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Cambridge Healthtech Institute’s 2nd Annual
Immunomodulatory Therapeutic Antibodies for Cancer
Discovery and Development of the Next Wave of Checkpoint Inhibitors
August 11-12, 2014


Overview/Description:Speaker Biographies 

The 2011 approval of BMS’ ipilumumab, and a succession of favorable clinical data from the PD-1/PDL-1 programs of major pharmas including BMS, Merck, GSK/Amplimmune, Genentech and MedImmune is spearheading a new focus on immune system modulating antibody therapeutics. These results are now driving interest across academic and industry research into a next generation of checkpoint blockades and co-stimulatory factors, and the application of these to additional tumor types and in exciting new roles in combination treatment regimens.

But the path forward for this important direction in cancer treatment is not an easy one for researchers. The lack of relevant preclinical models, biomarkers and established clinical endpoints creates a challenge in demonstrating efficacy and advancing therapeutics through development. And the management of immune-related adverse events has become an important consideration in the development and clinical application of this class of biotherapeutics.

Immunomodulatory Therapeutic Antibodies for Cancer will explore the developments in the models and tools used by researchers working in preclinical and clinical development of these emerging drug products, and offer updates of emerging targets and indications.


Recommended Dinner Short Course*

Cancer Vaccines: Clinical Updates, New Technologies and Challenges 


*Separate registration is required.


MONDAY, AUGUST 11

7:30 am Conference Registration & Morning Coffee

8:35 Chairperson’s Opening Remarks

Laszlo Radvanyi, Ph.D., Chief Scientific Officer, Lion Biotechnologies


8:45 Keynote Presentation:

Putting Cancer in Check with Novel Immunomodulatory Strategies

Michael PostowMichael A. Postow, M.D., Assistant Attending Physician, Melanoma and Immunotherapeutics Service, Memorial Sloan-Kettering Cancer Center

Immunomodulatory antibodies that enhance T cell mediated immunity continue to demonstrate remarkable clinical success for patients with a variety of cancers. Antagonistic antibodies increase T cell function through blockade of negative regulatory circuits, and agonistic antibodies directly augment T cell function through engagement of various co-stimulatory receptors. Ongoing research seeks to identify why some patients have dramatic benefits to these approaches and to investigate whether combining these immunomodulatory antibodies with other cancer treatments improves outcomes.


RESEARCH & DEVELOPMENT

9:30 Tim-3 and Other Checkpoint Inhibitors that Induce T Cell Exhaustion and Tolerance

Vijay K. Kuchroo, DVM, Ph.D., Samuel L. Wasserstrom Professor of Neurology, Harvard Medical School

We have now identified cytokines and trasncription factors that induce Tim-3 expression in naïve T cells and marks these T cells for dysfunction. This signaling axis is crucial for induction of Tim-3 and other genes including Lag3 and IL-10, that are coordinately epxressed to induce T cell dysfunction in vivo. We are beginning to identify at a genomic level the modules that control the expression of Tim-3 with other checkpoint blockers and mechanism by which these inhibitory receptors are co-regulated in exhausted/dysfunctional T cells.

10:00 Coffee Break

10:30 Humanized Mice as Preclinical in vivo Models For NKT Cell-Based Cancer Immunotherapy

Weiming YuanWeiming Yuan, Ph.D., Assistant Professor, Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California

Despite overall conservation, subtle but important differences exist between CD1d/Natural Killer T (NKT) lipid presentation systems in humans and mice. We recently published the first hCD1d knock-in (hCD1d-KI) mouse. Now we further introduced human iNKT cell TCR into these mice. These humanized mice will allow more accurate in vivo modeling of human NKT cell responses to lipid drugs and facilitate preclinical assessment of lipid drugs for NKT cell-based immunotherapies.

11:00 Identification of Novel Immune Checkpoints as Targets for Cancer Immunotherapy

John Hunter, Ph.D., Site Head and Vice President, Antibody R&D, Compugen USA Inc.

Utilizing a predictive discovery platform, Compugen has identified nine target proteins predicted as immune checkpoints. Here we present results obtained for a novel immune checkpoint, CGEN-15049. CGEN-15049 inhibits the activity of NK cells and CTLs. The CGEN-15049 fusion protein displays robust inhibition of T cell activation and enhances iTregs differentiation. CGEN-15049 is expressed in tumor cells of numerous types of cancers and in tumor infiltrating immune cells. Based on its immunomodulatory activities and its expression pattern,CGEN-15049 may serve as mAb target for cancer immunotherapy.

