Ascletis Announces Completion of 180 Patient Enrollment for Phase II Clinical Trial of FASN Inhibitor ASC40 for Acne

--To date,approximately 50% enrolled patients have completed 12-week treatment and all enrolled patients are expected to complete 12-week treatment by the end of February 2023

-- Clinical efficacy observed in patients who have completed 12-week treatment of ASC40 or placebo was comparable to that from two U.S. FDA approved acne drugs - WINLEVI® and TWYNEO®

--In the previous Phase II clinical trial of non-alcoholic steatohepatitis (NASH) patients with 12-week treatment of 50 mg ASC40 once daily,61% patients showed ≥ 30% relative decrease of liver fat

HANGZHOU and SHAOXING,China,Nov. 30,2022 --Ascletis Pharma Inc. (HKEX: 1672,"Ascletis") announces today the completion of 180 patient enrollment for the Phase II clinical trial of ASC40 (denifanstat) for treatment of moderate to severe acne. The study is currently still blind.

To date,approximately 50% enrolled patients have completed 12-week treatment and all enrolled patients are expected to complete 12-week treatment by the end of February 2023. Clinical efficacy observed in patients who have completed 12-week treatment of ASC40 or placebo was comparable to that from two recently approved acne drugs by U.S. Food and Drug Administration - WINLEVI®and TWYNEO®[1,2],in terms of percentage change from baseline in total lesion counts and percentage change from baseline in inflammatory and non-inflammatory lesion counts. To date,the preliminary data also indicated that ASC40 or placebo treatment in acne patients is safe and well tolerated,and majority of treatment-related adverse events are grade 1. In the previous Phase II clinical trial of non-alcoholic steatohepatitis (NASH) patients with 12-week treatment of 50 mg ASC40 once daily,61% patients showed ≥ 30% relative decrease of liver fat[3].

The current Phase II clinical trial is a randomized,double-blind,placebo-controlled,multicenter clinical trial in China to evaluate the safety and efficacy of ASC40 for the treatment of patients with moderate to severe acne. 180 enrolled patients have been randomized into three active treatment arms or one placebo control arm at the ratio of 1:1:1:1 to receive ASC40 (25 mg,50 mg or 75 mg) or matching placebo orally once daily for 12 weeks. The primary outcomes include percentage change of total lesion count at week 12 compared with baseline and/or ratio of subjects,whose Investigator's Global Assessment (IGA) grades are decreased by ≥2 grades at week 12 compared with baseline.

ASC40 is an oral,selective small molecule inhibitor of fatty acid synthase (FASN),a key enzyme which regulates de novo lipogenesis (DNL). Human sebum production requires de novo lipogenesis,which is increased in acne and can be suppressed by the FASN inhibitor ASC40.

Acne is the eighth most prevalent disease in the world and affects more than 640 million people globally[4]. The onset of acne often coincides with pubertal hormonal changes,and the condition affects approximately 85% of adolescents and young adults aged 12 to 25 years[5]. However,acne can also persist into or develop during adulthood. Current first-line treatments for acne include topical creams such as topical retinoids,androgen receptor inhibitor,oral isotretinoin,and antibiotics,but still have various limitations.

"Excess sebum production plays a significant role in the pathogenesis of acne and suppression of sebum production reduces acne incidence and severity. As a first-in-class drug with a novel mechanism,FASN inhibitor ASC40 has demonstrated exciting preliminary efficacy in Phase I clinical trial. We will continue to accelerate the Phase II study to provide more options for patients with moderate to severe acne." said Prof. Leihong Xiang,Chief Physician of Dermatological Department,Huashan Hospital,Fudan University,Executive Deputy Director of Institute of Dermatology,Deputy Director of Dermatology Division of Chinese Medical Doctor Association and principal investigator of ASC40 Phase II trial for moderate to severe acne.

"Moderate to severe acne poses lasting impact on patients and remains a huge unmet medical needs globally. I'm very happy that FASN inhibitor ASC40 for acne has completed the patient enrollment for Phase II study,which marks a new milestone as Ascletis is exploring the market of consumer healthcare." said Dr. Jinzi J. Wu,Founder,Chairman and CEO of Ascletis.

[1]Hebert A,Thiboutot D,Gold L S,et al. Efficacy and Safety of Topical Clascoterone Cream,1%,for Treatment in Patients With Facial Acne: Two Phase 3 Randomized Clinical Trials[J]. JAMA Dermatology,2020,156(6).

[2]Drug label of tretinoin and benzoyl peroxide cream https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214902s000lbl.pdf

[3]Loomba R,Mohseni R,Lucas K J,et al. TVB-2640 (FASN inhibitor) for the treatment of nonalcoholic steatohepatitis: FASCINATE-1,a randomized,placebo-controlled Ph2a trial[J]. Gastroenterology,2021.

[4]Tan J K,Bhate K. A global perspective on the epidemiology of acne [J]. Br J Dermatol 2015,172 Suppl 1(3-12. DOI: 10.1111/bjd.13462.

[5]Krowchuk D P. Managing acne in adolescents [J]. Pediatric clinics of North America 2000,47(4): 841-57. DOI: 10.1016/s0031-3955(05)70243-1.

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 22 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.