RFA-HL-26-016: Catalyze Enabling Technologies and Transformative Platforms for HLBS Research (R33)

RFA-HL-26-016: Catalyze Enabling Technologies and Transformative Platforms for HLBS Research (R33)

The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH), is accepting applications under RFA-HL-26-016, “Catalyze: Enabling Technologies and Transformative Platforms for HLBS Research.” This is an R33 Exploratory/Developmental Grants Phase II opportunity for projects that have moved beyond an early proof of concept but still need substantial development and rigorous validation. The focus is on technologies or platforms relevant to heart, lung, blood, and sleep (HLBS) diseases and disorders.

The next application due date listed in the official notice is 2026-10-21 at 5:00 PM local time of the applicant organization. The previously listed 2026-06-18 deadline has passed, but the notice also lists later dates of 2027-02-11, 2027-06-17, and 2027-10-21. This is therefore an active, fixed-deadline funding opportunity rather than a closed archive entry or a rolling program. The notice’s expiration date is 2027-12-24.

Key details at a glance

The planned funding and award counts are subject to NIH appropriations and the submission of a sufficient number of meritorious applications. The $350,000 figure is a direct-cost ceiling for each application year; it is not a promise that every award will receive that amount. The notice also says that the total budget must reflect the actual needs of the proposed project and the anticipated costs in each year.

What NHLBI wants to support

This R33 is for further development and validation of a novel enabling technology or transformative platform in a representative biological or clinically relevant system. A suitable project should offer a capability that could materially improve research or translation in an HLBS context. The technology may support early detection and screening, model development, clinical diagnosis, treatment, control, prevention, or epidemiology, but the central contribution must be the technology or platform itself.

The notice expects major feasibility gaps to have already been overcome. Applicants should provide preliminary data showing that the project has passed the pilot developmental stage and has a first-generation prototype or comparable working basis for the proposed validation. NHLBI describes the expected stage as a mid-stage Technology Readiness Level between TRL 3 and TRL 4. The R33 period is intended to establish repeatable, reliable performance in a relevant context of use, not to start with an untested concept.

Examples of responsive areas in the notice include novel materials, chemical reagents, instrumentation, devices, methods, and models for molecular, cellular, or organ-level work. The notice names drug-discovery platforms, clinically relevant in vitro and in vivo models, safer gene-delivery technologies, delivery systems for pharmaceutical or cell-based therapeutics, non-invasive diagnosis and monitoring, cell-expansion technologies, tools for clinically relevant biomarker work, improved animal models, epidemiology data-collection technologies, point-of-care technologies, stem-cell authentication standards, and approaches for tracking stem-cell therapies in vivo.

The project still needs a clear HLBS connection. A technology can have uses beyond one disease area, but the application must explain how it can improve the outlook for HLBS-related diseases or disorders. The proposal should also state what unmet technical need it addresses, what current approaches cannot do, and how the proposed capability could be transferred or demonstrated in a later product or research setting.

What is not responsive

The opportunity is not a general grant for applying an existing method to a new biological question. A project is at risk of being nonresponsive when its novelty rests mainly in the biological or clinical target rather than in a novel technical capability. The notice specifically identifies biomarker discovery or validation as nonresponsive when the underlying novelty is a traditional biological or clinical hypothesis instead of the technology being developed.

Other examples the notice treats as nonresponsive include development of a specific contrast agent, a drug or therapy intended only for one disease or condition, or a device intended only to treat one disease or condition. Projects focused primarily on software or informatics solutions, database development, data mining, statistical tools, or computational and mathematical modeling are also outside the intended scope, except for software embedded in a new device or limited computational work needed to develop a new device or method.

The maturity boundary matters in both directions. Projects without a first-generation prototype or without evidence that major feasibility gaps have been addressed should consider an earlier-stage NIH or NHLBI route. Projects with a proven prototype that has already satisfied rigorous performance measures may be better suited to a later Catalyze Product Definition opportunity. Applicants unsure about fit are encouraged by NHLBI to contact the scientific or research staff listed in the notice before submitting.

Eligibility and organizational readiness

The eligible-organization list is broad. It includes public and private higher education institutions; nonprofits with or without 501(c)(3) status; small businesses and other for-profit organizations; state, county, city, township, special-district, federal, and tribal governments; U.S. territories or possessions; independent school districts; public or Indian housing authorities; Native American tribal organizations; faith-based or community-based organizations; and regional organizations listed in the notice.

Foreign organizations are not eligible to apply as the applicant organization. The notice does allow non-domestic components of U.S. organizations and foreign components as defined by the NIH Grants Policy Statement. That distinction should be resolved with the organization’s grants office before the application is built.

The permitted application types are new applications and resubmissions. The notice does not allow clinical trials. It also allows an applicant organization to submit more than one application when the applications are scientifically distinct. NIH will not accept duplicate or highly overlapping applications under review at the same time.

Registrations must be complete before submission. The applicant organization needs active System for Award Management (SAM), eRA Commons, and Grants.gov registrations. The notice warns that registration can take 6 weeks or more and that an incomplete registration is not a valid reason for a late submission. Each PD/PI needs an eRA Commons account affiliated with the applicant organization; when one person serves as both PD/PI and signing official, the roles require distinct eRA Commons accounts.

