About DUR-928

DUR-928 is DURECT’s lead product candidate, an endogenous sulfated oxysterol and an epigenetic regulator. Epigenetic regulators are compounds that regulate patterns of gene expression without modifying the DNA sequence. For instance, the addition of methyl groups to certain regions of DNA, facilitated by the epigenetic regulating enzymes DNA methyltransferases (DNMTs), will generally result in downregulation of gene expression, while demethylation results in upregulation. DNA methylation/demethylation can regulate the expression of relevant genes that further modulate crucial cellular activities. Epigenetic dysregulation, which may be caused by DNA hypermethylation, has been found to be associated with many acute or chronic diseases, such as alcohol-associated hepatitis (AH) or non-alcoholic steatohepatitis (NASH), respectively.

Unique mechanism of action: DUR-928 binds to and inhibits the activity of DNMTs, DNMT-1, 3a and 3b, inhibiting DNA methylation, and thereby regulating the expression of genes that modulate crucial cellular activities, including those associated with cell death, stress response, and lipid biosynthesis.1  These modulations may lead to improved cell survival, and reduced lipid accumulation and inflammation, as has been observed in various in vivo animal models and in results from DURECT’s completed clinical trials in AH and NASH.

Demonstrated safety profile: Nearly 300 subjects have been dosed with DUR-928 by oral (PO), intramuscular (IM), or intravascular (IV) administration in a series of completed Phase 1 and Phase 2 clinical trials. DUR-928 was well tolerated at all doses in these trials. There was minimal food effect in the oral administration studies and no accumulation with repeat dosing in multiple pharmacokinetics (PK) studies.

Promising clinical profile: DUR-928 has demonstrated positive efficacy and safety in a Phase 2a clinical trial in alcohol-associated hepatitis (AH), via intravenous administration, and a Phase 2b trial in AH patients (AHFIRM) is currently underway.

Encouraging topline data were also observed in a Phase 1b trial in nonalcoholic steatohepatitis (NASH), via oral administration.

Given its proposed mechanism of action as an epigenetic regulator, its demonstrated safety profile, and promising efficacy signals, there is strong rationale for investigating DUR-928 for the treatment of multiple acute organ injury and chronic liver diseases.

DUR-928 is an investigational product and has not been approved by the FDA for marketing in the U.S. for any indication

There are risks and uncertainties associated with our business. Please see our most recent SEC filings (10-K or 10-Q) for a complete description of these risks and uncertainties, which are incorporated herein by reference.

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