Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. announced that China's National Medical Products Administration (NMPA) has accepted its New Drug Application (NDA) for A400/EP0031, a novel next-generation selective RET inhibitor, for treating adult patients with RET-fusion positive locally advanced or metastatic non-small cell lung cancer (NSCLC). The acceptance, announced on September 22, 2025, represents a significant regulatory milestone for the company's oncology pipeline.
Clinical Trial Success Drives Regulatory Progress
The NDA acceptance is based on positive results from two pivotal Phase 2 cohorts of the KL400-I/II-01 study, which evaluated A400/EP0031 at 90mg orally once daily in both first-line and second-line-plus treatment settings for advanced RET-fusion positive NSCLC. According to the company, primary efficacy endpoints were reached in both cohorts, with A400/EP0031 demonstrating favorable efficacy in pretreated and treatment-naïve NSCLC patients, including those with prior immunotherapy or brain metastases.
The drug also showed an encouraging and manageable tolerability and safety profile across the study population. These results were presented at the 2024 and 2025 ASCO Annual Meetings, providing additional validation of the clinical data supporting the regulatory submission.
Addressing Unmet Medical Needs in Rare Cancer Subtype
RET gene fusions represent a rare but significant driver mutation in NSCLC, occurring in 1.4% to 2.5% of Chinese NSCLC patients. Despite their rarity, these patients face limited treatment options, as they derive minimal benefit from conventional therapies. While recent advances in highly selective RET inhibitors have provided breakthroughs in clinical management, therapeutic benefits remain constrained by acquired drug-resistant mutations and safety issues including hypertension and hematological toxicity.
Dr. Michael Ge, CEO of Kelun-Biotech, emphasized the strategic importance of the development: "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."
Global Development Strategy Through Strategic Partnership
A400/EP0031 is being developed through a strategic collaboration with Ellipses Pharma Limited, a UK-based international oncology drug development company. In March 2021, Kelun-Biotech granted Ellipses Pharma exclusive licensing rights to develop, manufacture, and commercialize the agent outside Greater China and certain Asian countries under the designation EP0031.
The global development program received significant regulatory support when the FDA granted EP0031/A400 Fast Track designation in March 2024 for RET-fusion positive NSCLC treatment. The FDA subsequently cleared the drug to progress into Phase 2 clinical development in April 2024, with trials now active in the United States, United Kingdom, Europe, and United Arab Emirates.
Expanding Pipeline in RET-Altered Malignancies
Beyond NSCLC, Kelun-Biotech is conducting a Phase 1b/2 clinical study evaluating A400/EP0031 in RET-positive medullary thyroid cancer (MTC) and other solid tumors with high prevalence of RET alterations. Results from the Phase 1 study in patients with advanced RET-mutant MTC were presented at the 2025 ASCO Annual Meeting, demonstrating the drug's potential across multiple tumor types.
The company's broader oncology portfolio includes more than 30 ongoing innovative drug projects, with 3 projects already approved for marketing and 2 projects currently in the NDA stage. Kelun-Biotech has established proprietary ADC and novel drug conjugate platforms, including the OptiDC™ platform, with 1 ADC project approved for marketing and multiple assets in clinical development stages.
