2013 Archived Content
 

Oncology Stream

Inaugural
Advancing Bispecific Antibodies to the Clinic for Oncology

Review of Recent Results

May 1-2, 2013

Cancer represents one of the most intractable diseases and challenging areas of drug discovery, and bispecific antibody approaches are gaining widespread adoption by offering a multi-pronged and versatile approach for addressing cancer targets. This meeting will review preclinical and clinical results and investigate the remaining challenges for moving bispecific antibodies to the clinic.

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 Tuesday, April 30 from 4:15 - 5:30 PLENARY KEYNOTE PANEL 

Conventional vs. Non-Conventional Formats 

 Janice ReichertModerator: Janice Reichert, Ph.D., Editor-in-Chief, mAbs; Managing Director, Reichert Biotechnology Consulting LLC
With the explosion in the number of formats available, what are the potential benefits and risks to patients? This panel will discuss the realistic outlook and uncertainties with developing a diverse array of non-canonical antibodies in terms of immunogenicity, safety, competitive marketplace, commercial development, business strategies, regulatory approval, target validation and clinical development.
 

Panelists: 

David Meininger David Meininger, Ph.D., MBA, Executive Director, Molecular Discovery, Merck



 

Tillman GerngrossTillman Gerngross, Ph.D., CEO and Co-Founder, Adimab LLC; Professor, Bioengineering, Thayer School of Engineering, Dartmouth College


 

Trudi VeldmanTrudi Veldman, Ph.D., Senior Director, Biologics Generation, AbbVie



 


WEDNESDAY, MAY 1

7:00 am Conference Registration and Morning Coffee

8:30 Chairperson's Opening Remarks

Stanley R. Frankel, M.D., Medical Sciences Executive Medical Director, Amgen Rockville, Inc.


» KEYNOTE SESSION 

8:40 Bispecific Oncology Biologics: Challenges and Opportunities in Reducing R&D Cost and Enhancing Benefits to Patients

Rakesh DixitRakesh Dixit, Ph.D., DABT, Vice President, R&D, Global Head Biologics Safety Assessment, MedImmune

With the clinical success of bispecific armed antibodies, and antibody-drug conjugates, there is renewed enthusiasm in harnessing the benefits of two-in one antibodies. However, substantial preclinical, CMC and clinical challenges remain in the successful development of bispecific antibodies. The presentation will discuss the opportunities in reducing costs and enhancing the value of bispecific antibodies to patients through innovative technologies and smart drug development.

9:10 Clinical Applications of Bispecific T Cell Engaging Antibodies in Oncology

Stanley R. FrankelStanley R. Frankel, M.D., Medical Sciences Executive Medical Director, Amgen Rockville, Inc.

Bispecific T cell engager (BiTE®) antibodies possess dual specificity for CD3 and a target antigen of therapeutic interest. The most clinically advanced BiTE, blinatumomab, can transiently link CD19-expressing target cells to any cytotoxic T cell by bridging to the invariant CD3 epsilon subunit of the T cell receptor. The engaged T cell is redirected to lyse tumor cells that express the target antigen. BiTEs against other targets including EpCAM, CEA, and PSMA are at earlier stages of clinical investigation. The advances of the BiTE platform in the clinic will be reviewed.

9:40 Optimization of Bispecific DART Proteins for Oncology

Syd JohnsonSyd Johnson, Ph.D., Vice President, Antibody Engineering, Macrogenics

DART® proteins are stable and highly potent bispecific antibody derivatives with applications in oncology and autoimmunity. Multiple examples will be presented of DART proteins that redirect T-cells to tumor targets. Factors differentiating DART from other bispecific platforms will be discussed.


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


 preclinical and clinical data: understanding safety implications and lessons learned 

11:10 Concomitant Targeting of Her-Family Receptors through Antibody-Based Multi-Specific Therapies

David M. HilbertDavid M. Hilbert, Ph.D., CSO and Head, R&D, Zyngenia, Inc.

Tumor development is a function of multiple survival and resistance mechanisms that collectively lead to disregulated cell growth. Preclinical data will be presented that demonstrate concomitant targeting of Her-family receptors through antibody-based multi-specific therapies is an effective means of tumor killing.

11:40 SAR156597: An Innovative Bispecific IL-4/IL-13 Antibody as a Potential Treatment for Idiopathic Pulmonary Fibrosis

Ercole RaoErcole Rao, Ph.D., Group Leader, R&D Biologics Center Frankfurt, SANOFI Deutschland GmbH

SAR156597 simultaneously binds both IL-4 and IL-13 with high affinity and may attenuate the pathogenesis of idiopathic pulmonary fibrosis. SAR156597 suppresses IL-4/IL-13-mediated effects in vitro and allergen-induced airway hyperressponsivenes in sensitized monkeys. The safety, tolerability and PK of single subcutaneous doses of SAR156597 have been established in healthy human subjects.

