PEGS Europe 2010 | Day 1  |  Day 2

THURSDAY, 7 OCTOBER

9:00 Conference Registration and Morning Coffee

 

New Bispecific and Multi-Valent Constructs:
Optimizing Discovery for Best Results Downstream

9:30 Chairperson’s Remarks

Lutz JermutusLutz Jermutus, Ph.D., FRSC, Senior Director, Technology, MedImmune

 

 

 

 

 

9:35 Optimization of Variable Domain Combination, Orientation and Linkers to Construct Dual Variable Domain (DVD) – Ig TM Molecules

Tariq GhayurTariq Ghayur, Ph.D., Senior Principal Scientist & Research Fellow, Biologics, Abbott Bioresearch Center, Inc.

Bispecific antibodies (bsAb) offer great therapeutic potential. However, many of the bsAb formats reported require optimization of various drug-like properties to be therapeutically viable. We have recently reported on a novel format termed dual variable domain (DVD) – Ig TM. Various approaches used to optimize mammalian cell expression, function and physical stability of DVD-Ig TM molecules will be discussed.

10:05 Novel Multispecific Construct

Peter Kiener, CEO, Zyngenia

Multispecific antibody-based therapeutic drugs will be discussed that retain the structural and functional properties of traditional mAbs. These engineered proteins incorporate additional target-binding domains through the fusion of polypeptides, called Molecular Recognition Domains (MRDs), to the Ig heavy and light chains. The antibody has two copies of each MRD and each MRD independently binds its respective target(s) thereby achieving bivalent binding across multiple specificities. MRDs can be designed to enhance binding of the core mAb to cells, tissues and soluble factors.

Sponsored by
Precision Antibody
10:35 Coffee Break







11:00 Development of a Bispecific TandAb for Clinical Studies: Issues Relating to Immunogenicity, Production and Formulation

Melvyn Little, Ph.D., CSO, Affimed Therapeutics AG

TandAbs are tetravalent bispecific dimeric molecules constructed solely of antibody variable domains. They comprise two binding sites for binding a tumor cell and two further binding sites for binding an immune killer cell. This talk will focus on the challenges faced in developing a bispecific TandAb for the treatment of Hodgkin´s lymphoma.

11:30 Bispecific T Cell-Engaging Antibodies of the BiTE Class

Markus Muenz, Ph.D., Associate Director, EpCAM Research, Micromet

The presentation will demonstrate that BiTE antibodies can be generated to recognize a great variety of tumor-associated antigens. Like with conventional monoclonal antibodies, each BiTE antibodies shows very specific characteristics. Current BiTE candidates in development have been selected to fulfill high pharmaceutical standards for biologicals.

12:00 Improving the in vivo Utility of Targeted Toxins by Rendering them Bispecific

Daniel A. Vallera, Ph.D., Lion Scholar and Director, Section on Molecular Cancer Therapeutics, Professor of Therapeutic Radiology, University of Minnesota Cancer Center

Our research group focuses on the problems that have limited the development of a class of biological drugs known as targeted toxins in order to develop more effective anti-carcinoma therapeutic. Using genetic engineering, we have found that simultaneously targeting certain overexpressed tumor markers with dual ligands results in a more potent and efficacious drug. Since the anti-toxin response of the patient has been shown to reduce drug effectiveness, we also concentrated our efforts on mutating toxin in order to reduce serum anti-toxin levels. The results are new drugs that are highly effective in human xenograft models.

12:30 Lunch for Purchase in the Exhibit Hall

13:45 Dedicated Poster Viewing in the Exhibit Hall

 

Engineering for Enhanced Stability
and Manufacturability of Proteins

14:30 Chairperson’s Remarks

Bernhardt L. Trout, Ph.D., Director, Novartis-MIT Center for Continuous Manufacturing; Director, Concourse; Co-Chair, Singapore-MIT Alliance, Chemical and Pharmaceutical Engineering; Professor, Department of Chemical Engineering, MIT

14:35 KEYNOTE PRESENTATION
Incorporation of Developability and Manufacturability in Therapeutic Antibody Discovery

Bernhardt L. Trout, Ph.D., Director, Novartis-MIT Center for Continuous Manufacturing; Director, Concourse; Co-Chair, Singapore-MIT Alliance, Chemical and Pharmaceutical Engineering; Professor, Department of Chemical Engineering, MIT

We describe a new strategic approach to the formulation and stabilization of biotherapeutics. The approach is based on applying both molecular and macroscopic modeling tools in order to gain an understanding of degradation processes with unprecedented detail and accuracy. This approach allows the rational inclusion of screening molecules for developability and manufacturability during discovery, identifying key sites that are responsible for degradation for the purpose of removing them, identifying sites for conjugation of payloads, and identifying binding regions.

15:05 In Silico Methods to Reduce Development Risks in Biotherapeutics: Engineering Optimal Lead Compounds

Jesús Zurdo, Ph.D., Head of Innovation, LCM Development Services, Lonza Biologics plc

Protein aggregation and low stability imposes severe restraints in the development of biopharmaceuticals, potentially increasing the risks of undesired immune responses in patients. Predictive algorithms can be used to re-designing therapeutic antibodies with improved stability properties.

15:35 Refreshment Break

16:30 Screening Antibody Candidates for Manufacturability, Stability, and Deliverability

Andrew KoskyAndrew Kosky, Ph.D., Senior Manager, Early Stage Pharmaceutical Development, Genentech, Inc.

Monoclonal antibodies can be difficult to manufacture, stabilize, and administer to patients in a convenient format; this is especially the case for therapeutic agents that require high doses and subcutaneous delivery. The intrinsic physicochemical properties that govern the manufacturability and deliverability of these molecules can be difficult to predict from primary sequence.  The focus of this talk is a screening strategy that is designed to rapidly and accurately assess the manufacturability, stability, and deliverability of therapeutic antibody candidates.  Data from the screening studies can be used to inform the candidate selection process.

17:00 Engineered Ig-Like Bispecific Molecules with Enhanced Therapeutic Potential

Justin CaravellaJustin Caravella, Ph.D., Scientist, Physical Biochemistry, Drug Discovery, Biogen Idec, Inc.

Stabilized single chain Fv fragments are building blocks for constructing Ig-like bispecific antibodies. Focused engineering platform technology for stabilizing single chain Fv fragments will be discussed, as well as characterization of Ig-like bispecific molecules.

 

17:30 Close of Conference