Despite the success of immunomodulatory antibodies in immuno-oncology, challenges remain in expanding the target space, engineering next-generation antibodies with improved efficacy and safety, and addressing innate and acquired resistance to immunotherapy. CHI’s Sixth Annual Immunomodulatory Therapeutic Antibodies for Cancer meeting will explore next-generation immunotherapies, emerging targets and combinations, and strategies for overcoming resistance. It will provide case studies of antibody development in immuno-oncology from preclinical to clinical development.

Final Agenda

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MONDAY, AUGUST 27

7:30 am Registration & Morning Coffee

THERAPEUTIC STRATEGIES TO OVERCOME IMMUNE EVASION AND RESISTANCE TO CHECKPOINT INHIBITORS

8:25 Chairperson’s Opening Remarks

Osama Rahma, MD, Assistant Professor, Medicine, Harvard Medical School; Center for Immuno-Oncology, Dana-Farber Cancer Institute

8:30 Overcoming Resistance to PD-1 Inhibition in Pancreatic Cancer

Osama Rahma, MD, Assistant Professor, Medicine, Harvard Medical School; Center for Immuno-Oncology, Dana-Farber Cancer Institute

Pancreatic cancer doesn’t respond traditionally to immunotherapy including PD-1 inhibitors. This is due to the immune suppressive microenvironment and the lack of tumor infiltrating lymphocytes making pancreatic cancer known as an “immune desert.” We are currently investigating multiple strategies to overcome pancreatic cancer resistance to immunotherapy including combinational approaches of immunotherapies, radiation and chemotherapy.

9:00 Tumor-Mediated Modulation of Immunometabolism as a Mechanism of Immunotherapy Resistance: Implications for Combination Immunotherapy Development

Brent Hanks, MD, PhD, Assistant Professor, Cancer Immunology/Immunotherapy, Duke Cancer Institute, Duke University School of Medicine

We will discuss recently identified mechanisms by which tumors evade the host immune response by metabolically reprogramming the local immune microenvironment. This will include a discussion of novel pharmacologic strategies capable of reversing these pathways and enhancing the effectiveness of checkpoint inhibitor immunotherapy.

9:30 Tgfβ Attenuates Tumour Response to PD-L1 Blockade by Contributing to Exclusion of T Cells

Alessandra Castiglioni, PhD, Senior Scientific Researcher, Cancer Immunology, Genentech

CD8+ T-effector cell phenotype and high tumor mutation burden are predictors of good responses to therapy with atezolizumab in patients with metastatic urothelial cancer. Lack of response is associated with TGFβ signaling in fibroblasts, especially in patients with an immune-excluded phenotype. Combining TGFβ blockade with anti-PD-L1 antibody in mouse models with the same phenotype increases the anti-tumor efficacy of the therapy, reduced TGFβ signaling in stromal cells and facilitated T-cell penetration into the tumors.

10:00 Coffee Break

10:30 Strategies to Enhance Tumor Antigen Presentation and Interferon Response in Cancer: Implications for Immuno-Molecular Combinations

Justin Balko, PharmD, PhD, Assistant Professor, Medicine, Vanderbilt University Medical Center

Immunotherapies have changed the landscape of cancer treatment in a variety of tumor types. However, many tumors do not respond to the first generation of therapeutic antibodies targeting the immune system, such as anti-PD-1. While a variety of mechanisms may underlie acquired and intrinsic resistance to immunotherapy, anti-tumor immunity can be thwarted by ineffective antigen presentation by MHC-I and MHC-II and poor interferon responsiveness. Preclinical therapeutic strategies to overcome these factors and their translation to clinical trials will be discussed.

