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2014 Archived Content

Cambridge Healthtech Institute’s Third Annual
Bispecific Antibody Therapeutics
Engineering Multispecificity
January 16-17, 2014


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FRIDAY, JANUARY 17

7:15 am Conference Registration

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


Fighting Cancer with Bispecifics 

8:30 Chairperson’s Remarks

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

8:35 Novel Agonistic Bispecific Tetravalent DR5 Antibodies for Tumor Targeted Induction of Apoptosis with Superior in vivo Efficacy

Peter BrünkerPeter Brünker, Ph.D., Head, Large Molecule Research, Pharma Research and Early Development (pRED), Roche Glycart AG

We have rationally designed novel bispecific tetravalent antibodies for tumor targeted induction of apoptosis based on the CrossMab technology. In vitro, these bispecific agonistic DR5-FAP antibodies demonstrated specific induction of apoptosis of DR5 positive tumor cells exclusively in the presence of a FAP expressing second cell line through potent tumor-specific DR5 cross-linking. Efficacy studies in tumor mouse models revealed superiority of the bispecific DR5-FAP molecules over the agonistic DR5 antibody alone, making this a promising new approach for cancer therapy.

9:05 Targeting Notch/Delta-Like Ligand 4 (DLL4) and Vascular Endothelial Growth Factor (VEGF) Pathways by an Anti-DLL4/Anti-VEGF Bispecific Monoclonal Antibody Inhibits Tumor Growth and Reduces Cancer Stem Cell Frequency in Solid Tumors

Wan-Ching Yen, Ph.D., Senior Scientist II, Cancer Biology, OncoMed Pharmaceuticals, Inc.

We have developed a high binding affinity bispecific monoclonal antibody that targets both human DLL4 and human VEGF using our proprietary technology. The bispecific antibody demonstrates significant in vivo anti-tumor efficacy, down-regulation of vasculature-related genes and decreasing the frequency of tumor initiating cells compared to either anti-DLL4 antibody or bevacizumab treatment alone. Our data suggest that our anti-DLL4/anti-VEGF bispecific antibody is a potential candidate in treatment of tumors driven by VEGF and Notch/DLL4 signaling pathways.

9:35 Targeting of HER2 Receptor with Bispecific DARPin Agents

Martin SchwillMartin Schwill, Ph.D., Scientist, Biochemistry, University of Zurich

Designed Ankyrin Repeat Proteins (DARPins) recognizing individual domains of human HER2 have been used to construct high-affinity tumor targeting vehicles. Particular formats of such bispecific DARPins exhibited strong anti-tumor activity on HER2-addicted breast cancer cell lines both in vitro and in vivo, which was attributable to induction of apoptosis, growth arrest and inhibition of cell motility. On the receptor level, DARPins brought about both inactivation of HER2 homodimers and disintegration of HER2-EGFR/HER3 heterodimers, entailing a potent and sustained inhibition of downstream signaling.

10:05 Extended Q&A

10:20 Coffee Break in the Exhibit Hall with Poster Awards

 

NEXT-GENERATION ENGINEERING   

11:15 An Efficient Route to Generate Bispecific Antibodies with Natural Architecture from Distinct Half-Antibodies  

Christoph SpiessChristoph Spiess, Ph.D., Scientist, Antibody Engineering, Genentech, Inc.  

The presentation will cover a technology to use the knobs-into-holes technology to generate bispecific antibodies with non-common light chains. The solution eliminates the need of linkers to prevent light chain mispairing. Each heavy chain is expressed with its corresponding light chain in separate bacterial strains. Individual half-antibodies are purified, combined and finally the bispecific antibody purified by conventional means. The versatility and robustness of the approach will we demonstrated by a broad set of bispecific antibodies.

11:45 The Duobody Platform: Efficient Generation of Stable Bispecific Antibodies by Controlled Fab-Arm Exchange 

  Paul ParrenPaul Parren, Ph.D., Senior Vice President and Scientific Director, Genmab  

Duobody represents a novel and elegant post-production technology for the generation of bispecific antibodies. This bispecific antibody platform is built on the process of Fab-arm exchange which is leveraged to generate stable bispecific human IgG1 antibodies. Our data show that our platform ensures highly efficient generation of bispecific antibodies with a regular IgG1 structure, stability, Fc-mediated effector functions and in vivo half life, next to fully scalable manufacturing using standard unit operations.

