Clinical and Translational Biomarkers in Drug Development Banner

Wednesday, May 18

11:00 am Conference Registration

12:15 pm Luncheon Presentation: Potential Predictive and Prognostic Biomarkers Identified in Baseline Plasma Samples from the VELOUR Trial

Tasha Sims, Ph.D., Associate Director, Clinical Oncology and Translational Sciences, Regeneron Pharmaceuticals, Inc.

Biomarkers of resistance or susceptibility to vascular endothelial growth factor (VEGF) inhibition have not been validated. Ziv-aflibercept (ZT, ZALTRAP), a fusion protein that binds and neutralizes VEGF-A, PlGF, and VEGF-B, is approved for the treatment of metastatic colorectal cancer (mCRC) in combination with FOLFIRI in patients who have progressed after oxaliplatin therapy. We are currently analyzing plasma samples from VELOUR, the 1226 patient, Phase III registration trial of FOLFIRI +/- ziv-aflibercept, in an effort to identify prognostic and predictive factors.

12:45 Dessert Break in the Exhibit Hall with Poster Viewing

Translational Biomarkers in Drug Development

1:30 Chairperson’s Opening Remarks

Sihem Bihorel, MS, Pharm.D., Ph.D., Assistant Professor, Pharmaceutics, University of Florida, College of Pharmacy

1:35 The Evolving Role of Biomarkers in Quantitative Systems Pharmacology

Sihem Bihorel, MS, Pharm.D., Ph.D., Assistant Professor, Pharmaceutics, University of Florida, College of Pharmacy

The digital and computational revolution has enabled the building of multi-scale models of drug response. The tracking and measurement of changes in biomarkers is the most important building block of these models. They provide entrée into the world of systems pharmacology – where pharmacology and principles of systems biology collide – and present opportunities and challenges in applying systems pharmacology to important problems in drug development, regulatory science and health care in general. This presentation will explore how systems pharmacology models are being used to gain a better understanding of disease states and drug response.

2:00 Development and Application of Efficacy Biomarkers and Models for Non-Oncology Diseases

Eric Lai, Ph.D., Senior Vice President, Head of Pharmacogenomics & Companion Diagnostics, Takeda Pharmaceuticals International, Inc.

Pharmacogenomics has been applied successfully in mainly oncology but not in other therapeutic areas. This presentation will examine some of the factors that are limiting the use and success of pharmacogenomics in non-oncology areas.

2:25 A Novel rRNA Depletion Method to Enable Whole Transcriptome Analysis of Single Cells with RNA-Seq

Maureen Peterson, Ph.D., Product Development Scientist, Research & Development, NuGEN Technologies

RNA-Seq analyses of transcripts from large numbers of cells often mask biologically relevant differences that occur in individual cells. Understanding RNA expression in a single cell has great potential for biomarker development, and monitoring disease progression and response to therapies. We describe a novel method for generating stranded RNA-Seq libraries from single cells or input amounts as low as 10 pg RNA. This method enables effective removal of specific transcripts without perturbing the original total RNA population, providing a solution for biomarker discovery and diagnostic applications using extremely limited samples.

2:55 The SOMAscan® Assay & SOMAmer® Reagents: Translatable Tools from High-Throughput Biomarker Discovery to Targeted Assays

Sheri Wilcox, Ph.D., Director, Discovery Sciences, SomaLogic, Inc.

SOMAmer® reagents are novel affinity binders made from single-stranded DNA engineered with amino-acid like side chains. These reagents combine the best properties of antibodies and aptamers – high affinity to thousands of proteins, reproducibly made synthetically. These reagents are used in a proteomic assay called the SOMAscan® assay for biomarker discovery on over 1,300 human proteins simultaneously. The exact same reagents are used as individual life science tools for direct translation of biomarker discovery to targeted assays.

3:25 Refreshment Break in the Exhibit Hall with Poster Viewing

4:25 Biomarkers in Clinical Trials

Suso Platero, Ph.D., Senior Director, Translational Research Oncology, Janssen Pharmaceuticals

4:50 Preclinical Early Biomarkers of Doxorubicin-Induced Cardiotoxicity

Varsha Desai, Ph.D., Research Biologist, National Center for Toxicological Research, US Food and Drug Administration

By using a systems biology approach, molecular markers are being identified before the occurrence of myocardial injury in a mouse model of doxorubicin-induced chronic cardiotoxicity. These preclinical early biomarkers of cardiac injury may lead to development of translational biomarkers that will allow identification of patients at risk for doxorubicin-induced cardiomyopathy and may prove valuable in designing of new safer drugs with better efficacy.

5:15 Application of Novel and Conventional Safety Biomarkers in the Development of Epigenetics Drug Candidates in Oncology

Madhu S. Mondal, Ph.D., DABT, Toxicology Project Leader, Drug Safety & Metabolism (DSM), AstraZeneca

Epigenetic reader protein Brd4 plays a key role in cellular differentiation and proliferation, and is known to be frequently modified in cancer. AZN001, a Brd-selective small molecule inhibitor developed at AstraZeneca, has gone through testing in a number of in vitro and in vivo safety assays (mouse, rat, dog, and human in vitro). The key toxicities observed in these studies include gastrointestinal (GI), bone marrow and lympho-reticular organs, and these toxicities are primarily driven by an on-target brd4-inhibitory mechanism. The current presentation outlines the mechanism of AZN001-mediated target organ toxicities using a multitude of safety biomarkers and delves deeper into the tactics of safety assessment of AZN001, prior to its evaluation in advanced cancer patients for the first time.

