CStone Pharmaceuticals Announces NMPA Acceptance and Priority Review of New Drug Application for Pralsetinib in RET Fusion-Positive NSCLC

CStone Pharmaceuticals (Suzhou) Co., Ltd. (hereinafter referred to as“CStone Pharmaceuticals” (HKEX stock code: 2616) announced,ChinaNational Medical Products Administration (NMPA) has accepted the applicationCStone Pharmaceuticals' Pralsetinib Capsules (Pralsetinib Capsules (hereinafter referred to as “pralsetinib”) As a nation1.1Novel-like drugMarketing Authorization Applicationand included in the priority review,For the treatment ofPlatinum-based chemotherapy-treatedRET fusion-positiveNon-Small Cell Lung Cancer（NSCLC) patients.Pralsetinibby CStone Pharmaceuticals' strategic partnerBlueprint Medicines Corporationa developedOral (once daily),PotentandHighly Selective Targeting of OncogenicityInvestigational drugs for RET alterations (including predictable resistance mutations).

In the registration bridging trial currently being conducted by CStone Pharmaceuticals, pralsetinibFollowing platinum-based chemotherapySuperior and Durable Antitumor Activity in Chinese Patients with RET Fusion-Positive NSCLC, andGood safety and tolerability profile, this result is consistent withPreviouslyThe data results reported in the global patient population of the ARROW study were consistent.FromJulyGlobalI/IIPhaseARROWPivotalityTrialPublication of Study Results from Chinese Patients to SubmissionThe NDA review took only two months. According to overseas media reports, on September 4, pralsetinib was just approved by the FDA for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is RET fusion-positive. The FDA’s approval of pralsetinib was primarily based on globalPhase I/IIARROWCriticalityTrialResearch Data.

Professor Wu Yilong from Guangdong Provincial People's Hospital, the principal investigator of the ARROW study, stated: "In the field of precision therapy for lung cancer, the development targeting RET represents another major breakthrough following targets such as EGFR, ALK, ROS1, and NTRK. Currently, no selective RET inhibitors have been approved in China. There remains a significant unmet clinical need for patients with RET fusion-positive non-small cell lung cancer (NSCLC). The results of pralsetinib in global trials and in Chinese NSCLC patients give us great expectations for its market launch in China and the benefits it will bring to patients."

Dr. Jiang Ningjun, Chairman and Chief Executive Officer of CStone Pharmaceuticals, stated, “We are pleased to see that the National Medical Products Administration (NMPA) has accepted the marketing application for pralsetinib for the treatment of RET fusion-positive non-small cell lung cancer (NSCLC) after platinum-based chemotherapy and included it in the priority review program. This marks the third new drug marketing application submitted by CStone Pharmaceuticals globally this year, and the second submitted in mainland China, fully demonstrating that CStone Pharmaceuticals is accelerating its transition toward a commercialization-driven strategy. We look forward to the early launch of pralsetinib in China, bringing new therapeutic hope to the vast number of RET fusion-positive NSCLC patients in the country.”

Dr. Yang Jianxin, Chief Medical Officer of CStone Pharmaceuticals, stated, “We are pleased to see that pralsetinib has demonstrated rapid and durable antitumor activity, along with a favorable safety and tolerability profile, in clinical trials. Notably, it took only two years from the time we entered into a collaboration with Blueprint Medicines Corporation to the successful submission of the marketing application for pralsetinib in China. We will continue to fully advance the development of pralsetinib in China, more broadly evaluating its efficacy in patients with RET fusion-positive non-small cell lung cancer (NSCLC) who have not received prior platinum-based chemotherapy, as well as in those with medullary thyroid cancer and other solid tumors, so as to meet the urgent clinical needs of these cancer patients at the earliest possible time.”

Pursuant to the exclusive collaboration and license agreement entered into between CStone Pharmaceuticals and Blueprint Medicines Corporation, CStone Pharmaceuticals holds the rights for clinical development and commercialization of pralsetinib as monotherapy or in combination therapy within the Greater China region (including Mainland China, Hong Kong, Macau, and Taiwan). Outside of Greater China, Blueprint Medicines Corporation has established a global collaboration with Roche and Genentech (a member of the Roche Group) for pralsetinib. Through this collaboration, Roche will obtain the exclusive global license for pralsetinib in markets outside of Greater China (including Mainland China, Hong Kong, Macau, and Taiwan) and the United States, as well as the rights to co-develop and co-commercialize pralsetinib with Blueprint Medicines in the United States.

The ARROW study is a global clinical trial designed to evaluate the safety, tolerability, and efficacy of pralsetinib in patients with RET fusion-positive non-small cell lung cancer (NSCLC), thyroid cancer, and other advanced solid tumors harboring RET alterations. According to previously released information from CStone Pharmaceuticals, the first patient with platinum-pretreated, RET fusion-positive NSCLC was dosed at Chinese research centers in August 2019, and enrollment of the final patient was completed in December of the same year. CStone plans to present data on Chinese patients with RET fusion-positive NSCLC from the ARROW study at upcoming academic conferences.

Pralsetinib is an investigational, oral (once-daily), potent, and highly selective targeted therapy for oncogenic RET alterations. Blueprint Medicines Corporation is conducting the clinical development of pralsetinib for the treatment of patients with RET-altered non-small cell lung cancer (NSCLC), thyroid cancer, and other solid tumors. The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to pralsetinib for the treatment of RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy, and for the treatment of patients with RET-mutant positive medullary thyroid cancer who require systemic therapy and have no alternative treatment options. In May 2020, Blueprint Medicines Corporation announced that its marketing applications for pralsetinib for the treatment of locally advanced or metastatic RET fusion-positive NSCLC submitted in the United States and the European Union had been formally accepted and validated by the U.S. FDA and the European Medicines Agency (EMA), respectively.

Pralsetinib was designed by the research team at Blueprint Medicines Corporation based on its proprietary compound library. In preclinical studies, pralsetinib consistently demonstrated subnanomolar potency against the most common RET gene fusions, activating mutations, and predicted resistance mutations. Notably, pralsetinib exhibited an 80-fold higher selectivity for RET compared with VEGFR2. Furthermore, pralsetinib showed significantly improved RET selectivity relative to approved multikinase inhibitors. By inhibiting both primary and secondary mutations, pralsetinib is expected to overcome and prevent the development of clinical resistance. This therapy is anticipated to achieve durable clinical responses in patients harboring various RET alterations, with a favorable safety profile.