CStone announces GAVRETO® (pralsetinib) sNDA approval by China NMPA for first-line treatment of patients with locally advanced or metastatic RET fusion-positive non-small cell lung cancer

The approval for the first-line treatment of RET fusion-positive non-small cell lung cancer marks the third indication of GAVRETO in Mainland China,and the eleventh new drug application approval that CStone has obtained in Greater China overall.

In the ARROW study,GAVRETO had demonstrated robust and durable anti-tumor activity and a generally well-tolerated safety profile,regardless of prior treatment,in Chinese patients with locally advanced or metastatic RET fusion-positive non-small cell lung cancer.

SUZHOU,China,June 26,2023 --CStone Pharmaceuticals ("CStone",HKEX: 2616),a leading biopharmaceutical company focused on research,development,and commercialization of innovative immuno-oncology therapies and precision medicines,today announced that the National Medical Products Administration (NMPA) of China has approved the supplemental new drug application (sNDA) of GAVRETO® (pralsetinib),a selective rearranged during transfection (RET) inhibitor,for the first-line treatment of adults with locally advanced or metastatic RET fusion-positive non-small cell lung cancer (NSCLC).

GAVRETO was 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.

GAVRETO was the first targetedRET inhibitor approved by China NMPA,and the therapy received initial approval in March 2021 for the treatment of locally advanced or metastaticRET fusion-positive NSCLC after platinum-based chemotherapy. It was also granted approval by the NMPA as the first selective RET inhibitor for the treatment of advanced RET-altered thyroid cancer in March 2022. Since being marketed in Greater China,GAVRETO is accessible in approximately 200 hospitals and DTP pharmacies and is covered by commercial insurance programs in 130 cities. GAVRETO has been included in various clinical guidelines and consensus based on its strong clinical profile.

Dr. Jason Yang,CEO of CStone,said,"We are delighted to see the approval of GAVRETO for the first-line treatment of RET-fusion positive NSCLC in China,broadening its indications to cover both first-line and second-line settings,as well as first-line RET-altered thyroid cancer. GAVRETO has treated thousands of patients since being marketed in China. As a biopharmaceutical company specialized in precision medicines and immunotherapies,CStone is committed to bringing more first-in-class and best-in-class therapies to patients worldwide."

Professor Yi-Long Wu of Guangdong Provincial People's Hospital,the Principal Investigator of the ARROW study in China,"Being the first RET inhibitor approved in China,GAVRETO has been proven to be an effective precision therapy. In theARROW study,GAVRETO showed robust anti-tumor activity in Chinese patients with RET fusion-positive NSCLC regardless of prior treatments with a manageable safety profile and no new safety signals.This sNDA approval of GAVRETO is important to help improve clinical outcomes forChinese RET fusion-positive NSCLC patients."

This sNDA approval is based on the results from the ARROW study,which 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 medullary thyroid cancer (MTC) and other advanced solid tumors with RET alterations.

Mostly recently in June,the updated efficacy and safety data from the ARROW study of GAVRETO in Chinese patients with RET fusion-positive NSCLC has been published on Cancer,a world-renowned oncology journal,which represents one additional recognition from the international academic community since the prior presentation at the 2022 European Society for Medical Oncology Asia Congress (ESMO Asia). The data[1] showed that GAVRETO had robust and durable anti-tumor activity and a manageable safety profile in Chinese patients with locally advanced or metastatic RET fusion-positive NSCLC.

As of the data cut-off date (March 4,2022),a total of 68 patients with advanced RET fusion-positive NSCLC were enrolled at 10 sites in China and received a starting GAVRETO dose of 400 mg once daily. Among these patients,37 received prior platinum-based chemotherapy and 31 received no prior systemic treatment. Treatment response was assessed by Blinded Independent Central Review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Efficacy: Durable and long-term clinical benefit of GAVRETO was observed in both treatment-naïve and previously treated Chinese patients with advanced RET fusion-positive NSCLC. The response rate in treatment-naïve patients was higher than the previously treated patient population.

For patients who had previously received platinum-based chemotherapy (patients with measurable disease at baseline,n=33),the confirmed overall response rate (ORR) was 66.7%,including 1 complete response (CR) and 21 partial responses (PR). The disease control rate (DCR) reached 93.9%.

For patients who had not received prior systemic treatment (patients with measurable disease at baseline,n=30),the confirmed ORR was 83.3%,including 2 CRs and 23 PRs. The DCR was 86.7%.

Long-term survival benefit was observed. The median overall survival (OS) was not reached.

Safety: GAVRETO had a generally manageable safety profile in Chinese patients,with no new safety signals observed.

[1] Zhou Q,et al. Efficacy and safety of pralsetinib in patients with advanced RET fusion-positive non–small cell lung cancer. Cancer. 2023 Jun 6. doi: 10.1002/cncr.34897.

About GAVRETO®(pralsetinib)

GAVRETO is a once-daily oral targeted therapy approved by the NMPA of China for the treatment of adults with locally advanced or metastatic RET fusion-positive NSCLC,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,and in Taiwan,China for the treatment of adult patients with locally advanced or metastatic RET fusion-positive NSCLC,advanced or metastatic RET-mutant MTC who require systemic therapy,and 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 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 duration of response (DOR). Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials. The European Commission 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.

About CStone

CStone (HKEX: 2616) is a biopharmaceutical company focused on research,and commercialization of 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 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 eleven NDA approvals for its four drugs. Multiple late-stage drug candidates are now under pivotal clinical trials or registration. CStone's vision is to bring innovative oncology therapies to cancer patients worldwide.

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

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