vonafexor (EYP001) / Poxel SA, ENYO - LARVOL DELTA

Vonafexor in Patients With Impaired Renal Function and Suspected MASH (Metabolic Dysfunction-associated Steatohepatitis) (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Enyo Pharma

New P2 trial • Chronic Kidney Disease • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Renal Disease

Change in cT1 following interventions in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis (EASL 2025) - "By treatment type, fibroblast growth factor (FGF) analogues (aldafermin; pegozafermin), glucagon-like peptide (GLP)-1 receptor agonists (pemvidutide; tirzepatide) and farnesoid X receptor (FXR) agonists (vonafexor; ocaliva; TERN-101), cT1 had a mean change of -79ms [95% CI: -90, - 68], -68ms [95% CI: -77, -58] and -62ms [95% CI: -74, -49], respectively... Evidence to-date supports a significant treatment-induced reduction in cT1 as compared to minimal changes in the placebo group. Our findings could inform current and future study designs for investigational therapies for liver disease and support monitoring of treatment response in individuals with MASLD in clinical trials and clinical practice."

Retrospective data • Review • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF

A novel in vitro system for simultaneous infections with hepatitis B, C, D and E viruses. (PubMed, JHEP Rep) - "We recapitulated the known antiviral effect of sofosbuvir on HCV and HEV (>90% reduction in the levels of intracellular viral RNAs, p <0.0005) and of IFN-α on HCV, HEV and HDV (80% reduction in the levels of intracellular viral RNAs, p <0.0005)...Using HEV-infected HuHep mice, we confirmed the antiviral effect of vonafexor, an FXR agonist, that is currently being tested clinically against HBV/HDV...Moreover, the interplay between these four viruses in the context of co-infections remains unknown. In this study, we report the first in vitro system that allows for mono and multi-infections with these four viruses and characterize the broad antiviral activity of farnesoid X receptor agonists, paving the way for the development of new strategies for viral cure."

Journal • Preclinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation • APOB • IFNA1

Change in cT1 following interventions in MASLD: A systematic review and meta-analysis (APASL 2025) - "By treatment type, fibroblast growth factor (FGF) analogues (aldafermin; pegozafermin), glucagon-like peptide (GLP)-1 receptor agonists (pemvidutide; tirzepatide) and farnesoid X receptor (FXR) agonists (vonafexor; ocaliva; TERN-101), cT1 had a mean change of -79ms [95% CI: -90, -68], -68ms [95% CI: -77, -58] and -62ms [95% CI: -74, -49], respectively... Evidence to-date supports a significant treatment-induced reduction in cT1 as compared to minimal changes in the placebo group. Our findings could inform current and future study designs for investigational therapies for liver disease and support monitoring of treatment response in individuals with MASLD in clinical trials and clinical practice. Table and Figure:Figure 1.Figure."

Retrospective data • Review • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF

Vonafexor ALPort Syndrome Efficacy & Safety TRIAl-1 (ALPESTRIA-1) (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: Enyo Pharma | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • LCN2

Vonafexor ALPort Syndrome Efficacy & Safety TRIAl-1 (ALPESTRIA-1) (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Enyo Pharma | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • LCN2

Vonafexor ALPort Syndrome Efficacy & Safety TRIAl-1 (ALPESTRIA-1) (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Enyo Pharma

New P2 trial • Genetic Disorders • LCN2

VONAFEXOR AS A NOVEL THERAPY FOR CHRONIC KIDNEY DISEASE (ERA-EDTA 2023) - "The possible beneficial effect was compared to that of Losartan and other NR1H4 agonists. Altogether our results identified in Vonafexor a novel key drug to control CKD. This is consistent with recent results obtained in LIVIFY phase 2 clinical trial in which Vonafexor has already demonstrated beneficial effects on eGFR in NASH patients with mild to moderate CKD."

Chronic Kidney Disease • Fibrosis • Glomerulonephritis • Hepatology • Immunology • Inflammation • Nephrology • Non-alcoholic Steatohepatitis • Renal Disease • Collagen Type IV

[VIRTUAL] A phase 2 study testing FXR agonist Vonafexor in treatment naive patients with chronic hepatitis B (CHB): preliminary week 16 results (EASL-ILC 2021) - P2a | " In this ongoingmulti-center, randomized, open-label Phase 2 trial (NCT04365933) treatment naive CHB patients with HBsAg ≥300 IU/ml and HBV DNA ≥20’000 IU/ml for HBeAg+ and ≥2’000 for HBeAg- were randomized to a combination of oral V 200 mg QDwith sc pegylated interferon alpha2a (peg-IFN 180 mcg QW) to which entecavir (0.5 mg QD, ETV) was added (arm 1) or not (arm 2). Vonafexor combined with peg-IFN induces a marked HBsAg decline in HBeAg- treatment naive CHB patients. No relationship between transaminase flares and viral response was found. Additional data is being collected during the ongoing follow- up period."

