2016 Archived Content

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Cambridge Healthtech Institute’s 5th Annual
Bispecific Antibody Therapeutics
Engineering Multispecificity
January 21-22, 2016

Creating bioactive molecules that are multivalent and multifunctional offers the promise of more effective therapies. Empowered antibodies bind to at least two molecular targets simultaneously, thereby delivering a highly potent therapeutic, particularly for cancer. The Bispecific Antibody Therapeutics meeting explores the challenges of engineering multispecificity to ensure stability and efficacy, and reviews the numerous forms of multispecific antibodies in development, including next-generation antibody formats. Case studies highlight safety issues, along with preclinical and clinical data. Join colleagues from around the world in this discussion of the exciting breakthroughs in engineering antibodies, and see how cancer and other applications are advancing into a true therapeutic revolution.

Final Agenda

THURSDAY, JANUARY 21

7:45 am Conference Registration and Morning Coffee

8:15 Chairperson’s Opening Remarks

Robert Mabry, Ph.D., Director, Protein Sciences and Antibody Technology, Jounce Therapeutics

KEYNOTE PRESENTATION

8:20 Advancement in Novel Bispecific Biotherapeutics: Challenges and Opportunities

Rakesh_Dixit Rakesh Dixit, Ph.D., DABT, Vice President, Research & Development, and Global Head, Biologics Safety Assessment, MedImmune

Advancement in protein engineering has revolutionized the development of bipspecific biologics. There are more than 50 different formats/platforms through which multiple targets or functions can be modulated with one molecule. Despite overcoming many protein engineering challenges, there are newer CMC, manufacturing PK, immunogenicity, safety, efficacy challenges in the preclinical and clinical development. The presentation will provide a start-of-art overview of bispecific antibodies with opportunities to overcome challenges.

9:00 Bispecific Antibodies: Strategies, Considerations and Challenges

Christoph_Speiss Christoph Spiess, Ph.D., Senior Scientist, Antibody Engineering, Genentech, Inc., a member of the Roche Group

Bispecific antibodies are moving mainstream as therapeutics with currently two bispecific antibodies approved and about 30 in clinical development. The presentation will discuss novel approaches to produce bispecific antibodies in a single cell as well as strategies to screen for the best bispecific antibody. This includes considerations for designing bispecifics to match the proposed mechanism of action and intended clinical application.

9:30 Facile Generation of Common Light Chain Bispecific Antibodies

Paul_Windboom Paul Widboom, Ph.D., Senior Scientist, Antibody Engineering, Adimab LLC

A variety of bispecific constructs benefit from the use of a single variable light region pairing with multiple heavy regions. This talk will demonstrate the facile engineering of multiple VHs that pair with a single light chain. A panel of bispecific antibodies are generated to bind to each target with high affinity and exhibit favorable biophysical properties similar to traditional therapeutic antibodies.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 Updates on BiTE® Technology and Development Programs

Matthias_Klinger Matthias Klinger, Ph.D., Principal Scientist, BiTE Immunology, AMGEN Research Munich GmbH
BiTE® antibody constructs have reached the market with the recent conditional approval of blinatumomab for the treatment of Philadelphia chromosome-negative relapsed or refractory acute lymphoblastic leukemia by the U.S. Food and Drug Administration. This presentation will provide an update on further progress of blinatumomab as well as of other BiTE® antibody constructs in early clinical development. Additionally, the evolution of the BiTE® technology will be discussed.

