Helus Pharma Eyes Q4 Phase III Data for HLP-003 in Major Depression

Helus Pharma, formerly known as Cybin NASDAQ: HELP , outlined its late-stage development plans for HLP-003 in adjunctive major depressive disorder (MDD) and discussed its broader pipeline of serotonergic agonists during TD Cowen’s Novel Mechanisms in Neuropsychiatry virtual summit. Michael Halstead, who joined Helus as chief executive officer in early August, said the company is developing several programs intended to address mental health conditions. Its most advanced candidate, HLP-003, is deuterated psilocin and is in Phase III development as an add-on treatment for patients with MDD who have not adequately responded to background antidepressant medication. Halstead said the company expects top-line results from its first Phase III trial, called APPROACH, in the fourth quarter. Helus anticipates filing a New Drug Application for HLP-003 in 2028, supported by its broader Phase III program. Amir Inamdar, Helus Pharma’s chief medical officer, described APPROACH as a placebo-controlled study evaluating two 16-milligram doses of HLP-003 administered three weeks apart. The study’s primary endpoint is at six weeks, while a secondary endpoint at 12 weeks is intended to assess durability of effect. The trial enrolls patients with moderate-to-severe MDD who are receiving stable doses of antidepressants but remain inadequately responsive. Helus raised the minimum Montgomery-Åsberg Depression Rating Scale, or MADRS, score for enrollment to 24 from 21 in its Phase II trial. Participants may remain on background selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. However, monoamine oxidase inhibitors and tricyclic antidepressants are excluded, as are antipsychotics and mood stabilizers. Inamdar said antipsychotics could interfere with the pharmacodynamic effects of psychedelic compounds, while use of mood stabilizers may indicate conditions other than unipolar depression. Helus has not disclosed the statistical power of APPROACH. Halstead said the company believes the study is powered comparably with other late-stage trials in the drug class. Inamdar said that in the company’s Phase II study, a single dose of HLP-003 produced an approximately 13-point effect on MADRS, followed by an additional roughly 5.5-point benefit after a second administration. He said the Phase III design incorporates the second dose into the six-week primary endpoint. Halstead cautioned against comparing the adjunctive MDD study directly with monotherapy trials or studies in other conditions. He said currently marketed adjunctive antipsychotic therapies have shown roughly two to three points of improvement in some trials and four to five points for the strongest products, while carrying cardiometabolic and sexual-dysfunction side-effect burdens. The company expects to report the six-week primary efficacy endpoint, 12-week data, and customary safety and adverse-event information in its top-li...