Overview
TY-302 is a CDK4/6 inhibitor individually developed by TYK Medicines, Inc, a class I innovative drug in China. It is clinically intended for use in combination with endocrine therapy to treat Estrogen Receptor (ER) positive and Human Epidermal Growth Factor Receptor 2 (HER2) negative advanced breast cancer, or in combination with Abiraterone acetate tablets for the first-line treatment of metastatic castration-resistant prostate cancer (mCRPC). TY-302 received the clinical trial approval notification from the NMPA in 2019 and has completed the phase I dose-escalation study. Currently, a phase II study underway to evaluate TY-302 combined with Toremifene in breast cancer is ongoing, and a phase II/III study of TY-302 combined with Abiraterone in prostate cancer is planned.
Mechanism of Action
Cyclin-dependent kinases (CDKs) are a class of serine/threonine protein kinases, involved in the crucial process in cell cycle regulation. The absence of CDK inhibitors, CDK or cyclin overexpression and other cell cyclin-related genetic alternations can lead to cell cycle dysregulation and uncontrolled proliferation, which is also one of the important characteristics of malignant tumors. TY-302 downregulates the phosphorylation level of Rb by inhibiting the activity of Cyclin D-CDK4/6, leading to cell cycle arrest in the G1 phase and inhibiting the proliferation of tumor cells. CDK4/6 inhibitors in combination with other endocrine drugs have shown significant efficacy in the treatment of breast cancer. Preclinical studies have shown that TY-302 is similar to Palbociclib in terms of mechanism of action, antitumor activity, pharmacokinetic (PK) characteristics, and safety pharmacological characteristics, and is expected to have good safety and efficacy in clinical practice. Toremifene has an estrogen antagonist effect and is used in the treatment of estrogen receptor-positive breast cancer clinically, and TY-302 in combination with Toremifene will provide more treatment options for patients with advanced breast cancer.
Prostate cancer is an androgen-sensitive tumor, and androgens play a key role in the development of prostate cancer through the interaction with androgen receptor (AR). Abiraterone is an endocrine drug that blocks androgen synthesis, but increasing amounts of preclinical and clinical studies revealed that dysregulated signaling is often found in prostate cancer after abiraterone treatment, resulting in drug resistance, This highlights the urgent need for new therapeutic options clinically. Studies have confirmed that CDK4/6 inhibitors can inhibit tumor growth and reverse drug resistance in preclinical models such as prostate cancer. Therefore, the combination of TY-302 with abiraterone will have potential synergistic anti-tumor effects in prostate cancer.
