- Zalsupindole (DLX-001) is a first‑in‑class, non‑hallucinogenic neuroplastogen.

- Phase Ib data show clear effects on potential markers of plasticity as well as rapid, robust and durable antidepressant effects

- FDA clearance of the Phase II design including at‑home administration, validate its potential as an outpatient therapy.

Delix Therapeutics, a clinical‑stage neuroscience company pioneering a new class of treatments known as neuroplastogens, today announced positive results from its Phase Ib clinical trial of zalsupindole (DLX-001) in adults with major depressive disorder (MDD). The company also announced that the U.S. Food and Drug Administration has cleared its Investigational New Drug application for a Phase II trial design that includes at‑home self‑administration, validating the compound’s safety and Delix’s broader neuroplastogen platform.

Zalsupindole is a novel neuroplastogen, an analog of 5-MeO-DMT engineered to be orally bioavailable and promote structural and functional neuroplasticity without hallucinatory, sedative, or dissociative effects. Earlier Phase I data in healthy volunteers demonstrated safety, tolerability, target engagement and an absence of psychotomimetic effects. A recent publication shared preclinical data demonstrating that zalsupindole promotes neuroplasticity as quickly and robustly as ketamine and serotonergic psychedelics. This is the first clinical trial exploring efficacy for this compound.

Durable efficacy and equivalent outcomes across two dosing regimens were observed

The primary objective of this study was to assess the effects of zalsupindole on translational biomarkers of neuroplasticity in patients with Major Depressive Disorder (MDD). Secondary objectives included the assessment of safety, tolerability, pharmacokinetics and preliminary efficacy. Eighteen adult patients with MDD were enrolled to receive zalsupindole either once-daily for seven consecutive days (Cohort A) or just twice during the first week of the trial (Cohort B). Key results included:

• Robust translational biomarkers: Quantitative electroencephalography (qEEG) and polysomnography (PSG), the primary objectives of the study, showed robust results to be presented at upcoming conferences.
• Rapid and robust antidepressant response: patients in both cohorts demonstrated clinically meaningful reductions on the Montgomery–Åsberg Depression Rating Scale (MADRS) of 12 points corresponding to approximately a 50% reduction on the first day of measurement (Day 8) compared to baseline.
• Durable benefit: These improvements were maintained through Day 36, 4 weeks after the last dose, suggesting that a short course of therapy can trigger lasting neural changes.
• Equivalence of daily and intermittent dosing: Similar improvements in depressive symptoms and tolerability were observed whether participants received seven doses or only two doses within a one‑week period.
• Favorable safety and tolerability: No serious adverse events occurred; all adverse events were mild and resolved without intervention, and no hallucinatory, dissociative or psychotomimetic effects were reported.

“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.”

FDA clears Phase II trial design featuring at‑home administration

Delix also announced that the FDA has cleared its Investigational New Drug (IND) application detailing the design for a multi‑site, randomized, double‑blind, placebo‑controlled Phase II trial in MDD. The approved protocol includes three arms, placebo, once‑daily dosing, or twice‑weekly, and allows patients to self‑administer zalsupindole 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 of 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.”

Presentation at upcoming conferences

Interim results from the first cohort of the Phase Ib trial were presented at this year’s American Society of Clinical Psychopharmacology (ASCP) Annual Meeting. Full Phase Ib results will be presented at an upcoming conference. In this planned presentation, Delix will also share the unpublished translational biomarker data.

About Zalsupindole (DLX‑001)

Zalsupindole is a novel neuroplastogen isotryptamine engineered to promote structural and functional neural plasticity without hallucinatory, sedative or dissociative effects. It is currently being evaluated for the treatment of Major Depressive Disorder (MDD). Preclinical data have demonstrated that DLX-001 increases dendritic spine density in neurons in the prefrontal cortex and has rapid and enduring antidepressant-like effects in animal models after a single dose. Recent Phase I data have demonstrated that DLX-001 is associated with robust signs of CNS engagement and a favorable safety and tolerability profile, with no serious adverse events reported to date. Delix is completing a Phase Ib study in MDD patients.

About Neuroplastogens

Neuroplastogens are a novel class of potentially disease-modifying therapeutics for psychiatric and neurological conditions. These compounds promote rapid and sustained neuroplasticity in select neural circuits resulting in fast-acting therapeutic effects. Neuroplastogens are novel chemical entities inspired by compounds that are proving to be beneficial across a range of therapeutic areas including mood, anxiety, cognitive, and neurodegenerative disorders in addition to other synaptopathies. Leveraging our deep mechanistic understanding and unique drug discovery engine to generate distinct compounds, Delix seeks to bring to market a pipeline of neuroplastogens that aim to be the faster, stronger, and more effective medicines of the future.

About Major Depressive Disorder (MDD)

Major Depressive Disorder (MDD) is a prevalent and debilitating condition affecting over 280 million people globally, with 21 million people suffering in the United States alone. MDD represents the primary cause of disability in the world and is typically characterized by persistent feelings of sadness and loss of interest. Even with available approaches, many patients do not experience an optimal response to treatment, resulting in a significant need for new and differentiated treatments.

About Delix Therapeutics

Delix Therapeutics is a clinical-stage neuroscience company focused on harnessing the power of novel neuroplasticity‑promoting therapeutics to better treat patients struggling with difficult-to-treat neuropsychiatric and neurological disorders. The company's compounds are easily manufactured small molecules capable of rapidly inducing structural and functional neural changes in targeted areas of the brain. Through its novel Neuroplastogen Platform, Delix is pioneering a new class of fast-acting outpatient pharmacotherapies and rapidly advancing through preclinical and clinical development to bring patients FDA-approved, take-home medicines that are intended to serve several unmet needs and enhance the psychiatric treatment paradigm for patients and providers.

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