Cambridge Healthtech Institute’s 7th Annual

Immunomodulatory Therapeutic Antibodies for Cancer

Emerging Targets, Combinations, and Antibody Engineering for Next-Generation Immunotherapy

August 5-6, 2019



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 Seventh Annual Immunomodulatory Therapeutic Antibodies for Cancer conference 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

MONDAY, AUGUST 5

7:30 am Registration Open and Morning Coffee

CYTOKINES AS EMERGING IMMUNOTHERAPY TARGETS

8:25 Chairperson’s Opening Remarks

Dimitris Skokos, PhD, Director, Immune & Inflammatory Diseases, Regeneron Pharmaceuticals

8:30 Locking the Latency Cage: Anti-LAP Antibodies as a Novel Approach to Targeting TGFβ

English_JessieJessie English, PhD, CSO, Tilos Therapeutics

TGFβ is a major immunosuppressive cytokine co-opted by tumors to evade the immune system and is implicated in resistance to checkpoint inhibitors. Latency associated peptide (LAP) ensconces TGFβ, acting as a latency cage and major control mechanism for TGFβ activity. We have developed anti-LAP antibodies with preclinical data supporting therapeutic utility in oncology.

9:00 Targeting Soluble TNF to Improve Efficacy of Combination Immunotherapy

Tesi_RaymondRaymond Tesi, MD, CEO/CMO, INmune Bio

A new and fast-growing patient population in cancer is patients resistant to CPI. Combination therapy, a standard with chemotherapy, will become the standard in immunotherapy. Combination immunotherapy ideally combines drugs with different targets. An ideal target is soluble TNF of the TME. Soluble TNF increases MDSC population, promotes metastasis and EMT. Combination therapy targeting soluble TNF with CPI will improve CPI efficacy and reverse resistance to CPI in selected patients.

9:30 TNFR2 Agonism Induces Co-Stimulation of T Cells, Robust Anti-Tumor Activity and Immune Memory

Raue_AndreasAndreas Raue, PhD, Director, Research, HiFiBiO Therapeutics

TNFR2 has been implicated as a novel target for cancer immunotherapy. While it has been linked to enhanced suppressive activity of regulatory T (Treg) cells in auto-immune diseases, the effect of TNFR2-targeted therapy in cancer remains unclear. Here we present data from a novel agonistic monoclonal anti-TNFR2 antibody that is being developed as a potential novel immunotherapy option for cancer patients.

10:00 Coffee Break

EMERGING IMMUNOMODULATORY TARGETS FOR COMBINATION WITH CHECKPOINT INHIBITORS

10:30 KEYNOTE PRESENTATION: Tandem Immunotherapy Targeting PD-1 and GITR Achieves Synergy

Dimitris Skokos, PhD, Director, Immune & Inflammatory Diseases, Regeneron Pharmaceuticals

Immune checkpoint inhibitor therapies bolster the antitumor activity of CD8+ T lymphocytes. We used single-cell analysis of tumor-infiltrating lymphocytes to probe the mechanisms responsible for the synergy of PD-1 blocking and GITR agonist antibodies in enhancing tumor control in mouse cancer models. This combination immunotherapy resulted in a synergistic increase in memory precursor effector T cells that depended on availability of specific costimulatory pathways. These results provide a mechanistic rationale for conducting further clinical trials of combined anti-GITR and anti-PD-1 immunotherapy in human cancer.

11:00 Preclinical and Clinical Rationale for Combination of the ICOS Agonist Antibody Vopratelimab and CTLA-4 Inhibition

Harvey_ChristopherChristopher J. Harvey, PhD, Director of Preclinical Sciences and JTX-2011 Scientific Lead, Jounce Therapeutics

JTX-2011 (vopratelimab) is an agonist antibody targeting ICOS that selectively activates primed CD4 T effector cells. Vopratelimab is currently being tested as a monotherapy or in combination with either PD-1 or CTLA-4 in the Phase 1/2 ICONIC trial. This presentation will focus on both the preclinical data that informed combination selection and the reverse translational data from the ICONIC study that is being used to support ongoing clinical development.

