Clinical Safety and Efficacy of RL-007 from a Phase2a Study of Cognition in Schizophrenia Patients

This work was sponsored by Recognify Life Sciences and atai Life Sciences Background: Approximately 80% of schizophrenia patients are impacted by significant cognitive impairments. RL-007, an oral pro-cognitive neuromodulator, has been evaluated in pre-clinical and clinical trials and shown to be safe and well tolerated in > 500 human subjects. In addition, consistent, dose-dependent effects on cognition have been observed. Methods: This Phase 2a trial in patients with cognitive impairment associated with schizophrenia (CIAS) was a single-arm, single-blind, placebo lead-in, multiple-dose proof of concept study of oral RL-007. Patients received a placebo lead-in. Starting from Day 2, RL-007 was administered at one of 4 dose levels (TID): 10 mg, 20 mg, 40 mg, and 80 mg. Efficacy was assessed on Day 4. Results: The study enrolled 37 patients. The mean age was 37.4 years (range 23–50). No new or unexpected adverse events (AEs) were observed. AEs were assessed as mild or moderate with no SAEs and independent of any dose levels of RL-007. Among the cognitive endpoints assessed, potentially clinically meaningful changes were observed on the symbol coding task for the dose levels 20-80mg (TID) (Cohen’s d = 0.38–0.79). Additionally, changes were observed in the verbal learning task in the 20mg dose and category fluency in the 40mg dose. Discussion: RL-007 was safe and well tolerated. The demonstrated cognitive improvements are consistent with prior non-clinical and clinical data and supportive of the use of the 20–40 mg dose range. There is an on-going 6-week Ph2b study in CIAS to assess the safety and efficacy of a longer treatment duration.