Ascletis has announced that it has submitted an Investigational New Drug (IND) application to the U.S. FDA for ASC39, an oral small-molecule selective amylin receptor agonist, for the treatment of obesity.

Goli Pharmaceutical Co., Ltd. (Hong Kong Stock Exchange Code: 1672, referred to as "Goli") announced today that it has submitted a new drug clinical trial application (IND) for ASC39 oral tablets to the US Food and Drug Administration (FDA). ASC39 oral tablet is an oral small molecule selective amylin receptor agonist for the treatment of obesity.

ASC39 has a unique chemical skeleton, which was discovered independently using the Artificial Intelligence-assisted Structure-Based Drug Discovery (AISBDD) technology based on structure-based AI-assisted drug discovery. eloralintide of ASC39 and eloralintide (a selective amylin polypeptide analog) on human amylin type 1 receptor (hAMY1R) EC in head-to-head cyclic adenosine monophosphate (cAMP) activation experiments₅₀(half maximal effective concentrations) were 21.4 pM and 21.2 pM, respectively. ASC39 and eloralintide EC on the human calcitonin receptor (hCTR)₅₀846.1 pM and 1,350.8 pM, respectively. These data indicate that ASC39 is highly selective for hAMY1R compared to hCTR and that the selectivity of ASC39 for hAMY1R is comparable to that of eloralintide. ASC39 and eloralintide were 40-fold and 64-fold more selective for hAMY1R than for hCTR, respectively.

В проучване на плъхове за затлъстяване, предизвикано от диета (DIO), пероралното приложение на 5 mg kg ASC39 веднъж дневно в продължение на 6 последователни дни води до значителна коригирана с плацебо загуба на телесно тегло от 6,6% в сравнение с плъхове със затлъстяване, получаващи плацебо. ASC39 демонстрира благоприятни фармакокинетични профили при плъхове и нечовекоподобни примати, подкрепяйки неговото перорално приложение веднъж дневно при хора.

"ASC39 is the only oral, small-molecule, selective amylin receptor agonist in development that selectively acts on the amylin receptor rather than the calcitonin receptor. It is different from the non-selective dual-target agonist and can reproduce eloralintide pharmacological properties. We believe that amylin selectivity will be a key driver of efficacy and tolerability in long-term weight management." Dr. Wu Jinzi, founder, chairman and chief executive officer of Goli, said, "Following the progress made in our Phase III incretin (incretin) candidate ASC30, the IND submission of non-incretin candidate ASC39 is another important milestone for Goli and extends our oral metabolic disease pipeline beyond incretin."

ASC39, a potent oral small molecule amylin receptor agonist with selectivity for amylin, is being developed both as a single agent and in combination with ASC30 (ASC30 is an oral small molecule of amylin that is currently undergoing two pivotal global Phase III studies) for the treatment of metabolic diseases, including obesity. This new oral small molecule selective amylin receptor agonist further expands Geli's existing amylin polypeptide pipeline, which includes ASC36 (an amylin agonist polypeptide that is administered subcutaneously quarterly and orally administered once weekly).