EDP-305 / Enanta Pharma - LARVOL DELTA

Characteristics of contemporary drug clinical trials regarding the treatment of non-alcoholic steatohepatitis. (PubMed, Diabetes Metab Syndr) - "Old drugs are further repurposed for testing in NASH treatment, novel drugs are developed to try to cure NASH. We expect that the drug clinical trials will accelerate the frontier of therapeutic development in NASH, bring an innovative and efficacious medication therapeutic approach to prevent the development and progression of NASH, or even reverse NASH."

Journal • Review • Hepatology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis

ARGON-2: A Randomized, Double-blind Study to Assess the Safety and Efficacy of EDP-305 in Subjects With Liver-biopsy Proven NASH (clinicaltrials.gov) - P2b | N=98 | Terminated | Sponsor: Enanta Pharmaceuticals, Inc | made the strategic decision to discontinue the ARGON-2 study to prioritize combination treatment approaches. This decision was not based on safety concerns.

Biopsy • Enrollment change • Trial termination • Hepatology • Non-alcoholic Steatohepatitis

[VIRTUAL] EDP-305, a non-bile acid farnesoid X receptor (FXR) agonist, showed statistically significant improvements in liver biochemistry and hepatic steatosis in the phase 2a ARGON-1 study (EASL-ILC-I 2020) - P2 | "After 12-weeks of therapy, EDP-305 2.5mg achieved statistically significant improvements in liver biochemistry and hepatic steatosis. EDP-305 exhibited strong target engagement with reduction in C4 and increase in FGF-19. EDP-305 was generally safe; mild to moderate pruritus was more frequent with 2.5mg, with more treatment discontinuations."

P2a data • Dermatology • Fibrosis • Hepatology • Metabolic Disorders • Non-alcoholic Steatohepatitis • Pain • Pruritus • Type 2 Diabetes Mellitus • FGF • FGF19

EDP-305 in patients with NASH: A phase II double-blind placebo-controlled dose-ranging study. (PubMed, J Hepatol) - P2 | "EDP-305 reduced ALT levels and MRI-PDFF supporting development of EDP-305 in patients with NASH in a longer-term trial assessing liver histology."

Clinical • Journal • P2 data • Dermatology • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Pain • Pruritus • Transplantation • Type 2 Diabetes Mellitus • MRI

Assessment of Drug-Drug Interaction Potential with EDP-305, a Farnesoid X Receptor Agonist, in Healthy Subjects. (PubMed, Clin Transl Sci) - "The interaction potential of EDP-305 with drug transporters was low and of unlikely clinical significance. The EDP-305 drug drug interaction profile allows for convenient administration in NASH patients and other patient populations with comorbidities, with minimal dose modification of concomitant medications."

Journal • Review • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Steatohepatitis • CYP1A2 • CYP3A4

FXR agonists for NASH: How are they different and what difference do they make? (PubMed, J Hepatol) - No abstract available

Journal • Dermatology • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Steatohepatitis • Pruritus

[VIRTUAL] FINAL DATA OF THE PHASE 2a INTREPID STUDY WITH EDP-305, A NON-BILE ACID FARNESOID X RECEPTOR (FXR) AGONIST (AASLD 2020) - P2 | "The INTREPID study showed numerically higher response rates with EDP-305 at 1 mg and 2.5 mg compared to PBO. EDP-305 demonstrated evidence of target engagement with robust reductions in markers of liver injury. Mild to moderate pruritus was more frequent, with more treatment discontinuations, at the 2.5mg dose of EDP-305."

P2a data • CNS Disorders • Dermatology • Hepatology • Immunology • Insomnia • Liver Failure • Non-alcoholic Steatohepatitis • Pain • Primary Biliary Cholangitis • Pruritus • Sleep Disorder

ARGON-2: A Randomized, Double-blind Study to Assess the Safety and Efficacy of EDP-305 in Subjects With Liver-biopsy Proven NASH (clinicaltrials.gov) - P2b; N=336; Recruiting; Sponsor: Enanta Pharmaceuticals; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open • Hepatology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis

Bile acid modulators for the treatment of nonalcoholic steatohepatitis (NASH). (PubMed, Expert Opin Investig Drugs) - "EDP305, tropifexor, cilofexor, nidufexor, TERN.101, Px-104, EYP001, MET409...Efficacy of combining an FXR agonist with statins, CCR2, and ACC inhibitors is currently investigated. Identification of patient subsets would allow development of patients tailored therapy using a combination of drugs acting on different molecular mechanisms."

