CStone Pharmaceuticals and Blueprint Medicines Announce Exclusive Collaboration and License Agreement to Advance Avapritinib, BLU-554, and BLU-667 in Greater China

VCBeat (WeChat ID: vcbeat) has learned that CStone Pharmaceuticals and Blueprint Medicines (NASDAQ: BPMC) announced on June 4 that they had entered into an exclusive collaboration and license agreement to advance the clinical development and commercialization of avapritinib, BLU-554, and BLU-667, as monotherapies or in combination regimens, in mainland China and the Hong Kong, Macau, and Taiwan regions.

Blueprint Medicines is a leading biopharmaceutical company focused on the development of targeted kinase therapies for diseases with specific genetic profiles. CStone Pharmaceuticals is a clinical-stage, innovation-driven biopharmaceutical company dedicated to oncology drug development and combination therapy research centered on tumor immunotherapy, boasting a robust product pipeline. The management team at CStone Pharmaceuticals comprises senior executives from top-tier global pharmaceutical companies, having successfully established core competencies in clinical development and translational medicine. CStone Pharmaceuticals completed its $150 million Series A financing in July 2016 and its $260 million Series B financing in May 2018, both backed by renowned venture capital and private equity firms.

Avapritinib, BLU-554, and BLU-667 are investigational kinase drugs with high potency and selectivity developed by Blueprint Medicines, all of which have demonstrated clinical proof-of-concept in cancer patients with specific genetic profiles. Blueprint Medicines will retain all rights to the relevant products in all other countries worldwide.

This collaboration grants CStone Pharmaceuticals exclusive rights to three clinical-stage targeted therapies in Greater China, further strengthening its product portfolio. Blueprint Medicines expands its global footprint by addressing the significant unmet patient needs in China. Leveraging its advantages in drug registration and local resource networks, CStone Pharmaceuticals will drive the clinical development and commercialization of the licensed products as monotherapies and in combination regimens across Greater China.

In addition, the two companies plan to initiate a proof-of-concept clinical trial in China to evaluate the efficacy of BLU-554 in combination with CS1001 for the treatment of patients with first-line hepatocellular carcinoma. CS1001 is an investigational anti-programmed death-ligand 1 (PD-L1) immunotherapy developed by CStone Pharmaceuticals.

“CStone Pharmaceuticals was founded by seasoned executives with extensive global and local development experience, and boasts a growing and complementary portfolio of oncology products, making it our ideal partner in China,” said Jeff Albers, Chief Executive Officer of Blueprint Medicines. “In recent years, with the reform of China’s drug regulatory system and the emergence of innovative pharmaceutical companies represented by CStone Pharmaceuticals, we believe this forward-looking collaboration will help enhance our ability to meet the needs of patients in Greater China, while also supporting the global development of avapritinib, BLU-554, and BLU-667. More than half of new hepatocellular carcinoma cases worldwide occur in China, and we are delighted to initiate the clinical development of BLU-554 in China.”

“We are delighted to partner with Blueprint Medicines, an industry leader focused on the development of highly selective kinase inhibitors. This collaboration is expected to mark the first step in a long-term strategic partnership between the two companies,” said Dr. Jiang Ningjun, CEO of CStone Pharmaceuticals. “The current clinical data are very encouraging. We believe that Blueprint Medicines’ targeted therapies—avapritinib, BLU-554, and BLU-667—have the potential to significantly transform the treatment landscape for gastrointestinal stromal tumors, hepatocellular carcinoma, non-small cell lung cancer, and other cancers in China. Furthermore, CStone Pharmaceuticals’ robust pipeline of investigational oncology drugs will enable us to explore various combination therapies, ultimately benefiting patients worldwide.”

Under the terms of the agreement, Blueprint Medicines will receive a $40 million upfront cash payment from CStone Pharmaceuticals and is eligible to receive approximately $346 million in milestone payments, including $118.5 million for development and regulatory approval milestones and $227.5 million for sales performance milestones. In addition, Blueprint Medicines will be entitled to receive tiered royalties from CStone Pharmaceuticals based on annual net sales of the relevant products in Greater China.

Under the terms of the agreement, CStone Pharmaceuticals will be responsible for conducting clinical development and commercialization of the licensed products in Greater China. Meanwhile, CStone Pharmaceuticals will bear the development costs for the licensed products in Greater China, while the clinical development costs for BLU-554 combination therapy in Greater China will be shared by both parties.

About Avapritinib 

Avapritinib is an oral, highly potent and selective inhibitor of KIT and PDGFRα. There is currently a lack of effective treatments for various diseases harboring KIT and PDGFRα mutations (including KIT D816V, PDGFRα D842V, and KIT exon 17 mutations); avapritinib has demonstrated preclinical activity against these mutations. Blueprint Medicines is currently developing avapritinib for the treatment of advanced gastrointestinal stromal tumors (GIST) and advanced systemic mastocytosis.

In June 2017, avapritinib was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring the PDGFRα D842V mutation. Previously, avapritinib had been granted Orphan Drug Designation and Fast Track Designation by the FDA. Additionally, avapritinib received Orphan Drug Designation from the European Commission. In May 2018, Blueprint Medicines announced that it would submit a New Drug Application (NDA) to the FDA in the first half of 2019 for avapritinib for the treatment of PDGFRα D842V-driven GIST.

About BLU-554

BLU-554 is an oral, highly potent, and irreversible FGFR4 inhibitor. Designed by Blueprint Medicines, BLU-554 inhibits FGFR4 with exceptional specificity, thereby avoiding effects on FGFR1, FGFR2, and FGFR3. Blueprint Medicines is developing BLU-554 for the treatment of hepatocellular carcinoma driven by FGFR4 activation, a patient population estimated to account for approximately 30% of all hepatocellular carcinoma cases. BLU-554 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration.

About BLU-667 

BLU-667 is an oral, highly potent, and highly selective inhibitor targeting RET fusions, mutations, and anticipated resistance mutations. Blueprint Medicines is developing BLU-667 for the treatment of non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC), and other solid tumors with RET gene alterations. BLU-667 was discovered by Blueprint Medicines’ research team using its proprietary compound library. BLU-667 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA).

About CS1001 

CS1001 is an investigational anti-PD-L1 monoclonal antibody developed by CStone Pharmaceuticals. CS1001 is generated using the OMT transgenic animal platform licensed from Ligand Pharmaceuticals (USA), a platform that enables one-stop production of fully human antibodies. As a full-length, fully human anti-PD-L1 monoclonal antibody, CS1001 closely resembles the body’s natural immunoglobulin G4 (IgG4). It reduces the risk of immunogenicity and associated toxicity in patients, offering potential unique advantages over comparable agents.

Since October 2017, CStone Pharmaceuticals has conducted its first-in-human Phase I clinical study (CS1001-101), which aims to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of CS1001 in Chinese patients with advanced tumors. The Phase Ia clinical study (dose escalation) was completed in May 2018, and patient enrollment for the Phase Ib clinical study (dose expansion) has recently been initiated. Meanwhile, several pivotal clinical studies targeting cancer types with high prevalence in China are underway.