Cambridge Healthtech Institute’s 9th Annual

Preclinical Strategies, Models & Tools in Oncology

Translational Strategies, Novel Therapeutics and Tumor Models 

June 2-4, 2020


The rise of cancer immunotherapy instigated unique preclinical and translational challenges. In addition to immuno-oncology advances, we are witnessing a new wave of targeted and novel therapies that enrich the arsenal of combination cancer therapies. The demand for predictive and robust preclinical models and approaches to minimize translational failures in oncology and immuno-oncology is at an all-time high. The need for leveraging phenotypic features of models, for early identification of predictive biomarkers, for rational design of combination therapies, and for researching the cancer-immune cell interactions adds to the complexity of translational research in oncology and immuno-oncology. Cambridge Healthtech Institute’s 9th Annual Preclinical Strategies, Models & Tools in Oncology conference is designed as a forum for ideas and opinions exchange on how to decrease the rate of clinical failures in oncology and immuno-oncology.

Final Agenda


Download Preclinical Program Brochure


Recommended Short Course*

SC1: In vitro and in vivo Modeling for Cancer Research - Detailed Agenda

*Separate registration required.

Tuesday, June 2

10:00 am Main Conference Registration Open

MULTI-TARGETED PLATFORMS AND EXTERNAL COLLABORATIONS

11:15 Chairperson’s Remarks

Michael Woo, PharmD, Head, Search & Evaluation, Immuno-Oncology, Business Development & Licensing, Novartis Institutes for BioMedical Research, Inc.

11:25 KEYNOTE PRESENTATION: Leveraging Multi-Targeting for More Effective Cancer Immunotherapy

Wiederschain_DmitriDmitri Wiederschain, PhD, Global Head, Immuno-Oncology Research Therapeutic Area, Sanofi

Cancer immunotherapies with anti-PD-1/PD-L1 checkpoint blockers have revolutionized the treatment of a wide variety of malignancies. However, immunotherapy is ineffective in a significant subset of cancer patients or eventually results in the development of resistance with relapsed disease. Therefore, the future of immuno-oncology is identification of new multi-targeted agents that can elicit robust anti-tumor immunity as single agents and/or be combined with PD1/PDL1 inhibitors to increase the duration and durability of clinical responses. Sanofi is leveraging its rich internal toolbox of therapeutic modalities, including multispecific antibodies, nanobodies and ADCs, to reduce the concept of multi-targeting to practice and convert “cold” non-immunogenic tumors into “hot” tumors with rich and functionally active immune infiltrate.

11:55 Exploring Novel Immunotherapy Combinations to Overcome Resistance to PD-1 Blockade

Jenkins_RussellRussell Jenkins, MD, PhD, Assistant Professor, Medicine, Center for Cancer Research, Massachusetts General Hospital

Cancer immunotherapy with immune checkpoint blockade has transformed the treatment of patients with advanced melanoma, but strategies to overcome resistance are limited. Using molecular and pharmacologic tools, we have confirmed TANK-binding kinase 1 (TBK1) as a novel target to overcome resistance to PD-1 blockade, further supporting the preclinical and clinical development of this novel combination strategy.

12:25 pm External Collaboration in Immuno-Oncology: New Approaches and Business Models

Woo_MichaelMichael Woo, PharmD, Head, Search & Evaluation, Immuno-Oncology, Business Development & Licensing, Novartis Institutes for BioMedical Research, Inc.

The rapid expansion of the field of immune-oncology provoked a spike of venture capital activity and increased the level of external collaboration among pharmaceutical and biotechnology companies. This presentation will focus on strategic consequences of the IO wave for pharma, biotech, and the venture ecosystem.

12:55 Transition to Lunch

1:00 Luncheon Presentation to be Announced

1:30 Session Break

TRANSLATIONAL approaches and novel targets

2:00 Chairperson’s Remarks

Viviana Cremasco, PhD, Investigator III, Exploratory Immuno-Oncology, Novartis

2:05 In vivo Imaging Techniques for Model Characterization and Guiding Combination Strategies

Tapan Nayak, PhD, Director, Translational Imaging Biomarkers, Merck & Co., Inc.

