Cybin Inc. has commenced its Phase 3 PARADIGM program, a pivotal step in evaluating CYB003 for the adjunctive treatment of major depressive disorder (MDD). The program is designed with three pivotal efficacy studies: APPROACH, EMBRACE, and EXTEND, aiming to establish CYB003 as a potential paradigm shift in depression treatment.
Phase 3 Trial Designs
The APPROACH study is currently enrolling 220 participants across 36 sites in the U.S. and Europe. Participants are randomized 1:1 to receive either 16 mg of CYB003 or a placebo, administered in a two-dose regimen three weeks apart. The primary endpoint is the change in depressive symptoms, measured by the change in MADRS (Montgomery-Åsberg Depression Rating Scale) from baseline at six weeks after the first dose. Topline results are anticipated in 2026.
The EMBRACE study, expected to begin in the first half of 2025, will randomize 330 participants 1:1:1 to receive 16 mg of CYB003, 8 mg of CYB003, or a placebo. Like APPROACH, EMBRACE will use a two-dose regimen with doses administered three weeks apart. The primary endpoint mirrors APPROACH, focusing on the change in MADRS from baseline at six weeks after the first dose. This study will be conducted across 48 clinical sites, with minimal overlap with the APPROACH study sites.
The EXTEND study is an open-label extension where participants from APPROACH and EMBRACE can enroll (up to n=550) after completing the initial 12-week, double-blind, placebo-controlled periods. Participants who do not respond to treatment or relapse will be eligible to receive additional doses of CYB003.
CYB003: A Deuterated Psilocin Analog
CYB003 is a proprietary deuterated molecule related to psilocybin, designed to offer a potentially more durable treatment option for depression. It has been granted breakthrough therapy designation for moderate to severe depressive disorder. The innovative approach of CYB003 aims to move away from daily symptom management towards an intermittent treatment that could alter the course of the disease.
Phase 2 Data Highlights
Previous Phase 2 studies have shown promising results, with robust and sustained improvements in depression symptoms following two doses of 12 mg or 16 mg of CYB003. The mean reduction from baseline in the MADRS total score was approximately 22 points in both dosing cohorts. Notably, around 75% of patients experienced a ≥50% improvement in MADRS scores after two 16 mg doses, with 75% achieving remission (MADRS score ≤10).
Safety and Tolerability
In Phase 2 trials, CYB003 was well-tolerated, with no drug-related serious adverse events. All adverse events were mild or moderate in intensity, and there were no reports of suicidal ideation or behavior, nor any discontinuations due to adverse events.
Market Opportunity
MDD affects over 300 million people worldwide and 21 million in the U.S., highlighting the significant unmet need for improved treatments. Cybin's CYB003 aims to address this need with a novel treatment modality that demonstrates consistent and durable effects.
