Recursion Pharmaceuticals has announced the dosing of the first patient in its Phase 1 EXCELERIZE clinical trial evaluating REC-3565, a selective MALT1 inhibitor being developed for patients with relapsed or refractory B-cell lymphomas.
The clinical milestone represents a significant advancement for the company's oncology pipeline and highlights the potential of its AI-powered drug discovery platform. REC-3565 was developed using Recursion's proprietary Recursion OS platform, which combines physics-based modeling with molecular dynamics and hotspot analysis.
"REC-3565 showed durable tumor regressions in preclinical studies, both as a monotherapy and in combination with a BTK inhibitor," said Najat Khan, Chief R&D Officer and Chief Commercial Officer at Recursion. "Leveraging our AI-powered Recursion OS platform, we delivered a lead candidate in just 15 months."
Trial Design and Objectives
The EXCELERIZE study is designed as an open-label, multicenter dose-escalation trial that will proceed in two parts. Part A will focus on monotherapy dosing to identify a recommended dose for combination therapy, while Part B will evaluate combination regimens to inform future studies in B-cell cancers.
The trial aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of REC-3565 in patients with limited treatment options.
David Mauro, Chief Medical Officer at Recursion, emphasized the company's commitment to improving patient outcomes: "We're advancing REC-3565, a potential best-in-class MALT1 inhibitor, to improve outcomes for patients with B-cell malignancies with limited treatment options. This milestone reflects our unwavering commitment to advancing patient-centric solutions and recruitment with AI-driven innovation."
Mechanism of Action and Differentiation
REC-3565 targets MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1), a key protease in the NF-kB pathway that drives malignant B-cell proliferation in hematological cancers. While current therapies such as BTK inhibitors have advanced treatment options, resistance remains a significant challenge for many patients.
What potentially sets REC-3565 apart from other MALT1 inhibitors in development is its allosteric design, which the company claims enhances potency, selectivity, and safety. Specifically, REC-3565 is designed to minimize UGT1A1 inhibition, potentially reducing the risk of drug-drug interactions and liver toxicity that have been observed with other compounds targeting this pathway.
This safety profile could enable safer dose escalation and higher target engagement, potentially leading to better clinical efficacy. The compound is being positioned as either a monotherapy or in combination with BTK and BCL2 inhibitors to overcome resistance mechanisms.
Market Opportunity
According to Recursion, approximately 41,000 relapsed and/or refractory patients with chronic lymphocytic leukemia (CLL) and B-cell lymphomas in the U.S. and EU5 countries (France, Germany, Italy, Spain, and the United Kingdom) are eligible for treatment each year, representing a significant market opportunity.
About Recursion's Technology Platform
Recursion's approach to drug discovery leverages its Recursion OS platform, which continuously expands one of the world's largest proprietary biological and chemical datasets. The company utilizes sophisticated machine-learning algorithms to analyze this dataset, which contains trillions of searchable relationships across biology and chemistry.
The Salt Lake City-based company describes itself as a "TechBio" organization that conducts up to millions of wet lab experiments weekly while operating one of the world's most powerful supercomputers for biological and chemical analysis.
The development of REC-3565 demonstrates the potential efficiency of this approach, with the company reporting that it moved from concept to lead candidate in just 15 months—significantly faster than traditional drug discovery timelines.
As the EXCELERIZE trial progresses, oncologists and industry observers will be watching closely to see if REC-3565's preclinical promise translates into clinical benefit for patients with limited treatment options.
