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Cambridge Healthtech Institute’s 2nd Annual
Next-Generation Cancer Immunotherapies
New Targets and Pathways, Immunotherapy Combinations, Translational Strategies and Intellectual Property Updates to Support Entry into the Surging Cancer Immunotherapy Space
January 18-19, 2016

A succession of strong clinical successes with antibodies against checkpoint targets has spawned a surge of interest from across the industry in the development of antibody immunotherapeutics and agents that perform well in treatment combinations. The major challenges facing those now entering the field include establishing clinical proof of concept, product and target differentiation, selection of patient responders and the identification of effective treatment combinations. The Next-Generation Cancer Immunotherapies conference offers presentations of innovative approaches to checkpoint inhibition, protein engineering strategies to improve the efficacy of immunotherapies, the application of bispecific antibody platform to immunotherapy target pairs and ideas for approaching the development of novel IP in this crowded space.

Final Agenda

MONDAY, JANUARY 18

7:30 am Conference Registration and Morning Coffee

9:00 Chairperson’s Opening Remarks

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


KEYNOTE PRESENTATION

9:10 The Current State of Science in Immunotherapy: A Review of Pembrolizumab and Other Checkpoint Inhibitors

Michael_RosenzweigMichael Rosenzweig, DVM, Ph.D., Executive Director, Immuno-oncology, Merck Research Laboratories

Cancer immunotherapy has been revolutionized by the recent clinical successes of checkpoint blockades. Pembrolizumab, a checkpoint inhibitor, is an investigational, selective, humanized, monoclonal anti-PD-1 antibody designed to block the interaction of PD-1 on T-cells with its ligands to reactivate anti-tumor immunity. Pembrolizumab is being evaluated across more than 30 types of cancers, as monotherapy and in combination, and we are exploring different tumor characteristics such as PD-L1 expression as predictors of responsiveness.


PROTEIN ENGINEERING STRATEGIES FOR TARGETED IMMUNOTHERAPIES

9:50 Conformation of the Human Immunoglobulin G2 Hinge Imparts Superagonistic Properties to Immunostimulatory Anticancer Antibodies

Ann_WhiteAnn White, Ph.D., Senior Research Fellow, Cancer Sciences Unit, Southampton University

Monoclonal antibodies designed to stimulate anti-tumour immunity by engaging stimulatory receptors, such as CD40, 4-1BB and CD28, on immune cells generally require Fcγ receptor mediated cross-linking for activity. We demonstrate that human IgG2 is uniquely agonistic independent of FcγR interaction due to a structurally constrained conformation achieved through hinge region disulphide rearrangment. This allows the engineering of reagents with defined therapeutic activity regardless of FcγR expression levels in the local microenvironment.

10:20 Coffee Break

10:45 Modulation of in vivo Dynamics of Antibodies

Sally_WardE. Sally Ward, Ph.D., Professor, Molecular and Cellular Medicine, Texas A&M Health Science Center

FcRn-IgG interactions can be engineered to modulate the in vivo dynamics of antibodies and their target antigens. This is being combined with the use of fluorescence microscopy to inform the subcellular trafficking behavior of the engineered proteins. The presentation will cover recent developments on these topics.


11:15 In vivo Efficacy of a Bispecific Antibody Targeting EGFR and CTLA-4

Mihriban TunaMihriban Tuna, Ph.D., Vice President, Discovery, F-star GmbH & F-star Biotechnology Ltd.

A bispecific antibody was generated by engineering the constant region against EGFR and combining with the variable domain of CTLA-4. The ensuing EGFR/CTLA-4 bispecific showed efficacy in an in vivo model compared to either EGFR or CTLA-4 alone. Efficacy of the bispecific in the mouse model did not correlate with Treg depletion, suggestive of a novel biology.

11:45 Preclinical Evaluation of an Agonist Antibody Targeting ICOS

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

Jounce is developing an agonistic antibody to the co-stimulatory molecule ICOS. Preclinical studies demonstrate that anti-ICOS agonistic antibodies are efficacious in syngeneic tumor models, with enhanced efficacy observed in combination with PD-1 inhibition.

12:15 pm Sponsored Presentation (Opportunity Available)

12:45 Session Break

1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own


DEVELOPMENT OF BISPECIFIC ANTIBODIES FOR CANCER IMMUNOTHERAPY

2:00 Chairperson’s Remarks

Shyra Gardai, Ph.D., Principal Scientist, Preclinical Research, Seattle Genetics

2:05 Case Study: Development Challenges of BiTE® Antibodies for Cancer Immunotherapy

Richard_SmithRichard Smith, Ph.D., Director, Research, Protein Technologies, Amgen, Inc.

Bispecific T-cell Engager (BiTE®) antibody constructs enable specific targeting of cytotoxic T cells to tumors. Following clinical validation of this approach with the recently approved BLINCYTO™ (blinatumomab) we are advancing the platform with a discovery engine that integrates the identification of new targets with the development of BiTE® antibody constructs with improved pharmacokinetic properties.

2:35 Anti-CD20/CD3 T Cell Dependent Bispecific Antibody (TDB) as Potential Therapy for B Cell Malignancies

Laura_SunLaura Sun, Ph.D., Principal Research Associate, Translational Oncology, Genentech, Inc.

The preclinical development of a B cell targeting anti-CD20/CD3 T cell dependent bispecific antibody (CD20-TDB) will be described. CD20-TDB is highly active in killing B cells in vitro and in vivo as demonstrated in multiple murine models. In cynomolgus monkeys, CD20-TDB potently depletes B cells in peripheral blood and lymphoid tissues while demonstrating PK properties similar to those of conventional monoclonal antibodies.

