Request for Proposals (RFP) Executive Summary

Problem

IDENTIFICATION OF GENE EXPRESSION BIOMARKERS OF CLINICAL OUTCOMES IN RHEUMATOID ARTHRITIS

Problem Statement

Molecular Response to Oral and Injectable Disease-Modifying Anti-Rheumatic Drugs (DMARD) in Subjects with Rheumatoid Arthritis (RA) as Determined by Whole Blood mRNA Expression: The primary objective of this Translational Medicine Unit RFP is to determine if whole blood gene expression profiling can be utilized for early decision making [i.e. proof of concept (POC) or proof of non-viability (PONV)] for new DMARDs. Secondary bjectives include the identification of pathways or targets that merit further discovery efforts and identification of gene expression profiles associated with response or lack of response to particular therapies.

The development plan for an oral DMARD typically includes single and multiple dose escalation studies in healthy volunteers followed by a 2 – 4 week safety study in RA subjects. This is typically followed by a large randomized clinical trial of at least 12 weeks duration.

Further complicating this development paradigm is the difficulty in recruiting RA patients with active disease. The availability of effective biotherapeutics, including anti-TNF agents and Abatacept, has reduced the number of RA subjects with active disease that might qualify for POC studies.

The Pfizer Inflammation Therapeutic Area (TA) would be able to significantly reduce the time and cost from First in Human Study (FIH) until POC decision if an objective, sensitive biomarker were available for POC decision making for compounds with novel, unproven mechanisms. Additionally, the Inflammation TA would be able to prosecute a greater number of novel targets and devote resources to those compounds that demonstrated preliminary efficacy with regard to this biomarker.

RA has a key systemic inflammatory component that is manifested in the expression profile of peripheral blood mononuclear cells. The Inflammation TA has been exploring whole blood mRNA transcriptional profiling as a potential biomarker for early decision making. Preliminary Pfizer data from RA patients obtained from RA patients has demonstrated the feasibility of this approach.

Key Requirements for Successful RFP Bidders

1. Capability to rapidly receive, process, and store a large number of whole blood mRNA samples
2. Gene expression profiling capabilities
3. Gene expression data analysis
4. The ability to work collaboratively with Pfizer in developing the strategy for validating biomarkers. A history of previous similar interactions with the pharmaceutical industry is desirable. This strategy is envisioned to involve separating the data set into test and validation components. Once the marker has been identified, the bidder will work with Pfizer to plan prospective studies in new patient populations to further validate and develop the biomarker. Such studies may be planned with precedented agents and with novel compounds with unprecedented mechanisms of action.

Deliverables

1. Identification of a molecular fingerprint that demonstrates a robust short-term (2 – 4 weeks) change that is predictive of a long-term (12 weeks or more) clinical outcome.
2. The opportunity to identify novel drug targets through Affymetrix or Agilent profiling when combined with pathway and systems biology analyses.
3. Characterization of markers of response and non-response to therapy.

Time to Solve the Problem

The estimated timeframe is within 3 years. Please provide a best estimate of time in the proposal.

Request for Proposal (RFP) Due Date

All final proposals must be submitted no later than August 31, 2007.

Submitting a Proposal

If you are interested in submitting a proposal to address the above therapeutic area topic, please complete the following informational template and send it to: [email protected]

• Inflammation - RFI (PDF)