Harnessing Artificial Intelligence and Polypharmacology to Discover Pharmacotherapeutics for Substance Use Disorders (R43/R44 Clinical Trials Not Allowed)

Background
The National Institute on Drug Abuse (NIDA), a component of the National Institutes of Health (NIH), is offering a funding opportunity to develop artificial intelligence tools and experimental assays to identify new pharmacotherapeutics with lower toxicity and higher efficacy for substance use disorders (SUD). The traditional drug discovery paradigm involves identifying highly potent and selective molecules that act on specific targets, but this approach has lagged in AI/ML-driven drug discovery for SUDs due to the complex mechanisms and polysubstance use involved.

Polypharmacology, the study of how drug molecules interact with multiple targets, is emerging as a new paradigm that can advance drug development for multifactorial diseases such as SUDs.

Grant Details
The goal is to leverage AI/ML tools to identify pharmacotherapeutic development candidates with lower toxicity and higher efficacy to prevent or treat SUDs. Molecules may include new chemical entities, investigational compounds, and repurposed marketed medications. AI/ML tools can pinpoint the most promising targets, design effective ligands based on predicted drug-likeness, and guide in vitro and in vivo assays to assess the effects of these ligands on biological targets and functions.

The research objectives include identifying and validating disease targets, screening potential compounds to develop preliminary hits, developing assays to test the activities of candidate compounds in vitro, synthesizing novel series of compounds, testing efficacy and toxicities in vitro, testing pharmacokinetics and toxicity of selected compounds in relevant in vivo models on a non-GLP level, conducting non-GLP in vivo toxicity and efficacy of lead compound, and pharmacokinetic studies.

Eligibility Requirements
Only United States small business concerns (SBCs) are eligible to submit applications for this opportunity. A small business concern is one that meets specific criteria including being organized for profit with a place of business located in the United States, operating primarily within the United States or making a significant contribution to the United States economy through payment of taxes or use of American products, materials or labor. The concern must have not more than 500 employees. Additionally, foreign organizations are not eligible to apply.

Period of Performance
The award periods may not exceed 1 year for Phase I and 3 years for Phase II.

Grant Value
NIDA intends to commit $3M in FY 2025 to fund 4-7 awards depending on the mix of the different application types (e.g., Phase I, Fast-Track, or SBIR Direct Phase II) for both RFA-DA-25-054 and companion NOFO RFA-DA-25-053. Budgets up to $400,000 total costs for Phase I and up to $3,000,000 total costs for Phase II may be requested.