On September 22, 2025 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the "Company") reported that a new drug application (NDA) for the Company’s small molecule rearranged during transfection (RET) kinase inhibitor A400 (also known as EP0031) was accepted for review by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China for the treatment of adult patients with RET-fusion positive locally advanced, or metastatic non-small cell lung cancer (NSCLC) (Press release, Kelun, SEP 22, 2025, View Source [SID1234656156]). This acceptance for review is based on the positive results from the two pivotal Phase 2 cohorts of the KL400-I/II-01 study for both 1L and 2L+ advanced RET-fusion positive NSCLC.
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Cohort 1 and 2, the Phase 2 stage of the KL400-I/II-01 study, evaluate the efficacy and safety of A400/EP0031 90mg orally once daily (QD) for the treatment of patients with pre-treated and treatment-naïve RET-fusion positive locally advanced, or metastatic NSCLC, respectively. Primary efficacy endpoints of the two pivotal cohorts were reached, where A400/EP0031 demonstrated favorable efficacy in pretreated and treatment-naïve NSCLC including patients with prior immunotherapy or brain metastases. A400/EP0031 also demonstrated an encouraging, manageable tolerability and safety profile.
Dr. Michael Ge, CEO of Kelun-Biotech said, "We are pleased to report positive results from the clinical study of A400/EP0031 in treating RET-fusion positive NSCLC, which gives us confidence in its future clinical potential. As a tumor agnostic precision therapy, A400/EP0031 represents our significant strategic positioning in the solid tumor field. We look forward to working closely with regulatory authorities to expedite the review process for A400/EP0031, bringing this innovative therapy to patients with RET-fusion positive NSCLC as soon as possible."
About RET-fusion positive NSCLC
RET gene fusions represent one of the rare yet significant driver mutation types in NSCLC. In Chinese NSCLC patients, the incidence of RET gene fusions ranges from 1.4% to 2.5%[1]. Patients with RET fusions derive limited benefit from conventional treatments. In recent years, the emergence of novel highly selective inhibitors has led to breakthroughs in the clinical management of advanced RET-fusion positive NSCLC patients. However, their therapeutic benefits are limited, in part, by acquired RET drug-resistant mutations and safety issues such as hypertension and hematological toxicity, underscoring the need for novel selective RET inhibitors with improved safety and better efficacy against drug-resistant mutations.
About A400/EP0031
A400/EP0031 is a novel next-generation selective RET inhibitor for NSCLC, medullary thyroid cancer (MTC) and other solid tumors with a high prevalence of RET alterations. The Company is currently conducting a phase 1b/2 clinical study for RET+ MTC and solid tumor in China. The results from the Phase 1 study of A400/EP0031 in patients with advanced RET-mutant MTC were presented at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting.
In March 2021, the Company granted Ellipses Pharma Limited, a U.K.-based international oncology drug development company, an exclusive license to develop, manufacture and commercialize this agent outside Greater China and certain Asian countries under the code EP0031.
In March 2024, it was announced that EP0031/A400 was granted Fast Track designation by the Food and Drug Administration (FDA) for the treatment of RET-fusion positive NSCLC. In April 2024, EP0031/A400 was cleared by the FDA to progress into Phase 2 clinical development and is now open in the United States, United Kingdom, Europe and United Arab Emirates.