Gannex Announces Clinical and Preclinical Data of Four NASH Programs to be Presented in Oral or Poster Presentation at The Liver Meeting® 2021 by American Association for the Study of Liver Diseases

Gannex Pharma Co., Ltd., a wholly owned company of Ascletis Pharma Inc. (HKEX:1672), announces today that the latest clinical and preclinical data of four NASH programs (ASC40/TVB-2640 co-authored with Sagimet Biosciences Inc., ASC41, ASC42 and ASC43F) will be presented in oral or poster presentation at The Liver Meeting® 2021 of American Association for the Study of Liver Diseases (AASLD). The Liver Meeting® is one of the world's premier meeting on liver disease and will be held during November 12-15 this year.

Dr. Handan He, Chief Scientific Officer of Ascletis, stated, "I am encouraged by the progress of our NASH programs and proud of the execution excellence of our research and development team."

Melissa Palmer, MD, Chief Medical Officer of Gannex, said, "I am thrilled that all four abstracts from our NASH programs have been selected for either oral or poster presentation, which indicates that the innovative and promising work that Gannex is doing in the area of liver disease is acknowledged by professionals in this field."

The abstracts to be presented at The Liver Meeting® 2021 are as follows:

NOVEL, FIRST-IN-CLASS, FATTY ACID SYNTHASE (FASN) INHIBITOR TVB-2640 DEMONSTRATES ROBUST CLINICAL EFFICACY AND SAFETY IN A GLOBAL PHASE 2 RANDOMIZED PLACEBO-CONTROLLED NASH TRIAL (FASCINATE-1) CONDUCTED IN THE US AND CHINA

• Presentation Type: Oral, Parallel Session

• Publication Number: 141

• Session Title: Parallel 21: NAFLD and NASH: Clinical Trials of Novel Therapeutics

• Presenting Author: Dr. Rohit Loomba, MD, University of California

• Session Broadcast Date and Time: Sunday, November 14, 2021, 6:30 – 8:00 PM EST

• Highlights:
  - TVB-2640 is an oral, once-daily, first-in-class small molecule FASN inhibitor that reduces excess liver fat, inhibits inflammatory and fibrogenic pathways. 
  - Subjects with MRI-PDFF ≥8% and fibrosis (MRE ≥2.5 kPa or biopsy F1-F3) were randomized 2:1 to TVB-2640 or placebo once daily (US N=99; China N=30) for 12 weeks to access the efficacy and safety of TVB-2640.
  - TVB-2640 was well-tolerated, with no AEs ≥ Gr. 3 and no on treatment SAEs.
  - PK profiles (50mg) were similar in the U.S. and China.
  - TVB-2640 reduced liver fat and decreased alanine aminotransferase（ALT）in both populations, that combined had a relative PDFF reduction of 28.2% (50mg, N=48) at W12 v. 6.4% placebo (N=19, p=0.019) and absolute PDFF reduction of 5% v. 1.6% placebo (p<0.0001). The PDFF response rates were 56% (50mg) v. 15% placebo.

A PHASE Ib STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF ASC41, A THR-β AGONIST, FOR 28-DAYS IN OVERWEIGHT AND OBESE SUBJECTS WITH ELEVATED LDL-C, A POPULATION CHARACTERISTIC OF NAFLD

• Presentation Type: Poster Presentation

• Publication Number: 1851

• Session Title: NAFLD and NASH: Experimental: Clinical

• Presentation time: Friday, November 12, 2021, 6:00-11:55 AM EST

• Highlights:
  - ASC41 is a small molecule, hepatic targeting, potent and selective thyroid hormone receptor beta (THRβ) agonist prodrug, which is converted to its pharmacologically active metabolite ASC41-A by CYP3A4 in the liver.
  - Twenty overweight and obese subjects with elevated low density lipoprotein cholesterol (LDL-C) (>110 mg/dL) were treated with ASC41 10mg oral tablets or matching placebo tablets with the ratio of 3:1 once daily in this randomized, double-blind, placebo controlled clinical study to evaluate the safety, tolerability, pharmacokinetics and lipid lowering potential of ASC41 oral tablets.
  - Compared with placebo, lipid parameters (LDL-C, TG, TC, Apo-B, and LP (a)) for those treated with ASC41 showed clinically meaningful and statistically significant reductions (P<0.05).
  - ASC41 was tolerable and had a benign adverse event (AE) profile with no serious adverse reactions and no adverse reactions above Grade 3.

