Avapritinib receives Phase III clinical trial approval for GIST in China

SUZHOU,China,Feb. 15,2019 -- CStone Pharmaceuticals ("CStone") today announced that the National Medical Products Administration (NMPA) recently approved a Phase III clinical trial in China for its partnered drug candidate avapritinib as a third-line treatment against KIT-driven gastrointestinal stromal tumors (GIST).

The study will be part of the global VOYAGER Phase III trial comparing avapritinib against the current standard of care regorafenib in GIST patients who have previously received imatinib and one or two additional tyrosine kinase inhibitors (TKIs). The study is designed to evaluate avapritinib's safety and efficacy,with progression-free survival as the primary efficacy endpoint.

GIST,which is classed as a rare disease,is a form of sarcoma usually found in the walls of the stomach or the small intestine,and is typically diagnosed between the ages of 50 and 80. The most common forms of GIST are linked to mutations that lead to over-activation of the KIT or PDGFRα tyrosine kinases,resulting in deregulated cell growth. Approximately 90% of GIST cases are linked to mutations of KIT or PDGFRα.

According to data from the NAVIGATOR Phase I clinical trial reported as of October 15,2018,avapritinib was administered to 109 fourth-line or later GIST patients at doses of 300mg or 400mg.

Within that population,1 patient achieved complete response and there were 21 partial response (ORR[1] of 20%); stable disease was reported in 72 patients (DCR[2] of 66%); 60% of patients had tumor reductions; and mDOR[3] was 7.3 months.

Of 23 third/fourth-line GIST patients not previously treated with regorafenib,78% experienced tumor reductions,while 6 achieved partial response (ORR of 26%),13 achieved stable disease (DCR of 83%),and the mDOR was 10.2 months.

In 56 patients with PDGFRα D842V-driven GIST,tumor reduction was observed in 98% of patients,with 5 complete response and 42 partial response (ORR of 84%). The 12-month DoR was 76.3%,and the 12-month progression free survival rate was 81.3%.

Dr. Frank Jiang,chairman and CEO of CStone,commented: "Avapritinib is a first-in-class precision medicine drug that has been awarded Breakthrough Therapy Designation by the U.S. FDA due to its outstanding clinical efficacy. Current available clinical data already demonstrated the drug's great potential for advanced GIST patients. CStone is delighted to be able to introduce this product to Chinese patients via our partnership with Blueprint Medicines,and we look forward to generating positive clinical data in China."

CStone's Chief Medical Officer Dr. Jason Yang noted: "Avapritinib is the only inhibitor of KIT and PDGFRα D842V mutant kinases under clinical development in China at present. We aim to advance the Phase III VOYAGER study for avapritinib rapidly to benefit Chinese patients with KIT-mutated GIST. We are also planning trials of avapritinib for the treatment of earlier lines of GIST and systemic mastocytosis. In addition,we will consider exploring the potential of combination therapy with CStone's IO backbone assets."

About avapritinib

Avapritinib is an orally available,potent and highly selective inhibitor of KIT and PDGFRα. Preclinical data have shown that avapritinib is active across a broad spectrum of KIT and PDGFRα mutations,including KIT D816V,PDGFRα D842V and KIT exon 17 mutations,for which there are limited or no effective treatment options. Blueprint Medicines is initially developing avapritinib,an investigational medicine,as a treatment for patients with advanced GIST and advanced systemic mastocytosis (ASM).

In June 2017,avapritinib received Breakthrough Therapy from the U.S. Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic GIST harboring the PDGFRα D842V mutation. Previously,the FDA awarded avapritinib orphan drug and fast-track designation. In addition,the molecule has also been granted orphan drug status by the European Commission.

At the American Society of Hematology (ASH) 2018 Annual Meeting,data from the Phase I EXPLORER clinical trial was published showing that avapritinib produced sustained clinical response in patients with ASM,and the therapeutic effect was found to deepen over time regardless of disease subtype,previous treatment,or initial dose.

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 Greater China.

About CStone

CStone Pharmaceuticals is a biopharma company focused on developing and commercializing innovative immuno-oncology and molecularly-targeted drugs to address unmet medical needs for cancer patients in China and worldwide. Since company inception three years ago,CStone has assembled a world-class management team that has a full spectrum of complementary skillsets from preclinical research to clinical development and commercialization. Through a dual source of innovation,comprised of internal research and external partnership,the company has built a rich oncology pipeline of 14 drug candidates with significant mono- and combination-therapy potential and synergies. Among CStone's portfolio,4 late-stage drug candidates are under or close to registrational study. CStone's business model has a clear focus on clinical research and development,while rapidly developing its commercial and manufacturing capabilities. The company has been backed by prestigious VC and PE funds via record-breaking Series A and B finance rounds that raised a combined total of USD 412 million. 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 biopharma company by bringing innovative and differentiated oncology therapies to cancer patients in China and worldwide.

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

About Blueprint Medicines

Blueprint Medicines is developing a new generation of targeted and potent kinase medicines to improve the lives of patients with genomically defined diseases. Its approach is rooted in a deep understanding of the genetic blueprint of cancer and other diseases driven by the abnormal activation of kinases. Blueprint Medicines is advancing multiple programs in clinical development for subsets of patients with gastrointestinal stromal tumors,hepatocellular carcinoma,systemic mastocytosis,non-small cell lung cancer,medullary thyroid cancer and other advanced solid tumors,as well as multiple programs in research and preclinical development. For more information,please visit www.blueprintmedicines.com.

[1] ORR,overall response rate

[2] DCR,disease control rate

[3] mDOR,median duration of response