The success rate of experimental therapy is difficult to predict, as its efficacy often depends upon the characteristics of the preclinical animal models. The presentation will cover different non-invasive imaging techniques to characterize animal models and the information used to guide combination therapies in animal models.

2:25 TGFβ-Blockade Uncovers Stromal Plasticity in Tumors by Revealing the Existence of a Novel Subset of Interferon-Licensed Fibroblasts

Cremasco_VivianaViviana Cremasco, PhD, Investigator III, Exploratory Immuno-Oncology, Novartis

By performing an unbiased interrogation of tumor mesenchymal cells, our study shows that TGFβ-neutralization leads to a profound remodeling of CAF dynamics, greatly reducing the frequency and activity of myofibroblasts, while promoting the formation of a novel fibroblast population characterized by strong response to interferon and heightened immunomodulatory properties. These changes are sufficient to drive productive anti-tumor immunity, laying the foundation for future investigations aimed at defining strategies to reprogram CAF composition for cancer therapy.

2:45 Driving Clinical Decisions about Indications and Combination Partners Using Patient-Derived Xenograft Models

Clark_AndersonAnderson Clark, PhD, Director, Translational in vivo Pharmacology, Translational Innovation Platform, Oncology, EMD Serono

Preclinical tumor models can provide data to drive clinical decisions about responsive indications, biomarkers, suitable combination partners (both standard-of-care and novel agents), and dosing strategies.  In this talk, I will present the preclinical strategy that was used to support early clinical development of M2698, a dual inhibitor of p70S6K/AKT, at EMD Serono.

3:05 TAC Development for the Treatment of Solid and Liquid Tumors

Helsen_ChristopherChristopher Helsen, PhD, Director, R&D and Head, Platform Development, Triumvira Immunologics Inc.

Triumvira is a clinical-stage company developing T-cell therapies engineered with the proprietary T-cell antigen coupler (TAC). TAC is designed to co-opt the natural TCR independent of MHC showing safe and effective tumor rejection in mouse models of solid and liquid tumors. Triumvira successfully cleared IND/CTA submission for TAC01-CD19 to treat LBCL with a second solid tumor program in preclinical development. 

3:35 Presentation to be Announced


3:50 Using Quantitative Super-Resolution Imaging to Design Safe and Effective TherapiesOxford-Nanoimaging

Pereno_ValerioValerio Pereno, Business Development, ONI


 

4:05 Networking Refreshment Break and Transition to Keynote


PLENARY KEYNOTE SESSION

4:25 - 6:05 Driving Entrepreneurial Innovation to Accelerate Therapeutic Discoveries

The life sciences community has an unprecedented scientific arsenal to discovery, develop and implement treatments, cures and preventions that enhance human healthcare.

Moderator: Nadeem Sarwar, President, Eisai Center for Genetics Guided Dementia Discovery (G2D2), Eisai Inc.

Panelists: Anthony Philippakis, Chief Data Officer, Broad Institute; Venture Partner, GV

Barbara Sosnowski, Vice President and Global Head, Emerging Science & Innovation Leads, WWRDM, Pfizer

John Hallinan, Chief Business Officer, Massachusetts Biotechnology Council

6:05 Welcome Reception in the Exhibit Hall with Poster Viewing

7:10 Close of Day

Wednesday, June 3

7:30 am Registration Open and Morning Coffee

COMBINATION REGIMENS AND NOVEL THERAPEUTICS

8:10 Chairperson’s Remarks

Benno Rattel, PhD, Executive Director Research Amgen, CBSS, Amgen

8:15 KEYNOTE PRESENTATION: Rational Development of Immuno-Therapy Combination Regimens

Baynes_RoyRoy Baynes, MD, PhD, Senior Vice President and Head, Global Clinical Development, CMO, Merck Research Laboratories

After initially defining the breadth and depth of PD-1 antibody (pembrolizumab) monotherapy activity and deploying precision medicine tools across the program, certain biological leads led to the exploration of many combination therapeutic approaches. These included company-owned products, as well as a broad array of external collaborations. Broadly, the approach has encompassed combinations with anti-proliferative agents, targeted therapies, other immuno-therapeutic agents and those addressing specific resistance biology.

