[Federal Register Volume 77, Number 92 (Friday, May 11, 2012)]
[Notices]
[Pages 27785-27787]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-11511]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Request for Information Regarding the NIH-Industry Program To 
Discover New Therapeutic Uses for Existing Molecules

SUMMARY: As part of a larger initiative to help reengineer the process 
of translating scientific discoveries into new therapies, the recently 
established National Center for Advancing Translational Sciences 
(NCATS) at the National Institutes of Health (NIH) will be launching a 
new collaborative program to support the exploration of promising drug 
candidates (compounds and biologics) across a broad range of human 
diseases. As an initial effort, the program will focus on discovering 
new therapeutic uses of existing molecules (Therapeutics Discovery).
    The NIH-Industry Pilot Program: Discovering New Therapeutic Uses 
for Existing Molecules is designed to be carried out through 
collaborations between pharmaceutical companies and the biomedical 
research community. The Program will match drug candidates and 
associated data from participating companies with the best ideas for 
new therapeutic uses put forward by the biomedical research community.
    NCATS will be initiating this innovative concept as a limited pilot 
Program. If the pilot is successful, and depending on the level of 
interest and available funds, the Program may be expanded. To gauge the 
breadth and depth of potential interest in the Program and to obtain 
stakeholder input and perspectives on its novel features, NCATS is 
seeking input from the biomedical research community, prospective 
industry collaborators, and other members of the public on all aspects 
of the Program and more broadly on how the government can partner with 
the private sector in this area.

DATES: Comments in response to this notice are requested by June 1, 
2012. The NIH-Industry Pilot Program: Discovering New Therapeutic Uses 
for Existing Molecules funding announcement will be published in early 
June, 2012 in the NIH Guide to Grants and Contracts at http://grants.nih.gov/grants/guide/index.html.

FOR FURTHER INFORMATION CONTACT: Questions may be submitted 
electronically to [email protected]. For additional 
information, please contact Dr. Heng Xie, NCATS, at [email protected] 
or 301-443-8063.

SUPPLEMENTARY INFORMATION:

Background

    On December 23, 2011, Congress created NCATS, (Pub. L. 112-74 
passed December 23, 2011, amending the Public Health Service Act, 42 
U.S.C. 287). One aspect of the NCATS mission focuses on developing 
innovative strategies, 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 the capabilities of other sectors to bring 
safe and effective products to patients.
    One of the strategies that NCATS will be pursuing is to advance 
research and development (R&D) efforts to find uses for therapeutics 
different from those for which they were originally developed 
(Therapeutics Discovery). Many discontinued compounds and biologics 
that have already been tested in human subjects may have promising 
applications for other indications and many approved drugs may be put 
to new uses. Harnessing previous R&D efforts and building on data 
already gathered may be a way to speed the testing of new clinical 
hypotheses and bring forward new treatments for a range of human 
diseases. Along with opportunities, however, there are also scientific, 
economic, and administrative challenges that need to be addressed. 
These were explored in an April 2011 Roundtable with senior leaders and 
experts from the pharmaceutical industry, government, academia, and the 
non-profit sector (http://www.ncats.nih.gov/files/exploring_new_uses_for_abandoned_and_approved_therapeutics.pdf.pdf). Some of the 
challenges identified at the Roundtable include: Resource implications 
(the time and resources for a pharmaceutical company to maintain, 
update, and organize their therapeutics libraries for investigating new 
therapeutic uses prior (drug rescue) or subsequent to (drug 
repurposing) FDA approval; patent considerations (off-patent or drugs 
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 concluded that 
because the private sector holds a substantial portion of the requisite 
assets, data, and knowledge and the public sector has new ideas and the 
wherewithal to advance new applications, public-private collaborations 
are central to rescue and repurposing efforts. Streamlining the 
initiation and execution of such partnerships will help promote 
collaboration, leverage the strengths of both sectors, and facilitate 
the formation of partnerships that are so critical to success.

