When you think of immunotherapies you normally think of antagonist antibodies such as PD-1 and CTLA-4. However, it is clear that antagonists alone are not enough to elicit response in the majority of patients, hence a rising interest in agonists targets.
The Fourth Annual Agonist Immunotherapy Targets event will examine these modalities and their treating disease. Agonists showing the most promise, including OX40, CD27, GITR, and 4-1BB, will be covered in clinical case studies by examining the
data as well as the biology and mechanisms. Emerging agonists, including TNFR receptors, ICOS, and VISTA will also be discussed. Focus will be given throughout to potential combination immunotherapies to ensure durable antitumor response. Overall,
this event will emphasize strategies for target discovery to ensure continued growth and success for immunotherapies.
Final Agenda
SC10: Critical Considerations for the Design and Development of Antibody-Drug Conjugates
Isabel Figueroa, PhD, Scientist, PTPK, Genentech, Inc.
Shawn Owen, PhD, Assistant Professor, Pharmaceutics and Pharmaceutical Chemistry, University of Utah
*Separate registration required.
THURSDAY, MAY 3
12:00 pm Registration (Commonwealth Hall)
12:35 Luncheon in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
1:40 Chairperson’s Remarks
Peter Ellmark, PhD, Vice President, Discovery, Alligator Bioscience
1:50 PD1-Fc-OX40L for Cancer Immunotherapy
Taylor Schreiber, PhD, CSO, Research & Development, Shattuck Labs, Inc.
We have developed a novel two-sided fusion protein that co-localizes costimulation via OX40 to the tumor microenvironment, while simultaneously providing competitive inhibition of PD-L1 and PD-L2. PD1-Fc-OX40L stimulates OX40 signaling, out-competes
PD-1 in binding its ligands, stimulates T cell-mediated tumor cell killing, and leads to increased complete rejection of established tumors as compared to monotherapy or combinations of PD-1 and OX40 antibodies.
2:20 Combination Approaches with GITR and OX40 Agonists
Patrick Mayes, PhD, Executive Director, Head, IO Antibody Research, Incyte
2:50 A Novel FAP-Targeted 4-1BB Agonist and Its Combination with T Cell Bispecific Antibodies
Claudia Ferrara, PhD, Principal Scientist, Large Molecule Research, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zurich
CD137 (4-1BB) is a promising agonistic target for cancer immune therapy. The clinical development of first generation 4-1BB agonistic antibodies has however been hampered by hepatic toxicity. Here we describe a novel FAP-targeted 4-1BB agonist,
developed to be mainly retained at tumor site and as combination partner for T cell bispecific antibodies.
3:20 Poster Presentation: Multispecific and Multivalent Antibodies as OX40 Agonists
Francis Qufei Li, PhD, Invenra
3:35 Poster Presentation: Screening, Optimization and Characterization of a Novel 4-1BB x 5T4 ADAPTIR Bispecific Antibody
David Bienvenue, PhD, Senior Director, Protein Sciences, Aptevo Therapeutics
3:50 Networking Refreshment Break (Harbor & Mezzanine Level)
4:20 Tumor-Directed Targeting of Effector T Cells and Regulatory T Cells
Peter Ellmark, PhD, Vice President, Discovery, Alligator Bioscience
Two different approaches to tumor-directed immune activation by agonistic/antagonistic drug candidates will be presented. ATOR-1015 is a bispecific immune activating antibody that reduces the number of regulatory T-cells and activates effector
T-cells in the tumor, generating a strong anti-tumor effect. ATOR-1017 is a monospecific agonistic antibody targeting 4-1BB with best in class properties directing the immune activation to the tumor area.
4:50 Varlilumab, a Fully Human Agonist Anti-CD27 Antibody
Michael Yellin, MD, Vice President, Clinical Science, Celldex
The CD27 co-stimulation pathway for immune cells has shown potent activity in pre-clinical models to eliminate tumors both as single agent and in combination with checkpoint inhibitors. Clinical trials to date using varlilumab, an agonist anti-CD27
antibody, confirm this specific immune activation without significant immune toxicity. Durable single agent responses have been observed. Clinical studies of varlilumab in combination with other immune modulating agents will be discussed.
5:20 End of Day
5:20 Registration for Dinner Short Courses (Commonwealth Hall)
FRIDAY, MAY 4
8:00 am Morning Coffee (Harbor Level Lobby)
8:30 Chairperson’s Remarks
Deborah H. Charych, PhD, Executive Director, Nektar Therapeutics
8:35 The Appeal of the TNFR2 Target for Immunotherapy: Tregs and Tumor Oncogenes
Denise L. Faustman, MD, PhD, Director of Immunobiology, Massachusetts General Hospital, Associate Professor
of Medicine, Harvard Medical School
Immune checkpoint inhibitors have revolutionized cancer therapy but can exhibit variable efficacy. TNFR2 is a signaling molecule found on a subset of potent Treg cells that activates the proliferation of these cells. TNFR2 is also abundantly
expressed on the surface of many human tumors as an oncogene. We propose blocking TNFR2 might target abundant TNFR2+ tumor-infiltrating Tregs and directly kill TNFR2-expressing tumors. TNFR2 inhibitors might also potentially constitute
safer and more targeted immunotherapy.
