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Candidate selection of a LPAR1 antagonist for therapeutic application in NASH

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R44DK129071-02
Agency Tracking Number: R44DK129071
Amount: $971,732.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: 300
Solicitation Number: PA22-176
Timeline
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-09-01
Award End Date (Contract End Date): 2025-06-30
Small Business Information
6725 Mesa Ridge Road, Suite 260
San Diego, CA 92121-3938
United States
DUNS: 963248807
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 FABIO TUCCI
 (858) 657-0918
 ftucci@epigenbiosciences.com
Business Contact
 FABIO TUCCI
Phone: (858) 657-0918
Email: ftucci@epigenbiosciences.com
Research Institution
N/A
Abstract

Summary
The ultimate goal of this application is to develop one of Epigen’s proprietary antagonists of the lysophosphatidic
acid receptor 1 (LPAR1) for the effective treatment of liver fibrosis associated with chronic diseases such as non-
alcoholic steatohepatitis (NASH), a severe type of non-alcoholic fatty liver disease (NAFLD). NAFLD is the most
common liver disease and is associated with obesity and type-2 diabetes. There are currently no effective
treatments available for NASH except lifestyle changes.
The feasibility data presented in this application establishes the proof-of-concept of one of Epigen’s LPAR1 lead
antagonists, EPGN2154, in two different mouse models of NASH and liver fibrosis. In vitro mechanistic data
confirms that LPAR1 antagonism blocks hepatic stellate cell proliferation, thus blocking an important fibrotic
pathway. Furthermore, LPAR1 antagonists block migration of macrophages stimulated by MCP-1 indicating an
anti-inflammatory mechanism. During the course of our work, we have identified combinations of drugs with
complementary mechanisms of action to EPGN2154, which provide superior efficacy in the preclinical models
and may result in greater benefit to patients.
In this phase 2 SBIR grant, we propose an approach involving a more detailed pre-clinical evaluation of
EPGN2154 and combinations in one translational animal model of NASH. For optimizing the dose and
combination regimen of EPGN2154, the HFHC-fed wild type mouse model of NASH is considered adequate
because it presents with features of human NASH. In this application, we seek to: i) conduct a detailed dose-
response efficacy study of EPGN2154 in the HFHC mouse model of NASH to determine the minimum efficacious
dose (MED), ii) conduct efficacy studies with the optimized dose of EPGN2154 in combination with commercial
GLP-1R agonists and GIP/GLP-1R agonists, iii) complete GLP safety pharmacology studies and submit an IND
to the FDA to support phase 1 clinical trials in humans. Based on feedback from Pharma and investors, an IND-
ready asset with preclinical efficacy and safety established along with a delineated clinical path, is an attractive
asset for commercialization. The successful outcome of this work will likely trigger private investment to advance
the program towards initiation of clinical trials in humans.

* Information listed above is at the time of submission. *

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