Multiplex Assays

Summary

A great deal of descriptive material concerning multiplex assay technologies has been written and discussed during the past decade. Multiplex Assays: Evolving Technologies, Applications and Future Directions focuses mainly on significant recent developments in the multiplex assay field.

Pharmaceutical companies are also increasingly committing to associating their drugs with diagnostic assays. The majority of these are single-analyte biomarkers. However a number of multiplex biomarkers not directly associated with particular drugs are in use as approved or homebrew diagnostics, and these contribute in various ways to the broad field of translational medicine. This report examines the role of multiplex and multi-analyte biomarker assays in translational medicine. We deal with their direct contributions to drug discovery and development; their contributions as theranostics, companion diagnostics, etc.; and the reasons why they are not more prevalent despite their apparent high potential.

Following a brief introduction, Chapter 2 provides background, definitions, describes the evolution of multiplex assays, and the development of translational medicine as both a concept and a manifest reality.

Chapter 3 provides an in depth examination of technological aspects of multiplex assays with emphasis on transcriptomics, proteomics, and metabonomics. The emphasis here is on recent developments and newer players in the multiplex assay field. Also included is a discussion of the potential role of next-generation sequencing in replacing DNA microarray technology for transcriptomics.

Chapter 4 examines applications of multiplex assays in translational medicine, and does so from the perspective of pharma R&D, companion diagnostic products, and the new diagnostics as a contributor to translational medicine.

Chapter 5 places the emphasis on market perspectives in the field. We examine the competitive environment in "omics" technology via results of an online survey of people active in the field, and also examine recent deal activity and what it reveals about the market for multiplex assays and their technologies.

Chapter 6 of the report makes some general observations relevant to a number of issues raised in earlier chapters, leaning heavily on extracts from interviews conducted for this report with people highly knowledgeable in this field. Extracts from these interviews are also to be found in earlier chapters where relevant to highlight various issues. Complete transcripts of these interviews are contained in Chapter 7.

About the author:
Ken Rubenstein, PhD, a biochemist and molecular biologist, received his PhD at the University of Wisconsin and postdoctoral training at the University of Pennsylvania School of Medicine. He was a key innovator and research manager for Syva Company, the diagnostics branch of Syntex Corporation. During his 13 years with Syva, Dr. Rubenstein became vice president, scientific affairs, a function that included strategic planning. Since 1983, he has served as a technology and marketing consultant to biomedical companies and an industry analyst, with more than 40 published studies to his credit.

Contents

CHAPTER 1 INTRODUCTION

CHAPTER 2 EVOLUTION OF MULTIPLEX ASSAYS AND TRANSLATIONAL MEDICINE
2.1: The Evolution of Now-Classical Diagnostic Biomarkers
Sensitivity, Specificity, and Predictive Value of Biomarker Assays
2.2: Pre-Genomic Biomarkers and Technologies
Enzyme and Metabolite Assays
Immunodiagnostics
Enzyme Immunoassays
Molecular Diagnostics
Target Amplification: Polymerase Chain Reaction
Signal Amplification Methods
2.3: Biomarkers in Drug Discovery and Development
2.4: Translational Medicine

CHAPTER 3 MULTIPLEX TECHNOLOGIES
3.1: Nucleic Acid-based Multiplex Assays
Two-Dimensional Positional Microarrays
Affymetrix
Agilent Technologies
Roche NimbleGen
Encoded Particle Arrays
Illumina
True Materials
NanoString
Next-Generation Sequencing as Competition for DNA Microarrays
Applied Biosystems
Roche's NimbleGen
Agilent Technologies
Others
3.2: Multiplex Assays for Proteins
Mass Spectrometry
Positional Microarrays for Multiplex Protein Analysis
Randox Laboratories
Aushon Biosystems
Theranostics Health
Encoded Bead Technology
Luminex's xMAP Bead Array
Bio-Rad
Biosite's Triage Assays
Other
Theranos
3.3: Multiplex Assays for Small Molecule Metabolites
Metabolon
BG Medicine
Biosite

