Notice Number: NOT-NS-08-024

Key Dates
Release Date:  September 18, 2008
Response Due By: November 26, 2008

Issued by
National Institute of Neurological Disorders and Stroke (NINDS) http://www.ninds.nih.gov

Purpose

The National Institute of Neurological Disorders and Stroke (NINDS) is considering developing a medicinal chemistry program for therapy development. The goal of the program would be to develop lead compounds with sufficient potency, efficacy, and drug-likeness to begin the preclinical pharmacology and safety (ADMET) studies required for an investigational new drug (IND) application. The NINDS envisions awarding a contract for medicinal chemistry services. These services would be available to researchers who have small molecule compounds that show promise for treating neurological conditions but who cannot yet attract private sector investment. The Institute is exploring the interest in such a resource and seeks feedback on its structure from both potential contractors and potential users.

Background

High-throughput screens and basic research studies have led to the discovery of many small molecule compounds with activity in models of neurological disease. Some of these compounds might be transformed into drugs, with chemical modifications to improve their potency and pharmacological properties. However, biotechnology and pharmaceutical companies are hesitant to invest in the early development of compounds for rare diseases or new targets, given concerns about profitability and risk. Academic researchers who have identified a promising compound rarely have access to medicinal chemistry services. The NINDS is considering a medicinal chemistry program to overcome these barriers to drug development. This program is envisioned as a collaborative effort between a medicinal chemistry service facility and researchers with bioassays that model neurological disorders and a bioactive small molecule compound.

The medicinal chemistry facility would provide:

• Medicinal chemistry design and synthesisfor chemical optimization studies.
• In vitro and in vivo assays appropriate for characterizing and optimizing the pharmacological activities of compounds. These may include assays for solubility, metabolic and chemical stability, membrane permeability, inhibition of major metabolic enzymes, and mutagenicity. This program will not include IND-enabling ADMET studies.

Users of the facility would provide:

• Primary in vitro disease assay that is sufficiently robust and reproducible to reliably detect subtle differences in bioactivity among similar compounds and that is amenable to rapid screening.
• Secondary disease assay(s) sufficient to confirm the bioactivity detected in the primary assay and to provide sufficient proof of concept to justify clinical testing.
• Small molecule compound(s) that show(s) activity in the assays described above and serve(s) as a starting point for optimization.
• Laboratory staff and other resources to test analog compounds in the disease assays, in the home laboratory, on a routine schedule.

Potential users from the research community could apply for access to these medicinal chemistry services. Applications would be reviewed with rapid turn-around. Consultants with medicinal chemistry and drug development expertise would oversee the program and provide guidance on individual projects. The medicinal chemistry facility and consultants would assist users with preliminary studies to determine if the starting compound is amenable to chemical optimization. For the most promising compounds, the medicinal chemistry facility would conduct rapid, iterative rounds of analog synthesis and testing in close collaboration with the user. Typically, compounds would be tested on a weekly or biweekly schedule, with results of the primary screening informing the subsequent compound design and synthesis by the medicinal chemists. If requested, this work could be done confidentially. Facility users would conduct all of the tests involving disease-specific assays and models in their own laboratories.

The user would be expected to continue the development of lead compounds generated by the medicinal chemistry facility and facilitate their transition into clinical testing. The user may seek support for follow-up studies through the NINDS Cooperative Program in Translational Research (https://grants.nih.gov/grants/guide/pa-files/PAR-08-232.html) or NIH RAID (http://nihroadmap.nih.gov/raid/).

Information Requested

This Request for Information (RFI) seeks input on the design of this program both from potential medicinal chemistry service contractors and from potential users of these services. Please respond to one or both of the sections below, based on your interest in this program.

If you would be interested in competing for a contract to provide medicinal chemistry and lead optimization services to the NINDS and members of the NINDS research community, please provide the following information in no more than five (5) pages:

• Brief summary of your background and research interest related to this program.
• Brief summary of your capabilities, resources, and typical costs for the medicinal chemistry and pharmacology assay services described above. Please indicate what can be done in-house and what would/may require subcontracts.
• Brief description of a process and terms for handling intellectual property and the transfer of materials and information that would meet the needs of your organization and be attractive to facility users.
• Other comments and suggestions regarding the proposed program.

 Information Requested from Potential Users

If you anticipate having compound(s) for optimization, your input on any or all of following issues is appreciated. Please limit your response to a maximum of three (3) pages.

• Brief summary of your background and research interest related to this program, including a general description of the starting compound(s); availability of, or need to develop, disease-focused primary and secondary assays suitable for chemical optimization; and goals for optimization.
• Brief description of intellectual property terms that would be acceptable to you, and whether this information is highly confidential.
• Other comments and suggestions regarding the proposed program.

 Responses

This Request for Information (RFI) is for information and planning purposes only and shall not be construed as a solicitation or as an obligation on the part of the Government.  The Government does not intend to award a contract on the basis of responses nor otherwise pay for the preparation of any information submitted or the Government’s use of such information.  Acknowledgement of receipt of responses will not be made, nor will respondents be notified of the Government’s evaluation of the information received.  However, should such a requirement materialize, no basis for claims against the Government shall arise as a result of a response to this request for information or the Government’s use of such information as either part of our evaluation process or in developing specifications for any subsequent requirement.  Responses will be held in a confidential manner.  Any proprietary information should be so marked.

All respondents are asked to indicate the type and size of your business organization, e.g., Large Business, Small Business, Veteran-Owned Small Business, Service-Disabled Veteran-Owned Small Business, HUBZone Small Business, Small Disadvantaged Business, Women-Owned Business, 8(a), Historically Black College or University/Minority Institution (HBCU/MI), educational institution, profit/non-profit hospital, or other nonprofit organization.

Responses should be identified with NINDS RFI NS-08-024 and are due by November 26, 2008.  Please submit two (2) copies of your response to:

Annette Carter
Contracting Officer
NINDS R&D Contracts Management Branch
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3287, MSC 9531
Bethesda, Maryland 20892-9531
(for FedEx or courier, use: Rockville, MD 20852)
Phone Number: 301-496-1813
Fax Number: 301-402-4225

E-mail responses sent to cartera@mail.nih.gov will also be accepted.

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