Clinical • P2 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Pharmacological characterization of second generation FXR agonists as effective EphA2 antagonists: a successful application of target hopping approach. (PubMed, Biochem Pharmacol) - "Herein we characterize new commercially available FXR (Farnesoid X Receptor) agonists as potential Eph ligands including Cilofexor, Nidufexor, Tropifexor, Turofexorate isopropyl and Vonafexor. Furthermore, Cilofexor interferes with the phosphorylation of EphA2 and the cell retraction and rounding in PC3 prostate cancer cells, both events depending on EphA2 activation. In conclusion, we can confirm that target hopping can be a successful approach to discover new moiety of protein-protein inhibitors."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH. (PubMed, J Hepatol) - P2a | "In patients with suspected fibrotic NASH, Vonafexor was safe and induced potent liver fat reduction, improvement in liver enzymes, weight loss, and a possible renal benefit."

Journal • Chronic Kidney Disease • Dermatology • Fibrosis • Hepatitis C • Hepatology • Immunology • Liver Cirrhosis • Nephrology • Non-alcoholic Steatohepatitis • Pruritus • Renal Disease

Study of EYP001a to Assess Its Safety and Anti-viral Effect in CHB Patients in Combination With NA (ETV or TD) (clinicaltrials.gov) - P2a | N=26 | Terminated | Sponsor: Enyo Pharma | New randomizations were stopped. Already randomized subjects were followed up to W40.

Combination therapy • Enrollment change • Trial termination • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Solid Tumor

A Study of the Oral Farnesoid X Receptor Modulator EYP001a to Assess Its Safety and Anti-viral Effect in Chronic Hepatitis B Patients in Combination With Pegylated Interferon alpha2a Alone and With Entecavir (clinicaltrials.gov) - P2a | N=20 | Completed | Sponsor: Enyo Pharma | Active, not recruiting ➔ Completed | N=30 ➔ 20

Combination therapy • Enrollment change • Trial completion • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Solid Tumor • FGF19

Combined effect of Vonafexor and Interferon-alpha on HBV replication in primary human hepatocytes (EASL-ILC 2022) - P2a | "We were able to recapitulate, in cell culture models, the improved anti-HBV effect of combining Vonafexor and peg-IFNα. We also observed that the effect is achieved without inducing toxicity. This study provides support for the existence of a mechanism of action underlying the antiviral activity in combining Vonafexor and peg-IFNα, details of which should be explored further to eventually assist in identifying efficacy predictive factors in clinical trials."

Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNA1

Potential for FDA approval nears for emerging NASH therapies (Healio) - "'We [have] a huge armamentarium of drugs in development,' Manal F. Abdelmalek, MD...'In my opinion, the future of NASH is going to be binding combination therapies, for which we have a foundation of anti-metabolic therapy, coupled with anti-inflammatory or anti-fibrotic therapy, depending on where patients are in the disease spectrum.'"

Media quote

[VIRTUAL] VONAFEXOR, A FXR AGONIST, INDUCED HEPATIC AND RENAL IMPROVEMENT IN THE RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED LIVIFY NASH TRIAL (AASLD 2021) - "VONA induced a strong, consistent LFC reduction, and improvement in biochemical and imaging markers of liver inflammation with an added benefit on eGFR. VONA was safe and well tolerated, with the 100 mg dose showing a more favorable tolerability-efficacy profile. Larger trials are warranted to confirm the hepatic and renal benefits."

Clinical • Late-breaking abstract • Chronic Kidney Disease • Dermatology • Diabetic Nephropathy • Dyslipidemia • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Nephrology • Non-alcoholic Steatohepatitis • Pruritus • Renal Disease • MRI

ENYO Pharma Announces Two Vonafexor Data Presentations at AASLD The Liver Meeting (Businesswire) - "A poster on modelling efforts to optimize the study design of a combination of Vonafexor and Peg-IFN in chronic HBV patients...The second abstract refers to a poster presentation on modelling efforts by our collaborators from Novadiscovery to optimize the combination of Vonafexor and Peg-IFN in HBV patients."

