Foresee Pharmaceuticals, announced preclinical data in Nature Communications, demonstrating that activation of Aldehyde Dehydrogenase 2 with Foresee’s oral ALDH2 activator AD-9308, significantly ameliorates diet-induced obesity and fatty liver, and improves glucose homeostasis in both male Aldh2 wild-type and dominant-negative Glu504Lys knock-in mice with diet-induced obesity.
- AD-9308 is a potent, and highly selective oral ALDH2 activator ready for IND-enabling development.
- AD-9308 treatment ameliorates diet-induced obesity and fatty liver, and improves glucose homeostasis in both male Aldh2 wild-type and Aldh2*2 knock-in mice.
- A first-in-class oral ALDH2 activator in Foresee’s ALDH2 franchise, FP-045, has demonstrated an excellent safety and tolerability profile in Phase 1 studies and is currently in Phase 2 development.
TAIPEI, Sept. 29, 2023 /PRNewswire/ -- Foresee Pharmaceuticals (TPEx: 6576), (“Foresee”) announced today preclinical data in Nature Communications, demonstrating that activation of Aldehyde Dehydrogenase 2 (ALDH2) with Foresee’s oral ALDH2 activator AD-9308, significantly ameliorates diet-induced obesity and fatty liver, and improves glucose homeostasis in both male Aldh2 wild-type and dominant-negative Glu504Lys (ALDH2*2) knock-in mice with diet-induced obesity.
The article entitled: “A common East-Asian ALDH2 mutation causes metabolic disorders and the therapeutic effect of ALDH2 activators” is the result of a collaboration with leading academic clinical translation experts in the area of cardiometabolic diseases. The article is available at https://www.nature.com/articles/s41467-023-41570-6.
“The most common genetic variation of the ALDH2 gene in East Asian populations results in a significant reduction in the ALDH2 enzyme activity, consequently reducing its ability to remove toxic aldehydes, resulting in abnormalities in energy balance, carbohydrate and fat metabolism. By enhancing the activity of the ALDH2 enzyme with the novel compound AD-9308, these metabolic abnormalities are significantly improved, including obesity, glucose intolerance, and fatty liver induced by a high-fat diet. This research holds great potential for clinical translation and should not be underestimated as a potential approach for the prevention and treatment of common metabolic diseases in the future.” said Dr. Lee-Ming Chuang, National Chair Professorship in Medicine, adjunct attending physician, and adjunct professor in the Department of Internal Medicine at National Taiwan University Hospital.
“I am honored to be engaged in a long-term drug research collaboration with Foresee Pharmaceuticals. This research has revealed the positive effects of AD-9308 on diabetes, obesity, and fatty liver, elucidating its mechanisms of action concerning energy balance. Additionally, our team, in conjunction with other groups, has also discovered the therapeutic potential of AD-9308 in conditions such as heart disease, kidney disease, complications of diabetes, and muscular dystrophy. The efficacy of AD-9308 in diabetic cardiomyopathy has been published in an international scientific journal by our group. Subsequent research has further verified that elevating the activity of ALDH2 in the body, as facilitated by AD-9308, effectively reduces the concentration of harmful aldehydes, thereby achieving therapeutic benefits for related diseases,” said Dr. Yi-Cheng Chang, attending physician in the Department of Metabolism and Endocrinology at National Taiwan University Hospital and the Deputy Executive Director of the Center for Obesity, Life Style and Metabolic Surgery.
“We are very excited to have the opportunity to publish such compelling data related to ALDH2 and AD-9308 in this obesity model. The data strongly supports the role of ALDH2 in obesity and metabolic syndrome disease biology and further strengthens our view on the promise of our ALDH2 activators for the treatment of obesity and multiple cardiometabolic diseases,” said Dr. Wenjin Yang, Chief Scientific Officer at Foresee. “We are planning to initiate a Phase 2 study in patients with pulmonary hypertension-interstitial lung disease (PH-ILD) with our lead first-in-class oral ALDH2 activator, FP-045, in 2024. We are working diligently to build a broad franchise leveraging our multiple ALDH2 activators, including FP-045, AD-9308 and another 2nd generation compound, across several therapeutic areas, including cardiometabolic diseases,” added Dr. Yang.
About ALDH2
ALDH2 (Aldehyde Dehydrogenase 2) is a mitochondrial matrix enzyme and key regulator of mitochondrial quality control systems/health and regulator of reactive aldehydes/carbonyls, oxidative stress, inflammation, and fibrosis. Activation of ALDH2 is a compelling therapeutic strategy for improving mitochondrial quality and regulatory mechanisms for treating the treatment of rare/orphan diseases and severe diseases of aging, including cardiometabolic diseases. The key role of ALDH2 in disease is supported by strong genetic/GWAS evidence related to a dominant-negative ALDH2*2 polymorphism.
About Foresee Pharmaceuticals Co., Ltd.
Foresee is a Taiwan and US-based biopharmaceutical company listed on the Taipei Exchange (TPEx: 6576). Foresee’s R&D efforts are focused in two key areas, namely its unique Stabilized Injectable Formulation (SIF) long-acting injectable technology with derived drug products targeting specialty markets and secondly, its transformative preclinical and clinical first-in-class NCE programs targeting rare and severe disease areas with high unmet needs. Foresee’s product portfolio includes late and early-stage programs. CAMCEVI® 42 mg, for the treatment of advanced prostate cancer, is now approved in the U.S., Canada, EU and Taiwan and launched in the U.S. in April 2022. Additionally, U.S. and EU regulatory submissions are under preparation for CAMCEVI® 21 mg. The second indication of CAMCEVI® 42 mg – central precocious puberty (CPP), the phase 3 clinical study, has been initiated. FP-025 – a highly selective oral MMP-12 inhibitor targeting inflammatory and fibrotic diseases, a Phase 2 proof-of-concept study in allergic asthmatic patients. The study has been completed with positive outcomes, with future development in rare immune-fibrotic diseases. FP-045 – a highly selective oral small molecule allosteric activator of ALDH2, a mitochondrial enzyme, for which a Phase 1b/2 Fanconi Anemia study is currently being initiated, and a P2 study in pulmonary hypertension-interstitial lung disease (PH-ILD) patients is in planning. www.foreseepharma.com
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Company Codes: Gretai:6576, Taiwan:6576.TW
