Cambridge Healthtech Institute’s Sixth Annual
Bispecific Antibody Therapeutics
Engineering Multispecificity
January 12-13, 2017 | Hilton San Diego Bayfront | San Diego, CA
Cambridge Healthtech Institute’s Bispecific Antibody Therapeutics conference explores the challenges of engineering multispecificity in order to achieve more effective therapies that bind to at least two molecular targets simultaneously. Next-generation
antibody formats are proving fruitful in the efforts to conquer cancer and other diseases. Case studies highlight novel engineering approaches that address safety, stability, enhanced targeting, and manufacturability, as the conference examines current
developments and also future directions of these promising molecules.
THURSDAY, JANUARY 12
7:45 am Conference Registration and Morning Coffee
8:15 Chairperson’s Opening Remarks
Christoph Spiess, Ph.D., Senior Scientist, Antibody Engineering, Genentech
FEATURED PRESENTATION
8:20 T-Cell Vaccination Using Bispecific Antibody Armed T-Cells (BATs)
Lawrence G. Lum, M.D., D.Sc., Professor, Medicine, Director, Cellular Therapy, and Scientific Director, BMT, University of Virginia
Specific cytotoxicity mediated by anti-CD3 activated T-cells (ATC) armed with anti-CD3 x anti-Her2 BiAb in breast, prostate, and ovarian cancer, anti-CD3 x anti-EGFR for lung, brain, and pancreatic cancer, anti-CD3 x anti-CD20 BiAb for non-Hodgkin’s
lymphoma and multiple myeloma, and anti-CD3 x anti-GD2 for neuroblastoma. BATs exhibit clinical activity and immune activity in both solid and liquid tumors.
9:00 The Use of Bispecific Antibodies to Modulate Anti-Tumor Immune Responses
Neil D. Brewis, Ph.D., CSO, F-star Biotechnology, Ltd.
An attractive alternative to combining two antibodies is the development of bispecific antibodies that not only bring two biologies together but may result in novel biological mechanisms that are impossible to attain with combinations. A murine-specific
anti-LAG-3 and PD-L1 bispecific antibody was engineered that binds both antigens simultaneously and with nanomolar affinities. This potency translates into in vivo efficacy, where the anti-LAG-3/PD-L1 bispecific antibody
decreased tumor burden in the MC38 colon carcinoma model.
9:30 Development of MCLA-128 - A Bispecific Antibody Targeting HER2 and HER3
Mark Throsby, Ph.D., Executive Vice President & CSO, Merus B.V.
A proprietary platform technology was applied to generate the Biclonics® MCLA-128, a human common light chain bispecific antibody targeting HER2 and HER3. MCLA-128 specifically and potently inhibits ligand dependent HER2:HER3 signaling resulting in
suppression of tumor growth in vitro and in vivo. This novel full-length bispecific antibody, that features ADCC enhancement, is undergoing clinical evaluation in a Phase I/II study
of patients with HER2+ tumors.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
11:00 Improving on Cancer Therapy: The Duobody Technology
Paul W.H.I. Parren, Ph.D., Senior Vice President & Scientific Director, Genmab A/S
The Duobody technology provides unsurpassed opportunities for the generation and development of bispecific antibodies (bsAb) as biopharmaceuticals. This presentation will highlight recent examples of Duobody molecules directed against a number of relevant
tumor targets.
11:30 Engineering Next-Generation Biotherapeutics: Developability & Manufacturability
Christopher Smith, Ph.D., Senior Scientific Consultant, Biologics, Genedata
Next-generation biotherapeutics, specifically bi- and multispecifics, alternative scaffolds, and ADCs, provide significant advantages over traditional IgG-based molecules. As highly engineered molecules, they pose new design, cloning, expression, purification,
and analytics challenges. Our workflow platform automates the engineering, production, and testing of large panels of these candidate therapeutic molecules. We demonstrate the platform’s capability to explore the huge combinatorial space of
novel molecule-specific designs, its high-throughput capability, and its built-in tools for developability and manufacturability assessments.
12:00 pm Session Break
12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:15 Ice Cream Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Remarks
Neil D. Brewis, Ph.D., CSO, F-star Biotechnology, Ltd.
2:05 Engineered Fab Domains Promote Efficient Production of Bispecific Antibodies in a Single Cell
Christoph Spiess, Ph.D., Senior Scientist, Antibody Engineering, Genentech
Bispecific antibodies have gained increased relevance in research and therapeutic settings despite the complexities in their production and challenges in finding the right combination. The presentation will discuss strategies and consideration to screen
for the best bispecific antibody pair. In addition, a novel approach to produce a bispecific antibody with natural architecture in a single cell will be discussed. The technology now simplifies bispecific production for research and development.
