HEAL Initiative-Early-Stage Discovery of New Pain Targets Within the Understudied Druggable Proteome (R03 Clinical Trial Not Allowed)

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Description

This NIH opportunity, part of the HEAL (Helping to End Addiction Long-term) Initiative, solicits applications for pilot projects aimed at discovering new druggable targets for pain within the understudied druggable proteome. The program is designed to jumpstart research on specific, eligible understudied proteins (as listed in the NOFO) by providing funding for the generation of preliminary data and/or research tools. The ultimate goal is to accelerate the development of novel, non-addictive pain therapeutics and improve pain management, particularly in the context of opioid addiction.

Projects may include pilot or feasibility studies, development of research methodologies, assay development, or creation of human cell or animal models, provided they focus on the eligible proteins. The R03 mechanism supports discrete, well-defined projects that can be completed within one year and require limited funding.

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Due Dates

• New Applications: June 16, 2025 | October 16, 2025 | February 16, 2026 | June 16, 2026
• Renewal/Resubmission/Revision: July 16, 2025 | November 16, 2025 | March 16, 2026 | July 16, 2026

All applications are due by 5:00 PM local time of the applicant organization.

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Funding Amount

• Maximum Direct Costs: $100,000 for a one-year project period (excluding subcontract F&A).
• Project Duration: 1 year (non-renewable).
• Mechanism: NIH R03 Small Grant.

Budget requests must reflect the actual needs of the proposed project. No cost sharing is required.

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Eligibility

• Eligible Applicants:

  • Public/State and Private Institutions of Higher Education
  • Nonprofits (with or without 501(c)(3) status, other than higher education)
  • For-profit organizations (including small businesses)
  • State, County, City, Township, and Special District Governments
  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American tribal governments (federally recognized and other)
  • Native American tribal organizations (other than federally recognized)
  • Faith-based and community-based organizations
  • Regional organizations
  • U.S. Territories and Possessions
  • Eligible agencies of the federal government

• Ineligible:

  • Non-domestic (non-U.S.) entities (foreign organizations)
  • Non-domestic components of U.S. organizations

• Foreign components (as defined in the NIH Grants Policy Statement) are allowed within U.S. organizations.

• Eligible Individuals: Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as PD/PI.

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Application Process

• Submission: Applications must be submitted electronically via Grants.gov or the NIH ASSIST system.
• Required Registrations: SAM, eRA Commons, Grants.gov (can take 6+ weeks).
• Application Guide: Follow the NIH SF424 (R&R) Application Guide and the specific instructions in the NOFO.
• Research Plan: Must focus on one or more eligible proteins listed in the NOFO. The protein acronym(s) must be listed at the top of page one of the Research Plan.
• Preliminary Data: Not required, but justification for the approach should be provided.
• Budget: Include travel costs for one PD/PI to attend a 2-day, in-person HEAL Investigators meeting in Washington, DC.
• Data Sharing: All HEAL-funded data must be shared through the HEAL Initiative Data Ecosystem per HEAL data sharing policy.
• Appendix: Only limited materials allowed (e.g., blank questionnaires).

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Additional Information

• Scope: Only projects focusing on the eligible proteins (as listed in the NOFO) are responsive. Applications focusing on other proteins, proposing clinical trials, or clinical drug development are non-responsive and will not be reviewed.

• Types of Projects Supported:

  • Isolation and characterization of understudied proteins
  • Placement of proteins in pain-related signaling cascades
  • Identification/validation of pain biomarkers
  • Preclinical animal studies for therapeutic development
  • Characterization of protein expression/function in pain contexts
  • Development of tools for protein study
  • Preliminary structure-activity relationship studies

• PI Meeting Requirement: Awardees are expected to participate in annual HEAL Investigators Meetings and other coordination activities.

• Review Criteria: Emphasis on significance, innovation, rigor, feasibility, and investigator expertise. See the NOFO review section for details.

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External Links

• Full NOFO and Application Instructions (PAR-25-154)
• NIH HEAL Initiative Overview
• NIH SF424 (R&R) Application Guide (Forms-H)
• Grants.gov Opportunity Listing
• HEAL Data Sharing Policy

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Contact Information

Key Scientific Contacts (examples):

• Karlie Sharma, Ph.D. (NCATS): karlie.sharma@nih.gov, 301-451-4965
• Patrick C. Still, Ph.D. (NCCIH): patrick.still@nih.gov, 301-682-1895
• Mark Egli, Ph.D. (NIAAA): megli@mail.nih.gov, 301-594-6382
• D.P. Mohapatra, Ph.D. (NINDS): dp.mohapatra@nih.gov, 301-496-9964

For a full list of contacts by participating NIH institute, see Section VII of the NOFO.

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