Cambridge Healthtech Institute’s 4th Annual

Emerging Targets for Immunomodulatory Antibodies and Combinations

Novel Targets and Pathways for Cancer Immunotherapy and Combinations

October 7, 2020

While cancer immunotherapy has made a giant leap in the past five years, the majority of therapies at advanced stages of development are clustered in a similar target space. The increased investment in immuno-oncology has created an urgent opportunity to discover and populate new target spaces that either present new classes of immunotherapies or can be used in combination with existing products. Cambridge Healthtech Institute’s Fourth Annual Emerging Targets for Immunomodulatory Antibodies and Combinations conference will cover the emerging target space, including immunomodulatory inhibitor and agonist targets, stromal and immune cell targets, and strategies for rational combination immunotherapy. Case studies of preclinical and translational approaches to the discovery and validation of new immuno-oncology targets and combinations will be presented.

Wednesday, October 7

LESSONS LEARNED FROM PD-1 CHECKPOINT INHIBITORS AND COMBINATIONS

9:00 am PD-1 Antibodies Either as Monotherapy or Precision Medicine Informed Combinations Are Transforming Cancer Care
Roy Baynes, MD, PhD, Senior Vice President & Head, Global Clinical Development; CMO, Merck Research Laboratories

PD-1 antibodies are transformative in cancer therapeutics. They have shown significant anticancer activity as monotherapy across a large number of major cancer types and across lines of therapy. Precision medicine tools have enabled trial enrichment and patient segmentation. They have also provided insights to potential resistance biology and enabled informed combination selection. PD-1-based combination therapies are also showing promise broadly across tumors and lines of therapy.



9:20 am Independent Contributions Account for Clinical Activity of PD-1 Checkpoint Inhibitor Combination Therapies
Emmett Schmidt, MD, PhD, Vice President, External Collaborations, Oncology Early Development, Merck

Clinical combination studies including PD-1 checkpoint inhibitors exploded in the 7 years since the first PD-1 checkpoint inhibitor approvals. Expectations of combination success were high at first. Seven years on, it is important to assess these studies more realistically. The presenter recently published a cross sectional study of PD-1 pathway checkpoint inhibitor clinical trials. Encouraging and discouraging results will be reviewed to guide thinking about future combination strategies.


9:40 am Long-Term Outcomes and Responses to Retreatment in Melanoma Patients Treated with PD-1 Blockade
Allison Betof Warner, MD, PhD, Assistant Attending Physician, Memorial Sloan Kettering Cancer Center

In a single-institution cohort, long-term outcomes were assessed after discontinuation of anti-PD-1 for advanced melanoma (n=396). Of 102 complete responders, the probability of relapse was 27% at 3 years. No association was seen between treatment duration and relapse risk. Among patients treated with anti-PD-1 who were re-treated after relapse, response was observed in 15% (of 34) patients re-treated with anti-PD-1 and 25% (of 44) patients re-treated with ipilimumab + anti-PD-1.


10:00 am Sponsored Presentation (Opportunity Available)
10:20 am Session Break - View Our Virtual Exhibit Hall

EMERGING TARGETS AND COMBINATIONS TO OVERCOME RESISTANCE TO IMMUNE THERAPY

11:00 am Targeting a Tumor-Intrinsic PD-L1-NLRP3 Signaling Pathway to Overcome Adaptive Resistance to Anti-PD-1 Antibody Immunotherapy
Brent Hanks, MD, PhD, William Dalton Family Assistant Professor of Medical Oncology, Assistant Professor, Department of Pharmacology and Cancer Biology; Associate Director, Basic and Translational Research, Duke Center for Cancer Immunotherapy, Duke University Cancer Institute

We will discuss the discovery of a novel tumor-intrinsic adaptive resistance pathway to anti-PD-1 immunotherapy and explore the potential implications that this pathway has on therapeutic and biomarker development in immuno-oncology.

11:20 am

Preventing Drug Resistance to Targeted Therapeutics in ER+HER2- Breast Cancers

Nathaniel Wang, PhD, CEO/CSO, Replicate Bioscience, Inc.

Resistance to therapy in cancer is a major issue leading to treatment failures. Recently, there has been an increase in agents targeting intrinsic or acquired resistance. However, these approaches only target resistance mutations after they have occurred. Our proactive, anticipatory approach applies selective pressures through the immune system to prevent or reverse resistance prior to occurrence. While our initial focus is breast cancer, this approach is broadly applicable for other cancers.

