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- 肿瘤学领域临床前研究策略、模型、工具 -

The rise of cancer immunotherapy such as immune checkpoint modulators, bispecific antibodies, T cell therapy and personalized cancer vaccines instigated a wide range of unique preclinical and translational challenges. The demand for predictive and robust preclinical models and approaches to minimize translational failures in 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 add to the complexity of translational research in immune-oncology. Cambridge Healthtech Institute's Seventh Annual Preclinical Strategies, Models & Tools in Oncology: Executive Summit 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

Tuesday, June 19

7:30 am Registration Open and Morning Coffee

IMMUNO-ONCOLOGY STRATEGIES

8:15 Chairperson's Opening Remarks

Ken Hance, PhD, Senior Director & Head, Immune Biology, Immuno-Oncology & Combinations Discovery Performance Unit, GlaxoSmithKline

8:20 In vitro and in vivo Model Development to Support Drug Discovery in Immuno-Oncology

Ken Hance, PhD, Senior Director & Head, Immune Biology, Immuno-Oncology & Combinations Discovery Performance Unit, GlaxoSmithKline

Non-clinical research studies historically support preclinical development and regulatory submission satisfaction and provide critical support of early clinical development hypotheses and clinical trial design including managing expectations of single agent efficacy or setting strategic vision for combination value through biology synergies. Moreover, following early clinical development milestones, an experimental medicine requires ongoing translational review of the clinical readouts beyond efficacy which in turn requires additional non-clinical analyses and experimental execution to drive results-based decision making and data-informed design of late stage clinical trials in anticipation and hope of drug approvals.

8:50 Application of Human Germline Genetics and Novel Animal Disease Models for the Discovery and Development of Cancer Immunotherapy

Xingfeng Bao, PhD, Head, Immuno-Oncology, Integrated Biology Engine, Eisai AiM Institute, Eisai, Inc.

In the discovery and development of cancer immunotherapy, polymorphic nature of immune therapeutic targets and limited translatability of mouse models make prediction of human response to an immunotherapy challenging. In this presentation, we will discuss an application of human germline genetics and primary human tumor tissues for the characterization and translational biomarker discovery of a novel drug candidate.

9:20 Rational Immunotherapy Combination with Non-IO Agents through Preclinical Modeling

David Schaer, PhD, Principal Research Scientist, Cancer Immunobiology Experimental and Translational Immuno-Oncology Group, Eli Lilly and Company

The explosion of clinical trials testing IO checkpoint agents has placed the field at risk of becoming oversaturated with combination trials of IO agents with SOC, and new drugs entering clinical testing where IO agents are part of the therapeutic paradigm. Using mouse modeling and high content molecular profiling, we investigate novel combinations strategies involving immune checkpoint inhibitors and targeted therapeutics to help guide clinical translation/development of optimal combinations.

9:50 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

NEW TARGETS AND APPROACHES

10:35 Therapeutic Strategies for Targeting the EZH2 Methyltransferase in Cancer

Robert A. Rollins, PhD, Associate Director, Oncology Research & Development, Pfizer

Epigenetic alterations are a hallmark of cancer. This observation has prompted the development of targeted therapies that inhibit epigenetic modifiers and chromatin remodeling enzymes. As epigenetic regulators differ from classic oncogenic drivers, the challenge has been to identify optimal strategies for therapeutic intervention. We have discovered potent and selective inhibitors of the histone methyltransferase EZH2. Exploratory studies with these molecules have revealed genetic dependencies and novel combination strategies with both targeted and immunotherapies that may broaden the clinical landscape for this cancer target.

11:05 Discovery and Characterization of Functional Anti-Tumor Antibodies from Non-Progressing Cancer Patients Undergoing Immunotherapy

Norman Greenberg, PhD, CSO, Senior Vice President, Therapeutics, Atreca

We isolated plasmablasts from patients with metastatic non-progressing cancers that received check point inhibitor immunotherapy. Using our proprietary Immune Repertoire Capture™ technology we determined paired heavy and light chain antibody sequences from these plasmablasts. From these hyper-accurate sequences we subsequently expressed recombinant antibodies that bound non-autologous human tumor tissues and cell lines. Importantly, some of these antibodies caused regression of, and durable immunity toward, heterologous syngeneic tumors in mice. Our research program demonstrates that functional anti-tumor antibody responses in cancer patients target public antigens following checkpoint inhibitor therapy and provides an approach to identify and develop important therapeutic antibodies.

11:35 Talk Title to be Announced  

Raymond Chang, PhD, Imaging Research Scientist, Cardiovascular Research, Regeneron Pharmaceuticals

12:05 pm Session Break

12:10 Luncheon Presentation: Mouse Syngeneic Models: Biological Variability in Response to Therapy and Underlying Cellular and Molecular Factors Involved

Edgar Wood, Senior Research Director, Discovery, Charles River

Syngeneic models have greater animal to animal variability as well as inter-study variability than standard xenograft models. We will discuss potential biological explanations for this, the relationship between gene expression changes and individual animal response and practical implications for study design and interpretation.

