Agonist Immunotherapy Targets and Combination Therapies banner

- 促效剂标靶和并用 -

While much attention in immunotherapy to-date has been given to checkpoint inhibitors such as PD-1/PD-L1 and CTLA-4, there’s a rising interest in agonist targets such as OX40, 4-1BB, CD27, GITR, ICOS, TNFR receptors, STING, etc., as it’s been found that antagonists alone are not enough to elicit response in the majority of patients.

PEGS Europe’s Inaugural Agonist Immunotherapy Targets and Combination Therapies presents updates and exciting development of these co-stimulatory agonists in monotherapy or in combination with co-inhibitory antagonists.


Final Agenda

THURSDAY 15 NOVEMBER

13:00 Registration

13:15 Dessert Break in the Exhibit Hall with Poster Viewing

CYTOKINE RECEPTORS – IL2, TNFR-SF

14:00 Chairperson’s Opening Remarks

Patrick Mayes, PhD, Executive Director, Head of I-O Biotherapeutics, Incyte

14:05 Interleukin-2: Releasing an Immune System Brake to Attack Tumors

Christ_DanielDaniel Christ, PhD, Associate Professor, Director, Centre for Targeted Therapy, Garvan Institute of Medical Research

Interleukin-2 is an established therapeutic agent used for cancer immunotherapy. It is generally believed that treatment efficacy is mediated by CD8+ and NK cell activity, and considerable efforts have focused on generating IL-2 variants that expand these subsets systemically. Here we describe a second and unexpected mechanism, namely the selective depletion of CD25+ CD4+ regulatory T-cells (Tregs), as a major determinant of antitumour activity. Our results outline mechanisms of action and provide important guidance for the development of next-generation cytokine therapeutics.

14:35 NKTR-214: Cytokine Engineering to Access the IL-2 Pathway

Zalevsky_JonathanJonathan Zalevsky, PhD, Senior Vice President, Research, CSO, Nektar Therapeutics

NKTR-214 is a CD-122-biased agonist that targets the IL-2 pathway to provide sustained signaling through the heterodimeric IL-2 receptor pathway (IL-2RβƔ). NKTR-214 preferentially activates and expands NK and effector CD8+ T cells over T-regulatory cells in the tumor microenvironment. In addition, NKTR-214 promotes an invigorated immune phenotype and drives cell surface expression of costimulatory molecules, such as ICOS, and coinhibitory receptors, such as PD-1 on the surface of newly proliferating lymphocytes. The immune replenishing mechanism of action of NKTR-214 makes it an ideal combination partner with multiple immune oncology mechanisms.

15:05 Sponsored Presentation (Opportunity Available)

15:35 Networking Refreshment Break

16:00 HERA: Engineering Next-Generation TNFR-SF Agonists for Cancer Immunotherapy

Hill_OliverOliver Hill, PhD, Vice President, Molecular Biology/Protein Engineering, Apogenix AG

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 and HERA-GITRL will be presented.

16:30 Agonistic Activation of TNFR-SF Receptors by HexaBody IgG-induced Oligomerization

de_Jong_RobRob de Jong, PhD, Assistant Director, Protein Chemistry & CMC, Genmab BV


17:00 End of Day

17:00 Dinner Short Course Registration*

17:3020:30 Dinner Short Courses


Recommended Short Course*

SC10: Engineering of Bispecific Antibodies

Nicolas Fischer, PhD, Head, Research, Novimmune SA

Michela Silacci, PhD, Director, Discovery Research, Covagen AG, part of J&J

By attending this interactive workshop, you will learn about the various approaches used for the engineering of bispecific antibodies and bispecific scaffold-based binding proteins. Different technologies will be compared, and examples for applications of bispecific antibodies in drug development will be presented with a focus on candidates that are currently being evaluated in clinical trials. Opportunities and challenges as well as current trends in the field of bispecific antibodies will be discussed.

*Separate registration required.

FRIDAY 16 NOVEMBER

08:00 Registration and Morning Coffee

OX40, GITR AND 4-1BB AGONISTS

08:30 Chairperson’s Remarks

Daniel Christ, PhD, Associate Professor, Director, Centre for Targeted Therapy, Garvan Institute of Medical Research


08:35 KEYNOTE PRESENTATION: Deciphering 4-1BB (CD137) for Cancer Immunotherapy

Melero_IgnacioIgnacio Melero, MD, PhD, Professor, Immunology & Immunotherapy, University of Navarra


09:05 ATOR-1017 – An Agonistic Tumor Directed Fcγ-Receptor Cross Linking Dependent CD137 Antibody

Sall_AnnaAnna Säll, PhD, Scientist, Alligator Bioscience

ATOR-1017 is an agonistic CD137 IgG4 antibody with a unique functional profile compared to the 4-1BB antibodies currently in clinical development. The functional activity depends on cross-linking mediated by Fcγ receptors, which directs the immune activation to the tumor area and reduces the risk of inducing systemic immune activation and liver toxicity. ATOR-1017 is currently in preclinical development and clinical trials will start in the second half of 2019.

