Cambridge Healthtech Institute’s Second Annual

Cancer Immunotherapy

Emerging Biology, New Targets, Development Strategies and Clinical Studies

February 20-22, 2017 | Moscone North Convention Center | San Francisco, CA
Part of the 24th International Molecular Medicine Tri-Conference

 

Immuno-oncology research and the subsequent development of immunotherapies continue to rapidly advance the fight against cancer. First-generation agents achieving remarkable clinical success have inspired researchers to pursue a variety of new treatment modalities, creating a robust development landscape now centered on combinations strategies. These next-generation agents, in combination with targeted therapies or other immune-modulators such as checkpoint antibodies, are poised to significantly enhance clinical response in a wider range of cancers.

Due to the success of the inaugural event, Cambridge Healthtech Institute is proud to host the Second Annual Cancer Immunotherapy meeting, designed to convene a leading collection of immuno-oncologists, drug developers, and technology providers.



Monday, February 20

10:30 am Conference Program Registration Open

EMERGING CHECKPOINTS, COMBINATIONS AND CLINICAL STUDIES

11:50 Chairperson’s Opening Remarks

Christopher Shelton, Ph.D., Manager, Immuno-Oncology & Combinations DPU, Oncology R&D, GlaxoSmithKline

12:00 pm TACTI-mel, Two ACTive Immunotherapies in Melanoma: Combination of IMP321 (LAG-3Ig) with an Anti-PD-1 Antagonist in a Phase I Trial

Frédéric Triebel, M.D., Ph.D., CSO & CMO, Prima BioMed Ltd.

IMP321 (LAG-3Ig) binds to MHC class II molecules on the surface of antigen-presenting cells and activates the cellular immune response mechanisms known to mediate tumor recognition and killing. Inducing more TILs at the tumor site with an APC activator like IMP321 while releasing the PD-1 brake on TILs may lead to greater anti-tumor efficacy than anti-PD-1 alone. A Phase I trial called TACTI-mel for Two ACTive Immunotherapies in melanoma has been started in 2016 combining a low-dose agonist (IMP321) with a high-dose antagonist (pembrolizumab) in advanced or metastatic melanoma.

12:30 CPI-444 – A Novel Oral Checkpoint Inhibitor of Adenosine-Mediated Suppression of Tumor Immunity

Ian McCaffery, Ph.D., Vice President, Translational Sciences, Corvus Pharmaceuticals

CPI-444 is a novel, selective inhibitor of adenosine 2A receptor (A2AR), the key mediator of adenosine-mediated immune suppression. CPI-444 is being evaluated in a multicenter Phase I/Ib clinical trial in patients with various solid tumors both as a single agent and in combination with TECENTRIQTM (atezolizumab), Genentech’s investigational cancer immunotherapy that targets PD-L1. Insights into the underlying biological mechanisms of adenosine activity in tumors from ongoing preclinical and clinical studies of CPI-444 will be discussed.

1:00 Session Break

Clarivate Analytics1:10 Luncheon Presentation I: Hypothesizing Co-Immunotherapy Targets for Tumor Infiltrating Myeloid Derived Suppressor Cells

Matthew E. Wampole, Ph.D., Solution Scientist, Clarivate Analytics (formerly the IP & Science division of Thomson Reuters)

This presentation will overview the field of cancer immunotherapies and look at how data and knowledge driven approaches are being used to find potential new targets for treating resistant populations.

1:40 Luncheon Presentation II (Sponsorship Opportunity Available)

2:10 Session Break

TARGETING MACROPHAGE CHECKPOINTS FOR NEW IMMUNOTHERAPIES AND COMBINATIONS

2:30 Chairperson’s Remarks

Christopher Shelton, Ph.D., Manager, Immuno-Oncology & Combinations DPU, Oncology R&D, GlaxoSmithKline

2:40 TTI-621 (SIRPαFc): A Checkpoint Inhibitor of the Innate Immune System that Blocks the CD47 “Do Not Eat” Signal

Bob Uger, Ph.D., CSO, Trillium Therapeutics Inc.