11:30 Epitope Identification and Clinical Immune Monitoring in Gene Therapy and Immune Oncology Programs

Knowlton_EmileeEmilee Knowlton, PhD, Immunology Sales Specialist, Sales, ProImmune, Inc.

Epitope discovery is a crucial element in the development of vaccine candidates and drug therapeutics. In the immune-oncology space, identifying neoepitopes and tumor-associated antigens provide new targets for cancer diagnostics and enable the tracking of patient responses to treatment. ProImmune provides industry-leading tools for antigen characterization, epitope mapping and immune monitoring. In this presentation, case studies will be shared that detail how ProImmune’s integrated platform has identified novel epitopes in the immune-oncology field.

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

12:30 Session Break

1:25 Chairperson’s Remarks

Dimitris Skokos, PhD, Director, Immune & Inflammatory Diseases, Regeneron Pharmaceuticals

1:30 Understanding Immune Checkpoint TIM-3 Biology and Anti-TIM-3 Antibody for Cancer Immunotherapy

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

TIM-3 has critical roles in tumor-induced immune suppression. Blockade of TIM-3, alone or in combination with PD-1 pathway blockade, has shown anti-tumor efficacy in several preclinical cancer models. TIM-3/PD-1 pathway co-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.

2:00 Combining OX40 Agonists with TGFβ Receptor and PD-1 Inhibitors

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

OX40 agonists enhance CD4 and CD8 T cell function in tumor-bearing hosts leading to immune-enhanced tumor destruction. However, when the tumors become larger, immune suppressive components appear to decrease the function of OX40 agonists. Therefore, we tested whether blocking two immune suppressive pathways, TGFβ receptor and PD-1, in combination with an OX40 agonist, would enhance immunity leading to therapeutic results in mice with larger tumors. We found that blocking both pathways enhanced T cell function in combination with anti-OX40 but blocking the TGFβ receptor pathway had a more pronounced therapeutic effect.

2:30 Targeting Wnt Ligand Signaling as a Strategy for Overcoming Resistance to Anti-PD-1 Antibody Immunotherapy

Hanks_BrentBrent Hanks, MD, PhD, Assistant Professor, Medicine, Pharmacology and Cancer Biology, Duke Cancer Institute, Duke University School of Medicine

Emerging data has implicated the Wnt-beta-catenin signaling pathway as playing an important role in various aspects of tumor-mediated immune evasion and immunotherapy resistance. We will review this evidence and discuss the various therapeutic strategies for targeting this pathway as a strategy for enhancing the efficacy of anti-PD-1 antibody immunotherapy.

3:00 Breakout Discussion Groups and Refreshment Break

NEOADJUVANT IMMUNOTHERAPY

4:00 Neoadjuvant Immunotherapy in Solid Tumors

Amaria_RodabeRodabe Amaria, MD, Assistant Professor, Melanoma Medical Oncology, MD Anderson Cancer Center

This presentation will cover the currently available data on recent clinical trials of neoadjuvant immunotherapy in melanoma and other solid tumors; also, rationale for neoadjuvant immunotherapy, focus on expected response rates, toxicity concerns and potential surgical complications.

4:30 New Studies in Melanoma: A Better Way to Get Faster and More Mechanistic Data

Kirkwood_JohnJohn M. Kirkwood, MD, Usher Professor of Medicine, Dermatology and Translational Science, Co-Leader, Melanoma and Skin Cancer Program, UPMC Hillman Cancer Center

Neoadjuvant therapy, in which treatment precedes definitive surgery for high-risk operable melanoma, has been pursued for nearly 20 years now. The neoadjuvant evaluation of the first immunotherapeutic agent, interferon alfa-2b, first demonstrated the immunological effects of that agent given prior to surgery, utilizing the tissue biopsy at outset and at definitive surgery in 2006. The evaluation of anti-CTLA4 blocking antibody ipilimumab, and ipilimumab combined with IFN, as well as anti-PD1 therapy pembrolizumab and nivolumab in other combinations have now shown efficacy in terms of clinical and pathological response, as well as new insights into mechanisms of these agents and combinations. BRAF inhibitors and MEK inhibitors have also shown promising impact in the neoadjuvant setting—and neoadjuvant therapy has become critical to the development and understanding of new combinations for adjuvant therapy of melanoma, given the proliferation of active agents for which effects upon tumor in the neoadjuvant setting are important to decision-making for new Phase III trials and optimization of melanoma therapy.