Journal • Addiction (Opioid and Alcohol) • Dermatology • Fibrosis • Hepatology • Immunology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Pruritus

A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Primary Biliary Cholangitis (clinicaltrials.gov) - P2; N=68; Completed; Sponsor: Enanta Pharmaceuticals; Active, not recruiting ➔ Completed; N=119 ➔ 68

Clinical • Enrollment change • Trial completion • Hepatology • Immunology • Primary Biliary Cholangitis • FGF19 • PRO-C3

The farnesoid X receptor agonist EDP-305 reduces interstitial renal fibrosis in a mouse model of unilateral ureteral obstruction. (PubMed, FASEB J) - "Consistently, EDP-305 decreased TGF-β1-induced YAP nuclear localization in human kidney 2 cells by increasing inhibitory YAP phosphorylation. YAP inhibition may be a novel antifibrotic mechanism of FXR agonism, and EDP-305 could be used to treat renal fibrosis.-Li, S., Ghoshal, S., Sojoodi, M., Arora, G., Masia, R., Erstad, D. J., Ferriera, D. S., Li, Y., Wang, G., Lanuti, M., Caravan, P., Or, Y. S., Jiang, L.-J., Tanabe, K. K., Fuchs, B. C. The farnesoid X receptor agonist EDP-305 reduces interstitial renal fibrosis in a mouse model of unilateral ureteral obstruction."

Journal • Preclinical • Fibrosis • Immunology

"EDP-305..." (@KowdleyMd)

EDP-305: Preliminary data from P2 ARGON-1 trial (NCT03421431) in NASH in mid-2019 (Enanta) - Q3 2018 Results

P2 data • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis

Enanta to present new data for core inhibitor for hepatitis B virus and FXR agonist EDP-305 for NASH at The International Liver Congress 2018 (Enanta Press Release) - "Enanta Pharmaceuticals...announced that data from...EDP-305, an FXR agonist in development for non-alcoholic steatohepatitis (NASH) and primary biliary cholangitis (PBC), will be presented at The International Liver Congres...new preclinical data demonstrating EDP-305 favorably regulates the expression of key fibrogenic genes in vitro and in vivo and a second will show EDP-305 has distinct transcriptional and post-transcriptional regulatory mechanisms for LDLR and SRB1 expression. A third poster will present data from our previously released phase 1 study highlighting the pharmacokinetics, pharmacodynamics and safety of EDP-305 in healthy and presumptive NAFLD subjects."

PK/PD data • Preclinical • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis

ARGON-2: A Randomized, Double-blind Study to Assess the Safety and Efficacy of EDP-305 in Subjects With Liver-biopsy Proven NASH (clinicaltrials.gov) - P2b; N=336; Active, not recruiting; Sponsor: Enanta Pharmaceuticals

Clinical • New P2b trial • Gastroenterology • Hepatology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis

Enanta Pharmaceuticals to provide updates on its research and development programs and business outlook for 2019 during the 37th Annual J.P. Morgan Healthcare Conference (Businesswire) - "Enrollment in the 12-week Phase 2a NASH trial is expected to conclude in the first quarter of 2019 allowing Enanta to report preliminary top line data in the third quarter of 2019."

Enrollment status • P2a data • Fibrosis • Immunology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis

A novel non-bile acid FXR agonist EDP-305 potently suppresses liver injury and fibrosis without worsening of ductular reaction. (PubMed, Liver Int) - "EDP-305 potently improved pre-established liver injury and hepatic fibrosis in murine biliary and metabolic models of liver disease, supporting the clinical evaluation of EDP-305 in fibrotic liver diseases including cholangiopathies and NASH."

