Metabolic Syndrome

SHENZHEN, China, March 18, 2024 /PRNewswire/ -- On March 18 2024, Shenzhen chipscreen biosciences Co., Ltd. (hereinafter referred to as "chipscreen biosciences", stock code: 688321. SH) announced that the Phase II clinical trial (CGZ203 study) of chiglitazar monotherapy for non-alcoholic steatohepatitis (NASH) was successfully completed with data cleaning and database locking on February 22, 2024. The primary efficacy endpoint of the trial has been achieved, and further data analysis is currently underway. The incidence of non-alcoholic fatty liver disease (NAFLD) or metabolic associated fatty liver disease (MAFLD) in the general population of China exceeds 25%, of which about 25% will progress to NASH, and this proportion is even higher in patients with metabolic syndrome. Currently, there is only one thyroid receptor β (TRβ) agonist approved worldwide. The CGZ203 study is a randomized, double-blind, placebo-controlled, multicenter Phase II clinical trial aimed to evaluate the safety and preliminary efficacy of chiglitazar monotherapy in diagnosed NASH patients. The CGZ203 study was led by Beijing Friendship Hospital affiliated to Capital Medical University and conducted in 24 clinical sites nationwide. Preliminary results showed that both dose groups of chiglitazar produced significant and dose-dependent reductions at the primary efficacy endpoint (the proportion of changes from baseline in liver fat content evaluated by MRI-PDFF after 18 weeks of treatment), compared to placebo control group. In terms of secondary efficacy endpoints such as the proportion of patients with an over 30% decrease in liver fat content, non-invasive indicators related to hepatocyte damage, inflammation, and fibrosis and so on, both dose groups of chiglitazar also showed significant or dose-dependent trend of improvements. The overall safety is good. The detailed research results will be presented on an upcoming scientific conference or in research article. About Chiglitazar: Chiglitazar (Carfloglitazar) is a novel peroxisome proliferator activation related receptor (PPAR) pan-agonist, independently discovered and developed by Shenzhen chipscreen biosciences with global patent protection. It was firstly approved in China in October 2021, for clinical treatment of type 2 diabetes patients who cannot be effectively controlled by exercise and diet control. It is also the first approved PPAR pan-agonist in the world. Chiglitazar has already completed a phase III trial of combination with metformin to treat type 2 diabetes patients (RECAM study) and the current phase II trial in NASH patients (CGZ203) in China. About CGZ203: CGZ203 is an exploratory phase II trial aimed at treating NASH patients. It was designed as a randomized, double-blind, placebo-controlled multicenter clinical trial. The clinically diagnosed NASH patients were randomly enrolled in a ratio of 2:2:1 to receive oral administration of chiglitazar 48 mg, 64 mg, and placebo once a day respectively, with a treatment period of 18 weeks. The primary efficacy endpoint is the percentage of changes from baseline in liver fat content (LFC) evaluated by magnetic resonance proton density fat fraction (MRI-PDFF) after 18 weeks of treatment. Secondary endpoints include the absolute value of LFC changes, the proportion of people with a decrease of more than 30% in LFC, changes in other non-invasive indicators of liver cell damage, inflammation, and fibrosis, and the patient safety during the trial period. About Chipscreen: Shenzhen Chipscreen biosciences is a modern biopharmaceutical enterprise founded by a senior overseas Returnees team in 2001. The company specializes in the discovery and development of original new molecular entity drugs, focus on five major disease fields of cancer, metabolic diseases, autoimmune diseases, central nervous system diseases. With the independently created "integrated drug discovery and early evaluation platform based on chemical genomics", chipscreen has developed multiple original new drugs including two marketed products Chidamide (Tucidinostat) and Chiglitazar (Carfloglitazar), several clinical stage drug candidates Chiauranib (phase III), CS12192 (phase I), CS23546 (phase I), and CS32582 (Phase I). Till now, chipscreen has established a global industrial layout consisting of its headquarters, R&D center, a wholly-owned subsidiary of GMP production base (Shenzhen chipscreen Pharmaceutical Co., Ltd.) in Shenzhen, a wholly-owned subsidiary of its Chengdu regional headquarters/R&D center/innovative drug production base (Chengdu chipscreen Pharmaceutical Co., Ltd.) in Chengdu, Beijing branch (clinical research center), Shanghai branch (commercial center), and chipscreen Biosciences (USA) Co., Ltd. Chipscreen is one of the first batch of national "innovative drug incubation bases" and a national high-tech enterprise, independently undertakes dozens of national "863", "10th/11th/12th/13th five year plan of major scientific and technological special projects", and "major new drug creation" projects. A total of over 600 domestic and foreign invention patents have been applied, and over 160 have been authorized. SOURCE Shenzhen Chipscreen Biosciences Co., Ltd.

