Much focus in immunotherapy research has been given to antagonist antibodies, particularly PD-1 and CTLA-4. However, it is clear that antagonists alone are not enough to elicit response in the majority of patients. T cell co-stimulation through agonist receptors, such as OX40 or 4-1BB, provides a potent signal that promotes the expansion and proliferation of killer CD8 and helper CD4 T cells. The Third Annual Agonist Immunotherapy Targets event will examine these modalities and their potential role in successful disease treatment. 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
THURSDAY, MAY 4
12:00 pm Registration
12:35 Luncheon in the Exhibit Hall with Poster Viewing
1:40 Chairperson’s Remarks
Peter Ellmark, Ph.D., Principal Scientist, Research & Development, Alligator Bioscience
1:50 Engineering of an ICOS Agonist Antibody for Cancer Therapy
Patrick Mayes, Ph.D., Director, Early Development Leader, GlaxoSmithKline Pharmaceuticals, Inc
2:20 Tumor-Directed Immunotherapy – Tumor-Localized Immune Activation Using TNFR-SF Agonistic Antibodies
Peter Ellmark, Ph.D., Principal Scientist, R&D, Alligator Bioscience
Alligator Bioscience develops mono and bispecific agonistic antibodies, targeting TNFR-SF members, for tumor-directed immunotherapy of cancer. This approach provides new opportunities to generate an effective, immune-mediated, anti-tumor response. Alligators pipeline projects will be presented, including ADC-1013, a human monospecific agonistic IgG1 antibody in clinical development and ATOR-1015, a bispecific antibody targeting OX40 and CTLA-4 developed to deplete Tregs in the tumor microenvironment.
2:50 OX40: From Bench to Bedside and Back Again
Brendan Curti, Director, Genitourinary Oncology Research, Immunotherapy Clinical Program, Providence Medical Group
Cancer immunotherapy is an evolving treatment that boosts the immune system to recognize and destroy cancer cells. Head and neck squamous cell carcinomas (HNSCC) produce suppressive factors that impair the immune system, thus limiting effective antitumor immunity. OX40 is a member of the tumor necrosis factor (TNF) receptor family and a potent co-stimulatory pathway that when triggered can enhance T-cell memory, proliferation and anti-tumor activity in patients with metastatic cancer.
3:20 Targeting Co-Stimulatory TNF Receptors with Hexavalent TNF Receptor Agonists (HERA)
Harald Fricke, M.D., COO/CMO, Apogenix AG
HERA compounds currently under development at Apogenix, including HERA -CD27L, -CD40L, -GITRL and -4-1BBL bind their cognate receptors by clustering six receptor chains in a spatially defined manner. This binding mode confers potent biological activity without requiring cross-linking and functional studies reveal differences in receptor signaling and anti-tumor efficacy compared to “agonistic” antibodies. These qualities, plus a short half-life, have been proven to eliminate immunogenicity and toxicity as well as to ensure optimal immunostimulatory activity.
3:50 Refreshment Break
4:20 Varlilumab, an Agonist Anti-CD27 Antibody, as Single Agent and in Combination
Tom Davis, M.D., Executive Vice President and CMO, Celldex Therapeutics Inc.
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-CD-27 antibody, confirm this specific immune activation without significant immune toxicity. Single agent responses have been seen and multiple collaborative studies of varli in combination are ongoing.
4:50 JTX-2011: Development of an Agonist Antibody Targeting ICOS
Jennifer Michaelson, Ph.D., Executive Program Leader, Senior Director of Preclinical Development, Preclinical Development, Jounce Therapeutics Inc.
JTX-2011 is an agonist antibody to the co-stimulatory molecule ICOS. Preclinical studies demonstrated efficacy in syngeneic tumor models, with enhanced efficacy in combination with PD-1 inhibitors. JTX-2011 induces T effector cell activation and also preferentially reduces T regulatory cells in the tumors. This dual mechanism contributes to the significant anti-tumor response observed in preclinical models. A promising safety profile was revealed in preclinical studies. JTX-2011 is in clinical development as a monotherapy and in combination with anti-PD-1 therapy.
