BEDFORD, Mass. — Delix Therapeutics, a clinical-stage neuroscience company developing non-hallucinogenic compounds known as neuroplastogens, announced positive Phase Ib results for zalsupindole (DLX-001) in adults with major depressive disorder (MDD). The company also confirmed that the U.S. Food and Drug Administration has cleared its Investigational New Drug application for a Phase II study design that includes at-home self-administration, underscoring the compound’s safety and scalability as an outpatient therapy.
Zalsupindole is a first-in-class, orally bioavailable neuroplastogen derived from 5-MeO-DMT, designed to promote structural and functional neuroplasticity without hallucinatory, sedative, or dissociative effects. Earlier Phase I data in healthy volunteers demonstrated safety, tolerability, target engagement, and the absence of psychotomimetic effects. Preclinical studies showed zalsupindole promotes neuroplasticity as rapidly and effectively as ketamine and serotonergic psychedelics, but without altering perception.
In the Phase Ib study, 18 adult patients with MDD received either daily dosing for seven days or two doses within one week. Both regimens showed significant antidepressant effects. Patients demonstrated a mean 12-point (approximately 50 percent) reduction on the Montgomery–Åsberg Depression Rating Scale by Day 8, with improvements sustained through Day 36—four weeks after the final dose. Quantitative electroencephalography and polysomnography confirmed robust biomarker changes linked to neuroplasticity. The drug was well tolerated, with no serious adverse events or hallucinatory effects reported, and similar efficacy between daily and intermittent dosing.
“These Phase Ib data are a major step forward,” said Mark Rus, Chief Executive Officer of Delix Therapeutics. “We saw rapid and robust improvements in depressive symptoms that persisted for weeks after treatment ended and, importantly, patients experienced benefits whether they received seven doses or just two. Paired with the absence of hallucinogenic or dissociative side effects in over 120 people to date, these results underscore the safety of our approach. Together, these data represent early proof-of-concept, and with the FDA now clearing our Phase II protocol, including at-home self-administration, we’re closer to delivering scalable, non-hallucinogenic treatments that patients can take in the comfort of their own homes, work, or on-the-go.”
The FDA-cleared Phase II trial will be a multi-site, randomized, double-blind, placebo-controlled study evaluating once-daily and twice-weekly dosing regimens of zalsupindole, with participants self-administering the drug at home.
“The Phase Ib data reinforce the potential of zalsupindole and inform our clinical development plans,” said Eliseo Salinas, M.D., Head of R&D at Delix Therapeutics. “Similar to the Phase Ib study, our Phase II study will evaluate once-daily and twice-weekly dosing. This randomized, placebo-controlled Phase II trial including at-home self-administration and an adaptive interim analysis will allow us to rigorously assess safety and efficacy in an outpatient setting and determine the optimal dosing paradigm for adults with major depressive disorder.”
