Candidate selection of a LPAR1 antagonist for therapeutic application in nash

Ended Project Grant Awarded Last action

Award ID
R44DK129071
Recipient
Awarding agency
Obligated
$3,956,744

Award facts

Completion date
Place of performance
San Diego, CA 92121, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
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.

Transactions

Action Obligated Date
Amendment $1,041,548
Amendment $0
Amendment $0
Amendment $971,732
Amendment $971,732
Original award $971,732

Subawards

Subrecipient Amount Awarded
Children's Hospital LOS Angeles Scope of Work: Studies will be conducted on one therapeutic lead compound alone or in combination with up to two standard of care compounds (GLP1 agonists,… $333,845

Quick answers

Who received award R44DK129071?

R44DK129071 was awarded to Epigen Biosciences Inc. by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on September 20, 2021.

How much is award R44DK129071 worth?

$3,956,744 has been obligated on R44DK129071.

On GovTribe

See this award's full record

  • Every transaction and subaward
  • The recipient's other awards and teaming partners
  • Similar grant awards
  • Ask GovTribe AI about this award
Try for free Login