Meet the AdvisorsResurgence of Bispecific Antibodies:
The Future of Antibody Development


ANTIBODIES STREAM   May 11-12

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WEDNESDAY, MAY 11

7:00 am Registration and Morning Coffee

 

CONSTRUCTING BISPECIFICS WITH IMPROVED PROPERTIES 

8:20 Chairperson’s Opening Remarks and Overview of Bispecific Antibodies

Patrick Baeuerle Patrick Baeuerle, Ph.D., CSO & Senior Vice President, R&D, Micromet






 

8:40 The Impact of Fab-Arm Exchange on the Development of Antibody Therapeutics

Janine Schuurman Janine Schuurman, Ph.D., Associate Director, Strategic Research, Genmab BV

IgG4s are dynamic molecules that undergo Fab arm exchange by swapping an IgG4 heavy chain and attached light chain for a heavy-light chain pair from another IgG4 molecule. Thereby IgG4 antibodies acquire bispecific binding properties. The relevance of Fab arm exchange for immunotherapy is demonstrated and discussed.

 

9:10 COMBODY: One-Domain Antibody Multimer with Improved Avidity

Bin Gao Bin Gao, Ph.D., Professor and Director, The Centre for Molecular Immunology, Institute of Microbiology, CAS

The smallest possible antigen binding domain has been built into a multimer molecule, dubbed as Combody, by fusing to a coiled-coil structure derived from cartilage oligomeric matrix protein. Combody has high avidity to its antigen and can be multiple specific and possibly, has improved pharmacokinetics.

 

9:40 Heavy-Light Chain Fab Crossover: A Generic Approach for the Production of Bispecific IgG Antibodies

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

We describe a generic method for the production of bivalent bispecific IgG1 antibodies based on the crossover of domains within the Fab region of one half of a bispecific antibody combined with the knobs-into-holes technology. Based on this approach, we describe a bispecific CrossMab targeting VEGF-A and Angiopoietin-2 with potent anti-tumoral and anti-angiogenic efficacy.

 

10:10 Coffee Break in the Exhibit Hall with Poster Viewing

11:10 Bispecific/Multispecific SCORPION Scaffold for Autoimmune Diseases and Oncology

Phillip Tan Philip Tan, Ph.D., Associate Director, Research, Emergent Biosolutions

Using our SCORPION scaffold, we have generated bispecific and multispecific molecules to target multiple soluble ligands and multiple receptors on various cell types. These novel molecules often show potent and unique properties compared to single agents alone. Different case studies will be presented.

 

11:40 Pan-Specific Antibodies Targeting Redundant Signaling Pathways in Autoimmunity

Marie Kosco-Vilbois, Ph.D., CSO, NovImmune SA, Geneva

In certain diseases, targeting a single protein might not be sufficient to achieve efficacy and this has prompted the development of innovative formats that allow for multiple targeting. We describe the isolation and engineering of antibodies that are selectively cross-reactive and neutralize more than one target thus leading to improved neutralization of redundant signaling pathways.

12:10 pm Luncheon Presentations (Sponsorship Opportunity Available) or Lunch on Your Own

1:10 Break

1:30 Chairperson’s Remarks

Nazzareno Dimasi Nazzareno Dimasi, Ph.D., Senior Scientist, Antibody Discovery & Protein Engineering, MedImmune




 

1:35 Efficient Cell-Mediated Cytotoxicity Using Bispecific Domain Antibodies for Cancer Therapy

Patrick Chames Patrick Chames, Ph.D., Principal investigator, Antibody Therapeutics and Immunotargeting (ATI), INSERM, France

We are developing new bispecific antibodies, easy to produce and capable of circumventing most of the limitations faced by today’s therapeutic antibodies, including Fc receptor polymorphism, glycosylation issues, competition with endogenous IgG and binding to inhibitory receptors. The latest results obtained with these bispecific fragments will be discussed.

 

2:05 TRIBODYTM: Building Trispecificity by Fab-scFv Fusions

Nico Mertens Nico Mertens, Ph.D., MBA, Director, Antibody Engineering, Biotecnol SA

Tribodies are antibody fragment manifolds based on fusion to Fab-chains. The molecular structure allows easy engineering of bispecific, bivalent bispecific, trispecific or multivalent reagents. Tribodies behave superior as compared to scFv-scFv constructs. This is probably due to better PK properties of these intermediate sized molecules, and to the multivalent targeting. Tribodies hold much potential to be developed as a new generation of biopharmaceuticals, as they can target multiple antigens with a single molecule."
 

2:35 Dual Variable Domain (DVD)–IgTM Platform: Understanding the Biology of DVD–IgTM Format to Build Therapeutic Dual-Specific Biologics

Tariq Ghayur Tariq Ghayur, Ph.D., Senior Research Fellow, Abbott Bioresearch Center

The DVD-IgTM technology enables us to attach the target binding domain of one mAb on to an existing mAb via flexible linkers. We have now converted the construction, expression, purification and functional/physicochemical characterization of these molecules into a high throughput platform. Lessons learned from these studies will be discussed.

 

3:05 Refreshment Break in the Exhibit Hall with Poster Viewing

3:50 Sponsored Presentations (Opportunities Available)

 

4:20 Problem Solving Breakout Sessions 

Concurrent Problem Solving Breakouts are interactive sessions hosted by a moderator to discuss a topic in depth. They are open to all attendees, sponsors, exhibitors, and speakers and provide a forum for discussing key issues and meeting potential partners. Please pick a topic of your choice and join in. 

TABLE 14: Generic Approach to Producing Bispecific Antibodies 

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

• Where do you see the best potential for application of bispecific antibodies
• Which technolgies do you apply for generation of bispecific antibodies
• Which technologies do you consider most promising for generation and production of bispecific antibodies
• Fc-containing vs non-Fc containing bispecific antibodies incl. half life extension technologies: Pros & Cons
 

TABLE 15: PanSpecific Antibodies: Exploiting Promiscuity for Next Generation Drugs 

Co-Moderators: Marie Kosco-Vilbois, Ph.D., CSO, NovImmune SA, Geneva and Nicolas Fischer, Ph.D., Head, Research Department, NovImmune SA 

• Targeting redundant disease pathways
• Technical feasibility: Upstream/Downstream challenges and advantages
• Differentiating Pan versus Bi specific formats
 

TABLE 16: Bringing Safe and Efficacious Therapeutic Bispecific Antibodies to Clinic 

Moderator: Tariq Ghayur, Ph.D., Senior Research Fellow, Abbott Bioresearch Center 

• What are the challenges and opportunities for bispecific antibodies?
• Can our current assumptions from the mAb field be applied to the bispecific field? Do we need to develop new thinking and selection methods for therapeutic bispecific antibodies?
• How do we select target pairs that enhance efficacy without impacting safety?
 

o Are additive effects of blocking 2 targets sufficient? 

o What are specific challenges for re-directed toxicity? 

• What might be the potential regulatory hurdles in developing bispecific antibodies? 

TABLE 17: Developability of Bispecific Antibodies 

Moderator: Nazzareno Dimasi, Ph.D., Senior Scientist, Antibody Discovery & Protein Engineering, MedImmune 

• Is there a universal bispecific format?
• Can a bispecific format be tuned based on the targets?
• How to engineer bispecifics to improve expression, purification, solubility and stability?
• What could be the next revolutionary bispecific format?
 

5:15 Reception in the Exhibit Hall with Poster Viewing

6:00 End of Day



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