5:20 End of Day
5:20 Registration for Dinner Short Courses
Recommended Dinner Short Course*
SC18: Clinical Prospects of Cancer Immunotherapy - Detailed Agenda
*Separate registration required
FRIDAY, MAY 5
8:00 am Morning Coffee
8:30 Chairperson’s Remarks
Roland Kontermann, Ph.D., Professor of Biomedical Engineering, Institute of Cell Biology and Immunology, University of Stuttgart
8:35 Duokines: A New Class of Bifunctional Immunostimulatory Molecules
Roland Kontermann, Ph.D., Professor of Biomedical Engineering, Institute of Cell Biology and Immunology, University of Stuttgart
Duokines are bifunctional fusion proteins of TNF ligand superfamily members expressed either as homotrimer molecules or as single-chain derivatives. They act either in cis or in trans and are capable of amplifying immune responses, e.g., as shown for the antitumor activity of T-cell retargeting bispecific antibodies.
9:05 The Tetravalent, Bispecific CD30/CD16A TandAb AFM13 is a Prototype NK-Cell Engager with Unique CD16A-Binding Properties
Martin Treder, Ph.D., CSO, Affimed, NV.
AFM13 is currently in Phase II clinical development in Hodgkin lymphoma (HL) and other CD30+ malignancies. It engages NK-cells through CD16A with high affinity and specificity and confers significantly stronger NK-cell activation compared to other therapeutic antibodies. We have previously shown synergistic efficacy when NK-cell activation through AFM13 is combined with checkpoint modulation such as anti-PD-1 treatment, which is known to unleash T-cell and NK-cell activity. Mechanism of action as well as mono- and combination therapeutic approaches of an NK-cell engager will be discussed.
9:35 Activation of Myeloid IL-27 Production Initiates 4-1BB Agonist Hepatotoxicity
Michael A. Curran, Ph.D., Assistant Professor, Immunology, MD Anderson Cancer Center
The clinical progression of 4-1BB agonist antibodies has been stymied by limited understanding of their underlying mechanism of action and the resulting inability to separate off-target liver toxicity from on-target anti-tumor immunity. By analyzing the mechanisms underlying this toxicity, we have revealed novel insights into 4-1BB biology which can inform design of novel antibodies or combination strategies which favor tumor clearance over liver inflammation.
10:05 Coffee Break
10:35 Agonist Redirected Checkpoints for Cancer Immunotherapy
Taylor Schreiber, M.D., Ph.D., CSO, Shattuck Labs, Inc.
This presentation will outline the production, pre-clinical characterization and early GMP manufacturing for a lead ARC construct that simultaneously blocks signaling through PD-1 and activates signaling through OX40. This construct demonstrates significantly superior tumor rejection in multiple pre-clinical models as compared to either PD-1/L1 or OX40 specific antibody therapy.
11:05 Selection of Fc for Antibody Therapeutics to Achieve Optimal Antitumor Immunomodulating Activity
Jieyi Wang, Ph.D., CEO, Lyvgen Biopharma
Therapeutic antibodies have become important biologics for cancer immunotherapy. Their modes of action not only rely on variable domains responsible for specificity but also involve the constant domains that can interact with various Fc receptors. Blocking antibodies such as nivolumab and pembrolizumab were successfully developed in the clinic as IgG4 molecules. However, it is not clear what IgG isotypes would be optimal for agonist antibodies that are required to activate co-stimulatory targets such as CD40, OX40, CD27, CD137, GITR, ICOS and HVEM.
11:35 Enhancing Checkpoint Inhibitor Efficacy via Combination with CMP-001, a VLP Packaged TLR9 Agonist
Aaron Morris, Senior Director, Research, Checkmate Pharmaceuticals, Inc.
