May 5, 2025: Statement from Recursion Regarding Discontinuation of the REC-994 Trial
We have difficult news to share today. Recursion has made the decision to discontinue the SYCAMORE trial of REC-994, a treatment for Symptomatic Cerebral Cavernous Malformation. We understand this news may be disappointing, and we want to explain why this decision was made.
Early data from the trial, after patients had been on REC-994 for one year, suggested some promising trends with the 400mg dose. However, these positive trends were not sustained in the long-term extension of the trial, whether patients stayed on the 400mg dose, switched from the 200mg dose to 400mg, or most importantly those who were switched from the placebo (no active treatment) to 400 mg dose for the long term extension.
Further analysis of the long-term extension data showed that there were no significant improvements in MRI results or functional outcomes. The results were unfortunately similar to what we might expect without any treatment. The decision to discontinue the trial was made after a thorough review of all the data, especially the long-term results.
If you were participating in the trial, your study team will be reaching out to you very soon to discuss your individual situation and next steps. We know this is not the outcome we all hoped for, and we sincerely share in your disappointment that REC-994 did not prove to be the treatment we needed. However, we want to emphasize that the research conducted by Recursion and participation by many patients in the CCM community is invaluable and contributes to our overall understanding and search for a cure.
Chris Gibson, Recursion’s CEO, shared the following:
“This program has always held a special place in Recursion’s history. CCM was the first area we explored using AI-driven drug discovery, and the community impacted by this disease is one we deeply care about. We understand this is disappointing news for the CCM community and for us. We are deeply grateful to all the patients and families who participated in these trials. Our commitment to finding solutions for unmet medical needs remains strong, and what we have learned from the REC-994 program will guide our future research and efforts to find effective treatments for patients.”
From the Alliance to Cure Cavernous Malformation
How did the REC-994 trial advance CCM science?
We know that the vast majority of drugs tested in clinical trials do not end up becoming approved treatments, but clinical trials are a necessary part of drug development. Even though the REC-994 trial did not end in an approved treatment for CCM, it did get us closer to a cure. We now have the infrastructure, tools, and know-how to run CCM clinical trials in the future. We are immensely grateful to the volunteers who participated in the REC-994 trial and moved CCM research forward.
What are our next steps for CCM research?
The REC-994 trial discontinuation does not affect our mission to drive a cure for CCM. We continue to move critical research projects like the following forward:
- speeding up drug development by testing compounds in our CCM CureDriver Lab
- planning a clinical safety trial of focused ultrasound
- working with researchers on gene therapy and targeted drug-delivery.
history of rec-994 development
REC-994 was developed by Recursion Pharmaceuticals specifically for treating symptomatic cerebral cavernous malformations.
The Phase I trial of REC-994, using healthy volunteers, was completed in late 2020. The Phase II Sycamore trial testing the safety and tolerability of the medicine in patients with CCM enrolled its first patient in March 2022. It completed the enrollment of 60 patients ahead of schedule in June 2023. Patients were randomized into three groups: a high-dose group (400 mg/day), a low-dose group (200 mg/day), and a placebo group. This was a double-blinded trial, meaning neither the participants nor the study staff knew which group had been assigned.
Phase 2A sycamore trial Results
In February, 2025, Recursion presented detailed results of the Sycamore Trial at the International Stroke Conference indicating positive trends in the 400 mg group on imaging. From the news coverage:
According to the results of the 62-person Phase II study, 50% of patients with cerebral lesions on the highest dose of REC-994 (400 mg) showed reduction in total lesion volume compared to 28% of patients on the placebo after 12 months of treatment. Patients on the lower dose of REC-994 (200 mg) had similar changes in lesion volume compared to placebo. Similar trends were seen in patients with brainstem lesions, a population with high unmet need as cavernomas located in the brainstem are not amenable to surgical intervention.
Additionally, the modified Rankin Scale, which is widely recognized and approved by the U.S. Food and Drug Administration (FDA) to assess functional outcomes in acute stroke trials, indicated positive trends in patients on the 400 mg arm.
When additional data was analyzed from a long-term extension of the original trial, the trends did not hold up, and Recursion made the difficult decision to discontinue the trial.
More background
Chris Gibson, Recursion CEO, presents the results of the REC-994 Phase 2 Sycamore Trial during a March 2025 webinar.
Chris Gibson gave the keynote speech at our July 2023 Scientific Meeting and Family Conference. In this presentation, he offers detailed information about the history of REC-994 development and Recursion’s work.
Join one of our patients as he begins participating in the clinical trial.
READ MORE
In this blog post, Recursion’s CEO Chris Gibson shares the origin story of REC-994 beginning in graduate school at the University of Utah.
Updated 05.06.2025