11:00 Therapeutic Manipulation of Tumor Microenvironment to Improve Immune Response in Tumors

Allison Betof Warner, MD, PhD, Medical Oncology Fellow, Medicine, Memorial Sloan Kettering Cancer Center

Tumors are not simply collections of cancer cells that arise in a vacuum; they are instead complex structures composed of blood vessels, immune cells, and other supporting structures that interact, consume oxygen and other nutrients, and produce waste. Tumor microenvironment has long been viewed as a therapeutic target. I will discuss recent data on how microenvironmental factors, including changes in angiogenesis, metabolism, and exercise, influence immunobiology and our group’s approach to harness these interactions to improve therapeutic outcomes using murine models.

11:30 Long Term Time-Course Monitoring of NK Cell-Mediated ADCC Using the Celigo Image Cytometer

Leo Chan, Technology Research & Development Manager, Nexcelom Bioscience LLC

The traditional release assays for ADCC is inaccurate due to indirect measurement of supernatant for 4 hours. We demonstrated time-course monitoring of NK-mediated ADCC of A375 cells for 76 hours, and showed ADCC killing with decrease in ZsGreen cells. This can better characterize the effects of target antibodies on ADCC.

11:45 Sponsored Presentation (Opportunity Available)

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

12:30 Session Break

EMERGING IMMUNE CHECKPOINT TARGETS

1:25 Chairperson’s Remarks

Xingxing Zang, PhD, Louis Goldstein Swan Endowed Chair and Professor, Microbiology and Immunology & Medicine, Albert Einstein College of Medicine

1:30 FEATURED PRESENTATION: New Immune Checkpoints for Human Cancer Immunotherapy

Xingxing Zang, PhD, Louis Goldstein Swan Endowed Chair and Professor, Microbiology and Immunology & Medicine, Albert Einstein College of Medicine

Dr. Zang will discuss expression, function, structure, and immunotherapy of immune checkpoints HHLA2, TMIGD2, B7x, B7-H3, ICOS, and Tim-3.

2:00 Understanding Immune Checkpoint TIM-3 Biology and Implications for Targeting TIM-3 for Cancer Immunotherapy

Xiaomo Jiang, PhD, Investigator, Immuno-Oncology, Novartis Institutes for BioMedical Research

TIM-3 has critical roles in tumor-induced immune suppression on a multitude of cell types. TIM-3 blockade to activate immune response and control tumor growth could reflect the combined effects on modulating not only the functional phenotype of dysfunctional effector T cells, but also inhibiting the suppressive activity of various suppressor cells.

2:30 Targeting the CD200 Checkpoint Blockade: A New Avenue for Immunotherapy

Michael Olin, PhD, Assistant Professor, Pediatrics, University of Minnesota; CSO, OX2 Therapeutics

The CD200 immune checkpoint interferes with tumor-immune interactions through multiple mechanisms: i) CD200 is secreted from tumors to the graining lymph nodes where it induces an immunosuppressive environment, ii) CD200 is upregulated in tumor-associated vascular endothelial cells, creating an immunological barrier around the tumor microenvironment, and iii) CD200 within tumor-derived vaccines suppresses an antitumor response. To combat the suppressive mechanisms of CD200, we synthesized inhibitors of the CD200 checkpoint.

3:00 Breakout Discussion Groups and Refreshment Break

This session features discussion groups that are led by a moderator who ensures focused conversations around the key issues listed. Attendees choose to join a specific group, and the small, informal setting facilitates sharing of ideas and active networking. Details on the topics and moderators are available on the conference website.

4:15 FEATURED PRESENTATION: The Development of Agonist OX40 Monoclonal Antibody for Cancer Immunotherapy – Navigating the Bench to Bedside Journey

Niranjan Yanamandra, PhD, Scientific Director, Translational Research, Immuno-Oncology & Combinations DPU, Oncology R&D, GlaxoSmithKline

OX40 is a member of the tumor necrosis factor receptor (TNFR) superfamily and a co-stimulatory molecule expressed on the surface of activated CD4+ and CD8+ T cells. OX40 agonism stimulates both immune effector and memory functions while attenuating the function of immunosupressive regulatory T cells (Tregs). GSK317998, a humanized IgG1 agonistic anti-OX40 monoclonal antibody (mAb) is currently in Phase I clinical development. This presentation will review preclinical and translational research data to support OX40 clinical development.