8:45 Development of a T-Cell Redirecting CD3 Bispecific Antibody for the Treatment of Gastrointestinal Tumors

King_LindsayLindsay King, PhD, Associate Research Fellow, Biomedicines Design, Pfizer

PF-07062119 is a novel T-cell redirecting bispecific against tumors expressing Guanylate Cyclase 2C (GUCY2C), a target expressed in more than 90% of CRC, and in other gastrointestinal cancers. We demonstrate tumor selective and potent in vitro and in vivo efficacy with PF-07062119 in human xenograft models with T-cell adoptive transfer, as well as in an immunocompetent syngeneic model. PF-07062119 shows combination benefits with checkpoint inhibitors and with chemo- and anti-VEGF-therapy.

9:15 Bispecific T Cell Engagers: Overview of Amgen‘s BiTE® Pipeline

Rattel_BennoBenno Rattel, PhD, Executive Director Research Amgen, CBSS, Amgen

Bispecific T cell engagers, commonly referred to as BiTE® antibody constructs, can transiently link tumor cells with resting polyclonal T cells for induction of a surface target antigen-dependent redirected lysis of tumor cells. Blinatumomab (BLINCYTO®) is directed against CD19 and is the first approved T cell engaging antibody. The nonclinical characterizations of blinatumomab, as well as of various BiTE® antibody constructs, and their translation into the clinic will be presented.

9:45 Sponsored Presentation (Opportunity Available)

10:15 Coffee Break in the Exhibit Hall with Poster Viewing

TARGETING INFLAMMATORY MICROENVIRONMENTS AND INFLAMMASOMES

11:00 Friends & Enemies: Spatial Mapping of Regulatory T Lymphocytes in Inflammatory Microenvironments

O'Neil_ShawnShawn O’Neill, DVM, PhD, Senior Director, Global Pathology & Investigative Toxicology, Global Microscopic Imaging Lead, Drug Safety Research & Development, Pfizer Worldwide Research & Development

Tregs are CD4+ T lymphocytes that are central to peripheral immune tolerance, actively inhibiting inflammation upon antigenic stimulation. Tregs thus play a conflicting dual role: as endogenous suppressors of inflammation in autoimmune diseases, while also inhibiting effector CTL from killing tumor cells. In this presentation. we will localize Tregs and CTL by multiplex immunofluorescence and demonstrate spatial mapping of these cells in inflammatory microenvironments by digital pathology using artificial intelligence.

11:30 Targeting Tumor-Promoting Inflammation via the Inflammasome Pathway – Lessons Learned

Jayaraman_PushpaPushpa Jayaraman, PhD, Senior Investigator I, Exploratory Immuno-Oncology, Novartis Institutes for Biomedical Research

Chronic inflammation via the inflammasome pathway plays a key role in carcinogenesis by accelerating tumor invasiveness, growth, and metastatic spread by promoting an immunosuppressive tumor microenvironment. Our work highlights the pathophysiological role of inflammasome mediator, IL-1b in tumor immunomodulation and that IL-1b blockade might have important consequences on T cell function and checkpoint blockade in cancer.

12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Transition to Lunch

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

1:05 Session Break


PLENARY KEYNOTE SESSION

1:45 - 3:15

Lgr5 Stem Cell-Based Organoids in Human Disease

Clevers_HansHans Clevers, MD, PhD, Principal Investigator of Hubrecht Institute and Princess Máxima Center, CSO of HUB Organoids Technology

Organoid technology opens a range of applications in fields such as physiology, study of disease, drug development and personalized medicine. Human organoids represent excellent disease models, be it infectious, hereditary or malignant  Eventually, cultured mini-organs may be used to replace transplant organs from donors. I will describe how we originally created ‘mini-guts’ via 3D culture systems of stem cells of the small intestine and colon, and then expanded the technology to virtually all human organs.

