Broad Spectrum Products Against Multiple Neurotoxin Botulinum Serotypes (R61/R33 Clinical Trial Not Allowed)

The National Institutes of Health (NIH), specifically the National Institute of Allergy and Infectious Diseases (NIAID), has issued a funding opportunity announcement titled Broad Spectrum Products Against Multiple Neurotoxin Botulinum Serotypes under the R61/R33 Exploratory/Developmental Phased Award mechanism. This opportunity supports the development of novel therapeutic products targeting Botulinum Neurotoxin (BoNT) intoxication, focusing on reversing intoxication at the neuronal level. The background highlights the critical need for improved therapies against BoNT, which causes severe illness through neuronal paralysis and can lead to respiratory failure. Current treatment options, such as BAT® (Botulism Antitoxin Heptavalent), are effective only within a narrow time frame and cannot reverse intoxication. New products must address these limitations, mitigate adverse reactions, and provide a more comprehensive approach to BoNT intoxication. This phased initiative consists of two phases. The R61 phase, up to two years with a maximum budget of $300,000 per year, focuses on hypothesis-driven, milestone-based research to identify and characterize novel therapeutic targets and candidates. Projects must demonstrate proof-of-concept for therapeutic strategies, including natural or engineered multivalent antibodies, small molecules, peptides, nanobodies, or delivery platforms to reverse BoNT intoxication. The R33 phase, up to three years with a maximum budget of $750,000 per year, supports advanced preclinical development, including safety and efficacy testing in relevant models, pharmacokinetics, and manufacturing process optimization. To transition from the R61 phase to the R33 phase, applicants must achieve specific milestones demonstrating feasibility and progress. Milestones should include measurable and quantifiable success criteria, and a detailed transition package must be submitted for review by NIAID program staff. Eligible applicants include public and private higher education institutions, nonprofits, for-profit organizations, small businesses, tribal governments, and other U.S.-based entities. Foreign organizations and components are not eligible. Applications must include a Milestones and Timeline attachment, which outlines the key benchmarks for the project and future objectives for both phases. Key dates include a Letter of Intent deadline of April 2, 2025, with full applications due by May 2, 2025. Applicants are encouraged to contact NIH program staff for guidance and clarification during the proposal development process. Projects that propose clinical trials, focus solely on vaccines, or fail to address BoNT serotypes will be deemed nonresponsive and excluded from review. The initiative anticipates funding 5-6 awards in the R61 phase, with approximately 2-3 awards proceeding to the R33 phase based on performance and program priorities. Total funding available for the initiative is $2.9 million for Fiscal Year 2026. Applications will undergo NIH peer review based on the significance, innovation, rigor, and feasibility of the proposed work. Successful applicants will be notified through a Notice of Award. Compliance with NIH data management, sharing policies, and ethical requirements, including protections for human subjects and vertebrate animals, is mandatory.