4:45 Anti-OX40 Treatment in Humans Increases the Frequency of Tumor Ag-Specific T Cells

Andrew Weinberg, PhD, Chief, Laboratory of Basic Immunology, Providence Health & Services

Our group has been able to easily identify/enrich for tumor Ag-specific CD8 T cells from several different tumor types. In a recent neoadjuvant anti-OX40 clinical trial, we were able to obtain pre- and post-treatment biopsies and assess these samples by flow cytometry. We found that some patients showed a dramatic increase in the tumor Ag-specific CD8 T cells, and this correlated with tumor destruction. This work has implications not only for systemic Ab immunotherapy but also personalized adoptive T cell therapy.

5:15 ATOR-1017 – A Tumor-Directed Fcγ-Receptor Cross-Linking Dependent 4-1BB Agonistic Antibody

Christina Furebring, PhD, Senior Vice President, Research, Alligator Bioscience

ATOR-1017 is an agonistic CD137 IgG4 antibody with a unique functional profile compared to the 4-1BB antibodies currently in clinical development. The functional activity depends on cross-linking mediated by Fcγ receptors, which directs the immune activation to the tumor area and reduces the risk of inducing systemic immune activation and liver toxicity. ATOR-1017 is currently in preclinical development, and clinical trials will start in 2019.

5:45 End of Day

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TUESDAY, AUGUST 28

7:30 Morning Coffee

EMERGING TARGETS AND STRATEGIES FOR COMBINATION IMMUNOTHERAPY

8:25 Chairperson’s Remarks

Jun Tang, PhD, Senior Research Analyst, Venture Philanthropic Fund and Clinical Accelerator, Cancer Research Institute

8:30 Rational Combinations in an irRational World

Jun Tang, PhD, Senior Research Analyst, Venture Philanthropic Fund and Clinical Accelerator, Cancer Research Institute

We will discuss a number of important and actionable trends in the current IO landscape: a large number of companies developing agents against the same IO targets; a rapid increase in the number of anti-PD-1/L1 combination studies, many of which are testing the same combinations and following inefficient patterns; and a significant increase in the number of small, investigator-initiated studies. For each of the findings, we speculate the causes and discuss a few initiatives that aim to address some of these challenges.

9:00 Novel Clinical Trial Designs to Explore Immunotherapy Combinations

Hila Barak, PhD, Senior Clinical Scientist, Cancer Immunotherapy, Genentech

9:30 Sponsored Presentation (Opportunity Available)

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

10:55 Chairperson’s Remarks

Jun Tang, PhD, Senior Research Analyst, Venture Philanthropic Fund and Clinical Accelerator, Cancer Research Institute

11:00 EOS884448, a higG1 mAb Anti-TIGIT, Induces T Cell Mediated Anti-Tumor Immune Response and Demonstrates Strong Anti-Tumor Immunity in Monotherapy

Xavier Leroy, PhD, Director, Drug Discovery, iTeos Therapeutics

EOS884448 anti-TIGIT mAb displays a strong affinity to recombinant human TIGIT and to native TIGIT expressed on human primary T cells. It competes with CD155 for binding to human TIGIT and shows potency to restore cytokine production when human primary T cells are suppressed in presence of CD155. In addition, when produced in mammalian system on human IgG1 isotype, it shows preferential Treg depletion over conventional CD4+ and CD8+ T cells.

11:30 Smac Mimetics Can Trigger Immunogenic Cell Death in Cancer Cells

Jürgen Moll, PhD, Director, Pharmacology and Translational Research, Boehringer Ingelheim

12:00 pm Close of Immunodulatory Therapeutic Antibodies for Cancer

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