5:40 ThinkTank Registration

6:00-9:00 pm Dinner ThinkTank*

SC3: PD-L1 Assays for Biomarkers and Companion Diagnostics

*Separate registration required or all access

Thursday, May 19

7:30 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

Biomarker Validation and Qualification

8:25 Chairperson’s Remarks

Carolyn Compton, M.D., Ph.D., Professor, Life Sciences, Arizona State University

8:30 Biomarker Tests for Molecularly Targeted Therapies: Key to Unlocking Precision Medicine

Debra G.B. Leonard, M.D., Ph.D., Chair and Professor, Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine and Medical Center

An Institute of Medicine (IOM) committee examined the policy issues related to the clinical development and use of biomarker tests (including genomics-based tests) for targeting therapies to patients, including regulatory, reimbursement and clinical practice issues. Using previously published IOM reports, published literature and expert testimony, the committee has formulated recommendations to accelerate the progress of the development, validation and effective clinical use of biomarker tests for molecularly targeted therapies.

8:55 Development of Predictive Biomarkers for Treatment of Autoimmune Disease: Lessons Learned

Shannon Telesco, Ph.D., Department of Immunology Biomarkers, Janssen R&D

9:20 Assay and Kit Lot Bridging Considerations for Multiplex Biomarker Analysis in Support of Clinical Studies

Afshin Safavi, Ph.D., Founder and CSO, BioAgilytix Labs

Biomarker analysis has become a common practice by many pharmaceutical companies to help PK/PD modeling. The reliability of outcomes is heavily influenced by the quality of the reagents and commercial kits. One of the challenges that bioanalytical labs face when running biomarker studies is the control of lot-to-lot variability of critical reagents and commercial immunoassay kits. Case studies will be presented to highlight key bioanalytical considerations involved in running successful biomarker analyses in support of preclinical and clinical studies with consideration to platform selection and critical reagents.

9:50 From Discovery through Commercialization of Personalized Multiplex Biomarker Assays

Alfred Akowitz, Vice President, Strategic Sales, Meso Scale

Having a single platform from discovery to commercialization can reduce time to market and result in high-quality tests. We will show how MSD’s Biomarker Services are used to identify biomarkers, and how we design and validate custom assays that can be transferred to customers for their own studies.

10:20 Networking Coffee Break

10:45 The Top 5 List: Finding and Fixing the Most Important Specimen Compromisers for Biomarker Measurement

Carolyn Compton, M.D., Ph.D., Professor, Life Sciences, Arizona State University

The National Biomarker Development Alliance (NBDA) and the College of American Pathologists (CAP) have launched a strategic partnership to identify and control the pre-analytical issues that cause the greatest quality compromise for molecular analysis in human biospecimens. In a 4-day convergence conference sponsored by the NBDA in late 2014, a wide range of scientific experts, regulators, payors, funders, and physicians came to agreement on the pre-analytical variables that create the greatest molecular quality compromise in human samples, either tissue or blood, that are analyzed by next-generation sequencing and mass spectrometry. The CAP is now undertaking a 3-year project to define the performance metrics for specimen handlers that would control these variables, educate the practicing pathology community about them and enforce compliance with those metrics through the CAP Laboratory Accreditation Program. The ultimate goal is to dramatically increase the quality and consistency of the most common patient biospecimens in all CAP-approved institutions. This accomplishment would have the effect of simultaneously improving the reliability and reproducibility of biomarker analysis data for both clinical care and translational research through the standardization of patient samples.

11:10 Discovery of Genetic Biomarkers in Drug Therapy: What Is Needed for Clinical Utility?

Wolfgang Sadee, Ph.D., Professor & Director, College of Medicine Center for Pharmacogenomics, The Ohio State University

An increasing number of genetic variants have become useful and even required for personalized drug therapy. While discovery of causative markers with potential clinical impact continues, prioritizing genes and therapies for clinical applications has become critical. This talk will address progress in discovery and suggest guidelines for developing biomarker panels.

11:35 Fit-for-Purpose Inflammatory Biomarker Assay Development and Validation

Paolo Montanari, Ph.D., Senior Research Associate, Bioanalytical Sciences Section, Exploratory Science & Translational Medicine, Novimmune SA

We describe a tiered scientific approach to biomarker assay development and validation to support different clinical development phases of a monoclonal antibody (mAb) therapeutic for the treatment of an inflammatory disorder. During an observational phase in the intended disease-state population, screening of a large number inflammatory biomarkers was performed to assess which best correlated with disease activity. To support Phase II studies, a multiplex assay was developed and qualified to allow verification of the six lead biomarkers. In order to support Phase III studies further development and comprehensive validation of assays was undertaken for the biomarkers considered the best measures of target engagement and disease activity.

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

Biomarkers in Clinical Trials

1:00 Chairperson’s Remarks

Kelly Y. Kim, Ph.D., Program Director, Diagnostics Evaluation Branch, Cancer Diagnosis Program, National Cancer Institute

1:05 NCI-Sponsored Clinical Trials for Biomarker Development

Kelly Y. Kim, Ph.D., Program Director, Diagnostics Evaluation Branch, Cancer Diagnosis Program, National Cancer Institute

NCI is currently supporting several innovative clinical trials combining molecular analysis of patient specimens and targeted therapy, as part of its Precision Medicine Initiative. This talk will present an update on NCI’s experience with these trials, the challenges encountered, and the progress made to date.

1:30 A Novel Design for a Phase III Basket Trial in Multiple Tumor Types Based on a Putative Predictive Biomarker

Robert A. Beckman, M.D., Professor, Oncology, and Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center

Increasingly, tumors are defined based on molecular subtypes, which if shared across histologies, may be pooled into basket trials, facilitating development of agents targeted at small molecular subgroups. To date, basket trials have been used either for exploratory early development, or for confirmation only in cases where a transformational benefit is anticipated. This presentation discusses a confirmatory basket trial design that is generally applicable to all beneficial therapies.

2:20 Close of Conference