Journal • Cholestasis • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis

A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Primary Biliary Cholangitis (clinicaltrials.gov) - P2; N=119; Active, not recruiting; Sponsor: Enanta Pharmaceuticals; Recruiting ➔ Active, not recruiting; Trial completion date: Oct 2020 ➔ Jan 2020

Enrollment closed • Trial completion date • FGF19

A NOVEL NON-BILE ACID FXR AGONIST EDP-305 POTENTLY SUPPRESSES LIVER INJURY AND FIBROSIS WITHOUT WORSENING OF DUCTULAR REACTION (AASLD 2019) - "Herein we report therapeutic efficacy of EDP-305, in direct comparison with the first-in-class FXR agonist obeticholic acid (OCA), in mouse models of liver disease. Delayed therapy with EDP-305 (10 and 30mg/kg/day) or OCA (30mg/kg/day) was tested in mouse models of pre-established biliary fibrosis (BALBc.Mdr2-/-, n=9-12/group) and steatohepatitis induced by methionine/choline-deficient diet (MCD, n=7-12/group). EDP-305 potently improved pre-established liver injury, ductular reaction and hepatic fibrosis in biliary and metabolic models of liver disease in mice. These data support the clinical evaluation of EDP-305 in fibrotic liver diseases, including cholangiopathies and NASH.Conflict of interest/financial disclosures: none to be declared. Shucha Zhang, Yang Li, Yat Sun Or, Li-Juan Jiang are employees of Enanta Pharmaceuticals who own Enanta stock options and/or stock."

A NOVEL NON-BILE ACID FXR AGONIST EDP-305 PREVENTS PROGRESSION TO CIRRHOSIS IN THIOACETAMIDE-INDUCED MODEL IN RATS (AASLD 2019) - "Delayed treatment with new FXR agonist EDP-305 safely and effectively prevents development of TAA-induced cirrhosis in rats. By several key parameters, EDP-305 outperformed the first-in-class FXR agonist, obeticholic acid."

Preclinical

DECREASES IN SERUM 7-ALPHA-HYDROXY-4-CHOLESTEN-3-ONE (C4) CORRELATE WELL WITH ANTI-FIBROTIC EFFICACY OF EDP-305 IN NONALCOHOLIC STEATOHEPATITIS (NASH) AND BILIARY FIBROSIS ANIMAL MODELS (AASLD 2019) - "EDP-305 exhibited a strong FXR target engagement by measuring C4 reduction in several preclinical species, including mice, rats and monkeys. Serum C4 reduction correlated very well with anti-fibrotic efficacy of EDP-305 in preclinical NASH and biliary fibrosis models. Current results warrant further clinical trials of EDP-305 in the treatment of NASH and PBC."

Preclinical

A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P2; N=134; Completed; Sponsor: Enanta Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Trial completion

Enanta announces positive results of ARGON-1 study of its lead FXR agonist, EDP-305, for the treatment of NASH (Enanta Press Release) - P2, N=125; NCT03421431; Sponsor: Enanta; "Enanta Pharmaceuticals...announced topline results from its ARGON-1 Phase 2a study of EDP-305 for the treatment of non-alcoholic steatohepatitis (NASH)....The study’s primary endpoint was achieved with a statistically significant ALT reduction of 28 U/L in the EDP-305 2.5mg arm versus 15 U/L in the placebo arm at week 12 (p=0.049)."

P2a data

A Drug-drug Interaction Study to Investigate the Effect of Coadministration of EDP-305 on the PK of a Combined Oral Contraceptive in Healthy Female Subjects (clinicaltrials.gov) - P1; N=43; Completed; Sponsor: Enanta Pharmaceuticals; Recruiting ➔ Completed

Clinical • Trial completion

A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Primary Biliary Cholangitis (clinicaltrials.gov) - P2; N=119; Recruiting; Sponsor: Enanta Pharmaceuticals; Trial completion date: Apr 2019 ➔ Oct 2020; Trial primary completion date: Mar 2019 ➔ Sep 2020

Clinical • Trial completion date • Trial primary completion date