11:30 Immunotherapy of Ovarian Cancer with Combination Enhanced Antigen Modulating Antibodies: Clinical Progress

Madi R. MadiyalakanMadi R. Madiyalakan, CEO, Quest PharmaTech

Quest uses specific antibody to enhance immunity to the target tumor antigen and associated tumor. We are using our lead product oregovomab to optimize combinations of chemotherapy and immune modulators in human clinical trials. Our randomized phase II confirming the effects of carboplatin paclitaxel in front line chemo-immunotherapy of ovarian cancer is pending analysis. We also are evaluating effects of TLR3 stimulation with Hiltonol in this setting, and the combination with Gemcitabine and radiation therapy in pancreatic cancer.

12:00 pm Phosphatidylserine (PS) Targeting Antibodies Enhances Activity of Immune Checkpoint Inhibitors by Repolarizing Immunosuppressive Immune Cells Populating the Tumor Microenvironment

Jeff Hutchins, Ph.D., Vice President, Preclinical Development, Peregrine Pharmaceuticals

PS is a phospholipid normally residing in the inner leaflet of the plasma membrane and becomes exposed on cells of the tumor microenvironment, promoting an immunosuppressive microenvironment (MDSCs, immature dendritic cells, M2 macrophages, anti-inflammatory cytokines). Bavituximab, a PS-targeting antibody, repolarizes this microenvironment, enhancing innate and adaptive anti-tumor immunity. We demonstrate PS targeting antibodies enhance anti-tumor activity of multiple forms of standard therapy, including anti-CTLA-4 and anti-PD-1 checkpoint inhibitor antibodies without the side-effects of systemic immune activation.

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own


IMMUNE MODULATORY TARGETS FOR ANTIBODY THERAPEUTICS

1:55 Chairperson’s Remarks

Dmitry I. Gabrilovich, M.D., Ph.D., Christopher M. Davis Professor in Cancer Research, Program Leader, Translational Tumor Immunology, The Wistar Institute

2:00 The Next Wave of Immune Checkpoint Modulator Targets

Paul D. RennertPaul D. Rennert, Founder & Principal, SugarCone Biotech Consultants LLC

Immuno-oncology therapy covers diverse approaches including immune checkpoint modulators, cytotoxic antibodies & ADCs, and bispecific modalities. To further improve cancer care we must understand how best to match therapeutics with specific patients. We must understand how to combine these therapies with genetically engineered T cells, diverse cancer vaccine approaches and targeted drugs. Further, we must discover the next generation of immune checkpoint, ADC and other therapeutic targets.

2:30 Emerging T Cell Checkpoint Regulators

Ana Carrizosa AndersonAna Carrizosa Anderson, Ph.D., Assistant Professor, Neurology, Harvard Medical School

The field of cancer immunotherapy has seen an explosion in therapies targeting the checkpoint receptors CTLA-4 and PD-1. While therapies that interfere with these receptor signaling pathways have been very promising in the clinic, a significant fraction of treated patients remain unresponsive to these therapies. This has prompted investigation into the possibility of targeting other immune checkpoints for the treatment of cancer. Data on emerging checkpoint targets will be discussed.

3:00 Myeloid-Derived Suppressor Cells – Emerging Regulators of Immune Responses

Dmitry I. Gabrilovich, M.D., Ph.D., Christopher M. Davis Professor in Cancer Research, Program Leader, Translational Tumor Immunology, The Wistar Institute

Myeloid-derived suppressor cells (MDSC) is a major factor responsible for tumor escape. These cells accumulate in large numbers in tumor-bearing hosts and are characterized by their myeloid origin, immature state, and, most importantly, by their potent ability to suppress different aspects of immune responses, primarily T-cell proliferation and cytokine production. These cells were found to correlate with clinical outcome of the diseases. Their targeting represents an attractive therapeutic opportunity.

3:30 Refreshment Break

4:00 Humanized Monoclonal Antibodies as Agonists for GITR or OX40 Signaling

Robert B. SteinRobert B. Stein, M.D., Ph.D., CSO, Agenus

We now know that there are many checkpoints in addition to CTLA-4 and PD-1. A new category of CPMs includes agonist antibodies targeting other checkpoint proteins, such as the receptors on T-lymphocytes called GITR and OX40. They stimulate anti-tumor immune responses and may play major roles in treating patients with a broad range of cancers. They can be developed as single agents and in optimized combinations, possibly including combinations with anti-cancer vaccines and other agents.

