SUZHOU, China; November 10th, 2020--CStone Pharmaceuticals (“CStone”; HKEX: 2616) announced that it has submitted a New Drug Application (NDA) for ivosidenib to the Health Sciences Authority (HSA) of Singapore, for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (R/R AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation. Ivosidenib is a first-in-class, oral, highly selective and potent IDH1 inhibitor developed by Agios Pharmaceuticals, a CStone partner. It has been approved by the US FDA since July 2018 for the treatment of acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test in adult patients with R/R AML, and since May 2019 for the treatment of adult patients with newly diagnosed AML who are ≥75 years old or who have comorbidities that preclude use of intensive chemotherapy (IC).

AML , marked by rapid disease progression, is the most common acute leukemia found in adults and its patients are typically older . It affects adults with approximately 20,000 new cases in the US each year and the 5-year survival rate is approximately 29%. In Singapore, the annual incidence is increasing. Typically, older patients and R/R AML patients have a poor prognosis, and approximately 6 to 10% of AML patients carry IDH1 mutations.

The current standard of care treatment for newly diagnosed AML patients mainly includes intensive chemotherapy for induction therapy, approximately 35% to 40% of treated young patients achieve complete remission, while only about 10% of elderly patients achieve survival of 3 years or longer.The majority of AML patients develop acquired resistance to treatment or eventually relapse, making R/R AML extremely difficult for follow-up clinical treatment in the absence of a global care treatment standard. With the emergence of DNA sequencing technology, the detection of genetic mutations has presented new opportunities and challenges in AML treatment.

Ivosidenib, an oral, targeted inhibitor of the IDH1 enzyme, is globally the first and only FDA-approved therapy for patients with R/R AML and an IDH1 mutation. Ivosidenib was developed by Agios Pharmaceuticals. In 2018, CStone and Agios announced an exclusive collaboration and license agreement stating that CStone is responsible for the clinical development and commercialization of ivosidenib in the Greater China Region. In March 2020, CStone and Agios revised the agreement to expand its clinical development and commercialization area from the Greater China Region to Singapore.

Dr Frank Jiang, Chairman and CEO of CStone, commented: “We are very pleased to see that the company has successfully submitted an NDA for ivosidenib in Singapore for the treatment of R/R AML with an IDH1 mutation. This is the first time CStone has submitted an NDA outside Greater China, which is of great significance to the company's global commercialization process. We will continue to work to benefit more cancer patients from innovative anti-tumor therapies.”

Dr Jason Yang, Chief Medical Officer of CStone, noted: “The treatment of AML is facing urgent drug development needs, especially for IDH1-mutated R/R AML patients who lack effective drugs. At present, ivosidenib is the only FDA-approved therapy targeting IDH1 mutation for patients with R/R AML. We earnestly hope that ivosidenib will be approved in Singapore soon, thus benefiting these patients.”

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About TIBSOVO^®（Ivosidenib）

TIBSOVO^® was developed by Agios Pharmaceuticals (hereinafter referred to as "Agios"), a partner of CStone Pharmaceuticals, and received its first marketing approval in the US in 2018 for the treatment of R/R AML with susceptible IDH1 gene mutations. In 2019, the drug approval was extended by the US FDA to include the treatment of newly-diagnosed AML adult patients ≥75 years of age or AML patients who have comorbidities that preclude the use of intensive IC. In addition, the US FDA has granted Breakthrough Therapy Designation for TIBSOVO^® in combination with azacytidine for this supplemental indication."

The efficacy of TIBSOVO^® was evaluated in 174 adult patients with R/R AML with an IDH1 mutation. TIBSOVO^® was administered orally at a starting dose of 500 mg daily until disease progression, development of unacceptable toxicity, or undergoing HSCT. Data from the marketing application for TIBSOVO^® in the US show that TIBSOVO^® monotherapy for R/R AML patients with IDH1 mutations, resulted in a complete remission (CR) or complete remission with partial hematological improvement (CR+CRh) rate of 32.8% (57/174) (95% CI: 25.8, 40.3), and the median duration of CR + CRh was 8.2 (range 5.6–12) months .

The safety profile of TIBSOVO^® was evaluated in 179 patients with R/R AML with an IDH1 mutation who received an oral dose of 500 mg daily. The median duration of exposure to TIBSOVO^® was 3.9 (range 0.1–39.5) months. In the clinical trial, 19% (34/179) of patients treated with TIBSOVO^® experienced differentiation syndrome, which can be fatal if not treated. The most common adverse reactions (≥20%) of any grade included fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, electrocardiogram QT prolonged, rash, pyrexia, cough, and constipation. The most frequent serious adverse reactions (≥5%) were differentiation syndrome (10%), leukocytosis (10%), and electrocardiogram QT prolonged (7%).

In June 2018, CStone and Agios announced an exclusive collaboration and license agreement stating that CStone is responsible for the clinical development and commercialization of TIBSOVO^® in Mainland China, Hong Kong, Macau and Taiwan（“Greater China Region”）. In March 2020, CStone and Agios revised the agreement to expand its clinical development and commercialization area from the Greater China Region to also include Singapore.

About CStone

CStone 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 at the end of 2015, CStone has assembled a world-class management team with extensive experience in innovative drug development, clinical research, and commercialization. With a strategic emphasis on immuno-oncology combination therapies, the Company has built an oncology-focused pipeline of 16 drug candidates, including five late-stage candidates at pivotal trials or registration stages. With an experienced team, a rich pipeline, a robust clinical development-driven business model and substantial funding, CStone’s vision is to become a world-renowned biopharmaceutical company that is leading the way to conquering cancer.

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