Kelun-Biotech's A400/EP0031 NDA Acceptance: A Game-Changer in RET-Driven NSCLC Therapeutics

The recent acceptance of Kelun-Biotech's New Drug Application (NDA) for A400/EP0031 by China's National Medical Products Administration (NMPA) marks a pivotal moment in the development of next-generation RET inhibitors for non-small cell lung cancer (NSCLC). This regulatory milestone, announced in September 2025, underscores the growing demand for targeted therapies in RET-driven cancers and positions A400/EP0031 as a potential disruptor in a rapidly evolving marketKelun-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^[1]. With a robust clinical profile, global development partnerships, and a favorable regulatory trajectory, the drug's commercial potential is poised to reshape the competitive landscape.

Clinical Validation and Strategic Differentiation

A400/EP0031's NDA submission was anchored in the KL400-I/II-01 trial, which demonstrated its efficacy across both first-line (1L) and second-line and beyond (2L+) treatment settings for RET fusion-positive NSCLC. The trial reported durable responses in patients with brain metastases and a manageable safety profile, addressing unmet needs in a patient population historically challenged by poor outcomesKelun-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^[1]. Notably, the drug's ability to maintain efficacy in pretreated patients—many of whom had developed resistance to prior therapies—highlights its potential to overcome a critical limitation of existing RET inhibitorsA phase-1 dose escalation and expansion study of EP0031, a next ...^[2].

In comparison to leading therapies like Blueprint Medicines' Gavreto (pralsetinib) and Eli Lilly's Retsevmo (selpercatinib), A400/EP0031 appears to offer a balanced risk-benefit profile. While selpercatinib has demonstrated a median progression-free survival (PFS) of 22.1 months in indirect comparisonsMatching-adjusted indirect comparison of selpercatinib and pralsetinib in RET fusion-positive non-small cell lung cancer^[3], A400/EP0031's tolerability—marked by fewer grade ≥3 adverse events—could position it as a preferred option for long-term use. Additionally, its activity in brain metastases, a common site of disease progression in RET-driven NSCLC, differentiates it from competitorsKelun-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^[1].

Market Dynamics and Commercial Potential

The RET-driven NSCLC therapeutics market is projected to grow at a compound annual growth rate (CAGR) of 15%, reaching $2 billion by 2033RET Inhibitors 2025-2033 Trends and Competitor Dynamics^[4]. This expansion is fueled by the increasing adoption of precision oncology and the identification of RET as a key driver in approximately 1–2% of NSCLC cases. With over 135 companies developing more than 150 therapies, the pipeline is intensely competitive, but A400/EP0031's dual development by Kelun-Biotech and Ellipses Pharma—leveraging fast-track designations in the U.S. and regulatory momentum in China—creates a unique cross-border advantageKelun-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^[1]Matching-adjusted indirect comparison of selpercatinib and pralsetinib in RET fusion-positive non-small cell lung cancer^[3].

Key competitors, including Eli Lilly and Blueprint Medicines, have already established market presence with selpercatinib and pralsetinib. However, A400/EP0031's dual focus on efficacy in treatment-naïve and pretreated patients, coupled with its manageable toxicity, could carve out a distinct niche. For instance, while selpercatinib's 64.5% median PFS outperforms pralsetinib's 13.3 months in indirect comparisonsMatching-adjusted indirect comparison of selpercatinib and pralsetinib in RET fusion-positive non-small cell lung cancer^[3], A400/EP0031's Phase 2 data suggests it may bridge the gap between these benchmarks while reducing treatment discontinuations due to adverse eventsKelun-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^[1].

Global Expansion and Regulatory Synergies

The drug's global development strategy further amplifies its commercial appeal. Ellipses Pharma's Phase 2 trials in the U.S., U.K., and UAE, combined with Kelun-Biotech's NMPA filing, create a dual-track approach to market entry. This strategy not only mitigates regional regulatory risks but also aligns with the FDA's Fast Track and Orphan Drug Designations, which expedite development timelinesMatching-adjusted indirect comparison of selpercatinib and pralsetinib in RET fusion-positive non-small cell lung cancer^[3]. Such regulatory synergies are critical in a market where time-to-market can determine competitive positioning.

Moreover, the drug's potential to address resistance mechanisms—highlighted by its durable responses in patients with prior RET inhibitor exposure—positions it as a candidate for combination therapies. As the field shifts toward multi-modal approaches, A400/EP0031's compatibility with immunotherapies or other targeted agents could unlock additional valueA phase-1 dose escalation and expansion study of EP0031, a next ...^[2].

Investment Implications

For investors, A400/EP0031 represents a high-conviction opportunity in the next-gen oncology pipeline. Its NDA acceptance in China—a market projected to grow at 12.71% CAGR to $43.89 billion by 2030RET Inhibitors 2025-2033 Trends and Competitor Dynamics^[4]—provides immediate commercial traction, while its global Phase 2 trials open pathways to broader adoption. The drug's differentiation lies not only in its clinical profile but also in its strategic alignment with precision medicine trends, which are reshaping oncology care.

However, risks remain. The RET inhibitor market is crowded, and A400/EP0031 will face scrutiny on pricing and reimbursement, particularly in China. Additionally, the emergence of novel therapies—such as Boan Biotechnology's BA1302 or Dizal's Sunvozertinib—could intensify competitionKelun-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^[1]. Yet, given its dual development model, regulatory momentum, and unmet clinical needs, A400/EP0031 is well-positioned to capture a significant share of the $2 billion RET inhibitor market by 2033RET Inhibitors 2025-2033 Trends and Competitor Dynamics^[4].

Conclusion

Kelun-Biotech's A400/EP0031 NDA acceptance is more than a regulatory milestone—it is a testament to the drug's potential to redefine RET-driven NSCLC treatment. With a compelling clinical profile, strategic global partnerships, and a growing market, the therapy exemplifies the next wave of precision oncology. For investors, this represents a rare convergence of innovation, demand, and regulatory support, making A400/EP0031 a standout candidate in the oncology pipeline.