Agonist Immunotherapy Targets


The immunotherapies industry is currently dominated by 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.

CHI’s Agonist Immunotherapy Targets conference 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, STING, 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


12:00 pm Registration (Commonwealth Hall)

12:35 Luncheon in the Exhibit Hall with Poster Viewing (Commonwealth Hall)

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1:40 Chairperson’s Opening Remarks

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

1:50 KEYNOTE PRESENTATION: Harnessing Potent Cytokine Agonist Pathways by Polymer Engineering to Develop Novel Immune Therapeutic Agents

Madakamutil_LouiLoui Madakamutil, PhD, Vice President, Head of Discovery, Nektar Therapeutics

We have engineered cytokines using polymer technology to enable viable medicines. NKTR-214 is in Phase 3 clinical trials and a key example of how polymer conjugation can bias the well-known IL-2 receptor pathway to favor CD8 T cell tumor infiltration over Tregs. On the other hand, NKTR-358 selectively grows T regs in vivo. Finally, NKTR-255, an IL-15 receptor agonist stimulates NK cells. Each agent is conjugated in unique ways to elicit desirable and controlled pharmacological and immunological outcomes.

2:20 Agonists in Combination Immunotherapy

Redmond_WillWilliam L. Redmond, PhD, Associate Member, Laboratory of Cancer Immunotherapy, Director, Immune Monitoring Laboratory, Providence Portland Medical Center

Our previous studies helped elucidate the mechanisms by which OX40 agonist immunotherapy plus checkpoint blockade synergized with a novel cancer vaccine to boost the function of killer CD8 T cells and cause tumor regression. We are investigating how combination immunotherapy restores the function of killer CD8 T cells that have been paralyzed, or rendered anergic, by tumors. Additional studies seek to understand the mechanisms by which immunotherapy enhances the efficacy of conventional treatments, such as radiation therapy, with the goal of providing a path for rapid translation to the clinic.

2:50 OX40: Is Timing Everything?

Curti_BrendanBrendan Curti, MD, Robert W. Franz Chair for Clinical Research, Earle A. Chiles Research Institute, Providence Cancer Institute

We now have FDA-approved checkpoint immunotherapy for many stage III and IV cancers, but administration of immunotherapy before surgery has not been as extensively investigated. A clinical trial of the neoadjuvant administration of an agonist antibody to OX40, a T cell co-stimulatory agent, will be discussed, along with changes in tumor infiltrating CD39+CD103+ T cells that we hypothesize are relevant to achieving effective anti-tumor immunity.

3:20 NEW: Poster Presentation: Locking the Latency Cage: Anti-LAP Antibodies to Target TGF-beta in a Context Dependent Manner

Randall Burton, Director, PhD, Antibody Development, Tilos Therapeutics

3:35 NEW: Poster Presentation: Early Characterization of Fc Effector Function Towards Control Strategies

Diana A. Pippig, Senior Scientist, Roche Pharma Research and Early Development, Large Molecule Research, Roche Innovation Center Munich

3:50 Networking Refreshment Break (Harbor & Mezzanine Level)

4:20 Agonist Bispecific Antibodies Delivering the Next Immuno-Oncology Breakthrough

Tuna_MihribanMihriban Tuna, PhD, Vice President, Drug Discovery, F-star Biotechnology, Ltd.

Targeting T cell costimulatory pathways can strongly activate the immune system due to the broad expression of receptors such as OX40 and CD137 across multiple immune cell types. However, Fcg receptor (FcgR)-mediated crosslinking is often required for the activity of monoclonal antibodies, and we hypothesise that this likely limits clinical activity due to the inherently low affinity of Fc:FcgR interactions, as well as the potential for FcgR-mediated depletion of T cells through ADCC. Here we will present novel bispecific antibody programmes that do not rely on FcgR binding, but instead crosslink using their two target binding sites.

4:50 Development of SIRPa-Fc-CD40L for Cancer Immunotherapy

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

The CD47/SIRPa axis functions to enhance antigen cross-presentation within the context of anti-tumor immunity, which holds promise for the treatment of immune-neglected tumors. The subset of dendritic cells which are the most potent antigen cross-presenters express CD40, and stimulation of CD40 enhances activation of CD8+ lymphocytes by these cells. SIRPa-Fc-CD40L has demonstrated superiority to CD47/SIRPa blocking antibodies, CD40 agonist antibodies, and antibody combinations in both rodent and non-human primate studies, which position this compound to provide unique benefits to human cancer patients.

5:20 End of Day

5:20 Registration for Dinner Short Courses (Commonwealth Hall)

*Separate registration required.


8:00 am Morning Coffee (Harbor Level)

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8:30 Chairperson’s Remarks

Christopher Thanos, PhD, CEO, Actym Therapeutics

8:35 The Appeal of The TNFR2 Target for Immunotherapy: Tregs and Tumor Oncogenes

Faustman_DeniseDenise 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 Development of TNF Superfamily Agonists

Raue_AndreasAndreas Raue, PhD, Associate Director, Research, Merrimack Pharmaceuticals

Members of the TNF superfamily of costimulatory receptors have emerged as promising immuno-oncology targets, and agonistic antibodies are currently being evaluated clinically. Here, we describe our STIMULI platform, which consists of novel multispecific and multivalent TNF receptor agonists, engineered to provide more precise activation of immune cell subsets.

