Kelun-Biotech's A400/Ep0031: A Regulatory and Market Breakthrough in RET-Fusion Positive NSCLC

The recent acceptance of Sichuan Kelun-Biotech's New Drug Application (NDA) for its next-generation RET kinase inhibitor A400/Ep0031 by China's National Medical Products Administration (NMPA) marks a pivotal moment in the treatment of RET-fusion positive non-small cell lung cancer (NSCLC). This regulatory milestone, coupled with robust clinical data and a growing global demand for precision oncology therapies, positions A400/Ep0031 as a transformative player in a niche but high-growth market.

Regulatory Progress and Clinical Validation

Kelun-Biotech's NDA for A400/Ep0031 was accepted in September 2025 following the successful completion of two pivotal Phase 2 cohorts of the KL400-I/II-01 trial. These cohorts evaluated the drug's efficacy in both treatment-naïve and previously treated patients with RET-fusion positive locally advanced or metastatic NSCLC. The trial demonstrated that A400/Ep0031 achieved its primary endpoints, with a 90 mg once-daily oral dose showing robust activity, including in patients with brain metastases or prior immunotherapy exposure. The drug's safety profile was also favorable, with manageable tolerabilityKelun-Biotech’s RET Inhibitor NDA Accepted in China^[1].

This regulatory progress is further bolstered by global momentum. A400/Ep0031 has received Fast Track designation from the U.S. FDA and is licensed to Ellipses Pharma for development outside Greater China. Such cross-border collaboration underscores the drug's potential to address unmet needs in a market where current options remain limitedKelun-Biotech's A400/EP0031 Receives NMPA Review for NSCLC^[2].

Market Potential: A Niche with High Growth

RET-fusion positive NSCLC is a rare but actionable subset of lung cancer, accounting for approximately 1–2% of NSCLC cases in ChinaGenomic landscape of 891 RET fusions detected across diverse^[3]. Despite its low prevalence, the condition presents significant therapeutic challenges. Traditional treatments, such as platinum-based chemotherapy, yield a median progression-free survival (PFS) of just 9.22 months for advanced-stage patientsDiagnosis, Treatment Patterns, and Outcomes in Real-World Patients with RET Fusion-Positive Non-small Cell Lung Cancer in China^[4]. In contrast, selective RET inhibitors like pralsetinib and selpercatinib—approved in China since 2021 and 2022—have demonstrated superior outcomes, with pralsetinib achieving a median PFS of 16.03 monthsEvolution of treatment strategies for solid tumors with RET rearrangement^[5]. A400/Ep0031's next-generation profile, with improved tolerability and efficacy in brain metastases, could further differentiate it in this competitive landscape.

The broader NSCLC therapeutics market is expanding rapidly. The global market, valued at USD 28.61 billion in 2025, is projected to grow at a 9.6% CAGR to reach USD 54.38 billion by 2032Non-Small Cell Lung Cancer Market Size & Forecast^[6]. China's NSCLC market, driven by rising incidence and regulatory advancements, is expected to grow from USD 21.98 billion in 2025 to USD 36.5 billion by 2030, with a 10.12% CAGRNon-Small Cell Lung Cancer Therapeutics Market Size & Growth^[7]. Targeted therapies, which now dominate 50.4% of the NSCLC market, are central to this growthNon-small Cell Lung Cancer Therapeutics Market Report 2030^[8].

Competitive Landscape and Strategic Positioning

Kelun-Biotech faces competition from first-generation RET inhibitors like pralsetinib and selpercatinib, which are already established in China. However, A400/Ep0031's next-generation design—optimized for reduced off-target effects and enhanced CNS penetration—positions it to capture a significant share of the market. Clinical data from the KL400-I/II-01 trial, particularly its performance in patients with brain metastases (a common complication in RET-fusion positive NSCLC), provides a strong differentiatorKelun-Biotech's New Drug Application for Its Novel Next-Generation Selective RET Inhibitor A400/EP0031 Accepted for Review by the NMPA for the Treatment of RET-Fusion Positive NSCLC^[9].

Globally, the NSCLC therapeutics market is highly competitive, with key players such as AstraZeneca, Merck, and Amgen advancing pipelines focused on both early and advanced-stage diseaseNon-Small Cell Lung Cancer Therapeutics Market Report 2030^[10]. Yet, the niche nature of RET-fusion positive NSCLC, combined with Kelun-Biotech's first-mover advantage in China and Ellipses Pharma's international development rights, creates a unique value proposition.

Investment Implications

The acceptance of A400/Ep0031's NDA represents a critical inflection point for Kelun-Biotech. If approved, the drug could rapidly gain traction in China, a market where biomarker testing rates for RET fusions are rising (75% for early-stage, 78% for advanced-stage patients)Diagnosis, Treatment Patterns, and Outcomes in Real-World Patients with RET Fusion-Positive Non-small Cell Lung Cancer in China^[11]. With a projected 10.12% CAGR for China's NSCLC market and a growing emphasis on precision medicine, A400/Ep0031 is well-positioned to capture a meaningful share of the RET-inhibitor segment.

For investors, the combination of regulatory progress, clinical differentiation, and market tailwinds presents a compelling opportunity. Kelun-Biotech's strategic partnerships, including its collaboration with Ellipses Pharma, further enhance its ability to scale globally. As the NMPA review progresses, the company's ability to secure approval and demonstrate real-world efficacy will be key watchpoints.

Conclusion

Kelun-Biotech's A400/Ep0031 exemplifies the convergence of regulatory innovation, clinical rigor, and market demand in precision oncology. With its NDA under review and a robust clinical profile, the drug has the potential to redefine treatment standards for RET-fusion positive NSCLC in China and beyond. For investors, this represents not just a bet on a single molecule, but on the broader shift toward biomarker-driven therapies in a rapidly evolving therapeutic landscape.