# Selection of a lead LPAR1 antagonist for treatment of diabetic neuropathy

> **NIH NIH R44** · EPIGEN BIOSCIENCES, INC. · 2022 · $990,691

## Abstract

PROJECT SUMMARY
Diabetic neuropathy (DPN) is a major unmet health concern where over half of the estimated 33 million people
in the US with type 1 or type 2 diabetes will develop neuropathy1. There is no FDA-approved disease modifying
treatment for preventing or slowing progression of diabetic neuropathy other than a recommendation to maintain
glycemic control2 and current treatments are restricted to management of the symptomatic consequences of
neuropathy such as pain. It is becoming increasingly appreciated that diabetes also injures both the spinal cord
(myelopathy) and brain (encephalopathy) such that diabetes is recognized as a prominent risk factor for
developing cognitive dysfunction and Alzheimer’s disease14. Accordingly, agents that prevent or reverse
peripheral nerve and/or CNS insults during diabetes are of interest either as standalone agents or for adjunctive
use with symptomatic treatments. Epigen has developed expertise around the discovery and development of
novel lysophosphatidic acid receptor type 1 (LPAR1) antagonists for the treatment of fibrotic disease. In parallel
to the study of diabetic nephropathy data was obtained to suggest that lead compounds discovered at Epigen
also benefit endpoints of diabetic neuropathy for both nerve injury and markers for cognitive decline in models.
This proposal builds on these data to determine if one such lead compound, EPGN2154, may be developed to
treat diabetic neuropathy. The goal of this direct to phase 2 application is to conduct detailed pre-clinical efficacy
of EPGN2154 in rat DPN models, along with screening safety to allow nomination of a development candidate.
Compounds will be prepared and characterized at Epigen prior to testing at University of California San Diego
(UCSD) under the guidance of Dr. Nigel Calcutt. Dr. Calcutt’s laboratory will establish and maintain colonies of
diabetic rodents, treat them with test agents provided by Epigen and measure physiological, behavioral and
structural indices of peripheral and central neuropathy at assorted times throughout the study. Upon study
completion tissue will be dissected and processed for histological and biochemical evaluation to support
behavioral measurements. Epigen will conduct additional lead profiling to support candidacy of EPGN2154. Drug
distribution will also be evaluated to support mechanistic studies. Compound profiling will include a safety
assessment of EPGN2154. These studies will support the advancement of EPGN2154 to IND enabling studies
as a prelude to entry into clinical trials for DPN.

## Key facts

- **NIH application ID:** 10408164
- **Project number:** 5R44DK127879-02
- **Recipient organization:** EPIGEN BIOSCIENCES, INC.
- **Principal Investigator:** Graham Beaton
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $990,691
- **Award type:** 5
- **Project period:** 2021-05-20 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10408164

## Citation

> US National Institutes of Health, RePORTER application 10408164, Selection of a lead LPAR1 antagonist for treatment of diabetic neuropathy (5R44DK127879-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10408164. Licensed CC0.

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