The immunotherapies industry is currently dominated by antagonist antibodies such as PD-1 and CTLA-4, however, agonist targets play an equally critical role in improving the immune response across various types of cancer.

CHI’s Agonist Immunotherapy Targets conference brings together leading industry scientists and academics to examine the most promising agonist targets in development, supported by cutting-edge data and lessons learnt. Key targets include 4-1BB, OX40, CD137, CD40 and GITR, as well as developments in TNFR receptors, ICOS, STING, and VISTA – as monotherapies and in combination.

Final Agenda

Day 1 | Day 2

THURSDAY, MAY 7

12:00 pm Registration

12:35 Luncheon in the Exhibit Hall with Poster Viewing

ADVANCES IN ICOS AND CD137 AGONISTS

1:40 Chairperson’s Opening Remarks

Peter Ellmark, PhD, Vice President, Discovery, Alligator Bioscience

1:50 KEYNOTE PRESENTATION: ICOS Agonism – The Next Generation of Immune Checkpoint Modulation for Cancer

Axel Hoos, PhD, Senior Vice President, Therapeutic Area Head, Oncology, GSK

GSK3359609 is a non-T cell depleting ICOS costimulatory receptor agonist antibody. In non-clinical systems, it enhances immune-stimulatory and anti-tumor properties as monotherapy and in combination with other anti-cancer agents. INDUCE-1 study has demonstrated the pharmacology and anti-cancer properties of GSK3359609 including clinical activity as monotherapy and in combination with PD1 blockade in r/mHNSCC warranting randomized trials to evaluate overall survival.

2:20 Reverse Translational Approaches in Development of ICOS Agonist Vopratelimab

Elizabeth Trehu, MD, CMO, Jounce Therapeutics

Vopratelimab is an investigational ICOS agonist monoclonal antibody that results in activation and proliferation of CD4 T effector cells with high levels of ICOS. In the ICONIC trial, emergence of these cells was associated with improved ORR, PFS, and OS. An RNA signature in baseline tumor samples appears to predict for emergence of ICOS high CD4 T cells and improved clinical outcomes.

2:50 A CD137 Antibody with Differential Agonist Properties that Promotes Antitumor Immunity

Helen Kotanides, PhD, Senior Research Advisor, Cancer Immunobiology, Eli Lilly

3:20 Sponsored Presentation (Opportunity Available)

3:50 Networking Refreshment Break

4:20 CD137 Bispecific Antibody Targeting the Tumor Microenvironment

Patrick Mayes, PhD, Executive Director, Head, IO Antibody Research, Incyte

We have identified a CD137xPD-L1 bispecific antibody (MCLA-145) which drives transactivation of CD137, specifically in the vicinity of cells expressing PD-L1. MCLA-145 treatment resulted in significant immune cell activation in primary human immune cell assays as well as antitumor immune responses in two separate humanized mouse tumor models. These data support the clinical evaluation of MCLA-145 as a novel, PD-L1 dependent CD137 agonist immune therapy and clinical studies are ongoing (NCT03922204).

4:50 IGM Antibodies with Very Potent Agonism to DR-5 Induced Apoptosis and as Anti-Tumor Agents

Bruce Keyt, PhD, CSO, IGM Biosciences

IGM Biosciences has anti-DR5 antibodies prepared as IgG and IgM. Anti-DR5 as IgM exhibits very potent and robust tumor cell killing in vitro and in vivo. IgM has broad anti-cancer bioactivity against various epithelial and hematologic tumors, both as established tumor cell lines as well as PDX cells in vitro. In vivo studies show very strong positive results in single agent treatment or in combinations with chemotherapy. Primate models show very low to no evidence of toxicity. We are scaling these antibodies for IND enabling studies and FIH human trials.

5:20 End of Day

5:15 Registration for Dinner Short Courses

5:45-8:15 pm Recommended Dinner Short Course*

SC13: Design Strategies and Development of ADCs

*Separate registration required.

Day 1 | Day 2

FRIDAY, MAY 8

8:00 am Registration and Morning Coffee

ADVANCES IN OX-40, CD40 AGONISTS

8:30 Chairperson’s Remarks

Bin Zhang, MD, PhD, Professor, Department of Medicine – Division of Hematology/Oncology, Department of Microbiology-Immunology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine

8:35 Novel MOA of a PD1-OX40 Bispecific

Fiona Harding, PhD, Senior Research Fellow, Oncology Discovery, AbbVie

An OX40-PD-1 bispecific was designed to bind and block PD-1 while using binding to PD-1 to cross-link OX40. The molecule binds as expected and was modified to reduce FcR binding. The molecule induces dose dependent anti-tumor activity in the MC38 syngeneic model, but neither depletes Tregs nor increases CD8 infiltration. The novel mechanism of action will be discussed.

9:05 Elucidating How Nonlinked CD4+ Help Augment OX40 plus 4-1BB Agonist Immunotherapy

Adam Adler, Professor, Department of Immunology, University of Connecticut Health School of Medicine

Engaging tumor-unrelated CD4 T cells can boost the efficacy of costimulatory receptor agonist immunotherapy through a previously uncharacterized process termed "nonlinked help". The ability of the unrelated CD4 T cells to provide nonlinked help appears to be conferred via a TCR-independent, "innate-like" response that involves stimulation with a JAK/STAT activating cytokine plus an IL-1 family member.

