Next-generation Selective RET Inhibitor EP0031(A400) accepted
Ellipses Pharma (“Ellipses”), a global drug development company focused on accelerating the development of cancer treatments through an innovative drug development model, announced today that its partner, Kelun Biotech, has had a new drug application (NDA) for the next generation selective RET inhibitor EP0031/A400, for the potential treatment of RET-fusion positive Non-Small Cell Lung Cancer (NSCLC), accepted for review by the Centre for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China.
This acceptance for review, a key step in the regulatory approval process, is based on the positive results from the two pivotal Phase 2 cohorts of the KL400-I/II-01 study advanced RET-fusion positive NSCLC.
The Phase 2 stage of the KL400-I/II-01 study evaluated the efficacy and safety of EP0031/A400 90mg orally once daily (QD) in patients with pre-treated and treatment-naïve RET-fusion positive locally advanced, or metastatic, NSCLC. EP0031/A400 demonstrated favourable efficacy in both cohorts and an encouraging, manageable tolerability and safety profile.
EP0031/A400 is being developed jointly by Ellipses and Kelun Biotech. Ellipses has an exclusive licence to develop, manufacture and commercialise this agent outside Greater China and certain Asian countries under the code EP0031.
Ellipses has an ongoing Phase 1/2 trial in US, EU, UK and UAE (EP0031-101 NCT05443126). Data from the dose finding and optimisation cohorts were presented at ASCO in June 2025, showing promising evidence of activity, including CNS responses, in patients with advanced NSCLC that had received prior 1st generation Selective RET Inhibitor (SRI), with encouraging safety and tolerability (Journal of Clinical Oncology Volume 43, Number 16_suppl https://doi.org/10.1200/JCO.2025.43.16_suppl.8598). The trial is continuing with recruitment of Phase 2 cohorts of patients with and without prior 1st generation SRI.
In November 2023, Ellipses announced it had secured Orphan Drug designation for EP0031/A400 from the US Food and Drug Administration (FDA) and the following year it secured Fast Track designation from the FDA for EP0031/A400 for the treatment of RET-fusion positive NSCLC. Ellipses expects to complete its Phase 2 trials of EP0031/A400 in 2026 before submission to relevant regulatory authorities in non-Chinese geographies.
Ellipses Pharma has a robust pipeline of best-in-class programmes, including three programmes in Phase 2 clinical development and an additional programme entering Phase 1 early in 2026.
Professor Sir Christopher Evans, Chairman, Ellipses Pharma, commented: “We are delighted and greatly encouraged that EP0031/A400 has been accepted for review by the Chinese regulatory authorities – a very significant step in the development of this very promising treatment for patients globally. These are very exciting times for Ellipses.”
Professor Tobias Arkenau, Global Head of Drug Development and Chief Medical Officer, Ellipses Pharma, commented: “EP0031/A400 has great potential as a new treatment option for patients with RET fusion-positive NSCLC, which remains a progressive and fatal condition for many people worldwide despite available treatment options.”
Dr. Michael Ge, CEO of Kelun-Biotech, said: “We are very 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 tumour agnostic precision therapy, A400/EP0031 represents our significant strategic positioning in the solid tumour field. We look forward to working closely with the regulatory authorities in China and our international partner Ellipses Pharma to expedite the review process for A400/EP0031, bringing this innovative therapy to patients with RET-fusion positive NSCLC as soon as possible.”
About EP0031/A400
EP0031/A400 has broad and potent activity against the spectrum of common RET fusions and mutations, as well as RET resistance mutations that have been shown to emerge on progression on 1st gen SRIs. EP0031 has a differentiated preclinical profile compared with 1st gen SRIs with greater potency and antitumour activity in SRI naïve and SRI resistant PDX models as well as greater tissue permeability, with increased exposure in the CNS and improved survival in orthotopic models.
(Annual of Oncology35(S2):S824.204, Molecular Cancer Therapeutics 22(12). suppl.B043.2023 https://aacrjournals.org/mct/article/22/12_Supplement/B043/730626/Abstract-B043-Preliminary-results-from-a-phase-I)
About RET altered malignancies
Activating RET mutations and rearrangements have been identified as actionable drivers of oncogenesis in numerous tumour types and are most prevalent in non-small cell lung and thyroid cancer. It is estimated that RET mutations and rearrangements may be responsible for ~2% of all solid tumours. After the successful development of first generation SRIs and an increasing understanding of escape mechanisms to these agents, there is an unmet need to develop new treatments that can address acquired resistance, including the development of next-generation SRIs.
About Ellipses Pharma Limited
Ellipses Pharma is a global drug development company based in London, focused on accelerating the development of cancer treatments through an innovative drug development model that combines unbiased vetting to de-risk initial asset selection, the expertise of a Scientific Affairs Group, which comprises more than 300 leading KOLs and an uninterrupted funding flow to minimise the time it takes to advance lead products through clinical trials and reach patients.
About Kelun-Biotech
Kelun-Biotech（6990.HK）is a holding subsidiary of Kelun Pharmaceutical (002422.SZ), which focuses on the R&D, manufacturing, commercialisation and global collaboration of innovative biological drugs and small molecule drugs. The company focuses on major disease areas such as solid tumours, autoimmune, inflammatory, and metabolic diseases, and in establishing a globalized drug development and industrialization platform to address the unmet medical needs in China and the rest of world. The Company is committed to becoming a leading global enterprise in the field of innovative drugs.
At present, the company has more than 30 ongoing innovative drug projects, of which 3 projects have been approved for marketing, 2 projects at the NDA stage and more than 10 are in the clinical stage. The company has established one of the world’s leading proprietary ADC and novel DC platforms, OptiDC™, and has 1 ADC project approved for marketing, 1 ADC project in NDA stage and multiple ADC and novel DC assets in clinical or preclinical research stage. For more information, please visit https://kelun-biotech.com/.
The Centre for Drug Evaluation.
The Centre for Drug Evaluation (CDE) is a specialised body responsible for the technical evaluation of drug applications, including clinical trial and marketing authorization applications for new and existing drugs, as well as emerging medical products. The centre operates under China’s National Medical Products Administration (NMPA), which is the primary government body in China responsible for regulating pharmaceuticals.
