Recursion Advances Two Investigational Oncology Drugs to Clinical Trials
Recursion Pharmaceuticals announced the progression of two investigational oncology drugs, REC-3565 and REC-4539, into clinical trials, targeting critical unmet needs in hematologic malignancies and small-cell lung cancer (SCLC). Both therapies leverage precision design and advanced AI models from Recursion’s proprietary platform to enhance patient outcomes.
REC-3565: A Selective MALT1 Inhibitor for B-cell Malignancies
REC-3565 is a potential best-in-class MALT1 inhibitor targeting hematologic cancers such as chronic lymphocytic leukemia (CLL) and B-cell lymphomas, which collectively affect approximately 41,000 patients annually in the US and EU5. Unlike other MALT1 inhibitors, REC-3565 is designed to avoid significant off-target inhibition of UGT1A1, a protein involved in bilirubin metabolism, thereby reducing the risk of hyperbilirubinemia—a common side effect that limits dose escalation in existing therapies.
Preclinical studies of REC-3565 demonstrated:
- Tumor growth inhibition in multiple hematologic cancer models, with durable tumor eradication when combined with BTK inhibitors.
- Selective inhibition of MALT1 with minimal impact on UGT1A1, improving its safety and combination potential.
- A favorable pharmacokinetic profile enabling daily oral dosing.
The Phase 1 EXCELERIZE clinical trial will begin in Q1 2025 to evaluate REC-3565’s safety, tolerability, and potential for combination with standard-of-care therapies.
REC-4539: A Reversible, Brain-Penetrant LSD1 Inhibitor for SCLC
REC-4539 is the first reversible and CNS-penetrant LSD1 inhibitor, addressing SCLC, which affects approximately 45,000 patients annually in the US and EU5. Brain metastases occur in nearly half of SCLC cases during treatment, significantly worsening survival outcomes. REC-4539 aims to treat both peripheral and brain metastases effectively.
Preclinical data highlight REC-4539’s potential:
- Dose-dependent tumor inhibition in SCLC models, with demonstrated brain penetration.
- A reversible mechanism and shorter half-life, reducing thrombocytopenia risk compared to other LSD1 inhibitors.
The Phase 1/2 ENLYGHT trial will commence in H1 2025 to evaluate REC-4539 as monotherapy and in combination with durvalumab.
Leveraging the Recursion OS Platform
Both programs exemplify the capabilities of Recursion OS, which integrates multimodal data and causal AI models to optimize patient selection. Following its merger with Exscientia in late 2024, Recursion OS now combines its computational framework with Exscientia’s molecular design expertise, creating a pipeline of over 10 clinical and preclinical programs and leveraging 60 petabytes of proprietary data. The platform’s iterative approach aims to accelerate drug discovery, with future plans to develop virtual cells for in silico clinical trials, potentially reducing reliance on early-stage physical experiments.
Chris Gibson, PhD, Recursion’s CEO, emphasized the potential of these programs:
“REC-3565 and REC-4539 showcase how our advanced AI-driven platform identifies and optimizes molecules with unique properties. These developments are a testament to our mission of decoding biology to transform medicine.”
Topics: Clinical Trials
