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.

Grant Number: 1R43DK141319-01
NIH Institute/Center: NIH
Principal Investigator: Calvin Carter