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Second Annual
Bispecific Antibody Therapeutics
Engineering Multi-Specificity
January 24-25, 2013 
 

  

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FRIDAY, JANUARY 25

7:15 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

 

Revolutionary Engineering 

7:45  Chairperson’s Remarks 

Eugene Zhukovsky, Ph.D., CSO, Research, Affimed Therapeutics AG 

7:50  Optimization of Bispecific DART Proteins for Oncology

Syd JohnsonSyd Johnson, Ph.D., Vice President, Antibody Engineering, MacroGenics, Inc.

Bispecific antibodies that recruit effector cells to tumors represent a highly potent class of immunotherapeutic agents.  The major challenges to development and effective clinical use of fragment-based bispecific formats have been manufacturability, stability and pharmacokinetics.  We have developed and optimized several formats of our stable dual-affinity retargeting (DART) format that address these issues with an emphasis on oncologic applications.  Multiple examples will be presented of half-life extended DART proteins that redirect T-cells to tumor-associated antigens, including CMC strategies and in vitro and in vivo potency.

8:20  How Mathematical Modeling Can Inform the Design and Format Selection of Bispecific Antibodies

Rachel Rennard, Senior Scientist, Merrimack Pharmaceuticals

Monoclonal antibodies are valuable as anticancer therapeutics because of their ability to selectively bind tumor-associated target proteins like receptor tyrosine kinases. However, most tumors are addicted to more than one pathway which asks for rational antibody combinations or bispecific antibodies.  This talk will illustrate the use of kinetic computational models that capture protein–protein interactions to explore antibody combinations vs. bispecific antibodies, different formats of bispecific antibodies, to set antibody design specifications such as affinity and valence, and to predict potency

8:50 Engineering Bispecific Antibodies in the Final Therapeutic Format

Robert MabryRobert Mabry, Ph.D., Associate Director, Antibody Engineering, Adimab, LLC

As alternative strategies such as antibody cocktails and bispecific antibodies gain momentum in the clinic, there is a need to investigate these avenues upstream during the drug discovery process. Here, we demonstrate the ability to generate diverse libraries of therapeutic bispecific formats presented on the surface of yeast to select for antigen specificity, chain pairing, thermal stability, and expression. The ability to select in a final therapeutic format from a diverse library obviates the need for additional downstream engineering.

9:20 Generating Bispecific Human IgG1 and IgG2 Antibodies from Any Antibody Pair

Pavel StropPavel Strop, Ph.D., Associate Research Fellow, Protein Engineering, Rinat-Pfizer - Biography 

We have engineered both human IgG1 and IgG2 subtypes, with minimal point mutations, to form full-length bispecific human antibodies with high efficiency and in high purity. In our system, the two antibodies of interest can be expressed and purified separately, mixed together under appropriate redox conditions, resulting in a formation of a stable bispecific antibody with high yields. With this approach it is not necessary to generate new antibodies that share a common light chain, therefore allowing the immediate use of an existing antibody.

Selexis9:50 Bispecific Antibodies From a Novel Stable Expression Platform – Case Study: Development of an Azymetric™ Antibody Using the Selexis SUREtechnology Platform™David Poon, Ph.D., Director, External R&D and Alliances, ZymeworksThe Zymeworks Azymetric™ platform is an IgG1-based bispecific antibody formed by assembly of engineered heterodimeric heavy chains.  Stable, high-expressing CHO clones of an Azymetric™ antibody were isolated in 7 weeks using Selexis SUREtechnology™. The bispecific antibody product was > 97% pure heterodimer as assessed by MS.

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

 

Designing to Fight Disease 

11:00 SAR156597: An Innovative Bi-Specific IL-4/IL-13 Antibody as a Potential Treatment for Idiopathic Pulmonary Fibrosis

Ercole RaoErcole Rao, Ph.D., Senior Scientist, R&D Biologics, Research Solutions FF, Sanofi-Aventis Deutschland GmbH

SAR156597, an engineered bispecific antibody, simultaneously binds both IL-4 and IL-13 with high affinity and may attenuate the pathogenesis of idiopathic pulmonary fibrosis, a severe disease with few therapeutic options and a mean survival time of 3 years. SAR156597 suppresses IL-4/IL-13-mediated effects in vitro and allergen-induced airway hyper ressponsivenes in sensitized monkeys. The safety, tolerability and PK of single subcutaneous doses of SAR156597 have been established in healthy human subjects.

