Catalyze Product Definition Medical Device prototype design/testing and disease target identification and assay development (R61/R33 - Clinical Trial Not Allowed)

The goal of the NHLBI Catalyze Program is to provide a comprehensive suite of support and services to facilitate the transition of basic science discoveries into viable diagnostic and therapeutic candidates that have been cleared for human testing, and to develop translational researchers fluent in product development and entrepreneurship. This specific Catalyze Product Definition initiative will provide the early stage translational support needed for the activities required to develop and test device prototypes, identify diagnostic disease targets and develop associated assays, and develop research tools to treat HLBS diseases and disorders. This is a phased initiative for early stage projects. The R61 phase provides support to identify and test initial prototype designs, to identify a disease target and generate experimental design, and to identify, test and pilot research tools. The R33 phase provides support for continued prototype development and testing, in addition to modifying design features and user feedback, diagnostic product generation, exploration of assay components, and characterization of a load design, and research tool improvement, large trial testing and data integration. Following successful completion of the program, it is expected that the potential products will be poised to move forward for in vivo testing (optimization, safety, efficacy) with additional support from NIH and/or other federal and private programs. This initiative has a companion initiative that supports development of therapeutics and combination products and is also part of a suite of innovation grants to advance projects to the point where they can meet the entry criteria for the NHLBI Catalyze Preclinical Program.

Funding Opportunity Number: RFA-HL-26-019. Assistance Listing: 93.233,93.837,93.838,93.839. Funding Instrument: G. Category: HL.

Product Definition - Apply by: Jun 18, 2026 Preclinical EOI - Sep 14, 2026 - Oct 2, 2026 General Information Product Definition Preclinical Maximum Direct Cost increased for all NOFOs All Combination products with a drug component should apply to the therapeutic NOFOs (HL-26-017 (R61/R33) or HL-26-018 (R33)) In addition to New and Resubmission applications, the R33 NOFOs for Therapeutics (HL-26-018) and Devices (HL-26-020) now accept Renewal applications of Catalyze R33 awards.

Catalyze: Enabling Technologies and Transformative Platforms for HLBS Research (R33 - Clinical Trials Not Allowed) R33 Exploratory/Developmental Grants Phase II This NOFO solicits R33 applications where major feasibility gaps for the enabling technology or transformative platform have already been overcome, as demonstrated with supportive preliminary data, but still requires further development and rigorous validation to encourage downstream demonstration, utilization and adoption.

Well-suited applications must offer the potential to accelerate and/or transform the areas of early detection and screening, model development, clinical diagnosis, treatment, control, prevention or epidemiology, while addressing issues associated with HLBS-related diseases and disorders.

Projects proposing application of existing technologies where the novelty resides in the biological or clinical target/question being pursued are not appropriate for this solicitation. Applications considered nonresponsive to the NOFO will not be reviewed.

Catalyze: Product Definition for Small Molecules, Biologics and Combination Products - Target Identification and Validation, and Preliminary Product/Lead Series Identification (R61/R33 – Clinical Trials Not Allowed) R61/R33 Phase 1 Exploratory/Developmental Grant/ Exploratory/Developmental Grants Phase II This Notice of Funding Opportunity (NOFO) will provide the early stage translational support needed to identify and characterize potential therapeutic candidates (compound and lead series) to treat heart, lung, blood, and sleep (HLBS) diseases and disorders.

Catalyze: Product Definition for Small Molecules, Biologics, and Combination Products - Preliminary Product/Lead Series Identification and Combination Product Prototype (R33 - Clinical Trial Not Allowed) R33 Exploratory/Developmental Grants Phase II This Notice of Funding Opportunity (NOFO) will provide the early stage translational support needed to identify a lead compound series toward development of potential therapeutic agents to treat heart, lung, blood, and sleep (HLBS) diseases and disorders.

Catalyze: Product Definition – Medical Device prototype design/testing and disease target identification and assay development (R61/R33 - Clinical Trial Not Allowed) R61/R33 Phase 1 Exploratory/Developmental Grant/ Exploratory/Developmental Grants Phase II This Notice of Funding Opportunity (NOFO) will provide the early stage translational support needed to develop and test device prototype designs, identify diagnostic disease targets and develop associated assays, and develop research tools for use in the treatment of heart, lung, blood and sleep (HLBS) diseases and disorders.

Catalyze: Product Definition – Medical Device Prototype Optimization (R33 - Clinical Trial Not Allowed) R33 Exploratory/Developmental Grants Phase II This Notice of Funding Opportunity (NOFO) will provide the early stage translational support needed for prototype testing/design modification, assay development for diagnostic disease targets, and development of research tools for use in the treatment of heart, lung, blood, and sleep (HLBS) diseases and disorders.

