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Archived Content

Bispecific Antibody Therapeutics


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FRIDAY, JANUARY 13

7:30 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

 

Innovating the Design of Bispecifics

8:15 Chairperson's Remarks

Rakesh Dixit, Ph.D., Vice President, Research & Development; Global Head, Biologics Safety Assessments, MedImmune

8:20  A Molecular Engineering Approach to Generate Bispecific Antibodies with Enhanced Effector Functions

Wei Yan, Ph.D., Director, Protein Science, Amgen, Inc. - Biography

We have modified the CH3 domain interface of the antibody Fc region with selected mutations so that the engineered Fc proteins preferentially form heterodimers.  This new strategy allows the production of asymmetrical fusions base on Fc heterodimer where each chain is individually engineered to maximize functionality and selectivity of the fusion protein.   An example will be given on the generation of a heterodimeric IgG in which asymmetrical mutations are introduced at the two different Fc chains so that each chain is individually optimized for maximum binding to Fc receptors to enhance ADCC activities of the antibody.

8:50 Dual-Affinity ReTargeting (DARTTM) Proteins for the Treatment of Cancer and Autoimmune Disease

Paul Moore, Ph.D., Vice President, Cell Biology & Immunology, MacroGenics, Inc.

The ability of the DART platform to support assembly of varying Fv regions while retaining their anticipated antigen binding properties, combined with the efficient assembly, expression and stability of DART molecules has afforded the feasibility to explore various bi-specific targeting approaches.  Strategies have also been developed to incorporate the desired binding valency and pharmacokinetic properties into DART molecules for specific therapeutic applications. Examples of these various DART based approaches will be presented in the context of novel therapeutic modalities for the treatment of autoimmune disease and cancer.

9:20 Treatment of ALL with BiTE Antibody Blinatumomab

Patrick BaeuerlePatrick A. Baeuerle, Ph.D., Professor of Immunology, CSO & Senior Vice President, Micromet, Inc.Biography 

Relapsed/refractory (r/r) ALL is a disease with a dismal prognosis. It is currently treated with a cocktail of chemotherapeutics associated with significant treatment-related mortality. Single-agent therapy of ALL patients with the CD19/CD3-bispecific antibody construct blinatumomab has shown very high response rates (75-80% range) in adult patients with relapsed disease or minimal residual disease, and a favorable benefit risk ratio.

9:50 Sponsored Presentation (Opportunity Available)

10:05 Networking Coffee Break in the Exhibit Hall with Poster Awards

11:00 Enhancing Bispecific Antibody Function for Cancer Therapy

Matthew RobinsonMatthew Robinson, Ph.D., Assistant Professor, Medical Oncology, Fox Chase Cancer Center

Advances in antibody engineering have led to the development of bispecific antibodies that are emerging as a promising class of agents for the treatment of cancer. We have focused on developing bispecific antibodies targeting the ERBB family of receptor tyrosine kinases. Work will be presented on our efforts to enhance the intrinsic activity of bispecific antibodies through rationale protein design and functional genomic strategies.

11:30 CVX-241: A VEGF and Ang2 Targeting Bispecific CovX-Body

Dingguo Liu, Ph.D., Principal Scientist, CovX, Biotherapeutic Division, Pfizer

Bispecific antibodies are promising therapeutic agents due to their ability to simultaneously bind two different antigens. The CovX technology enables rapid discovery and development of antibody based bispecific agents. Here, we present CVX-241, a bispecific CovX-Body that binds vascular endothelial growth factor and angiopoietin-2 simultaneously, inhibits their function and shows efficacy in tumor xenograft studies. This novel anti-angiogenic bispecific agent is in phase I clinical trials.

12:00 pm Generation of Bispecific Antibodies via Controlled Fab-Arm Exchange

Paul ParrenPaul W.H.I. Parren, Ph.D., Senior Vice President and Scientific Director, Genmab AS - Biography

We have invented a novel, highly efficient, method to generate bispecific antibodies based on the process of Fab-arm exchange. Bispecific antibodies developed with this platform (DuoBodyTM) retain the biochemical structure of regular human IgGs, have Fc-mediated effector functions and regular IgG1 pharmacokinetics. The technology, scientific background and proof-of-concept studies will be discussed.

12:30 Close of Morning Session

12:45 Luncheon Presentations (Sponsorship Opportunity Available) or Lunch on Your Own

 

OVERCOMING CHALLENGES--
THE REVOLUTION IN MULTISPECIFICITY

2:00 Chairperson's Opening Remarks

Paul W.H.I. Parren, Ph.D., Senior Vice President and Scientific Director, Genmab AS

2:05 Zybodies™: Novel Therapeutics that are able to Simultaneously Target Multiple Disease Pathways

Peter A. Kiener, D.Phil., President, CEO and Co-Founder, Zyngenia, Inc.

Mono-specificity therapies such as mAbs, cytokines and even small molecule drugs are often insufficient due to the complexity of disease processes. Zybodies, a new class of mAb-like multi-specific therapeutics, address this complexity through their ability to simultaneously engage multiple targets and thus agonize and/or antagonize multiple disease pathways. Each Zybody is recombinantly engineered and produced to have the physiochemical and pharmacokinetic properties of a conventional mAb. The Zybody's unique features create new opportunities for better disease control in multiple therapeutic indications, but at the cost and with the development paradigm of a single biologic therapy. Examples of their possible use in cancer and inflammatory diseases will be explored.

2:35 Safety Challenges to the Development of Bispecific Antibodies

Rakesh DixitRakesh Dixit, Ph.D., Vice President, Research & Development; Global Head, Biologics Safety Assessments, MedImmune

Given the fact that multiple pathways are often perturbed in human diseases, simultaneous targeting of several key targets with a single antibody has great potential in improving the efficacy and advancing biological therapies to treat many debilitating human diseases. However, there are numerous challenges to developing bispecific mAbs with regard to optimization of molecular properties, including affinity, avidity, molecular format and stability. From a safety perspective, it is possible that simultaneous targeting of pathways or new molecular formats or biopharmaceutical properties can lead to unexpected new or synergistic or additive toxicities of two pathways.

3:05 End of Conference


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Links to Companion Meetings

Pipeline 3

Antibodies for the 21st Century

Recombinant Protein Therapeutics


Dingguo Liu, Ph.D., Principal Scientist, CovX Research LLC