Early-Stage Preclinical Validation of Therapeutic Leads for Diseases of Interest to the NIDDK (R01 Clinical Trial Not Allowed)

The NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is offering funding under the “Early-Stage Preclinical Validation of Therapeutic Leads for Diseases of Interest to the NIDDK” program, which supports projects advancing preclinical validation of therapeutic leads for diseases within NIDDK’s mission. This opportunity targets therapeutic leads, such as novel small molecules or non-viral biologics, that are not currently in development by major pharmaceutical or biotech firms. Projects should aim to establish a significant foundation for future clinical studies and commercialization, without overlapping with common industry targets. Funding supports validation research only, excluding initial therapeutic identification, clinical development, and understanding mechanisms of action in disease. This program prioritizes projects that offer innovative treatments and clear differentiation from current therapies, with a preference for leads that show novelty in both target and therapeutic mechanism. Proposed projects should focus on areas such as metabolic and endocrine disorders, liver and digestive diseases, obesity, kidney and urological conditions, nutritional disorders, and hematologic diseases. Eligible activities may include optimizing the structure-activity relationship of therapeutic molecules, pharmacological assessments using animal or human cell models, and protein engineering with proof-of-concept in tissue or animal models. Projects with a higher potential to improve upon standard clinical care and positively impact health outcomes will receive priority. Eligible applicants include higher education institutions, nonprofits, for-profit entities (including small businesses), local government, and faith-based organizations. Foreign institutions may participate only as components of U.S.-based organizations. Applicants should also maintain active registrations with SAM, eRA Commons, and Grants.gov to be eligible for funding. While letters of intent are not required, applicants are encouraged to submit one to help NIDDK plan for the review process. Each application should clearly document the therapeutic’s novelty, the competitive landscape, intellectual property considerations, and milestones that support progress toward validation. Funding provides 3-4 awards annually, with a total annual budget of $1.5 million. Project budgets are capped at $500,000 in total costs per year, with a typical direct cost of $250,000 to $300,000. Each project can extend up to a maximum period of five years. All applications should focus strictly on early-stage validation and may not propose clinical trials. Additionally, a detailed plan for the use and validation of therapeutic leads, including significant improvements over existing treatments, should be provided. Applications should avoid proposals centered on mechanistic studies, therapeutic identification, repurposing, or exploratory screening, which are outside the program’s scope. Applications must follow the SF424 (R&R) instructions, with specific guidelines to address significant improvements over current treatments, competitive analysis, intellectual property status, and a robust timeline with defined milestones. Proposals lacking these sections will be deemed incomplete. The application should also include a data-sharing plan, addressing NIH requirements for research generating scientific data. Key deadlines are standard NIH submission dates, with earliest submission dates being June 14 and October 14, annually. Applications will be evaluated based on their scientific merit, alignment with NIDDK priorities, and feasibility to meet preclinical validation goals within the program’s framework. Successful applications will demonstrate a clear path toward later-stage development and commercialization, with potential for significant clinical impact.