Cybin Eyes Q4 Phase 3 Data for Depression Drug HLP003

Key Points

• Cybin expects fourth-quarter Phase 3 data for HLP003, a deuterated psilocin analog being tested as an adjunctive treatment for major depressive disorder. The PARADIGM program includes two pivotal studies and a one-year extension study.
• Management cited encouraging Phase 2 results, including roughly 13- to 14-point improvements and remission rates above 70% through one year after two 16-milligram doses, but noted these findings must be replicated in Phase 3.
• HLP003 has received Breakthrough Therapy designation, with a potential 2028 U.S. approval target. Cybin is also advancing HLP004 for generalized anxiety disorder and reported approximately $166 million in cash as of June 30.

Cybin NASDAQ: HELP executives outlined plans for its late-stage depression program, including an expected fourth-quarter Phase 3 data readout for HLP003, during H.C. Wainwright’s 28th Annual Global Investment Conference. The company, referred to in the presentation as Helus Pharma, is developing serotonergic agonists and neuromodulators for mental health conditions.

Michael Halstead, who joined as chief executive officer in August, said the company’s lead program is evaluating HLP003, a deuterated psilocin analog, as an adjunctive treatment for major depressive disorder, or MDD. The company has completed enrollment in its first Phase 3 study and expects top-line results during the fourth quarter, although Halstead did not provide a more specific timing update.

Phase 3 Program Targets Adjunctive MDD Use

Chief Medical Officer Amir Inamdar said the Phase 3 PARADIGM program consists of two short-term pivotal studies, APPROACH and EMBRACE, along with the EXTEND long-term extension study.

• APPROACH compares two 16-milligram administrations of HLP003 with inactive placebo, with doses given three weeks apart. The primary endpoint is at six weeks, with a secondary endpoint at 12 weeks.
• EMBRACE has a similar design but also includes an 8-milligram dose, intended to assess dose response.
• EXTEND allows patients from the short-term studies to enter a blinded extension study lasting up to one year, with provisions for retreatment following relapse.

Inamdar said APPROACH is expected to enroll 220 patients, or about 110 per arm. He said the company has not disclosed the study’s formal powering assumptions.

Halstead emphasized that HLP003 is being studied alongside standard antidepressant treatments, including SSRIs and SNRIs, rather than as a replacement monotherapy. He said this adjunctive approach could allow clinicians to preserve any benefit a patient receives from existing standard-of-care treatments while seeking additional symptom improvement.

Management Cites Phase 2 Findings

According to Inamdar, a Phase 2 study of HLP003 showed approximately 13- to 14-point improvements at 12-milligram and 16-milligram doses three weeks after a single administration. A second dose produced an additional improvement of about five points, he said.

Inamdar said the Phase 3 primary endpoint incorporates the second dose, unlike the Phase 2 primary analysis. He also cited Phase 2 durability findings showing remission rates above 70% through one year after two 16-milligram doses, while cautioning that the smaller Phase 2 results will need to be replicated in Phase 3.

Management said deuteration is intended to stabilize psilocin and may improve drug delivery characteristics. Inamdar said preclinical studies showed HLP003 reached the brain rapidly and produced concentrations approximately 1.5 times higher at maximum concentration and 2.5 times higher in exposure, or area under the curve, compared with referenced measures.

Halstead said the Phase 2 safety profile included no severe drug-related adverse events. He described adverse events as generally mild to moderate and transient, primarily occurring on the treatment day, including headache, nausea, upset stomach and high blood pressure.

Regulatory and Pipeline Plans

Halstead said HLP003 has received Breakthrough Therapy designation. The company expects to file a new drug application in 2028 and, based on its anticipated review timeline, expects potential approval in the same year. He said recent FDA guidance and broader regulatory developments have provided greater clarity around the development path for psychedelic-based therapies.

Beyond HLP003, the company is advancing HLP004, a deuterated DMT program for generalized anxiety disorder. Halstead said the company completed a Phase 2 signal-finding study earlier in 2026 and is finalizing the design of its next clinical trial, with additional details expected soon.

The company also has an earlier-stage HLP005 compound library, with plans to move a lead candidate forward in 2027. Halstead said the company’s intellectual-property portfolio is expected to provide protection for HLP003 and HLP004 through at least 2041.

As of June 30, Halstead said the company had approximately $166 million on its balance sheet. He said management is comfortable that its current cash position can support near-term catalysts, while adding that longer-term cash runway guidance would be provided after further review.

About Cybin (NASDAQ:HELP)

Cybin Inc is a clinical-stage biopharmaceutical company focused on developing psychedelic-based therapeutics for the treatment of mental health conditions. The company combines drug discovery, clinical development and proprietary formulation technologies to design potentially more efficient and scalable psychedelic treatments.

Cybin's development programs have included CYB003, an investigational deuterated psilocybin analog being studied for major depressive disorder, and CYB004, an investigational deuterated DMT molecule being evaluated for generalized anxiety disorder and other mental health indications.

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