Cybin Secures FDA Alignment for CYB003 Phase 3 Depression Trial—With Impressive Four-Month Efficacy Data Leading the Way

Cybin Inc. (NYSE American: CYBN) has unveiled encouraging outcomes from its End-of-Phase 2 consultation with the U.S. Food and Drug Administration regarding CYB003, a deuterated psilocybin compound designed as an add-on therapy for Major Depressive Disorder. The regulatory meeting has paved the way for the company to advance into Phase 3 clinical development, marking a significant milestone in psychedelic-assisted mental health treatment.

FDA Backing Accelerates Path to Phase 3

Following successful completion of the Phase 2 study in late 2023, Cybin received formal FDA meeting minutes and achieved consensus on its comprehensive Phase 3 program strategy. The company intends to launch enrollment for the multinational, multisite Phase 3 program during mid-2024. This initiative represents the first-ever multinational adjunctive Phase 3 deuterated psilocybin analog depression study globally.

The regulatory pathway has been further strengthened by CYB003’s Breakthrough Therapy Designation, which grants expedited FDA review and enhanced communication with regulators—a designation typically reserved for treatments addressing critical unmet medical needs.

Clinical Trial Infrastructure Takes Shape

Cybin has identified 15 U.S. investigational sites, all equipped with prior psychedelic trial experience and DEA Schedule I licensing credentials. The company is planning to establish approximately 8 additional European study sites. The engagement of Worldwide Clinical Trials, a specialized contract research organization with extensive psychedelic psychiatry trial management expertise, underscores the operational sophistication of the program.

Compelling Four-Month Efficacy Profile

The Phase 2 data presented a robust clinical picture. At the four-month assessment point—the primary efficacy window—the trial demonstrated:

• Approximately 75% of participants receiving 16mg CYB003 achieved remission from depression symptoms following two doses administered three weeks apart
• Sustained symptom improvement, with mean MADRS (Montgomery-Åsberg Depression Rating Scale) scores decreasing roughly 22 points from baseline across both dosing cohorts
• Approximately 75% of the 16mg group and 60% of the 12mg group qualified as responders, defined as ≥50% reduction in MADRS scores
• Durable treatment effects maintained through at least four months post-dosing

Phase 3 Study Architecture

The pivotal program will consist of two primary efficacy trials plus a long-term extension:

• CYB003-002 (n=220): A fixed-dose study comparing two administrations of 16mg CYB003 against placebo, designed to reproduce the Phase 2 treatment response
• CYB003-003 (n=330): A three-arm comparison evaluating 16mg and 8mg CYB003 versus placebo, each using two doses spaced three weeks apart

Both studies will employ Week 6 MADRS score change as the primary efficacy endpoint, with secondary analysis at Week 12. Notably, the trial design positions CYB003 as an adjunctive treatment—meaning enrolled moderate-to-severe MDD patients will continue their existing antidepressant regimens rather than tapering off, a design feature intended to streamline patient recruitment.

Both Phase 3 trials will include a one-year extension phase permitting non-responders and relapsing patients to receive a complete CYB003 16mg treatment cycle.

CYB003-002 is expected to open enrollment around mid-year 2024, with CYB003-003 anticipated to launch several months thereafter. Each study is projected to operate for approximately 18-24 months.

Strategic Implications

Doug Drysdale, Cybin’s Chief Executive Officer, commented on the regulatory progress: “The FDA’s thorough guidance and our alignment on pivotal program design components position us to advance efficiently. The clinical evidence—demonstrating sustained remission rates of 75% at four months, combined with Breakthrough Therapy designation and durable efficacy data—provides a compelling foundation for Phase 3 execution. We are now positioned to accelerate delivery of treatment alternatives to patients with treatment-resistant depression.”

The adjunctive treatment model represents a clinically pragmatic approach, as it accommodates the reality that many MDD patients remain on background antidepressant therapy, potentially expanding the addressable patient population for CYB003.