Cambridge Healthtech Institute's Fourth Annual

Agonist Immunotherapy Targets

( アゴニスト免疫療法の標的 )

共刺激剤による効能の強化

2018年5月3-4日 | World Trade Center | マサチューセッツ州ボストン

 

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

Recommended Short Course(s)*

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.

5月3日 (木)

最新の研究成果−OX40、4-1BB

12:00 pm Registration

12:35 Luncheon in the Exhibit Hall with Poster Viewing

1:40 Chairperson's Remarks

Peter Ellmark, PhD, Principal Scientist, R&D, Alligator Bioscience

1:50 PD1-Fc-OX40L for Cancer Immunotherapy

Taylor SchreiberTaylor 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 MayesPatrick 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 Sponsored Presentation (Opportunity Available)

3:50 Networking Refreshment Break

4:20 Tumor Directed T Cell Modulation Using a Bispecific Targeting OX40 and CTLA-4

Peter EllmarkPeter Ellmark, PhD, Principal Scientist, R&D, 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

5月4日 (金)

8:00 am Morning Coffee

細胞壊死因子受容体 (TNFR) アゴニスト

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. FaustmanDenise 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 HillOliver 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 Sponsored Presentation (Opportunity Available)

10:05 Networking Coffee Break

新たなアゴニスト−ICOS、TLR

10:35 KEYNOTE: Development of JTX-2011, A Novel ICOS Agonist Antibody

Debbie LawDebbie 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. AdlerAdam 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 Agonist Pathways to Make New Oncology Medicines

Deborah H. CharychDeborah H. Charych, PhD, Executive Director, Nektar Therapeutics

We have engineered endogenous proteins and exogenous small molecules into viable 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 Preclinical and Clinical Updates in Agonist Immunotherapy Targets

Adi DiabAdi Diab, PhD, Assistant Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston



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

1:05 Networking Refreshment Break

STINGアゴニストと新たな標的

1:35 Chairperson's Remarks

Harpreet Singh, President & CEO, Immatics US

1:40 Addressing Solid Cancers with Novel Targets and TCR-T Approaches

Harpreet SinghHarpreet 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 AgerCasey 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 CemerskiSaso 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. SteinRobert B. Stein, MD, PhD, Senior Advisor, R&D, Agenus, Inc.

 

 

 

 

 

3:40 End of Conference

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

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