Clinical biomarkers and companion diagnostics play pivotal roles in clinical development and market access of new therapeutics as well as deliver significant patient benefits, healthcare cost savings, and revenue opportunities. Population genetics and
pharmacogenomics became platforms for new drug discovery with NGS enabling sophisticated approaches for target and pathway identification and validation. Pharmaceutical companies are embracing biomarkers as a way to decrease drug failures in the clinic
by streamlining patient selection and stratification. These current trends emphasize the need for open discussion between pharma and diagnostics partners to find common ground, address strategy and technology issues, and form strong mutually beneficial
and sustainable partnerships. Cambridge Healthtech Institute’s Companion Diagnostics and Clinical Biomarkers program is designed to bring together major stakeholders in the field of drug diagnostics co-development to foster the science and business
strategies that allow
to succeed in rapidly changing healthcare environment.
Final Agenda
Monday, March 11
10:30 am Conference Program Registration Open (South Lobby)
11:50 Chairperson’s Opening Remarks
Paul Robbins, Senior Director, Immuno-Oncology, Early Development & Translational Oncology, Pfizer, Inc.
12:00 pm Biomarkers to Inform Trial Design and Combinations in Immuno-Oncology
Ron Mazumder,
PhD, MBA, Vice President, Oncology Biomarker Development & Companion Diagnostics, Genentech
I will discuss PD/MOA, predictive and surrogate biomarkers and their use in drug development.
12:30 The Targeted Agent and Profiling Utilization Registry Study: Rationale, Design
and Preliminary Findings
Richard L. Schilsky, MD, FACP, FSCT, FASCO, Senior Vice
President, CMO, American Society of Clinical Oncology
The TAPUR Study, a Phase II, prospective, non-randomized, multi-basket, pragmatic clinical trial aims to identify signals of drug activity when FDA approved drugs are matched to pre-specified genomic targets in patients with advanced cancer. More than
1100 participants have thus far received one of 15 possible treatments. Four study cohorts have closed due to lack of anti-tumor activity and 16 have expanded to the second stage due to promising preliminary results.
1:00 Session Break
1:10 Luncheon Presentation I: Multiplex Image Analysis in The Tumor Microenvironment Using Artificial Intelligence
Ben Freiberg, Visiopharm
The phenotypes of cells within the tumor microenvironment has been shown to correlate with disease progression and outcome in cancer patients. Artificial Intelligence, including machine learning and deep learning, provides tools to accurately define
these phenotypes to better understand cancer.
1:40 Luncheon Presentation II: TCR Repertoire as a Biomarker for Immunotherapy Research
Ankita Das, PhD, Marketing Manager, MedGenome Inc
2:10 Session Break
2:30 Chairperson’s Remarks
Hakan Sakul,
PhD, Vice President and Head of Diagnostics, Pfizer
2:40 Global Commercial and Partnership Considerations for Companion Diagnostics
Joseph V.
Ferrara, CEO & President, Boston Healthcare Associates
Key commercialization considerations for drug and test innovators, including balancing test access and quality, and embedding CDx global commercial considerations in pharma and diagnostic company partnerships will be highlighted.
