Recursion Begins First-in-Human Trial for AI-Discovered Protein Degrader for Biomarker-Enriched Solid Tumors and Lymphoma

In October 2024, Recursion Pharmaceuticals received FDA clearance to initiate clinical trials for REC-1245, an investigational RBM39 degrader targeting biomarker-enriched solid tumors and lymphoma.

Now, just two months later, the company has dosed its first patient in the Phase 1/2 DAHLIA trial, a milestone for the AI-enabled drug discovery platform that accelerated REC-1245 from target identification to regulatory approval in under 18 months.

The Compound

REC-1245 is a novel molecular glue that degrades RBM39, a protein critical to DNA damage response (DDR) and cell cycle regulation. By disrupting RNA splicing, the drug downregulates DDR pathways and halts tumor progression. Recursion’s AI-powered Operating System (OS) identified RBM39 as a viable target using biological maps, synthesizing approximately 200 compounds during development.

See also: Protein Degraders Take Industry By Storm

The drug addresses an unmet need in oncology by targeting biomarker-enriched cancers. Preclinical studies indicate REC-1245 induces splicing defects, offering therapeutic potential in hard-to-treat cancers. The company estimates a patient population of over 100,000 across the U.S. and EU5 for this first-in-class therapeutic.

DAHLIA Trial

The DAHLIA trial is a multi-center, open-label Phase 1/2 study designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy (ORR) of REC-1245. It includes dose-escalation and dose-confirmation phases, with plans to enroll multiple patient cohorts for parallel evaluation.

REC-1245 is administered orally to patients with unresectable or metastatic cancers who have relapsed or are intolerant to standard treatments. It is being tested both as a monotherapy and in combination with other therapies, such as DDR inhibitors and checkpoint inhibitors.

Dr. Najat Khan, Chief R&D Officer at Recursion, noted:

“REC-1245 exemplifies our ability to rapidly translate novel insights into clinical programs. This milestone marks a pivotal step in transforming cancer treatment with speed and precision.”

Topics: Clinical Trials