3:05 Next-Generation Bispecific Immunomodulatory Antibodies for Tumor Directed Immune Activation

Peter_EllmarkPeter Ellmark, Ph.D., Principal Scientist, Research, Alligator Bioscience AB

Increasing the response rate while minimizing toxicity can be achieved by combining agents towards different immune modulatory targets and by directing the immune activation to the tumor. Intratumoral administration is currently evaluated in the clinic with a CD40 agonistic antibody (ADC-1013). In addition, bispecific antibodies targeting two different immunomodulating receptors provides new opportunities to increase the effect and direct the immune system to the tumor.

3:35 SELECTED POSTER PRESENTATION
Notch Antibodies: Potential Cancer Immunotherapeutics

Rajan Dighe, Ph.D., Professor, Molecular Reproduction Development and Genetics, Indian Institute of Science

3:50 Refreshment Break in the Exhibit Hall with Poster Viewing

4:30 Chemically-Generated Immunomodulatory Bispecific Antibodies

Yanwen_FuYanwen Fu, Ph.D., Associate Director, Antibody Technologies and Chemical Biology, Sorrento Therapeutics

Bispecific antibodies (BsAbs) capable of engaging cytotoxic T lymphocytes for tumor cell lysis are emerging as a new option for cancer treatment. Sorrento has developed a robust platform to generate BsAbs through hetero-dimerization of two chemically-modified half antibodies. Using this approach, we synthesized a variety of immunomodulatory bispecific IgGs and F(ab)2. Results from BsAb assembly, biophysical characterization and effector-cell mediated cytoxicity assays will be presented.


INTELLECTUAL PROPERTY ISSUES FOR CANCER IMMUNOTHERAPY

5:00 Intellectual Property Review of Major Immunotherapy Targets: Non-Composition of Matter Approaches to Developing Unique IP in Cancer Immunotherapy

Konstantin_LinnikKonstantin M. Linnik, Ph.D., Partner, Intellectual Property, Nutter, McClennen & Fish, LLP

Immunoncology IP is crowded – the number of drugs in R&D far exceeds the number of targets. Navigating the IP around major targets is critical but, more importantly, every drug developer faces challenges in protecting its own intellectual property. What are the patenting approaches that allow entry into this crowded IP space, while preserving the broadest scope of protection?

5:45 BuzZ Session A

Join your peers and colleagues for interactive roundtable discussions.

Freeslate6:30-7:45 Welcome Reception in the Exhibit Hall with Poster Viewing


7:45 Close of Day

TUESDAY, JANUARY 19

8:00 am Conference Registration and Morning Coffee


NEXT-GENERATION STRATEGIES FOR TARGETING CHECKPOINT INHIBITORS

8:30 Chairperson’s Remarks

Peter Ellmark, Ph.D., Principal Scientist, Research, Alligator Bioscience AB

8:35 Clinical Updates for Novel Targets and Pathways

Bernard_FoxBernard A. Fox, Ph.D., Harder Family Chair and Chief, Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Providence Cancer Center

Clinical success of novel immunotherapies in tumors other than melanoma is fueling a sea change, and observations of a strong T cell infiltrate being a good prognostic factor, independent of tumor stage, are providing insight into the mechanisms responsible. We are performing assessments of gene signatures to guide an evaluation of the tumor with multispectral imaging and objective assessment tools. This information will be used to guide treatment decisions.

9:05 Characterization and In Vivo Evaluation of Blocking Antibodies Against GARP, a Novel Immune Checkpoint Target

Bas van der WoningBas van der Woning, Ph.D., Principal Scientist, arGEN-X, Belgium

GARP is required for TGF-β activation from Tregs. We have identified anti-GARP antibodies which inhibit active TGF-β production from human Tregs. Using a model of xenogeneic graft-versus-host disease induced by transplantation of human PBMCs in NSG mice, we show that blocking antibodies against hGARP inhibit the immune suppressive function of human Tregs in vivo. mAbs against GARP that inhibit human Treg function may therefore represent new immunotherapeutic approaches for the treatment of cancer.

9:35 SELECTED POSTER PRESENTATION
Rapid Fine Conformational Epitope Mapping Using Comprehensive Mutagenesis and Deep Sequencing

Caitlin Kowalsky, Ph.D. Candidate, Whitehead Lab, College of Engineering, Michigan State University

9:50 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 Proxinium, an Anti-EpCam-PE40 Targeted Protein Therapeutic (TPT) Mediates Direct Anti-Tumor Efficacy and Induces Anti-Tumor Immune Responses

Greg_AdamsGregory Adams, Ph.D., Chief Development Officer, Viventia Bio

TPTs mediate direct tumor killing and offer the ability to activate anti-tumor immunity. In early phase clinical studies, intratumoral injection of Proxinium mediated impressive effects directly on injected tumors and indirectly on uninjected tumors, suggesting the generation of an anti-tumor immune response. Clinical trial results and preclinical studies will be presented both examining the mechanisms underlying the indirect anti-tumor effect and evaluating the potential of combining Proxinium with checkpoint inhibitors.

11:30 A Sugar Engineered Non-Fucosylated Anti-CD40 Antibody, SEA-CD40, with Enhanced Immune Stimulatory Activity Alone and in Combination with Immune Checkpoint Inhibitors

Shyra J. Gardai, Ph.D., Principal Scientist, Immunology, Seattle Genetics

SEA-CD40 is a novel first-in-class therapeutic antibody using Seattle Genetics’ proprietary sugar-engineered antibody (SEA) technology. Preclinically, SEA-CD40 mediates enhanced CD40 signaling to antigen-presenting cells resulting in robust APC activation and expansion of tumor-associated antigen specific T-cells. While SEA-CD40 drives immune activation as a single agent, it also demonstrates substantial combinatorial activity with immune checkpoint inhibitors preclinically.

12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Session Break

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:45 Close of Conference



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