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

1:40 Session Break


Preclinical and Clinical Data: Understanding Safety Implications and Lessons Learned 

2:00 Chairperson's Remarks

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

2:05 Selective Elimination of Cancer Cells Mediated by Dual-Targeting Triplebodies

Georg FeyGeorg H. Fey, Ph.D., Professor emeritus, Genetics, Department of Biology, University of Erlangen-Nuremberg

The two distal binding sites of a single-chain triplebody can simultaneously bind two antigens on the same cancer cell, the central site recruits effector cells via a trigger. Preferential lysis of antigen double-positive over single-positive cells is uniquely achieved by dual-targeting. Triplebody 33-16-123 eliminates both bulk acute myeloid leukemia (AML) cells and leukemia stem cells (LSCs) via targets CD33 and CD123 through the recruitment of CD16-bearing NK-cells. Data on triplebodies recruiting T-cells are also presented.

2:35 Network Biology-Driven Discovery and Development of Bispecific Antibodies in Oncology

Ulrik B. NielsenUlrik B. Nielsen, Ph.D., Senior Vice President & Chief Scientific Officer, Merrimack Pharmaceuticals

Bispecific antibodies offer the potential to create highly specific therapeutics, with greater potency and even have the ability to inhibit multiple targets. This makes the therapeutic design process extremely complex because specificity, affinity and valency all need to be optimized in parallel. In our design process, we employ computational network models to engineer bispecific antibodies that embrace these complexities and address issues of tumor cell heterogeneity and network redundancies.

3:05 F-star: Advancing Novel Bispecific Antibody Biologics in Oncology

John Haurum, D.Phil., M.D., CEO, f star

F-star’s Modular Antibody Technology uses straight forward “mix-and-matching” of antibody components to create unique mAb2 bispecific antibodies and allows rapid exploration of their novel biology. An Fcab against a single target, with a site introduced in the constant region, can either be developed as a therapeutic agent or be combined with the variable regions of different existing antibodies to create a panel of bispecific antibodies. F-star’s mAb2™ bispecific antibodies retain all conventional antibody properties such as Fc-mediated effector function, manufacturability, stability, and PK and can be progressed from Fcab™ to in vivo pharmacology testing in very short periods of time. F-star is now developing a preclinical oncology product pipeline based on this next generation biologics technology platform.

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing

4:20 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.

TABLE: Developing Bispecifics through Network Biology

Moderator: Ulrik B. Nielsen, Ph.D., Senior Vice President & Chief Scientific Officer, Merrimack Pharmaceuticals

   • Modeling to understand receptor mediated signaling
   • Computer simulation of bispecific antibodies for affinity, valency, down regulation, etc.
   • Translating simulation insights into clinical development

TABLE: Hurdles in the Development of Dual-Targeting Antibody-Derivatives Against Cancer

Moderator: Georg H. Fey, Ph.D., Professor emeritus, Genetics, Department of Biology, University of Erlangen-Nuremberg

   • Suitable format of dual-targeting antibody-agents: cross-mAbs, duo-mAbs, triplebodies?
   • Choice from the "zoo of dual-targeting formats"; agents with or without an fc-domain?
   • Manufacturing problems; production yields, stability issues
   • Choice of a suitable pair of target antigens on the cancer cell
   • Ability to eliminate cancer stem cells with dual targeting agents
   • Recruitment of suitable type of effector cells: NK-cells, macrophages, T-cells, granulocytes?
   • Dual-targeting of the effector cell rather than the cancer cell? Silencing inhibitory signals?
   • Dual-targeting chimeric antigen receptors (CARs) on T-cells?
   • Suitability mainly for hematologic malignancies or also for solid tumors?
   • Are there particular obstacles in adapting the formats to solid tumors?

TABLE: Epitope, Valency, and Affinity: The Holy Trinity When Designing Your Bispecific Antibodies for Oncology?

Moderator: Stanislas Blein, Ph.D., Head, Antibody Engineering, Biologics, Glenmark Pharmaceuticals S.A.

   • Which bispecific format to target multiple receptors or redirect T-cell killing?
   • Mixing and matching binders with different epitopes
   • Balancing affinities between the two antigen-binding sites
   • Mode-of-action

TABLE: When is Bi-Specificity Not Enough?

Moderator: David M. Hilbert, Ph.D., CSO and Head, R&D, Zyngenia, Inc.

   • How many variables influence tumor promotion and progression?
   • How does one define a “specificity”?
   • Clinical settings where bi-specificity may not be effective
   • Expanded therapeutic opportunities as a function of specificity and valency

Blue Sky Bioservices5:20 Networking Reception in the Exhibit Hall with Poster Viewing
 


6:15 Poster Award

6:30 End of Day



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