2:35 Design Principles for Bispecific IgGs – Opportunities and Pitfalls of Artificial Disulfide Bonds
Itai Benhar, Ph.D., Professor, Biotechnology, Tel Aviv University
We present a solution for correct pairing of heavy and light chains of bispecific IgGs; an engineered disulfide bond between the antibodies’ variable domains that asymmetrically replaces the natural disulfide bond between CH1 and CL. A novel
approach for precise evaluation of correct chain pairing by LC-MC-MS combined with chemical crosslinking is presented. Examples will be provided for some of these bsAbs and future directions of the study will be discussed.
3:05 A Stable Episomal Expression System to Streamline Antibody Production
Meelis Kadaja, Ph.D., MBA, Director, Business Development, Icosagen Technologies Inc.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15 Engineering Multivalent and Bispecific Death Receptor Agonists for Cancer Therapy
Eric Tam, Ph.D., Principal Scientist, Antibody Engineering, Merrimack Pharmaceuticals, Inc.
4:45 Production and Characterization of Bispecific Antibodies
Chen Gu, M.S., Research Associate, Protein Chemistry, Genentech, Inc.
The discovery of bispecific antibodies (bsAb) promised to usher in a new era of cancer treatment. However, the first generation bsAbs were difficult to produce and had limited efficacy. Since then, advances in antibody engineering and protein production
have resolved the production challenges, allowing for the evaluation of bsAbs for the treatment of a myriad of diseases. We will describe different approaches used at Genentech Inc. to produce and characterize bsAbs for pre-clinical evaluations.
Using a diverse toolbox, we can rapidly generate bsAbs for candidate selection. We will also describe the analytical testing that we employ to ensure we produce high purity bsAbs.
5:15 Antibody Based Nucleic Acid Delivery Vehicles
Ulrich Brinkmann, Ph.D., Expert Scientist, Pharma Research & Early Development, Roche Innovation Center Munich
Bispecific antibody derivatives can be applied for specific targeting of nucleic acids to and delivery into cells. Targeting of nucleic acids to desired cells can be achieved by ‘standard’ engineering approaches. Uptake into cells and
escape from vesicular compartments is a bottleneck that needs to be overcome to achieve intracellular activity.
5:45 Close of Day
FRIDAY, JANUARY 13
8:00 am Conference Registration and Morning Coffee
9:00 Chairperson’s Remarks
Mark Throsby, Ph.D., Executive Vice President & CSO, Merus B.V.
9:05 From DART to Trident: Tailoring Bi- or Multispecific Formats and Specificities for Different Therapeutic Modalities
Syd Johnson, Ph.D., Vice President, Antibody Engineering, MacroGenics, Inc.
This presentation will focus on the optimization of bi- and tri-specific formats for research and clinical use. Factors such as affinity, avidity or the valency of the binding domains and how they can influence and be optimized for specific indications
will be discussed. Examples will highlight several molecules in the DART or Trident formats to demonstrate the power and flexibility of the platform.
9:35 Utilizing the CrossMAb Engineering Platform to Suit Biological Needs
Jörg Thomas Regula, Ph.D., Head, Functional Characterization, pRED Large Molecule Research, Roche Diagnostics
GmbH
The CrossMAb technology (Schäfer, et al., 2011) can be used to generate a bispecific antibody from two independent parental antibodies by immunoglobulin domain exchange. Besides the initial CH1-CL domain exchange, the Vl-Vh domain exchange can
be enabled by the exchange of charged amino acids. This CrossMAb engineering toolbox can be used to design bispecific molecules to suit their biological need.
10:05 Coffee Break with a Poster Pavilion
Keynote Presentation
10:50 Bispecific T-Cell-Engaging BiTE Antibodies for Cancer Therapy
Benno Rattel, Ph.D., Executive Director, Nonclinical Development ARM, AMGEN Research (Munich) GmbH
Bispecific T-cell engagers, commonly referred to as BiTE® antibody constructs, can transiently link tumor cells with resting polyclonal T-cells for induction of a surface target antigen-dependent re-directed lysis of tumor cells. Blinatumomab
(BLINCYTO®) is directed against CD19 and is the first approved T-cell engaging antibody. The nonclinical characterizations of blinatumomab as well as of various BiTE® antibody constructs and their translation into the clinic will be presented.
11:30 Using Multivalent and Multispecific Nanobodies to Create Differentiated Drugs
Antonin De Fougerolles, Ph.D., CSO, Ablynx NV
This presentation will provide an outline of our Nanobody® platform, and how the flexibility of Nanobody formatting can be used to create differentiated drugs. My talk will include examples of multi-specific Nanobody drugs that are in preclinical
development and in the clinic.
1:15 Close of Conference