3:10 PANEL DISCUSSION: Novel Approaches to Deal-Making in Companion Dx
The last several years have seen a substantial increase in the number of pharma/diagnostics company deals in
development of companion diagnostics. This is in part due to the emerging science generating robust diagnostics biomarkers, providing substrate to develop precision medicines aimed at smaller patient populations. As the dealmaking space continues
to be very active, it is the right time to explore new business models to enable efficient co-development of drugs and diagnostics. This panel will focus on the following:
- Lessons learned from
current model of pharma-diagnostics partnerships
- Challenges that pharma and diagnostics companies have run into in these partnerships
- New partnership models that could implement solutions to challenges faced and lessons learned
- Global commercialization of drug and diagnostics test combinations
Moderator:
Hakan Sakul,
PhD, Vice President and Head of Diagnostics, Pfizer
Panelists:
Joydeep Goswami,
PhD, President, Clinical
Next Gen Sequencing and Oncology Division (CSD), Life SciencesSolutions, Thermo Fisher Scientific
Andrew J. Beard,
PhD, Head, Business Development & Partnering, Siemens Healthcare Laboratory
Cecilia Schott, PharmD, MBA, Former Vice President, Precision
Medicine, Global Product & Portfolio Strategy, AstraZeneca
Phil Febbo, MD, CMO, Senior Vice President, Clinical Genomics,
Illumina
4:40 Refreshment Break and Transition to Plenary Session
5:00 Plenary Keynote Session (Room Location: 3 & 7)
6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing
7:30 Close of Day
Tuesday, March 12
7:30 am Registration Open and Morning Coffee (South Lobby)
8:00 Plenary Keynote Session (Room Location: 3 & 7)
9:15 Refreshment Break in the Exhibit Hall with Poster Viewing
10:15 Chairperson’s Remarks
Cecilia Schott, PharmD, MBA, Former Vice President, Precision Medicine, Global Product & Portfolio Strategy, AstraZeneca
10:25 Progress toward Personalized Medicine and Prediction of Response in Autoimmune Disease
Mark Curran,
PhD, Vice President, Immunology, Head, Companion Diagnostics, Janssen R&D LLC
Rheumatoid Arthritis and Inflammatory Bowel Disease are severe immune diseases. Despite advances in
treatment there remains a significant unmet clinical need for new therapies and integrated treatment solutions. We are focused on transforming
treatment of autoimmune diseases by applying precision medicine approaches and developing companion diagnostics to achieve higher response rates, deeper remission,
interception and eventually prevention of these diseases. Progress and learning toward these objectives will be discussed.
10:55 Validation Tips and Strategies to Receive FDA Authorization for NGS Assays
Donna Roscoe,
PhD, Chief, Molecular Genetics Branch, Division of Molecular Genetics and Pathology Devices, Office of In Vitro Diagnostics and Radiological Health, FDA CDRH
This presentation will discuss the regulatory path to successful FDA approval of
oncopanels for companion diagnostics and tumor profiling claims, including validation strategies for pan tumor claims. Strategies for validating
evolving spectrum of tests using ct/cfDNA will also be discussed.
11:25 Regulatory Landscape for Precision Medicine
Brian Abbott, Global
Regulatory Lead, CDx Advisor, Amgen
FDA’s Oncology Center of Excellence appears to be running on all cylinders – demonstrating the benefit of this joined approach through coordinated reviews, joint meetings with sponsors and timely and innovative approvals. This presentation
will provide a current view of the approvals in the precision medicine space.
11:55 Ultra-Sensitive Biomarker Measurement in Immunotherapy Research Using
Simoa Platforms
Greg Warner,
PhD, Senior Field Applications Scientist, Quanterix Corporation
We will describe the use of the Simoa technology platforms to measure low abundant, yet important, proteins that are emerging as biomarkers for the effectiveness of immuno-oncology therapies. Multiplex measurement of cytokines and other markers of T-cell
activation as a response to immunotherapy treatment using these platforms will be highlighted.
12:10 pm Optimizing TMB Use in Cancer Research and Care: The Friends of Cancer Research TMB Harmonization Effort
Mark Stewart, PhD, Vice
President, Science Policy, Friends of Cancer Research
Harmonization of methods to quantify TMB will facilitate robust biomarker development and optimize clinical utilization and treatment decision-making. Friends
aims to better understand the impact of assay variation on clinical outcomes, align standards, and define best practices for TMB assessment.
12:25 Enjoy Lunch on Your Own
1:35 Refreshment Break in the Exhibit Hall with Poster Viewing
2:05 Chairperson’s Remarks
Cecilia Schott, PharmD, MBA, Former Vice President, Precision Medicine, Global Product & Portfolio Strategy, AstraZeneca
2:10 The Importance of Facilitating High Quality Companion Diagnostic Testing for Patients Around the Globe upon Co-Approval of a Drug and a Device
Eslie Dennis, MD, Vice President and Head of Global Medical Affairs, Roche Tissue Diagnostics
Launching a companion diagnostic globally requires a strong, aligned strategic partnership between pharma and diagnostic companies. This aligned strategy is further amplified when the respective Medical Affairs teams collaborate, demonstrating the increasingly
important role of Medical Affairs to faciliate successful launches. This presentation will provide a high-level overview on developing a collaborative global Medical co- launch strategy. A broad range of activities preceding and following co-approval
enabling patients globally to have access to high quality diagnostic testing will be discussed with representative examples highlighting our experience.
