Gannex Announces Poster Presentation of Positive Interim 12-Week Results from Phase II Clinical Trial of ASC41 in Patients with Biopsy-Confirmed MASH at EASL CONGRESS 2024

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Jun 10, 2024, 20:10 ET

--Up to 68.2% mean relative reduction in liver fat content from baseline among biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) patients receiving 12-week treatment of ASC41

--Significant and clinically meaningful reductions in liver fat, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lipids as well as excellent safety and tolerability profile demonstrated by ASC41 in MASH patients

HANGZHOU, China, June 10, 2024 /PRNewswire/ -- Gannex Pharma Co., Ltd. ("Gannex"), a wholly-owned company of Ascletis Pharma Inc. (HKEX:1672, "Ascletis") dedicated to the research and development and commercialization of new drugs in the field of metabolic dysfunction-associated steatohepatitis (MASH), today announced a poster presentation at the European Association for the Study of the Liver (EASL) Congress 2024, held June 5-8, 2024 in Milan, Italy. A copy of the poster is available under the Posters/Publications page of Gannex's website at www.gannexpharma.com.

The poster presentation titled, "ASC41, a selective THRβ agonist significantly reduces liver fat and ALT in biopsy-confirmed MASH patients after 12-week treatment: an interim analysis of a 52-week serial liver biopsy study", describes significant and clinically meaningful reductions in liver fat, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in biopsy-confirmed MASH patients receiving 12-week treatment of ASC41 tablet, among which the data of ALT and AST notably differentiates ASC41 from other thyroid hormone receptor β (THRβ) agonists currently at clinical or commercial stages. In addition, baseline characteristics from Phase II clinical trials were comparable between ASC41, conducted in China, and resmetirom, except for lower body mass index (BMI) and more males for ASC41. Please refer to Table 1 below for more details.

Table 1. Baseline Characteristics

Characteristics	ASC41 Phase 2			Resmetirom Phase 2^[1]
Characteristics	PBO (n=14)	2 mg (n=13)	4mg (n=15)	Placebo (n=41)	60/80 mg (n=84)
Age, years	41.2(11.6)	36.1(11.0)	34.7(6.5)	47.3 (11.7)	51.8 (10.4)
Male, n(%)	9(64.3 %)	12(92.3 %)	13(86.7 %)	24 (59 %)	38 (45 %)
MRI-proton density fat fraction, % fat fraction (SD)	18.2%(6.7)	17.8%(5.4)	18.9%(7.9)	19.6% (8.2)	20.2% (6.8)
Diabetes, n(%)	4(28.6 %)	3(23.1 %)	3(20.0 %)	13 (32 %)	36 (43 %)
Body-mass index, kg/m²	28.7(3.1)	29.7(4.8)	30.4(5.1)	33.6 (5.8)	35.8 (6.2)
ALT (U/L)	77.6(56.2)	65.9(31.2)	84.8(32.6)	60.1 (32.2)	50.0 (29.2)
AST (U/L)	47.9(31.6)	44.2(23.0)	53.8(18.2)	38.0 (20.7)	35.1 (17.7)
HDL-C (mg/dL)	44.8(8.7)	58.4(6.0)	41.5(6.3)	45.2 (13.4)	43.8 (12.5)
LDL-C (mg/dL)	116.0(25.4)	127.5(24.6)	122.61(25.1)	116.9 (30.0)	111.3 (30.4)
TG (mg/dL)	156.8(54.0)	180.4(74.3)	228.6(126.5)	161.1 (75.2)	178.5 (82.4)
Data are mean (SD) or n (%) unless otherwise stated.
^[1]. Harrison, S. A., et al.[J] Lancet, (2019).DOI: 10.1016/s0140-6736(19)32517-6

In Table 1, "PBO" stands for placebo, "MRI" stands for magnetic resonance imaging, "ALT" stands for alanine aminotransferase, "AST" stands for aspartate aminotransferase, "HDL-C" stands for high-density lipoprotein cholesterol, "LDL-C" stands for low-density lipoprotein cholesterol and "TG" stands for triglycerides.

ASC41, a once-daily oral tablet, is a liver targeted small molecule and is highly THRβ-selective. The oral tablet formulation was developed utilizing Ascletis' in-house proprietary technology. Three Phase I or Ib studies in China were completed in healthy or obese subjects with elevated low-density lipoprotein cholesterol (LDL-C) > 110 mg/dL. A U.S. Phase I study demonstrated no clinically significant drug-drug interactions between ASC41/ASC41-A and most frequently used antidepressants and statins, as well as no significant difference in drug exposure between Americans and Chinese at the same dose.

Table 2. Changes from Baseline (CFB) in LFC, Liver Enzymes and Lipids Biomarkers at Week 12

Parameters	Placebo (n = 14)	ASC41 Tablet
		2 mg, QD (n = 13)	4 mg, QD (n = 15)
Mean relative CFB in LFC	-13.1 %	-55.0 %	-68.2 %
		(p = 0.0001)	(p ＜ 0.0001)
Percentage of patients achieving LFC reduction ≥ 30%	21.4 %	92.3 %	93.3 %
		(p = 0.0002)	(p ＜ 0.0001)
Percentage of patients achieving LFC reduction ≥ 50%	21.4 %	46.2 %	86.7 %
		(p = 0.24)	(p = 0.0004)
Percentage of patients achieving ≤5% absolute LFC	0.0 %	30.8 %	66.7 %
		(p = 0.16)	(p = 0.0017)
Mean relative CFB in ALT	5.2 %	-8.5 %	-32.6 %
		(p = 0.61)	(p = 0.0051)
Percentage of patients achieving ALT reduction > 17 U/L	21.4 %	30.8 %	73.3 %
		(p = 0.68)	(p = 0.0052)
Mean relative CFB in AST	17.3 %	-3.6 %	-24.2 %
		(p = 0.67)	(p = 0.041)
Mean relative CFB in LDL-C	4.3 %	-19.4 %	-23.4 %
		(p = 0.0002)	(p ＜ 0.0001)
Mean relative CFB in TC	3.4 %	-16.8 %	-20.0 %
		(p ＜ 0.0001)	(p ＜ 0.0001)
Mean relative CFB in TG	3.9 %	-30.6 %	-42.6 %
		(p = 0.0001)	(p ＜ 0.0001)

In Table 2, "LFC" stands for liver fat content, "ALT" stands for alanine aminotransferase, "AST" stands for aspartate aminotransferase, "LDL-C" stands for low-density lipoprotein cholesterol, "TC" stands for total cholesterol and "TG" stands for triglycerides.