CHAPTER 4 APPLICATIONS
4.1: Pharma
Eli Lilly
Novartis
The Theranos Approach
4.2: Predictive Toxicology and Multiplex Biomarkers
4.3: Diagnostics
Ridge Diagnostics
Satoris
Rules-Based Medicine
Proteome Sciences
Tethys Bioscience
Pathwork Diagnostics
BioTheranostics
Health Discovery Corporation
Quest Diagnostics
Celera Corporation
Decision Biomarkers
Banyan Biomarkers

CHAPTER 5 MARKET-RELATED CONSIDERATIONS
5.1: The Competitive Environment
5.2 Deal Patterns
5.3 User Survey Results

CHAPTER 6 GENERAL OBSERVATIONS AND CONCLUSIONS
6.1 Issues Slowing the Deployment of Multiplex Biomarkers
6.2 Pharma's Shift in R&D Emphasis
6.3 Translation in Theory versus Practice
6.4 Translational Medicine-How Well is it Working?
6.5 Discussion of User Survey Results

CHAPTER 7 INTERVIEW TRANSCRIPTS
David Lester, VP, Human Health Solutions, Theranos
Brian Edmonds, Ph.D., Research Advisor, Global External R&D, Eli Lilly
Stephen Naylor, Ph.D., Founder and Chairman of PPM, Inc.
Stephen A. Williams, M.D., Chief Medical Officer, SomaLogic
Michael Spain, M.D., Chief Medical Officer, Rules-Based Medicine
Peter Tolias, Ph.D., Executive Director, Institute of Genomic
Medicine, Research Director, The Autism Center, University of
Medicine & Dentistry of New Jersey

REFERENCES

COMPANY INDEX WITH WEB ADDRESSES

Exhibits

Exhibit 3.1 Readout from an Affymetrix DNA microarray experiment
Exhibit 3.2 Affymetrix photolithographic process for DNA microarray manufacturing
Exhibit 3.3 Roche NimbleGen microarray preparation process
Exhibit 3.4 Image of a scan from the NanoString Digital Analyzer showing immobilized and aligned reporter molecules
Exhibit 4.1: Consortia and Joint Programs for Developing Multiplex Biomarkers for Predictive Toxicology
Exhibit 5.1 Selected Deals Involving Multiplex Biomarkers
Exhibit 5.2 Company Category
Exhibit 5.4 Work Function/Pipeline Stage
Exhibit 5.5 Employment of Multiplex Biomarkers in Preclinical Development
Exhibit 5.6 Employment of Multiplex Biomarkers in Phase 0 Clinical Studies
Exhibit 5.7 Employment of Multiplex Biomarkers in Phase I/IIA Clinical Studies
Exhibit 5.8 Employment of Multiplex Biomarkers in Phase IIB/III Clinical Studies
Exhibit 5.9 Employment of Multiplex Biomarkers in Phase IV Clinical Studies
Exhibit 5.10 Use of the Same Multiplex Biomarkers in both Preclinical and Early Clinical Studies
Exhibit 5.11 Would Like to Use Same Multiplex Biomarkers in both Preclinical and Early Clinical Studies
Exhibit 5.12 Organizational Preference to Use Single-Analyte Biomarkers Whenever Possible
Exhibit 5.13 Reasons to Prefer Single Analyte Biomarkers
Exhibit 5.14 Respondent's Organization Uses Multiplex Biomarkers Preclinically without Formal Validation
Exhibit 5.15 Respondent's Organization Uses Multiplex Biomarkers in Phase 0 Studies without Formal Validation
Exhibit 5.16 Respondent's Organization Uses Multiplex Biomarkers in Phase I/IIA Clinical Studies without Formal Validation
Exhibit 5.17 During the Next Three Years, Organization's Expectation for Multiplex Biomarkers in Preclinical Development
Exhibit 5.18 During the Next Three Years, Organization's Expectation for Multiplex Biomarkers in Phases I/IIA Clinical Development
Exhibit 5.19 During the Next Three Years, Organization's Expectation for Multiplex Biomarkers in Phases IIB/III Clinical Development
Exhibit 5.20 Organization has a Drug in Development that Will Have a Companion Diagnostic
Exhibit 5.21 Diagnostic in Development is Single or Multianalyte
Exhibit 5.22 Organization's View of Companion Diagnostics
Exhibit 5.23 Organization Has a Formal Translational Medicine Group or Function?
Exhibit 5.24 Contribution of Translational Medicine to Respondent's Organization