2:40 Integrating China in Global Clinical Trials with a Companion Diagnostic: Challenges and Opportunities
Marielena Mata,
PhD, Director and Diagnostic Lead, Companion
Diagnosticas, Pfizer
The health challenges of China offer big opportunities for multinational pharma companies. Cases of chronic diseases are on the rise in the region, as are lung, gastric, and liver cancers. China alone is likely to be the world’s third-largest pharmaceutical
market with sales of more than $50 billion. While the unmet need for oncology drugs in the China market represents a large opportunity, conducting the clinical trials needed for registration presents a number of challenges. Changing regulations, restrictions
for the exportation of samples, IP requirements and availability of CROs represent a few of the obstacles that need to be overcome to successfully conduct global registration studies in China. In this talk, we will discuss in more depth these challenges
and potential solutions.
3:10 NEW: Streamlined CDx™
Jason Gerhold, Global Director, Regulatory Affairs and Quality Assurance, Invivoscribe
Companion Diagnostics have revolutionized precision medicine as they play a pivotal role in defining the efficacy of targeted therapies. Invivoscribe’s Streamlined CDx™ program has been shown to collapse development timelines, improve and
accelerate selection of patient cohorts, leading to earlier submissions and accelerated FDA, EMA and PMDA approvals of new targeted therapies. Streamlined CDx™ partnership model has proven successful in approval of the first ever AML companion
diagnostic – The LeukoStrat® CDx FLT3 Mutation Assay.
3:40 PANEL DISCUSSION: Driving Innovation through Global Precision Medicine Implementation
This panel will discuss the global implementation of precision medicine across therapeutic areas through multi-disciplinary teams. Advances in technology are moving from
lab to the clinic, driving the implementation of new approaches for disease treatment. The regulatory landscape is evolving at a fast pace enabling patients access to targeted therapies. The panel debate will include:
- Clinical trial design and regulatory considerations: thinking ahead
- What does it take for patients to access new testing modalities thus new therapies?
- The ever-growing importance and impact of real-world evidence in clinical practice and regulatory environment
Moderator: Cecilia Schott, PharmD, MBA, Former Vice President, Precision Medicine, Global Product & Portfolio Strategy, AstraZeneca
Panelists: Speakers of the Day
4:10 St. Patrick’s Day Celebration in the Exhibit Hall with Poster Viewing
5:00 Breakout Discussions in the Exhibit Hall
Around the Globe Strategies for Diagnostics and Clinical Biomarkers
Marielena Mata,
PhD, Director and Diagnostic Lead, Companion Diagnostics, Pfizer
Mark Curran,
PhD, Vice President, Immunology, Head, Companion Diagnostics, Janssen R&D LLC
- Preparing for the implementation of the new EU regulatory framework for CDx
- Challenges with single site PMAs and worldwide implementation
- Similarities and differences in regulatory requirements across the world. How to plan Dx global strategy and satisfy all requirements
Evolutionary Biomarkers: New Ways to Work with Pharma Companies
Alex Vadas,
PhD, L.E.K. Consulting
6:00 Close of Day
Wednesday, March 13
7:30 am Registration Open and Morning Coffee (South Lobby)
8:00 Plenary Keynote Session (Room Location: 3 & 7)
10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall
10:50 Chairperson’s Remarks
Jean-Claude Marshall,
PhD, Head, Clinical Biomarkers, Early Clinical Development, Pfizer
11:00 Biomarkers in Early Clinical Trials, an Industry Perspective
Jean-Claude Marshall,
PhD, Head, Clinical Biomarkers, Early Clinical Development, Pfizer
This talk will focus on the implementation and utilization of clinical biomarkers in early clinical development in multiple therapeutic areas. The discovery, development and validation of these assays to a variety of regulatory levels is an increasing
challenge against the need for faster and more focused Phase I and II clinical trials.
11:30 Strategies for Integrating Biomarkers into Antibody-Drug Conjugates Development Programs
Matt Onsum, Director & Head, Diagnostics, Analytics & Biomarkers,
Seattle Genetics
The co-development of a predictive biomarker with a targeted therapy has the potential to accelerate development timelines and improve the probability of technical success of the drug candidate. The identification, validation, and clinical application
of a predictive biomarker, however, remains challenging. In this talk I will present a framework for predictive biomarker development with an emphasis on applications to antibody-drug conjugate development.
