A Phase 1, Open-Label, Drug-Drug Interaction, Study to Evaluate the Effect of ASC42 on the Pharmacokinetics of Atorvastatin Tablets in Healthy Volunteers (HVs)

The purpose of this study is to determine whether ASC42 alters the pharmacokinetics of atorvastatin in healthy subjects.

Start Date08 Aug 2022

Sponsor / Collaborator

Gannex Pharma Co Ltd.

NCT05190523

/ CompletedPhase 2

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of ASC42 Tablets in Subjects With Primary Biliary Cholangitis

This study is a phase II, multicenter, randomized, double-blind, placebo-controlled, seamless adaptive design clinical study, aiming to evaluate the safety and effectiveness of three doses of ASC42 matched placebo in subjects with primary biliary cholangitis.

Start Date06 Apr 2022

Sponsor / Collaborator

Gannex Pharma Co Ltd.

NCT05107778

/ CompletedPhase 2

A Phase II Multi-center, Randomized, Single-blind, Placebo-controlled to Evaluate Safety and Efficacy of ASC42 Tablets in Combination With Entecavir and Pegylated Interferon α-2a in Subjects With Chronic Hepatitis B Virus

This is a phase2, randomized, single-blind, placebo controlled and multi-center study in adults with chronic hepatitis B virus. The study is aimed at evaluating efficacy and safety of ASC42 in combination with entecavir and pegylated interferon α-2a in subjects with chronic hepatitis B virus.

Start Date10 Jan 2022

Sponsor / Collaborator

Ascletis Pharmaceuticals Co., Ltd.

100 Clinical Results associated with ASC-42

100 Translational Medicine associated with ASC-42

100 Patents (Medical) associated with ASC-42

Literatures (Medical) associated with ASC-42

01 Dec 2023·Drugs in R&D

Human Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ASC42, a Novel Farnesoid X Receptor Agonist

Article

Author: Wu, Jinzi J ; He, Handan

BACKGROUND:

ASC42 is a non-steroidal farnesoid X receptor agonist currently in clinical development for chronic liver diseases, such as nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) and primary biliary cirrhosis (PBC).

OBJECTIVE:

The objective of this study was to assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ASC42 in healthy subjects.

METHODS:

We conducted the first-in-human study of ASC42 following single and multiple ascending doses (SAD/MAD) and food effect in healthy subjects. The SAD study included five cohorts receiving 5-200 mg ASC42 or placebo and one cohort that was given 15 mg ASC42 with a high-fat meal. The MAD study included three cohorts receiving 5-50 mg ASC42 or placebo once-daily (QD) for 14 days.

RESULTS:

A total of 65 healthy subjects were enrolled and one subject in the MAD study (cohort 8, ASC42 50 mg) withdrew from the study due to an unrelated serious adverse event (SAE) of atrial fibrillation. Pruritus was observed at the highest doses (200 mg cohort in SAD and 50 mg cohort in MAD). Most AEs were mild or moderate. No life-threatening or fatal AEs occurred. ASC42 showed a proportional increase in exposure and elimination half-life following both single and multiple dosing. There was a 21% and 37% decrease in area under the curve (AUC) and maximum plasma concentration (C_max) when ASC42 was coadministered with food. The steady state was reached on day 4 with a mild accumulation (1.02-1.74-fold). ASC42 showed dose-dependent increases in fibroblast growth factor 19 and decreases in 7α-hydroxy-4-cholesten-3-one. Cholesterol remained within normal limits during study.

CONCLUSION:

ASC42 was well tolerated with a pharmacokinetic profile suitable for QD dosing, and demonstrated dose-dependent targets engagement without altering plasma cholesterol in healthy subjects.

TRIAL REGISTRATION NUMBER:

NCT04679129.