12:40 Session Break

AI FOR ONCOLOGY RESEARCH

1:15 Chairperson's Remarks

David Schaer, PhD, Principal Research Scientist, Cancer Immunobiology Experimental and Translational Immuno-Oncology Group, Eli Lilly and Company

1:20 CO-PRESENTATION: Leveraging Artificial Intelligence for Drug Discovery to Help Identify and Rank Potential Promising Immuno-Oncology Targets

Nick Iannotti, PhD, Manager, Precision Medicine Technology, R&D Business Technology, Pfizer

John Gregory, Director, R&D Project & Portfolio Management Business Technology, Pfizer

Pfizer's private cloud-based implementation of IBM Watson for drug discovery is intelligently helping our Oncology R&D researchers to analyze millions of scientific documents, and supporting Pfizer data, to help identify and rank potential promising immuno-oncology targets, and identify potential adverse events.

1:50 Machine Learning to Predict Combined Drug Response from Genomic Data

Jonathan Dry, Principal Scientist, Bioinformatics, Oncology, Innovative Medicines & Early Development, AstraZeneca

This presentation will discuss AI algorithms that can help predict drug response in oncology and other therapeutic areas using genomic data from clinical trials and patient care.

2:20 Triple Humanized Mouse Models

Benjamin Cuiffo, PhD, Principal Scientist, Oncology, Biomodels, LLC

2:35 Hollow Fiber Model - In vivo Prescreen in Cancer Drug Discovery

Anja Baumgart, Business Development Manager, Sales, ProQinase

Anticancer lead compounds need to be prioritized for in vivo analysis. The Hollow Fiber Model (HFM) evaluates the anticancer efficacy of a drug in three cell lines simultaneously in a single mouse. The HFM prediction was tested for Crizotinib and appeared better than in vitro proliferation for the outcome of xenograft studies. The HFM prescreen is highly predictive, cost- and time-effective, saving compound and mice.

2:50 Refreshment Break in the Exhibit Hall with Poster Viewing

VC AND SEARCH & EVALUATION PERSPECTIVE

3:30 Chairperson's Remarks

Leigh Zawel, PhD, Managing Director, MPM


3:45 FEATURED PANEL DISCUSSION: Partnering Ecosystem in Immuno-Oncology

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 panel discussion will focus on strategic consequences of the IO wave for pharma, biotech, and the venture ecosystem.

Panelists:

Leigh Zawel, PhD, Managing Director, MPM

Michael Gladstone, MD, Principal, Atlas Venture

Nilesh Kumar, PhD, Partner, Novo Ventures

Michael Woo, PharmD, MBA, Head, Search & Evaluation, Immuno-Oncology, External Innovation, EMD Serono Research & Development Institute

Maude Tessier, Executive Director, Business Development, Merck

Topics to be discussed include, but are not limited to:

· Can we expect to see new IO therapies with single agent activity akin to PD1, or is the future going to be all about combination partners?

· Are more investments happening in the discovery of new IO targets or in strategies to enhance PD1/CTLA4 efficacy?

· What critical data is coming in the next 12 months in the cancer vaccine and/or cell therapy space?

· For your firm to consider an investment in an IO asset, what are the "must haves" in a data package?

5:00 Find Your Table and Meet Your Moderator

5:05 Interactive Breakout Discussion Groups

This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas and active networking

Preclinical Strategies for Combination Therapies

Mithun Khattar, PhD, Immuno-Oncology Lead, Cancer Pharmacology, Takeda Pharmaceuticals

  • Key factors to consider when selecting combination strategy
  • Immunomodulatory effects of small molecules
  • Translating preclinical models to the clinic - the expected and unexpected

VC Perspective on Immuno-Oncology

Leigh Zawel, PhD, Managing Director, MPM

Michael Gladstone, MD, Principal, Atlas Venture

  • Are more investments happening in the discovery of new IO targets or in strategies to enhance PD1/CTLA4 efficacy?
  • What critical data is coming in the next 12 months in the cancer vaccine and/or cell therapy space?
  • For your firm to consider an investment in an IO asset, what are the "must haves" in a data package?
  • Are there translational tools that are truly predictive of what kind of patients are most likely to respond to a given non-PD1 drug to predict (or at least narrow) populations to focus on in Ph1? Or are we going to have to continue to rely on empirical exploration large All-comer Ph1 studies?

5:45 Reception in the Exhibit Hall with Poster Viewing

7:00 Close of Day

Wednesday, June 20

7:45 am Registration Open and Morning Coffee

DESIGNING POTENTIAL COMBINATION THERAPIES

8:25 Chairperson's Remarks

Mithun Khattar, PhD, Immuno-Oncology Lead, Cancer Pharmacology, Takeda Pharmaceuticals

8:30 Tumor Microenvironment Biomarkers to Guide Translational Decisions in Immuno-Oncology

Mithun Khattar, PhD, Immuno-Oncology Lead, Cancer Pharmacology, Takeda Pharmaceuticals

Murine models for pre-clinical studies in immuno-oncology and cancer pharmacology have greatly evolved. However, not all pre-clinical breakthrough therapies translate into clinical successes. Fundamental differences in the immune composition, tumor microenvironments, progression of disease, etc. between mice and humans may contribute to translational failures. A deeper exploration of the relevant immunological MoAs and biomarker strategies can minimize such failures by facilitating patient selection as well as designing potential combination therapies.


