HLP003, Deuterated Psilocin, as an Adjunctive Therapy for Major Depressive Disorder

HLP003, an investigational novel serotonergic agonist under development at Helus Pharma, is positioned as an adjunctive treatment for major depressive disorder (MDD), said Ken Kramer, PhD. An estimated 23 million people in the United States and more than 300 million people worldwide live with MDD, and at least 50% of those on monotherapy with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) have an inadequate response to treatment, Kramer said. HLP003 is a deuterated analogue of psilocin, the active metabolite of psilocybin; deuteration stabilizes the otherwise unstable psilocin molecule, eliminating the need for in vivo conversion from psilocybin before it reaches the brain.

Unlike other psychedelic-derived compounds in development that target treatment-resistant depression, which affects only 20% to 25% of patients with MDD, HLP003 targets the larger adjunctive population, comprising 50% to nearly 60% of patients with MDD who show partial but inadequate response to first- or second-line therapy, Kramer said. "By adding on a complementary medication like HLP003, we are hopefully able to increase their response to their total medication," he emphasized. Because HLP003 is being evaluated as an add-on to an existing antidepressant rather than requiring a treatment-resistant designation, it could be used earlier in the treatment paradigm.

Current adjunctive options—lithium, thyroid hormone, and atypical antipsychotics—carry efficacy and tolerability limitations. Atypical antipsychotics, used for adjunctive MDD treatment for nearly 30 years, are associated with weight gain, sedation, akathisia, and extrapyramidal symptoms, and carry a higher risk of discontinuation due to adverse events than placebo.¹ These agents also require daily dosing on top of a background antidepressant, Kramer said. HLP003 is currently being evaluated in a phase 3 program as an add-on to an existing SSRI, SNRI, or other antidepressant.² Kramer noted, "If we get approved for adjunctive treatment of MDD and we slot into that line of therapy, then we will be able to treat not only a larger portion of patients with MDD, but we see ourselves being used prior to somebody being determined to be treatment resistant."

Dr Kramer is senior vice president and head of medical affairs at Helus Pharma.

References

1. Nelson JC, Papakostas GI. Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials. Am J Psychiatry. 2009;166(9):980-991.

2. Helus Pharma completes enrollment in phase 3 APPROACH study of HLP003 in adjunctive treatment of major depressive disorder ahead of schedule. Press release. July 21, 2026. Accessed August 14, 2026. https://ir.helus.com/news-releases/news-release-details/helus-pharma-completes-enrollment-phase-3-approach-study-hlp003