Clinical protocol • Hepatitis B • Infectious Disease

[VIRTUAL] MECHANISTIC MODELLING TO OPTIMIZE PHASE 2b CLINICAL TRIAL DESIGN OF A NEW COMBINATION THERAPY FOR CHRONIC HBV (AASLD 2021) - "and simulation outputs for serum HBV DNA and HBsAg response to entecavir and IFN combination. Our mechanistic modelling approach allowed testing a large set of possible treatment combinations to help design the next clinical trial of Vonafexor CHB therapy. Goodness of fit shows accuracy of the hypotheses implemented in the model and its parameters’ values . Data of prospective clinical trials will be used for further model validation which could be adapted to other investigational treatments ."

Clinical • Combination therapy • P2b data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Safety, Tolerability, Pharmacokinetics and Efficacy of EYP001a in Patients With Nonalcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P2a; N=120; Completed; Sponsor: Enyo Pharma; Recruiting ➔ Completed

Clinical • Trial completion • Hepatology • Non-alcoholic Steatohepatitis • FN1 • MRI

Farnesoid X receptor agonist for the treatment of chronic hepatitis B; a safety study. (PubMed, J Viral Hepat) - "Patients were randomized to receive oral Vonafexor (100mg, 200mg and 400mg once daily, or 200mg twice daily), placebo, or entecavir (Part A, n=48) or to receive Vonafexor (300mg once daily or 150mg twice daily), or placebo, combined with pegylated-interferon-α2a (Part B, n=25) for 29 days. Vonafexor monotherapy of 400mg once daily decreased HBsAg concentrations (-0.1 log IU/mL, p<0.05), and Vonafexor/pegylated-IFN-α2a combination therapy decreased HBcrAg and pgRNA. In conclusion, Vonafexor was safe with a decline in HBV-markers observed in CHB patients suggesting a potential antiviral effect the therapeutic potential of which has to be evaluated in larger trials."

Clinical • Journal • Dermatology • Gastrointestinal Disorder • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Pruritus • IFNA1

ENYO Pharma Announces 16 Weeks Vonafexor (EYP001) Top-Line Interim Results from Two on-going Phase 2a Studies in Chronic Hepatitis B Patients (Businesswire) - P2, N=30; NCT04365933; P2, N=49; NCT04465916; Sponsor: Enyo Pharma; "ENYO Pharma...announced positive proof of concept data from Study EYP001-203 of Vonafexor in combination with pegylated-Interferon (peg-IFN) in viremic patients with chronic hepatitis B (CHB). Vonafexor met the primary endpoint of lowering HBsAg by an average of ≥ 1 log10, a key biomarker of viral activity in the liver, after 16 weeks of treatment...In the second Phase 2a study...concluded that Vonafexor was well tolerated and safe (no ALT/AST flares were observed) but there was no apparent efficacy benefit of Vonafexor with Entecavir in these virally suppressed CHB patients."

P2a data • Hepatitis B • Infectious Disease

Enyo Pharma's NASH results show boost in kidney function, differentiating vonafexor from busy field (FierceBiotech) - '"The additional positive impact on renal function is very interesting and is a potential differentiator in this class of drugs to treat NASH,' said the study's principal investigator, Prof. Stephen Harrison...NASH patients typically have other conditions like diabetes that can impact kidney function."

Media quote

A Study of the Oral Farnesoid X Receptor Modulator EYP001a to Assess Its Safety and Anti-viral Effect in Chronic Hepatitis B Patients in Combination With Pegylated Interferon alpha2a Alone and With Entecavir (clinicaltrials.gov) - P2a; N=30; Active, not recruiting; Sponsor: Enyo Pharma; Recruiting ➔ Active, not recruiting; Trial completion date: Jul 2021 ➔ Dec 2021; Trial primary completion date: Jan 2021 ➔ Jun 2021

Clinical • Combination therapy • Enrollment closed • Trial completion date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • FGF19

Study of EYP001a to Assess Its Safety and Anti-viral Effect in CHB Patients in Combination With NA (ETV or TD) (clinicaltrials.gov) - P2a; N=49; Recruiting; Sponsor: Enyo Pharma

Clinical • Combination therapy • New P2a trial • Hepatitis B • Hepatology • Infectious Disease • FGF19

Study of EYP001a to Assess Its Safety and Anti-viral Effect in CHB Patients in Combination With NA (ETV or TD) (clinicaltrials.gov) - P2a; N=49; Active, not recruiting; Sponsor: Enyo Pharma; Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatitis B • Hepatology • Infectious Disease • FGF19