Notice Number: NOT-NS-05-011

Key Dates
Release Date: July 19, 2005

The National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Allergy and Infectious Diseases (NIAID), (http://www.niaid.nih.gov/), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), (http://www.niams.nih.gov/), National Institute of Environmental Health Sciences (NIEHS), (http://www.niehs.nih.gov/), National Eye Institute (NEI), (http://www.nei.nih.gov/), and the National Institute of General Medical Sciences (NIGMS), (http://www.nigms.nih.gov/) are exploring interest and capabilities relating to the development of medical countermeasures against chemicals that could be used in a terrorist attack. These Institutes are designing a program to discover and develop specific post-exposure therapeutics and diagnostic tools, and move them through the regulatory process for eventual inclusion in the Strategic National Stockpile.

Background

The increased risk of a terrorist attack in the U.S. involving chemical agents has created new challenges for many departments and agencies across the federal government. Within the Department of Health and Human Services (DHHS), the NIH is leading the development of new and improved medical countermeasures designed to prevent, diagnose, and treat the conditions caused by potential agents of terrorism. Historically, biomedical research aimed at countering the effects of chemical warfare agent exposure has been supported primarily through the Department of Defense (DoD), which has focused on developing medical countermeasures to be used in the context of traditional warfare. The NIH Chemical Threats program is part of the larger biodefense program coordinated by the NIAID that includes Biological and Radiation/Nuclear threats. The NIAID and the NINDS, working with the DoD, held a series of workshops to identify research gaps in our knowledge of medical countermeasures effective against chemical threat agents. The NINDS and NIEHS have supported research on countermeasures against neurotoxic agents through an administrative supplement program http://grants.nih.gov/grants/guide/notice-files/NOT-NS-05-004.html.

Goal of the Proposed Initiative

The primary objective of the program will be to develop medical countermeasures against chemical threat agents. The civilian chemical threat spectrum includes chemical warfare agents, toxic industrial chemicals (TICs), plant/animal toxins and other chemicals.

High Priority Chemical Threats

• Neurotoxic Agents, such as organophosphorus Nerve Gases
• Vesicating Agents, such a sulfur mustard
• Pulmonary Agents, such as chlorine gas
• Metabolic/Cellular Poisons, such as cyanide

General Research Needs and Scope of Program

• Mechanistic research to identify targets for therapeutic/diagnostic development
• Development of in vitro and animal models for efficacy screening of therapeutics and diagnostic tools
• Efficacy screening of therapeutics/diagnostics using new and existing validated in vitro and animal models that are appropriate
• Advanced efficacy GLP studies with appropriate animal models including non-human primates.
• Analytical and preclinical ADME toxicology, current Good Manufacturing Practices (cGMP) and Good Laboratory Practices (GLP) studies with promising therapeutics
• Phase 1 Clinical Trials
• Special consideration will be given to research relevant to people who are particularly vulnerable, including the young, the elderly, and individuals with pre-existing medical conditions.

Program Structure

A network of cooperative agreement awards, SBIR/STTR grants, and contracts is being considered to facilitate discovery and development of candidate therapeutics/diagnostics. These therapeutic candidates will enter into a centralized and standardized Efficacy Testing Program in collaboration with the DoD. Once such countermeasures have demonstrated efficacy against a chemical threat with appropriate animal models under GLP experimental conditions, they will enter into a Preclinical Testing and Safety Program and if successful will move on to Phase 1 Clinical Trials. The Food and Drug Administration (FDA) will be consulted to ensure that studies are carried out in compliance with regulatory requirements. Although this program plan suggests a serial progression of research activities, our preliminary analysis indicates that several candidate therapies are currently candidates for entry into this program at each of the various stages, e.g. efficacy testing, advanced preclinical testing, and clinical testing.

Special Considerations

Partnerships among academia, industry and government are essential for this type pf program. While Intellectual Property will remain with the supplier, once a countermeasure has entered into this program, its full development as a medical countermeasure against a chemical threat(s) is governed by the NIH. An agreement to this effect will be signed by all parties.

For restricted agents such as nerve agents, special biosafety approvals are required. Since the vast majority of laboratories do not have facilities approved for the use of some high priority chemical agents, the development of in vitro and animal models that simulate agent exposure and effects is desirable. Subsequent to the demonstration of efficacy using these models, a countermeasure will be tested with the actual agent at a centralized NIH/DoD-sponsored facility. In some cases, other certified laboratories may be supported to work with restricted agents as well to generate efficacy information.

Medical countermeasures that have progressed through advanced development and Phase 1 clinical studies may be eligible for additional support under Project BioShield (http://www.hhs.gov/ophep/bioshield/) which is legislation designed to accelerate the process of research, development, purchase, and availability of effective countermeasures against agents of bioterror .

Information Requested

The information supplied in any response to this request should address, but not be limited to, the following:

• One paragraph introductory description of general background and research interest related to this program. For example, applicants should specify the aspects of the program (mechanistic, efficacy, safety, clinical) in which they are interested.
• Existing candidate therapeutics for the program at various stages of development.
• Scientific and infrastructure capabilities in support of this program, including GLP and cGMP.
• Models for testing efficacy of medical therapeutics and/or diagnostics.
• Animal subjects concerns, or limitations, if any, on sharing of animal models or testing paradigms.
• Intellectual Property concerns.
• Other comments and suggestion on the general program outline given above.

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 make any award 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 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 organizations including those within the federal government.

Responses should be limited to a maximum of 5 pages and should be identified with NINDS RFI No. NOT-NS-05-011. Responses are due by September 15, 2005. Please submit three (3) copies of your response to:

David A. Jett, Ph.D.
Program Director
National Institute of Neurological Disorders and Stroke, NIH
6001 Executive Boulevard, Room 2177 MSC 9535
Bethesda, Maryland 20892-9531.
(for FedEx or courier, use: Rockville, MD 20852)

E-mail responses, sent to jettd@ninds.nih.gov will also be accepted.

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