11:30 A Bispecific SCORPION Molecule that Targets CD86 and Delivers an Immunosuppressive Cytokine, IL10, is a Potent Inhibitor of Antigen Presenting Cells

Philip TanPhilip Tan, Ph.D., Associate Director, Emergent Product Development Seattle - Biography 

I will discuss the SCORPION molecule that is used to target and block a co-stimulation receptor, CD86 and deliver an immunosuppressive cytokine, IL10, to antigen presenting cells. By targeting multiple pathways, a SCORPION molecule can effectively inhibit antigen presenting cells, thereby preventing T cells stimulation, and may have potential application in autoimmunity and inflammatory diseases. We will present pre-clinical data of our SCORPION molecule showing high levels of in vitro and in vivo efficacy at low doses.

12:00 pm Case Study:  Development of a Fully Human Bispecific Antibody Platform Using the VelocImmune Technology

Eric SmithEric Smith, Ph.D., Associate Director, Regeneron Pharmaceuticals - Biography 

Bispecific antibodies are an important new class of therapeutic currently in clinical and pre-clinical development.  This presentation will describe the generation of a platform technology that can be used to generate fully human bispecific antibodies through the combination of Fc modifications that allow selective protein A purification and VelocImmune generated antibodies that utilize a single defined light chain.  Molecular characterization and in vitro/in vivo data showing the efficacy of this format will be discussed.

12:30 Close of Morning Session

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

 

Emerging Platform Technologies  

2:00 Chairperson’s Remarks

Syd Johnson, Ph.D., Vice President, Antibody Engineering, MacroGenics, Inc.

2:05 A Novel Platform for Full-Length Bispecific Antibodies Enables Binding of Two Distinct Target Antigens Coupled with Optimized Fc-Mediated Effector Functions and Long Half-Life

David E. Szymkowski David E. Szymkowski, Ph.D., Senior Director, Biotherapeutics, Xencor, Inc. - Biography 

Bispecific antibodies based on full-length antibodies have advantages over fragment-based formats due to the favorable drug properties of the Fc region. This presentation will describe an antibody engineering platform that employs a heterodimeric Fc region to enable efficient expression and purification of antibodies containing two variable regions coupled to an Fc domain optimized for superior effector function and half-life.

2:35 RECRUIT TandAbs: Tetravalent Bifunctional Antibodies Immunotherapeutics for Treatment of Cancer

Eugene Zhukovsky Eugene Zhukovsky, Ph.D., CSO, Research, Affimed Therapeutics AG - Biography 

The TandAb platform offers several advantages unattainable by most competing technologies: high efficacy with minimal side effects, the ability to create tri- and tetra- valent antibodies, etc. The presentation should serve many in the biotherapeutcis development community since the development of multi-specific biologics has been widely embraced.

 

3:05  Structure-Guided Engineering and the Development of Novel Bi-Specific and Multi-Specific Therapeutics: The IgG1-Based Azymetric and the Albumin-Based AlbuCORE Scaffolds

Thomas Spreter Von Kreudenstein, Ph.D., Senior Scientist, Protein Engineering, Zymeworks, Inc.

Rational structure-based designs were used to engineer the classical antibody IgG1 and human serum albumin molecules into novel multi-specific scaffolds with unique therapeutic applications. Aspects of the design, including biophysical characterization, pharmacology, pharmacokinetics, and manufacturability will be discussed in support of these best-in-class multi-specific formats.

3:35  Development of PMC-001, Novel Bispecific Antibody Neutralizing Both VEGF-KDR and ANG-Tie2 Pathways Simultaneously

Jin-San YooJin-San Yoo, Ph.D., CEO, PharmAbcine, Inc. - Biography 

PMC-001 is a novel bispecific molecule derived from DIG-Body platform with PoC. PMC-001 binds both KDR and TIE2 simultaneously, and in in vitro studies, exhibits superior performance as compared to monospecific antibody. In animal model systems, PMC-001 overcomes Avastin-resistant tumor.  This presentation will discuss the data for this platform.


4:05 End of Conference



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