# A dual-acting small molecule for the treatment of type 1 diabetes

> **NIH NIH R42** · ASAKE BIOTECHNOLOGY, LLC · 2024 · $740,897

## Abstract

Project Summary:
Over 1.5 million Americans suffer from type 1 diabetes (T1D), an autoimmune disorder involving insulin, a
hormone that is essential for blood glucose regulation and overall energy metabolism. When first diagnosed
with T1D, it is estimated that the patient’s insulin has been reduced by 70-90%. By this point, the immune
system has already targeted and destroyed a vast majority of insulin-producing beta cells found in islets of
Langerhans within the pancreas. This destruction occurs, in large part, through a barrage of pro-inflammatory
cytokines triggering cell death. For a century since its discovery, no other substantial therapeutic
advancements have occurred outside of insulin therapy to treat T1D. However, recent advancements focused
on beta-cell health have resulted in several clinical trials. ASAKE Biotech, in collaboration with investigators at
Ohio University, is developing a small-molecule therapeutic that may be able to treat T1D in two important
ways. In tests of rodent and human pancreatic islets in a dish, our lead compound MSB-3 protected beta-cells
from cytokine-induced cell death and also stimulated these cells to produce and secrete more insulin without
depleting insulin reserves. In our phase 1 grant, we collected data in non-obese diabetic (NOD) mice, a mouse
model of T1D, to show that giving MSB-3 daily beginning at 12-weeks of age completely blocked any rise in
blood glucose and reduced insulitis (a sign of reduced autoimmunity), whereas 60% of naïve control mice
developed T1D. Moreover, In NOD mice that already had diabetes (blood glucose >300 mg/dL), daily MSB-3
treatment stabilized blood glucose and even appeared to reverse the disease entirely with no other therapy
given at any point in the trial. Despite these promising effects in disease treatment, we are not certain how
MSB-3 works. In Aim 1 of this proposal, ASAKE has partnered with one of the leading experts in small-
molecule target identification to use photoaffinity chromatography and other techniques to identify the protein
target(s) of our lead compound. These data will be used to better inform compound development by medicinal
chemistry and to assess effects of new compounds on insulin secretion and beta-cell protection. To advance
product development, we will also test several routes of administration including a novel long-acting
subcutaneous pellet in Aim 2 and determine pharmacokinetics and pharmacodynamics in Aim 3. As a possible
clinical application, Aim 4 will determine whether MSB-3 could be a used as an additive to improve the efficacy
of human islet transplantation procedures. If successful, these studies will greatly aid the development of a
potential novel product to treat T1D.

## Key facts

- **NIH application ID:** 10880698
- **Project number:** 5R42DK131839-03
- **Recipient organization:** ASAKE BIOTECHNOLOGY, LLC
- **Principal Investigator:** Craig S Nunemaker
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $740,897
- **Award type:** 5
- **Project period:** 2021-09-20 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880698

## Citation

> US National Institutes of Health, RePORTER application 10880698, A dual-acting small molecule for the treatment of type 1 diabetes (5R42DK131839-03). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/10880698. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*