9:05 HERA: Engineering Next Generation TNFR-SF Agonists for Cancer Immunotherapy
Oliver Hill, PhD, Vice President, Molecular Biology, Apogenix
The HERA technology platform developed by Apogenix is based on trivalent but single-chain molecular mimics of the TNF-SF Receptor binding domains (scTNFSF-RBDs) fused to a dimerization scaffold. Being hexavalent by design, the HERA fusion
proteins are potent TNFR-SF agonists on their own and do not need secondary crosslinking events for their activity. The underlying engineering concept as well as selected in vitro and in vivo data obtained with HERA-CD40L, HERA-CD27L, HERA-GITRL, HERA-LIGHT and HERA-CD137L will be presented.
9:35 Bi-and Trifunctional Antibody-Cytokine Fusion Proteins for Cancer Immunotherapy
Dafne Müller, PhD., Group Leader, Institute of Cell Biology and Immunology, University of Stuttgart
IL-15 and costimulatory members of the TNF-superfamily have shown great potential to support the generation and development of an antitumor immune response. In order to improve the efficacy of such molecules at the tumor site we designed bi-
and trifunctional antibody-fusion proteins, focusing on targeted presentation and combined mode of action of diverse immunomodulatory molecules, demonstrating enhanced immune responsiveness in vitro and antitumor activity in a mouse model
in vivo.
10:05 Networking Coffee Break (Harbor & Mezzanine Level)
Debbie Law, DPhil, CSO, Jounce Therapeutics
JTX-2011 is an ICOS (Inducible T cell CO-Stimulator) agonist antibody currently in clinical development. It is designed to shift the balance in tumors from immunosuppressive towards anti-tumor activity by stimulating T effector cells and reducing
intratumoral T regulatory cells. The preclinical data supporting the development of JTX-2011 as well as the safety evaluation of JTX-2011 from the Phase I portion of the biomarker-driven ICONIC trial will be described.
11:05 A Novel, Dual-Specific Antibody Conjugate Targeting CD134 and CD137 Costimulates T Cells and Elicits Antitumor Immunity
Adam J. Adler, PhD, Professor, Immunology, University of Connecticut
Combining agonists to different costimulatory receptors can be more effective in controlling tumors compared to individual agonists, but presents logistical challenges and increases the potential for adverse events. We developed a novel immunotherapeutic
agent by fusing agonists to CD134 and CD137 into a single biologic, OrthomAb, that potentiates cytokine secretion from TCR-stimulated T cells more potently than non-conjugated CD134 + CD137 agonists in vitro,
and reduces tumor growth in vivo.
11:35 Harnessing Potent Immunological Pathways for Better Medicine
Deborah H. Charych, PhD, Executive Director, Nektar Therapeutics
Many validated potent biological pathways do not translate well to therapy because of toxicities, poor pharmacokinetics or undesirable pharmacodynamics. We have engineered endogenous proteins and exogenous small molecules into accessible medicines
using polymer conjugation technology. NKTR-214 is in Phase II clinical trials and is a key example of how polymer conjugation can bias the well-known IL2 receptor pathway to promote CD8 T cell tumor infiltration over Tregs. Other examples
to be discussed are NKTR-255, an IL15 receptor agonist and NKTR-262, a small molecule conjugate that stimulates toll-like receptor (TLR). Each has been conjugated in unique ways to elicit desirable and controlled pharmacological and immunological
outcomes.
12:05 pm Using Structural Insights for the Design of Improved TNFR Agonists
Eva Vanamee, PhD, Co-Founder and CSO, FusionBio, Inc.
12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:05 Networking Refreshment Break (Harbor & Mezzanine Level)
1:35 Chairperson’s Remarks
Harpreet Singh, President & CEO, Immatics US
1:40 Addressing Solid Cancers with Novel Targets and TCR-T Approaches
Harpreet Singh, President & CEO, Immatics US
Novel targets are required to address the unmet medical need particularly in solid cancers. The high-throughput mass spectometry-based XPRESIDENT® platform was applied to identify dozens of novel targets followed by generation of specific
T-cell receptors (TCRs). Three adoptive cell therapy (ACT) approaches are being developed on this basis: (1) ACTolog using multiple endogenous T cells products, (2) ACTengine using gene-engineered T cells and (3) ACTallo using allogeneic
gamma-delta T cells.
2:10 Intratumoral Delivery of Novel STING Agonists Synergizes with Checkpoint Modulation to Regress Multi-Focal Cancer
Casey Ager, Graduate Research Assistant, Department of Immunology, University of Texas MD Anderson Cancer Center
Therapeutic modulation of innate immune cells within the tumor microenvironment can complement checkpoint blockade regimens by ameliorating myeloid suppression and promoting T cell priming. We have developed novel high-affinity STING agonists
and are investigating how intratumoral delivery of these agents can activate tumor myeloid populations and sensitize poorly immunogenic solid tumors to checkpoint blockade, and additionally whether this approach can effectively mobilize
abscopal immunity against disseminated lesions.
2:40 In vitro Characterization and in vivo Anti-Tumor Efficacy of a Novel STING Agonist, MK-1454
Saso Cemerski, PhD, Principal Scientist, Merck Research Labs
MK-1454, a novel STING agonist, induces potent cytokine responses and activates several immune cell types in vitro including MDSCs and M2-macrophages, key suppressive myeloid cells in the TME. MK-1454 induces
robust anti-tumor activity in mouse syngeneic tumor models and cytokine production and gene expression changes in ex vivo-stimulated human primary tumors. MK-1454 is currently being evaluated in cancer
patients both as monotherapy and in combination with Keytruda.
3:10 Latest Progress and Learnings on Agenus’s Agonist Portfolio
Robert B. Stein, MD, PhD, Senior Advisor, R&D, Agenus, Inc.
3:40 End of Conference