Systematically Drugging Ras

Fesik_StephenStephen Fesik, PhD, Professor of Biochemistry, Pharmacology, and Chemistry, Orrin H. Ingram II Chair in Cancer Research, Vanderbilt University School of Medicine

K-Ras is a small GTPase that is mutated in pancreatic (90%), colon (50%), and lung (30%) carcinomas. Downregulation of activated Ras reverses the transformed phenotype of cells and results in the dramatic regression of tumors in murine xenograft models. Thus, K-Ras inhibition represents an attractive therapeutic strategy for many cancers. In this presentation, I will discuss our efforts to directly target Ras at two sites and target SOS, a molecular partner of Ras, with activators and inhibitors. 

 

3:15 Refreshment Break in the Exhibit Hall with Poster Viewing

new modalities

4:00 Chairperson’s Remarks

Aaron Goldman, PhD, Faculty and Principal Investigator, Goldman Laboratory Drug Resistance Group, Harvard Medical School

4:05 Targeting Immune Checkpoint TIM-3 for Cancer Immunotherapy

Jiang_XiaomoXiaomo Jiang, PhD, Principal Scientist II, Immuno-Oncology, Novartis Institutes for BioMedical Research

TIM-3 has critical roles in tumor-induced immune suppression. Blockade of TIM-3, alone or in combination with PD-1 pathway blockade, has shown anti-tumor efficacy in several preclinical cancer models and in clinical trials. TIM-3 blockade to activate immune response and control tumor growth could reflect the combined effects on modulating multiple cell types in the complex interactions between cancer and the immune system.

4:25 Novel Fully Synthetic Bicyclic Peptides as Tumor Targeted Immune Cell Modulators

Battula_SailajaSailaja Battula, PhD, Associate Director, Immuno-Oncology, Bicycle Therapeutics

CD137 is a validated target for cancer immunotherapy, but antibody approaches targeting CD137 thus far had limited success, likely due to systemic immune activation. We demonstrated that Bicycle’s tumor targeted immune cell agonists (TICA TM) showed tumor target-dependent immune activation localized to tumor with superior anti-tumor activity in pre-clinical models.

4:45 ‘Smart’ Release Therapeutics Target Multi-Drug Resistance in Solid Cancers

Goldman_AaronAaron Goldman, PhD, Faculty and Principal Investigator, Goldman Laboratory Drug Resistance Group, Harvard Medical School

The ability for cancer cells to phenotypically switch and survive under drug pressure, referred to as drug-induced resistance or tolerance, is an emerging, yet poorly understood, mechanism of anticancer therapy failure. We discovered a novel metabolic pathway induced by the first drug in a standard chemotherapy combination leads to multi-drug resistance. To target this mechanism, we engineered small molecule inhibitors of upstream glucose metabolism with anthracyclines using a ‘smart’ release mechanism, which improves response to therapy in vivo.

5:05 Find Your Table, Meet Your Moderator

5:10 Roundtable Breakout Discussions - View Details

TABLE: Preclinical Strategies for T Cell Therapy

Moderator: Lindsay King, PhD, Associate Research Fellow, Biomedicines Design, Pfizer

TABLE: Targeting Inflammasome in Cancer & Beyond

Moderator: Pushpa Jayaraman, PhD, Senior Investigator I, Exploratory Immuno Oncology, Novartis Institutes for Biomedical Research

5:45 Reception in the Exhibit Hall with Poster Viewing

6:45 Close of Day

Thursday, June 4

8:00 am Registration Open and Morning Coffee


PLENARY KEYNOTE SESSION

8:30 - 9:40 Applications of Artificial Intelligence in Drug Discovery – Separating Hype from Utility

Walters_PatrickPatrick Walters, PhD, Senior Vice President, Computation, Relay Therapeutics

Over the last few years, there has been tremendous interest in the application of artificial intelligence and machine learning in drug discovery. Ultimately, the success of any predictive model comes down to three factors: data, representation, and algorithms. This presentation will provide an overview of these factors and how they are critical to the successful implementation and deployment of AI methods.