12:00 pm Coding and Coverage Considerations to
Broad Based Genomic Profiling in Clinical Laboratories
Anthony (Nino) Sireci, Medical Director, Diagnostics Lead,
Medical Affairs, Loxo Oncology
The development and maturation of precision oncology is expanding the number of targetable biomarkers across both solid and heme tumors.
Broad based genomic profiling of tumor tissue which can detect all classes of genomic alterations in a small tissue sample are likely to be the most efficient way to identify patients for targeted therapies while conserving precious tissue.
Various coding and coverage realities play a part in the laboratory’s ability to implement such efficient testing over single gene algorithms.
12:30 Enjoy Lunch on Your Own
1:10 Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing
1:50 Chairperson’s Remarks
Alex Vadas, PhD, L.E.K. Consulting
2:00 SESSION PANEL: What Should be the FDA’s Role in Oversight of LDTs? A Town Hall Discussion
There are multiple ways in which the industry strives for quality including FDA, CLIA and CAP accreditations, clinical quality controls, and laboratory medicine training programs. The purpose of these approaches is to limit risk from bad actors and
poor laboratory medicine and are necessary. However diagnostics innovation is evolving at rapid pace and there are (and will continue to be) a number of areas where oversight mechanisms fall short, these may include:
- Tests with evolutionary content and interpretation (e.g., BRCA, F1CDx, opioid monitoring)
- Personalized tests that are designed uniquely for each patient (e.g., Signatera)
TriConference has assembled a panel of experts coming from different industry vantage points which gives us a unique opportunity to discuss the role of oversight, situations where current approaches fall short, and potential solutions to address deficiencies
going forward. The topics to be discussed include:
- What is the purpose of oversight in diagnostics?
- What mechanisms are in place to ensure quality?
- What are ongoing legislative or other changes that may impact laboratory oversight?
- What is the role of LDTs (e.g., fill a gap, address deficiencies with FDA-approved tests)?
- What are situations where existing regulatory or oversight approaches fall short (panel to identify specific examples and highlight key issues)? For example:
- What are real-world issues that may arise from these shortfalls? How do they impact various stakeholders?
- Picking two specific examples of evolutionary content and personalized tests what is the path forward?
- What are insights for diagnostics companies? What about pharma?
Moderator:
Alex Vadas, PhD, L.E.K. Consulting
Participants:
Girish Putcha, MD,
PhD, CMO & Clinical Laboratory Director, Freenome
Alberto Gutierrez,
PhD, Partner, NDA Partners LLC; Former Director, Office of In Vitro Diagnostics and Radiological Health, FDA
Brian Abbott, Global
Regulatory Lead, CDx Advisor, Amgen
Victoria Pratt,
PhD, FACMG, Director, Pharmacogenomics and Molecular Genetics Laboratories, Medical and Molecular Genetics, Indiana University School of Medicine; President, AMP
Dennis Dietzen,
PhD, Associate Professor of Pediatrics and Pathology, Washington University
Solomon Moshkevich, General Manager, Oncology & Transplant Businesses,
Natera
3:30 Session Break
3:40 Chairperson’s Remarks
Kurt A. Schalper, MD,
PhD, Assistant Professor, Pathology and Medicine (Medical Oncology); Director, Translational Immuno-Oncology Laboratory, Yale Cancer Center
3:45 Deconvoluting Cellular Determinants of Anti-Tumor Immune Recognition
Ash Alizadeh, PhD, Associate Professor of Medicine, Divisions of Oncology & Hematology, Stanford
University School of Medicine
I will discuss our work on developing techniques to characterize the cellular organization of tumor microenvironments, with a focus on compositional diversity and clinical significance of hematopoietic cell subsets. I will describe the genesis and
application of deconvolution algorithms to resolve tumor subpopulations and cell type-specific expression programs from genomic profiles of diverse human tumors. I will discuss the clinical translational potential in the context of individualized
approaches to immuno-oncology.
