CStone announces enrollment target reached in the global Phase III VOYAGER trial of avapritinib in Chinese patients with third-line GIST

CStone Pharmaceuticals ("CStone" or the "Company", HKEX: 2616) today announced that the on-going, global Phase III VOYAGER clinical trial of avapritinib, an investigational drug discovered by CStone's partner, Blueprint Medicines, has completed target patient enrollment in China. In addition, the VOYAGER trial's enrollment target has been reached globally. The study was designed to evaluate the safety and efficacy of avapritinib as a third- or fourth-line treatment for patients with advanced gastrointestinal stromal tumors (GIST), in comparison with that of regorafenib, the current standard-of-care treatment for third-line GIST. On July 10, 2019, CStone announced the dosing of the first patient in China for the VOYAGER trial.

Blueprint Medicines expects to report top-line VOYAGER trial data in the second quarter of 2020. In August 2019, the U.S. Food & Drug Administration (FDA) accepted Blueprint Medicines' New Drug Application (NDA) for avapritinib for the treatment of adult patients with PDGFRA Exon 18 mutant GIST, regardless of prior therapy, and fourth-line GIST. Subject to an initial approval of avapritinib, Blueprint Medicines plans to submit a supplemental NDA to the U.S. FDA for avapritinib for third-line GIST in the second half of 2020. CStone plans to submit an NDA for the treatment of third-line GIST to the China National Medical Products Administration (NMPA) in the second half of 2020.

GIST is the most common mesenchymal tumor of the GI tract, and it is most prevalent in patients aged 50 to 80. Around 90% of all GIST cases are associated with dysregulated cell growth due to mutations in KIT and PDGFRA tyrosine kinases. Existing data on regorafenib, the current standard third-line GIST treatment, shows a median progression-free survival of 4.8 months and an objective response rate (ORR) of only about 5%. There is currently no approved treatment for GIST patients who have failed third-line treatment. Thus, there are high unmet clinical needs in patients with third-line and later GIST.

Avapritinib is an investigational, orally available, potent and highly selective inhibitor of KIT and PDGFRA. Clinical data on avapritinib have demonstrated encouraging anti-tumor activity and benign tolerability in patients with PDGFRA Exon 18 mutants (primarily includes patients with the D842V mutation) and fourth-line GIST, two patient populations currently lacking effective therapies.

Data from the on-going Phase I NAVIGATOR trial were presented in November 2019 at the Connective Tissue Oncology Society Annual Meeting. As of the data cutoff date of November 16, 2018, these results showed:

• An ORR of 86% (one response pending confirmation) in 43 response-evaluable patients with PDGFRA Exon 18 mutant GIST (including 38 patients with PDGFRα D842V-mutant GIST), and the median duration of response (DOR) was not reached.
• An ORR of 22% (one response pending confirmation) and a median DOR of 10.2 months in 111 response-evaluable patients with fourth-line GIST.
• Avapritinib was generally well-tolerated, and most adverse events were Grade 1 or 2 as assessed by investigators.

"We are pleased that in China, the global Phase III VOYAGER trial has completed its enrollment target sooner than planned, and this rapid progress reaffirms the urgent clinical needs of GIST patients in China," said Dr. Frank Jiang, Chairman and CEO of CStone. "With the appointment of Ms. Shirley Zhao, a seasoned pharmaceutical executive who has led the successful launches of numerous major brands, to the position of General Manager for Greater China and Head of Commercial, we are more confident than ever in our ability to accelerate CStone's transition toward a commercial-stage company and to potentially bring avapritinib and other key assets to the China market."

CStone's Chief Medical Officer, Dr. Jason Yang, noted: "GIST is a rare disease, and completing target enrollment in China in less than 4 months is a testament to the effective collaborations among CStone, investigators, and business partners. Currently available data on this highly selective inhibitor of KIT and PDGFRA mutant kinases has already demonstrated its clinical potential. At the same time, we are also conducting a Phase I/II bridging study of avapritinib in patients with advanced GIST in China."

About Avapritinib

Avapritinib is an investigational, oral precision therapy that selectively and potently inhibits KIT and PDGFRA mutant kinases. It is a type 1 inhibitor designed to target the active kinase conformation; all oncogenic kinases signal via this conformation. Avapritinib has demonstrated broad inhibition of KIT and PDGFRA mutations associated with GIST, including potent activity against activation loop mutations that are associated with resistance to currently approved therapies.

Blueprint Medicines is initially developing avapritinib for the treatment of advanced GIST, advanced systemic mastocytosis (SM), and indolent and smoldering SM. The U.S. FDA has granted Breakthrough Therapy Designation to avapritinib for two indications: one for the treatment of unresectable or metastatic GIST harboring the PDGFRA D842V mutation and one for the treatment of advanced SM, including the subtypes of aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of avapritinib and certain other drug candidates in Mainland China, Hong Kong, S.A.R., China, Macau, S.A.R., China and Taiwan, China. Blueprint Medicines retains development and commercial rights for avapritinib in the rest of the world.

About CStone

CStone Pharmaceuticals (HKEX:2616) is a biopharmaceutical company focused on 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, 5 late-stage candidates are at pivotal trials. With an experienced team, a rich pipeline, a robust clinical development-driven business model and substantial funding, CStone's vision is to become globally recognized as a leading Chinese biopharmaceutical company by bringing innovative oncology therapies to cancer patients worldwide.

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