Recursion Pharmaceuticals has reported encouraging efficacy data from its Phase II trial of REC-994, an artificial intelligence-discovered drug candidate for cerebral cavernous malformation (CCM), marking a significant milestone for AI-driven drug development.
The results, presented at the International Stroke Conference in Los Angeles, showed that 50% of patients receiving the highest dose (400 mg) of REC-994 experienced a reduction in total lesion volume, compared to 28% in the placebo group after 12 months of treatment. The trial involved 62 participants, with patients on the lower dose (200 mg) showing similar outcomes to placebo.
Clinical Impact and Disease Background
CCM affects approximately 360,000 symptomatic individuals across the U.S. and EU. The condition is characterized by enlarged, irregular blood vessels in the brain that can lead to seizures, headaches, neurological deficits, and potentially fatal hemorrhagic stroke. Currently, treatment options are limited to surgery and radiation therapy, highlighting the urgent need for pharmacological interventions.
"My co-investigators and I are encouraged by these initial findings," said Dr. Jan-Karl Burkhardt, division head of cerebrovascular surgery at the University of Pennsylvania and principal investigator of the study. The results are particularly significant for patients with brainstem lesions, who cannot undergo surgical intervention.
Mechanism of Action and Safety Profile
REC-994 functions as a redox-cycling nitroxide compound and free-radical scavenger, targeting the underlying disease mechanism of CCM, which involves gene mutations affecting redox homeostasis. The drug had previously met its primary endpoint of safety and tolerability in September 2023.
Dr. Najat Khan, chief R&D officer at Recursion, emphasized the significance of the findings: "These preliminary results show promising MRI-based and functional outcome signals." The study also demonstrated positive trends in functional outcomes using the FDA-approved modified Rankin Scale.
AI Drug Discovery Implications
The success of REC-994 represents an important validation point for AI-driven drug discovery, though experts note these results reflect earlier AI technology. "The first wave of AI-driven drug candidates has fueled both optimism and skepticism," said Dr. Krish Ramadurai, partner at AIX Ventures. "Positive efficacy data for REC-994 would illustrate that AI-generated hypotheses can yield real patient benefits."
Dylan Reid, managing director at Zetta Venture Partners, added perspective on the timeline of AI innovation in drug development: "The early signals look strong, but it will be a couple of years before we see the impact of modern AI in the clinic."
Patient Community Response
The results have generated hope within the CCM patient community. "With no approved therapy and brain surgery as an option for only a subset of the population, these data show tremendous progress," said Dr. Connie Lee, CEO of the Alliance to Cure Cavernous Malformation.
Future Directions
Recursion continues to expand its AI-driven drug development platform, with 10 clinical and preclinical programs in development. The company recently completed a merger with Exscientia and has established partnerships with major pharmaceutical companies including Roche, Bayer, and Sanofi.
As the first company to conduct an institutionally backed clinical trial in CCM, Recursion faces both opportunities and challenges. CEO Chris Gibson noted, "The challenge of being first in disease is, it's an exciting opportunity to make an impact for patients. It also means that there's an increased burden to not only prove out the molecule, but the path itself towards the treatment."
