# Targeting LRRC8 signaling to prevent & treat arterial thrombosis in type 2 diabetes

> **NIH NIH R44** · SENSEION THERAPEUTICS, INC. · 2024 · $982,162

## Abstract

Project Summary
 Cardiovascular disease (CVD) including stroke and myocardial infarction (MI), and Type 2 diabetes (T2D) are
 overlapping global pandemics. CVD is the most common cause of death in patients with T2D and the economic
 burden of stroke and myocardial ischemia in patients with T2D is staggering. While newer glycemic control
 agents like SGLT2 inhibitors and GLP1 agonists can help reduce CVD events in T2D, significant residual CVD
risk remains. Stroke and MI most often occur when a platelet-rich thrombus form at the site of a ruptured
 atherosclerotic plaque, occluding the vessel lumen, and resulting in downstream ischemia. There are at least
 four classes of drugs available to inhibit platelet rich thrombi formation including aspirin, P2Y12 receptor inhibitors,
and thrombin receptor inhibitors. While current antiplatelet drugs can reduce CVD events and death, their
 therapeutic potential is limited by major bleeding. Thus, there is a large unmet clinical and commercial need
 for a drug that improves glycemic control in T2D and also safely prevents cerebral and coronary vascular
 thrombosis. Senseion Therapeutics Inc. has been developing novel glycemic control agents derived from a tool
 compound SN-401 (SN-4XX) targeting LRRC8 proteins. In the course of developing these T2D therapeutics,
 we discovered human genetic evidence implicating LRRC8 regulation of platelet function in humans. We
 then validated LRRC8 proteins as a target for antiplatelet activity using targeted mouse genetics, and confirmed
both in vitro and in vivo antiplatelet/antithrombotic activity of a novel SN-401 derived compound that also
demonstrates glycemic control activity. We propose that SN-4XX compounds represent a first-in-class
 therapeutic approach with dual glycemic control and antithrombotic activity. We anticipate these drugs
 to fill a large unmet clinical need to improve glycemic control in T2D and also safely prevent cerebral
 and coronary vascular thrombosis, reducing the large residual risk of CVD events associated with T2D.
 Phase 1 AIMS:
· AIM 1: Evaluate previously synthesized compounds for in vitro antiplatelet and in vivo antithrombotic
activity.
· AIM 2: Complete in vitro Absorption, Distribution, Metabolism, Excretion, Toxicity.
 Phase 2 AIMS:
· AIM 1: Perform in vivo oral dosing pharmacokinetics, in vitro ion channel selectivity studies, and in vivo
 dose range-finding toxicity studies.
· AIM 2: Perform pre-clinical SN-4XX dose-response, head-to-head efficacy, combination therapy and
 reversibility for antithrombotic activity versus bleeding.
· AIM 3: Manufacture the lead SN-4XX compound under cGMP conditions required for all IND-enabling
 studies, at least Phase I clinical studies, and all 24-month stability studies.

## Key facts

- **NIH application ID:** 10972804
- **Project number:** 4R44HL169181-02
- **Recipient organization:** SENSEION THERAPEUTICS, INC.
- **Principal Investigator:** Jaehyung Cho
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $982,162
- **Award type:** 4N
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10972804

## Citation

> US National Institutes of Health, RePORTER application 10972804, Targeting LRRC8 signaling to prevent & treat arterial thrombosis in type 2 diabetes (4R44HL169181-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10972804. Licensed CC0.

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