Electromagnetic reprogramming of systemic metabolism for the treatment of type 2 diabetes

Abstract: Over half of patients with type 2 diabetes (T2D) do not achieve healthy glycemic goals, increasing their risk of complications and premature death. A primary cause of treatment failure is non-adherence. Fifty percent of patients with T2D do not take their medications as prescribed, typically because the drug regimens are too complex, or too painful. The FDA and WHO confirm that there is an urgent need to develop safe/effective therapies that improve adherence. Bioelectronic medicine is an exciting solution that uses electromagnetic fields (EMFs) to treat T2D. These EMF treatments offer adherence advantages over traditional drugs: 1) EMFs are non-invasive, minimizing complexity and discomfort; 2) EMFs can be automated, simplifying self-administration; and 3) EMFs can be targeted, reducing off target effects. Yet, emerging bioelectronic approaches fail to take full advantage of the noninvasive nature of an EMF-based approach and instead rely on implantable devices that have high failure rates and necessitate surgery or on approaches that require the use of exogenous transgenes, limiting clinical utility. Most importantly, these approaches do not target insulin resistance—the central hallmark of T2D. To overcome these limitations, Geminii is developing the NeuWave, a “sleep to treat” technology that delivers unique magnetic and electric fields during sleep to rewire carbohydrate and lipid metabolism, increasing glucose utilization and boosting insulin sensitivity in T2D. Preliminary results in T2D mouse models—published in Cell Metabolism—demonstrate that the approach is feasible when using a distinct combination of magnetic and electric fields, applied for at least 7 hours per day. Geminii’s goal with this multi-phase SBIR project is to develop this digital therapeutic platform into a commercial wearable technology for T2D and beyond. In this proposal, we aim to demonstrate feasibility of NeuWave in a second model of T2D to address FDA comments, which indicated the need for additional animal studies (proposed here) to support an IDE application and an early feasibility trial. Therefore, the Phase I objective is to determine the feasibility of safely applying NeuWave during sleep to passively manage T2D. We will achieve our objective in a multi-part Aim using lean and obese- diabetic rats as follows: Aim 1A will determine the dose-response/feasibility of NeuWave; Aim 1B will identify robust predictive biomarkers for therapeutic responses; and Aim 1C will assess toxicity. NeuWave will be deemed feasible when we meet/exceed Go/No-Go metrics that are aligned with FDA guidelines for developing T2D therapies: a) improvements in glycemic responses; b) insulin sensitivity; c) identification of predictive biomarkers; and d) a robust safety profile. The outcomes of this proposal will address the need for additional non-GLP animal studies and will allow Geminii to pursue more comprehensive Phase II studies in which a clinical wearable device will be developed and tested on larger animals in combination with standard of care therapies. These data will be used to support IDE submission to set the stage for early feasibility clinical testing. NeuWave would provide patients with accessible/convenient at-home healthcare to improve patient outcomes.