ASC42, A NOVEL NON-STEROIDAL FXR AGONIST, DEMONSTRATES A NORMAL CHOLESTEROL PROFILE AND LACK OF PRURITUS AT THERAPEUTIC DOSES IN A 14-DAY PHASE I RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED STUDY IN HEALTHY VOLUNTEERS

• Presentation Type: Poster Presentation

• Publication Number: 1854

• Session Title: NAFLD and NASH: Experimental: Clinical

• Presentation time: Friday, November 12, 2021, 6:00-11:55 AM EST

• Highlights:
  - ASC42 is a potent, orally available, non-steroidal farnesoid X receptor (FXR) agonist under clinical development for NASH.
  - Sixty-four healthy volunteers (8 cohorts n=8 (6 active:2 placebo) were dosed with 5-200mg (single-ascending doses) and 14 days of 5-50mg qd (multi-ascending doses), to evaluate the safety and tolerability of ASC42 and to establish the PK and PD profiles of ASC42.
  - No pruritus was observed during the 14-day treatment at the human therapeutic dose of 15mg.
  - ASC42 for 14-days was well tolerated and safe, without elevated ALT/ aspartate aminotransferase (AST) or lipid parameter abnormalities at doses within the therapeutic dose range.
  - FXR targets activated biomarker of fibroblast growth factor 19 (FGF19) levels increased 1,632% from baseline at Day-14 with the dose of 15mg.
  - FXR targets activated biomarker of 7α-hydroxy-4-cholesten-3-one (C4) levels decreased 93% from baseline at Day-14 with the Dose of 15mg.
  - Based on the study data, 15 mg qd has been selected as one of 3 doses to be studied in the Phase II trial in patients with NASH.

ASC43F TABLET AS A ONE-PILL, ONCE-A-DAY FIXED-DOSE COMBINATION (FDC) OF ASC41, A THR-β AGONIST, AND ASC42, AN FXR AGONIST, DEMONSTRATED COMPARABLE DISSOLUTION PROFILES AND IN VIVO PHARMACOKINETICS VS. SINGLE ASC41 AND ASC42 TABLET

• Presentation Type: Poster Presentation

• Publication Number: 1762

• Session Title: NAFLD and NASH: Experimental: Basic

• Presentation time: Friday, November 12, 2021, 6:00-11:55 AM EST

• Highlights:
  - ASC43F is a One-Pill, Once-a-Day FDC of ASC41, an oral hepatic targeting THR-β agonist prodrug, and ASC42, a non-steroidal, selective, potent, oral FXR agonist.
  - Three male beagle dogs were dosed with ASC42 tablet (15mg), ASC41 tablet (5mg) and ASC43F tablet (ASC42/ASC41 15mg/5mg) in a cross-over study design with a 5-day washout period to evaluate in vivo PK. Dissolution profiles of ASC43F tablets were compared with those of single ASC41 and ASC42 tablets.
  - In beagle dogs, the PK parameters of ASC42 and ASC41A in/from ASC43F tablets remained approximately unchanged as compared to those of single ASC41 and ASC42 tablets.
  - The dissolution profiles of ASC41/ASC42 in ASC43F tablets were similar to those of single ASC41 and ASC42 tablets using 4 different pH dissolution media.
  - The stability data demonstrated that ASC43F tablets were stable in the accelerated condition of 40℃/75%RH for 4.5 months (equivalent to 1.5 years in the normal condition).

About Ascletis

Ascletis is an innovative R&D driven biotech listed on the Hong Kong, S.A.R., China Stock Exchange (1672.HK). Ascletis is committed to developing and commercializing innovative drugs in the areas of NASH, cancer lipid metabolism and oral checkpoint inhibitors, and viral diseases to address unmet medical needs both in China and globally. Led by a management team with deep expertise and a proven track record, Ascletis has developed into a fully integrated platform covering the entire value chain from discovery and development to manufacturing and commercialization. Ascletis has three marketed products and a robust R&D pipeline of drug candidates.

1. NASH: Gannex, a wholly-owned company of Ascletis, is dedicated to the R&D and commercialization of new drugs in the field of NASH. Gannex has three clinical stage drug candidates against three different targets – FASN, THRβ and FXR, and three fixed-dose combinations. 2. Cancer lipid metabolism and oral checkpoint inhibitors: a pipeline of oral inhibitors targeting FASN, which plays a key role in cancer lipid metabolism, and a pipeline of oral PD-L1 small molecule next generation checkpoint inhibitors. 3. Viral diseases: (1) Hepatitis B: focus on breakthrough therapies for CHB functional cure with a subcutaneously-injected PD-L1 antibody – ASC22 and Pegasys® as cornerstone drugs. (2) Hepatitis C: successfully launched an all-oral regimen of combining ASCLEVIR® and GANOVO® (RDV/DNV regimen). (3) HIV/AIDS: ASC22, an immune therapy to restore HIV-specific immune responses and eventually lead to a functional cure of HIV-infected patients. For more information, please visit www.ascletis.com.

Source: Ascletis Pharma Inc.