Phase III Studies of APG-2449 in NSCLC Cleared by China CDE

ALK-positive NSCLC is a type of lung cancer with a specific molecular profile characterized by the abnormal arrangement or the fusion of the ALK gene which occurs in approximately 3%-5% of all lung cancer cases. Most patients with ALK-positive NSCLC are relatively young, non-smoking or only have a light smoking history, and have a higher risk of brain metastasis.

Despite that multiple ALK-targeted therapies have already been approved, more than half of patients with NSCLC treated with second-generation ALK TKIs would develop acquired resistance, thus the Chinese Society of Clinical Oncology (CSCO) guidelines’ recommendation of platinum-based chemotherapies as a treatment option for patients who had failed on second-generation ALK-targeted therapies. It is widely acknowledged that chemotherapies are commonly associated with strong side effects and there is a growing general preference for chemotherapy-free regimens for the treatment of advanced tumors. Therefore, patients with resistance to second-generation ALK TKIs have an enormous unmet clinical need for new therapies that are effective and safe.

APG-2449, developed by Ascentage Pharma, is an orally-active small molecule FAK inhibitor and a third-generation ALK/ROS1 TKI, and the first FAK inhibitor cleared by the CDE to enter clinical study in China. In the first-in-human trial, APG-2449 demonstrated preliminary clinical benefit and favorable tolerability in patients with NSCLC who were either second-generation ALK TKI resistant or treatment-naïve. APG-2449 also showed potential inhibitory effect on brain metastases, with its ability to cross the blood-brain barrier confirmed through pharmacokinetics (PK) analysis on cerebrospinal fluid. Biomarker analysis found that the phosphorylated FAK (pFAK) expression in tumor tissues at baseline in patients with NSCLC who were second-generation ALK TKI-resistant, were positively correlated with the progress-free survival (PFS) after treatment with APG-2449, indicating that elevated phosphorylated FAK could be associated with drug resistance to second-generation ALK TKIs.

Ascentage Pharma (6855.HK) is a global, integrated biopharmaceutical company engaged in discovering, developing and commercializing therapies to address global unmet medical needs primarily in malignancies. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK.

The company has built a rich pipeline of innovative drug candidates that includes novel, highly potent Bcl-2 and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation TKIs. Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company has conducted more than 40 clinical trials in the US, Australia, Europe, and China, including 11 registrational studies (completed/ ongoing/planned).

Olverembatinib, the company’s first lead asset developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company’s first approved product in China, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted Orphan Drug Designations (ODDs) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU.

To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company’s investigational drug candidates. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships and other relationships with numerous leading biotechnology and pharmaceutical companies such as Takeda, AstraZeneca, Merck, Pfizer and Innovent; and research and development relationships with leading research institutions such as Dana-Farber Cancer Institute, Mayo Clinic, MD Anderson Cancer Center, National Cancer Institute and the University of Michigan.

The company has built a talented team with a wealth of global experience in the discovery and development of innovative drugs and fully functional commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients.

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