DUR-928 / Durect - LARVOL DELTA

A comparison of the protective effects of Rimtoregtide (HTD4010) and DUR-928 on acute liver failure in mice (EASL 2025) - "Treatment with HTD4010 resulted in significant protective effects in an LPS-induced mouse model mimicking acute liver failure. These findings provide evidence that HTD4010 may have a beneficial effect on acute liver conditions including alcohol-related hepatitis and other acute- inflammatory-related conditions."

Preclinical • Hepatology • Inflammation • Liver Failure • REG3A

AHFIRM: A Phase 2b Study in Subjects With Alcoholic Hepatitis to Evaluate Safety and Efficacy of DUR-928 Treatment (clinicaltrials.gov) - P2 | N=307 | Completed | Sponsor: Durect | Active, not recruiting ➔ Completed | Phase classification: P2b ➔ P2

Phase classification • Trial completion • Hepatology • Inflammation

Larsucosterol: Endogenous Epigenetic Regulator for Treating Chronic & Acute Liver Diseases. (PubMed, Am J Physiol Endocrinol Metab) - "Furthermore, we elucidate the pathophysiological pathways of Metabolic Dysfunction-associated Steatotic Liver Diseases (MASLD), Metabolic Associated Steatohepatitis (MASH), and acute liver injuries. A central focus of the review is the exploration of the therapeutic potential of 25HC3S in treating life-threatening conditions, including acetaminophen overdose, endotoxin shock, MASLD, MASH, hepatectomy, and alcoholic hepatitis."

Journal • Review • Addiction (Opioid and Alcohol) • Hepatology • Inflammation • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • TNFA

25HC3S ALLEVIATES INJURED LIVER FUNCTION AND DECREASES MORTALITY BY PROMOTER 5mCpG DEMETHYLATION SIGNALING PATHWAYS (AASLD 2023) - "25-Hydroxycholesterol 3-sulfate (25HC3S, DUR928, or larsucosterol) has been demonstrated to alleviate injured liver function and decrease mortality in the acute liver failure in mouse models... 25HC3S is a potent epigenetic regulator and has the potential to serve as a novel biomedicine in the therapy of ALF and acute multiple organ failure."

Hepatology • Inflammation • Liver Failure • Renal Disease

DUR-928/AH: DUR-928 in Patients With Alcoholic Hepatitis (clinicaltrials.gov) - P2 | N=43 | Completed | Sponsor: Craig James McClain | Recruiting ➔ Completed | Trial completion date: Sep 2024 ➔ Sep 2023

Trial completion • Trial completion date • Hepatology • Inflammation • CRP • CXCL8 • IL6 • KRT18

AHFIRM: A Phase 2b Study in Subjects With Alcoholic Hepatitis to Evaluate Safety and Efficacy of DUR-928 Treatment (clinicaltrials.gov) - P2b | N=301 | Active, not recruiting | Sponsor: Durect | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology • Inflammation

DURECT Corporation to Host KOL Event on Alcohol-Associated Hepatitis (Durect)

Live event

Safety, Pharmacokinetics, & Efficacy Signals of Larsucosterol (DUR-928) in Alcohol-associated Hepatitis. (PubMed, Am J Gastroenterol) - "Larsucosterol was well tolerated at all 3 doses in AH subjects without safety concerns. Data from this pilot study showed promising efficacy signals in AH subjects. Larsucosterol is being evaluated in a Phase 2b multicenter, randomized, double-blinded, placebo-controlled (AHFIRM) trial."

Clinical • Journal • PK/PD data • Hepatology • Inflammation

Emerging Pharmacotherapies in Alcohol-Associated Hepatitis. (PubMed, J Clin Exp Hepatol) - "Their result could potentially make a difference in the clinical course of the disease. DUR-928 and granulocyte colony-stimulating factor had promising results and further trials are ongoing to evaluate their efficacy in the large patient sample."

Journal • Review • Dyslipidemia • Hepatology • Inflammation • Oncology • Transplantation • CCL2

DUR-928/AH: DUR-928 in Patients With Alcoholic Hepatitis (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Craig James McClain | Trial completion date: Sep 2023 ➔ Sep 2024 | Trial primary completion date: Sep 2022 ➔ Sep 2023

Trial completion date • Trial primary completion date • Hepatology • Inflammation • CRP • CXCL8 • IL6 • KRT18

DUR-928/AH: DUR-928 in Patients With Alcoholic Hepatitis (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Craig James McClain | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology • Inflammation • CRP • CXCL8 • IL6 • KRT18

[VIRTUAL] ROLE OF EPIGENETIC REGULATORS, 25HC AND 25HC3S, IN NAFLD DEVELOPMENT AND TREATMENT (AASLD 2021) - "The sulfated oxysterol, 25HC3S/DUR928, has been shown to decrease lipid accumulation, anti-inflammatory responses, and promote cell survival... Our results indicate that the development of NAFLD involves multiple dysregulated signaling pathways . The expression of the key elements and enzymes in the signaling pathways can be regulated by DNA CpG methylation and demethylation in promoter regions . 25HC and 25HC3S are DNMT agonist and antagonist ."

