On August 17th, 2023, TYK Medicines announced that the first patient in the Shandong Cancer Hospital has been dosed in Phase 1 clinical trial (CTR20231575) of TY-2699a, its novel and highly selective cyclin-dependent kinase 7 (CDK7) inhibitor, which is the first patient in China Mainland. This is the first CDK7 inhibitor in China to receive both FDA and NMPA approval to enter clinical studies and complete the first patient enrollment.

This trial comprises 2 parts, dose escalation and dose expansion, led by Prof. Binghe Xu of Cancer Hospital Chinese Academy of Medical Science, aiming to evaluate the safety and tolerability of TY-2699a in patients with advanced/metastatic solid tumors, determine the maximum tolerated dose (MTD), Phase II recommended dose (RP2D) as well the treatment schema, and assess preliminary efficacy.

Yusheng Wu, Ph.D., Chairman/CEO of TYK Medicines, said:

“We are making every effort to seeking for a novel approach for improving survival and life quality of patients with malignancies. The promising potential has been observed in preclinical studies in terms of anti-tumor efficacy and safety, which prompted us to accelerate the promotion of TY-2699a into further clinical studies. The enrollment of this patient is the first case of the compounds of CDK7 inhibitors in China, which can be considered as a milestone.

Xiugui Chen, vice president of TYK Medicines, said:

“TY-2699a demonstrated striking anti-tumor activities in breast cancer and a range of transcriptionally driven cancer models, which possess significant unmet clinical needs, like breast cancer, small cell lung cancer (SCLC), pancreatic cancer etc. TY-2699a is a novel target therapy via attacking two processes attributing to cancer formation: dysregulation of the cell cycle process and over transcription of oncogenes. We expect the smooth development of clinical trial, boosting dose escalation effectively and reporting sparking signals of brand-new clinical treatment to those who may mostly benefit from the response of TY-2699a.”

About CDK7

CDK7 is a member of the cyclin-dependent kinases (CDK) family and a subunit of the multi-protein transcription factor, TFIIH, playing key roles in both transcription and regulation of the cell cycle, emerging as an attractive and promising target for anti-cancer therapeutics. In the cell cycle, CDK7 forms the CDK-activating kinase (CAK) with cyclin H and MAT1 and controls cell cycle progression, particularly in malignant cells, by activating other CDK family kinases (CDK1/2/4/6). Concerning transcription, the CAK module is a component of TFIIH, a multi-protein complex essential for transcription and regulation. CDK7 has been implicated in multiple tumor types driven by aberrant transcriptional control (e.g., MYC-, ESR1-activation) and/or aberrant cell cycle control (e.g., RB1, CCNE1, CDKN2A alterations). Multiple tumors, including but not limited to triple-negative breast cancer (TNBC), relapsed or refractory ovarian cancer (OC), pancreatic ductal adenocarcinoma (PDAC), and blood cancers, have been demonstrated to be highly dependent on CDK7. CDK7 inhibitors are expected to be a promising treatment for such cancers.