HLP003 Phase 3 Enrollment Complete; Psychedelic Depression Field Advances

Helus Pharma, the commercial operating name of Cybin Inc., has completed enrollment in APPROACH, the first pivotal Phase 3 study of its investigational drug HLP003 in patients living with major depressive disorder (MDD), ahead of schedule, with topline data on track for the fourth quarter of 2026. HLP003 is an investigational deuterated psilocin analogue that has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration. The broader psychedelic depression field is also advancing, with Compass Pathways' COMP360 on track to finalize its New Drug Application and a phase 2a trial of an ayahuasca-derived psychoactive ingredient showing promise.

The APPROACH study enrolled 223 participants with moderate to severe MDD, defined by a MADRS score of at least 24, who remain on a stable dose of antidepressant medication but continue to respond inadequately. Participants were randomized on a one-to-one basis to receive either HLP003 at 16 milligrams or placebo, with each arm evaluating a two-dose regimen given three weeks apart. The primary endpoint is the change from baseline in the Montgomery-Asberg Depression Rating Scale, or MADRS, at six weeks after the first dose compared with placebo, with a key secondary endpoint measuring the same scale at 12 weeks.

In its earlier Phase 2 study, Helus reported a mean reduction of roughly 23 points on the MADRS scale from baseline at 12 months following two 16-milligram doses administered three weeks apart, along with high response and remission rates. Phase 2 findings, however, are a signal rather than proof, and results in a larger, placebo-controlled Phase 3 setting can differ materially. The company has pointed toward a potential FDA New Drug Application in 2028.

Compass Pathways is developing COMP360, a proprietary synthetic psilocybin formulated for treatment-resistant depression (TRD). In final, large-scale human trials, COMP360 demonstrated the ability to deliver rapid and durable relief for patients with TRD, providing three to six months of relief. Currently, around 3 million patients in the US suffer from TRD, yet fewer than 5% are treated with medications developed specifically for the condition. Compass is on track to finalize its New Drug Application in the fourth quarter of this year.

A psychoactive ingredient found in ayahuasca, a brew used in shamanistic rituals in South America, has shown promise as a treatment for depression in a phase 2a trial.

In the psychedelic intellectual property landscape, 2025 saw 156 PCTs and 271 U.S. relevant patent applications added to the industry tracker, and 122 U.S. patents were issued to companies operating in the space. The database now spans nearly 1,500 U.S. patents and applications and over 1,000 PCT filings. CaaMTech, GH Research, Gilgamesh, Atai/Beckley, and Compass Pathways were among the most active filers, each with more than a dozen new publications.