Cybin Inc. announced Phase 2 interim results for CYB003, its proprietary deuterated psilocybin analog, demonstrating a rapid, robust and statistically significant reduction in symptoms of depression three weeks following a single 12mg dose compared to placebo. At the 3-week primary efficacy endpoint, the reduction in major depressive disorder (MDD) symptoms, defined as change from baseline in MADRS total score, was superior in participants assigned to CYB003 compared to the participants who received placebo by 14.08 points (p=0.0005, Cohen?s d=2.15). A p-value indicates statistical significance.

Generally, values <0.05 are considered statistically significant and values <0.001 are considered highly statistically significant. The Phase 2 clinical trial is evaluating efficacy using the MADRS scale, with a primary efficacy endpoint of reduction in depression symptoms (change from baseline in MADRS) at week 3 after a single administration. To date, dosing has been completed in all dose cohorts up to 16mg, with a favorable safety and tolerability profile and no treatment-related serious adverse events observed.

Interim results from the 12mg dose cohort have demonstrated a statistically significant and clinically meaningful reduction in symptoms of depression with a single dose at three weeks after treatment. The MADRS is a 10-item, clinician-administered scale designed to measure overall severity of depressive symptoms in subjects with MDD. It is widely used in clinical trials and accepted by regulatory authorities worldwide as a measure of symptoms of depression.

The MADRS includes items ranging from sadness of mood, reduction in sleep and appetite, to difficulties in concentration, anhedonia, and negative and suicidal thoughts that are scored from 0 to 6 giving a total score ranging from 0 to 60. Typical score ranges for severity are: 0-6 normal; 7-19 mild; 20-34 moderate; and >34 severe depression. In the CYB003 study, mean baseline total scores on the MADRS were 32.6 and 33.3 in the active and placebo groups, respectively.

Summary of CYB003 12mg interim efficacy data at three weeks: Rapid and statistically significant improvements in depression symptoms observed after single doses of CYB003: Improvements in depression symptoms evident on the day after dosing, reaching a peak 10 days after dosing, and maintained thereafter. Robust and statistically significant reduction in depression symptoms compared to placebo at 3 weeks, with a -14.08 difference in change from baseline in MADRS for CYB003 vs. placebo (p=0.0005) Robust response (=50% reduction in MADRS) and remission (MADRS scores =10) rates at three weeks after single dose: 53.3% response rate for CYB003 (12mg) vs.

0% for placebo, 20.0% remission rate for CYB003 (12mg) vs. 0% for placebo. Safety and tolerability: CYB003 was well tolerated with no drug-related Serious Adverse Events, All Adverse Events were mild or moderate in intensity and resolved spontaneously without intervention.

Upcoming milestones: Full topline safety and efficacy data from the CYB003 MDD study is expected by the end Fourth Quarter 2023, with 12-week durability data anticipated in First Quarter 2024. Cybin plans to submit this topline data to the FDA and request an end of Phase 2 meeting to be held in First Quarter 2024. Recruiting for a CYB003 Phase 3 study is anticipated to begin by the end of First Quarter 2024.

The Company also expects to share topline Phase 1 data for CYB004 and SPL028, its proprietary novel deuterated N,N-dimethyltryptamine (?DMT?) compounds, before the end of 2023, supporting the initiation of a Phase 2 study in participants with generalized anxiety disorder in First Quarter 2024. The Phase 1/2 trial is a randomized, double-blind, placebo-controlled study evaluating CYB003 in participants with moderate to severe MDD and in healthy volunteers. Participants with MDD received two administrations (placebo/active and active/active) three weeks apart and response/remission are assessed three weeks after each dose.

MDD participants in the trial that are currently being treated with antidepressants are allowed to remain on their antidepressant medication. The study is evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics, and psychedelic effect of ascending oral doses of CYB003. In participants with MDD, the trial evaluates rapid onset of antidepressant effect on the day of dosing, using MADRS to evaluate the incremental benefit of a second dose of CYB003 when administered at Week 3. An optional period of assessment will help determine the durability of treatment effect out to 12 weeks.