Archived Content

ANTIBODIES STREAM  

3rd Annual  

Bispecific Antibodies May 2 - 3


Bispecific and multiclonal antibodies are one of the most promising and exciting areas of protein engineering. Since 2009, there have been deals made in excess of $6.5 billion on bispecifics, and the range of therapeutic uses for bispecific antibodies are being expanding beyond oncology to diseases of the immune system, heart and CNS. This meeting will explore the remaining challenges and profile creative problem solving that has been used to make successful bispecific formats.  The latest approaches for dual-targeting as well as targeting two different epitopes of the same receptor will be explored for improving efficacy.

Meet the Scientific Advisory Board 

Patrick Baeuerle, Ph.D., CSO & Senior Vice President, Research &Development, Micromet - Biography 

Michael J. Feldhaus, Ph.D., Vice President, Antibody Discovery, Adimab, LLC - Biography 

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

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

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

 

Day 1 | Day 2 | Download Brochure 

 

WEDNESDAY, MAY 2

7:00 am Registration and Morning Coffee

 

OPTIMAL ROUTE TO BISPECIFIC ANTIBODIES 

8:30 Chairperson’s Opening Remarks

Michael J. Feldhaus, Ph.D., Vice President, Antibody Discovery, Adimab, LLC

8:40 A Simple and Smart Route to Bispecific Antibodies: Kappa/Lambda-Bodies

François Rousseau, Ph.D., Head, Protein Engineering, Research, NovImmune SA

The discussion will focus on strategies for mitigating risk around the choice of targets for bispecific antibodies as well as one or more case studies regarding the use of biochemical and biophysical data for choosing antibody partners. Kappa/Lambda bodies have the characteristics inherent to bispecific antibodies as they can bind multiple targets and have novel modes of action. In contrast to other bispecific formats, Kappa/Lambda-bodies are unmodified fully human IgGs. They depend on the assembly of a kappa and a lambda light chain with a common heavy chain, thus, their stability and in vivo pharmacokinetic properties are indistinguishable to a human IgG. Despite relying on light chain diversity, efficient blockers have been generated. To further expand the versatility of the platform, we generated a new set of Kappa/Lambda-bodies that combine either two lambda or two kappa variable domains with kappa and lambda constant domains. Using this approach, we combine the benefits of a generic purification process with the flexibility of using any light chain type.
 

9:10 DuoBodyTM: Efficient Generation of Bispecific IgG1 via Controlled Fab-Arm Exchange

Aran Labrijn, Ph.D., Senior Scientist, Antibody Sciences, Genmab (biography)

The DuoBodyTM platform generates highly efficiently bispecific antibodies by a controlled Fab-arm exchange process. These bispecific antibodies retain the biochemical structure of regular human IgG1, have Fc-mediated effector functions and regular IgG1 pharmaco kinetics. The technological background and proof-of-concept studies will be discussed.

9:40 TandAbs: A Bispecific Platform that Directs Immune Cells to Kill Cancer Cells and Extends the Half-Life of Immunotherapeutics

Eugene Zhukovsky, Ph.D., CSO, Research, Affimed Therapeutics AG (biography)

The TandAb technology comprises CD3 RECRUIT and CD16 RECRUIT modules for the respective activation (recruitment?) of T and NK effector cells that lyse target cells expressing targeted cell-surface antigens. The PROLONG-TandAb platform is under development to optimize the pharmacokinetic properties of our bispecific antibodies by introducing a human serum albumin binding moiety for extended half-life. I will present examples profiling both platforms.

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

 

PRE-CLINICAL DATA 

11:05 Chairperson’s Remarks

Michael J. Feldhaus, Ph.D., Vice President, Antibody Discovery, Adimab, LLC

11:10 Two-in-One Antibody: A Platform to Target Two Molecules as IgG or Fab

Germaine-FuhGermaine Fuh, Ph.D., Senior Scientist, Antibody Engineering, Genentech (biography)

Two-in-One antibodies are conventional antibodies in molecular structure generated by evolving the antigen-binding site on each Fab arm of a mono-specific antibody to become dual specific. Variants of HER2 targeting antibody Herceptin that also bind and block VEGF is initial proof-of-concept. In clinical development is an EGFR/HER3 two-in-one antibody that inhibits a broad range of epithelial tumor in mouse models.
 

