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The Agonist Immunotherapy Targets conference at PEGS Europe will showcase the expanding formats and design principles toward agonist targets and pathways; discuss strategies to enhance specificity and reduce toxicity; and present the latest updates and lessons learned from molecules in preclinical to clinical development.
Day 1 | Day 2
13:00 Registration (Foyer A)
13:15 Dessert Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)
ENHANCING TUMOR TARGETING AND AUTOIMMUNITY
14:00 Chairperson’s Opening Remarks
Elizabeth Trehu, MD, FACP, CMO, Jounce Therapeutics
14:05 FEATURED PRESENTATION: Controlling STING, Infectious Disease, Inflammation and Cancer
Glen Barber, PhD, Professor, Cell Biology, University of Miami
Regulation of the immune system to facilitate anti-tumor cytotoxic T cell (CTC) responses is proving to be a powerful approach for the treatment of cancers. STING controls a key innate immune signaling pathway that influences cytokine production essential for robust CTC activity, although chronic signaling can invoke inflammation. Understanding these processes has shed significant insight into mechanisms of viral pathogenesis, inflammation as well as anti-tumor immunity and is leading to the generation of novel strategies to help treat such diseases.
14:35 Enhancing Antibody Tumor Targeting with Immunostimulation
Sean Hua Lim, PhD, CRUK Associate Professor, Honorary Consultant, Haematological Oncology, Antibody & Vaccine Group, CCI, University of Southampton
Tumour-targeting monoclonal antibodies have proven but limited anti-tumour efficacy. Here, we discuss how immunostimulatory antibodies can enhance the efficacy of tumour-targeting antibodies through bystander myeloid cell activation.
15:05 SELECTED POSTER PRESENTATION: Developing New Antibodies to Target Treg Cells Using the Patient Centric F.I.R.S.T.™ Platform
David Ermert, PhD, Senior Research Scientist
Petra Holmkvist, PhD, Research Scientist, Antibody Discovery & Target ID, Bioinvent Intl AB
As many of the most well-established immune receptors such as CD40, OX40, CTLA4, and PD-1, have already been specifically targeted using conventional antibody generation approaches, alternative approaches are required to generate the next generation of novel immunomodulatory antibodies. We therefore applied an unbiased, phenotypic strategy to identify new first-in-class immunomodulatory antibodies. With our patient-centric F.I.R.S.T.™ platform we isolate tumor associated immune cells from primary tumour tissue, and use them to screen for novel antibodies from our fully human n-CoDeR® phage display library. This target-agnostic, holistic approach allows us to identify and develop first-(and best)-in-class antibodies directed to novel targets and antibodies, which by conventional target-focused approaches based on well-established known receptor functions would be neglected and disregarded.
15:35 Networking Refreshment Break (Foyer D)
16:00 Development of ONCR-177, a miR-Attenuated Oncolytic HSV-1 Designed to Potently Activate Systemic Anti-Tumor Immunity
Christophe Queva, PhD, CSO, Oncorus, Inc.
ONCR-177 is an oncolytic Herpes Simplex Virus engineered with complementary safety mechanisms, such as tissue-specific miR attenuation and UL37 mutation to reduce replication, neuropathic activity, and latency in normal cells, while preserving oncolytic ability in tumor cells. ONCR-177 is armed with five transgenes: IL-12, CCL4, FLT3LG, and antagonists to PD-1 and CTLA-4. Mouse ONCR-177 mediates potent anti-tumor efficacy in multiple syngeneic models, and elicit durable complete responses and protective immunity warranting its clinical investigation for the treatment of metastatic cancer.
16:30 Immunomodulatory Properties of the Glyco-Optimized Anti-EGFR Antibody Tomuzotuximab and Their Relevance for Combinatory Immunotherapy
Christoph Goletz, PhD, Associate Director, Preclinical Pharmacology & Cancer Immunology, Glycotope GmbH
Tomuzotuximab (previously known as CetuGEX) is a defucosylated anti-EGFR antibody with enhanced capacity to mediate antibody-dependent cellular cytotoxicity (ADCC) compared to its fucosylated counterpart cetuximab. In this study, we evaluated the immune activation by tomuzotuximab beyond NK cell-mediated ADCC in comparison to cetuximab in order to build up rationales for combinatory therapies with agonistic and antagonistic antibodies targeting immune checkpoint molecules.
