Lead Optimization and Preclinical Development of Therapeutic Candidates for Diseases of Interest to the NIDDK (R41/R42) | PA 17 131

Opportunity Information: Apply for PA 17 131

The grant opportunity "Lead Optimization and Preclinical Development of Therapeutic Candidates for Diseases of Interest to the NIDDK (R41/R42)" (Funding Opportunity Number PA-17-131) is a National Institutes of Health (NIH) Small Business Technology Transfer (STTR) funding announcement aimed at moving promising therapeutic ideas closer to the clinic. It is designed specifically to support small businesses that are developing new therapies aligned with the mission areas of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). In practical terms, it targets projects working on diseases and conditions within NIDDKs scope, which broadly includes diabetes, endocrinology and metabolic diseases, digestive diseases, nutritional disorders, obesity, and kidney, urologic, and hematologic diseases. The overall emphasis is not on basic discovery, but on the hard, translational work required to turn a research concept or early lead into a well-characterized development candidate that is ready for formal regulatory submission.

This FOA uses the R41/R42 mechanism, meaning it supports both STTR Phase I and STTR Phase II work under one umbrella. Phase I funding is intended for the earlier, risk-reducing steps that set up a viable development program. That typically means generating the initial data needed to justify the chosen therapeutic approach and to demonstrate that the lead series or prototype has a plausible path forward. Within the context of this announcement, Phase I is framed as supporting preliminary steps in either lead optimization (improving potency, selectivity, stability, manufacturability, dosing profile, and similar attributes) or early preclinical development (such as feasibility work related to pharmacology, early safety signals, or initial formulation and delivery concepts). The point is to get from an early lead to a more credible, better-defined candidate, while also establishing a disciplined development plan.

Phase II support is positioned as the main engine for advancing a lead candidate through more complete lead optimization and preclinical development. Under this FOA, Phase II projects are expected to be sufficiently advanced by the end of the award that the applicant is prepared to submit an Investigational New Drug (IND) application or Investigational Device Exemption (IDE) application to the US Food and Drug Administration (FDA). That expectation is an important signal about the level of maturity required: applicants need to be thinking in terms of a regulatory-grade development package rather than purely academic proof-of-concept. Although the announcement does not list every possible activity, the intent aligns with typical IND/IDE-enabling work, such as establishing robust preclinical efficacy evidence, defining pharmacokinetics and pharmacodynamics where appropriate, performing GLP-aligned toxicology or biocompatibility studies when needed, developing scalable manufacturing and quality approaches, and producing the documentation and datasets that support a credible regulatory submission strategy. The FOA also notes the possibility of a Phase IIB endpoint in the same general trajectory, reinforcing that the deliverable is a submission-ready package rather than an open-ended research program.

A central requirement of this opportunity is that applications include clear Milestones and Timelines. These milestones are not meant to be vague aspirations; they are expected to function like a development plan with objective performance criteria and explicit go/no-go decision points. In other words, the application should spell out what success looks like at each stage (for example, specific potency thresholds, exposure targets, safety margins, manufacturability criteria, or device performance specifications), how long each stage will take, and what decision will be made if the data do or do not meet the predefined benchmarks. This milestone-driven structure reflects the translational nature of the program and the expectation that the project will be actively managed toward a regulatory submission outcome.

Eligibility is focused on small businesses, consistent with STTR requirements, where the project is carried out through a formal collaboration between a small business concern and a research institution partner. The FOA makes the foreign eligibility rules explicit: non-domestic (non-US) entities are not eligible to apply, and non-domestic components of US organizations are not eligible to apply. At the same time, it indicates that foreign components, as defined in the NIH Grants Policy Statement, may be allowed in some cases. Practically, that means the applicant organization must be US-based and the core work cannot be routed through a non-US organizational component, though certain narrowly justified foreign components may be permissible under NIH policy if they are well justified and allowable. Applicants would need to pay close attention to NIH definitions and documentation expectations if any part of the proposed work involves foreign sites, foreign performance, or foreign collaborations.

Administratively, the opportunity is categorized as a discretionary grant under NIH, with an activity category listed under food and nutrition and health, and it is associated with CFDA number 93.847. The record shows an original closing date of 2020-01-05 and a creation date of 2017-01-24. The publicly provided fields in the source data do not specify an award ceiling or expected number of awards, so applicants would typically need to consult the full FOA text and NIH STTR budget guidelines for the most accurate and current funding details, project periods, and allowable cost structures.

Overall, this FOA is best understood as a targeted funding pathway for small businesses that already have a credible therapeutic concept and are ready to do the structured, milestone-based work required to progress from a lead or prototype to an IND/IDE-ready candidate within NIDDK-relevant disease areas. It is explicitly focused on development execution: optimizing the candidate, de-risking the program, and producing the kind of data package and decision logic that regulators and downstream investors or partners expect before first-in-human studies.

• The National Institutes of Health in the food and nutrition, health sector is offering a public funding opportunity titled "Lead Optimization and Preclinical Development of Therapeutic Candidates for Diseases of Interest to the NIDDK (R41/R42)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.847.
• This funding opportunity was created on 2017-01-24.
• Applicants must submit their applications by 2020-01-05. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: Small businesses.

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