Cybin Inc. announced the initiation of PARADIGM, its Phase 3 pivotal program evaluating the efficacy and safety of CYB003 for the adjunctive treatment of Major Depressive Disorder (?MDD?). The program name, PARADIGM, represents the Company's belief that CYB003 could have the potential for a paradigm shift in the treatment of depression. The Company also now reported unaudited financial results for its second quarter ended September 30, 2024.

The Company?s Phase 3 program comprises three pivotal efficacy studies: Pivotal study 1 (APPROACH): Participants (n=220) will be randomized 1:1 to receive either 16 mg of CYB003 (n=110) or inactive placebo (n=110). Each study arm will evaluate a two-dose regimen, with doses administered three weeks apart. The study will enroll patients suffering from moderate to severe MDD (MADRS=24) who are on a stable dose of antidepressant medication but are responding inadequately.

The primary endpoint will be change in depressive symptoms as measured by change in MADRS from baseline at six weeks after the first dose. APPROACH will enroll participants at 36 clinical sites across the U.S. and Europe. Pivotal study 2 (EMBRACE): Participants (n=330) will be randomized 1:1:1 to receive 16 mg of CYB003 (n=110), 8 mg of CYB003 (n=110), or inactive placebo (n=110).

Each arm will evaluate a two-dose regimen, with doses administered three weeks apart. The study will enroll patients suffering from moderate to severe MDD (MADRS=24) who are on a stable dose of antidepressant medication but are responding inadequately. The primary endpoint will be change in depressive symptoms as measured by change in MADRS from baseline at six weeks after the first dose.

EMBRACE is expected to enroll at 48 clinical sites, with minimal site overlap with the APPROACHstudy. Pivotal study 3 (EXTEND): Participants from APPROACH and EMBRACE will roll over into EXTEND (up to n=550) after the completion of the 12-week, double-blind, placebo-controlled treatment periods.During EXTEND, all participants who did not respond to treatment in the APPROACH and EMBRACE studies or who relapse during the EXTEND study will be eligible to receive an additional two doses of CYB003 (16 mg) administered three weeks apart. Participants who do not respond to these two doses or relapse again will be eligible to receive an additional single 16 mg dose of CYB003.

Safety and tolerability: CYB003 was well tolerated with no drug-related serious adverse events. All adverse events were mild or moderate in intensity. No incidents of suicidal ideation or behavior.

No discontinuations due to adverse events. Upcoming Clinical Milestones and Future Studies Across Cybin?s Pipeline: CYB003 - Deuterated Psilocin Program. 12-month efficacy data from Phase 2 MDD study expected Fourth Quarter 2024.

The first pivotal study APPROACH has been initiated, with topline results expected in 2026. The second pivotal study EMBRACE is expected to begin in the first half of 2025. CYB004 ?

Deuterated DMT Program: Dosing is underway in a Phase 2 study in generalized anxiety disorder with topline safety and efficacy results expected in First Quarter 2025.CYB004 is being developed as a novel intramuscular formulation expected to deliver an experience lasting approximately 90 minutes.