9:35 NEW: Poster Presentation: HERA-CD40L: A Unique Hexavalent CD40 Agonist for Cancer Immunotherapy

Karl Heinonen, MSc, Laboratory Head Protein Production, Apogenix

10:05 Networking Coffee Break (Harbor & Mezzanine Level)

10:35 IGM Antibodies with Very Potent Agonism to DR-5 Induced Apoptosis and as Anti-Tumor Agents

Keyt_BruceBruce 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.

11:05 ATOR-1017, A 4-1BB Antibody Developed for Tumor Directed Immunotherapy of Cancer

Enell_Smith_KarinKarin Enell Smith, PhD., Senior Scientist, Immuno-oncology, Alligator Bioscience

ATOR-1017 is a 4-1BB agonistic IgG4 antibody designed for optimal efficacy and safety. The agonistic activity of ATOR-1017 depends on engagement with certain FcγRs, and it will thereby induce a tumor directed immune activation in patients with tumors co-expressing these FcγRs and 4-1BB. The preclinical data package supports a favorable safety/efficacy profile. Clinical studies with ATOR-1017 are planned for 2019.

11:35 Structure of the 4-1BB/4-1BBL Complex and Distinct Binding and Functional Properties of Utomilumab and Urelumab

chaparro-riggers_javierJavier Chaparro-Riggers, PhD., Director, Antibody Technology, Pfizer

4-1BB is an inducible costimulatory receptor expressed on activated T cells. Two agonist antibodies, utomilumab (PF-05082566) and urelumab (BMS-663513), demonstrate distinct activities in the clinic. To understand these differences, we solved structures of the human 4-1BB/4-1BBL complex, the 4-1BBL trimer alone, and 4-1BB bound to utomilumab or urelumab. Additionally, cell-based assays demonstrate utomilumab is a milder agonist than urelumab. Collectively, our data provide a deeper understanding of the 4-1BB signaling complex, providing a template for future development of next generation 4-1BB targeted biologics.

12:05 pm CB307, A Novel T-Cell Agonist Humabody Therapeutic for PSMA-Positive Tumours

Legg_JamesJames Legg, PhD, Vice President, Research and Development, Crescendo Biologics

Crescendo Biologics has initiated pre-clinical development of CB307 a novel bispecific Humabody VH targeting CD137 (4-1BB) and prostate specific membrane antigen (PSMA). The talk will describe the identification, mechanism of action and preclinical characterisation of the CB307 drug candidate. The benefits of using the modular Humabody VH platform, rather than an IgG format to develop this molecule will be discussed, including optimal (monovalent) engagement of both targets with small VH domains and the avoidance of Fc receptor interactions. The unique design of CB307 enables highly potent and tumour selective T-cell co-stimulation.

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

1:05 Networking Refreshment Break (Harbor & Mezzanine Level)

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1:35 Chairperson’s Remarks

Christopher Thanos, PhD, CEO, Actym Therapeutics

1:40 CTX-471 Eradicates Very Large Tumors without Causing Hepatic Toxicity

Eskiocak_UgurUgur Eskiocak, PhD, Associate Director, Translational Immunology & Immunopharmacology, Compass Therapeutics

CTX-471 is a fully human IgG4 agonistic antibody targeting a unique CD137 (4-1BB) epitope and displays differentiated pharmacology and toxicology profile. In vitro, CTX-471 increased IFN-γ production by human T cells in an FcγR-dependent manner, displaying an intermediate level of activity between two clinical-stage anti-CD137 antibodies. In mice, CTX-471 exhibited curative monotherapy activity in various syngeneic tumor models and showed a unique ability to cure very large (~500 mm3) tumors compared to validated antibodies against checkpoints and TNFR superfamily members. In mice and monkeys, extremely high doses of CTX-471 (up to 100 mg/kg weekly for 4 weeks) were well-tolerated, with no signs of hepatic toxicity. Phase 1 trial for CTX-471 is planned for 2019.

2:10 ImmunoSTATs: A Novel Biologics Therapeutic Platform for Antigen-Specific Immunotherapy

Anish Suri, PhD., CSO, Cue Bio

ImmunoSTATs are proprietary biologics that incorporate, in a single molecular framework, key signals needed to selectively modulate antigen-specific T cells: namely, the pMHC-complex and relevant co-stimulatory/co-inhibitory signals, dependent upon the disease indication. The lead clinical candidate CUE-101 is comprised of HLA-A*0201, genetically bound to a HPV16 epitope (E7 protein, peptide 11-20), along with affinity-attenuated human interleukin-2 to selectively activate and expand HPV16 E711-20-specific CD8+ T cells for HPV-driven malignancies.

2:40 A Novel Systemically Delivered STING Pathway Agonist Therapy Demonstrates Robust Anti-Tumor Efficacy in Multiple Murine Cancer Models

Christopher Thanos, PhD, CEO, Actym Therapeutics

Delivery of immunotherapy to directly activate tumor-resident immune cells is required to elicit durable anti-tumor immunity. To this end, we have generated an immunotherapy platform that allows for tumor-specific delivery of engineered RNAi towards any tumor/immune target of interest (alone or in combination). For our initial RNAi target selection, a therapy targeting TREX1 was designed. TREX1 is a 3′ exonuclease immune checkpoint that degrades cytosolic DNA, thereby preventing it from binding cGAS and activating the STING pathway.

3:10 CANCELLED: Beyond PD1: Targeting STING and Other Novel Pathways

Desbien_AnthonyAnthony Desbien, PhD., Senior Scientist, Translation Immunology, Aduro Biotech

3:40 End of Conference

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