News (Medical) associated with ASC-42

03 Apr 2024

·www.fiercebiotech.com

Ascletis pulls FXR agonist from pipeline over phase 2 primary biliary cholangitis data

Ascletis’ most advanced candidate is ASC22, an injected PD-L1 antibody in phase 2 development as a functional cure for chronic hepatitis B and HIV. China’s Ascletis has been developing the farnesoid X receptor (FXR) agonist ASC42 in a raft of conditions ranging from primary biliary cholangitis (PBC) to metabolic-associated steatohepatitis (MASH). But the company announced this morning that work is being halted on the drug after getting a glimpse of data from a phase 2 trial of three different doses of ASC42 to treat PBC. The results “indicated that ASC42 did not show competitiveness to new PBC drug candidates currently in development and registrational stages,” the company explained in an April 4 release. Based on this failure, Ascletis has also decided to drop other programs involving the drug. These include testing the therapy for hepatitis B virus (HBV) as well as part of a combo treatment for MASH. The biotech, which entered the year with cash and equivalents of 2.4 billion Chinese Yuan ($330 million), attributed today’s decision to “efforts to continue to evaluate and optimize its research and development pipeline to increase efficiency and preserve cash.” With ASC42 thrown on the discard pile, Ascletis still has more promising options to treat MASH, a fatty liver disease that has previously been known as non-alcoholic steatohepatitis (NASH). At the start of the year, the company’s subsidiary Gannex Pharma linked a THRβ agonist, dubbed ASC41, to significant reductions in liver fat and pointed to findings that it sees providing an edge over Madrigal Pharmaceuticals and Viking Therapeutics. Viking has previously accused Ascletis of stealing trade secrets to support the development of a drug candidate to rival its MASH prospect VK2809. That dispute rumbled on throughout last year, during which time Gannex continued to work toward midphase data on the molecule at the center of the row. Ascletis’ most advanced candidate is ASC22, an injected PD-L1-targeted antibody in phase 2 development as a functional cure for chronic hepatitis B and HIV. The company's clinical-stage pipeline also includes a FASN inhibitor called ASC40 that’s being assessed as a treatment for both MASH and acne, as well as a PD-L1 small molecule inhibitor called ASC61 in early-stage trials for solid tumors. Part of the savings from discontinuing the various ASC42 programs will be funneled into the continued clinical development of ASC41 and ASC40 for MASH, the biotech explained in today’s release.

Phase 2

03 Apr 2024

·www.prnewswire.com

Ascletis Announces Strategic Decisions on FXR agonist ASC42

HANGZHOU, China and SHAOXING, China, April 3, 2024 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX:1672, "Ascletis") announces today the strategic decisions on farnesoid X receptor (FXR) agonist ASC42. After thorough analysis of the Phase II trial data of ASC42 for primary biliary cholangitis (PBC) (ClinicalTrials.gov: NCT05190523), the Company made a strategic decision not to pursue further clinical trials of ASC42 for PBC indication. This decision is based on the efficacy and safety data from the 12-week Phase II study, which consisted of three ASC42 active treatment arms (5 mg, 10 mg and 15 mg QD) and one placebo control arm. The results indicated that ASC42 did not show competitiveness to new PBC drug candidates currently in development and registrational stages. Furthermore, the Company also decided not to pursue further clinical studies of ASC42 as an FXR agonist in combination for non-alcoholic steatohepatitis (NASH) (ASC43F) and clinical studies of ASC42 for hepatitis B virus (HBV) indication. As of December 31, 2023, the Group had cash and cash equivalent and time deposits of approximately RMB 2.3 billion. These strategic decisions are part of the Company's efforts to continue to evaluate and optimize its research & development pipeline to increase efficiency and preserve cash. The savings from discontinuing these planned clinical trials will be used to accelerate clinical development of ASC41 and ASC40 for NASH indication and in-house discovery for global first-in-class or best-in-class drug candidates. The positive interim results from ASC41 Phase II trial in biopsy-confirmed NASH patients demonstrated ASC41 as a potential best-in-class thyroid hormone receptor β (THRβ) agonist. As a first-in-class FASN inhibitor, the Phase IIb study showed ASC40 (denifanstat) achieved statistically significant results for both NASH resolution and fibrosis improvement in biopsy-confirmed NASH patients with stage 2 or 3 fibrosis after 52-week treatment. About Ascletis Ascletis is an innovative R&D driven biotech listed on the Hong Kong Stock Exchange (1672.HK), covering the entire value chain from discovery and development to manufacturing and commercialization. Led by a management team with deep expertise and a proven track record, Ascletis focuses on three therapeutic areas with unmet medical needs from a global perspective: viral diseases, non-alcoholic steatohepatitis (NASH) and oncology. Through excellent execution, Ascletis rapidly advances its drug pipeline with an aim of leading in global competition. To date, Ascletis has multiple drug candidates in its R&D pipeline. The most advanced drug candidates include ASC22 (CHB functional cure), ASC40 (acne), ASC40 (recurrent glioblastoma), ASC40 (NASH), ASC41 (NASH) and ASC61 (advanced solid tumors). For more information, please visit . SOURCE Ascletis Pharma Inc.