CD47 binds to SIRPα on the surface of macrophages and delivers a “do not eat” signal that suppresses phagocytosis. There is strong evidence that many tumors express high levels of CD47 to escape macrophage-mediated immune surveillance. Trillium Therapeutics is developing TTI-621 (SIRPαFc), a fusion protein consisting of the CD47-binding domain of human SIRPα linked to the Fc region of human IgG1. This presentation will discuss the preclinical rationale and emerging clinical data for this novel innate immune system checkpoint inhibitor.

3:10 The Anti-CD47 Antibody Hu5F9-G4 Is a Novel Innate Immune Checkpoint Inhibitor with Broad Anti-Tumor Activity

Mark Chao, M.D., Ph.D., Co-Founder and Medical Director, Forty Seven Inc.

The anti-CD47 antibody Hu5F9-G4 is a first-in-class therapeutic that blocks CD47 signaling and eliminates tumors through phagocytosis. This anti-tumor activity is demonstrated across many solid tumor and hematologic malignancies in preclinical models. Furthermore, Hu5F9-G4 is able to combine with multiple cancer therapeutic classes to induce a synergistic anti-tumor effect. First-in-class, first-in-human Phase I trials have been initiated in solid tumors and acute myeloid leukemia. During this talk, preclinical data for monotherapy and combination therapy efficacy with Hu5F9-G4 will be presented as well as data from ongoing clinical studies.

3:40 Targeting SIRPα to Control Myeloid-Derived Suppressor Cells and Tumor-Associated Macrophages

Bernard Vanhove, Ph.D., COO, OSE Immunotherapeutics

We recently developed Effi-dem, a new anti-SIRPα antagonist IgG4 mAb. In contrast with agents targeting CD47, Effi-dem and other surrogate mAbs prevent M2 polarization of monocyte-derived macrophages differentiated with M-CSF + IL-4 while increase pro-inflammatory M1 cytokines. Anti-SIRPα mAbs also induce differentiation of MDSC into non-suppressive mature myeloid cells overexpressing CD80, CD86 and CD103. This in vitro activity of anti-SIRPα mAbs revealed a therapeutic potential in preclinical models of orthotopic hepatocellular carcinoma (HCC), melanoma and breast cancer models.

4:10 Test Validation to Predict Response to Checkpoint Inhibitors

Carl Morrison, M.D., DVM, President, CSO & Founder, OmniSeq Precision Medicine

Testing for response to checkpoint inhibitors is a current and future target of immunotherapy. Our approach to this problem is the development of a multianalyte assay algorithm analysis (MAAA) using a targeted RNA-seq panel of immune related genes. A requirement of the validation of this assay, Immune Advance, was to meet regulatory requirements of NYS Clinical Laboratory Evaluation Program. In this talk, we will discuss the fundamental aspects of analytical validation, clinical validation, and clinical utility.

4:40 Refreshment Break and Transition to Plenary Session

5:00 Plenary Keynote Session

6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Day

Tuesday, February 21

7:30 am Registration Open and Morning Coffee

8:00 Plenary Keynote Session

9:00 Refreshment Break in the Exhibit Hall with Poster Viewing

ADVANCES IN NK CELL-BASED THERAPY

10:05 Chairperson’s Remarks

Hans Klingemann, M.D., Ph.D., Vice President, Research & Development, NantKwest, Inc.

10:15 FEATURED PRESENTATION: Novel Ways to Target and Activate NK Cells to Treat Cancer

Jeffrey Miller, M.D., Professor, Medicine; Deputy Director, Masonic Cancer Center; Roger L. and Lynn C. Headrick Chair in Cancer Therapeutics, University of Minnesota

The major limitation of NK cells is their lack of specificity and their inability to proliferate when targeted through antibody dependent cellular cytotoxicity. IL-15, a natural cytokine that is critical for NK cell development and homeostasis, will be discussed. We have recently developed a class of molecules that combine antigen specificity and IL-15’s proliferative activity together into a novel class of multifunctional molecules we call trispecific killer engagers (TriKEs). Lastly, we have discovered a new subset of NK cells termed adaptive with properties of immunologic memory.