11:40 EGFRvIII-Targeted Bispecific T Cell Engagers for Brain Tumor Therapy

Chein-Tsun-KuanChien-Tsun Kuan, Ph.D., Assistant Professor, Pathology; Member, Preston Robert Tisch Brain Tumor Center, Duke University Medical Center (biography)

Bispecific T-cell engagers targeting EGFRvIII were designed to redirect a patient’s T-cells to kill cancer cells by targeting to tumor cells expressing GBM-specific EGFRvIII. Our pre-clinical study showing this reagent leading to highly efficient lysis of target cells and significant anti-tumor efficacy in intracranial animal models will be presented.

 

12:10 pm Luncheon Presentation (Sponsorship Opportunities Available) or Lunch on Your Own

 

NOVEL SCAFFOLDS AND FORMATS FOR BISPECIFICS AND MULTICLONALS 

1:30 Chairperson’s Remarks

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

1:35 Computational Modeling to Build a Better Bispecific Scaffold

Surjit DixitSurjit Dixit, Ph.D., CTO, Zymeworks, Inc. (biography)

Bispecific Azymetric™ antibodies are immunoglobulins engineered using structure guided and computational modelling techniques. They consist of two heterodimeric heavy chains which facilitate the potential to bind two different antigens or drug targets. Pure and stable Azymetric™ antibodies can be expressed in high yields while retaining natural IgG-like effector function and serum half-life.

 

2:05 Next-Generation Tri-Epitopic Anti-EGFR Antibodies: Overcoming Resistance by Enhanced Clustering and Downregulation

Jamie Spangler, Ph.D., Postdoctoral Research Associate, Departments of Molecular & Cellular Physiology and Structural Biology, K. Christopher Garcia Lab, Stanford University

Current EGFR-targeted therapeutics are hampered by resistance resulting from mutations in signal effectors downstream of the receptor. We present the design antibody-based fusion constructs that simultaneously target multiple epitopes of EGFR to induce receptor clustering and downregulation and demonstrate that our constructs ablate EGFR signaling and potently inhibit tumor growth in models of BRAF- and KRAS-mutant cancers.

2:35 High Affinity CD3 RECRUIT TandAbs for T Cell-Mediated Lysis of Malignant CD19+ B Cells

Uwe Reusch, Ph.D., Head, Cell Culture, Affimed Therapeutics AG (biography)

AFM11 is a CD19/CD3 bispecific tetravalent antibody that recruits T cells to CD19+ target cells resulting in their lysis. Functional assays including biosensor analysis on cells demonstrate that AFM11 is a highly efficacious novel drug candidate for the treatment of B cell malignancies with an advantageous safety profile.

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


3:50 Problem Solving Breakout Discussions

Concurrent problem solving breakout discussions, open to all attendees, speakers, sponsors, and exhibitors, provide a forum for discussing key issues and meeting potential collaborators. Plan to take part and explore these topics in-depth. Please pick a topic of your choice, find your table and join in.

In the Pipeline: Bispecifics in Development

Moderator: Germaine Fuh, Ph.D., Senior Scientist, Antibody Engineering, Genentech

• The strategies of bi or dual specific antibodies in development
• Do formats matter?
• Does ease of manufacturing matter

Building a Better Bispecific

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

• Current key technical issues in making bispecific antibodies
• Are there ways to select better building blocks for bispecific ?
• What biophysical/biochemical properties are required in a therapeutically viable bispecific antibody?
• How different bispecific antibody formats will impact upon biology and drug-like properties

Safety Challenges in Pre-Clinical Development

Moderator: Brian Swanson, Ph.D., Senior Director, Clinical & Exploratory Pharmacology, Sanofi

• Impact of anti-drug antibodies.
• Species-specific surrogate antibodies
• Screening for complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC)
• Adjustments in hERG, CV and CNS safety pharmacology, and mutagenicity testing (vs small molecule drugs)

Bispecifics Against Cell Surface Targets

Moderator: Robert Mabry, PhD, Group Leader, Antibody Engineering, Adimab, LLC

• When are bi-paratopics/bi-epitopics advantageous?
• Is there gaining momentum to apply bispecifics to GPCRs and other membrane spanning targets?
• How can you leverage avid interactions against membrane targets?
• Current state of combining ADCs with bispecifics

Consideration Factors and Regulations of Bispcific Antibody Development

Moderator: Jin-San Yoo, Ph.D., CEO, PharmAbcine, Inc.

• Target Combination for Higher Clinical Value
• Quality and Manufacturing Challenges
• Development of Key Analytical Assay Systems
• IND requirements for Phase I study
• Patients stratification for Clinical Trials

4:50-6:00 Networking Reception in the Exhibit Hall with Poster Viewing
Emerald BioPoster Awards Sponsored by



Day 1 | Day 2 | Download Brochure