# Effect of a semi-synthetic oxysterol drug candidate, Oxy210, on atherosclerosis in a mouse model of NASH

> **NIH NIH R43** · MAX BIOPHARMA, INC. · 2022 · $320,724

## Abstract

ABSTRACT
Cardiovascular disease (CVD) remains the leading cause of death in the United States and worldwide. The
large majority of CVD-related deaths are the direct result of atherosclerosis and its cardiovascular complications.
Atherosclerosis is a chronic inflammatory disease triggered by low density lipoprotein cholesterol (LDL-C), its
accumulation and oxidation in the artery wall, and recruitment of macrophages that become foam cells as they
try to remove the lipoprotein oxidation products but die in the process before exiting the vascular wall. Despite
recent improvements in the management of atherosclerosis, including the use of lipid lowering drugs and
promotion of lifestyle changes, the mortality from CVC is expected to increase from over 17 million in 2018 to
almost 24 million by 2030 globally. In recent years, in addition to classic risk factors for atherosclerosis, namely
diabetes, hypercholesterolemia, hypertension and smoking, a significant correlation between non-alcoholic fatty
liver disease (NAFLD) and atherosclerosis has been reported. Patients with NAFLD die from CVD more
frequently than from liver disease, and NAFLD and its more severe condition, non-alcoholic steatohepatitis
(NASH), are now considered independent, and likely causal, risk factors for the development of atherosclerosis.
It has been therefore proposed that therapies that treat NAFLD may also inhibit atherogenesis, especially since
these diseases share common underlying factors including inflammation, lipid deposition and oxidation, and
dysfunctional macrophages. At MAX BioPharma we have identified a lead proprietary semi-synthetic oxysterol,
Oxy210, that significantly inhibits NASH in a humanized mouse model, ApoE*3-Leiden.CETP, as evidenced by
reduction in hepatic lipid deposition, inflammation, and fibrosis as well as reduced inflammatory cytokines in the
circulation. Oxy210 is orally bioavailable and has favorable pharmacokinetic and safety profiles and is readily
scalable. In preliminary studies we have found that Oxy210 has anti-inflammatory effects in macrophages
treated with lipopolysaccharide or the atherogenic phospholipid, PGPC, through inhibition of toll-like receptor
signaling. We hypothesize that given Oxy210’s inhibitory effects on NASH and inflammation, and given the
common mediators of NASH and atherosclerosis, Oxy210 may also possess anti-atherosclerosis properties. In
the present application we propose to test this hypothesis in vitro and in vivo through studies outlined in 3 specific
Aims: 1) Examination of the effect of Oxy210 on the activation of HSCs, Kupffer cells and vascular endothelial
cells treated with LPS or a synthetic TLR2 agonist in vitro; 2) Examination of the molecular mechanisms of action
(MoAs) for anti-inflammatory effects of Oxy210 in vitro; and 3) Assessment of the effect of Oxy210 on
atherogenesis in ApoE*3-Leiden.CETP transgenic humanized mouse model of NASH in vivo. Findings from the
proposed studies will demonstrate the ...

## Key facts

- **NIH application ID:** 10474926
- **Project number:** 1R43HL162245-01A1
- **Recipient organization:** MAX BIOPHARMA, INC.
- **Principal Investigator:** FARHAD PARHAMI
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $320,724
- **Award type:** 1
- **Project period:** 2022-05-23 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474926

## Citation

> US National Institutes of Health, RePORTER application 10474926, Effect of a semi-synthetic oxysterol drug candidate, Oxy210, on atherosclerosis in a mouse model of NASH (1R43HL162245-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10474926. Licensed CC0.

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