Ascletis Announces Poster Presentation of Phase II Study of ASC42 FXR Agonist for Functional Cure of Chronic Hepatitis B at EASL CONGRESS 2023

HANGZHOU and SHAOXING,China,June 26,2023 --Ascletis Pharma Inc. (HKEX:1672,"Ascletis") today announces the poster presentation of ASC42,a novel farnesoid X receptor (FXR) agonist,in combination with PEGylated interferon (PEG-IFN) and entecavir (ETV) in chronic hepatitis B (CHB) patients with 12-week treatment at European Association for the Study of the Liver (EASL) CONGRESS 2023. The summary of the abstract is shown as below:

Title: A phase 2 study of ASC42,in combination with PEGylated interferon (PEG-IFN) and entecavir (ETV) in chronic hepatitis B patients with 12-week treatment

Presenter:Jinzi J. Wu,Ph.D.

Principal Investigator: Prof. Jinlin Hou,Nanfang Hospital of Southern Medical University

Poster Number: SAT-201

Category: Viral Hepatitis B and D

Study Design:

This Phase 2 trial (NCT05107778) was a multi-center,randomized,single-blind,placebo-controlled study conducted in China. Forty-three HBeAg negative,hepatitis B virus (HBV) DNA<LLOQ (lower limit of quantitation,20 IU/mL),CHB patients on ETV were randomized equally into 3 cohorts of 10 mg ASC42,15 mg ASC42 and placebo (PBO) orally once daily (QD) in combination with ETV (0.5 mg,orally QD) and PEG-IFN-α-2a (180 μg,subcutaneous injection once a week). Patients were treated for 12 weeks,and followed for 24 weeks (still on ETV). Serum hepatitis B surface antigen (HBsAg) and HBV pregenomic RNA (pgRNA) changes from baseline were measured during the 12-week intervention period and 24-week follow-up period.

Results:

In total,122,119,and 107 adverse events (AEs) were reported in 10 mg ASC42,15 mg ASC42 and PBO cohorts,respectively,and most AEs (94.3%) were mild (grade 1) or moderate (grade 2) in severity. One subject in 15 mg ASC42 cohort experienced a grade 3 serious AE (SAE) of liver function injury with a final outcome of recovered. Pruritus is the most common AE,and study drug-related pruritus was reported in 1 (6.7%),7 (50%) and 0 (0%) subjects in 10 mg ASC42,respectively. Pruritus rate of 10 mg ASC42 (6.7%) is lower than other FXR agonists in non-alcoholic steatohepatitis (NASH) patients.

Comparison of incidences of pruritus of ASC42 with other FXR agonists and PEG-IFN-α-2a

ASC42

Obeticholic

Acid

PEG-IFN-α-2a

Cilofexor

Tropifexor

10 mg

10 mg

180 μg

30 mg

140 μg

(N=15)

(N=653)

(N=271)

(N=40)

(N=50)

Patient type

CHB

NASH

CHB

NASH

NASH

Treatmentduration

12weeks

18 months

48 weeks

48 weeks

48 weeks

Pruritus,No. of

patients (%)

1 (6.7)

183 (28)

26 (10)

8 (20)

20 (40)

Reference No.

[1]

[2]

[3]

[4]

[5]

Conclusion:

In CHB patients,12-week treatment of 10 mg ASC42 in combination of PEG-IFN-α-2a and ETV was safe and well-tolerated and showed minimum and mild pruritus (6.7%). Previous study indicated that in healthy subjects,14-day treatment of ASC42 alone demonstrated 471%~1,780% increase of fibroblast growth factor 19 (FGF19) and 53%~91% decrease of 7α-hydroxy-4-cholesten-3-one (C4) at a dose range of 5 mg~15 mg. Data suggest that at the therapeutic dose of 10 mg,the novel FXR agonist ASC42 is differentiated from other FXR agonists in terms of pruritus.

[1]. Data on file

[2]. Younossi Z.M.,Ratziu V.,Loomba R.,et al. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre,randomised,placebo-controlled phase 3 trial [J]. The Lancet,2019,394(10215): 2184-96.DOI: 10.1016/s0140-6736(19)33041-7

[3]. Lau G.K.,Piratvisuth T.,Luo K.X.,et al. Peginterferon Alfa-2a,lamivudine,and the combination for HBeAg-positive chronic hepatitis B [J]. N Engl J Med,2005,352(26): 2682-95.DOI: 10.1056/NEJMoa043470

[4]. Loomba R.,Noureddin M.,Kowdley K.V.,et al. Combination Therapies Including Cilofexor and Firsocostat for Bridging Fibrosis and Cirrhosis Attributable to NASH [J]. Hepatology,2021,73(2): 625-43.DOI: 10.1002/hep.31622

[5]. Anstee Q.M.,Lucas K.J.,Francque S.,et al. Tropifexor plus cenicriviroc combination versus monotherapy in non-alcoholic steatohepatitis: Results from the Phase 2b TANDEM study [J]. Hepatology,2023.DOI: 10.1097/hep.0000000000000439

About EASL

EASL,the European Association for the Study of the Liver,founded in 1966,is a medical association dedicated to pursuing excellence in liver research,to the clinical practice of liver disorders,and to providing education to all those interested in hepatology. As of 2022,EASL serves 4,900 members from 112 countries.

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 three marketed products,i.e. ritonavir tablets,GANOVO® and ASCLEVIR®,and 23 drug candidates in its R&D pipeline. The most advanced drug candidates include ASC22 (HBV functional cure),ASC10 and ASC11(oral small molecules for COVID-19 treatment),ASC40 (recurrent glioblastoma),ASC42 (PBC,primary biliary cholangitis),and ASC40 (acne).

For more information,please visit www.ascletis.com.