CStone presents ARROW study data for GAVRETO® (pralsetinib) in Chinese patients with RET-mutant medullary thyroid cancer (MTC) for the first time in a late breaking oral abstract session at the 90th Annual Meeting of the American Thyroid Association 2021

Primary efficacy results showed GAVRETO had robust and durable anti-tumor activity in the Chinese patients with advanced or metastatic RET-mutant medullary thyroid cancer (MTC),with a confirmed objective response rate (ORR) of 73.1%. And the 9-month duration of response (DOR) rate was 100%

In April 2021,the National Medical Products Administration (NMPA) of China accepted the supplemental new drug (sNDA) application of GAVRETO with priority review designation for the treatment of patients with advanced or metastatic RET-mutant medullary thyroid cancer and with advanced or metastatic RET fusion-positive thyroid cancer

SUZHOU,China,Oct. 2,2021 -- CStone Pharmaceuticals ("CStone",HKEX: 2616),a leading biopharmaceutical company focused on researching,developing and commercializing innovative immuno-oncology therapies and precision medicines,today announced that the detailed registrational data of selective RET inhibitor GAVRETO® (pralsetinib) for the treatment of Chinese patients with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) in the ARROW study,a global phase 1/2 clinical study,has been presented during a late breaking oral abstract session at the 90th Annual Meeting of the American Thyroid Association (ATA) 2021. Primary efficacy results showed GAVRETO had broad and durable anti-tumor activity in the Chinese patients with advanced or metastatic RET-mutant MTC,consistent with the data previously reported in the global ARROW study. The safety profile was manageable,with no new safety signals detected.

Discovered by CStone's partner Blueprint Medicines,GAVRETO is the first selective RET inhibitor in China approved for the treatment of adults with local advanced or metastatic RET fusion-positive NSCLC after platinum-based chemotherapy. 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.

Session title: Friday Clinical Oral Abstracts Session

Date:00:00-1:00 am,October 2,2021(Beijing time)

Format: Oral Presentation

Title: Efficacy and safety of pralsetinib,a selective RET inhibitor,in Chinese patients with advanced RET-mutant medullary thyroid cancer (MTC)

Presentation number: Late Breaking Oral 3

Principal investigator: Professor Gao Ming,President of Tianjin Union Medical Center

Presenter: Professor Xiangqian Zheng,Tianjin Medical University Cancer Institute & Hospital

As of a data cutoff date of April 12,2021,a total of 28 patients with advanced RET-mutant MTC were enrolled in the China MTC registrational bridging cohort of the global ARROW study,and received a starting GAVRETO dose of 400 mg once daily. Tumor response was assessed by blinded independent central review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Efficacy: GAVRETO showed robust and durable anti-tumor activity in Chinese patients with advanced or metastatic RET-mutant MTC who require systemic therapy

The confirmed ORR of 26 RET-mutant MTC patients with measurable disease at baseline was 73.1%,including 3 with complete response (CR) and 16 with partial responses (PR); the disease control rate (DCR) reached 84.6%.

Responses were observed regardless of RET mutation genotype.

Among the 19 patients with confirmed response,the median DOR was not reached,and the 9-month DOR rate was 100%.

Calcitonin and carcinoembryonic antigen (CEA) levels were substantially reduced.

Safety: GAVRETO was well tolerated and had a generally manageable safety profile

GAVRETO was well-tolerated. The overall safety in Chinese patients was generally manageable,with no new safety signals detected.

"The incidence rate of thyroid cancer has increased over the past several decades. There are limited treatment options available for patients with RET-mutant MTC,and there is an unmet need for targeted therapies," said Professor Gao Ming,a Principal Investigator of the ARROW study,and President of Tianjin Union Medical Center. "The data from the ARROW study reported at this conference highlighted that GAVRETO had robust and durable anti-tumor activity and well-tolerated safety profile. These results may be a promising advancement for patients with RET-mutant advanced MTC."

"We are encouraged that GAVRETO has shown durable efficacy and a well-tolerated safety profile in Chinese patients with RET-mutant MTC," said Dr. Jason Yang,Chief Medical Officer of CStone. "The NMPA granted breakthrough therapy designation to GAVRETO for the treatment of RET-mutant advanced MTC that requires systemic treatment. In April 2021,CStone submitted a supplemental NDA (sNDA) for GAVRETO to the NMPA with priority review for the treatment of patients with RET-mutant MTC and RET fusion-positive thyroid cancer. We hope the sNDA will be approved as early as possible to benefit Chinese patients with RET-altered thyroid cancer."

About the ARROW Study

The ARROW study is a global phase 1/2 clinical study designed to evaluate the safety,tolerability and efficacy of GAVRETO in patients with RET fusion-positive NSCLC,RET-mutant MTC and other advanced solid tumors with RET fusions.

Results from the ARROW trial in global patients with RET-altered thyroid cancer were published in The Lancet Diabetes and Endocrinology in August 2021. As of a data cutoff date of May 22,2020,GAVRETO showed robust and durable anti-tumor activity in patients with RET-altered thyroid cancer who received a starting dose of 400 mg once daily. In 55 patients with RET-mutant MTC previously treated with cabozantinib or vandetanib,the ORR was 60 percent (95% CI: 46%,73%) and the median DOR was not reached (95% CI: 15.1 months,not estimable). In 21 systemic treatment-naïve patients with RET-mutant MTC,the ORR was 71 percent (95% CI: 48%,89%) and the median DOR was not reached (95% CI: not estimable,not estimable). In nine patients with RET fusion-positive thyroid cancer,the ORR was 89 percent (95% CI: 52%,100%) and the median DOR was not reached (95% CI: not estimable,not estimable). In 142 patients with RET-altered thyroid cancer,the most common adverse events were anemia,musculoskeletal pain,constipation,increased aspartate aminotransferase and hypertension.

About Thyroid Cancer

Thyroid cancer is the most common endocrine malignancy with significantly increasing incidence in recent years. According to the latest estimates on the global burden of cancer released by International Agency for Research on Cancer (IARC),in 2020,there were about 220,000 new cases of thyroid cancer and the number of new cases in females reached about 170,000 in China[1]. The incidence of thyroid cancer ranked 4th among all malignant tumors in females in urban areas.

Thyroid cancer is clinically divided into multiple subtypes,including papillary,follicular,undifferentiated and medullary. 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 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 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.

In April 2021,the NMPA of China accepted the supplemental new drug application of GAVRETO with priority review designation for the treatment of patients with advanced or metastatic MTC who require systemic therapy,and advanced or metastatic RET fusion-positive thyroid cancers who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine 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.

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

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). In September 2021,the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommended the approval of GAVRETO as a monotherapy for the treatment of adult patients with RET fusion-positive advanced NSCLC not previously treated with a RET inhibitor. 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 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 three drug approvals in Greater China,including two in Mainland China and one in Taiwan. 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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[1] https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf