CStone Announces the NDA Approval of GAVRETO® (pralsetinib) for the Treatment of RET Fusion-Positive treatment-naïve (first-line) and pretreated Non-Small Cell Lung Cancer (NSCLC) in Hong Kong, China

GAVRETO is the first highly selective rearranged during transfection (RET) inhibitor approved in Hong Kong,China for the treatment of RET fusion-positive metastatic non-small cell lung cancer

GAVRETO is CStone's second therapy approved in Hong Kong,China

GAVRETO is CStone's ninth NDA approval in the Greater China region

SUZHOU,China,July 15,2022 -- 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 GAVRETO® (pralsetinib) has been approved in Hong Kong,China for the treatment of adult patients with rearranged during transfection (RET) fusion-positive metastatic non-small cell lung cancer (NSCLC).

GAVRETO 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 GAVRETO in Greater China,which encompasses Mainland China,Hong Kong,Macau and Taiwan.

Dr. Frank Jiang,Chief Executive Officer of CStone,said,"We are very glad about the NDA approval of GAVRETO in Hong Kong,which came only four months after its NDA acceptance. This came on the heels of the NDA approval of our first-in-class precision therapy AYVAKIT® (avapritinib) in this city. GAVRETO has already been approved in Mainland China,and we are very excited to bring forward this innovative therapy to more patients in the Greater China region. CStone is committed to providing high-quality innovative medicines for patients worldwide. Moving forward,we will continue our efforts to accelerate the development of innovative drugs to fulfill the unmet medical needs of more cancer patients."

The NDA approval of GAVRETO 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 GAVRETO 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 American Society of Clinical Oncology (ASCO) Annual Meeting in June 2021. As of a data cutoff date of November 6,2020,GAVRETO 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. 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 GAVRETO®(pralsetinib)

GAVRETOis a once-daily oral targeted therapy,approved by the National Medical Products Administration (NMPA) of China 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 thyroid cancer who requires systemic therapy and radioactive iodine-refractory (if radioactive iodine treatment is appropriate). GAVRETO has been approved in Hong Kong,China for the treatment of adult patients with RET fusion-positive metastatic NSCLC.

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.

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

GAVRETO 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 (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 nine NDA approvals for four drugs. Multiple late-stage drug candidates are now under pivotal clinical trials or registration. 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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