DLX-001 · program

Zalsupindole (DLX-001) for Major depressive disorder

Phase 1ActiveDelix Therapeutics, Inc.

Zalsupindole (DLX-001), an oral non-hallucinogenic neuroplastogen, for major depressive disorder — Delix Therapeutics' lead program and the only indication in which the compound has been dosed in patients. Development to date is two completed studies, NEITHER OF WHICH IS REGISTERED ON ANY PUBLIC TRIAL REGISTRY (see the record comment; ClinicalTrials.gov, EU CTIS and ISRCTN all return zero for the compound and for the sponsor). Phase 1 (initiated 2023-05-09 at the Center for Human Drug Research, Leiden, Netherlands) enrolled 106 healthy volunteers across three parts — placebo-controlled single ascending dose, open-label food effect, and placebo-controlled 7-day multiple ascending dose — covering 2 mg to 360 mg orally; full results were presented at ACNP 2024 on 2024-12-12 showing no serious adverse events, no psychotomimetic, hallucinatory or dissociative effects at any dose, dose- and time-dependent resting-state qEEG change consistent with synaptic potentiation, and measurable cerebrospinal-fluid drug concentrations confirming CNS penetration. Phase 1b (first patient dosed 2024-12-04) was a dose-blinded, single-centre, multiple-dose study in 18 adults with recurrent MDD, randomised to once-daily dosing for 7 days (Cohort A, n=9) or intermittent dosing on Days 1 and 4 (Cohort B, n=9), with in-clinic assessment through Day 8 and follow-up through Day 36; primary endpoints were pharmacodynamic (qEEG, polysomnography) and safety/PK, with MADRS as a preliminary efficacy measure. All 18 participants completed treatment. Topline was announced 2025-10-28: well tolerated with no serious adverse events, the most common treatment-related events transient nausea and headache, no psychotomimetic or dissociative effects and no acute or persistent cognitive impairment on digital cognitive testing, plasma concentrations consistent with target exposures, increased absolute slow-wave delta and theta qEEG power in both cohorts, and approximately 50% MADRS reduction by Day 8 sustained through Day 36 in BOTH the daily and the intermittent cohort. That efficacy signal is uncontrolled (n=18, no placebo arm) and hypothesis-generating. The same release disclosed that the FDA has cleared the IND for a Phase 2 program: multi-site, randomised, double-blind, placebo-controlled, three arms (placebo, once-daily, twice-weekly), with at-home patient self-administration permitted — the first FDA-cleared at-home design for a psychedelic-derived antidepressant and the core of the commercial thesis. As of 2026-07-24 Delix has not announced a Phase 2 start, first patient dosed, or a topline date, and no Phase 2 registration exists, so the program is recorded at phase_1. No discontinuations, dose-arm drops, clinical holds or safety signals have been disclosed; Delix is private, so there is no SEC filing against which to check that.

Data current as of

Development timeline

Phase 1May 2023 – Oct 2025
  1. metPhase 1b topline in 18 adults with recurrent MDD: well tolerated with no serious adverse events, no psychotomimetic, hallucinatory or dissociative effects and no acute or persistent cognitive impairment; increased absolute slow-wave delta and theta qEEG power in both cohorts; and approximately 50% MADRS reduction by Day 8 sustained through Day 36 in BOTH the once-daily (7-day) and the intermittent (Days 1 and 4) cohort. Announced together with FDA clearance of the Phase 2 IND including at-home self-administration.↗
  2. metFull Phase 1 results for DLX-001 in 106 healthy volunteers, presented at the 2024 ACNP Annual Meeting: no serious adverse events, no psychotomimetic, hallucinatory or dissociative effects at any dose across 2-360 mg oral, dose- and time-dependent resting-state qEEG changes consistent with synaptic strengthening, and measurable cerebrospinal-fluid concentrations confirming CNS penetration at expected therapeutic doses.↗
  3. First MDD PATIENT dosed. Delix announced dosing of the first patient in the Phase 1b trial of DLX-001 in major depressive disorder — approximately 20 patients, evaluating pharmacodynamics (qEEG, polysomnography and exploratory biomarkers), safety, tolerability, pharmacokinetics and preliminary efficacy, dosed daily for seven days at exposures that had produced significant qEEG change in healthy volunteers. Not a phase advance (still Phase 1) but the transition from healthy volunteers to the target patient population, and the point at which this became a patient-stage program. Also unregistered.↗
  4. First-in-human. Delix announced initiation of the Phase 1 trial of DLX-001 at the Center for Human Drug Research (CHDR) in the Netherlands, planned for approximately 100 healthy volunteers and assessing safety, pharmacokinetics, psychometric function and measures of brain activity/synaptic plasticity. This is the compound's entry into clinical development under the MDD program; it was not registered on ClinicalTrials.gov or any other public registry, so this date comes from the company release rather than a registry record.↗

