In response to the alarming increase of drug-resistant Gram-negative bacteria, NIAID has put out a notice of funding opportunity (NOFO) Partnerships for the Development of Tools to Advance Therapeutic Discovery for Select Antibiotic-Resistant Gram-Negative Bacteria (R01, Clinical Trial Not Allowed).
Gram-negative bacterial pathogens such as carbapenem-resistant Acinetobacter, carbapenem-resistant Enterobacterales (CRE), and multidrug-resistant (MDR) Pseudomonas aeruginosa pose grave risks to public health, especially due to the lack of effective therapeutic options to treat some of these infections—an issue that’s exacerbated by the scarcity of novel compounds effective against antimicrobial resistant (AR) and MDR Gram-negative bacteria in the discovery and development pipeline.
Research Objectives and Scope
The objective of this NOFO is to support milestone-driven projects focused on developing and utilizing novel predictive models, assays, tools, or platforms aimed at gaining a better understanding of the rules and compound properties that govern the penetration and efflux of drug-like small molecules into Gram-negative bacterial pathogens. This NOFO also encourages the preclinical development of novel Gram-negative antibacterial therapeutics based on the tools and models hereby developed.
Note that applications must focus on one or more of the following Gram-negative bacterial pathogens: carbapenem-resistant Acinetobacter, CRE, and MDR Pseudomonas aeruginosa. Projects should complete assay/tool/model development prior to the end of the third year of the project period and initiate discovery activities to demonstrate its utility in supporting a corresponding medicinal chemistry program to generate a lead chemical series with demonstrated activity against one or more targeted Gram-negative bacteria. This NOFO also encourages subsequent preclinical development of a promising lead antibacterial.
Given the complex challenges of this research, this initiative encourages applications from multidisciplinary teams composed of relevant experts in areas such as bacterial physiology, microbiology, bacterial membrane biology, medicinal chemistry, pharmacology, computation, and specialized technologies. It also encourages close collaboration between academic and industry partners to optimally combine innovative basic science with drug discovery expertise and proper access to compound libraries more typically available from industry. In addition, we recommend collaboration with the NIAID Chemistry Center for Combating Antibiotic-Resistant Bacteria (CC4CARB) for completion of project relevant medicinal chemistry tasks.
Refer to the NOFO for examples of assay and model development activities.
NIAID will consider applications including the following to be nonresponsive and not review them:
- Projects that do not focus on at least one select Gram-negative pathogen (carbapenem-resistant Acinetobacter, carbapenem-resistant Enterobacterales, or MDR Pseudomonas aeruginosa).
- Projects focused only on Gram-positive bacteria or Mycobacterium tuberculosis.
- Projects that do not focus on penetration and efflux of small molecules.
- Applications not containing a Milestone and Timeline attachment.
- Applications proposing clinical trials.
- Research on HIV/AIDS.
Award and Deadline Information
The application due date for this NOFO is August 20, 2024. NIAID plans to fund seven to nine awards.
Application budgets are not expected to exceed $750,000 in annual direct costs. The scope of your project should determine the requested project period, but note that the maximum project period is 5 years.
Applications must also include a “Milestones and Timeline” attachment under “Other Attachments”. This attachment must not exceed five pages and should provide:
- A clear description of all interim objectives (research and/or developmental milestones) to be achieved during the project. Applicants should highlight potential impediments that could require a revision in the work plan or milestones, with a discussion of alternative approaches.
- Detailed quantitative criteria by which milestone achievement will be assessed.
- A detailed schedule or timeline for the anticipated attainment of each milestone and the overall goal(s).
Applicant organizations may submit more than one application, provided each application is scientifically distinct.
Contacts
For questions related to your application, contact Dr. Zuoyu Xu at xuzuoyu@niaid.nih.gov or 240-627-3394. For peer review questions, contact Dr. Maryam Feili-Hariri at haririmf@niaid.nih.gov or 240-669-5026.