Gelonghui, May 3 | Columbotai Bio-B (06990.HK) announced that the company's main product, A400 (EP0031) (rearrangement during transfection (RET) small molecule kinase inhibitor project, also known as KL590586 or EP0031), was approved by the US Food and Drug Administration (FDA) to enter phase 2 clinical development.
A400 (EP0031) is a second-generation selective RET inhibitor (SRI) and has broad activity against common RET gene fusions and mutations. In March 2021, the company granted an exclusive, royalty-free, sublicensable license to Ellipses Pharma Limited (“Ellipses”), an international drug development company headquartered in the United Kingdom to develop, manufacture and commercialize A400 (EP0031) in all countries outside of Greater China, North Korea, South Korea, Singapore, Malaysia and Thailand.
In June 2022, A400 (EP0031) obtained a new drug clinical research application approved by the FDA to conduct a phase 1/2 trial on patients with malignant tumors with altered RET genes. In November 2023, A400 (EP0031) was granted orphan drug qualification by the FDA for the treatment of RET fusion positive solid tumors. In March 2024, A400 (EP0031) received fast-track approval from the FDA for the treatment of RET fusion positive non-small cell lung cancer (NSCLC).
In preclinical studies, A400 (EP0031) showed good inhibitory activity against major RET kinases in vitro and in vivo. A400 (EP0031) also showed good blood-brain barrier penetration in animal models. According to data on A400 (EP0031) shared at the 2023 American Society of Clinical Oncology (ASCO) annual meeting, according to the results of its ongoing phase 1/2 trial, A400 (EP0031) showed good anti-tumor efficacy in patients with advanced RET+ solid tumors. In particular, the ORR in first-line and second-line advanced RET+NSCLC was 80.8% and 69.7%, respectively. According to reports, the DCR in both cases was over 96%.
According to information published on the ASCO website, Ellipses will present clinical data obtained from the A400 (EP0031) phase 1 dose escalation and expansion study in patients with advanced RET variant NSCLC and other tumors who have never used SRI or have been treated at the 2024 ASCO annual meeting to be held on June 3, 2024 (local time).
Currently, the company is conducting key clinical research on A400 (EP0031) for RET positive NSCLC in China.