Cambridge Healthtech Institute’s 10th Annual

Clinical and Translational Biomarkers

Precision Medicine, Liquid Biopsy, and Clinical Trials

June 2-4, 2020


The promise of precision medicine has been driven by the need to accurately predict patient response to therapy while ensuring drug efficacy and safety. Reducing costs and the time required for drug development is also a driving force in the use of biomarkers. Cambridge Healthtech Institute’s 10th annual Clinical and Translational Biomarkers meeting will cover novel biomarker discovery, clinical and analytical biomarker validation, and the role of biomarkers in clinical decision making.

Final Agenda

Recommended Short Course*

SC3: Fit-for-Purpose Biomarker Assay Development – Performance Characterization and Validation to “Context of Use” - Detailed Agenda

*Separate registration required.

Tuesday, June 2

10:00 am Main Conference Registration Open

PRECISION MEDICINE IN ONCOLOGY

11:15 Chairperson’s Remarks

Tracy Lively, PhD, Chief, Diagnostics Evaluation Branch; Deputy Associate Director, Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute

11:25 Precision Medicine Initiatives at the NCI

Lively_TracyTracy Lively, PhD, Chief, Diagnostics Evaluation Branch; Deputy Associate Director, Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute

The development of predictive markers to guide the use of emerging therapeutic agents requires new approaches to both clinical trials and correlative laboratory science. This talk will present NCI’s experience with novel trial designs, including lessons learned from NCI MATCH, and additional approaches to more effective integration of biomarker development into cancer therapy trials.

11:55 Oncology Biomarker Development Strategies in Precision Therapies

Li_YanYan Li, PhD, Director, Oncology Biomarkers, Bayer U.S.

This presentation will discuss combining tissue and liquid biopsy to follow the patient’s tumor evolution and adding RNA gene expression profiling to DNA to expand clinical options for patients.

12:25 pm How to Catch Them All: Genomic Panels Big and Small

Morrissette_JenniferJennifer Morrissette, PhD, Director, Clinical CytoGenomics Laboratory, Associate Professor, Pathology, University of Pennsylvania

High volume clinical laboratories need to accommodate a variety of specimen types, qualities and quantities. This typically cannot be accomplished using a single method; we have validated a large hybrid-capture based panel and a small amplicon-based companion panel for low-input and/or low quality DNA. This talk will discuss the decision making process for panel design, both inter- and intra-laboratory. The large panel includes content shared across multiple institutions which have decided to utilize similar methodologies allowing for cross-validation.

12:55 Transition to Lunch

1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:30 Session Break

BIOMARKERS FOR PATIENT SELECTION

2:00 Chairperson’s Remarks

Hua Gong, MD, PhD, Senior Director, Head of Genomics Biomarker Development, Navigate Biopharma, a Novartis company

2:05 Accelerating Oncology Drug Development by Patient Stratification

Gong_HuaHua Gong, MD, PhD, Senior Director, Head of Genomics Biomarker Development, Navigate Biopharma, a Novartis company

This presentation will cover: 1) validation and implementation of “fit-for-purpose” CTA/IUO assays for patient selection; 2) bridging IUO assay to CDx to enable drug approval; 3) emerging technologies for future biomarker assays.

2:35 Predictive Molecular Marker for C. Difficile Infection Recurrence

Xuemei Zhao, PhD, Senior Principal Scientist, Merck

This presentation will discuss endogenous serum IgG antibodies to clostridium difficile toxin B which are associated with protection against C. difficile infection recurrence.

3:05 Cytogenetic and Genomic Correlates Within AML Prognostic Stratification Strategies

Sussman_RobynRobyn Sussman, PhD, Assistant Director, Molecular Development, Pathology, University of Pennsylvania

Newly diagnosed AML can be stratified into prognostic groups using cytogenetic and genomic findings. We have identified 152 de novo AMLs that received both a karyotype and next-generation sequencing study at the time of diagnosis. We compared mutations and cytogenetic abnormalities within prognostic categorizations defined by the European Leukemia Net (ELN) and Medical Research Council (MRC) and found that the functional characterization of a mutation can predict the prognostic category of AMLs.

3:35 Phenotyping the Tumor Microenvironment with Advanced Tissue-Based Multiplexing Assays

Patel_MichaelKatir Patel, PhD, Field Applications Manager, Ultivue, Inc.

