2021.7 Academia Sinica's Institute of Plant and Microbial Biology Develops First-in-Class Small Molecule Drug with Potential to Cure Diabetes, Licensed to Pharmasaga for Clinical Advancement
Diabetes Future Research and Application Symposium
Academia Sinica's Institute of Plant and Microbial Biology Develops First-in-Class Small Molecule Drug with Potential to Cure Diabetes, Licensed to Pharmasaga for Clinical Advancement
李林璦 Reporter/2021-07-31
Yesterday (the 30th), the Agricultural Biotechnology Research Center and the Center for Translational Medicine jointly held the "Diabetes Future Research and Application" Symposium. Experts including Dr. Yi-Cheng Chang from National Taiwan University Hospital, Dr. Wen-Ching Yang (Deputy Director of the Agricultural Biotechnology Center), Shawn Pan (CEO of Pharmasaga), and Alex Chen (Vice President of Huain An Biomedical) were invited to share the latest research and development progress in novel diabetes drugs.
Dr. Yi-Cheng Chang stated that eating causes blood glucose levels to rise, and the human body constantly compensates by secreting insulin to stabilize blood sugar. This excessive compensation leads to the death of pancreatic beta-cells. Studies show that when diabetes is diagnosed, only about 50% of beta-cells remain. Dr. Chang shared that large-scale gene variation studies reveal that 40–60% of diabetes is influenced by genes, with the other half by the environment. Research has identified 600 diabetes-causing genes, surprisingly, most of which are related to beta-cell function. Dr. Chang pointed out that obesity and diabetes are closely linked, and analysis shows that 90% of obesity is associated with appetite. Recent research also indicates that hyper-palatable food can easily trigger the brain's reward mechanism, leading to addiction, followed by obesity, insulin resistance, and diabetes. Dr. Chang concluded that while multiple drugs currently lower blood glucose through various mechanisms, future diabetes drugs should focus on two areas: suppressing appetite and resolving oxidative stress in pancreatic beta-cells.
Dr. Wen-Ching Yang shared his journey in developing the first-in-class novel drug PS001. He noted that 461 million people worldwide suffer from diabetes, and while over 30 types of diabetes drugs are on the market, both their efficacy and side effects need improvement. Dr. Yang pointed out that type 2 diabetes can be prevented and its progression delayed. Studies indicate that for high-risk groups, using the anti-diabetic drug Metformin can lower the incidence rate by 31%, while diet and lifestyle control can reduce it by 58%.
Dr. Yang emphasized that the failure of beta-cells is a key factor in the progression of diabetes. Using proteomics, he identified the PDIA4 protein target on the beta-cells of diabetic patients, noting that the concentration of PDIA4 in the blood of diabetic patients increases and can serve as a diagnostic marker. Research also showed that PDIA4 knockout mice with diabetes developed borderline diabetes, with blood glucose levels near the pathological boundary; 42% of these mice developed the disease, while 58% did not.
Dr. Yang then synthesized PS001, a specific small-molecule inhibitor of PDIA4, selected from natural compounds. After treating diabetic mice for 16 weeks and then withdrawing the drug for 32 weeks, 60% of the mice maintained normal blood glucose levels. In the treatment group combining PS001 and Metformin, 100% of mice maintained normal blood glucose, and their pancreatic beta-cells showed no inflammation or death. In vitro assays also showed that PS001 can reduce beta-cell death induced by high glucose.
Shawn Pan, CEO of Pharmasaga, introduced the Company, established in January 2021 as a spin-off startup through the Ministry of Science and Technology's Value Creation Program. The Company will continue to leverage the PDIA4 drug target, maximizing the value of the R&D achievement. PS001 will target patients in the early-to-mid-stages of diabetes who use small-molecule drugs, aiming to reverse the disease progression. PS001 synthesis requires only 4 steps, with a yield of up to 60%. Preclinical, pharmacokinetics, and safety trials are completed.
In April this year, the Company applied for a pre-IND meeting with the US FDA and obtained FDA agreement. Following anticipated IND approval, clinical trials are scheduled to commence at National Taiwan University Hospital in Q1 2022, recruiting 25 Type 2 Diabetes patients using Metformin, with trial completion estimated for September 2022. Future plans include expanding indications to autoimmune diseases and cancer. The Angel Round funding is set to launch in the second half of this year, aiming to raise 120 million TWD.
Alex Chen, Vice President of Huain An Biomedical, shared their company's profile. Established in 2012, it is currently listed on the emerging stock market. Its pipeline includes treatments for epidermolysis bullosa (Butterfly Disease), diabetic foot and leg ulcers, lower extremity venous ulcers, hair loss prevention, and Parkinson's disease. Mr. Chen stated that 15–20% of diabetic patients suffer from chronic wounds, which often recur and can lead to amputation, with a survival rate of less than 50% five years post-amputation.
Mr. Chen pointed out that Huain An's drug D703 utilizes its unique ENERGI drug development platform. It works by activating AMP-activated protein kinase (AMPK), a key enzyme in cellular energy regulation, to increase cellular energy (adenosine triphosphate, ATP) and promote the body's self-healing through epidermal cell growth. The Phase II clinical trial for D703 is complete. It was a double-blind trial involving 105 patients, with twice-daily use for 12 weeks, combined with standard wound care. Results showed that 43.9% of patients with wounds measuring 1.5–25 cm² achieved 100% healing, compared to only 10% in the placebo group. The company plans to file an IND application with the US FDA for a Phase III clinical trial in 2022.
[translated from Chinese; Note: The Taiwan calendar year in the original has been translated into the corresponding Gregorian calendar year for clarity in English (e.g., Q1 2022).]