TYK Medicine announced that its self-developed next-generation oral, highly potent small molecule CDK2 inhibitor, TYK-00540, has received formal approval from the Center for Drug Evaluation (CDE) of the National Medical Products Administration to proceed with Phase II clinical trial for combination therapy. The company is going to initiate the trial recently to accelerate the clinical development of TYK-00540.

Currently, there are no approved CDK2 inhibitors on the global market. Results of Phase I trial showed that TYK-00540 has a manageable safety and the preliminary efficacy on solid tumor. The Phase II clinical trial approval will further advance the development of TYK-00540 for CDK4/6 inhibitor-resistant breast cancer and prostate cancer indications, positioning it as a promising candidate in TYK Medicine’s oncology pipeline to solve the unmet medical needs.

About TYK-00540

TYK-00540 is an oral, highly potent small molecule CDK2 inhibitor independently developed by Zhejiang TYK Medicine Co., Ltd. Currently, Phase Ia/Ib clinical trials of TYK-00540 have been conducted at leading medical institutions, including the Affiliated Tumor Hospital of Fudan University. Preliminary findings indicate that the drug exhibits excellent safety, tolerability, and initial efficacy.

About CDK2

Selective inhibition of CDK4/6 to regulate the cell cycle has proven effective in breast cancer treatment. However, with the widespread use of CDK4/6 inhibitors, many patients have developed resistance, highlighting the urgent need for novel therapeutic strategies.

A 2021 Cancer Cell publication using CRISPR screening revealed that resistance to CDK4/6 inhibitors is linked to the activation of the cyclinE-CDK2 and Myc signaling pathways. Patients with high CCNE1 expression exhibit resistance to PAL/fulvestrant combination therapy. CCNE1 and CDK2 collaboratively promote the G1/S phase transition, indicating that CDK2 activation is associated with PAL resistance. CDK2 activation and CDK4/6 inhibitor resistance can arise through various mechanisms, including alterations in CCNE1, MYC, and CDKN1A activity. Simultaneously targeting CDK2 has been shown to significantly reduce the likelihood of tumor cells developing resistance .