12:15 pm CrossMAb Ang2-VEGF: From Idea to Technical Development  

Jörg T. RegulaJörg T. Regula, Ph.D., Head, Protein Analytics, Pharma Research and Early Development (pRED), Roche Diagnostics  

VEGF-A blockade has been validated clinically as a treatment for human cancers. Angiopoietin-2 (Ang-2) expression has been shown to function as a key regulator of tumor angiogenesis. The CrossMAb technology is an innovative approach to generate human bispecific antibodies by IgGdomain exchange. Utilizing this technologywe generated a bispecific human IgG1 antibody (CrossMab) blocking VEGF-A and Ang-2 function simultaneously. Initial experiments showed the technical feasibility of this approach and guided the way for process development. Clinical Ph I trials are ongoing.

ForteBio logo 12:45 Binning Strategies for Characterization of a Large Panel of Fully Human Therapeutic Monoclonal Antibodies  

Kamat_VishalVishal Kamat, Ph.D., Scientist, Biomolecular HTS Center, Therapeutic Proteins, Regeneron Pharmaceuticals
The therapeutic use of monoclonal antibodies is one of the fastest growing areas in the pharmaceutical industry. Advancement in antibody engineering techniques has been instrumental in the development of different antibody moieties. Variant small sized antibody fragments as well as innovative bispecific antibodies binding to the same target or to different targets are currently being engineered. Selection of antibodies with broader epitope diversity is critical for the successful design of such engineered molecules. This necessitates the identification of antibodies binding to distinct, non-overlapping epitopes during the early stage of drug discovery. Epitope binning would also aid in the selection of appropriate antibody pairs for designing bispecific antibodies. The various binning strategies used to cluster a large panel of antibodies to support our drug discovery platform will be presented. 

1:15 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own  

 

ENHANCING PROPERTIES   

2:00 Chairperson’s Remarks  

Christopher L. Reyes, Vice President, Research and Development Biologics, Bionomics

2:05 Human Bispecific IgG Antibodies with a Common Light Chain: Combining Superior Functionality and Developmental Reliability  

 John de KruifJohn de Kruif, Ph.D., CSO, Merus Biopharmaceuticals  

Bispecific antibodies allow the simultaneous targeting of different molecules, thus providing more efficacious biotherapeutics in many applications. This approach benefits from antibodies with a natural human IgG format. A novel transgenic mouse harbouring a common rearranged human light chain, MeMo®, has been created to efficiently discover human common light chain antibodies. Upon transfection of producer cells with constructs encoding two different common light chain mAbs that simultaneously facilitate efficient heterodimerization, highly pure bispecific human IgG are obtained.

2:35 Stable Variable Domains as Building Blocks for the Engineering of Bispecific Antibody Fragments with Unique Characteristics  

David UrechDavid Urech, Ph.D., CSO and Co-CEO, Numab AG  

The use of a single human variable domain scaffold allows for the reproducible engineering of highly stable and potent humanized rabbit antibody variable domains. Such variable domains are used as building blocks for the engineering of bispecific single-chain diabodies (scDb) with excellent CMC properties. Numab is exploiting bispecific scDbs with T killer cell redirecting activity for the therapy of chronic inflammatory diseases.
 

3:05 Unlocking New Biology through Flexible Architecture  

Wibke LembkeWibke Lembke, Ph.D., Scientist, Covagen AG  

Covagen develops bispecific FynomAbs by fusing its fully human Fynomer binding proteins to antibodies resulting in more effective therapeutics with novel modes-of-action for inflammatory diseases and cancer. The ability to fuse Fynomers to multiple sites on the antibody allows Covagen to tailor the mode-of-action to maximize efficacy. We will show case studies of our bispecific FynomAbs (bispecific TNF/IL-17 inhibitor; a FynomAb targeting two epitopes on HER2 and FynomAbs for CD3 targeted immunotherapy).

3:35  Close of Conference 



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