On October 15, 2024, the list of selected candidates for the oral report of the American Association for the Study of the Liver (AASLD 2024) annual meeting was officially announced online. The abstract of the Phase II clinical study (CGZ203 trial) on the treatment of non-alcoholic steatohepatitis (NASH)/metabolic associated steatohepatitis (MASH) with our independently developed Chiglitazar （Carfloglitazar） will be presented orally at the annual meeting to be held in San Diego, USA from November 15th to 19th.

The incidence of metabolic associated fatty liver disease (MAFLD) in China is over 25%, of which about 25% of patients will further develop MASH. Among patients with metabolic syndrome, this proportion is even higher. However, Currently, there is only one approved thyroid hormone receptor beta (THR - β) agonist drug in the global regulated market for the treatment of MASH. China has not yet approved any drugs for this treatment field.

CGZ203 is a randomized, double-blind, placebo-controlled, phase II clinical trial aimed at evaluating the safety and preliminary efficacy of Chiglitazar (Carfloglitazar) monotherapy in the MASH population. Patients clinically diagnosed with MASH were randomly assigned to receive Chiglitazar 48mg (n=42), 64mg (n=41), or placebo (n=21) at a ratio of 2:2:1, orally once daily for a treatment period of 18 weeks. 

The study results showed that the liver fat content (LFC) evaluated by MRI-PDFF decreased from baseline by 28.1% and 39.5% respectively after 18 weeks of treatment with Chiglitazar 48mg or 64mg (decrease of 3.2% in the Placebo). The proportion of patients achieved over 30% decrease in LFC was 40.5% and 65.9% respectively (14.3% in the placebo). The plasma biochemical indicators related to chronic inflammation and liver injury, such as CK-18, liver transaminase, bilirubin, etc., also significantly decreased after treatment with Chiglitazar. The alanine aminotransferase (ALT) level in the high-dose group decreased by more than 50% from baseline, and the ALT level returned to the normal range in more than 70% of patients. 

Regarding to liver fibrosis evaluated by Fibroscan LSM, Chiglitazar produced a dose - and time-dependent decrease in liver stiffness values, with the high-dose group showing a decrease of 2 Kpa in LSM values after 18 weeks of treatment. When comparing with the placebo, Chiglitazar groups showed comparable good safety. In terms of potential side effects related to PPAR agonists, there was no significant body weight gain in the Chiglitazar treatment groups, whiles a slight decrease in the high-dose group; and only one mild edema occurred in the low-dose group. 

This study demonstrates the good safety tolerance and preliminary promising efficacy of Chiglitazar on the multiple pathological aspects such as liver fat accumulation, chronic inflammation, and liver fibrosis in patients with MASH, although, it remains to be confirmed in further clinical trials.

ABSTRACT PRESENTATION DETAILS

Abstract Number：（2603）
Session Date / Time: 11/17/2024，2:00pm - 3:30 pm
Title: MASLD and MASH - New Therapies Type: Abstract Parallel
Speaker: Professor You Hong, Beijing Friendship Hospital Affiliated to Capital Medical University
Presentation: A randomized, double-blind, placebo-controlled phase 2 trial to evaluate the efficacy and safety of Chiglitazar in NASH patients 
Presentation Time:2:15 pm - 2:30 pm 
Presentation Duration:15 minutes
Publication Number:54

About Chiglitazar:
Chiglitazar is a new mechanism hypoglycemic drug independently developed by the company, and also the first fully PPAR agonist approved to treat type 2 diabetes in the world. At present, Chiglitazar sodium has been approved for blood glucose control in adult patients with type 2 diabetes. It can be taken alone or combined with metformin.The Phase II clinical study of monotherapy for the treatment of nonalcoholic steatohepatitis (NASH) has concluded and achieved its primary endpoint.

Chiglitazar Sodium targets insulin resistance, a core mechanism in the occurrence and development of type 2 diabetes mellitus (T2DM). It moderately activates all three PPAR subtypes to achieve a dynamic balance of glucose, lipid, energy, and protein metabolism. Preliminary comprehensive clinical studies indicate that Chiglitazar Sodium has excellent safety, pharmacokinetic, and pharmacodynamic profiles, demonstrating efficacy in regulating blood glucose, blood lipids, and energy in patients with T2DM.

About Chipscreen:

Chipscreen Biosciences is an innovative drug company driven by core technologies with globally competitive pipelines. As a pioneer in drug innovation & development in China, adhering to the concept of "Constant Innovation for Life", we focus on developing revolutionary innovative drugs with new mechanisms of action, to address patients' pressing clinical needs. Our complete industry chain that covers early exploratory discovery through commercialization allows us to provide innovative Chinese drugs for patients worldwide.

With a global development strategy based on early-stage research in China, Chipscreen Biosciences has leveraged the top scientists and teams with extensive experience in related fields from the Shenzhen Small Molecule Early R&D Center and Chengdu Small Molecule Early R&D Center to create an integrated technology platform based on AI-driven design and chemical genomics, which spanned the whole process from basic science to clinical translation. We have successfully developed first-in-class and best-in-class innovative drugs. Currently, 2 drugs with 6 indications have been marketed worldwide. In addition, we have launched a number of R&D projects with differentiated advantages and global competitiveness in the five major areas, including malignant tumors, metabolic diseases, autoimmune diseases, central nervous system diseases, and antivirals.

Chipscreen Biosciences has formed a global industrial layout consisting of Shenzhen Head Office/R&D Center/GMP production base, Chengdu Regional Head Office/R&D Center/GMP production base, Beijing Branch, Shanghai Branch, and Chipscreen Biosciences (USA) Co., Ltd. Meanwhile, as one of the first batches of national "innovative drug incubation bases" and national high-tech enterprises, Chipscreen Biosciences has independently undertaken many national "863" plans and national major science and technology projects, such as "10th five-year plan", "11th five-year plan", "12th five-year plan" and "13th five-year plan", and National Science and Technology primary Project for Innovative Drug Development. We have filed over 680 invention patents in China and worldwide, with over 200 granted.