Notice Number: NOT-TR-12-002
Release Date: May 3, 2012
Response Date: 4 weeks from issue date
National Center for Advancing Translational Sciences (NCATS)
On December 23, 2011, Congress created a new center at the National Institutes of Health (NIH), the National Center for Advancing Translational Sciences (NCATS, Public Law 112-74 (December 23, 2011), amending the Public Health Service Act, 42 U.S.C. § 287). One aspect of the NCATS mission is to focus on developing innovative new methods and tools to reduce or eliminate barriers to drug and diagnostic development. By developing new methods that can be adopted across the entire medical product development sector, NCATS will enhance others’ ability to bring safe and effective products to patients. One important way that NCATS will do this is to develop innovative public-private partnerships with pharmaceutical companies and the biomedical research community. To this end, NCATS is developing the NIH-Industry Pilot Program: Discovering New Therapeutic Uses for Existing Molecules to match discontinued proprietary drug candidates (compounds and biologics) from pharmaceutical companies with the best ideas from the biomedical research community for new therapeutic uses.
NIH seeks input from the biomedical research community, potential biotechnology and pharmaceutical company partners, and other members of the public on this proposed therapeutics discovery program and more broadly on how the Government can partner with the private sector in this area. The Program will fund research to explore new therapeutic uses for proprietary drug candidates (Agents) across a broad range of human diseases. NCATS plans to initiate this Program through a limited pilot. If the pilot is successful, the Program will be expanded to include additional pharmaceutical and biotechnology company partners, Agents, and new therapeutics discovery projects, subject to the availability of funding.
The goal of the Program is to discover new therapeutic uses for Agents, with known pharmacologic mechanisms of action, in previously unexplored disease areas. Through this Program, investigators will have an opportunity to investigate Agents, which have been made available by pharmaceutical company partners, for pre-clinical and/or clinical validation studies for the new therapeutic use and for clinical trials in the indicated disease population. The clinical data resulting from a successful research project should provide sufficient evidence that the Agent is safe, modulates the target/mechanism, and shows potential for efficacy in the proposed disease population. NCATS is currently engaging pharmaceutical company partners to develop a framework under which they will provide Agents and partner with investigators under template Collaborative Research Agreements (CRAs) that NCATS anticipates will be executed between each investigator's organization and pharmaceutical company partner. It is anticipated that through the CRA, the investigator will obtain access to the Agent and the pharmaceutical company partner will obtain license options that it can exercise to further develop and commercialize the Agent for new indications of interest, including requisite Phase III clinical trials, ultimately providing a novel therapeutic intervention for that disease whenever feasible. Additional details on the research program are available in Notice NOT-TR-12-001, Intent to Publish a Request for Pre-Applications for the NIH-Industry Program: Discovering New Therapeutic Uses for Existing Molecules (X02), cited above under "Related Notices".
Information obtained via this RFI will help NCATS develop the new Program and the underlying terms of implementing this public-private partnership as we seek to continue beyond the pilot phase. NCATS invites comments on all aspects of the Program and, more broadly on how NIH can partner with others to advance the development of understanding from existing molecules and the development of new effective treatments.
Drug rescue and repurposing are examples of cost-effective approaches to speed the development of new drugs and diagnostics (1). At this time of unprecedented challenge and opportunity in translational science, NIH has an important role to play in accelerating and advancing therapeutics development (2), and drug rescue and repurposing efforts are a priority area with the potential to yield tangible and significant progress in the short term.
While the private sector holds many of the Agents and data that are needed for efficient rescue and repurposing, innovative ideas for new uses of these resources come from a variety of organizations, including NIH. As such, partnerships and collaborations are critical to enable this research to proceed.
In April 2011, NIH convened an NIH-Industry Roundtable that included a group of senior leaders and experts from the pharmaceutical industry, government, academia, and the non-profit sector to explore opportunities to foster new NIH-industry partnerships that facilitate drug rescue and repurposing. Some of the challenges that were identified include: resource implications (the time and resources for a pharmaceutical company to maintain, update, and organize their compound libraries for drug rescue and repurposing); patent considerations (off-patent compounds or compounds whose patents are close to expiring, may not be attractive to industry because the financial return and market incentives for the product may be limited); and transactional hurdles related to developing, negotiating and implementing appropriate legal agreements among the parties, including addressing such concerns as intellectual property rights and liability.
The Roundtable participants agreed that more can and should be done to increase engagement and partnerships in drug rescue and repurposing and to enhance the success of these efforts. In response to one of the recommendations from the meeting, NCATS is developing the current Program. As an initial effort, the Program will focus on discovering new uses of existing molecules (drug rescue) and anticipates launching a limited number of projects as a pilot, subject to the availability of Agents and funding.
The NIH-Industry Program: Discovering New Therapeutic Uses for Existing Molecules will focus on identifying novel therapeutic uses of high-quality, proprietary Agents made available by participating pharmaceutical company partners. A Memorandum of Understanding (MOU) between NCATS and the pharmaceutical company partner defines the activities to be conducted under the pilot program. NCATS anticipates that applicants will use template agreements for the Program: a Confidential Disclosure Agreement (CDA) and a CRA between the pharmaceutical company partner and the academic institution(s). These proposed template agreements are intended to streamline interactions among the parties, expediting the discovery efforts. Applicants will be able to access these agreements prior to submitting an NIH X02 pre-application. For more details, please see Notice NOT-TR-12-001.