11:40 am

IO Target Discovery at Jounce Therapeutics

Donald R. Shaffer, PhD, Senior Director, Head of Discovery, Jounce Therapeutics

Jounce’s translational platform utilizes thousands of human tumor samples and advanced bioinformatics to probe the tumor microenvironment for immuno-oncology targets that could be relevant in T cell checkpoint-resistant tumors and/or expand the number of patients benefiting from checkpoint therapy. The first therapeutic candidate to emerge from this platform is JTX-8064, a monoclonal antibody that antagonizes LILRB2 (ILT4), and promotes a pro-inflammatory, anti-tumor phenotype in macrophages and other myeloid cells. In an ex vivo human tumor histoculture system, JTX-8064 induced gene signature changes consistent with M1 skewing of macrophages and also induced IFN-g and T cell inflamed gene signatures suggesting activation of T cell immunity within the tumor microenvironment. Thus, we believe JTX-8064 antagonism of LILRB2 will directly improve the function of myeloid cells and indirectly stimulate anti-tumor T cell immunity.

12:00 pm Session Break – View Our Virtual Exhibit Hall
12:10 pm Interactive Breakout Discussions - View Our Virtual Exhibit Hall

Join your colleagues and fellow delegates for a focused, informal discussion moderated by a member of our speaking faculty.  A small group format allows participants to meet potential collaborators, share examples from their own work and discuss ideas with peers.


Strategies to Overcome Resistance to Immunotherapy

Nathaniel Wang, PhD, CEO/CSO, Replicate Bioscience, Inc.
12:40 pm Session Break – View Our Virtual Exhibit Hall

TARGETING INNATE IMMUNITY

12:55 pm Targeting Soluble NKG2D Ligands to Remodulate Tumor Microenvironment and Enhance the Response to Immunotherapy
Jennifer Wu, PhD, Mary and Patrick Scanlan Professor of Urology, Professor of Immunology, Feinberg School of Medicine, Robert Lurie Comprehensive Cancer Center, Northwestern University

Oncogenic-induced, membrane-bound NKG2D ligands stimulate NK and Cd8 T cell anti-tumor immunity. Conversely, tumor-edited soluble NKG2D ligands in the tumor microenvironment suppress anti-tumor immunity via multiple mechanisms. Here we present evidence that tumors shed soluble NKG2D ligand, the soluble MHC I chain-related molecule (sMIC), facilitates immune suppression of MDSCs. We also present evidence that targeting soluble MIC reprograms MDSC and primes the tumor immune microenvironment.

1:15 pm

HERA-CD40L: A Two-Fold-Three-Based CD40 Agonist for Cancer Immunotherapy

Katharina Billian-Frey, PhD, Head, Protein Engineering, Apogenix AG

Apogenix hexavalent TNFR-SF agonists (HERA) are developed for immune-therapeutic treatment of cancer. Due to its structural layout with two trivalent CD40L-receptor-binding domains, HERA-CD40L mimics the natural ligand and enables efficient receptor agonism. Treatment increases the pro-inflammatory state of all CD40-expressing cells examined and shows single-agent antitumor activity both in vitro and in vivo. The MoA has been well defined, and the biological activity has been demonstrated to be distinct from and superior to clinical benchmark “agonistic” antibodies.

1:35 pm Novel Macrophage Checkpoint Modulation in Immuno-Oncology
Tatiana Novobrantseva, PhD, Co-Founder & CSO, R&D, Verseau Therapeutics

Macrophages can adopt different functional roles in response to signals from their environment, including the ability to direct pro-inflammatory and anti-inflammatory immune responses. In cancer, tumor-associated macrophages (TAMs) are key regulators of the interactions between the immune system and cancer. TAMs fuel tumor progression and negatively impact responses to therapy. Verseau has found novel targets that change macrophages into antitumor response enablers. At Verseau, we have nominated and validated more than two dozen targets that modulate human macrophage biology. The lead program targeting PSGL-1 reprograms macrophages to a pro-inflammatory state, activates T cells, and attracts other immune cells to generate a coordinated and powerful anti-tumor response.

1:55 pm Sponsored Presentation (Opportunity Available)
2:15 pm PANEL DISCUSSION:

Emerging Immuno-Oncology Targets and Combinations

Panel Moderator:
Emmett Schmidt, MD, PhD, Vice President, External Collaborations, Oncology Early Development, Merck
Panelists:
Nathaniel Wang, PhD, CEO/CSO, Replicate Bioscience, Inc.
Donald R. Shaffer, PhD, Senior Director, Head of Discovery, Jounce Therapeutics
Katharina Billian-Frey, PhD, Head, Protein Engineering, Apogenix AG
2:45 pm Session Break - View Our Virtual Exhibit Hall
3:05 pm Interactive Breakout Discussions - View Our Virtual Exhibit Hall

Join your colleagues and fellow delegates for a focused, informal discussion moderated by a member of our speaking faculty.  A small group format allows participants to meet potential collaborators, share examples from their own work and discuss ideas with peers.


Targeting Innate Immunity

Jennifer Wu, PhD, Mary and Patrick Scanlan Professor of Urology, Professor of Immunology, Feinberg School of Medicine, Robert Lurie Comprehensive Cancer Center, Northwestern University
3:35 pm Close of Emerging Targets for Immunomodulatory Antibodies and Combinations Conference





Final Agenda Available

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