Breakthrough T1D Request for Applications: Development of Devices and Drugs for Fully Automated Insulin Delivery at Meals

Funding over a maximum of three years for clinical or preclinical research – including clinical trials – to develop automated insulin delivery (AID) systems.

Breakthrough T1D, based in the United States, is an international organisation that funds innovative research in pursuit of its mission to advance the treatment, prevention and cure of type-1 diabetes (T1D).

This Request for Applications – Development of Devices and Drugs for Fully Automated Insulin Delivery at Meals – is seeking research proposals for the development of technologies to allow for automated insulin delivery at meals, as aligned with the Breakthrough T1D objective of achieving true full closed loop (FCL) automated insulin delivery (AID). Letters of intent are sought from academic and industry applicants to develop AID systems, or to develop components of such systems (eg rapid-acting insulins) that will be incorporated into AID systems in the future.

The current standard of hybrid closed loop (HCL) systems significantly improves glycaemic outcomes and reduces the individual burden of diabetes management. The quality-of-life improvements conferred by today’s AID systems are, however, limited by the requirement for manual user inputs to handle glucose changes associated with meals.

Systems that can fully automate insulin delivery around meals promise to improve the experience of people already using AID systems and encourage others to try AID systems for the first time. This RFA is seeking to support pre-clinical and clinical research, including clinical trials, to develop AID systems, or system components, that are fully automated around meals.

Systems should have the following features:

• No user interactions, even simple meal announcements, required for adequate coverage of typical meals and snacks.
• AID systems must manage mealtime glucose excursions while mitigating the risk of delayed hypoglycemia and hyperglycemia.
• Not impose additional burdens on users (for example, additional external wearables), and would ideally improve upon current levels of usability.
• AID systems developed for a target population that includes people not currently achieving recommended glycemic targets, rather than just the most highly engaged users already achieving optimal glucose outcomes, will be prioritised (for example, new systems should be minimally complex, and trials should include people currently achieving suboptimal glycemic outcomes (eg high A1c, low time in range), as feasible).

Breakthrough T1D anticipates that successful approaches will combine advanced algorithms and drugs, including adjunctive/non-insulin therapies (including insulin-pramlintide co-formulations) and ultra-rapid insulin (URI).

Examples of research appropriate for this RFA include, but are not limited to:

• Preclinical development of URIs, either novel insulin analogs or existing analogs in novel formulations, designed to be ‘fast-on, fast-off’ (while the ultimate goal must be incorporation into an AID system, Breakthrough T1D will consider supporting development efforts that must be completed first, such as pharmacokinetic studies in animal models outside the AID context. URIs in any stage of development are eligible for funding, but priority will be given to projects supporting insulins that have been validated in animal models).
• Clinical development of URIs, including trials to investigate pharmacokinetics/pharmacodynamics and/or assess efficacy in an AID context without meal announcements.
• Clinical development of adjunctive therapies that normalise prandial blood glucose excursions, alleviating the need for announcements of meals. Adjunctive therapies may be either co-formulated with insulin or stand-alone products, and may be designed for T1D or repurposed from other indications.
• Clinical development of AID algorithms that forego the requirement for meal announcements. Only trial-ready algorithms with strong preliminary data (eg from simulations or previous clinical trials) will be considered for funding.
• Clinical development of an AID system composed of more than one of the above approaches (URI, adjunctive therapy, algorithm).
• Trials in populations most likely to clinically benefit from full mealtime automation of insulin delivery.
• Trials of AID systems with full automation at mealtime focused on capturing measures of user experience in addition to blood glucose and other clinical endpoints.
• Other innovative approaches aligned with the goal of developing AID systems with full automation around meals.