- Profound effects on muscle gain, fat loss, and insulin sensitization, along with a dual anabolic/anti-resorptive action on bone, pave the way for Phase 2 clinical development THOUSAND OAKS, Calif.--(BUSINESS WIRE)-- AliveGen USA Inc. (AliveGen), a clinical-stage biopharmaceutical company dedicated to developing first-in-class and best-in-class therapeutics for treating muscle wasting, metabolic disorders, and neuromuscular diseases, is delighted to announce the successful completion of its Phase 1b multiple-ascending dose (MAD) clinical trial for ALG-801. ALG-801 is a novel, next-generation ligand trap, which selectively sequesters a subset of TGF-beta family, including growth differentiation factors and activins. The Phase 1b MAD clinical study was conducted in healthy volunteers. This achievement marks a significant milestone in AliveGen’s mission to discover and deliver innovative therapies that address unmet medical needs. Key Highlights: Study Design: The Phase 1b MAD study is a randomized double-blind placebo-controlled trial in postmenopausal women. Safety Profile: ALG-801 was found to be safe and well-tolerated across all dosing cohorts. Efficacy Signal: ALG-801 exhibited linear pharmacokinetic (PK) exposures, along with dose-dependent and statistically significant pharmacodynamic (PD) responses. These included muscle gain, fat loss, and increased insulin sensitivity, as well as a dual anabolic/anti-resorptive effect on bone. These findings highlight ALG-801’s therapeutic potential in treating a wide range of medical conditions, such as muscle wasting, obesity, cardiometabolic disorders, neuromuscular diseases, chronic kidney disease, liver steatosis and fibrosis, and osteosarcopenia in old age. Differentiated Mechanism: By selectively inhibiting multiple ligands of the Smad2/3 signaling pathway, ALG-801 demonstrates an outstanding efficacy and metabolic effect. Next Step: Following the successful Phase 1b MAD study, AliveGen plans to advance ALG-801 to Phase 2 clinical development. “We are grateful to the healthy volunteers and healthcare professionals who actively participated in our Phase 1b clinical trial,” said HQ Han, MD, PhD, CEO of AliveGen. “We are thrilled with the excellent dose-response data on muscle gain, fat lose, and insulin sensitization from our Phase 1b MAD study. ALG-801, an innovative and powerful therapeutic approach, holds significant promise for addressing unmet needs across a diverse range of diseases. We look forward to advancing ALG-801 into Phase 2 clinical development.” About AliveGen AliveGen USA Inc. is a privately held biopharmaceutical company located in Thousand Oaks, California. The company is focused on the discovery and development of next-generation biotherapeutics to treat the debilitating muscle wasting and loss of functional capacity as occurs in various metabolic disorders, neuromuscular diseases, and age-related frailty.

Researchers discovered a mechanism behind middle-age obesity in rat brains. They believe that a similar mechanism exists in humans as well. This discovery may lead to improvements in preventing obesity and metabolic syndrome. Nagoya University researchers and their colleagues in Japan have found that middle-age obesity is caused by age-related changes in the shape of neurons in the hypothalamus, a region of the brain that controls metabolism and appetite. A protein called melanocortin-4 receptor (MC4R) detects overnutrition and regulates metabolism and appetite to prevent obesity. According to their study in rats, MC4Rs were concentrated in primary cilia (antenna-like structures) that extend from a couple of groups of hypothalamic neurons. The study also showed that the primary cilia became shorter with age, which decreased MC4Rs accordingly, resulting in weight gain. "We believe that a similar mechanism exists in humans as well," said Professor Kazuhiro Nakamura of the Nagoya University Graduate School of Medicine, the lead author of the study. "We hope our finding will lead to a fundamental treatment for obesity." The researchers published the results of the study in the journal Cell Metabolism. As we get older, we become more prone to being overweight and obesity. Obese people are more susceptible to diabetes, hyperlipidemia, and other chronic diseases. Previous studies have suggested that middle-age weight gain is caused by a decline in overall metabolism due to aging, but the mechanism was unclear. A research team of the Nagoya University Graduate School of Medicine, in collaboration with researchers from Osaka University, the University of Tokyo, and the Nagoya University Research Institute of Environmental Medicine, conducted a study focusing on MC4Rs. MC4Rs stimulate metabolism and suppress food intake in response to an overeating signal from melanocortin. Initially, the research team examined the distribution of MC4Rs in the rat brain by utilizing an antibody they had developed specifically to make MC4Rs visible. They found that MC4Rs are present exclusively in primary cilia of specific groups of hypothalamic neurons. The team next investigated the length of the primary cilia that had MC4Rs (MC4R+ cilia) in the brains of 9-week-old (young) rats and 6-month-old (middle-age) rats. The team found that MC4R+ cilia in middle-aged rats were significantly shorter than those in young rats. Accordingly, the metabolism and the fat-burning capacity of middle-aged rats were much lower than those of young rats. The team next analyzed MC4R+ cilia in rats under different dietary conditions. The results showed that MC4R+ cilia in rats on a normal diet gradually shortened with age. On the other hand, MC4R+ cilia in rats on a high-fat diet shortened at a faster pace, while those in rats on a restricted diet shortened at a slower pace. Interestingly, the team also found that MC4R+ cilia that once disappeared with age were regenerated in rats raised under two months of dietary restriction. In the study, the team also used genetic technologies to make MC4R+ cilia shorter in young rats. These rats showed increased food intake and decreased metabolism, leading to weight gain. The team also administered a hormone called leptin to the brains of rats with artificially shortened MC4R+ cilia. Leptin is thought to help reduce food intake. Surprisingly, however, their appetite was not reduced, indicating that leptin could not exert anti-obesity effects. "This phenomenon, called leptin resistance, is often observed in obese human patients as well. This is an obstacle to the treatment of obesity, but the cause has long been unknown," explained Dr. Manami Oya, the first author of the study. "In obese patients, adipose tissue secretes excessive leptin, which triggers the chronic action of melanocortin. Our study suggests that this may promote the age-related shortening of MC4R+ cilia and put animals into a downward spiral where melanocortin becomes ineffective, increasing the risk of obesity." The study concluded that the age-related shortening of MC4R+ cilia causes middle-age obesity and leptin resistance in rats. The researchers demonstrated that dietary restriction is one method to prevent and treat overweight and obesity. Prof. Nakamura said, "Moderate eating habits could maintain MC4R+ cilia long enough to keep the brain's anti-obesity system in good shape even as we age."