Positive 12-Month Data for REC-994

The Company announced in September 2024 that the signal-finding study met its primary endpoint.

These results were presented at the Late-Breaking Science Concurrent Oral Abstract Sessions at the International Stroke Conference (ISC) in Los Angeles, CA. Recursion will also hold a webinar on Thursday, February 6th at 6:30am MT/8:30am ET/1:30pm GMT to present the Phase II data. The webinar will be broadcast from Recursion’s X (formerly Twitter), LinkedIn, and YouTube accounts with an opportunity to submit questions here. The full presentation can be accessed after the webinar on Recursion’s events & presentation page.

"The results of the SYCAMORE trial demonstrate safety of REC 994 for CCM patients and promising trends of efficacy including 50% of patients achieving a reduction in mean lesion volume after 12 months of treatment and improved functional outcome as assessed by mRS at the 400 mg dose. My co-investigators and I are encouraged by these initial findings and we look forward to continued work with Recursion on the REC 994 program,” said Dr. Jan-Karl Burkhardt, MD, Division Head, Cerebrovascular Surgery, University of Pennsylvania and Principal Investigator of the study.

As the first industry-initiated trial in CCM, the SYCAMORE study was designed to evaluate safety as well as efficacy signals with broad patient populations. The trial was not powered to demonstrate statistical difference against placebo, and patients were not stratified or enriched across dose levels.

REC 994 SYCAMORE Phase II Trial Results;

Safety & Tolerability (primary endpoint)

• i.  No safety signals observed, with incidence of adverse events comparable between treatment and placebo arms.
• ii. Most common adverse events reported in at least 10% of participants included: Covid-19, dizziness, headache, back pain, and constipation.
  • iii. No SAEs related to study drug.
  • iv. Majority of TEAEs were Grade 1-2.
  • v.  No treatment-related adverse events that led to discontinuations.
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  • Total Cerebral Lesion Volume;
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  • i. After 12 months of treatment, 50% of patients on REC 994 400 mg (N=20) demonstrated reduction in total lesion volume (LV) versus 28% observed in placebo (N=18) . Patients on REC 994 200 mg (N=17) had similar changes in lesion volume compared to placebo.
  • ii. An absolute mean decrease in total lesion volume of −457 mm³ was observed in the 400 mg arm vs. an absolute mean increase of 61 mm³ and 53 mm³ in the 200 mg and placebo arms, respectively.
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  • Modified Rankin Scale (mRS) scores;
  • • i. The modified Rankin Scale (mRS) is widely recognized and approved by the FDA as a clinically meaningful endpoint for assessing functional outcomes in acute stroke trials. A single point change on the mRS is clinically relevant, with precedent for the FDA accepting dichotomous approaches using mRS cutoffs.
    • ii. At baseline, patients on REC 994 400 mg had a greater proportion of mRS scores ≥ 3, including an mRS score of 4-5, indicating that at the start of study these patients had worse clinical function versus the placebo arm.
    • iii. After 12 months of treatment, patients on REC 994 400 mg demonstrated trends toward improvement and/or stabilization of symptoms versus the placebo arm, which observed trends towards functional decline.
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    • Brainstem Cohort;
    • • i. Similar trends in lesion volume reduction and improvement or stabilization as assessed by mRS in the 400 mg REC 994 arm were seen in patients with brainstem lesions
      • ii. These observations support further investigation in a population of high unmet need, as cavernomas located in the brainstem are not amenable to surgical intervention
         
    • Additional secondary and exploratory analyses;
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    • i. Time-dependent reductions in hemosiderin ring size observed in the 400 mg arm as compared to 200 mg and placebo.
    • ii. Seizure frequency appeared to be reduced in the 400 mg arm as compared to 200 mg and placebo however, there was imbalance with respect to seizure history and frequency across the arms.
    • iii. Incidence of new symptomatic hemorrhage events were comparable across arms and in line with natural history studies.
    • iv. Other PROs including PROMIS29, CCM-HI, NIHSS, SMSS, CGI, and PGI did not demonstrate differences between the treatment arms of the study nor placebo.
    • Recursion intends to submit these data for publication in a peer reviewed scientific journal. Next steps will be guided by regulatory discussions and on-going long term extension study.