9:00 KEYNOTE PRESENTATION: Immunotherapy for Cancer: The Need for More Effective Combination Therapies

Ronald Herbst, PhD, Vice President, R&D and Head, Oncology Research, MedImmune

Combination approaches are the keys to improving clinical response. From preclinical immune-oncology mouse models to patients enrolled on clinical trials, novel high throughput technologies enable us to understand the mechanisms underlying the complex interactions between the immune system and cancer, identify predictive biomarkers for the patients who will most likely benefit from current immunotherapies, avoid immune-related adverse events, and guide the future combination cancer immunotherapy.

9:30 Talk Title to be Announced

John Swart, PhD, President, Exemplar Genetics

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

PDX MODELS AND TUMOROIDS: LOGISTICS, TECHNOLOGY AND APPLICATIONS

10:45 CO-PRESENTATION: Creation of Patient Derived Cancer Models at Scale Leverages Patient Diversity for Improved Clinical Trials Predictions

Kin-Hoe Chow, PhD, Associate Director, Center for Patient Derived Models, Dana-Farber Cancer Institute

Keith L. Ligon, MD, PhD, Director, Department of Oncologic Pathology, Center for Patient Derived Models, Dana-Farber Cancer Institute

The Center for Patient Derived Models is created to support large-scale generation of cancer models to sufficiently capture the diversity of patient biology encountered in clinical trials and makes them readily available to the cancer community. Currently supporting the studies of hundreds of CNS, hematologic, and solid cancer models, the Center aims to accelerate clinical trial results interpretation, foster collaborations with industry, and advance patient models into clinical functional diagnostic tools.

11:15 Human Tumor Organoids as a Novel Model for Drug Discovery and Screening

Janica Wong, PhD, Senior Scientist, Translational Pathology, Merck Research Labs

Stem cell-derived organoids are self-organizing three-dimensional (3D) structures generated in vitro recapitulating the cellular architecture and functions of the tumor, which may be a more relevant model to study cancer biology. 3D in vitro tumoroids were established from human tumor tissues. Tumoroids transplanted into humanized mice produced tumors that resembled primary human tumors, suggesting organoids are a useful model for predicting drug responses with potential for use in precision medicine.

11:45 Session Break

11:50 Bridging Luncheon Presentation: From Syngeneic to Humanized Mouse Models: Addressing the Needs for Novel Immunotherapies

Francis Bichat, Head, In Vivo Sciences, Oncodesign

Discovery of novel immunotherapy represents a main and intense focus of research in oncology. Proof-of-concept studies in animals represent a challenge and require well-characterized and appropriate animal models with most of the time customized approaches. Some recent development and data generated for immune checkpoint modulators, adoptive cell transfer therapy, vaccines and bispecific T cell engagers will be presented.

12:20 pm Dessert and Coffee Break in the Exhibit Hall with Poster Viewing


1:00 PLENARY KEYNOTE SESSION

Partnering for Sustainable Funding

The panel is designed to discuss partnering between various stake holders such as drug discovery startups, VC firms, large pharmaceutical companies and academic labs in order to advance new target discovery and preclinical research. VC companies, and pharma search & evaluation departments will be represented on the panel.

Jens Eckstein, PhD, President, SR One

Barbara K. Sosnowski, PhD, Vice President and Global Head, External R&D Innovation, Pharmatherapeutics and WRD External Partnerships, Pfizer, Inc.

Kevin Bitterman, PhD, Partner, Atlas Venture

Vivian Berlin, PhD, Director of Business Development, Life Sciences, Office of Technology Development, Harvard University

Plenary Technology Panel

Advancing Innovation in Drug Discovery and Translational Research

This year's Plenary Technology Panel features a group of technical experts from life science technology and service companies, who share their perspectives on various trends and tools that will likely change the way in which we traditionally approach preclinical drug discovery and development. Attendees will have an opportunity to ask questions and understand the impact of recent technical advances.

Ashley Rae Kark, MBS, Director, Corporate Relations, Scientist.com

Additional Panelists will be Announced

Sponsorship Opportunities Available

2:30 Refreshment Break in the Exhibit Hall with Poster Viewing

3:10 Close of Conference


Recommended Event Package

Short Course 5: Impact of Convergence of Immunotherapy and Epigenetics in Oncology

Short Course 9: How to Best Utilize 3D Cells, Spheroids, PDX Models in Oncology

Short Course 12: Humanized Mouse Models for Preclinical Assessment of Cancer Immunotherapy

Conference: Preclinical Strategies, Models & Tools in Oncology

Conference: Tumor Models for Cancer Immunotherapy or Immuno-Oncology Targets


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* 活动内容有可能不事先告知作更动及调整。