5:00 Close of Day

TUESDAY, AUGUST 6

7:30 am Registration Open and Morning Coffee

TARGETING INNATE IMMUNITY TO INCREASE RESPONSE TO CHECKPOINT MODULATORS

8:25 Chairperson’s Remarks

Michael Wichroski, PhD, Senior Principal Scientist, Immuno-Oncology, Bristol-Myers Squibb

8:30 Preclinical Characterization of BMS-986299, a First-in-Class NLRP3 Agonist with Potent Antitumor Activity, Alone and in Combination with Checkpoint Blockade

Wichroski_MichaelMichael Wichroski, PhD, Senior Principal Scientist, Immuno-Oncology, Bristol-Myers Squibb

Immune checkpoint inhibitors (CPI) targeting adaptive immunity have significantly improved patient outcomes in many tumor types, but other approaches are needed to extend clinical benefit to more patients. Targeting innate immunity to provide broader activation of the immune system may be one approach to complement CPI activity. Here, we present the pre-clinical evaluation of BMS-986299, a first-in-class, NLRP3 inflammasome agonist, which shows promising combination potential with CPI.

9:00 KEYNOTE PRESENTATION: Induction of Durable Regression in PD-1 Refractory Melanoma Following Intratumoral Injection of a CpG-A TLR9 Agonist, CMP-001 in Combination with Systemic Pembrolizumab

Arthur Krieg, MD, Founder & CSO, Checkmate Pharmaceuticals

Checkpoint inhibitor therapies such as anti-PD-1 antibodies can induce dramatic regression of “hot” tumors where the immune system already has been activated against the tumor but are generally ineffective against “cold” tumors. We hypothesized that modification of the tumor microenvironment by intratumoral injection of a Toll-like receptor 9 (TLR9) agonist CpG-A oligodeoxynucleotide would convert “cold” tumors into “hot” tumors, resulting in an increased response rate to anti-PD-1 therapy. In human clinical trials we have achieved durable tumor regression in patients with PD-1-refractory advanced melanoma.

9:30 Sponsored Presentation (Opportunity Available)

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

10:55 Chairperson’s Remarks

Michael Wichroski, PhD, Senior Principal Scientist, Immuno-Oncology, Bristol-Myers Squibb

11:00 Assessing the Impact of Intratumoral Immune Modulation in Metastatic Melanoma

Haymaker_CaraCara Haymaker, PhD, Assistant Professor, Director, Oncology Research and Immuno-Monitoring Core (ORION), Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center

The use of innate immune modulators to improve response to checkpoint blockade holds tremendous promise for patients with solid tumors. Intratumoral administration of these agents provides a direct activation of the target innate cell(s) that could improve antigen-presentation and subsequent anti-tumor T-cell activation. This study will demonstrate how the use of longitudinal tissue and blood collections is key to understanding both response and resistance mechanisms.

11:30 Bempegaldesleukin (NKTR-214): Accessing the IL-2 Pathway for Immuno-Oncology

Lin_WeiWei Lin, PhD, Senior Vice President, Oncology Development, Nektar Therapeutics

Bempegaldesleukin is an IL-2 receptor pathway agonist that stimulates rapid proliferation and activation of effector T cells, increased T cell infiltration of the tumor and sustained signaling that is maintained with successive treatment cycles without significantly over-activating the immune system. Bempegaldesleukin is being evaluated in combination with the checkpoint inhibitor, nivolumab, in a broad clinical program. Preliminary clinical data in melanoma and urothelial carcinoma has demonstrated a deepening of responses over time with a favorable safety profile.

12:00 pm Close of Immunomodulatory Therapeutic Antibodies for Cancer

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