Suzhou, China, March 18, 2022 — CStone Pharmaceuticals ("CStone", HKEX: 2616), a leading biopharmaceutical company focused on research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, announced today that the new drug application (NDA) for pralsetinib for the treatment of rearranged during transfection (RET) fusion-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) has been accepted in Hong Kong, China.

Pralsetinib is a potent and selective RET inhibitor discovered by CStone’s partner Blueprint Medicines. CStone has an exclusive collaboration and license agreement with Blueprint Medicines for the development and commercialization of pralsetinib in Greater China, which encompasses Mainland China, Hong Kong, Macau and Taiwan.

Dr. Jason Yang, Chief Medical Officer of CStone, said, "We are very glad that the NDA of another innovative precision medicine, pralsetinib, is accepted for the treatment of advanced RET fusion-positive NSCLC, after AYVAKIT^® (avapritinib) was approved for the treatment of unresectable or metastatic PDGFRA D842V mutant gastrointestinal stromal tumors in Hong Kong, China in December 2021. In the global phase 1/2 ARROW study, pralsetinib demonstrated durable clinical benefits and a generally well-tolerated safety profile in patients with RET fusion-positive locally advanced or metastatic NSCLC. We look forward to the potential approval of pralsetinib in Hong Kong, China to help benefit more patients as quickly as possible."

The NDA acceptance of pralsetinib in Hong Kong, China is based on results from the global phase 1/2 ARROW study. This trial is designed to evaluate the safety, tolerability, and efficacy of pralsetinib in patients with RET-fusion positive NSCLC, RET-mutant medullary thyroid cancer (MTC), and other advanced solid tumors with RET fusions.

Results from the ARROW trial in global patients with advanced RET fusion-positive NSCLC were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting in June 2021. As of a date cutoff date of November 6, 2020, pralsetinib showed durable clinical benefits in patients with RET fusion-positive NSCLC who had measurable disease at baseline and received a starting dose of 400 mg once daily.

• In 68 treatment-naïve patients, the overall response rate (ORR) was 79 percent (95% CI: 68%, 88%). The complete response (CR) rate was 6 percent, 10 percent of patients had complete regression of target tumors, and 74 percent of patients had a partial response (PR). The median duration of response (DOR) was not reached (95% CI: 9.0 months, not reached).
• In 126 patients who previously received platinum-based chemotherapy, the ORR was 62 percent (95% CI: 53%, 70%). The CR rate was 4 percent, 12 percent of patients had complete regression of target tumors, and 58 percent of patients had a PR. The median DOR was 22.3 months (95% CI: 15.1 months, not reached).
• As of the data cutoff date, a total of 471 patients were enrolled across tumor types with a pralsetinib dose starting at 400 mg once daily. The most common treatment-related adverse events (AEs) reported by investigators were neutropenia, increased aspartate aminotransferase, anemia, decreased white blood cell count, increased alanine aminotransferase, hypertension, constipation and asthenia.

About RET fusion-positive NSCLC

In recent years, China has had rising lung cancer incidence. According to the latest estimates on the global burden of cancer released by International Agency for Research on Cancer (IARC), in 2020, an estimated 0.82 million new lung cancer cases and 0.71 million new lung cancer deaths occurred in China. Among all Chinese cancer patients, lung cancer is the leading cause of cancer-related deaths. NSCLC is the most common type of lung cancer.

In lung cancer, there are a number of somatic mutations, including EGFR, ALK, and ROS1, that can be targeted with approved therapies. RET fusions account for 1-2% of NSCLC patients, the majority of whom are non-smokers.

About Pralsetinib

Pralsetinib is a once-daily oral targeted therapy approved by the NMPA of China under the brand name GAVRETO® for the treatment of adults with locally advanced or metastatic rearranged during transfection (RET) fusion-positive NSCLC after platinum-based chemotherapy, and for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant MTC who requires systemic therapy, and adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive TC who requires systemic therapy and radioactive iodine-refractory (if radioactive iodine treatment is appropriate).

GAVRETO is approved by the U.S. Food and Drug Administration (FDA) for the treatment of three indications: 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). These indications are approved under accelerated approval based on ORR and DOR. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

The European Commission (EC) has granted conditional marketing authorization for GAVRETO as a monotherapy for the treatment of adult patients with RET fusion-positive advanced NSCLC not previously treated with a RET inhibitor.

Pralsetinib is not approved for the treatment of any other indication in China, U.S. or Europe.

Pralsetinib is designed to selectively and potently target oncogenic RET alterations, including secondary RET mutations predicted to drive resistance to treatment. In preclinical studies, pralsetinib 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). 

About CStone

CStone Pharmaceuticals (HKEX: 2616) is a biopharmaceutical company focused on researching, developing, and commercializing innovative immuno-oncology and precision medicines to address the unmet medical needs of cancer patients in China and worldwide. Established in 2015, CStone has assembled a world-class management team with extensive experience in innovative drug development, clinical research, and commercialization. The company has built an oncology-focused pipeline of 15 drug candidates with a strategic emphasis on immuno-oncology combination therapies. Currently, CStone has received 7 NDA approvals for its 4 drugs. CStone's vision is to become globally recognized as a world-renowned biopharmaceutical company by bringing innovative oncology therapies to cancer patients worldwide.

For more information about CStone, please visit: www.cstonepharma.com.

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