Catalyze Key Dates to Remember Application Due Dates Review and Award Cycles New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date February 11, 2025 February 11, 2025 April 21, 2025 July 1, 2025 October 1, 2025 December 1, 2025 June 18, 2025 June 18, 2025 August 21, 2025 November 1, 2025 January 1, 2026 April 1, 2026 October 21, 2025 October 21, 2025 December 22, 2025 March 1, 2026 May 1, 2026 July 1, 2026 February 11, 2026 February 11, 2026 April 21, 2026 July 1, 2026 October 1, 2026 December 1, 2026 June 18, 2026 June 18, 2026 August 21, 2026 November 1, 2026 January 1, 2027 April 1, 2027 October 21, 2026 October 21, 2026 December 23, 2026 March 1, 2027 May 1, 2027 July 1, 2027 February 11, 2027 February 11, 2027 April 23, 2027 July 1, 2027 October 1, 2027 December 1, 2027 June 17, 2027 June 17, 2027 August 23, 2027 November 1, 2027 January 1, 2028 April 1, 2028 October 21, 2027 October 21, 2027 December 23, 2027 March 1, 2028 May 1, 2028 July 1, 2028 Phased Awards (R61/R33) and Direct to R33 Catalyze funding mechanism requirements (budget limits, cost sharing, Accelerator Partnerships, etc.) differ according to the type of technology under development, the stage of development, and the duration of the project.

For therapeutic and device/diagnostic/tool development, both phased (R61/R33) and R33 awards are available. Researchers with projects that are earlier in development may apply for phased awards, while those with more advanced projects may apply directly for an R33 opportunity. In a phased award, transition from the R61 phase to the R33 phase is based on successful completion of the R61 phase and meeting additional R33 requirements.

This table summarizes the differences between the funding mechanisms: Enabling Technologies & Transformative Platforms Devices/Diagnostics/Tools Devices/Diagnostics/Tools Catalyze: Enabling Technologies and Transformative Platforms for HLBS Research Catalyze: Product Definition for Small Molecules, Biologics and Combination Products - Target Identification and Validation, and Preliminary Product/Lead Series Identification Catalyze: Product Definition for Small Molecules, Biologics, and Combination Products - Preliminary Product/Lead Series Identification and Combination Product Prototype Catalyze: Product Definition – Medical Device prototype design/testing and disease target identification and assay development Catalyze: Product Definition – Medical Device Prototype Optimization (R33 - Clinical Trials Not Allowed) (R61/R33 – Clinical Trials Not Allowed) (R33 - Clinical Trial Not Allowed) (R61/R33 - Clinical Trial Not Allowed) (R33 - Clinical Trial Not Allowed) Application budgets must not exceed $350,000 direct costs per year.

Application budgets must not exceed direct costs of $400,000 per year during the R61 phase and also must not exceed direct costs of $400,000 per year during the R33 phase. The total budget (Federal award and non-Federal matching contributions) should reflect the actual needs of the overall proposed project. Annual project budgets should reflect the actual costs anticipated in each year.

Application budgets must not exceed direct costs of $400,000 per year. The total budget (Federal award and non-Federal matching contributions) should reflect the actual needs of the overall proposed project. Annual project budgets should reflect the actual costs anticipated in each year.

Application budgets must not exceed direct costs of $300,000 per year during the R61 phase and also must not exceed direct costs of $300,000 per year during the R33 phase. The total budget (Federal award and non-Federal matching contributions) should reflect the actual needs of the overall proposed project. Annual project budgets should reflect the actual costs anticipated in each year.

Application budgets must not exceed direct costs of $300,000 per year. The total budget (Federal award and non-Federal matching contributions) should reflect the actual needs of the overall proposed project. Annual project budgets should reflect the actual costs anticipated in each year.

Cost sharing expectations For the R33 portion of this award, the recipient is expected to provide at least a 0. 25:1 non-Federal match of the Federal direct costs requested. The recipient is expected to provide at least a 0.

25:1 non-Federal match of the Federal direct costs requested. For the R33 portion of this award, the recipient is expected to provide at least a 0. 25:1 non-Federal match of the Federal direct costs requested.

The recipient is expected to provide at least a 0. 25:1 non-Federal match of the Federal direct costs requested.

Letter of support for cost sharing funds Required to transition from R61 to R33 phase Required at time of application Required to transition from R61 to R33 Required at time of application Requires description of the milestones, timeline and project management plan including identification of team member to serve as project manager.

In addition, within the Research Strategy Section applicants must include a subsection to describe performance measures. Also requires one page attachment describing potential impact. For both phases, requires description of milestones, timeline, performance measures, and project management plan including identification of a team member to serve as project manager.