09:35 Tumor-Targeted DARPin® Drug Candidates for Tumor-Restricted Immune Cell Co-Activation

Reichen_ChristianChristian Reichen, PhD, Senior Scientist Lead Generation, Protein Engineering, Molecular Partners AG

Dose-limiting toxicity can hamper effective dosing and combination with checkpoint inhibitors and other immune stimulating drugs. By using the DARPin® toolbox, we have developed a set of multi-specific molecules that enable tumor-restricted immune cell activation, thereby largely reducing the risk of systemic side effects. Data from the preclinical development of tumor-restricted agonists will be presented on MP0310, a 4-1BB/FAP bispecific DARPin drug candidate promoting T cell expansion in a strictly FAP-dependent manner. FAP is highly expressed in human tumor stroma cells.

10:05 Networking Coffee Break

10:35 Multispecific and Multivalent Antibodies as OX40 Agonists

Li_FrancisFrancis Qufei Li, PhD, Senior Scientist, R&D, Invenra, Inc.

OX40 agonists have demonstrated significant therapeutic potential in preclinical models; however, their efficacy in clinical trials is minimum. We hypothesize the efficacy in humans is limited by insufficient crosslinking in the tumor microenvironment. Thus, we aimed for biparatopic antibody to directly crosslink OX40 and successfully developed soluble agonists, which are potent in the absence additional crosslinker. This strategy together with high-throughput bispecific antibody screening is applicable to agonist discovery for a wide range of receptors.

11:05 What’s Next for GITR and OX40 Agonists?

Mayes_PatrickPatrick Mayes, PhD, Executive Director, Head of I-O Biotherapeutics, Incyte

A discussion of combination approaches for GITR and OX40 agonist antibodies in cancer. Integration of tumor biomarker analyses in response to agonist antibody treatment to inform upon GITR and OX40 combinations.


11:35 Sponsored Presentation (Opportunity Available)

12:05 Problem-Solving Breakout Discussions with a Light Snack

NOVEL AGONISTS AND COMBINATION THERAPIES

13:00 Chairperson’s Remarks

Jonathan Zalevsky, PhD, Senior Vice President, Resesarch, CSO, Nektar Therapeutics

13:05 Discovery and Development of Novel STING Agonists for Immuno-Oncology

Iyer_RR.P. Iyer, PhD, Co-Founder and CSO, Spring Bank Pharmaceuticals


13:35 AcTakines: A Novel Class of Cancer Immunotherapeutics

Depla_ErikErik Depla, PhD, Director, Biology, Orionis Biosciences

Type I IFN-derived AcTakines targeting dendritic cells displayed strong antitumor activity in murine melanoma, breast carcinoma, and lymphoma models and against human lymphoma in humanized mice without detectable toxic side effects. Combined with immune checkpoint blockade or chemotherapy, complete tumor regression and long-lasting tumor immunity were observed. Our findings indicate that AcTakines targeted to dendritic cells provide a novel class of highly efficient, safe, and broad-spectrum cancer immunotherapeutics.

14:05 Chemotherapy Combinations to Enhance Tumor Response to Agonist Antibodies

BetofWarner_AllisonAllison Betof Warner, MD, PhD, Medical Oncology Fellow, Memorial Sloan Kettering Cancer Center

Stimulation of glucocorticoid-induced tumor necrosis factor receptor (GITR) has been shown to enhance antitumor immunity by stimulating effector CD4+ and CD8+ T cells and attenuating suppression and depleting by CD4+Foxp3+ regulatory T cells (Treg). However, GITR monotherapy does not effectively control tumor growth. I will discuss our data showing that cyclophosphamide (CTX), a cytotoxic chemotherapeutic agent with key immunomodulatory properties, can enhance the potency of GITR engagement anti-tumor effects.

14:35 Tumor-Targeted Combination of TNFSF Agonists and IL-15 for Cancer Immunotherapy

Mueller_DafneDafne Muller, PhD, Group Leader, Institute of Cell Biology and Immunology, University of Stuttgart

Costimulatory members of the TNF-superfamily and IL-15 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 different formats of bi- and trifunctional antibody-fusion proteins, focusing on tumor-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.

15:05 Oncorus Oncolytic HSV, a Platform for Combination Immunotherapy

Queva_ChristopheChristophe Queva, PhD, CSO, Oncorus

Oncorus is developing the next generation HSV-based oncolytic virus with enhanced potency for tumor cell killing and recruitment of the immune system. Our innovative miR-attenuation strategy enables robust viral replication in tumor cells, while preventing replication in healthy tissue. Oncorus’ oHSV are armed with multiple immunomodulatory payloads to synergistically increase recruitment and effector function of immune cells, thus harnessing the full potential of OVs to evoke an abscopal immune response.

15:35 End of Summit

* 活动内容有可能不事先告知作更动及调整。

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