10:45 Adoptive Immunotherapy with Expanded NK Cells - The Impact of STAT3 Signaling and Crosstalk with Adaptive Immunity

Dean Anthony Lee, M.D., Ph.D., Professor, Pediatrics; Director, Cellular Therapy and Cancer Immunotherapy Program, Nationwide Children’s Hospital; James Comprehensive Cancer Center/Solove Research Institute, The Ohio State University

We developed a system for ex vivo NK cell expansion based on genetically modified feeder cells expressing IL-21, which through STAT3 signaling induces robust activation and proliferation of NK cells from normal donors, patients, cord blood, and embryonic/pluripotent stem cells. We established the GMP infrastructure to manufacture clinical-grade NK cells using this approach, and infused expanded NK cells into patients as monotherapy, in single or repeated infusions, or in combination with chemotherapy or stem cell transplantation, delivering ~200 infusions to over 60 patients at doses up to 108 cells/kg, with no infusion-related or dose-limiting toxicities observed.

11:15 Off the Shelf, Engineered Allogeneic Natural Killer Cell Therapeutics: aNK, haNK, taNK

Hans Klingemann, M.D., Ph.D., Vice President, Research & Development, NantKwest, Inc.

NantKwest has developed the NK cell line NK-92 into an “off the shelf” activated NK (aNK) cell therapeutic. The safety of aNK as well as their activity against a broad range of cancers have been confirmed in several Phase I clinical trials in the U.S., Canada and Europe. The aNK cells can be administered in the outpatient setting and serve as a universal cell-based therapy without need for individualized patient matching. Moreover, the aNK cell platform has been bioengineered to incorporate a high-affinity antibody binding Fc-receptor (haNK). Both aNK and haNK cells can be equipped with CARs.

 11:45 Cells of The Immune System and Cancer: Friends or Foe

Winfried Elis, Project Manager, Discovery Charles River

The rise of immune-oncology has necessitated the development of experimental in vivo platforms to support the drug discovery process. The strengths and weaknesses of genetically engineered and syngeneic mouse models as well as of humanized PDX models will be discussed.

12:15 pm Session Break

 NanoString12:25 Luncheon Presentation I: Beyond PD-L1 IHC: A Gene Expression-Based Test in Development for Anti-PD-1 Response the nCounter® Dx Analysis System

Sarah Warren, Ph.D., Senior Scientist, Immune Oncology, NanoString Technologies Inc.

NanoString Technologies is collaborating with a major pharmaceutical partner to develop an anti-PD-1 response assay that digitally measures a multi- gene expression signature and thus circumvents many of the difficulties associated with PD-L1 IHC.

12:55 Luncheon Presentation II to be Announced

1:25 Refreshment Break in the Exhibit Hall with Poster Viewing

ANTI-PD-1 COMBINATION STUDIES

2:00 Chairperson’s Remarks

Ezio Bonvini, M.D., Senior Vice President, Research, MacroGenics, Inc.

2:10 Engaging Innate and Adaptive Immunity to Fight Cancer

Martin Treder, Ph.D., CSO, Affimed

Bispecific immune cell engagers developed through Affimed’s proprietary antibody platform are well differentiated not only through their bivalent, high avidity binding and specificity, but also due to their limited competition with circulating IgGs, resulting in significantly stronger activation and modulation of NK- or T-cells. Preclinical experiments for Affimed’s lead candidate, AFM13, a prototypic NK-cell engager currently in Phase II clinical development, have demonstrated synergistic efficacy of AFM13 in combination with checkpoint modulators such as anti-PD-1 antibodies, resulting in activation of both innate and adaptive immunity.

