Notice of Intent to Publish a Request for Pre-Applications for the NIH-Industry Pilot Program: Discovering New Therapeutic Uses for Existing Molecules (X02, UH2/UH3)


Notice Number: NOT-TR-12-001

Key Dates

Release Date:  May 3, 2012
Estimated Publication Date of Announcement:  May 2012 
First Estimated Application Due Date:  mid July 2012 

Related Notices

NOT-TR-12-002, Request for Information (RFI): Input on the NIH-Industry Program to Discover New Therapeutic Uses for Existing Molecules

Issued by

National Center for Advancing Translational Sciences (NCATS)

Purpose

The National Center for Advancing Translational Sciences (NCATS) intends to publish a Request for Applications (RFA) for the NIH-Industry Pilot Program: Discovering New Therapeutic Uses for Existing Molecules.  The therapeutics discovery program will explore new uses for discontinued proprietary drug candidates (compounds and biologics) across a broad range of human diseases.  NCATS intends to initiate the Program as a pilot with a limited set of high-quality drug candidates (Agents) and pharmaceutical company partners.  If the pilot is successful, NCATS will expand the Program to include additional pharmaceutical company partners, Agents, and new therapeutics discovery projects, subject to the availability of funding.  This innovative Program will match Agents and associated data from participating pharmaceutical company partners with the best ideas from the biomedical research community for new therapeutic uses. 

Through this Program, NCATS will provide support for investigators to assess the use of Agents for potential efficacy as interventions in new disease areas. The clinical data resulting from research funded through the Program should provide sufficient evidence that the Agent is safe, modulates the target/mechanism, and has efficacy in the disease population.  A Memorandum of Understanding (MOU) between NCATS and the pharmaceutical company partner will define the activities to be conducted under the Program. NCATS is engaging with pharmaceutical company partners to develop a framework under which they will provide Agents and partner with NIH/NCATS-supported investigators.  A template Confidential Disclosure Agreement (CDA) and template Collaborative Research Agreements (CRAs) have been developed for the Program.  NCATS anticipates that these agreements will be executed by the investigator's organization and the 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, ultimately providing a novel therapeutic intervention for that disease whenever feasible. Additional details and an opportunity to comment on the new NCATS Program are available in Notice NOT-TR-12-002, Request for Information (RFI): Input on the NIH-Industry Program to Discover Therapeutic Uses for Existing Molecules, cited above under "Related Notices."  

This Notice is being provided to allow potential applicants sufficient time to plan the development of responsive projects and to encourage comments through the RFI cited above. 

The FOA is expected to be published in May 2012 with an expected receipt date for the pre-application X02 in July 2012.

Research Initiative Details

This Notice encourages investigators with expertise and proficiency in the development of therapeutic interventions and who recognize the potential (based on the available data) for one or more of the available Agents for use in an unexplored disease area, to consider applying for this new FOA, Limited Competition for the NIH-Industry Pilot Program: Discovering New Therapeutic Uses for Existing Molecules (UH2/UH3).

This Program intends to utilize the NIH pre-application (X02) process.  Investigators will be provided feedback on their pre-applications through NIH peer review; X02 applicants with the most meritorious projects will be invited to submit a UH2/UH3 or UH3 application.  The X02 announcement will provide information on the Agents to be made available by the pharmaceutical company partners (e.g., mechanism of action, route of administration, and any limitations in use based on safety and tolerability properties). Given that the Agents have previously been investigated in clinical studies, the expectation is that investigators should have a team assembled that is prepared to rapidly move from pre-clinical validation studies for the new therapeutic use to clinical validation in the indicated disease population (UH2 to UH3).  Therefore, the total project period of the UH2/UH3 will not exceed 3 years.  Investigators will be expected to submit an investigator-sponsored Investigational New Drug (IND) application to the Food and Drug Administration (FDA) for the proposed clinical studies.      

The X02 pre-application will be used to identify applicants with the requisite competencies, capabilities, creativity, and environment necessary to carry out the clinical trials and any pre-clinical studies of the Agents that may be needed to provide evidence of the selected mechanism (biological target or disease mechanism) in new disease areas. 

An X02 announcement will be issued and submissions will be evaluated through NIH peer review to assess significance of the project, competencies, capabilities, and environment of the applicant qualifications to carry out these projects, and readiness of the team to rapidly implement the project.  No awards will be made under this pre-application announcement.  X02 applicants in the top tier, based on NIH peer review and program priorities, will be invited to submit a UH2/UH3 or UH3 application using the Agent and disease population specified in the pre-application. 