9:40 Coffee Break in the Exhibit Hall with Poster Viewing

NEXT-GENERATION MODELING SYSTEMS AND WHAT WE CAN LEARN WITH THEIR HELP

10:25 Chairperson’s Remarks

Christopher Kemball, PhD, Scientist, Biochemical & Cellular Pharmacology, Genentech

10:30 Preclinical Modeling Using Human Cancer Xenografts Grown in Immune-Deficient Zebrafish

Langenau_DavidDavid Langenau, PhD, Associate Chief of Research and Director of Molecular Pathology, Massachusetts General Hospital; Associate Professor, Pathology, Harvard Medical School

We have generated immune-compromised zebrafish that lack T-, B- and NK-cells that robustly engraft human cancers. Capitalizing on the optical clarity of zebrafish and facile imaging approaches, we have documented small-molecule therapy responses and dynamic cell killing by CAR T cell- and bispecific T cell-engager antibodies (BITES) at single-cell resolution. Our studies credential the immune-deficient zebrafish as a new platform for preclinical drug studies.

11:00 CD34+ Stem Cell-Derived Human Dendritic Cells Provide a Physiologically Relevant System to Evaluate the Pharmacology of Therapeutic Molecules

Kemball_ChristopherChristopher Kemball, PhD, Scientist, Biochemical & Cellular Pharmacology, Genentech

Anti-tumor immunity may be enhanced by therapeutic agents that promote dendritic cell expansion and differentiation. To better characterize the pharmacology of these therapies, in vitro models are needed that recapitulate physiologically relevant human DC subsets. DCs generated in vitro from human CD34+ progenitor cells closely resemble primary blood DCs. We show that CD34-derived DCs can be used to characterize the potency of a therapeutic molecule to drive cDC1 differentiation.

11:30 Is There a Key Node in the TME to Tip the Balance?

Chen_ZhaoZhao Chen, PhD, Investigator III, Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research, Inc.

The efficacy of the host immune response against cancer largely depends on the behavior of the tumor microenvironment (TME). Many TME components were shown to impact different aspect of cancer immunity, ranging from T cell priming, effector function, exhaustion to memory. However, the highly heterogeneous TME is often a big hurdle for the clinical translation of TME targets. We are interested in the interplay between components of the TME and the key node that can truly perturb the TME balance.

12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Transition to Lunch

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

1:05 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing

2:00 Chairperson’s Remarks

Virna Cortez-Retamozo, PhD, Lab Head, Senior Principal Scientist, Oncology-Pharmacology, Sanofi

2:05 Transplanted Syngeneic Metastasis Models for Preclinical Applications

Muthusamy_ViswanathanViswanathan Muthusamy, PhD, Research Scientist; Executive Director, Center for Precision Cancer Modeling, Yale School of Medicine

There is a great need for robust in vivo preclinical models for evaluation of drugs interfering with metastasis. We have developed several transplantable, syngeneic metastasis models and used these to assess: 1) interventions to prevent colonization and growth in distant organs; and 2) treatment-induced abscopal effects on distant metastases. In preliminary studies, an immune-targeting, intratumorally injected drug candidate reduced metastatic burden and improved survival in one such model.

2:35 Using Humanized Mouse Models to Evaluate IO Therapeutics

Cortez-Retamozo_VirnaVirna Cortez-Retamozo, PhD, Lab Head, Senior Principal Scientist, Oncology-Pharmacology, Sanofi

The success of early cancer immunotherapies has led to the development of several new therapeutic approaches, including T cell engagers. T cell engagers are typically bispecific Abs directed against the T cell and a tumor-associated antigen, whose therapeutic strategy is to: 1) engage T cells; 2) activate the T cells; and 3) engage tumor cells and induce tumor cell killing. Preclinical evaluation relies on development of models that mirror some properties of a human setting to assess the therapeutic properties of T cell engagers.

3:05 PANEL DISCUSSION: Next-Generation Modeling Systems and What We Can Learn with Their Help

Chen_ZhaoModerator: Zhao Chen, PhD, Investigator III, Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research, Inc.


Panelists: Speakers of the Session

3:35 Close of Conference