, if requested, co-delivery of co-stimulatory or blocking signals. Armed effector T cells were able to efficiently lyse target cells while redirected Tregs failed but were fully functional in suppression of effector cells.

9:05 Developing Full-Length CD3 Bispecific Antibodies: From Bench to NHP

Javier Chaparro-Riggers, Ph.D., Director, Antibody Technology, Rinat Pfizer, Inc.

The T cell engaging antibody Blinatumumab against CD19 has been approved recently, but the short half-life makes continuous infusions necessary. We implemented a full-length IgG T cell engaging platform, which increases the half-life and allows conventional dosing. Optimization of the platform from bench to NHP will be presented.

9:35 (scFab)2-Fc Type Bispecific Antibodies Engaging T Cells for Cancer Immunotherapy

Hyung-Kwon_LimHyung-Kwon Lim, Ph.D., Senior Research Scientist, Antibody Engineering, MOGAM Biotechnology Institute

This presentation will describe a recent work for the (scFab)2-Fc format bispecific antibodies and its applications toward T cell engagement for cancer immunotherapy. Using this platform, several bi-specific antibodies targeting T cell and tumor specific antigens were constructed. The challenges and opportunities of this format in terms of heterodimerization yield between two heavy chains, any modifications of Fc functions and mass analyses will be shared. In addition, performance of these antibodies such as T cell activation and cytotoxic activities against several antigen specific tumor cells in the various experimental settings will be demonstrated.

10:05 Coffee Break

10:35 A Bispecific Antibody Targeting CD47 and CD20 Selectively Binds and Eliminates Dual Antigen Expressing Lymphoma Cells

Jie Liu, M.D., Ph.D., Senior Scientist, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University

Anti-CD47 and CD20 BsAbs have been developed with reduced affinity for CD47, while retaining strong binding to CD20. These characteristics facilitate selective binding of BsAbs to tumor cells, leading to phagocytosis. BsAbs reduced tumor burden and extended survival in mouse xenograft lymphoma models, recapitulating the synergistic efficacy of anti-CD47 and anti-CD20 combination therapy. It may be broadly applied to cancer to add a CD47 blocking component to existing antibody therapies.

11:05 Engineering Bispecific Antibodies via Cell-Free and Conventional Mammalian Expression Systems

Jeonghoon_SunJeonghoon Sun, Ph.D., Principal Scientist, Biotherapeutics, Celgene Corporation

Engineering asymmetric IgG-like bispecific antibodies via cell-free and conventional mammalian expression systems will be presented. Biophysical, biochemical and/or biological data sets will be compared between the two systems.

11:35 ADAPTIR Immunotherapeutics: A Unique Platform for Engaging T Cells

John_BlankenshipJohn W. Blankenship, Ph.D., Lead Scientist, Molecular Biology and Protein Engineering, BioSciences Division, Emergent BioSolutions

Emergent’s ADAPTIRTM (modular protein technology) platform of bispecific protein therapeutics has unique and distinguishing properties, such as redirection of T cell cytotoxicity with induction of minimal cytokine release compared to other formats. A pipeline of ADAPTIR therapeutics is currently under development from early discovery to clinical stage, targeting both solid and hematologic malignancies. Case studies will be presented for the development of two ADAPTIR therapeutics - MOR209/ES414 and ES425.

Applications Outside Oncology

12:05 pm Chairperson’s Remarks

Eric Smith, Ph.D., Associate Director, Bispecifics, Regeneron Pharmaceuticals

12:10 Case Study: Engineering of a Tetraspecific Anticalin Scaffold to Combat Pseudomonas Aeruginosa Infections

Carsten_CorveyCarsten Corvey, Ph.D., Project Leader, Global Biotherapeutics, Sanofi-Aventis Deutschland GmbH

Highly specific Anticalin® binders were selected and further engineered against all iron-binding siderophores (Pvd I, Pvd II, Pvd III or Pch) of Pseudomonas aeruginosa. In this talk, we will show how siderophores-specific Anticalin proteins can possibly be used in the management of cystic fibrosis patients chronically infected by P. aeruginosa in order to improve lung health and safeguard the quality of life of patients.
12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:10 Refreshment Break

1:40 A Tale of Two Bacteria: Developing Bispecific Antibody Drugs for Pseudomonas aeruginosa and Clostridium difficile

Jonah_RaineyG. Jonah Rainey, Ph.D., Senior Scientist, ADPE, MedImmune, LLC

Pathogen-specific therapeutic strategies are gaining prominence as the antibiotic resistance crisis continues to grow. Ultra-narrow spectrum drugs provide unmet medical needs without contributing to broad antibiotic resistance. Given the adaptive nature of microbes to acquire resistance, two critical survival determinants often need to be targeted. A comprehensive strategic approach to select the most appropriate antibody technology platform given the target and pathogen will be described.

2:10 Bispecific Antibodies Perform a Disappearing Act

Katherine_CygnarKatherine Cygnar, Ph.D., Staff Scientist, Genome Engineering Technologies, Regeneron Pharmaceuticals, Inc.

Herein we will present a novel method to block or destroy a target when the canonical blocking antibody approach has proved insufficient. We show that by using a bispecific antibody to couple a target to an internalizing ‘effector’ protein we are able to drive internalization and clearance of a target protein in vitro and in vivo. Several applications will be discussed.

2:40 Unique Application of Bispecific Antibody for Non-Oncology Disease Area

Shinya_IshiiShinya Ishii, Ph.D., Research Scientist, Research Division, Chugai Pharmaceutical Co., Ltd.

This talk will demonstrate two unique applications of bispecific antibody for non-oncology disease area. First application is a bispecific antibody against activated factor IXa and Factor X that mimics factor VIII function for the treatment of hemophilia A. Second application is biparatopic antibody against soluble antigen with pH dependent antigen property to accelerate the antigen clearance from plasma. Molecular design and in vivo data will be presented.

3:10 Synergy Generates Picomolar Potency and A High Resistance Barrier in Combinectin: A Novel Trispecific HIV-1 Entry Inhibitor with Clinical Promise

Jonathan_DavisJonathan H. Davis, Ph.D., Principal Scientist, Protein Design, Bristol-Myers Squibb

We have designed a biological HIV-1 entry inhibitor with three linked active domains (two Adnectins and a helical peptide) that have separate inhibitory actions. Each of the individual components has an EC50 in the low nM range, but when fused into a single molecule, two different synergistic mechanisms enhance the potency by up to 100-fold or more, with a concomitant boost in the resistance barrier. We describe the design and optimization of the Combinectin, and discuss the general principal of how symmetric and asymmetric synergy can be used and combined to create extremely potent therapeutics.

3:40 End of Engineering Bispecific Antibodies


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