Cybin Eyes Q4 Phase III Depression Readout as Psychedelic Pipeline Advances

Key Points

• Helus expects a fourth-quarter Phase III readout for HLP003, its deuterated psilocin treatment for adjunctive major depressive disorder. The APPROACH trial enrolled 223 patients and will report six-week MADRS efficacy, 12-week durability, and safety results.
• The broader PARADIGM program includes a second pivotal study, EMBRACE, with 330 planned patients, plus a one-year extension study. If successful, Helus is targeting a potential NDA filing and approval in 2028, supported by HLP003’s FDA breakthrough therapy designation.
• Helus is also advancing HLP004, a deuterated DMT program for generalized anxiety disorder, while developing preclinical compounds under HLP005. Management is focused on clinical execution and building infrastructure for a potential commercial launch.

Helus Pharma Chief Executive Officer Michael Halstead said the company expects a pivotal Phase III readout for its HLP003 program in adjunctive major depressive disorder in the fourth quarter, describing the data as a key near-term catalyst for the company’s mental health treatment pipeline.

Speaking at the Morgan Stanley 24th Annual Global Healthcare Conference, Halstead, who joined Helus in early August, outlined a platform spanning late-stage, mid-stage and preclinical serotonergic agonist programs. He said the company is advancing deuterated psilocin, HLP003, for adjunctive major depressive disorder, or MDD; deuterated DMT, HLP004, for generalized anxiety disorder; and HLP005, a preclinical library of compounds that Helus expects to begin advancing with a lead molecule in 2027.

Phase III depression program

Halstead said Helus’ Phase III PARADIGM program includes two pivotal studies and a long-term extension study intended to support a New Drug Application. The first pivotal trial, APPROACH, completed enrollment at the end of July, according to Halstead.

The APPROACH trial enrolled 223 patients and compares a 16-milligram dose of deuterated psilocin with placebo. Patients receive two doses, one at the start of the study and another at week three. The primary endpoint is efficacy at six weeks, measured using the Montgomery-Åsberg Depression Rating Scale, or MADRS, with a secondary assessment at week 12 intended to evaluate durability.

The second pivotal study, EMBRACE, is designed to enroll 330 patients and includes 16-milligram and 8-milligram dose arms as well as placebo, Halstead said. Participants from both pivotal studies may enter a long-term extension study that will collect safety and efficacy information over one year.

Helus has guided to a potential NDA filing in 2028. Halstead said HLP003 has FDA breakthrough therapy designation and that, if the program proceeds successfully, the company would anticipate approval in 2028 using a rolling-submission process.

Adjunctive MDD strategy

Halstead said the company selected adjunctive MDD because it provides access to a broader patient population than treatment-resistant depression. He estimated that approximately 23 million people in the United States have MDD, with about 70% receiving standard-of-care treatments such as SSRIs and SNRIs. Of those patients, he said roughly two-thirds do not receive optimal benefit from those therapies.

Using an adjunctive approach enables patients to remain on an existing treatment while adding another therapy, rather than undergoing a four-to-six-week washout period before beginning a new monotherapy, Halstead said. He characterized treatment-resistant depression as the later end of the treatment spectrum, involving multiple prior treatment failures, and estimated that population at about 3 million U.S. patients.

Halstead cited prior Phase II findings for HLP003, while noting that the results must translate into Phase III. He said the study showed 13 to 14 points of improvement after one dose at the three-week primary endpoint, followed by another five points of improvement on a raw basis after a second dose in an extension. He also said the company observed durability out to one year, with 100% of treated patients categorized as responders and more than 70% in remission.

According to Halstead, adverse events in the Phase II study were mild to moderate and temporary, generally occurring on the treatment day, with no serious adverse events associated with the drug.

For the upcoming APPROACH readout, Helus expects to disclose primary-endpoint results, the 12-week key secondary endpoint and standard safety data. Additional trial data may be presented at medical conferences as it becomes available, Halstead said.

Other pipeline priorities

For HLP004 in generalized anxiety disorder, Halstead said Helus completed a Phase II signal-finding study earlier this year and is finalizing the design of its next clinical trial this quarter. He described generalized anxiety disorder as an area with significant unmet need and said estimates place the U.S. patient population at roughly 20 million people.

Halstead said his immediate priorities are “execution, execution, execution,” including clinical development across the pipeline and building scalable infrastructure to support a potential commercial launch.

Addressing recent acquisitions in the central nervous system and psychedelic-treatment sectors, Halstead pointed to Eli Lilly’s acquisition of Atai and said large pharmaceutical companies appear to be responding to emerging clinical evidence, FDA guidance outlining a path toward approval, and the potential for clinician acceptance and viable reimbursement and commercial models.

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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