2:40 Development of an Agonist Antibody Targeting ICOS

Jennifer Michaelson, Ph.D., Executive Program Leader and Senior Director, Preclinical Development, Jounce Therapeutics

Jounce is developing an agonistic antibody to the co-stimulatory molecule ICOS. Preclinical studies demonstrate that anti-ICOS agonistic antibodies are efficacious in syngeneic tumor models, with enhanced efficacy observed in combination with PD-1 inhibition.

3:10 Circulating Stromal Cells for Immunotherapy

Daniel Adams, Senior Research Scientist, Creatv MicroTech, Inc.

Systems Imagination3:25 Multiscalar Systems Modeling to Design Rational Cancer Immunotherapy Combinations

Spyro Mousses, Ph.D., President, Systems Imagination, Inc.

This case study will describe the mining and modeling of disparate types of information ranging from WGS data to deep clinical phenotype data including pathological and radiological images. Results identified hidden insights that can be leveraged to design safer and more effective drug combinations for cancer immunotherapy.

3:40 Immunotherapy Potency Analysis Using Cellular Impedance

Brandon Lamarche, Ph.D., Research Scientist, ACEA Biosciences

The kinetics of cancer cell destruction by diverse immunotherapies is monitored in a label-free manner using the xCELLigence instruments. Examples of analyzing potency and serial killing capacity, and optimizing constructs/conditions for treating both liquid and solid tumor targets are provided.

4:10 Hollywood Oscar Dessert Reception in the Exhibit Hall with Poster Viewing

5:00 Breakout Discussions in the Exhibit Hall

interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion. Pre-registration to sign up for one of the topics will occur a week or two prior to the Event via the App.

Addressing NK Cell Complexity in Clinical Trials

Dean Anthony Lee, M.D., Ph.D., Professor, Pediatrics; Director, Cellular Therapy and Cancer Immunotherapy Program, Nationwide Children’s Hospital; James Comprehensive Cancer Center/Solove Research Institute, The Ohio State University

  • Which subsets predict response?
  • Which phenotypes are generated by selection or expansion methods?
  • How to address these questions systematically and consistently in clinical trials?

Combination Cancer Immunotherapy and New Immunomodulatory Targets

Paul M. Sondel, M.D., Ph.D., Walker Professor of Pediatrics, Human Oncology; Director, Research, UW Division of Pediatric Hematology, Oncology and BMT; UW Carbone Cancer Center and American Family Children’s Hospital, University of Wisconsin

Gordon J. Freeman, Ph.D., Professor, Medicine, Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School

  • What are emerging strategies for checkpoint combinations?
  • How can preclinical and clinical data determine rational combinations?
  • How can we use biomarkers to inform new combinations?

6:00 Close of Day

Wednesday, February 22

7:00 am Registration Open

7:00 Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

8:00 Plenary Keynote Session

10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall

EMERGING APPROACHES FOR CHECKPOINT INHIBITOR COMBINATION IMMUNOTHERAPY

10:50 Chairperson’s Remarks

Gordon J. Freeman, Ph.D., Professor, Medicine, Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School

10:55 PD-1 Cancer Immunotherapy

Gordon J. Freeman, Ph.D., Professor, Medicine, Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School

My laboratory studies the role of costimulatory signals in the development of an immune response. T cell activation requires two signals. Specificity is provided by TCR recognition of peptide-MHC complexes but a second, costimulatory signal is required for full T cell activation. Recently, we have cloned two novel members of the B7 gene family. These new B7s bind to receptors expressed on activated T cells and further regulate the development of an immune response. We are currently focusing on the function of these novel B7 genes and their interactions with the B7/CD28-CTLA4 pathway.

11:20 Computational Identification of Novel Immune Checkpoints: The Progression from Database to Drug

John Hunter, Ph.D., Site Head and Vice President, Antibody R&D, Compugen USA, Inc.

