Nature Medicine Publishes Helus Pharma's Phase 2a Trial of SPL026 for Major Depression
Helus Pharma announced publication in Nature Medicine of Phase 2a trial results showing its short-acting psychedelic SPL026 met its primary endpoint with significant reductions in depressive symptoms at two weeks in moderate-to-severe MDD patients. The company also appointed a new SVP of Medical Affairs and is advancing HLP003 (Breakthrough Therapy Designation from FDA) and HLP004 in its pipeline.
Helus Pharma announced that results from its Phase 2a randomized, placebo-controlled clinical trial of SPL026 in participants with moderate-to-severe major depressive disorder have been published in Nature Medicine. The study met its primary endpoint, demonstrating statistically significant and clinically meaningful reductions in depressive symptoms at two weeks as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS).
Participants receiving a single 21.5 mg intravenous dose of SPL026 (n=17) showed a significant reduction in MADRS score compared to placebo (n=17) at two weeks (mean difference: -7.35; 95% CI, -13.62 to -1.08; p=0.023). The treatment effect was evident as early as one week (mean difference: -10.75; 95% CI, -16.95 to -4.55; p=0.002). Response rates (≥50% MADRS reduction) at Week 2 were 35% for SPL026 versus 12% for placebo, with remission rates (MADRS ≤10) at 29% versus 12%. Reductions in depressive symptoms were sustained at three months, with effects lasting up to six months in some participants. The treatment was generally well tolerated, with no treatment-related serious adverse events reported.
The trial enrolled 34 participants (mean age 32.8 years, 29.4% female) who had experienced depression for an average of 10.5 years. The study was conducted at Hammersmith Medicines Research in London, MAC Clinical Research in Liverpool, and Imperial College London. Lead investigator Dr. David Erritzoe from Imperial's Department of Brain Sciences noted that the data show the promise of DMT as a potentially more cost-effective treatment for clinical depression than related serotonergic agonists with longer psychoactive action, due to shorter dosing sessions.
The chief executive officer of Helus Pharma stated that the publication represents an important validation of short-acting serotonergic agonists as a clinically meaningful approach in mental health treatments. The findings provide clinical proof-of-concept for short-acting serotonergic modulation and support the company's conviction that its novel serotonergic agonist molecules, such as HLP004, can potentially deliver meaningful outcomes with greater consistency and commercial feasibility. The company said it expects to report topline data from its Phase 2 study of HLP004 in generalized anxiety disorder later this quarter.
Although Helus Pharma is not advancing intravenous SPL026 in its current form, the mechanistic and clinical insights generated from this trial continue to inform the company's HLP004 development program. HLP004 is designed to optimize pharmacology, consistency, and scalability for generalized anxiety disorder, and SPL026 is a nondeuterated analog of HLP004.
Helus Pharma is also developing HLP003, a proprietary novel serotonergic agonist (NSA), in Phase 3 clinical development for the adjunctive treatment of major depressive disorder. HLP003 has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration. The company describes NSAs as synthetic molecules designed to activate serotonin pathways believed to promote neuroplasticity.
In a separate development, Helus Pharma in April 2026 appointed Dr. Ken Kramer, PhD, as Senior Vice President, Medical Affairs. Kramer joins with more than two decades of experience leading medical affairs strategy across neuroscience programs, including global launch readiness and evidence generation. Most recently, he served as Vice President and Head of Medical Neuroscience at Bristol Myers Squibb, where he led an integrated medical strategy team that successfully launched the first new treatment for schizophrenia in over seven decades. Previously, Kramer served as VP and Head of Medical Affairs at Karuna Therapeutics, where he built medical capabilities during a period of significant organizational growth and supported the organization through its acquisition. Earlier in his career, he spent more than a decade leading U.S. psychiatry medical affairs teams at AbbVie and its predecessor organizations. Kramer holds a Ph.D. in Neuropharmacology from New York University.
Helus Pharma, the commercial operating name of Cybin Inc., is a clinical-stage pharmaceutical company trading on Nasdaq (HELP) and Cboe Canada (HELP). The company operates in Canada, the United States, the United Kingdom, and Ireland.