Diabetes • Hepatology • Inflammation • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • DNMT1 • DNMT3A • IR • PPARA

[VIRTUAL] Uncovering DUR-928, DNMTs, Alcohol-Associated Hepatitis & NASH (NASH Summit-US 2021) - "Synopsis Outlining how DUR-928 acts as an epigenetic Regulator that inhibits DNMTs Learning about hypermethylation and elevated DNMTs in Alcohol-Associated Hepatitis Revealing DUR-928 clinical results and outlining our ongoing program in Alcohol-Associated Hepatitis & NASH"

Hepatology • Inflammation • Non-alcoholic Steatohepatitis

DURECT Corporation Presents Additional Clinical Data from DUR-928 Phase 1b Trial in NASH and Phase 1 Trial in Hepatic Impairment at the International Liver Conference 2021 (EASL) (PRNewswire) - "Poster #1198 entitled 'Efficacy Signals of 4-Week Oral DUR-928 in NASH Subjects,' presented by Eric Lawitz, M.D...disclosed additional potential efficacy signals from DURECT's Phase 1b clinical study of orally administered DUR-928 in nonalcoholic steatohepatitis (NASH) patients."

[VIRTUAL] Efficacy Signals Of 4-Week Oral DUR-928 in NASH Subjects (EASL-ILC 2021) - "Daily oral DUR-928 (50–600 mg) for 4 weeks in F1-F3 NASH subjects was well tolerated and resulted in overall improve- ment in liver enzymes, liver fat content by MRI-PDFF, serum lipid profiles, liver stiffness by TE and MRE, insulin resistance, and biomarkers (including the liver fibrosis marker, pro-C3). The results suggest that epigenetic regulation of gene expression and their signalling pathways is an attractive approach to treat NASH. Further studyof DUR-928 in subjectswithmetabolic disorders, such asNASH, is warranted."

Clinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Non-alcoholic Steatohepatitis • MRI

[VIRTUAL] Safety and pharmacokinetics of DUR-928 in hepatic function impaired subjects (EASL-ILC 2021) - "DUR-928 was well tolerated in all subjects with HI, including severe HI. As expected, HI resulted in higher exposure due to slower clearance of DUR-928 than MCS."

Clinical • PK/PD data • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Non-alcoholic Steatohepatitis • Novel Coronavirus Disease

[VIRTUAL] SAFETY AND EFFICACY SIGNALS OF 4-WEEK ORAL DUR-928 IN NASH SUBJECTS (AASLD 2020) - "This study demonstrated that daily oral DUR-928 (50-600mg) for 4 weeks was well tolerated and had an overall improvement in multiple markers, including liver enzymes, liver imaging, and serum lipid profiles, in NASH subjects. The results warrant further study of DUR-928 in subjects with NASH, and suggest that epigenetic modulation of multiple master genes and signaling pathways is an attractive approach to treat NASH."

Clinical • Hepatology • Inflammation • Non-alcoholic Steatohepatitis • MRI

DURECT Corporation Announces Additional Safety Data and Efficacy Signals from Phase 1b Clinical Trial of DUR-928 in NASH Patients at The Liver Meeting Digital Experience 2020 (Cision) - P1, N=65; "'The additional safety and efficacy data presented, including improvements in multiple biomarkers of liver health such as a significant reduction in cytokeratin-18 among the patients who also experienced at least a 10% reduction in liver fat, continue to strengthen the promising profile of DUR-928 for NASH,' stated Eric Lawitz, M.D....principal investigator of the study. 'Together with previously reported overall global reduction from baseline of liver enzymes, liver fat, stiffness as measured by imaging and serum lipids, this additional biomarker data suggests that epigenetic modulation by DUR-928 is worthy of further study in NASH patients.'"

P1 data

DUR-928/AH: DUR-928 in Patients With Alcoholic Hepatitis (clinicaltrials.gov) - P2; N=36; Not yet recruiting; Sponsor: Craig James McClain; Initiation date: Jul 2019 ➔ Nov 2019

Clinical • Trial initiation date • Hepatology • CRP • CXCL8 • IL6

DUR-928/AH: DUR-928 in Patients With Alcoholic Hepatitis (clinicaltrials.gov) - P2; N=36; Not yet recruiting; Sponsor: Craig James McClain

Clinical • New P2 trial • Hepatology • CRP • CXCL8 • IL6

DUR-928/AH: DUR-928 in Patients With Alcoholic Hepatitis (clinicaltrials.gov) - P2; N=36; Not yet recruiting; Sponsor: Craig James McClain; Initiation date: Nov 2019 ➔ Jun 2020

Clinical • Trial initiation date • Hepatology • CRP • CXCL8 • IL6

DUR-928 in Subjects With SARS-CoV-2 With Acute Lung, Liver or Kidney Injury (clinicaltrials.gov) - P2; N=2; Terminated; Sponsor: Durect; N=80 ➔ 2; Trial completion date: Oct 2021 ➔ Mar 2021; Recruiting ➔ Terminated; Trial primary completion date: Sep 2021 ➔ Mar 2021; low enrollment

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Infectious Disease • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases

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AHFIRM: A Phase 2b Study in Subjects With Alcoholic Hepatitis to Evaluate Safety and Efficacy of DUR-928 Treatment (clinicaltrials.gov) - P2b; N=300; Recruiting; Sponsor: Durect; Not yet recruiting ➔ Recruiting; Initiation date: Oct 2020 ➔ Jan 2021

Clinical • Enrollment open • Trial initiation date • Hepatology