The UH2/UH3 is a cooperative agreement mechanism.  These applications will also be evaluated through NIH peer review.  The UH2/UH3 research plans should be milestone-driven with clearly defined go/no go decision criteria.  The description of the milestones and their value in guiding go/no go decisions will be an important part of the additional review criteria of these applications.  The UH2/UH3 will support the following two stages of research:

1.  The UH2:  Pre-clinical studies using the selected Agent to provide sufficient evidence in the biological rationale for the new therapeutic use.  The UH2 will provide up to 12 months of support for: a) in vitro, in vivo, or ex vivo assays or models of human disease that are critical to go/no go decision criteria; and/or b) clinical studies with biomarkers that link the Agent's mechanism of action (target or pathway) to disease pathophysiology or change in disease state in the proposed patient group.  Note that pre-clinical animal studies may not be necessary in all cases and their inclusion should be tied to a decision to test the Agent in the proposed patient group.  Phase I clinical trials should provide evidence of dose- or exposure-related effects of the Agent consistent with the mechanism of action and will be used to guide Phase IIa studies.  Proposed UH2 studies should include well-specified go/no go decision criteria that must be achieved in order for the project to advance to the second stage, the UH3 stage clinical validation or clinical proof of concept. 

2.  The UH3:  Clinical trials using the selected Agent in the proposed new disease area.  The UH3 will provide up to 2 years of support for exploratory, biomarker-driven interventional studies designed to establish the relationship between the magnitude and duration of target modulation and clinical efficacy in the indicated disease population.  Patient stratification strategies, based on molecular markers of disease, pharmacogenomics, or other biomarkers, are encouraged when applicable.  The sample size, power, and duration of the Phase IIa clinical trials should be justified for the specific disease population.  The clinical data resulting from the UH3 component should provide sufficient evidence that the drug candidate is safe, modulates the target/mechanism, and has efficacy in the disease population.  If successful, it is anticipated that the clinical studies will de-risk further development of the drug candidate for the new therapeutic indication.  Proposed UH3 studies must include a timeline with specified milestones.

Limited, non-confidential information for the Agents to be made available for use in this Program will be available to investigators at the X02 pre-application stage of the NIH-Industry Pilot Program: Discovering New Therapeutic Uses for Existing Molecules (e.g., mechanism of action, route of administration, and any limitations in use based on safety and tolerability properties).  X02 applicants invited to submit a UH2/UH3 application in response to the Limited Competition must contact the pharmaceutical company partner to execute a CDA.  Under the CDA, the applicant and pharmaceutical company partner will exchange confidential information (e.g., information on the Agent and studies to test the proposed new therapeutic use of the Agent), as deemed necessary, for the development of an NIH UH2/UH3 application.  The applicant must provide the NIH with documentation of access to the Agent and associated data needed for conducting the proposed studies (e.g., an executed CRA).  The agreement will not become effective unless the UH2/UH3 application is selected for funding.  Until that time, applicants who have signed the CDA will have access to data on the Agents, but not the Agents themselves.  X02 applicants should consider their willingness to agree to the conditions in the CRA prior to submitting the X02 pre-application. The UH2/UH3 will be submitted as a single application with two stages.  Recipients of a UH2 award are not guaranteed the stage 2, UH3 award.

Overview of the main stages of the process and who is involved for obtaining and submitting materials related to this Program:

Action

Description or Parties Involved

Request for Information (NOT-TR-12-002)

Comment period for interested stakeholders

Templates available on NCATS website:

Memorandum of Understanding (MOU)
Confidential Disclosure Agreement (CDA)
Collaborative Research Agreements (CRAs)

Prepared by NIH/NCATS and pharmaceutical company partner

Release of solicitation of pre-application (X02) submissions and Request for Applications for Cooperative Agreements (UH2/UH3)

NIH/NCATS

Information on Agents provided

NIH/NCATS and pharmaceutical company partner(s)

Pre-applications (X02s) submitted

Biomedical scientific community, including the NIH Intramural Research Program (applicants)

NIH peer review of X02 pre-applications

NIH/NCATS and scientific peer reviewers

Top-tier X02 applicants invited to submit UH2/UH3 applications

NIH/NCATS, applicants

CDA executed, confidential information shared on Agent(s)
Development of research plan initiated for UH2/UH3 application
CRA executed but not effective until an NIH award is made

Applicant, pharmaceutical company partner

UH2/UH3 application submission

Applicants

NIH peer review of UH2/UH3 applications

NIH/NCATS and scientific peer reviewers

Awards made

NIH/NCATS


Required Registrations

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Directors/Principal Investigators (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 4-6 weeks prior to the application due date.

APPLICATIONS ARE NOT BEING SOLICITED AT THIS TIME.

Inquiries

Please direct all inquiries to:

Heng Xie, M.D., M.P.H., Ph.D.
Supervisory Medical Officer
Division of Clinical Innovation
National Center for Advancing Translational Sciences, NIH
6701 Democracy Blvd., Democracy I, Rm. 908
Bethesda MD 20892-4874 (Regular mail)
Bethesda MD 20817 (FedEx)
Phone: 301-443-8063
Fax: 301-480-3661
E-mail: XieHe@mail.nih.gov
http://ncats.nih.gov/
Email box:  Therapeutics.Discovery@nih.gov


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