# Evaluation of anti-fibrotic and anti-inflammatory semi-synthetic oxysterol, Oxy210, as a therapeutic drug candidate for non-alcoholic steatohepatitis

> **NIH NIH R44** · MAX BIOPHARMA, INC. · 2023 · $896,990

## Abstract

ABSTRACT
Pathologic tissue fibrosis, impelled by uncontrolled wound healing responses to acute or chronic injury is a
significant problem in many organs including kidney, lung, and liver. Liver fibrosis is a major health problem
that causes morbidity and mortality in the affected patient population. Liver fibrosis occurs in various
pathologies including chronic alcohol exposure, non-alcoholic fatty liver disease (NAFLD) that can lead to non-
alcoholic steatohepatitis (NASH), and viral infection, and can lead to cirrhosis and hepatocellular carcinoma. A
number of molecular mechanisms have been scrutinized to identify the root causes of liver fibrosis. Among these,
prominent studies point to aberrant Hedgehog (Hh) and transforming growth factor-β (TGF-β) signaling as prime
factors underlying the pathogenesis of liver fibrosis, and hence extensively investigated. Accumulating evidence
also suggests the role of Toll-Like Receptors (TLRs) in mediating the inflammatory responses of liver cells to
endogenous factors and bacterial products present in the liver in NAFLD and NASH.
At MAX BioPharma, we have identified semi-synthetic oxysterols that act as Hh pathway modulators, both as
agonists and antagonists. We found oxysterol Hh pathway antagonists that also have potent inhibitory effects
on TGF-β signaling in fibroblastic cells and in primary human hepatic stellate cells (HSC). With support from
an SBIR Phase 1 grant from NIDDK, we recently published findings about the anti-NASH properties of an
oxysterol analogue, Oxy210, that has led to the present application. Oxy210 has anti-fibrotic as well as anti-
inflammatory properties that are mediated through inhibition of Hh, TGF-β and TLR signaling. Oxy210 induced
robust inhibitory effects in a humanized hyperlipidemic mouse model of NASH, ApoE*3-Leiden.CETP mice on
a high fat Western Diet, evidenced by inhibition of hepatic lipid deposition, inflammatory cytokine expression
and fibrosis, associated with reduced hepatic cell apoptosis and improved circulating ALT levels. Based on
these properties of Oxy210, in addition to its favorable pharmacokinetic and safety profiles, oral availability, and
scalability, in the present SBIR Phase 2 application we propose to continue the examination of the disease
modifying effects of Oxy210 in ApoE*3-Leiden.CETP mice in reversing already established disease in contrast to
our published report when Oxy210 was administered at the initiation of the disease. We propose to identify the
molecular and cellular mechanisms of anti-NASH properties of Oxy210 by performing metabolic tests as well
as RNA-sequencing studies in livers of NASH mice with or without Oxy210 treatment. We propose to perform
non-GLP in vitro and in vivo safety studies that will provide essential information for future IND-enabling GLP
studies required in our anticipated IND filing for Oxy210 as a first-in-class new drug candidate for targeting
NASH. NASH is a huge unmet medical need since there are no FDA a...

## Key facts

- **NIH application ID:** 10697132
- **Project number:** 1R44DK136405-01
- **Recipient organization:** MAX BIOPHARMA, INC.
- **Principal Investigator:** FARHAD PARHAMI
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $896,990
- **Award type:** 1
- **Project period:** 2023-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10697132

## Citation

> US National Institutes of Health, RePORTER application 10697132, Evaluation of anti-fibrotic and anti-inflammatory semi-synthetic oxysterol, Oxy210, as a therapeutic drug candidate for non-alcoholic steatohepatitis (1R44DK136405-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10697132. Licensed CC0.

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