This RFI invites input from the scientific community, potential industry partners, and other members of the public on all aspects of the program. NCATS is particularly interested in receiving input on the following issues:
1. Partnerships with industry have been used throughout government and the biomedical research community o leverage each sector’s expertise to speed scientific research and corresponding commercial development. We are interested in hearing about innovative strategies and practices that have proven successful to develop novel uses for discontinued Agents that have no known development limitations and are safe for use in humans. Your response can include your opinion of the most significant challenges for public-private partnerships that foster drug rescue between biomedical researchers and the pharmaceutical industry as well as your experiences with drug rescue or repurposing partnerships. Your input on options NCATS can consider which promise to nurture academic efforts to foster greater translation through projects such as the NIH-Industry Pilot Program: Discovering New Therapeutic Uses for Existing Molecules. Your response can also include input on how NIH can identify partners that would like to provide drugs and biologics that are no longer being pursued internally to the NIH research community for investigation for new therapeutic uses.
2. Because this Program involves obtaining permission to use, and work with, privately owned Agents, exclusive patent or regulatory rights will likely be important incentives for the commercial success of the new therapeutic use for a drug candidate identified under the NIH-Industry Pilot Program: Discovering New Therapeutic Uses for Existing Molecules. The ability to achieve an exclusive right to market a drug product, whether through a new use or other patentable subject matter related to the Agent, is likely to significantly affect the pharmaceutical partner's or other developer’s incentive to commercialize rescued drugs or biologics based on new research results arising from the Program.
NCATS understands that a significant impediment to government, academic, non-profit, and industry partnerships involved in discovering and commercializing new uses of Agents is the "transaction cost" of negotiating appropriate legal agreements on a case-by-case basis. Thus, to address this concern, a key feature of the Program is that template agreements will be offered as a means of implementing the partnership. We are interested in the views of potential academic and industry partners on the transaction cost of developing individual agreements as well as the desirability of using template agreements and incorporating them into this Program. We are interested in your comments on how the use of template CDAs and CRAs in general and the current CDA and CRA might affect your institution's participation in the therapeutics discovery program. Applicants will be able to access these agreements prior to submitting an NIH X02 pre-application. For more details, please see Notice NOT-TR-12-001.
3. Comments on how working with a Clinical and Translational Science Award site (CTSAs) could advance drug rescue research projects, particularly for rare and neglected diseases.
4. Comment on how working with NIH Intramural Research Program investigators (http://www.irp.nih.gov) and the NIH Clinical Center resources (http://www.cc.nih.gov/index.html) could advance your drug rescue research project.
5. Discuss whether the goals and incentives of the NIH-Industry Program: Discovering New Therapeutic Uses for Existing Molecules are sufficient for biotechnology and pharmaceutical companies to participate in the Program. Your perspective on how success of the therapeutics discovery program would be defined.
6. Comment on the resources that a biotechnology or pharmaceutical company partner might realistically contribute to an NCATS program on therapeutics discovery in addition to the Agent and the associated data. You can also comment on the type of information about the molecules that you would be willing to disclose publicly.
7. Comment on the pharmacologic activity or biological target of the drug candidate that you need access to in order to test your biological hypothesis of disease intervention.How to Submit a Response
Response to this RFI is voluntary. Interested parties are invited to respond. Responders are free to address any or all of the above items. Please note that the United States (U.S.) Government will not pay for response preparation or for the use of any information contained in the response.
All comments must be submitted electronically to http://grants.nih.gov/grants/rfi/therapeutics_discovery/index.cfm?ID=24
Responses to this RFI will be accepted through June 1 2012. You will receive an electronic confirmation acknowledging receipt of your response, but will not receive individualized feedback on any suggestions. No basis for claims against the U.S. Government shall arise as a result of a response to this request for information or from the Government’s use of such information.
A summary of responsive input will be made publicly available. Personally identifiable information will be removed to the extent possible prior to making the comments public. We recommend that respondents remove personal identifiers prior to submission and that no proprietary information be included in the response.
This RFI is for planning purposes only and is not a solicitation for applications or an obligation on the part of the U.S. Government to provide support for any ideas identified in response to it.General Information
Note: All of the following fields are optional. Proprietary, classified, confidential, or sensitive information should not be included in your response.
1. Please identify the nature of your interest in the area (e.g., are you a biomedical or clinical researcher, a pharmaceutical company partner interested in participating in this initiative, a member of an advocacy or community group, or other?).
2. Please indicate the name of the organization if any.
3. Please indicate your main area of research interest.
4. Your name.
5. Your email address.
1. Drug rescue refers to research involving discontinued compounds or drug candidates that are not currently in development, whereas repurposing refers to research on approved drugs for new indications.
2. Collins F.S., Opportunities for Research and NIH. Science 327: 36-37, 2010. http://www.sciencemag.org/content/327/5961/36.full.pdf.
Please direct all inquiries to: Therapeutics.Discovery@nih.gov
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