Addition of TLR9 agonist CMP-001 to a standard checkpoint inhibitor regimen can induce a strong anti-tumor response when checkpoint inhibition alone has failed. CMP-001 is a formulation of a CpG-A oligonucleotide, G10, within a Qb virus-like particle (VLP). Preclinical studies and a phase Ib clinical trial have shown induction of robust anti-tumor immunity and tumor regression when CMP-001 is combined with anti-PD-1 therapy.
12:05 pm Novel Immunotherapy Combinations in Non-Small Cell Lung Cancer and Head and Neck Cancers
Erminia Massarelli, M.D., Ph.D., MS, Associate Clinical Professor, Medical Oncology and Therapeutics Research, City of Hope
Checkpoint inhibitors have become the standard second line treatment for patients with metastatic/incurable non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) with an overall survival advantage of 4-5 months compared to second line standard chemotherapy. I will review promising immunotherapy combinations that are currently under investigation with particular focus on T cell agonist targeting OX-40 and 41BB receptors in NSCLC and HNSCC.
12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:05 Refreshment Break
1:35 Chairperson’s Remarks
Harpreet Singh, Ph.D., President & CEO, Immatics US, Inc.
1:40 Exploring the Intracellular Proteome for the Identification and Validation of Novel Targets for Cancer Immunotherapy
Yoram Reiter, Ph.D., Professor & Head, Laboratory of Molecular Immunology, Technion-Israel Institute of Technology
T-cell receptor-like (TCRL) antibodies bind HLA-peptide complexes on the surface of cells and can bind specifically to the cell surface of diseased cells, thus, transforming intracellular disease-specific targets expressed inside malignant cells into targets that can be recognized on the cell surface by soluble TCRL antibodies. These antibodies can be armed with various modalities or they can be used as naked molecules to modulate responses or environments associated with immunity towards the target cells. This approach expands the pool of novel therapeutic targets and antibodies beyond the limits of currently available antibodies.
2:10 Novel Targets for Cancer Immunotherapies: The XPRESIDENT® Approach
Harpreet Singh, Ph.D., President & CEO, Immatics US, Inc.
Targeted adoptive cell therapies have been highly successful in achieving durable clinical responses in B-cell malignancies based on targeting CD19. Novel T-cell targets are required to expand this success to solid cancers. Here we present the outcome of the Human Immunopeptidome Program through applying our proprietary XPRESIDENT® target discovery strategy which employs systematic high-throughput and ultra-sensitive quantitative tandem mass spectrometry combined with next-generation sequencing and T-cell receptor discovery.
2:40 Development and Validation of a Phenotypic Screening Platform for the Identification of Novel Immuno-Oncology Targets
Christophe Quéva, Ph.D., CSO, iTeos Therapeutics SA
A co-culture assay combining immune suppressive cells and T-cells has been set up to allow the identification of novel immune-oncology targets by screening chemicogenomics, shRNA and cDNA libraries. Multi-parameter readouts are combined to assess both T cell activation and proliferation, through high content imaging, complemented with detection of IFNγ secretion, as well as tumor cell death, as assessed using a cytotoxicity assay. Application of this screening assay to the identification of rationale combinations will be described.
3:10 Emerging Innate Immune Targets for Enhancing Adaptive Anti-Tumor Responses
Gretchen Baltus, Associate Principal Scientist, Oncology Discovery, Merck Research Labs
Novel cancer immunotherapies targeting T cell checkpoint proteins have emerged as powerful tools to induce profound, durable regression and remission of many types of cancer. Despite these advances, multiple studies have demonstrated that not all patients respond to these therapies, and the ability to predict which patients may respond is limited. Harnessing the innate immune system to augment the adaptive anti-tumor response represents an attractive target for therapy, which has the potential to enhance both the percentage and rate of response to checkpoint blockade.
3:40 End of Conference