The goal of Broad Spectrum Products Against Multiple Neurotoxin Botulinum Serotypes (R61/R33, Clinical Trial Not Allowed) is to support the development of improved products for treating Botulinum Neurotoxin (BoNT) intoxication.
Background and Research Goals
Countermeasures to BoNT intoxication are limited and have a small therapeutic window for treating BoNT, as well as significant potential adverse effects. Crucially, there are no FDA-approved countermeasures that can reverse neuronal intoxication once the neurotoxin has bound to a neuron. Agents that are intended to reverse BoNT intoxication are a critical need, and proposals for these agents are highly encouraged.
This notice of funding opportunity (NOFO) seeks to stimulate basic, proof-of-concept, and preclinical development research focused on development of novel therapeutic strategies that address BoNT intoxication of the neurons. The initiative promotes discovery of novel, improved candidates for treating BoNT toxicity, as well as platforms for the intraneuronal delivery of antitoxins to reverse BoNT intoxication.
Specific Areas of Research Interest
Examples of areas to be studied under the R61 phase include, but are not limited to:
- Identifying novel therapeutic targets.
- Characterizing candidate therapeutics.
- Screening and identification of new therapeutic agents.
- Optimizing and down-selecting candidate(s).
- Synthesizing, purifying, and testing candidate therapeutic delivery platforms.
- Advancing preclinical development and translation of novel BoNT therapeutics.
Examples of areas to be studied under the R33 phase include, but are not limited to:
- Further preclinical development and translation of novel BoNT therapeutics.
- Safety and efficacy testing in relevant models.
- Pharmacokinetic, pharmacodynamic, and pharmacotoxicity studies.
- Process development for product manufacture.
- Good Laboratory Practices (GLP) or Current Good Manufacturing Practice (cGMP) manufacture of lead candidate(s).
The NOFO specifies a milestone-driven approach to the research. The R61 phase provides up to 2 years of funding for innovative hypothesis-driven project supported by limited or no preliminary data to allow investigators to demonstrate feasibility of candidate technologies. Support during the R61 phase is intended to enable proof-of-concept, milestone-driven research for novel BoNT targets and/or candidate therapeutics and to describe how the potential candidate(s) will be further developed in the R33 phase—transition to the R33 phase will depend on the successful completion of specific milestones during the R61 phase. During the R33 phase, support will be provided for an additional 3 years. It is anticipated that preclinical testing for safety and efficacy in animal models will be conducted in the R33 phase. Proposed transition milestones will be reviewed and negotiated prior to award.
Transition to the R33 phase is neither automatic nor guaranteed. R33 funding decisions will be based on the original R61/R33 peer review recommendations, successful completion of transition milestones, program priorities, and availability of funds. It is expected that approximately 50 percent of awards funded in the R61 phase will transition to the R33 phase.
Check the NOFO for additional details and conditions for funding.
Note that applications proposing the following will be considered nonresponsive and will not be reviewed:
- Projects not targeting at least one BoNT serotype.
- Projects proposing to develop vaccine agents or adjuvants.
- Projects that propose clinical trials.
- Applications that propose only the R61 or the R33 activities.
- Applications proposing an R33 phase that do not utilize candidates generated within the R61 phase.
Award Budgets and Project Periods
Application budgets are not to exceed $300,000 in direct costs per year for the 2-year R61 project period. For the R33 award phase, application budgets are not expected to exceed $750,000 in direct costs per year and should reflect the actual needs of the project. Applicants may request up to 2 years of support for the R61 phase and up to 3 years of support for the R33 phase. The maximum project period for an application submitted in response to this NOFO cannot exceed 5 years total.
Application and Submission Information
Applicants are required to provide detailed milestones and timeline objectives for the R61 phase and research goals and timeline for the R33 phase in a separate attachment; without this attachment, applications will be deemed incomplete and will not be reviewed.
Milestones must be specific, measurable, achievable, relevant, time-bound, and must adhere to the six-page limit. This section must not circumvent the 12-page Research Strategy page limits. Review specifics and inclusion details in the published NOFO to ensure compliance with the milestones and timeline requirements.
Applications are due by May 2, 2025, at 5:00 p.m. local time of the applicant organization. We anticipate funding five or six awards in fiscal year 2026 for the R61 phase, and two or three awards will proceed to the R33 phase.
Address scientific and research questions to Dr. Amir Zeituni at amir.zeituni@nih.gov or 301-761-6872. Questions about peer review will be handled by Dr. Frank De Silva at fdesilva@niaid.nih.gov or 240-669-5023.