Next-generation multiplex fluorescence immunohistochemistry methods offer new capabilities for scientists to explore the biology of disease within patient tissues. These methods have the potential to enable in-depth cell phenotype characterization and spatial context for more accurate co-expression analysis of the TME through a streamlined multiplex assay.

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.

Sarwar_NadeemModerator: 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

LIQUID BIOPSY IN PRECISION MEDICINE

8:10 Chairperson’s Remarks

Christian Klose, PhD, Head, Research & Development, Lipotype GmbH

8:15 Liquid Biopsies Enabling Precision Medicine

Beer_JonathanJonathan Beer, Director, FPM Lead of Disruptive Technologies, Novartis Precision Medicine

Liquid biopsies are a minimally invasive source of biomarker data with clear benefits in monitoring response to therapy and early detection of disease progression. The US FDA has approved the detection of CTCs as a prognostic marker for several cancer types and has now approved two CDx assays to detect variants in ctDNA. Further technology advances are required in order to deliver on the promise of liquid biopsies utility in precision medicine.

8:45 High-Resolution, High-Throughput Single Vesicle Analysis

Nolan_JohnJohn Nolan, PhD, Professor, The Scintillon Institute

Extracellular vesicles (EVs, aka exosomes, microvesicles, etc.) are released by all cells and can carry molecular cargo to nearby or distant cells to affect their function. I will review the current state of EV analytics, highlight new minimum information (MI) guidelines for methods and reporting, and present new high-resolution analysis methods for single EV analysis that shed new light on the origins and composition of EVs in biofluids.

9:15 Personalized Serial Detection of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients with Pediatric Cancers

Rachel Nga Wan Tam, PhD, Senior Scientific Researcher, Oncology Biomarker Development, Genentech

We have utilized a novel highly sensitive and specific approach (Signetera RUO assay) for the detection and quantification of circulating tumor DNA (ctDNA) by tracking personalized cancer signatures in plasma. By targeting 16 somatic mutations present in the tumor, we can detect ctDNA presence longitudinally in pediatric CNS and solid tumor patients with an estimated LOD of 0.01% tumor DNA in a patient’s plasma. It has the potential for the diagnosis and therapeutic monitoring to improve clinical outcomes for children.

9:45 The Lipidomics BMI: A Clinical Index for Classification, Stratification and Monitoring of Systemic Lipid Metabolism

Klose_ChristianChristian Klose, PhD, Head, Research & Development, Lipotype GmbH

Machine learning was used to predict the BMI of more than 1000 subjects based on plasma lipidomics data. The lipidomics BMI was designed to be integrated into routine clinical trial workflows, holds further information on body fat distribution and revealed a clinically relevant BMI misclassification of 15% of test subjects.

10:00 Sponsored Presentation (Opportunity Available)

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

LIQUID BIOPSY IN PRECISION MEDICINE (CONT.)

11:00 Evaluation of NGS Assay Sensitivities in Liquid Biopsies for MRD

Amelia Raymond, Scientist, Translational Medicine, AstraZeneca

11:30 Liquid Biopsy for Brain Tumors

Nahed_BrianBrian Nahed, MD, MSc, Associate Professor, Neurosurgery, Harvard Medical School; Associate Director, Neurosurgery Residency Program, Massachusetts General Hospital

Advances in liquid biopsy modalities in cancer have created the pathway for similar analyses in brain tumor patients; however, until recently this has been unsuccessful. Circulating tumor cells, extracellular vesicles, and circulating DNA may provide the long-awaited ability to diagnose and monitor brain tumors.

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

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

Mataraza_JenniferJennifer 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 demonstrate 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 mechanisms. 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 - View Details

TABLE: Genomics and Biomarker Data Analysis

Moderator: Viswanath Devanarayan, PhD, Global Health of Statistics & Data Sciences, Charles River Laboratories

TABLE: Big Data to Select Patient Populations

Moderator: Dirk Brockstedt, PhD, CSO, RAPT Therapeutics

5:45 Reception in the Exhibit Hall with Poster Viewing

6:45 Close of Day

Thursday, June 4


PLENARY KEYNOTE SESSION

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

Walters_Patrick
               Patrick 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

INTEGRATED APPROACH TO TRANSLATIONAL BIOMARKERS

10:25 Chairperson’s Remarks

 

10:30 Translational Biomarkers – From Discovery to the Clinic

Call_KatherineKatherine Call, PhD, Senior Director, Head, Proteogenomics, Sanofi Translational Sciences

Biomarkers are a critical component to advance therapeutic programs and to make informed decisions along the value chain. In Sanofi Translational Sciences, we utilize genomics, genetics, proteomics, molecular histology and informatics approaches to identify candidate biomarkers. This presentation will illustrate multi-pronged and integrated approaches to discover and qualify biomarkers for hand-off for use in development and in the clinic. Several biomarker case studies will be presented.

