Cybin Inc. announced a positive End-of-Phase 2 meeting with the FDA for CYB003, its deuterated psilocybin analog for the adjunctive treatment of Major Depressive Disorder (MDD). This program will be the first ever adjunctive Phase 3 deuterated psilocybin analog depression study globally and follows the successful completion of the Company?s Phase 2 study in MDD completed at the end of 2023. The Company has received minutes from its End-of-Phase-2 meeting with the FDA and reached alignment on its Phase 3 program design.

The Company intends to commence enrollment for the multinational, multisite Phase 3 program in mid-year 2024. Fifteen U.S. study sites have been targeted, all of which have experience running psychedelic clinical trials and are DEA Schedule I licensed. The preliminary targeting of specific study sites will serve to expedite site initiation.

The Company intends to add approximately 8 additional sites in Europe. The Company has engaged Worldwide Clinical Trials (Worldwide), a global, full-service contract research organization with deep expertise managing clinical trials for mental health conditions, including major depressive disorder. Worldwide has a track record of successful patient recruitment for psychedelic trials and global relationships with best-in-class investigative sites.

Worldwide has recent experience managing psychedelic studies in psychiatric populations, including clinical trials conducted in the U.S., Canada, United Kingdom, and other European countries, across a range of psychedelic compounds and treatment models. CYB003 Phase 3 Pivotal Program Outline: The Phase 3 pivotal program will comprise two adequate and well controlled studies and a long-term extension, designed as follows: CYB003-002 (n=220): Fixed repeat dose study of 16mg CYB003, with two doses 3 weeks apart compared to two doses of placebo. The trial is designed to replicate the treatment response seen in the Company?s Phase 2 study.

CYB003-003 (n=330): Three-arm fixed repeat dose study of CYB003 (16mg or 8mg), with two doses 3 weeks apart. Each active arm will be compared to two doses of placebo. The primary endpoint of both studies is the change in MADRS total score from baseline at Week 6, with a secondary endpoint at Week 12, each compared to placebo.

Patients from each of these Phase 3 trials will enroll in a one-year extension study, during which time non-responders and relapsing patients will receive one full cycle of CYB003 16mg (two doses, three weeks apart). Moderate to severe MDD patients enrolled in both studies (MADRS >/=24) will be on stable doses of background antidepressant medication, positioning CYB003 as a convenient, adjunctive treatment option. CYB003-002 is anticipated to begin around mid-year 2024, with CYB003-003 anticipated to initiate a few months later.

Each study is expected to run for approximately 18-24 months. Patient recruitment for the Phase 3 program will include a broad MDD population including only patients that are currently on antidepressants. Importantly, patients will not be required to titrate off their background antidepressants which will reduce some of the inherent recruitment challenges seen in other depression studies.

Summary of Positive Four-Month Efficacy Data for CYB003: Robust and sustained improvements in symptoms of depression four months after two doses of 12mg or 16mg of CYB003: Mean reduction from baseline in the MADRS total score was approximately 22 points from baseline in both dosing cohorts. Approximately 75% of the patients were responders (>/= 50% improvement in MADRS scores) following two doses of 16mg. 60% of patients on 12mg and 75% on 16mg were in remission from depression following 2 doses (MADRS score).

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. Earlier this week, Cybin announced the granting of BTD for CYB003 by the FDA. If approved by the FDA, CYB003 would be the first known adjunctive psychedelic-based therapeutic for the treatment of MDD.