Cambridge Healthtech Institute’s 4th Annual

Immuno-Oncology Advances
( 癌症免疫疗法进步 )

转译研究策略、小分子药物标靶、免疫剖析

2020年6月2日~4日


Immuno-oncology research and the subsequent development of immunotherapies continue to rapidly advance the fight against cancer. First-generation agents that achieved remarkable clinical success have inspired researchers to pursue a variety of new treatment modalities and created a robust development landscape centered on combinations strategies. The 4th Annual Immuno-Oncology Advances conference, part of World Pharma Week, will feature three key areas that include preclinical and translational strategies, small molecule targets in immuno-oncology, and immune profiling and monitoring.

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 Sponsored Presentation (Opportunity Available)

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

INTEGRATED IMMUNE PROFILING AND TUMOR MICROENVIRONMENT

8:10 Chairperson’s Remarks

Samir Hanash, MD, PhD, Director, McCombs Institute for Cancer Early Detection and Treatment, MD Anderson Cancer Center

8:15 Integrative Analyses of Environment, Microbiome, Immunity, and Tumor for Precision Oncology

Shuji Ogino, MD, PhD, MS, Professor of Pathology, Brigham & Women’s Hospital, Harvard Medical School; Professor, Epidemiology, Harvard T.H. Chan School of Public Health; Chief of Molecular Pathological Epidemiology (MPE) Program, Brigham & Women’s Hospital; Associate Member, Broad Institute of MIT and Harvard

The integrative field of immunology-MPE (molecular pathological epidemiology) is an emerging paradigm and can investigate influences of the exposome on tumor-immune interactions, thereby informing immunotherapy research. Using over 1500 colorectal cancer cases with rich data on immune response, whole exome sequencing, RNA-sequencing, tumor neoantigens, and clinical outcomes, proof-of-principle immunology-MPE studies have shown great promise for precision prevention and immuno-oncology.

8:45 The Tumor Immune Microenvironment of Pre-Malignant Lesion in the Pancreas

Elizabeth Thompson MD, PhD, Assistant Professor, Pathology and Oncology, The Johns Hopkins Hospital

While much work has focused on the tumor immune microenvironment of established cancers, little is known about the immune response to the earliest stages of tumor development. This talk will explore the immune microenvironment of neoplastic precursor lesions in the pancreas, focusing on pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms (IPMN) with emphasis on features predicting grade of dysplastic change and recurrence/progression to malignancies.

9:15 Immune Profiling

Veena Kandaswamy, PhD, Immuno-Oncology Biomarkers, Eli Lilly

9:45 How Biospecimen Sourcing Can Impact Your R&D Results

Vanessa Tumilasci, PhD, Commercial Director, Trans-Hit Bio

Biospecimen sourcing is becoming a challenge for many scientists who need to respect timelines for R&D plans as well as regulatory and ethical constraints. Are the scientists working with the samples aware of all the imperatives to obtain them; quality, respect of laws, ethics and regulations?

10:00 Sponsored Presentation (Opportunity Available)

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

INTEGRATED IMMUNE PROFILING AND TUMOR MICROENVIRONMENT (CONT.)

11:00 Molecular Signatures of Tumor Immune Evasion

Samir Hanash, MD, PhD, Director, McCombs Institute for Cancer Early Detection and Treatment, MD Anderson Cancer Center

A wide world of mechanisms leading to tumor immune evasion have emerged. Assessment of these mechanisms has relevance to immunotherapy applications.

11:30 Multiplex Immunofluorescence Tyramide Signal Amplification and Multispectral Imaging Assay to Support Translational Oncology Studies

Edwin Roger Parra Cuentas, MD, PhD, Assistant Professor, Translational Molecular Pathology; Director of the Multiplex Immunofluorescence and Image Analysis Laboratory, MD Anderson Cancer Center

Multiplex immunofluorescence (mIF) have emerged in the last years as a very powerful tool to study tumor tissues. This revolutionary technology provides important visual technique for tumor examination in formalin-fixed paraffin-embedded specimens to improve the understanding of the tumor microenvironment, promote new treatment discoveries, aid in cancer prevention, as well as allowing translational studies to be carried out.

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

BIOMARKERS FOR ONCOLOGY CLINICAL TRIALS

4:00 Chairperson’s Remarks

Samir Hanash, MD, PhD, Director, McCombs Institute for Cancer Early Detection and Treatment, MD Anderson Cancer Center

4:05 Pharmacodynamic Profiling of Patients Treated with BLZ945 Demonstrates On-Target Peripheral and Tumor Immune Microenvironment Modulation

Jennifer Mataraza, PhD, Head, Translational Immuno-Oncology, Novartis Institutes for BioMedical Research

BLZ945 is an oral, highly selective and potent kinase inhibitor of CSF-1R. Both preclinical and clinical evidence demonstrates that blocking (CSF-1R) signaling may lead to depletion of TAMs and increased T cell activation. BLZ945X2101 is an ongoing clinical trial investigating the use of BLZ945 as single agent and in combination with spartalizumab (anti-PD-1) in advanced solid tumors. Biomarker analyses will be discussed as evidence of on-target pharmacodynamic effects of BLZ945 in treated patients.

4:35 Overview of Genomic Biomarkers in Clinical Trials

Chetan Deshpande, Clinical Biomarker Assay Lead, Pfizer

Genomics biomarkers have been implemented routinely in clinical trials, especially in oncology, for exploratory endpoints. Over the last few years, molecular testing by NGS has been applied not only to understand the molecular mechanism of the underlying disease, but also to gain insights into resistance mechanism. This presentation will review the current trends in implementing genomic biomarkers in oncology clinical trials.

5:05 Find Your Table, Meet Your Moderator

5:10 Roundtable Breakout Discussions

TABLE: Tumor Immune Microenvironment

Moderator: Elizabeth Thompson MD, PhD, Assistant Professor, Pathology and Oncology, The Johns Hopkins Hospital

TABLE: Theranostics in Immuno-Oncology

Moderator: Michael Roehrl, MD, PhD, Director, Precision Pathology Center, Memorial Sloan Kettering Cancer Center; Associate Professor, Pathology and Laboratory Medicine, Weill Cornell Medicine

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-Based Models in Drug Discovery: Developments, Caveats, and Future Perspectives

Danilo Maddalo, PhD, PharmD, Laboratory Head, Oncology, Novartis

The development and the application of genome-editing techniques in vivo has expanded the toolkit of preclinical models to assess drug efficacy and toxicology, as well as the effect of compounds on tumour-microenvironment interaction. Cost- and time-efficient, the talk will give an overview of CRISPR models, how they impacted significantly the workflow of preclinical drug discovery, and their limitations and caveats.

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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