Cybin Eyes Q4 Phase III Depression Data as Anxiety Program Advances

Key Points

• Top-line Phase III data for HLP003, a deuterated psilocin candidate for adjunctive major depressive disorder, is expected in the fourth quarter of 2026. The APPROACH study enrolled 223 participants and remains on schedule, with results including MADRS scores, response and remission rates, and safety data.
• The company is positioning HLP003 as a potential alternative to adjunctive antipsychotics, citing earlier Phase II improvements of roughly 13–14 MADRS points versus placebo after three weeks and additional improvement after a second dose.
• HLP004, a deuterated DMT candidate for generalized anxiety disorder, is expected to enter a 144-patient Phase II trial in the first quarter of 2027. The randomized study will assess two 30-milligram intramuscular doses using HAM-A scores at six and 12 weeks.

Cybin NASDAQ: HELP outlined plans for two late-stage mental health programs, with top-line data from its Phase III APPROACH study of HLP003 in major depressive disorder expected later in the fourth quarter of 2026.

Helus Pharma Chief Executive Officer Michael Halstead said the company is developing novel serotonergic agonists for mental health conditions. Its lead candidate, HLP003, is deuterated psilocin and is being studied as an adjunctive treatment for major depressive disorder, or MDD. The company’s HLP004 program, a deuterated DMT candidate for generalized anxiety disorder, or GAD, is expected to enter its next Phase II trial in the first quarter of 2027.

HLP003 Phase III Program Advances

Halstead said APPROACH, one of two Phase III efficacy studies for HLP003, completed enrollment and remains on schedule for a top-line readout later in the quarter. The trial enrolled 223 participants across 45 U.S. sites. Participants receive two administrations of either 16 milligrams of HLP003 or placebo, given three weeks apart, while continuing standard antidepressant treatment.

The trial’s primary endpoint is the change from baseline in the Montgomery-Åsberg Depression Rating Scale, or MADRS, at six weeks, with a key secondary endpoint at 12 weeks. Chief Medical Officer Amir Inamdar said the company plans to disclose demographic and baseline data, MADRS outcomes, responder and remitter rates, and adverse-event information in its top-line release.

Inamdar said the Phase III entry threshold was raised from a MADRS score of at least 21 in Phase II to at least 24 in Phase III. He said patients in APPROACH had an average baseline MADRS score of about 33, indicating moderate-to-severe depression.

In the company’s earlier Phase II study, a single dose of HLP003 produced an improvement in depression symptoms of approximately 13 to 14 MADRS points versus placebo at three weeks, according to Inamdar. Patients who received a second active dose experienced an additional improvement of about five points, he said. Helus also reported that, among a subset followed for one year after receiving two 16-milligram doses, all were responders and about 70% were in remission.

HLP003 has received FDA Breakthrough Therapy designation, which Inamdar said provides access to ongoing agency guidance and may allow a rolling review. The broader Phase III program includes the ongoing EMBRACE efficacy study and the EXTEND long-term extension study. EXTEND allows eligible participants from APPROACH and EMBRACE to receive up to three additional doses under prespecified conditions.

Focus on Adjunctive Depression Treatment

Management said it chose the adjunctive MDD setting because many patients do not achieve remission with initial antidepressant treatment. Halstead said there are more than 25 FDA-approved monotherapies for depression, most of which are generic, while five approved adjunctive treatments are atypical antipsychotics.

University of Toronto professor Roger McIntyre said existing adjunctive antipsychotic options can provide benefits but may be limited by side effects such as weight gain, metabolic disruption, sedation, akathisia and movement disorders. Panelists Rakesh Jain of Texas Tech University School of Medicine and Martha Koo of Your Behavioral Health also cited adherence and tolerability concerns in clinical practice.

Halstead said Helus views four- to five-point MADRS improvements as a best-in-class benchmark among approved antipsychotic adjunctive therapies. He said the company would view comparable efficacy, durability and a favorable tolerability profile as a strong potential commercial proposition for HLP003.

Addressing safety, Inamdar said suicidal ideation and behavior can occur as features of MDD and that Helus will report any suicidality adverse events in its top-line data. He added that APPROACH was monitored by an independent data monitoring committee and was not stopped for safety reasons.

HLP004 Study Planned for GAD

Helus also detailed plans for HLP004, its deuterated DMT candidate for GAD. Inamdar said deuteration is intended to stabilize DMT and extend its effects, while the company’s intramuscular formulation is designed to smooth the pharmacokinetic curve.

The company plans to initiate a randomized, double-blind, placebo-controlled Phase II monotherapy study in the first quarter of 2027. The study is expected to enroll about 144 adults with GAD, randomized equally to receive either 30 milligrams of HLP004 or placebo in two intramuscular administrations three weeks apart.

The primary endpoint will be change from baseline in the Hamilton Anxiety Rating Scale, or HAM-A, at six weeks, with a secondary assessment at 12 weeks. Eligible participants must have HAM-A scores of at least 20 at screening and baseline, while individuals with certain psychiatric conditions, clinically significant suicide risk, recent psychedelic exposure or substance-use disorders will be excluded.

Inamdar said the company selected the 30-milligram dose based on Phase I and Phase II findings, including dose-dependent effects and associations between emotional breakthrough measures and anxiety symptom improvements. He said the dose was well tolerated in the company’s studies.

Halstead said Helus expects its preclinical HLP005 library to provide another potential source of pipeline expansion, with a lead candidate expected to advance in the second half of 2027.

About Cybin (NASDAQ:HELP)

Cybin Inc is a clinical-stage biotechnology company focused on developing psychedelic-based therapeutics for mental health conditions. The company combines psychedelic compounds with drug-delivery technologies and treatment protocols designed to improve the safety, consistency and duration of psychedelic-assisted therapies.

Cybin's development programs have included CYB003, an investigational deuterated psilocybin therapy being studied for major depressive disorder, and CYB004, an investigational formulation of N,N-dimethyltryptamine (DMT) being evaluated for generalized anxiety disorder.

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