4:15 Development and Validation Considerations for Clinical Laboratory Methods for Mutational Burden Determination
Eric Konnick, MD, MS,
Assistant Professor; Associate Director, Genetics and Solid
Tumors Laboratory, University of Washington
Recent studies have indicated that increased mutational burden and microsatellite instability may predict response to anti-cancer therapies targeting the immune system. Many pre-analytical, analytical, and design factors may contribute to the ability
of a clinical diagnostic test to appropriately measure the biomarker of interest. A thorough understanding of the relevant factors that can impact patient results will allow an appropriate comparison of existing methods and implementation of new
assays.
4:45 Selected Poster Presentation: Development and Validation of a Deep Learning Algorithm for PD-L1 Scoring in Tumour Cells and Immune Cells
Michel Vandenberghe, PharmD, PhD, Senior Scientist, Precision Medicine Labs, Precision Medicine and Genomics, IMED Biotech Unit, AstraZeneca
Treatment decisions in oncology are commonly informed by the visual assessment of immunohistochemistry (IHC) biomarkers (such as PD-L1 expression) by pathologists. However, pathology services face mounting pressure as diagnostic demand increases and
workforce decreases. Digital pathology and artificial intelligence have the potential to streamline the diagnostic workflow thereby improving pathologists' workload, accelerating turn-around-times and facilitating access to testing. Here, we report
the in-house development and analytical validation of a deep learning algorithm for automated scoring of PD-L1 expression in samples processed with the VENTANA PD-L1 (SP263) Assay. The algorithm was trained to score PD-L1 expression in tumour
cells and in immune cells using 29318 manually annotated cells across a set of 150 PD-L1 IHC images from 30 urothelial carcinoma (UC) samples. The algorithm was then validated in an independent cohort of UC samples. In the validation cohort, the
algorithm demonstrated high inter-scan reproducibility (99% overall percent agreement, N=197), high inter-scanner reproducibility (100% overall percent agreement, N=33) and substantial agreement with pathologist-based scoring of PD-L1 expression
(84% overall percent agreement, N=195). In conclusion, this study shows that our deep learning algorithm has favourable analytical characteristics to assist pathologists in scoring PD-L1 in both tumour cells and immune cells.
4:55 Selected Poster Presentation: Multiparametric Flow Cytometry Analysis of Checkpoint Inhibitors (PD-1 and PD-L1) in Dissociated Tumor and Normal Tissues
Shawn Fahl, PhD,
Senior Research Scientist, Research & Development, Discovery Life Sciences
Immune checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1, have been approved as first or second-line therapies in melanoma, lung cancer, renal cancer, and urothelial cancer. More recently, these therapies have been approved in MSI-high colorectal
cancer. In the Discovery Life Sciences clinical network, we observe high percentages of patients on PD-1 and PD-L1 immunotherapies across the relevant indications. However, despite these successes, there are still some patients that have no or
partial remission in response to these therapies. Understanding the expression of checkpoint inhibitors within the complex cellular components of the tumor microenvironment provides not only crucial information on the potential functionality of
these therapies, but also allows for the identification of potential companion diagnostic markers to stratify patients prior to treatment. We present below our initial exploration of these markers in our dissociated tumor and normal tissues via
multiparametric flow cytometry to evaluate their expression on cellular subsets in both cancerous and non-cancerous tissues.
5:05 Selected Poster Presentation: Tumor Mutational Burden (TMB) Analysis Using an Ultra-High Multiplexed 20,000-Amplicon NGS Panel in a Rapid 4-Hour Workflow
Kathryn Pendleton, PhD, Scientist, Paragon Genomics, Inc.
Tumor mutational burden (TMB) is currently gaining significant importance in the field of immuno-oncology due to its correlation with patient response to checkpoint inhibitor chemotherapy. Traditionally, TMB is calculated using whole exome sequencing
via laborious hybrid-capture based methods. However, targeted sequencing approaches provide better coverage of the genetic regions of interest at lower costs. Here we present an ultrafast, 4-hour method for preparing target enriched NGS libraries
for assessing TMB - the CleanPlex® technology. This method would streamline and lower the cost of immuno-oncology studies. This is a multiplex-PCR-based technology, that provides a highly efficient, accurate and robust method for unbiased
enrichment of tens of thousands of target regions while minimizing non-specific primer-primer interactions and GC bias and maximizing coverage uniformity.
5:15 Close of Conference Program