FDA Clears Investigational New Drug Application for REC-4539 in SCLC
The FDA cleared the investigational new drug application for REC-4539, allowing for the start of a phase 1/2 trial in small cell lung cancer and other solid tumor indications.
- The FDA cleared an investigational new drug (IND) application for a phase 1/2 clinical trial to investigate REC-4539.
- REC-4539 a potential best-in-classlysine-specific demethylase 1 (LSD1) inhibitor for small cell lung cancer (SCLC).
- The initial clinical investigation will focus on SCLC and several other solid tumor indications.
The FDA has cleared the IND application for REC-4539, a novel LSD1 inhibitor, initiating a phase 1/2 clinical trial in SCLC and other solid tumor indications.1
REC-4539 is the first LSD1 inhibitor designed to be both CNS-penetrant and reversible.2 LSD1 overexpression is implicated in the proliferation and survival of various tumors, including SCLC. REC-4539 selectively inhibits LSD1, targeting both peripheral and CNS disease. Unlike other LSD1 inhibitors, REC-4539 offers the potential to minimize platelet-related toxicities, such as thrombocytopenia, which are common with this class of drugs.
In preclinical studies, REC-4539 demonstrated dose-dependent tumor inhibition in SCLC xenograft models with brain penetration.1 With its selective activity and reversible mechanism, data suggest an improved safety profile compared with other LSD1 inhibitors in clinical development.
Small cell lung cancer: © Констянтин Батыльчук- stock.adobe.com
Additionally, REC-4539 showed limited effects on platelet levels, indicating reduced risk for thrombocytopenia. The agent also exhibited a favorable absorption, distribution, metabolism, excretion profile, with a shorter half-life in humans compared to other LSD1 inhibitors.
The phase 1/2 ENLYGHT trial plans to evaluate REC-4539 as both a monotherapy and in combination with durvalumab (Imfinzi), an anti-PD-L1 antibody, in patients with extensive-stage SCLC. The trial plans to assess REC-4539’s ability to improve radiographic progression-free survival and overall survival while minimizing common adverse events associated with LSD1 inhibition, particularly thrombocytopenia.
The first patient is expected to be dosed in the first half of 2025, with results anticipated in the coming years.
REC-4539 is also being developed for other indications, including acute myeloid leukemia.
REFERENCES:
Recursion announces two key investigational oncology drugs advancing to clinical trials, targeting high unmet needs in hematologic malignancies, small-cell lung cancer, & more. News release. Recursion. January 7, 2025. Accessed January 8, 2025. https://tinyurl.com/bdfuc2hc
Pipeline. Recursion. Accessed January 8, 2025. https://www.recursion.com/pipeline
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