Introduction:
The Bill & Melinda Gates Foundation, in partnership with the Global Health Innovative Technology (GHIT) Fund, is seeking innovative approaches to discover new antibiotics targeting Gram-negative bacteria.

General Description:
The call focuses on discovering novel antibiotics that can effectively target Gram-negative bacteria, which are responsible for many serious infections and are increasingly resistant to existing treatments.

The ultimate objective of Gr-ADI will be to enable discovery of safe and simple first-line broad-spectrum drugs for syndromic management, through:

• Development of novel and emerging biological, chemical, and AI tools that could be applied broadly for antibiotic discovery to identify new antibiotic targets.
• Application of these innovative approaches to generate chemical starting points for project-based drug discovery.
• Fostering a collective mindset to address gaps in knowledge, solve problems, and manage a portfolio of targets and hits.

This Grand Challenges RFP will identify and select the first projects within the consortium. The focus of this RFP will be on the discovery of antibiotics with broad spectrum activity against Enterobacteriaceae, using Klebsiella spp. as the pathogen to initiate a discovery program.

Proposals must address at least one of the following themes:

1. Development of genome-scale tools or other innovative technologies to identify new chemical starting points linked to targets as well as assessment of potential drug target vulnerability, singly or in combination.
2. Development of innovative technologies to select targets and chemical leads with a very high bar to resistance.
3. Gaining a better understanding of the chemistry underlying penetration of compounds to different compartments of the bacterial cell to build a platform to rapidly test whether compounds reach and accumulate at their target.
4. Development of novel and coordinated approaches to identifying new chemical leads for clinically or in vivo validated drug targets, for which there is currently no agent in Phase 3.

The application process will be conducted in two stages:

1. A letter of inquiry, with a scientific proposal not to exceed five pages, should be submitted through this Grand Challenges RFP.
2. Applicants selected to provide a full proposal will be informed by the end of June 2025 and will receive further details on the submission, review, and decision timeline at that time.

Eligibility Criteria

• This initiative is open to nonprofit organizations, for-profit companies, international organizations, government agencies, and academic institutions.
• Only individuals who are applying through a legally recognized corporate entity are eligible.
• We particularly encourage applications from institutions based in LMICs and projects led by women and other groups that are historically under-represented in the drug discovery field. All applications received will then be reviewed on their merits.
• Lead applicants must be able to demonstrate the experience needed to drive and lead a project and to deliver on the objectives.
• Applications can be from multi- and inter-disciplinary teams, and we encourage lead applicants to put together diverse teams, promoting a diverse, inclusive, and supportive research environment.
• Researchers may participate as co-applicants or collaborators on multiple proposals but may submit only one application as a lead applicant to this RFP. If researchers are co-applicants or collaborators on multiple proposals, they must be able to demonstrate that they can dedicate enough time and resources to all projects if all the projects they are involved in are funded.
• Applicants must be able to sign up to the terms and conditions of at least one of the funders to be eligible to apply.

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