CFAs: Artificial Intelligence Powered Approaches for T1D Cell Therapy

Pancreatic islet transplantation has proven to restore metabolic control, reduce glycemic variability and improve quality of life in T1D patients that experience severe hypoglycemic events and impaired hypoglycemia unawareness. While improvements have been made in donor pancreas procurement and methods to isolate, purify, and preserve islets, major scientific and technical challenges remain that must be addressed before beta cell replacement can be expanded to broader T1D populations.

Breakthrough T1D is soliciting Letters of Intent (LOI) aimed at addressing one or more of the following gaps in T1D cell therapy research using AI/ML:

• Improving the function and/or survival of renewable sources of insulin-producing cells (e.g., stem cell-derived islets).
• Developing immune protection strategies to prevent rejection of transplanted cells that do not rely on chronic systemic immunosuppression.
• Establishing methods of predicting transplanted cell survival and function prior to decline in c-peptide levels or glycemic control.
• Implications of a specific therapeutic approach (cell type and protection strategy, site of implantation) for efficacy, safety and patient selection.

Examples of topics pertinent to this call include but are not limited to:

• Generating and analyzing clinical and/or preclinical datasets to identify signatures of human beta cell stress or immune rejection to better measure and predict graft health/failure prior to decline in beta cell function or recipient’s immune status.
• Leveraging single cell datasets from other fields such as solid organ transplant or oncology to identify mechanisms capable of reducing immunogenicity or improving survival (immune checkpoint expression, vascularization, metabolism, etc.)
• Generating and analyzing datasets on foreign body response or oxygenation requirements to understand mechanisms of tissue response at different implant sites and mitigate biomaterial rejection in cell delivery devices.
• Using large multi-well screens of small molecule libraries to identify islet or stem cellderived islet responses that may improve transplant outcomes.

Funding Information

• This initiative will award grants to academic investigators and industry partners of up to $750,000.00 over 3 years.
• Letters of Intent (LOI) can be submitted under the following mechanism(s):
  • Strategic Research Agreements (SRAs):
    • Strategic Research Agreements are intended for support of research activities at non-for profit entities such as academic institutions. For SRAs, proposed budgets for projects should not exceed $750,000.00 USD (including 10% indirect costs) total costs for up to three (3) years. The level of funding will vary depending on the scope, data available, need to
    • perform additional laboratory assays, access to samples, degree of data analysis to be performed, and overall objectives of the proposal.
  • Industry Discovery and Development Partnerships (IDDPs):
    • For-profit entities may apply under Breakthrough T1D’s Industry Discovery & Development Partnership (IDDP) funding mechanism, which entails additional requirements and typically has a modest royalty payback to Breakthrough T1D.

Eligibility Criteria

• Applications may be submitted by domestic and foreign non-profit organization, public and private, such as universities, colleges, hospitals and laboratories, units of state and local governments and eligible agencies of the federal government, for-profit entities, or industry collaborations with academia. Applicants must hold an M.D., D.M.D., D.V.M., Ph.D., or equivalent and have a faculty position or equivalent at a college, university, medical school, or other research facility.
• Applications from for-profit entities or industry collaborations with academia may be submitted in response to this RFA. Additional information will be requested from for-profit entities if invited to submit a full proposal.
• There are no citizenship requirements for this program. To assure continued excellence and diversity among applicants and awardees, Breakthrough T1D welcomes applications from all qualified individuals and encourages applications from persons with disabilities, women, and members of minority groups underrepresented in the sciences.

For more information, visit Breakthrough T1D.