Cambridge Healthtech Institute’s 9th Annual

Preclinical Strategies, Models & Tools in Oncology
( 肿瘤治疗领域临床前研究策略的模式与工具 )

转译研究策略、新治疗药、肿瘤模型

2020年6月2日~4日


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

Recommended Short Course*

SC1: In vitro and in vivo Modeling for Cancer Research

*Separate registration required.

6月2日 (二)

10:00 am Main Conference Registration Open

MULTI-TARGETED PLATFORMS AND EXTERNAL COLLABORATIONS

11:15 Chairperson’s Remarks

Michael Woo, PhD, 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

Dmitri 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

Russell 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

Michael Woo, PhD, 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 IMAGING, TUMOR MICROENVIRONMENT

2:00 Chairperson’s Remarks

Charles Glaus, PhD, Scientific Director, Quantitative & Translational Science, Imaging, Takeda Pharmaceuticals

2:05 Preclinical and Translational Imaging Methods in the Development of Immuno-Oncology Therapeutics

Charles Glaus, PhD, Scientific Director, Quantitative & Translational Science, Imaging, Takeda Pharmaceuticals

The primary method to measure biomarkers of IO therapeutic activity in solid tumors is biopsy, yet it is widely understood that biopsies spatially and temporally under-sample the tissues in question. Imaging technologies can provide whole-body, longitudinal, noninvasive monitoring of IO drug distribution, PD, and lymphocyte infiltration. In this talk, we will review examples of advanced imaging biomarkers that will play a key role in the development of new immune-oncology therapeutics.

2:35 TGFβ-Blockade Uncovers Stromal Plasticity in Tumors by Revealing the Existence of a Novel Subset of Interferon-Licensed Fibroblasts

Viviana 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.

3:05 Driving Clinical Decisions about Indications and Combination Partners Using Patient-Derived Xenograft Models

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

Small Cell Lung Cancer (SCLC) is characterized by rapid tumor growth and currently, there are few therapeutic options or predictive biomarkers. In a Phase I clinical trial of the p70S6K/AKT1/3 inhibitor M2698, one SCLC patient had prolonged stable disease while on treatment. A follow-up screen in 45 preclinical in vivo patient-derived xenograft (PDX) models resulted in a tumor control rate of roughly 27%.

3:35 Presentation to be Announced

 

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

Valerio 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

6月3日 (三)

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

Roy 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 Targeting Immune Checkpoint TIM-3 for Cancer Immunotherapy

Xiaomo 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.

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

Benno 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 Presentation to be Announced

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

Shawn 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

Pushpa 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

Hans Clevers, MD, CSO, Director of Research, Princess Máxima Center for Pediatric Oncology, University Medical Center Utrecht; Principal Investigator, Hubrecht Institute for Developmental Biology and Stem Cell Research

Systematically Drugging Ras

Stephen Fesik, PhD, Professor of Biochemistry, Pharmacology, and

Chemistry, Orrin H. Ingram II Chair in Cancer Research, Vanderbilt

University School of Medicine

 

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

FIGHTING CANCER DRUG RESISTANCE

4:00 Chairperson’s Remarks

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

4:05 Novel Fully Synthetic Bicyclic Peptides as Tumor Targeted Immune Cell Modulators

Sailaja 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 (TICATM) showed tumor target-dependent immune activation localized to tumor with superior anti-tumor activity in pre-clinical models.

4:35 ‘Smart’ Release Therapeutics Target Multi-Drug Resistance in Solid Cancers

Aaron 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

TABLE: Preclinical Strategies for T Cell Therapy

Moderator to be Announced

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

6月4日 (四)

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

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

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

David 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

Christopher 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 Imaging Biomarkers to Guide Development of Cancer Immunotherapeutics

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

The success rate of cancer immunotherapy is difficult to predict, as its efficacy often depends not only upon characteristics of the tumor lesions, but also of the tumor microenvironment involving immune cells and soluble mediators. Molecular imaging with Positron Emission Tomography (PET) allows repeated noninvasive in vivo measurement of many critical molecular features of tumor lesions and microenvironment, such as metabolism, hypoxia, and immune cell infiltrate, which can assist the knowledge of how cancer immunotherapy works and also facilitates decision making in development of novel cancer immunotherapeutics.

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 Scientist, Oncology-Pharmacology, Sanofi

2:05 CRISPR for Tumor Modeling 

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

2:35 Transplanted Syngeneic Metastasis Models for Preclinical Applications

Viswanathan 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.

3:05 Using Humanized Mouse Models to Evaluate T Cell Engagers

Virna Cortez-Retamozo, PhD, Lab Head, Senior 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.

3:35 Close of Conference

* 活动内容有可能不事先告知作更动及调整。

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6月2日~4日

加速标靶发现

扩大化合物与Druggable空间

新小分子标靶

新适应症与模态

癌症免疫疗法进步

疾病模型

肿瘤治疗领域临床前研究策略的模式与工具

药物代谢与安全性测试的进步

癌症免疫疗法生物标记

临床与转译生物标记

新药发现与开发的AI

6月3日~4日

新药发现的技术


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