# A novel therapy for acute alcoholic hepatitis

> **NIH NIH R43** · SEAL ROCK THERAPEUTICS, INC. · 2022 · $358,239

## Abstract

Each year approximately 5 million people in the US develop acute alcoholic hepatitis
(AH), a syndrome of progressive inflammatory liver injury. In most patients with AH, the
illness is mild. However, in patients with severe acute AH, risk of early death is high and
intensive management is required with minimal pharmacological agents available. Seal
Rock Therapeutics is developing SRT-015, a potent and selective inhibitor of the
activated ASK1 kinase to address this unmet need. ASK1 is present in all cells and
activated in response to stress factors including reactive oxygen species (ROS),
cytokines and LPS. SRT-015 demonstrates direct anti-inflammatory, anti-fibrotic and
anti-apoptotic activity in vitro on stimulated human immune cells, fibroblasts and
hepatocytes, respectively. SRT-015 treatment was also proven efficacious in vivo using
acute and chronic liver disease mouse models and demonstrated safe in GLP toxicology
studies. In a Phase 1 clinical trial SRT-015 was well tolerated with no dose-limiting
toxicities. SRT-015 is a possible therapeutic for multiple liver diseases including AH.
In this SBIR R43, we will conduct IND-enabling efficacy studies of SRT-015 for treatment
of severe AH. These studies are designed to determine the minimal efficacious
exposure, define clinically relevant biomarkers, and characterize changes in the
microbiota and intestinal permeability after SRT-015 treatment in an AH animal model
Aim 1: Estimate of minimal efficacious exposure of SRT-015 and efficacy biomarkers in
a chronic ethanol plus binge therapeutic AH animal model. We will be using the mouse
chronic Lieber-DeCarli ethanol liquid diet (8 weeks) plus binge ethanol model that best
reflects human AH disease. The minimum efficacious dose will be identified using three
dose levels of SRT-015 treatment administered during the final four weeks of chronic
ethanol feeding and biomarkers for fibrosis, inflammation and hepatoxicity evaluated.
Aim 2: Evaluation of intestinal permeability, bacterial translocation and intestinal
dysbiosis after SRT-015 treatment in a therapeutic AH animal model. To complement
and extend the efficacy data, a full characterization of SRT-015 effects on intestinal
inflammation and gut barrier function will be conducted.
Demonstrating preclinical efficacy of SRT-015 in a chronic plus binge therapeutic AH
model will be critical to conduct clinical trials in AH patients. Once approved, SRT-015 is
anticipated to greatly improve the lives of patients with severe AH.

## Key facts

- **NIH application ID:** 10604068
- **Project number:** 1R43AA029931-01A1
- **Recipient organization:** SEAL ROCK THERAPEUTICS, INC.
- **Principal Investigator:** Neil McDonnell
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $358,239
- **Award type:** 1
- **Project period:** 2022-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10604068

## Citation

> US National Institutes of Health, RePORTER application 10604068, A novel therapy for acute alcoholic hepatitis (1R43AA029931-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10604068. Licensed CC0.

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