"93.3% of patients receiving treatment with ASC41 experienced at least 30% relative reduction from baseline in liver fat content as assessed by magnetic resonance imaging, proton density fat fraction (MRI-PDFF), which we believe is a strong predictor of fibrosis reduction." said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis, "Reductions in liver inflammatory biomarkers ALT and AST, important for assessing hepatic injury and malfunction, LDL-C, total cholesterol (TC) and triglyceride (TG), which may reduce the risk of cardiovascular-related events, combined with an excellent safety and tolerability profile support our belief that ASC41 is a potentially best-in-class THRβ agonist. We look forward to continuing the clinical development of ASC41."

ASC41 was generally well tolerated, with adverse events (AEs) being grade 1 in majority across all cohorts in the Phase II clinical trial, including the placebo cohort (see Table 3). No treatment-related serious adverse event (SAE) was reported in any patients receiving ASC41 treatment or placebo. As in prior studies, ASC41 demonstrated excellent gastrointestinal (GI) tolerability.

Table 3. Safety Data

Event, n(%)	Placebo (n = 14 )	ASC41 Tablet
Event, n(%)	Placebo (n = 14 )	2 mg, QD (n = 13)	4 mg, QD (n = 15)
TEAEs	13(92.9 %)	13(100 %)	15(100 %)
Drug-related TEAEs	6(42.9 %)	7(53.9 %)	7(46.7 %)
Grade 1	6(42.9 %)	7(53.9 %)	7(46.7 %)
Drug-related GI AEs	2(14.3 %)	3(23.1 %)	1(6.7 %)
Nausea	0(0.0 %)	0(0.0 %)	0(0.0 %)
Vomiting	0(0.0 %)	0(0.0 %)	0(0.0 %)
Diarrhea	1(7.1 %)	3(23.1 %)	1(6.7 %)
Abdominal distension	1(7.1 %)	0(0.0 %)	0(0.0 %)
Abdominal pain (upper)	0(0.0 %)	0(0.0 %)	0(0.0 %)
Constipation	0(0.0 %)	0(0.0 %)	0(0.0 %)
Dyspepsia	0(0.0 %)	0(0.0 %)	0(0.0 %)
Frequent bowel movements	0(0.0 %)	0(0.0 %)	0(0.0 %)

In Table 3, "TEAEs" stands for treatment emergent adverse events, "GI" stands for gastrointestinal, "AEs" stands for adverse events and "QD" stands for every day.

About ASC41

ASC41, a once-daily oral tablet in clinical development for the treatment of MASH, is a liver targeted small molecule which is converted into its active metabolite, ASC41-A, a potent and highly selective THRβ agonist. ASC41 tablet was developed using Ascletis' in-house proprietary formulation technology. The patent of ASC41 tablet formulation has been granted in the U.S.

About the Phase II Clinical Trial

The randomized, double-blind, placebo-controlled and multi-center Phase II clinical trial (ClinicalTrials.gov: NCT05462353) is being conducted in China and is expected to enroll approximately 180 liver biopsy-confirmed MASH patients to be randomized into two treatment cohorts of ASC41 tablet (2 mg or 4 mg), once-daily and one placebo control cohort at the ratio of 1:1:1 for 52-week treatment and 4-week follow-up. Enrollment included patients with at least 7.5% liver fat content at baseline as measured by MRI-PDFF, as well as F2 and F3 liver fibrosis. The study allows up to 15% of enrolled patients to have F1 liver fibrosis. Two liver biopsies will be performed, one at baseline and the other at the end of 52-week treatment. MRI-PDFF will be performed at baseline, Week 12 and Week 52, respectively. The pre-specified interim analysis was conducted when 42 enrolled patients completed 12-week treatment of ASC41 tablet or placebo. Primary objective is a histological reduction in nonalcoholic fatty liver disease (NAFLD) activity score (NAS) ≥ 2 points that results from reduction of necro-inflammation (inflammation or ballooning) without worsening fibrosis. Secondary objectives include MASH resolution and fibrosis improvement.

About Ascletis Pharma Inc.

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 GMP manufacturing. 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, MASH and oncology. Through excellent execution, Ascletis rapidly advances its drug pipeline with an aim of leading in global competition. To date, Ascletis has multiple clinical stage drug candidates in its R&D pipeline. The most advanced drug candidates include ASC22 (CHB functional cure), ASC40 (acne), ASC40 (recurrent glioblastoma), ASC40 (MASH), ASC41 (MASH) and ASC61 (advanced solid tumors).

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

About Gannex Pharma Co., Ltd.

Founded in 2019, Gannex is a clinical-stage, wholly-owned company of Ascletis, dedicated to the R&D and commercialization of new drugs in the field of MASH. Gannex has two clinical-stage drug candidates against two different targets, i.e. THRβ (ASC41) and fatty acid synthase (FASN) (ASC40).

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

SOURCE Ascletis Pharma Inc.