17:00 End of Day
Day 1 | Day 2
17:00 Dinner Short Course Registration*
17:30 – 20:30 Dinner Short Courses
Recommended Short Course*
SC10: Engineering of Bispecific Antibodies and Multi-Specific Non-Antibody Scaffolds - LEARN MORE
*Separate registration required.
08:00 Registration (Foyer A) and Morning Coffee (Foyer D)
08:30 Chairperson’s Remarks
Peter Ellmark, PhD, Vice President Discovery, Alligator Bioscience AB
8:35 KEYNOTE PRESENTATION: Agonists to the TNF Superfamily: Lessons Learned for TNFR2 for Autoimmunity
Denise L. Faustman, MD, PhD, Director, Immunology, Massachusetts General Hospital; Associate Professor, Medicine, Harvard Medical Schoolx
TNFR2 is a bi-directional switch for Treg expansion or contraction and therefore an attractive target for autoimmunity versus cancer therapies. Over the last 10 years we have worked on the perfection of agonistic antibodies to the TNF superfamily to identify candidates that do not require the natural ligand and do not require ADCC engagement, both traits that limit the clinical effectiveness due to ligand availability and could be associated with liver toxicity. New candidates with these traits have been identified to the human TNFR2 receptor and in autoimmune cells in culture restore the potent immunsupression of Tregs that were weak prior to exposure to novel agonistic proteins.
09:05 Emergence of ICOS hi CD4 T Cells Correlates with Tumor Reduction, Progression-Free Survival, and Overall Survival in Advanced Cancer Patients Treated with Vopratelimab, an ICOS Agonist
Elizabeth Trehu, MD, FACP, CMO, Jounce Therapeutics
Vopratelimab is an ICOS agonist antibody intended to stimulate primed CD4 T effector cells. In the ICONIC trial, peripheral T cell phenotyping demonstrated emergence of an ICOS hi subset of activated CD4 T effector cells associated with tumor reductions and improved PFS and OS in mono and combo patients, with expansion of peripheral T cell receptor clones found in the original matched archival tumor. Future development focuses on settings in which CD4 T effector cells are primed to respond to vopratelimab.
09:35 GSK3359609- Anti-ICOS IgG4 Antibody Engineered for Optimized T Cell Agonist Effects Translating to Anti-Tumor Responses in the Clinic
Sapna Yadavilli, PhD, Associate Fellow, Precision Medicine Lead, Clinical Biomarkers and Experimental Medicine, Oncology TA, GSK
ICOS is a T cell costimulatory receptor with unique function in T and B cell-mediated immune responses. GSK3359609 is a humanized IgG4PE with strong binding to ICOS without ADCC mediated T cell depletion which exhibits immune-stimulatory activity and efficacy in non-clinical tumor models. In the INDUCE-1 study, pharmacodynamic evaluation of GSK3359609 demonstrates dose-dependent changes in immune activation as well as promising clinical activity as monotherapy and in combination with PD1 blockade.
10:05 Networking Coffee Break (Foyer D)
10:35 CTX-471, a CD137 Agonist Undergoing Clinical Development in Patients with Advanced Solid Tumors
Michael J. Schmidt, SVP & Head, Research, Compass Therapeutics
CTX-471 is a fully human monoclonal antibody that binds and activates a novel epitope of the co-stimulatory receptor CD137. Preclinical data suggest that CTX-471 has the potential to become a best-in-class CD137 agonist displaying curative monotherapy efficacy against multiple syngeneic tumor models and generation of long-term functional immunological memory. Most notably, CTX-471 is able to induce the complete eradication of large, established tumors where other preclinical CD137 antibodies and antibodies against PD-1, PDL-1, CTLA-4, and OX40 have minimal effect.
11:05 T Cell Enhancers for Focused CD137/4-1BB Co-Stimulation in the Tumor Microenvironment
James Legg, PhD, Senior Vice President, Research, Crescendo Biologics
Agonist antibodies binding to CD137 have shown great promise in preclinical models, but clinical development has been frustrated by severe toxicity and a narrow therapeutic index due to on-target, out-of-tumour activation leading to liver toxicity. Crescendo Biologics has initiated preclinical development of CB307, a novel tri-specific T cell enhancer targeting CD137, prostate specific membrane antigen (PSMA) and human serum albumin. This molecule has been designed to focus CD137 co-stimulation in the tumour and achieve an improved therapeutic index. The talk will describe the mechanism of action and preclinical characterisation of CB307 as well as an update on preclinical development.