4:30 Costimulatory Pathways to Enhance Melanoma Adoptive T-Cell Therapy

Laszlo RadvanyiLaszlo Radvanyi, Ph.D., Chief Scientific Officer, Lion Biotechnologies

The infusion of expanded tumor-infiltrating lymphocytes (TIL), initially expanded from small 3-5 mm2 tumor fragments with IL-2, is a powerful therapy option for metastatic melanoma. This talk will present work on how we are beginning to manipulate T-cell costimulatory pathways in the tumor microenvironment in these early tumor fragment cultures, as well as at later stages of cell expansion, to generate TIL with enhanced survival and anti-tumor potential.

5:00 Comparative T Cell Costimulation by Targeting OX40, 4-1BB And TNFRSF25

Taylor SchreiberTaylor Schreiber, M.D., Ph.D., Chairman, Scientific Advisory Board, Pelican Therapeutics

OX40 and 4-1BB are well accepted T cell costimulators that diverge in their specificity for CD4+ or CD8+ T cells. TNFRSF25 is a highly related receptor with similar expression by T cells that has potent costimulatory activity of both CD8+ T cells and T regulatory cells. Here we will present a systematic comparison of the activity of each of these molecules during both primary and memory T cell mediated immune responses and in the context of therapeutic treatment of multiple murine tumor models.

5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

6:30 Close of Day


TUESDAY, AUGUST 12

7:45 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee


BIOMARKERS AND SURROGATE ENDPOINTS

8:25 Chairperson’s Opening Remarks

Llew Keltner, MD, PhD, CEO, EPISTAT

8:30 Challenges and Current Status of Developing Biomarkers for Cancer Immunotherapy

Janice MehnertJanice Mehnert, M.D., Associate Professor, Medical Oncology, Rutgers Cancer Institute of New Jersey




9:00 New Clinical Endpoint Concepts for Immunomodulatory Therapies

Llew KeltnerLlew Keltner, MD, PhD, CEO, EPISTAT

The promise of cancer immunotherapy for patients will only be realized if the most optimal combination immunotherapies are brought forward, as combinations. As a result, new models for combined regulatory and payer approval must be enabled in the clinical phases of drug development, and new clinical endpoints must be designed and validated. The FDA has strongly signaled that sponsors should work early and openly with the agency to build trials that can provide reasonable assurance of efficacy and safety, but can bring promising immunotherapies to market very rapidly. CMS and private payers are balking at mounting new-entity costs


EMERGING SCIENCE AND TARGETS

9:30 Novel Method for Suppression of Human Regulatory T Cells (Tregs) via Tnfr2 Antagonism

Denise FaustmanDenise Faustman, M.D., Ph.D., Director, Immunobiology; Associate Professor, Medicine, Immunobiology, Massachusetts General Hospital & Harvard Medical School

In cancer, overabundant Treg activity inhibits host defenses. Inhibiting Treg activity is a cancer approach. The recently discovered restricted tissue distribution of TNFR2 on human Tregs makes this receptor a possible therapeutic target. The generation of human directed TNFR2 monoclonal antibodies uncovered antagonists that inhibited Treg proliferation, signaling and function. Selective inhibition of Tregs through tissue restricted TNFR2 receptor allows the development of in vivo therapeutic regimens with decreased toxicity.

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

10:45 Preclinical and Clinical Evidence for Immune Checkpoint Modulation by ARGX-110, an Antibody Targeting CD70

Torsten Dreier, Ph.D., Chief Development Officer, arGEN-X BV, The Netherlands

11:15 Empowering Therapeutic Monoclonal Antibodies with a Biologic Payload for Cancers

Sanjay Khare, Ph.D., CEO, ImmunGene

We empower therapeutic antibodies by fusing them with IFN-alpha, thereby combining the targeting specificity of antibodies with the cytotoxic effects of IFN-alpha, which results in biologically pay-loaded antibodies that are more potent than native antibodies or soluble IFN-alpha. Data showing our molecules selectively targeting tumor cells while reducing the systemic toxicity of the payload and demonstrating considerably increased therapeutic index will be presented.

11:45 Modular Antibody Technology™ to Create Bispecific mAb2™
Jacqueline Doody, Vice President, Immunology, F-star Biotechnology Ltd 

F-star creates unique Fcab™s by engineering the constant region of antibodies against a single target, which can be developed as a mono-therapeutic agent or combined with the variable regions of differing antibodies to create a bispecific. F-star’s mAb2™ bispecific antibodies retain antibody properties such as Fc-mediated effector function, manufacturability, stability, and PK.

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

12:30 Close of Conference