Nature Medicine Publishes Helus Pharma's Randomized, Placebo-Controlled Phase 2a Trial of SPL026 in Major Depressive Disorder

Executive Summary

• Helus Pharma announced that its Phase 2a randomized, placebo‑controlled trial of SPL026 met its primary endpoint, showing a statistically significant and clinically meaningful reduction in MADRS scores versus placebo at two weeks (mean difference = ‑7.35; p = 0.023).
• Antidepressant effects were observed as early as one week and persisted for up to three months (with some participants maintaining benefit for six months); the single 21.5 mg IV dose was well tolerated with no treatment‑related serious adverse events.
• The results, published in Nature Medicine, provide proof‑of‑concept for short‑acting serotonergic agonists and support Helus’s ongoing HLP004 program, with topline Phase 2 data for generalized anxiety disorder expected in Q1 2026.

Key Details

• Study Design: Randomized, double‑blind, placebo‑controlled Phase 2a trial; 34 participants (17 SPL026, 17 placebo).
• Dose & Administration: Single 21.5 mg intravenous infusion of SPL026 over 10 minutes.
• Primary Endpoint (Week 2): Mean MADRS reduction ‑7.35 vs. placebo (95 % CI: ‑13.62 to –1.08; p = 0.023).
• Early Efficacy (Week 1): Mean MADRS reduction ‑10.75 vs. placebo (95 % CI: ‑16.95 to –4.55; p = 0.002).
• Response Rates (≥50 % MADRS reduction) at Week 2: 35 % SPL026 vs. 12 % placebo.
• Remission Rates (MADRS ≤10) at Week 2: 29 % SPL026 vs. 12 % placebo.
• Durability: Open‑label extension showed maintained effect up to three months; some participants reported benefit lasting six months.
• Safety: No treatment‑related serious adverse events; overall tolerability was favorable.
• Publication: Results appear in Nature Medicine (DOI 10.1038/s41591-025-04154-z).
• Implications for Pipeline: Data reinforce the therapeutic potential of short‑acting serotonergic agonists and inform Helus’s HLP004 development for generalized anxiety disorder; Phase 2 topline data for HLP004 expected Q1 2026.
• Future Plans: Helus will not advance intravenous SPL026 in its current form but will leverage mechanistic insights for HLP004, a non‑deuterated analog optimized for scalability and consistency.

Notable Quotes

“We have shown that a single dose of SPL026 is safe, effective and durable, with treatment effects comparable to other promising interventional treatments often requiring much longer treatment sessions.” – Dr. David Erritzoe, Lead Investigator

“The findings provide clinical proof‑of‑concept for short‑acting serotonergic modulation and further support our conviction that our novel serotonergic agonist molecules, such as HLP004, can potentially deliver meaningful outcomes with greater consistency and commercial feasibility.” – Michael Cola, CEO, Helus Pharma