The B7/CD28 immune checkpoint proteins CTLA4, PD1, and PDL-1 play critical roles in T cell regulation, and have emerged as exciting drug targets for cancer immunotherapy. Utilizing Compugen’s predictive discovery platform, we identified a number of novel checkpoint candidates that were then assessed as potential antibody targets for cancer treatment. Candidates meeting these validation criteria are being moved forward for therapeutic antibody development at Compugen, with CGEN-15029 the most advanced program in the therapeutic pipeline.

11:45 Imprime PGG - A Yeast-Derived Pathogen-Associated Molecular Pattern (PAMP) Triggers the Anti-Cancer Immunity Cycle to Potentiate the Efficacy of Immune Checkpoint Inhibitors

Jeremy R. Graff, Ph.D., CSO and Senior Vice President, Research, Biothera Pharmaceuticals, Inc.

Imprime PGG is being developed as a novel cancer immunotherapeutic. Imprime has been safely administered to >400 human subjects. Imprime triggers a cascade of immune activating events that re-polarize the immunosuppressive tumor microenvironment and elicit maturation of antigen presenting cells. Unlike other PAMPs (TLR and STING agonists), Imprime is administered systemically. In preclinical tumor models, Imprime robustly enhances the anti-tumor efficacy of CPIs. Accordingly, Imprime is now being explored in multiple Phase II clinical trials in combination with pembrolizumab.

12:10 pm The Immune Repertoire Capture (IRC) Technology Platform

Daniel Emerling, Ph.D., Senior Vice President, Research, Atreca, Inc.

Atreca’s proprietary Immune Repertoire Capture™ (IRC™) technology delivers high-fidelity data from the active and clinically productive anti-cancer immune responses of patients who respond well to checkpoint inhibition or other immuno-modulatory treatments. By analyzing these quantitative data, such robust anti-cancer immune responses are mined to generate biotherapeutics that provide the “engine and steering” in combination with checkpoint inhibitors and immune activators, driving anti-cancer immune responses more robustly and specifically to improve treatment outcomes.

12:35 Session Break

12:40 Luncheon Presentation: Syngeneic and Tumor-Bearing Humanized Mouse Models to Address Efficacy of Novel Compounds or Their Combination

Philippe Slos, Director, Scientific Operations, Operations, Oncodesign

Recent breakthroughs in treating malignancies with antibodies harnessing self-immunity against neoplastic cells showed a great promise of immunotherapy for cancer therapy. Oncodesign will discuss case studies and relevant preclinical mouse models to address efficacy of novel compounds or their combination.

1:10 Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing

EMERGING TARGETS AND STRATEGIES: TREGS AND NEO-ANTIGENS

1:50 Chairperson’s Remarks

Denise Faustman, M.D., Ph.D., Director, Immunobiology & Associate Professor, Medicine, Immunobiology, Massachusetts General Hospital/Harvard Medical School

1:55 Dominant Antibody Antagonists: A Novel Immunotherapy Approach Targeting the TNFR2 Receptor for Direct Oncogene-Targeted Cancer Killing and Selective Tumor Treg Killing

Denise Faustman, M.D., Ph.D., Director, Immunobiology & Associate Professor, Medicine, Immunobiology, Massachusetts General Hospital/Harvard Medical School

Tumor necrosis factor receptor 2 (TNFR2) is a target protein with restricted expression on the most potent Tregs of the tumor infiltrate and on human tumors as a newly discovered human oncogene. We characterized the effect of TNFR2 antibody antagonists via TNFR2 in human samples from ovarian ascites compared to healthy controls, finding that dominant TNFR2 antagonists demonstrate tumor-specific Treg depletion. Further, blocking TNFR2 signaling with antagonist antibodies also creates a novel tool to possibly eliminate tumors expressing the TNFR2 oncogene and to more potently suppress Tregs.

