Cybin Inc. CYBN has launched its Phase 3 pivotal program called PARADIGM, which is aimed at testing the efficacy of its lead candidate, CYB003, for treating Major Depressive Disorder (MDD) in a move that comes after three years of development.

“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, CEO of Cybin.

The design of the PARADIGM program, according to Drysdale, has been shaped by a collaborative process with the Food and Drug Administration (FDA), taking into account the challenges faced by other companies in this space. He said the trials are recruiting from a broader MDD population, allowing patients to stay on their existing antidepressant regimen while testing CYB003 as an additional treatment.

“The program name, PARADIGM, represents our belief that CYB003 could have the potential for a paradigm shift in the treatment of depression,” the company shared in a press release.

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Breaking Down The Phase 3 Program

The PARADIGM program consists of three key studies:

1. APPROACH will enroll 220 participants across 36 sites in the U.S. and Europe. The study compares a 16 mg dose of CYB003 against a placebo, with two doses given three weeks apart. The main goal is to assess the change in depressive symptoms using the MADRS score at the six-week mark.
2. EMBRACE will involve 330 participants, testing 16 mg and 8 mg doses of CYB003 alongside a placebo. It follows a similar two-dose regimen, focusing on patients whose current antidepressants are not providing adequate relief. This trial spans 48 clinical sites.
3. EXTEND will roll over participants from the first two studies, offering additional doses of CYB003 to those who do not respond or who relapse. The aim is to evaluate the long-term effects of the treatment.

“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% remission rate in the 16 mg dose group,” explained Amir Inamdar, Cybin’s chief medical officer.

Promising Results From Phase 2

The Phase 2 trial results set the stage for these new studies. Both the 12 mg and 16 mg dosing groups showed a mean reduction of about 22 points in MADRS scores. For the 16 mg group, 75% of patients achieved a response, defined as at least a 50% reduction in MADRS scores and the same percentage reached remission (MADRS score ≤10).

In terms of safety, CYB003 was well tolerated, with only mild or moderate adverse events reported. No serious drug-related adverse events were noted and there were no cases of suicidal ideation or discontinuations due to side effects.

Next Steps And Future Plans

The APPROACH study is already underway, with initial results expected in 2026. EMBRACE is slated to begin in early 2025. Beyond CYB003, Cybin is also progressing with its deuterated DMT program, CYB004, now in Phase 2 trials for generalized anxiety disorder. Results from this study are anticipated in the first quarter of 2025.

“The need for improved treatments for mental health disorders has never been greater,” said Inamdar.

Financial Update: Q2 Fiscal Year 2025

Cybin also reported its financial results for the second quarter ending September 30, 2024:

• Cash totaled C$154.3 million as of September 30, 2024. With the completion of offerings and assuming the full exercise of issued warrants, the company has access to over C$219.2 million.
• Cash-based operating expenses, including research, general, and administrative costs, amounted to C$24.8 million, a significant increase from C$12.4 million during the same quarter last year.
• The company reported a net loss of C$57.2 million for the quarter, compared to a net loss of C$11.9 million in the prior year, which includes a one-time, non-cash expense related to share-based compensation.
• Cash flows used in operating activities were C$25.9 million, up from C$11.5 million in the same period last year.

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