You are here

USE OF DYRK1A/B KINASE INHIBITORS FOR THE TREATMENT OF LIVER DISEASES

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43DK134232-01A1
Agency Tracking Number: R43DK134232
Amount: $349,235.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: 300
Solicitation Number: PA22-176
Timeline
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-08-01
Award End Date (Contract End Date): 2024-07-31
Small Business Information
57 VARSITY BLVD
East Setauket, NY 11733-1068
United States
DUNS: 830565797
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: Yes
Principal Investigator
 GIANLUCA ARALDI
 (631) 903-3746
 garaldi@avantibiosciences.com
Business Contact
 GIAN LUCA ARALDI
Phone: (631) 903-3746
Email: garaldi@avantibiosciences.com
Research Institution
N/A
Abstract

PROJECT SUMMARYNonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease. One-fourth of the adult
population suffers from NAFLD worldwide. Nonalcoholic steatohepatitis (NASH), the aggressive form of NAFLD, can
progress to cirrhosis and hepatocellular cancer (HCC) and is rapidly becoming the leading cause of end-stage liver disease
and liver transplantation. Liver fibrosis is a major consequence of chronic liver disease, where the excess extracellular
matrix is deposited, which is caused by the activation of hepatic stellate cells (HSCs). There is an urgent public health need
to develop safe and effective pharmacological treatments to alleviate hepatic inflammation, fibrosis, and steatohepatitis.
However, there are no FDA-approved medications for NAFLD.This SBIR Phase I proposal seeks to evaluate ABI-171, a novel compound with demonstrated selectivity for
DYRK1A and its close family member DYRK1B in biochemical and cellular assays. ABI-171 exhibits pharmacological
activity with evidence of efficacy in several animal models of disease. We hypothesize that its broad anti-inflammatory and
cytoprotective activities combined with its potential health-promoting activities to thwart diabetes, reduce fatty acid uptake,
and suppress collagen accumulation may effectively combat NAFLD.In this Phase I study, two specific aims are proposed: in Aim 1 we will evaluate the accumulation of ABI-171 in
the organs of interest, namely the liver, to advance its safety profile. In Aim 2, we will test the efficacy of ABI-171 in the
high-fat diet model of NASH, which is well-established for providing mechanistic insight of treatments and its potential for
research translation. Detailed readouts for this study will be bodyweight and food intake, insulin resistance, liver injury
biomarkers, liver pathology including histological and biochemical assessments, and expression levels of genes and proteins
involved in DYRK1A/1B-mediated regulation of cellular cytoprotection, inflammation, lipogenesis, and fibrogenesis.The successful completion of this application will significantly advance the efficacy and mechanism of action of
our selective DYRK inhibitor in NASH, thus forming strong foundation for a Phase 2 project in which drug activity will be
examined in more detail for the treatment of metabolic disorders and complete the development work needed to move ABI-
171 into an early-stage clinical trial.

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

US Flag An Official Website of the United States Government