NIH-Industry Pilot Program: Discovering New Therapeutic Uses for 
Existing Molecules

    The NIH-Industry Pilot Program: Discovering New Therapeutic Uses 
for Existing Molecules Program is designed to be carried out through 
collaborations between pharmaceutical companies and investigators from 
the biomedical research community. The Program will match drug 
candidates and associated data from participating companies with the 
best ideas for new therapeutic uses put forward by the biomedical 
research community. Funded investigators will

[[Page 27786]]

work to validate novel human mechanisms of disease using drug 
candidates that have been made available by pharmaceutical companies 
for use in small interventional clinical validation studies. The 
Program will be initiated as a limited pilot, (see: http://www.ncats.nih.gov/research/reengineering/rescue-repurpose/therapeutic-uses/therapeutic-uses.html), which if successful and depending on 
availability of funding, may be expanded as to number of participating 
pharmaceutical companies, number of drugs candidates, areas of 
interest, and number of projects.
    NCATS is currently engaging industry partners to develop a 
framework under which they will agree to provide drug candidates and 
partner with potential funding recipients under a pre-negotiated 
``Collaborative Research Agreement'' that NCATS anticipates will be 
executed between each funding recipient and industry partner.
    NCATS will be soliciting grant applications from investigators 
interested in working with a participating company to carry out studies 
of the company's drug candidate. The Request for Applications will be 
published in early June in the NIH Guide to Grants and Contracts 
(http://grants.nih.gov/grants/guide/index.html). Each company 
participating in the Program will have signed a Memorandum of 
Understanding with NCATS that articulates the goals and general terms 
of the Program. NCATS also anticipates that applicants will use 
template agreements (the Collaborative Research Agreement discussed 
above and a Confidential Disclosure Agreement, to formalize the 
relationship between the pharmaceutical partner and the biomedical 
investigator's institution. The template agreements will help 
streamline interactions among the parties, expediting the initiation of 
the discovery efforts. The template agreements are available for 
comment at: http://www.ncats.nih.gov/research/reengineering/rescue-repurpose/therapeutic-uses/agreements.htm.
    NCATS will use a two-stage application process to identify 
meritorious projects and a cooperative agreement mechanism to fund the 
research. The first step in the process is the submission of a pre-
application, called an X02. The second step is submission of a full 
application using a funding mechanism that can be used for clinical 
research known as UH2/UH3 or stand-alone UH3. Information on the drug 
candidates such as the drug's mechanism of action and any limitations 
in use based on the toxicological profile will be available when the 
X02 funding opportunity announcement is published in the NIH Guide. 
Investigators who submit pre-applications will be expected to 
demonstrate that they have the requisite competencies, capabilities, 
creativity, and environment necessary to carry out clinical trials as 
well as any necessary pre-clinical studies to provide evidence a drug 
candidate could target critical biological processes in a new disease 
area. The pre-application will be peer reviewed. Submitters of the most 
meritorious of the pre-applications will be invited to submit a full 
application for funding to conduct pre-clinical or non-interventional 
clinical studies (UH2) to provide sufficient confidence in the 
biological rationale for the new therapeutic use and clinical trials 
(UH3) in the new selected disease area using the drug candidate. The 
total project period will not exceed three years. Prior to the proposed 
clinical studies, investigators will be expected to submit an 
investigator-sponsored Investigational New Drug (IND) application to 
the Food and Drug Administration (FDA). More details about the funding 
mechanism and application process are published as NIH Notice of intent 
NOT-TR-12-001 in the NIH Guide for Grants and Contracts (http://grants.nih.gov/grants/guide/notice-files/NOT-TR-12-001.html). A Request 
for Information, NOT-TR-12-002, is also published in the NIH Guide for 
Grants and Contracts (http://grants.nih.gov/grants/guide/notice-files/NOT-TR-12-002.html).

Request for Information

    To gauge the breadth and depth of potential interest in the Program 
and to obtain stakeholder input and perspectives on its novel features, 
NCATS is seeking input from the scientific community, potential 
industry collaborators, and other members of the public on all aspects 
of the Program. NCATS is particularly interested in but not limited to 
feedback on the following issues:
    1. Partnerships with industry have been used throughout government 
and the biomedical research community to 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. Comments on how working with NIH Intramural Research Program

[[Page 27787]]

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. Discussion of whether the goals and incentives of the NIH-
Industry Program: Discovering New Therapeutic Uses for Existing 
Molecules are sufficient for biotechnology and pharmaceutical companies 
and the biomedical research community to participate in the Program. 
Discuss the most important steps NCATS should take to promote and 
facilitate partnerships for therapeutics discovery between industry and 
the biomedical research community. Your perspective on how success of 
the therapeutics discovery program might be defined.
    6. Comments 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. Comments 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.
    Comments in response to the topics above should be submitted to 
http://grants.nih.gov/grants/rfi/therapeutics_discovery/index.cfm?ID=24 and will be accepted through June 1, 2012. Other 
questions or comments relevant to this initiative may be submitted to 
[email protected].

    Dated: May 7, 2012.
Thomas R. Insel,
Acting Director, NCATS, National Institutes of Health.
[FR Doc. 2012-11511 Filed 5-10-12; 8:45 am]
BILLING CODE 4140-01-P