# IND Enabling Studies for the Development of NASH Therapeutic TB-019

> **NIH NIH R44** · TAMUROBIO INC. · 2023 · $1

## Abstract

SUMMARY
Nonalcoholic steatohepatitis (NASH) is a significant, worldwide health problem affecting an estimated 14 million
people in the US. It is characterized by hepatic inflammation and injury and fibrosis. Subjects diagnosed with
NASH are at significantly increased risk of morbidity and mortality due to cirrhosis, and hepatocellular carcinoma.
Without any currently available FDA approved treatments, NASH has become a significant unmet medical need.
In NASH patients, lipid accumulation along with generation of lipotoxic intermediates leads to the induction of
cell stress triggering apoptotic, inflammatory, and fibrotic signaling pathways. Reactive aldehydes, the product
of oxidative modification (i.e. peroxidation) of polyunsaturated fatty acids (PUFA), can bind proteins by indirect
or secondary protein modification, resulting in an increased risk for aggregation, loss of function, and cell
damage. Published evidence points to the critical role of 4-Hydroxynonenal (4-HNE), the most abundant reactive
aldehyde, contributing to the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and NASH. 4-HNE has
been implicated as a specific driver of multiple pathways in NASH etiology including: a) loss of insulin inhibition
of adipocyte lipolytic activity leading to increased fatty acid flux to the liver and generation of lipotoxic products,
b) direct activation of inflammatory pathways, and c) as the direct driver of hepatic stellate cell activation and
liver fibrosis. While 4-HNE production results from lipid peroxidation, the ability to control its levels by
endogenous or exogenous antioxidants is limited; lipophilic reservoirs can provide a long-lasting discharge of 4-
HNE beyond the temporal source of oxidant generation. Therefore, controlling 4-HNE levels represents a unique
and novel therapeutic approach for the treatment of NASH.
TamuroBio has synthesized a new chemical entity, TB-019, that is able to act as a nucleophilic scavenger. TB-
019 binds to 4-HNE, thereby reducing its levels in cells and has been shown in two rodent models of NASH to
be effective in reducing liver fat, inflammation, and fibrosis progression. TB-019 has favorable physicochemical
and ADME properties, as well as a preliminary good safety profile. This proposal aims to complete IND-enabling
GLP safety and toxicology studies and to produce drug supply for the Phase I first-in human trial. This work will
be performed by high quality contract research organizations in the US, overseen by the experienced team at
TamuroBio.
In summary, the overall goal of TamuroBio is to develop TB-019 as a novel therapeutic for the treatment of NASH
and to mitigate the progression of fibrosis.

## Key facts

- **NIH application ID:** 10693602
- **Project number:** 1R44DK134208-01A1
- **Recipient organization:** TAMUROBIO INC.
- **Principal Investigator:** MAHMOUD N GHAZZI
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1
- **Award type:** 1
- **Project period:** 2023-05-01 → 2024-03-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693602

## Citation

> US National Institutes of Health, RePORTER application 10693602, IND Enabling Studies for the Development of NASH Therapeutic TB-019 (1R44DK134208-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10693602. Licensed CC0.

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