Phase 2Clinical Result

03 Apr 2024

·firstwordpharma.com

Ascletis drops FXR agonist after disappointing mid-stage PBC data

Ascletis Pharma is pulling the plug on its farnesoid X receptor (FXR) agonist ASC42, which was being developed across multiple indications. The move follows an analysis of Phase II efficacy and safety data in primary biliary cholangitis (PBC), revealing that ASC42 "did not show competitiveness" compared to other drug candidates currently in late-stage testing for the same indication.In addition to halting the PBC programme, Ascletis is also terminating further clinical studies of ASC42 as part of a combination regimen for metabolic dysfunction-associated steatohepatitis (MASH), formerly referred to as non-alcoholic steatohepatitis (NASH), and as a monotherapy for hepatitis B virus infection.Speed work on other MASH assetsAscletis says the savings generated from discontinuing the planned clinical trials will be redirected towards accelerating development of two other potential MASH candidates, ASC41 and ASC40, as well as supporting the Chinese biotech's in-house discovery efforts.ASC41 is a once-daily oral THRβ agonist that led to significant reductions in fat content in patients with biopsy-confirmed MASH, according to interim Phase II results unveiled earlier this year. The compound is in the same class as Madrigal Pharmaceuticals' Rezdiffra (resmetirom), which became the first approved MASH treatment when US regulators signed off on it last month.Ascletis' drug has also been at the centre of a dispute with Viking Therapeutics, which claimed that ASC41 is based on stolen trade secrets revolving around its own THRβ drug, VK2809.Meanwhile, Asceltis said its FASN inhibitor ASC40, also known as denifanstat, achieved statistically significant results for both MASH resolution and fibrosis improvement in a Phase IIb study of NASH patients with stage 2 or 3 fibrosis after 52 weeks of treatment. ASC40 is also in late-stage development as an acne treatment, and in combination with bevacizumab for patients with recurrent glioblastoma.The company's most advanced drug candidate is ASC22, a subcutaneously injected PD-L1 antibody currently in Phase II as a potential functional cure for both chronic hepatitis B and HIV.

Phase 2Clinical ResultDrug Approval

100 Deals associated with ASC-42

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Familial Primary Biliary Cirrhosis	Phase 2	China	Ascletis Pharma, Inc.	20 Mar 2022
Primary Biliary Cholangitis	Phase 2	China	Ascletis Pharma, Inc.	20 Mar 2022
Liver Cirrhosis, Biliary	Phase 2	United States	Gannex Pharma Co Ltd.	30 Jan 2022
Hepatitis B, Chronic	Phase 2	China	Ascletis BioScience Co., Ltd.	22 Dec 2021
Metabolic Dysfunction Associated Steatohepatitis	Phase 1	United States	Ascletis Pharma, Inc.	28 Dec 2020

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04679129 (Literature \| Pubmed \| Drugs R D) Manual	Phase 1	-	65	ASC42	fijlstmsjp(teqerlouqo) = Pruritus was observed at the highest doses (200 mg cohort in SAD and 50 mg cohort in MAD). Most AEs were mild or moderate. No life-threatening or fatal AEs occurred. tkefemhzss (agultfoymr )	Positive	06 Nov 2023

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