11:00 Utility of Biomarker Post-Translational Modifications Enabling Patient Stratification

Baratta_MikeMichael Baratta, BA/MCAHPM, Scientific Director and Chief of Staff, Clinical Biomarker Development Innovation, Takeda

Advances in analytical instrumentation and reagents have afforded researchers the opportunity to interrogate post-translational modifications (PTMs) of protein biomarkers. Analysis of Tau and p181 Tau levels in CSF has been utilized in clinical trials to gain insight as a diagnostic compliment to PET scans, monitoring disease progression and response to therapeutic intervention. Incorporation of expanded Tau PTM analysis as part of a translational research strategy will be presented.

11:30 Leveraging CyTOF Technology for Biomarker Discovery in a Clinical Setting

Thrash_EmilyEmily Thrash, PhD, Scientist, Center for Immuno-Oncology Immune Assessment Laboratory, Dana-Farber Cancer Institute

Biomarker discovery in the clinical immuno-oncology setting is limited by the inherent complexity of the disease and immune response, as well as a lack of developed validated immunophenotyping methodology. With the capability to measure up to 50 parameters from a single cell, mass cytometry (CyTOF) is well poised to overcome these constraints and provide greater breadth and depth of cellular analyses within a sample compared to traditional assays like flow cytometry. Here, I will present our optimized clinical sample CyTOF workflow for high-throughput data generation and biomarker analysis pipeline.

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

BIOMARKER DISCOVERY AND ASSAY DEVELOPMENT FOR ONCOLOGY AND IMMUNO-ONCOLOGY

2:00 Chairperson’s Remarks

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

2:05 Maximizing the Return on Clinical Samples: Considerations for IO Discovery Biomarker Analysis

Donahue_AmberAmber Donahue, PhD, Senior Manager, Biomarker Clinical Assay Lead, Oncology Clinical Assay Group, Pfizer

Clinical samples are precious and generally limited. There are ways to stretch specimens further, such as aliquoting, or provision of extracted nucleic acid or even data rather than FFPE sections to analyzing laboratories. However, there are considerations necessary to this approach, including careful specimen tracking, freeze/thaw stability, fit-for-purpose cross-validation, and assay limitations.

2:35 Molecular Cytometry: Application to Immuno-Oncology and Possibilities for Precision Oncology

Chattopadhyay_PratipPratip Chattopadhyay, PhD, Associate Professor, Pathology, Isaac and Laura Perlmutter Cancer Center, NYU-Langone Medical Center


3:05 PANEL DISCUSSION: Integrated Biomarker Approaches

Coverage includes:

  • Integrating genomics, genetics, proteomics, post-translational modifications, molecular histology and other data for biomarker discovery
  • Informatics tools and data requirements for biomarker identification
  • Translational approaches for biomarker discovery, qualification and clinical development
  • High-throughput biomarker analysis and data generation
  • Integrated biomarker approaches for disease progression monitoring and predicting response to therapy

Call_KatherineModerator: Katherine Call, PhD, Senior Director, Head, Proteogenomics, Sanofi Translational Sciences


Panelists:

Baratta_MikeMichael Baratta, BA/MCAHPM, Scientific Director and Chief of Staff, Clinical Biomarker Development Innovation, Takeda


Chattopadhyay_PratipPratip Chattopadhyay, PhD, Associate Professor, Pathology, Isaac and Laura Perlmutter Cancer Center, NYU-Langone Medical Center


Amber Donahue, PhD, Senior Manager, Biomarker Clinical Assay Lead, Oncology Clinical Assay Group, Pfizer

 

Emily Thrash, PhD, Scientist, Center for Immuno-Oncology, Immune Assessment Laboratory, Dana-Farber Cancer Institute

 

3:35 Close of Conference