9:35 Sponsored Presentation (Opportunity Available)

10:05 Networking Coffee Break

10:35 Developing Novel Combinations to Enhance the Therapeutic Efficacy of OX40 Agonists

William Redmond, PhD, Associate Member and Director, Immune Monitoring Laboratory, Earle A. Chiles Research Institute, Providence Cancer Institute

Novel combinatorial approaches are needed to improve the efficacy of cancer immunotherapy. Therefore, we investigated the efficacy of combined therapy with pegzilarginase, a human arginase 1 enzyme engineered to have superior stability and enzymatic activity relative to native human arginase 1, plus anti-PD-L1 or agonist anti-OX40 mAb. Combined pegzilarginase/immunotherapy induced robust anti-tumor immunity characterized by increased intratumoral CD8+ T cells and M1-polarization of tumor-associated macrophages and provides a strong rationale for clinical translation of this approach.

11:05 CD40 Enhances Type I Interferon Responses Downstream of CD47 Blockade to Bridge Innate and Adaptive Immunity

Taylor Schreiber, PhD, CSO, Research & Development, Shattuck Labs, Inc.

CD47/SIRPa blockade enhances macrophage-mediated phagocytosis of tumor cells that are dying, or have been tagged with an ADCP-competent antibody, however this event does not enhance anti-tumor immunity in the absence of antigen presentation to CD8+ T cells. SIRPa-Fc-CD40L (SL-172154) links these two mechanisms via a Type I interferon response, and has shown profound activity in both mouse and non-human primate studies.

11:35 CD40 and Anti-CD40 mAb Programs

Michael Yellin, MD, Vice President, Clinical Science, Celldex

CDX-1140 is a fully human IgG2 agonist anti-CD40 mAb selected based on a linear dose response and hypothesized to achieve good systemic exposure and tumor penetration without dose-limiting toxicity observed with other potent agonist anti-CD40 mAbs. CDX1140-01 is a Phase I dose-escalation study with tumor specific expansion cohorts of CDX-1140 alone or in combination with CDX-301, a potent dendritic cell growth factor, in patients with advanced cancer; preliminary data from the study will be presented.

12:05 pm Targeting CD40 to Unleash Dendritic Cells in Immuno-Oncology – Expanding the Tumor Specific T Cell Repertoire

Peter Ellmark, PhD, Vice President, Discovery, Alligator Bioscience

Tumors that lack tumor infiltrating T cells, so called cold tumors, do not respond to checkpoint therapies. In many cases, the lack of T cell infiltration is a result of insufficient activation of dendritic cells. Alligator Bioscience develops therapies targeting CD40, including the Phase II ready CD40 agonistic antibody (Mitazalimab) that activates dendritic cells. Activation of dendritic cells can increase the frequency and activation of tumor infiltrating T cells resulting in anti-tumor responses.

12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:05 Networking Refreshment Break

LATEST UPDATES IN AGONIST RESISTANCE, COMBINATIONS AND TNFRS

1:35 Chairperson’s Remarks

Adam Adler, Professor, Department of Immunology, UConn Health School of Medicine

1:40 Overcoming the Resistance to Agonist Immunotherapy

Bin Zhang, MD, PhD, Professor, Department of Medicine – Division of Hematology/Oncology, Department of Microbiology-Immunology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine

The underlying mechanisms of agonist immunotherapy remain incompletely understood. We recently demonstrated an inhibitory role of ecto-enzyme CD73 (generating extracellular adenosine) for agonistic anti-4-1BB/CD137 Ab therapy. In particular, the TGF-β-rich tumor milieu confers resistance to anti-4-1BB therapy by sustaining CD73 expression primarily on infiltrating CD8+ T cells across several tumor models. Thus, our findings identify a novel resistance mechanism targeting of 4-1BB and other costimulatory molecules.

2:10 Fc-Silenced Bispecific Antibodies Targeting PD-L1 and 4-1BB Combine Checkpoint Blockade and T Cell Co-Stimulation to Promote Anti-Tumor Activity

Alexander Muik, PhD, Head, Immunomodulators, BioNTech

2:40 IL-15-Based Trifunctional Antibody-Fusion Proteins with Costimulatory TNF-Superfamily Ligands for Cancer Immunotherapy

Dafne Müller, PhD, Group Leader, Institute of Cell Biology and Immunology, University of Stuttgart

In order to support the generation and efficacy of an antitumor response, we have designed trifunctional antibody-fusion proteins for tumor-directed combined delivery of IL-15 and costimulatory members of the TNF-superfamily, demonstrating enhanced immune responsiveness in vitro and antitumor activity in a mouse model in vivo.

3:10 HERA-GITRL: A Unique Hexavalent GITR Agonist for Cancer Immunotherapy

Oliver Hill, PhD, Vice President, Molecular Biology, Apogenix

HERA-GITRL is a member of a novel class of hexavalent TNFR superfamily agonists that share the natural ligand conformation. The biological activities of HERA-GITRL, boosting antigen-specific T cell response and anti-tumor efficacy in mouse models, are crosslinking independent. As the Fc-mediated mixed mode of actions observed for antibodies are avoided, HERA-GITRL is an excellent candidate for further development into a next-generation GITR agonistic immuno-oncology drug.

3:40 End of Conference

Day 1 | Day 2

* The program is subject to change without notice, due to unforeseen reason.