11:35 Novel Strategies in Targeting CD137 in Solid Tumors
Erminia Massarelli, MD, PhD, Associate Clinical Professor, Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center
CD137 is an attractive target in solid tumors to activate and enhance anti-cancer immune responses as well as suppress oncogenic cells. Anti-CD137 antibodies have shown safety and efficacy in selected solid tumors and trials are ongoing studying safety and efficacy of these antibodies in combination with other immunotherapy strategies. In this talk current knowledge of targeting CD137 strategies and future perspectives will be discussed.
12:05 Problem-Solving Breakout Discussions with a Light Snack*
Topic 32: Clinical Relevance of in vitro Mouse Data to in vivo Results for Single and Combination Studies
Moderator: Erminia Massarelli, MD, PhD, Assoc Clinical Prof, Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center?
- Advantages/disadvantages of in vitro and in vivo models
- Translational applications of in vitro and in vivo models: what dp they tell us about the efficacy of monotherapy and combination treatments?
- Are in vitro and in vivo cancer models of any translational significance in testing immunotherapy?
Topic 33: Combining Virotherapy with Immunotherapy – Challenges and Opportunities
Moderator: Christope Queva, PhD, CSO, Oncorus, Inc.
- Rationale for the combination of virotherapy and immunotherapy?
- Beside the combination with checkpoint inhibitors, is there anything else that make sense?
- Do IO drugs accelerate the clearance or limit the replication of Interferon sensitive virus, thus limiting the efficacy of virotherapy?
- Is it best to combine virotherapy with systemic administration of checkpoint inhibitors or to encode those checkpoints inhibitors in the virus?
CD40, GITR AND OX40
13:00 Chairperson’s Remarks
Denise L. Faustman, MD, PhD, Director, Immunology, Massachusetts General Hospital; Associate Professor, Medicine, Harvard Medical School
13:05 Bispecific Agonistic Antibodies for Tumor Directed Immunotherapy
Peter Ellmark, PhD, Vice President, Discovery, Alligator Bioscience AB
Preclinical data on Alligator’s bispecific programs will be presented, including a novel concept involving bispecific agonistic antibodies designed to increase the tumor-specific T cell repertoire. In vitro data and in vivo data using a transgenic mouse model will also be presented.
13:35 Development of a Novel Bi-Functional Fusion Protein: SIRPa-Fc-CD40L for Cancer Immunotherapy
George Fromm, PhD, Vice President, R&D, Shattuck Labs, Inc.
The SIRPa/CD47 axis has emerged as an exciting clinical target, whereby blockade could enhance antigen cross-presentation in immune-neglected (anti-PD1 refractory) tumors. The most potent antigen cross-presenters (DCs/Macs) express CD40, and stimulation of CD40 enhances CD8+ lymphocyte activation by these cells. Dual CD47-blockade and CD40-costimulation by SIRPa-Fc-CD40L performs both of these important functions, and has demonstrated superior activity compared to CD47/CD40 antibody combinations; which may position this compound to provide unique benefits to cancer patients.
14:05 Tumor Localized Agonistic Anti-CD40 Therapy and Beyond
Sara Mangsbo, PhD, Associate Senior Lecturer, Biologics, Uppsala University
Anti-CD40 agonistic therapy is a promising cornerstone in tumor immunotherapy. We have evaluated therapeutic effects of both agonistic CD40 antibodies along with CD40L expressing viruses in preclinical models, and some of our evaluated therapies have also reached clinical testing. Herein I will present the current work of our group with a focus on CD40 agonistic therapeutic strategies.
14:35 HERA-GITRL: A Unique Hexavalent GITR Agonist for Cancer Immunotherapy
Oliver Hill, PhD, Vice President, Drug Discovery/Lead Optimization, Apogenix AG
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.
15:05 Multispecific and Multivalent Antibodies as OX40 Agonists
Mandar Bawadekar, PhD, Senior Scientist, Immunology, Invenra
OX40 and other TNFR-Super Family members are notorious for requiring secondary cross-linking strategies to achieve activity with monoclonal antibodies, and thus present significant clinical challenge. In this presentation, we will talk about the OX40 agonist antibodies developed using Invenra’s B-Body™ platform, that exceed the potency of the OX40 ligand in NF-kB activation. Our lead agonist antibody has been optimized for activity and in vivo tumor efficacy and is currently under preclinical development.
15:35 End of Agonist Immunotherapy Targets