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Lead candidate identification of LPAR1 antagonists for therapeutic application in NASH

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43DK129071-01A1
Agency Tracking Number: R43DK129071
Amount: $397,398.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: 300
Solicitation Number: PA20-260
Timeline
Solicitation Year: 2020
Award Year: 2021
Award Start Date (Proposal Award Date): 2021-09-20
Award End Date (Contract End Date): 2022-09-19
Small Business Information
10225 BARNES CANYON RD, STE A104
San Diego, CA 92121-2734
United States
DUNS: 963248807
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 FABIO TUCCI
 (619) 917-0639
 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. Preliminary data presented in this application
establishes the proof-of-concept of one of Epigen’s LPAR1 lead antagonists, EPGN696, in three 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
in kidney disease, we have identified EPGN2154, an improved LPAR1 antagonist, that has proven safe and
more efficacious than EPGN696 in kidney disease models.
In this phase 1 SBIR grant, we propose an approach which will involve the pre-clinical evaluation of EPGN2154
in two translational animal models of NASH. The disease will be induced for a longer period and chronic
therapeutic treatment with the LPAR1 antagonists will be extended. EPGN696 will be used as a comparator in
these studies. We expect that this will allow characterization of a minimum efficacious dose of EPGN2154 in
NASH relevant endpoints. The successful outcome of this work will lauch efforts in toxicology and chemistry,
manufacturing and controls (CMC) work to support filing of an investigational new drug (IND) application and
eventually initiation of clinical trials in humans.Narrative
The objective is to develop new drugs for treating diseases that lead to liver fibrosis, including nonalcoholic
steato hepatitis (NASH), a significant cause of mortality.

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

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