11:30 Engineering Next-Generation Biotherapeutics: Developability & Manufacturability

Christopher Smith, Ph.D., Senior Scientific Consultant, Biologics, Genedata

Next-gen biotherapeutics, specifically bi- and multispecifics, alternative scaffolds, and ADCs, provide many 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 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

James Ernst, Ph.D., Senior Scientist, Protein Therapeutics, Genentech, Inc., a member of the Roche Group

2:05 CrossMAb Vh-Vl

Joerg_Regula Jörg Thomas Regula, Ph.D., Head, Functional Characterization, Large Molecule Research, Roche Pharma Research & Early Development

The CrossMAb technology can be used to generate a bispecific antibody from two independent parental antibodies by immunoglobulin domain exchange. The three different CrossMAb designs were named for their exchanged domains: CH1-CL, Vh-Vl and Fab. The CrossMAb CH1-CL was used for the Ang2-VEGF CrossMAb. Additional modifications renders the CrossMAb Vh-Vl to a suitable alternative. The CrossMAb technology enables several bispecific molecules with 1+1, 2+1 or 2+2 binding sites.

2:35 Bispecific FynomAbs: Novel Modes of Action through Tailored Architecture

Michela Silacci Melkko, Ph.D., Director, Discovery Research, Covagen AG, one of the Janssen Pharmaceutical Companies of J&J

Covagen develops bispecific FynomAbs by fusing its Fynomer binding proteins to antibodies resulting in multi-specific therapeutics with novel modes-of-action and enhanced efficacy. FynomAbs have optimal biophysical and pharmacokinetic properties, making them attractive as drug candidates. Here we present the discovery and development of COVA322, a clinical-stage bispecific TNF/IL-17A inhibitor for the treatment of inflammatory diseases. Furthermore, FynomAbs with tailored anti-tumor activities will be presented.

3:05 POSTER SPOTLIGHT
Engineered Bispecific Antibodies with Improved Developability
Srinath Kasturirangan, Ph.D., Scientist 1, MedImmune LLC

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

4:15 Optimization and Application of an Fc-Containing Bispecific Platform

Matthew_Bennett Matthew J. Bernett, Ph.D., Senior Scientist, Protein Engineering, Xencor, Inc.

Xencor has developed a new platform for long-lived and easy-to-manufacture bispecific antibodies. We have applied it to rapidly produce CD3 bispecific antibodies targeting CD123 for AML, CD20 for B cell malignancies, and CD38 for multiple myeloma. Each antibody is shown to be potently active in non-human primate studies, and GMP manufacturing is straightforward with yields over 2 g/L. Application to multiple formats and target combinations will be discussed.

4:45 The DuoBody Technology: A Versatile Platform for Bispecific Antibody Discovery and Development

Paul_Parren Paul W.H.I. Parren, Ph.D., Senior Vice President & Scientific Director, Genmab BV

The DuoBody platform is based on the convenient post-production method of controlled Fab-arm exchange which yields bispecific antibodies that retain the time-honored molecular structure and quality attributes of therapeutic IgGs. The process is proven to be highly robust with linear scalability from bench to manufacturing scale. This presentation will highlight recent advances in the application of the DuoBody technology for randomized library generation and screening of large antibody panels.

5:15 Development of Bispecific AffiMab Antibody Engineered using Affibody Molecule for Target Therapy

Kyu-Tae_Kim Kyu-Tae Kim, Ph.D., Director, ADDs Program, AbClon

Antibodies are functionalized using Affibody Molecules to create bispecific AffiMabs. AffiMab is an innovative bispecific antibody generated from a genetic link between therapeutic antibody and Affibody molecule. AffiMab efficiently targets two disease proteins simultaneously and it contains full human IgG functions with increased specificities. ADA-zIL6 is an AffiMab simultaneously targeting the IL-6 and TNF. ADA-zIL6 blocks combined IL-6 and TNF-triggered serum amyloid A secretion in vivo.

5:45 Close of Day

6:00-7:00 Reception in the Tiki Pavilion

FRIDAY, JANUARY 22

8:00 am Conference Registration and Morning Coffee

8:30 Chairperson’s Remarks

Paul Widboom, Ph.D., Senior Scientist, Antibody Engineering, Adimab LLC

8:35 Preclinical Development of the Tribody Tb535, a 5T4 Targeting Bispecific T-Cell Engager

Nico_Mertens Nico Mertens, Ph.D., Vice President and Head, Antibody Research, R&D, Biotecnol Ltd.

