CStone Announces NMPA Acceptance of New Drug Application of Selective Inhibitor GAVRETO(R) (Pralsetinib) with Priority Review Designation for the Treatment of Advanced or Metastatic RET-Altered Thyroi

CStone Pharmaceuticals, a leading biopharmaceutical company focused on developing and commercializing innovative immuno-oncology therapies and precision medicines, today announces that the National Medical Products Administration (NMPA) of China has accepted the New Drug Application (NDA) of selective inhibitor GAVRETO® (Pralsetinib) with priority review designation for the treatment of the patients with advanced or metastatic RET-altered thyroid cancer. This may expand the labeled indications for GAVRETO® in China to include advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, or with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and radioactive iodine-refractory (if radioactive iodine is appropriate).

In March 2021, the NMPA granted approval of pralsetinib under the brand name GAVRETO® for the treatment of adult patients with locally advanced or metastatic RET fusion-positive non-small cell lung cancer (NSCLC) after platinum-based chemotherapy. Discovered by CStone's partner Blueprint Medicines, GAVRETO® is the first approved selective RET inhibitor in China.

Dr. Jason Yang, Chief Medical Officer of CStone, said: "We are excited to see that this NDA has been accepted by the NMPA, which is six months in advance of our schedule. There has been a lack of precision medicines for RET-altered thyroid cancer in China and patients can only be treated with multi-targeted drugs. Study results showed that GAVRETO® had robust and durable efficacy and a well-tolerated safety profile among patients with RET-mutant MTC and RET fusion-positive thyroid cancer. We thank the NMPA for granting priority review for this indication and look forward to getting approval and hope benefit more patients in China in the future."

This NDA acceptance is based on efficacy and safety results from the global Phase 1/2 ARROW trial, designed to evaluate pralsetinib in patients with RET fusion-positive NSCLC, RET-mutant MTC, and other advanced solid tumors with RET fusions.

Results from the ARROW trial in patients with RET-mutant MTC were presented at the European Society for Medical Oncology Virtual Congress in September 2020. As of a data cutoff date of February 13, 2020, the results showed that pralsetinib had robust and durable anti-tumor activity in response-evaluable patients who received a starting dose of 400 mg once daily. In 53 patients previously treated with cabozantinib or vandetanib, the overall response rate (ORR) was 60 percent (95% CI: 46%, 74%) with one response pending confirmation, and the median duration of response (DOR) was not reached (95% CI: not reached, not reached). In 19 systemic treatment-naïve patients who were ineligible for standard therapy per the study protocol, the confirmed ORR was 74 percent (95% CI: 49%, 91%), and the median DOR was not reached (95% CI: 7 months, not reached). In 438 ARROW trial patients across RET-altered tumor types, the most common treatment-related adverse events reported by investigators (≥ 15 percent) were increased aspartate aminotransferase, anemia, increased alanine aminotransferase, hypertension, constipation, decreased white blood cell count, neutropenia, decreased neutrophil count and hyperphosphatemia.

CStone has an exclusive collaboration and license agreement with Blueprint Medicines for the development and commercialization of GAVRETO® in Greater China, which encompasses Mainland China, Hong Kong, S.A.R., China, Macau, S.A.R., China, and Taiwan, China.

About GAVRETO (pralsetinib)

GAVRETO (pralsetinib) is a once-daily oral targeted therapy approved by the NMPA of China for the treatment of adults with locally advanced or metastatic rearranged during transfection (RET) fusion-positive NSCLC after platinum-based chemotherapy.

GAVRETO has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with metastatic RET fusion-positive NSCLC as detected by an FDA approved test, adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant MTC, and adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).

GAVRETO is not approved for the treatment of any other indication in China by the NMPA or in the U.S. by the FDA, or for any indication in any other jurisdiction by any other health authority.

GAVRETO is designed to selectively and potently target oncogenic RET alterations, including secondary RET mutations predicted to drive resistance to treatment. In preclinical studies, GAVRETO inhibited RET at lower concentrations than other pharmacologically relevant kinases, including VEGFR2, FGFR2, and JAK2.

Blueprint Medicines and Roche are co-developing GAVRETO globally (excluding Greater China) for the treatment of patients with RET-altered NSCLC, thyroid cancer, and other solid tumors. Blueprint Medicines and Genentech, a member of the Roche Group, are co-commercializing GAVRETO in the U.S., and Roche has exclusive commercialization rights for GAVRETO outside of the U.S. (excluding greater China). The European Medicines Agency validated a marketing authorization application for GAVRETO for the treatment of RET fusion-positive NSCLC, and the review is ongoing. The FDA granted breakthrough therapy designation to GAVRETO for the treatment of RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy and for RET mutation-positive MTC that requires systemic treatment and for which there are no alternative treatments.

About Thyroid Cancer

Thyroid cancer is the most common endocrine malignancy with significantly increasing incidence in recent years. According to the data released by the National Cancer Center in 2019, the incidence of thyroid cancer ranked 4th among all malignant tumors in female in urban areas and 7th in o among all cancer types in China. There are about 90,000 new cases of thyroid cancer and about 6,800 deaths each year in China. Thyroid cancer is clinically divided into papillary cancer, follicular cancer, undifferentiated cancer, and medullary cancer and so on. The treatment and prognosis of different types of thyroid cancer vary according to the characteristics of the tumor.

RET fusions and mutations are key disease drivers in many cancer types (including NSCLC and several types of thyroid cancer). Approximately 10-20% of patients with papillary thyroid cancer (the most common type of thyroid cancer) carry RET fusions, and approximately 50-90% of patients with advanced MTC (approximately 2-5% of thyroid cancers) carry RET mutations. There is currently no effective approved standard treatment regimen for patients with RET-mutant MTC in China.

About CStone

CStone is a biopharmaceutical company focused on the development and commercialization of innovative tumor immunotherapy and precision medicines to meet the ardent medical needs of cancer patients in China and worldwide. Established at the end of 2015, CStone Pharmaceuticals has assembled a world-class management team with extensive experience in innovative drug development, clinical research, and commercialization. With a strategic emphasis on immuno-oncology combination therapies, the Company has built an oncology-focused pipeline of 14 drug candidates. Currently, two products have been approved by China NMPA and multiple late-stage candidates are at pivotal clinical trials or registration stages. CStone's vision is to become a world-renowned biopharmaceutical company leading the way to conquering cancer.