2:20 Intratumoral mAb and IL2 with Local Radiotherapy as an “in situ Vaccine”

Paul M. Sondel, M.D., Ph.D., Reed and Carolee Walker Professor of Pediatrics and Human Oncology; Head, Division of Pediatric Hematology, Oncology and BMT; University of Wisconsin

We have identified a cooperative interaction between local radiation and intratumoral injection of hu14.18-IL2 immunocytokine (IC, anti-GD2 antibody linked to IL2) in mice bearing a single subcutaneous tumor, resulting in 71% complete regression. However, when two tumors of the same type are present and only one is treated with RT and IT-IC, the enhanced response is not seen. The non-treated tumor induces a systemic suppressive effect on the efficacy of RT and IT-IC. Our recent data indicate that this “concomitant immune tolerance” is, at least in part, a tumor-specific effect of Tregs.

2:45 Fully Individualized Tumor Neo-Antigen-Based Vaccine Approaches to Cancer Therapy

Karin Jooss, Ph.D., CSO, Gritstone Oncology

Genetic instability in tumors generates tumor-specific neo-antigens which have been identified as the targets of new T cells in patients responding to checkpoint inhibitor therapy. Predicting neo-antigens by sequencing routine clinical biopsy material, and then incorporating them into therapeutic cancer vaccines, is an attractive concept being developed by Gritstone Oncology. The complexities of neo-antigen prediction will be discussed, together with insights into how vaccine vectors are selected and designed.

3:10 Immune Designs Discovery Platforms: Targeting Dendritic Cells and the Tumor Microenvironment for Systemic and in situ Cancer Immunotherapy

Jan ter Meulen, M.D., Dr.habil., DTM&H, CSO, Immune Design

Immune Design is developing the dendritic cell-targeting viral vector platform ZVex® for systemic therapy and the synthetic TLR4 agonist platform GLAAS™ for intratumoral therapy. These two novel technologies are currently being tested in several Phase I through II trials alone and in combination with each other and other IO modalities. Supportive mechanistic preclinical studies and updated clinical data demonstrating the potency of these approaches will be presented.

3:25 Session Break

NEXT-GENERATION ANTIBODIES FOR CANCER IMMUNOTHERAPY

3:40 Chairperson’s Remarks

Paul M. Sondel, M.D., Ph.D., Reed and Carolee Walker Professor of Pediatrics and Human Oncology; Head, Division of Pediatric Hematology, Oncology and BMT; University of Wisconsin

3:45 From DART® to TRIDENT™: Flexible Multispecific Antibody-Based Molecules for Multiple Clinical Applications

Ezio Bonvini, M.D., Senior Vice President, Research, MacroGenics, Inc.

The presentation will focus on the DART® and TRIDENT™ platforms and their applications as a means to redirect effector cells against tumors and/or to engage multiple checkpoint molecules to enhance the immune response in cancer. MacroGenics’s preclinical pharmacology and development experience will be discussed.

4:15 Monoclonal Antibody Drug Discovery for Cancer Immunotherapy

Christopher Shelton, Ph.D., Manager, Immuno-Oncology & Combinations DPU, Oncology R&D, GlaxoSmithKline

4:45 Anti-CD20/CD3 T Cell Dependent Bispecific Antibody (TDB) as Potential Therapy for B Cell Malignancies

Liping Laura Sun, Ph.D., Principal Scientific Researcher, Translational Oncology, Genentech, Inc.

The anti-CD20/CD3 T cell recruiting bispecific antibody (CD20-TDB) is a full-length, fully humanized IgG1 molecule currently under clinical investigation in B cell malignancies. CD20-TDB can have broad clinical applicability, either combining with chemo reagents to enable flexible treatment strategies to incorporate CD20-TDB into current standard of therapy for B cell malignancies or with immune checkpoint inhibitors such as anti-PD-L1/PD-1 to improve upon single-agent efficacy.

5:15 Close of Conference Program


Stay on for these Tri-Conference Symposium, taking place at February 23-24, 2017 at Moscone South Convention Center


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