Core Technology

Dr. Wen-Ching Yang, the founder of Pharmasaga, was the first to identify the novel diabetes target, PDIA4, which regulates pancreatic beta-cell failure and diabetes progression. Utilizing a molecular docking platform for screening, a lead compound that inhibits PDIA4 was identified from 46,000 compounds. After a series of optimization and selection processes, three drug candidates were identified, leading to the development of PS1 as a first-in-class small-molecule drug for the diabetes market. The Company has secured the global exclusive license for the aforementioned patent from Academia Sinica, establishing it as the core technology and product for our drug development.

The mechanism of PDIA4 is as follows:

• Over-nutrition (metabolic stress) increases PDIA4 expression, leading to the generation of excessive reactive oxygen species (ROS), which causes pancreatic beta-cell failure and the onset of diabetes.

• PS-001 inhibits PDIA4 activity, which suppresses ROS generation, prevents beta-cell failure, and treats diabetes (Reference: EMBO Mol. Med. (2021) e11668).

Under long-term over-nutrition, individuals may develop diabetes and insulin resistance. Pancreatic beta-cells must secrete more insulin to maintain stable blood glucose, gradually leading to beta-cell failure.

Pharmasaga founder Dr. Wen-Ching Yang discovered that chronic over-nutrition causes the upregulation of the PDIA4 protein in beta-cells, leading to an increase in oxidative stress and free radicals, which ultimately causes beta-cell failure. He therefore designed [ML1] the small-molecule inhibitor PS1 for[ML2] the PDIA4 protein. Inhibiting PDIA4 protein prevents beta-cell death and restores their function.

A fundamental curative approach: PS1 inhibits PDIA4, preventing beta-cell death. Coupled with existing pancreatic stem cells to allow for islet regeneration, there is an opportunity to reverse diabetes.