Grand Challenges: Innovations for Gram-Negative Antibiotic Discovery

Background

Bacterial AMR is now the 3rd-leading cause of death globally, behind ischemic heart disease and stroke. The WHO has classified life-threatening community- and hospital-acquired infections due to Gram-negative bacteria, highlighting carbapenem-resistant Enterobacteriaceae (CRE) (including K. pneumoniae and E. coli) and Acinetobacter baumannii (CRAB) as the most critical AMR global health threats.

The Challenge

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. This provides a common focus point on Klebsiella spp. for all projects in the consortium and facilitates sharing of knowledge and data for mutual benefit. As such, proposals must have a primary focus on Klebsiella spp. but can also include investigation of other Enterobacteriaceae.

Proposals must address at least one of the following themes:

• 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.
• Development of innovative technologies to select targets and chemical leads with a very high bar to resistance.
• 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.
• 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.

Please see FAQs for additional guidelines.

Eligibility

_You can learn more about this opportunity by visiting the funder's website._

• 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.
  • 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.

Ineligibility

• We will not consider funding proposals that:
  • Do not directly address the core objectives as outlined above.
  • Are not focused on direct-acting small molecules (for example, proposals focused on vaccines, phages, peptides, and microbiome are not in scope).
  • Do not include Klebsiella spp.
  • Use surrogate organisms to develop tools or identify leads that will then need to be validated in pathogens of interest.
  • Are focused solely on basic exploratory scientific research without a direct connection to or impact on advancing antibiotic discovery. There must be a component of development of novel tools and technologies or methodologies.
  • Focus on development of technologies that do not have a direct link to development of small molecules.
  • Describe a distributed, broad approach to fixing the portfolio and/or pipeline.
  • Are submitted by teams not committed to collaborating with other projects funded through this RFP.
  • Are not willing to agree to sign up to the data sharing agreement between the cohort of successful projects.
  • Aim to conduct clinical trials or randomized control trials.
  • Cannot be accomplished within a three-year project duration or have a requested budget exceeding $5,000,000 USD.
  • Support researchers or research teams who are affiliated with the tobacco industry, or who receive (or are applying for) funding from the tobacco industry, which includes manufacturers and distributors of e-cigarettes or vaping products.