Funding and project structure

NHLBI intends to commit total costs of up to $2,156,000 in FY 2026, $2,156,000 in FY 2027, and $2,156,000 in FY 2028. The notice anticipates up to 4 new awards in each of those fiscal years, for up to 12 new awards in total. These are planning figures and depend on appropriations and scientific merit.

Each application may request no more than $350,000 in direct costs per year. The maximum project period is 2 years, with the actual period determined by the proposed work. Budgets should be tied to validation activities, performance measures, personnel, equipment or materials, and project management needs. The application should include appropriate support for the PD/PI to attend a 1.5-day NHLBI innovation meeting or workshop in the Washington, DC/Metropolitan area once each budget year. Applicants should also budget for appropriate project-management support.

Project management is a substantive requirement, not an administrative afterthought. Each project must identify a team member who will hold project-management responsibility, even if the project does not need a full-time manager. That person is expected to help develop milestones, timelines, risks, and mitigation strategies and to work with the program officer and Catalyze Coordinating Center. NHLBI staff may monitor progress through quarterly meetings and make non-competing award decisions annually based on achievement of milestones.

Application steps and required content

1. Confirm responsiveness. Map the proposed technology to an HLBS-relevant context of use, explain the unmet technical need, and assemble preliminary data showing that the project is beyond the pilot stage. If the fit is uncertain, contact the scientific or research staff named in the notice.

2. Finish registrations early. Confirm active SAM, eRA Commons, and Grants.gov registrations for the organization. Confirm an eRA Commons account for every PD/PI and the correct organizational affiliations before the submission window.

3. Choose a submission route. The application package must be accessed through NIH ASSIST, an institutional system-to-system solution, or Grants.gov Workspace. Paper submission is not an option. Institutional applicants should coordinate with their sponsored-research office because the system-to-system route depends on institutional availability.

4. Follow the NIH Research application instructions. Prepare the SF424(R&R) cover, project and performance-site information, other project information, senior/key person profiles, budget, subaward budget when applicable, PHS 398 cover-page supplement, and research plan. The NIH Research (R) Instructions and the notice’s program-specific instructions both apply, and page limits must be followed.

5. Attach the Statement of Potential Impact. A required one-page attachment must use the filename “Statement of Potential Impact.pdf.” It should explain why the new capability could have unusually high impact on biomedical research or medicine, how it improves on available alternatives, and what steps or partnerships could move the capability toward a prototype product or broader use.

6. Build the research strategy around validation. Address advanced development and validation of the HLBS-relevant technology, substantial improvement or new capabilities, transformative potential, and explicit performance measures. The research strategy must contain a dedicated subsection labeled “Performance Measures.” Measures should be numerically described, objectively assessable, scientifically justified, and compared with existing technologies or approaches where relevant.

7. Define milestones and a timeline. Each specific aim needs at least one decision-oriented milestone. The notice does not treat a specific aim or a list of annual activities as a milestone by itself. Include a detailed timeline, with specific, measurable, achievable, relevant, and time-bound milestones, and explain how the team will use progress reviews to make decisions. Address rigor, reproducibility, controls, analysis, and the feasibility of completing the work within the proposed project period.

8. Submit by the fixed deadline. The next listed deadline is 2026-10-21 at 5:00 PM local time of the applicant organization. Submit early enough to correct errors found in the electronic submission process. The later listed deadlines are 2027-02-11, 2027-06-17, and 2027-10-21. The notice does not describe this opportunity as continuously open, so applicants should plan around one of the listed dates rather than assume late or rolling acceptance.

How applications will be judged

NIH peer review will assess scientific and technical merit, but this NOFO adds several fit and execution questions. Reviewers will consider whether the feasibility gaps have been overcome, whether the technology is likely to be adopted by the relevant research and development community, and whether the project could have transformative impact on biomedical research or medicine.

For rigor and feasibility, reviewers will examine the experimental design, controls, sample-size justification where relevant, analysis plan, biological variables, reproducibility, and ability to address problems that emerge. They will specifically assess whether milestones are measurable and achievable, whether the timeline is realistic and non-duplicative, and whether performance measures are quantifiable and scientifically justified. The project-management structure will also be evaluated for its ability to keep work on schedule.

The strongest applications will connect each requested cost and research activity to a validation decision. They will show what success looks like numerically, what evidence would trigger a change in direction, and how the team will handle a result that does not meet a target. A broad promise of future clinical impact is not a substitute for preliminary evidence, a relevant context of use, and a credible measurement plan.

Bottom line

RFA-HL-26-016 is a focused R33 for a technology or platform that already has enough evidence to justify advanced development, but still needs rigorous HLBS-relevant validation. It is not a discovery-only award, a single-disease treatment-development award, or a general software-development grant. Eligible U.S. organizations and their permitted components can apply through ASSIST, an institutional system-to-system route, or Grants.gov Workspace, provided they complete the required registrations and submit a compliant research package.

The immediate planning date is 2026-10-21, followed by the later dates published in the NOFO. Applications should be organized around a first-generation prototype or equivalent feasibility evidence, a transformative technical capability, objective performance measures, explicit milestones, project-management ownership, and a two-year budget that stays within the $350,000 direct-cost ceiling per year. The official opportunity page is the authoritative source for the application package, instructions, contacts, and any later notice affecting the listed schedule.

Official source

• NIH official NOFO: https://grants.nih.gov/grants/guide/rfa-files/RFA-HL-26-016.html