Mr. Michael Cola reports

NATURE MEDICINE PUBLISHES HELUS PHARMA'S RANDOMIZED, PLACEBO-CONTROLLED PHASE 2A TRIAL OF SPL026 IN MAJOR DEPRESSIVE DISORDER

Cybin Inc., operating as Helus Pharma, has noted the publication in Nature Medicine of results from a phase 2a randomized, placebo-controlled clinical trial evaluating SPL026, in participants with moderate-to-severe major depressive disorder (MDD).

• Randomized, placebo-controlled phase 2a study of SPL026 met its primary end point demonstrating a clinically significant reduction in depressive symptoms as measured by MADRS score (mean difference: negative 7.35) versus placebo at two weeks.
• Antidepressant treatment effects observed within one week and sustained for up to three months.
• Findings reinforce the therapeutic potential of short-acting serotonergic agonists and inform Helus Pharma's HLP004 development program, with phase 2 top-line data in generalized anxiety disorder (GAD) expected in Q1 2026.
• This news release constitutes a designated news release for the purpose of the company's prospectus supplement dated Dec. 30, 2025, to it short form base shelf prospectus dated Sept. 17, 2025, as amended on Dec. 19, 2025.

The study met its primary end point demonstrating statistically significant and clinically meaningful reductions in depressive symptoms at two weeks, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) in participants treated with SPL026 compared with placebo. Reductions in depressive symptoms were observed as early as one week following dosing and were sustained at three months, with effects lasting up to six months in some participants. The treatment was generally well tolerated, with no treatment-related serious adverse events reported.

"We have shown that a single dose of SPL026 is safe, effective and durable, with treatment effects comparable to other promising interventional treatments often requiring much longer treatment sessions." Dr David Erritzoe, from Imperial's Department of Brain Sciences, and lead investigator of the trial, continued, "Although such early trial results should always be interpreted with some caution, these data show the promise of DMT as a potentially more cost-effective treatment for clinical depression than related serotonergic agonists with longer psychoactive action due to the shorter dosing sessions."

This phase 2a study evaluated the efficacy and safety of SPL026. Participants receiving a single 21.5-milligram dose of SPL026 (n equals 17) demonstrated a significant reduction in MADRS score compared to placebo (n equals 17) at two weeks meeting the primary end point (mean difference: negative 7.35; 95 per cent CI (confidence interval), negative 13.62 to negative 1.08; p equals 0.023). The treatment effect of SPL026 was evident at one week (mean difference: negative 10.75; 95-per-cent CI, negative 16.95 to negative 4.55; p equals 0.002). Response rates (greater than or equal to 50-per-cent MADRS reduction) at week 2 were 35 per cent for SPL026 versus 12 per cent for placebo, with remission rates (MADRS less than or equal to 10) at 29 per cent vs. 12 per cent. During the open-label portion of the study, the treatment effect was maintained for up to three months.

"This publication represents an important validation of short-acting serotonergic agonists as a clinically meaningful approach in mental health treatments," said Michael Cola, chief executive officer of Helus Pharma. "The findings provide clinical proof of concept for short-acting serotonergic modulation and further support our conviction that our novel serotonergic agonist molecules, such as HLP004, can potentially deliver meaningful outcomes with greater consistency and commercial feasibility. We look forward to reporting top-line data from our phase 2 study of HLP004 in generalized anxiety disorder later this quarter."

Although Helus Pharma is not advancing intravenous SPL026 in its current form, the mechanistic and clinical insights generated from this trial continue to inform the company's HLP004 development program. Helus is currently advancing HLP004, a proprietary NSA, that is designed to optimize pharmacology, consistency and scalability for GAD, of which SPL026 is a nondeuterated analog.

About the study

The study was conducted at Hammersmith Medicines Research Ltd (London), MAC Clinical Research (Liverpool) and Imperial College London. This study was conducted by Helus Pharma Corp., a wholly owned subsidiary of Helus Pharma and the successor entity to Small Pharma Inc. The study was a phase 2a randomized placebo-controlled trial evaluating the safety and efficacy of SPL026, in adults with moderate-to-severe major depressive disorder. The trial enrolled 34 participants (mean age 32.8 years, 29.4-per-cent female, predominantly white) who had experienced depression for an average of 10.5 years. Participants were randomized in a double-blind manner to receive either a single 21.5 mg intravenous infusion of SPL026 over 10 minutes or placebo, combined with supportive psychotherapy sessions focused on preparation, integration and emotional processing.

In the blinded stage 1, the primary end point was the change in MADRS scores from baseline to week 2. Stage 2 was an open-label extension where all participants could receive a second SPL026 dose two weeks later; antidepressant effects persisted up to three months postfirst dose.

About Helus Pharma

Helus Pharma, the commercial operating name of Cybin Inc., is a clinical stage pharmaceutical company committed to helping minds heal by developing proprietary NSAs: synthetic molecules designed to activate serotonin pathways that are believed to promote neuroplasticity. The company's proprietary NSAs are intended to potentially address the large unmet need for people who suffer from depression, anxiety and other mental health conditions.

With class-leading data, Helus Pharma aims to improve the treatment landscape through the introduction of NSAs that aim to provide durable improvements in mental health. Helus Pharma is currently developing HLP003, a proprietary NSA, in phase 3 clinical development for the adjunctive treatment of major depressive disorder that has received breakthrough therapy designation from the United States Food and Drug Administration and HLP004, also a proprietary NSA in phase 2 for generalized anxiety disorder. Additionally, Helus Pharma has an extensive research portfolio of investigational NSAs.

The company operates in Canada, the United States, the United Kingdom and Ireland.

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