Tribodies use the natural heterodimerization present in a Fab molecule to create trivalent or trispecific recombinant antibody fragment fusion proteins. Biotecnol used its Tribody platform to create Tb535, a fully humanized bispecific antibody fragment which binds bivalently to the oncofoetal glycoprotein 5T4 and monovalent to the T-cell activating CD3 cluster. Tb535 is a highly stable molecule with excellent manufacturability properties and is highly active against a wide range of carcinomas.

9:05 A Novel Tissue-Specific Agonist of the FGF21 Pathway for the Treatment of Type 2 Diabetes

James_Ernst James Ernst, Ph.D., Senior Scientist, Protein Therapeutics, Genentech, Inc., a member of the Roche Group

Type 2 diabetes is a large and growing healthcare problem throughout the world. Activation of the FGF21 pathway has been shown to improve several features of type 2 diabetes in mice and humans. We have discovered a novel bispecific antibody that mimics the function and metabolic effects of FGF21. Treatment with this antibody improves glycemic and lipid profiles in mouse disease models, and reduces weight in mice and non-human primates.

9:35 Getting TRAIL Back on Track: RG7386, A Novel Bispecific FAP-DR5 Antibody for the Treatment of Cancer

Oliver Krieter, M.D., Senior Translational Medicine Leader, pRED Innovation Center Penzberg, Roche

Activation of the extrinsic apoptotic pathway by TRAIL is dependent on clustering of death receptors (DR) on the surface of cells. However, current TRAIL-based strategies have proven ineffective in clustering DRs, hence in extrinsic pathway activation and failed to demonstrate robust activity in clinical trials. RG7386 is a novel bispecific FAP-DR5 antibody, binding with high affinity to fibroblast activation protein (FAP) and with low affinity to DR5.

10:05 Coffee Break with a Poster Pavilion

PepTalk is proud to support and recognize the protein scientists of tomorrow during the Poster Pavilion. This time has been set aside to view the Student Fellowship posters and interact with presenters one on one. This opportunity gives job seekers the chance to share their expertise with future/potential employers or develop contacts to further their research.

11:00 Modular mAb2 Technology Enables Rapid Assessment of Bispecific Modality

Mateusz_Wydro Mateusz Wydro, Ph.D., Principal Scientist, Protein Sciences, F-star Biotechnology, Ltd.

One of the bottlenecks of bispecific approach is the lengthy process of generating stable molecules with sufficient quality and quantity to enable functional assessment and in vivo PoC studies. F-star’s proprietary modular antibody technology addresses this limitation by a robust “plug and play” process so multiple modalities can be produced and assessed in parallel; this makes it possible to pick the best candidates efficiently and confidently.

11:30 The BEAT Bispecific Antibody Technology: An Industry-Applicable Platform for the Development of Highly Potent Biologics

Greg_Elson Greg Elson, Ph.D., Vice President, Biologics Manufacturing, Glenmark Pharmaceuticals

Glenmark Pharmaceutical`s BEAT® format is a robust and versatile bispecific heavy chain hetero-dimerization technology based on a unique concept of bio-mimicry. Several T cell recruiting bispecific antibodies against different cancers are currently under evaluation, with GBR 1302 being Glenmark’s most advanced development candidate. This BEAT® antibody potently re-directs T cells to HER2 positive cancer cells and demonstrates strong tumour cell lysis activity. Bioprocess and preclinical biological data will be presented.

IT’S A WRAP:
PEPTALK 2016 CLOSING PLENARY PANEL DISCUSSION
Friday, January 22, 12:00 pm

Protein therapeutics is one of the fastest-growing global markets, driven by increasing adoption of protein- over non-protein drugs, growing funding for protein engineering and reduced drug discovery timelines and costs. As the science improves, so does the complexity of the R&D organization: it really does “take a village” to bring nextgeneration therapies to market and patients who need them. Ensuring product quality plus speed to market requires collective insights from experts working across the stages of protein science R&D – as embodied by panelists representing each PepTalk Pipeline topic.

They discuss: