Catalyze: Product Definition for Small Molecules, Biologics, and Combination Products - Preliminary Product/Lead Series Identification and Combination Product Prototype (R33 - Clinical Trial Not Allowed)

The Catalyze Product Definition initiative, administered by the National Heart, Lung, and Blood Institute (NHLBI), supports the development of small molecules, biologics, and combination products for treating heart, lung, blood, and sleep (HLBS) diseases. This program, titled Catalyze: Product Definition for Small Molecules, Biologics, and Combination Products, aims to advance early-stage projects to a point where they can proceed to preclinical testing. It focuses on identifying and validating lead compound series and early-stage prototypes for combination products, ensuring readiness for further development. This funding opportunity emphasizes innovation and translational potential. Projects must address critical therapeutic gaps and demonstrate a strong biological rationale with robust preliminary data. Activities supported include synthesis and characterization of therapeutic agents, in vitro testing, pharmacokinetic studies, and validation of combination product prototypes. The program excludes clinical trials and manufacturing for clinical use. Applicants are expected to identify clear unmet needs, characterize target patient populations, and propose detailed intellectual property and regulatory strategies. Annual funding of up to $4.466 million will be allocated for fiscal years 2026 through 2028, supporting up to eight new awards per year. Each award can request up to $400,000 in direct costs per year, with an expectation of at least a 25 percent non-federal cost match. Eligible applicants include higher education institutions, nonprofits, small businesses, and local and state governments. Non-U.S. entities may participate as components of U.S.-based organizations. Applicants must secure an Accelerator Partner to provide expertise in development, regulatory strategy, and commercialization. Applications must include specific, measurable, achievable, relevant, and time-bound milestones presented in a timeline or Gantt chart. Preliminary intellectual property and regulatory strategies must also be provided, even if not fully developed. Evidence of cost-matching funds and letters of support from partners, including Accelerator Partners, are required. Applicants must also address rigor and reproducibility and submit a data management and sharing plan. Projects will be reviewed for significance, innovation, feasibility, and the qualifications of the research team. Applications are accepted annually, with due dates on February 11, June 18, and October 21, beginning in 2025. The earliest submission date is January 11, 2025, and the first awards will be announced in December 2025. Submissions must be completed electronically through NIH ASSIST or Grants.gov, with all required registrations completed in advance. This funding opportunity represents a significant investment in the early-stage development of therapeutic agents and combination products. It aims to advance projects that can address critical gaps in HLBS disease treatment, laying the groundwork for further preclinical and clinical development. Applicants are encouraged to contact NHLBI program staff for guidance and ensure their applications align with program priorities and requirements.