TYK Medicines, Inc (hereinafter referred to as TYK Medicines), a Chinese-based leader in the research and development of new oncology drugs with a global presence, announced that on March 11, 2021, China National Medical Products Administration Center for Drug Evaluation (CDE) approved TY-9591 tablets, a third-generation EGFR (epidermal growth factor receptor) inhibitor developed by TYK Medicines to enter critical Phase III clinical trial.

This is a randomized, double-blind, multi-center Phase III study to assess the efficacy and safety of TY-9591 versus Osimertinib (Tagrisso®) as first-line treatment in patients with EGFR-sensitive mutation, locally advanced or metastatic NSCLC (FLETEO). The study is led by Professor Baohui Han from Shanghai Chest Hospital, and plans to be carried out in about 70 study sites in China.

TY-9591 is a third-generation EGFR inhibitor developed by TYK Medicines with the characteristics of high activity, high selectivity and good safety. Compared with Osimertinib, TY-9591 can significantly reduce the production of toxic metabolite AZ5104 by shielding the original metabolic sites of Osimertinib. Preclinical studies showed that TY-9591 had significant antitumor activity and good pharmacokinetic characteristics, and is superior to Osimertinib in terms of non-clinical safety, with a wider safety window.

Phase I trial results confirmed that the ratio of exposure of the metabolite D1 (AZ5104) of TY-9591 to the original drug was only 5.11-6.78%, and this metabolite was reduced by about 50% compared with Osimertinib. The objective response rate (ORR) for first-line treatment of NSCLC was 84.8%, and the intracranial objective response rate (iORR) for NSCLC patients with BMs was up to 100%.

The most common AEs of TY-9591 was white blood cell count decreased, which reduced the incidence of EGFR TKI typical adverse reactions such as rash, diarrhea, parathylitis, etc. The rate of Grade ≥3 adverse reactions was 21.4%, and serious adverse events (SAE) was 6.8%. No interstitial lung disease, cardiomyopathy and keratitis occurred which Osimertinib special interest. TY-9591 achieves the best balance of clinical efficacy and safety.

TY-9591 is the first product in the world to compare with Osimertinib in phase III clinical study, expected to be the only product in the world to show superior efficacy compared to with Osimertinib in a large-scale head-to-head clinical trial.

Dr. Yusheng Wu, Chairman /CEO of TYK Medicines said, “The approval of the pivotal clinical study of TY-9591 is an important milestone in the development of our company. Based on the compelling data available, we believe that TY-9591 is expected to provide a new first-line treatment option for patients with advanced NSCLC, and will also improve the accessibility of the standard of clinical treatment in China. We look forward to working with Chinese investigators, patients and partners to advance this clinical study to expedite the marketing of TY-9591 so as to benefit cancer patients with better clinical efficacy, safety and convenience.”

About TY-9591

TY-9591 is an orally, irreversible, third-generation inhibitor of Epidermal Growth Factor Receptor (EGFR) harboring sensitising-mutations (EGFRm) and TKI-resistance mutation T790M, individually developed by TYK Medicines, Inc. TY-9591 has good stability, high bioavailability, and is capable of penetrating the blood-brain barrier to achieve intracranial efficacy. With similar efficacy and development characteristics to Osimertinib, TY-9591 differs in its drug metabolism characteristics, which can significantly reduce the production of toxic metabolites AZD5104 (TY-9591-D1) and reduce toxic side effects, thus suggesting a potentially wider clinical therapeutic window. TY-9591 is a potent inhibitor for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutation (including exon 19 deletions or exon 21 L858R substitution mutation) or the treatment of adult patients with advanced EGFR mutation positive NSCLC with central nervous system metastases.

About TYK Medicines, Inc.

TYK Medicines is an innovative biotechnology company based in China, facing the global, focusing on researching and developing international cutting-edge new drugs. The company has established a high-efficiency innovative drug research and development platform, with fully functioned instruments, covering multiple pharmaceutical fields including drug synthesis, biological fermentation, drug analysis, bioanalysis, and formulation research, and is committed to becoming the best domestic and world-class new drug research and development company.