Mr. Doug Drysdale reports

CYBIN INITIATES PARADIGM: A MULTINATIONAL PIVOTAL PHASE 3 PROGRAM EVALUATING CYB003 FOR THE ADJUNCTIVE TREATMENT OF MAJOR DEPRESSIVE DISORDER AND REPORTS SECOND QUARTER FINANCIAL RESULTS

Cybin Inc. has initiated 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 today reported unaudited financial results for its second quarter ended Sept. 30, 2024.

"Just three years after filing an investigational new drug application for CYB003, the initiation of our phase 3 program is a truly significant and gratifying milestone," said Doug Drysdale, chief executive officer of Cybin. "Following a highly collaborative and thorough design and review process with the U.S. Food and Drug Administration, we believe that Paradigm incorporates appropriate protocols that pro-actively address some of the challenges encountered by peers developing molecules with similar mechanisms of action by: (i) recruiting from the larger MDD population; (ii) administering CYB003 as an adjunctive treatment and not requiring patients to titrate off their existing antidepressants; and (iii) utilizing a 12-week blinded period to maximize the number of patients that remain in the study through the blinded stage. Our innovative approach represents a potential paradigm shift, moving away from the daily treatment of depression symptoms and toward an intermittent, more durable treatment like CYB003 that could potentially change the course of the disease. Our clinical team has accomplished an extraordinary amount in a short time, and we are eager to continue investigating CYB003's potential to provide long-lasting relief from depressive symptoms and disrupt the standard of care in MDD," concluded Mr. Drysdale.

About the phase 3 paradigm pivotal program

The company's phase 3 program comprises three pivotal efficacy studies:

Pivotal study 1 (Approach)

Participants (n equal to 220) will be randomized 1:1 to receive either 16 milligrams of CYB003 (n equal to 110) or inactive placebo (n equal to 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 (Montgomery-Asberg Depression Rating Scale greater or equal to 24) who are on a stable dose of antidepressant medication but are responding inadequately.

The primary end point 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 United States and Europe.

Pivotal study 2 (Embrace)

Participants (n equal to 330) will be randomized 1:1:1 to receive 16 milligrams of CYB003 (n equal to 110), eight milligrams of CYB003 (n equal to 110) or inactive placebo (n equal to 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 greater or equal to 24) who are on a stable dose of antidepressant medication but are responding inadequately.

The primary end point 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 Approach study.

Pivotal study 3 (Extend)

Participants from Approach and Embrace will roll over into Extend (up to n equal to 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 milligrams) 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-milligram dose of CYB003.

Across all three studies, raters will be remote, independent and blinded, with no information on the dose received or the participant's dosing experience. Effects during the dosing session will be firewalled to ensure that the study team stays blinded.

"Our unique phase 3 pivotal program design has been informed by the impressive phase 2 (four-month) data showing rapid, robust improvements in symptoms of depression with a single dose of CYB003 and durable effects four months after two doses with a 75-per-cent remission rate in the 16-milligram dose group. For our pivotal program, we have preserved the two-dose regimen used in our phase 2 study, given the strong durability results seen to date," said Amir Inamdar, chief medical officer of Cybin. "The need for improved treatments for mental health disorders has never been greater. We believe that our phase 3 program can build on the positive results demonstrated in phase 2 to date and could potentially lead to the approval and commercialization of a novel treatment modality whose effects are consistent and durable for patients with MDD."

Positive phase 2 four-month efficacy data for CYB003 in MDD:

• Robust and sustained improvements in symptoms of depression with two doses of 12 milligrams or 16 milligrams of CYB003:
  • Mean reduction from baseline in the MADRS total score was approximately 22 points from baseline in both dosing cohorts.
  • Approximately 75 per cent of the patients were responders (greater than or equal to 50-per-cent improvement in MADRS scores) following two doses of 16 milligrams.
  • Seventy-five per cent of patients on 16 milligrams were in remission from depression following two doses (MADRS score greater than or equal to 10).

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 behaviour.
• There were no discontinuations due to adverse events.

Coming clinical milestones and future studies across Cybin's pipeline:

• CYB003 -- deuterated psilocin program:
  • 12-month efficacy data from phase 2 MDD study expected Q4 2024;
  • The first pivotal study (Approach) has been initiated, with top-line results expected in 2026;
  • The second pivotal study (Embrace) is expected to begin in the first half of 2025;
• CYB004 -- deuterated DMT (N,N-dimethyltryptamine) program:
  • Dosing is under way in a phase 2 study in generalized anxiety disorder with top-line safety and efficacy results expected in Q1 2025; CYB004 is being developed as a novel intramuscular formulation expected to deliver an experience lasting approximately 90 minutes.

Second quarter fiscal year 2025 financial information

• Cash totalled $154.3-million as of Sept. 30, 2024.
• With the completion of offerings and a combination of the company's current cash position and assuming the exercise in full of warrants issued pursuant to certain of the company's offerings, the company has access to over $217.7-million.
• Cash-based operating expenses consisting of research, general and administrative costs totalled $24.8-million for the quarter ended Sept. 30, 2024, compared with $12.4-million in the same period last year.
• Net loss was $57.2-million for the quarter ended Sept. 30, 2024, which includes a non-recurring, non-cash component related to share-based compensation, compared with a net loss of $11.9-million in the same period last year.
• Cash flows used in operating activities were $25.9-million for the quarter ended Sept. 30, 2024, compared with $11.5-million in the same period last year.

About Cybin Inc.

Cybin is a late-stage breakthrough neuropsychiatry company committed to revolutionizing mental health care by developing new and innovative next-generation treatment options to address the large unmet need for people who suffer from mental health conditions.

With industry-leading proof-of-concept data, Cybin is working to change the mental health treatment landscape through the introduction of intermittent treatments that provide long-lasting results. The company is currently developing CYB003, a proprietary deuterated psilocin program, in phase 3 development for the adjunctive treatment of MDD; and CYB004, a proprietary deuterated DMT program in a phase 2 study for generalized anxiety disorder. The company also has a research pipeline of investigational, 5-HT-receptor-focused compounds.

Founded in 2019, Cybin is operational in Canada, the United States, the United Kingdom, the Netherlands and Ireland.

We seek Safe Harbor.