Progressing to R33 phase requires identification of at least one Accelerator Partner, provision of evidence of cost match, and continued development of IP and regulatory strategies. Requires description of milestones, timeline, performance measures, and project management plan including identification of a team member to serve as project manager. Contains cost matching component.

Requires identification of at least one Accelerator Partner. Requires a separate attachment describing preliminary IP and regulatory plans. Requires description of milestones, timeline, performance measures, and project management plan including identification of a team member to serve as project manager.

Progressing to R33 phase requires identification of at least one Accelerator Partner, provision of evidence of cost match, and continued development of IP and regulatory strategies. Requires description of milestones, timeline, performance measures, and project management plan including identification of a team member to serve as project manager. Contains cost match component.

Requires at least one Accelerator Partner. Requires a separate attachment describing preliminary IP and regulatory plans. R61/R33 Transition for development of therapeutics (RFA-HL-26-017) and devices/diagnostics/tools (RFA-HL-26-019) For phased awards, evidence of the cost match and identification of the Accelerator Partner is not required for the initial application.

To transition from the R61 to R33 phase, awardees must do the following: Achieve acceptable progress toward milestones. Demonstrate the ability to secure third-party investment by providing evidence of non-federal cost match by inclusion of a letter of support addressed to NIH. Provide a letter of support as evidence that an Accelerator Partner has been identified.

Expectations for phased awards (RFA-HL-26-017 and RFA-HL-26-019) Proof of matching funds is not required at the time of initial application and activation of the R61 phase of these awards. As the R61 phase nears its end, evidence of non-Federal matching funds must be provided to NIH in the form of a letter of support prior to the meeting of the NHLBI committee that makes the advancement decisions. NHLBI recommends a minimum of a 0.

25:1 non-Federal cost match of the Federal direct costs. Example: For every $100,000 in Federal direct costs requested, the recipient is expected to provide an additional $25,000 in non Federal matching funds. Match required = 0.

25 × Federal direct costs requested (e.g., $100,000 × 0. 25 = $25,000) To be considered responsive to these FOAs, applicants are expected to include a description in the Budget Justification of how the matching funds will be used for the R33 phase of the award. Evidence of the cost match is expected prior to release of R33 federal funds.

The Enabling Technologies and Transformative Platforms for HLBS research RFA (RFA-HL-26-016) does not have a cost sharing component. Progress and achievement of these requirements will be evaluated by an NHLBI committee tasked with making advancement decisions.

Catalyze R33 Renewal Application If interested, investigators must submit a renewal application for the existing R33 grant for a period subsequent to that provided by a current award Renewal applications compete for funding with all other peer reviewed applications and must be developed as though applicant is applying for the first time. (previously referred to as "competing continuation.")

If the renewal and subsequent resubmission of renewal application are not funded, investigators must use the "new" application type to compete for additional funding and continuity with previous award will not be retained.

New milestones must be requested for the same indication Supports all technology types except exploratory phase enabling technology Cost matching is also required for a renewal application NIH Grants Policy Reference Expectations for the non-phased R33 awards for therapeutics (RFA-HL-26-018) and device / diagnostics/tools (RFA-HL-26-020) The non-phased applications must include a letter of support from the non-Federal source(s) of cost matching.

Applications that do not include this letter will be considered nonresponsive and will not be peer reviewed. Recipients will be expected to provide evidence of non-Federal matching funds prior to the R61 to R33 transition review. The Enabling Technologies and Transformative Platforms for HLBS Research RFA (RFA-HL-26-016) does not have a cost sharing component.

Cost Matching Component Requirements Sources of non-federal funding could include, but are not necessarily limited to, foundations, participating institutions, a state or local governmental body, angel investors, venture capital firms, individual benefactors, or any combination of the above. In-kind contributions are encouraged, but do NOT apply to the cost matching requirements.

Institutions must be able to document their actual contributions to the project and provide assurances that the organization(s) are committed to providing the funds and resources for their share of the project. NHLBI recommends a minimum of a 0. 25:1 non-Federal cost match of the Federal direct costs.

Example: For every $100,000 in Federal direct costs requested, the recipient is expected to provide an additional $25,000 in non Federal matching funds. Match required = 0. 25 × Federal direct costs requested (e.g., $100,000 × 0.

25 = $25,000) It is acceptable for an Accelerator Partner to provide cost matching funds for the R33 stage, but it is not required. Federal funds may NOT be used as a source of cost sharing.

Generally, cost share requirements may NOT be met from the following sources: Costs borne by another Federal grant or sub award Costs or contributions toward cost sharing on another Federal grant, a Federal procurement contract, or any other award of Federal funds Cost of services or property financed by income earned by contractors under a contract from the recipient (or sub recipient)