PepTalk 2017
PepTalk 2017
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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.


Sunday, January 8

4:00 - 5:30 Short Course Registration

5:00 - 8:00 Dinner Short Courses*

Recommended Course: (SC1) Production Challenges for Complex Biologics: ADCs, Bispecifics and Fusion Proteins

* Separate registration required


TUESDAY, JANUARY 10

5:30 - 5:45 Short Course Registration

5:45-8:45 Dinner Short Courses*

Recommended Course: (SC9) Troubleshooting and Engineering of Antibody Constructs - Detailed Agenda

* Separate registration required

THURSDAY, JANUARY 12

7:45 am Conference Registration and Morning Coffee

BISPECIFICS TO FIGHT CANCER

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)

Larry_LumLawrence 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_BrewisNeil 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_ThrosbyMark 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_ParrenPaul 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_SmithChristopher 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

ENGINEERING INNOVATIONS

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

Christopher_SpiessChristoph 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.

Icosagen 3:05 A Stable Episomal Expression System to Streamline Antibody Production

Meelis_KadajaMeelis 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 Creating Multivalent Bispecific Antibody Forms through Bio-Conjugation

Julie Q. Hang, Ph.D., Senior Scientist, Protein Chemistry, Genentech

Bio-conjugation of multivalent bispecific Fab arms is achieved with branched PEGs carrying maleimides generated Fab multimers with variable valencies such as tetramers and octamers. The multivalent formats provide unique biological activities from high avidity and dosing options of two bispecific arms at variable ratios. The branched PEG had no interference on the activities of the multivalent bispecific Fabs. Case examples of multivalent bispecific generation and activity assessment are explored.

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

PLATFORM INNOVATIONS

8:30 Chairperson’s Remarks

Mark Throsby, Ph.D., Executive Vice President & CSO, Merus B.V.

8:35 Novel Bispecific Antibody Constructs for Targeting Tumor-Specific Carbohydrate Antigens

Steffen_GoletzSteffen Goletz, Ph.D., CEO and CSO, Glycotope GmbH

Carbohydrate targeting antibodies have great potential for the generation of bispecific antibodies. As shown for novel glyco-epitope targeting antibodies, carbohydrates on the surface of cancer cells represent promising targets for different approaches like dual-antigen targeting or effector cell recruitment. Tumor specificity and effector functions were shown by immunohistochemistry and antibody-dependent cellular cytotoxicity, respectively. Moreover, several constructs were generated to demonstrate the feasibility of carbohydrates as valuable targets for different bispecific approaches. The antibody constructs were glycooptimized for improvement of effector functions.

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

Joerg_RegulaJörg 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

ADVANCING BISPECIFICS INTO THE CLINIC

Keynote Presentation

10:50 Bispecific T-Cell-Engaging BiTE Antibodies for Cancer Therapy

Benno_RattelBenno 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

Tony_De_FougerollesAntonin 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.


12:00 pm IT’S A WRAP: PEPTALK 2017 CLOSING PLENARY PANEL DISCUSSION

1:15 Close of Conference