Readouts

  • 2025-10-28ReportedTopline datamet

    Phase 1b topline in 18 adults with recurrent MDD: well tolerated with no serious adverse events, no psychotomimetic, hallucinatory or dissociative effects and no acute or persistent cognitive impairment; increased absolute slow-wave delta and theta qEEG power in both cohorts; and approximately 50% MADRS reduction by Day 8 sustained through Day 36 in BOTH the once-daily (7-day) and the intermittent (Days 1 and 4) cohort. Announced together with FDA clearance of the Phase 2 IND including at-home self-administration. ↗

  • 2024-12-12ReportedFull resultsmet

    Full Phase 1 results for DLX-001 in 106 healthy volunteers, presented at the 2024 ACNP Annual Meeting: no serious adverse events, no psychotomimetic, hallucinatory or dissociative effects at any dose across 2-360 mg oral, dose- and time-dependent resting-state qEEG changes consistent with synaptic strengthening, and measurable cerebrospinal-fluid concentrations confirming CNS penetration at expected therapeutic doses. ↗

Formulations

FormulationRouteRegimenPharmacokinetics
Zalsupindole oral (2-360 mg, daily or intermittent dosing)
Oral administration throughout. Phase 1 (n=106 healthy volunteers, three parts): randomised, double-blind, placebo-controlled single ascending dose (Part A); open-label crossover food-effect study (Part B); randomised, double-blind, placebo-controlled multiple ascending dose over 7 days (Part C). The overall Phase 1 dose range explored was 2 mg to 360 mg orally, non-hallucinogenic across the whole range. Phase 1b (n=18 adults with recurrent MDD) used two dose-blinded paradigms at doses that had produced significant qEEG change in healthy volunteers: once-daily dosing for 7 days (Cohort A, n=9) and intermittent dosing on Days 1 and 4 only (Cohort B, n=9). The FDA-cleared Phase 2 carries the same two paradigms forward as three arms — placebo, once-daily, and twice-weekly — with at-home patient self-administration permitted.
OralOnce daily—

Mechanism of action (compound-wide)

Low-potency, low-efficacy partial agonist at the serotonin 5-HT2A receptor (HTR2A), a Gq-coupled class-A GPCR, with moderate-efficacy partial agonism at 5-HT2C and antagonism (no measurable agonism) at 5-HT2B. The compound is selective for the 5-HT2 receptor family over 5-HT1A, dopamine receptors, adrenergic receptors and the kappa-opioid receptor. The therapeutic hypothesis is efficacy-threshold separation rather than target separation: zalsupindole activates 5-HT2A with sufficient intrinsic activity to engage the downstream plasticity machinery (protein synthesis, neuritogenesis, spinogenesis; mTOR-pathway participation is suggested by rapamycin-inhibition studies) but with too little intrinsic activity to produce the perceptual signalling of a hallucinogen. Support for a genuinely 5-HT2A-mediated mechanism is that ketanserin, a 5-HT2A antagonist, abolishes the psychoplastogenic effect. In rats the drug is orally bioavailable, brain-penetrant, and produces cortical neuritogenesis in vitro and increased prefrontal dendritic spine density in vivo comparable to or greater than ketamine, psilocybin and N,N-dimethyltryptamine, with rapid and sustained antidepressant-like responses in the forced swim test and VMAT2-deficient models after a single dose — all without the head-twitch response, without hyperlocomotion at therapeutic doses and without a glutamate surge. The absence of 5-HT2B agonism is the stated basis for the lack of cardiovascular safety signals, a known liability of 5-HT2B agonists. In humans the pharmacodynamic footprint is dose- and time-dependent change in resting-state qEEG power spectra (delta and theta) associated with synaptic potentiation, with measurable cerebrospinal-fluid concentrations confirming CNS penetration.

TargetActionAffinity
5-HT2AprimaryHTR2APartial agonist—ⓘ
5-HT2BHTR2BAntagonist—ⓘ
5-HT2CHTR2CPartial agonist—ⓘ

← Full DLX-001 compound page (identity, identifiers, all indications)

Sources

  1. Delix Presents Full Results from Phase 1 Trial of DLX-001 at ACNP Annual Meeting (2024-12-12) — three-part design, 106 healthy volunteers, qEEG and CSF findings — Delix Therapeutics, Inc.
  2. Delix Therapeutics Announces Dosing of First Patient in Phase 1b Clinical Trial for DLX-001 in Major Depressive Disorder (2024-12-04) — Delix Therapeutics, Inc.
  3. Delix Therapeutics Announces Positive Efficacy Data for DLX-001 (Zalsupindole) and FDA Clearance of Phase II Trial Design Featuring At-Home Administration (2025-10-28) — Delix Therapeutics, Inc.
  4. Delix Therapeutics Initiates Phase I Trial for Novel Compound DLX-001 (2023-05-09) — ~100 healthy volunteers at the Center for Human Drug Research, Netherlands — Delix Therapeutics, Inc.
  5. Koenig A, van der Aa L, Pelletier N, Patat A, Viardot G, Olson D, Rasmussen K, van der Heijden K, Borghans L, Doll RJ, Jacobs G, Salinas E. P163. Phase I Results for DLX-001, a Novel Neuroplastogen Under Development for the Treatment of Major Depressive Disorder. ACNP 63rd Annual Meeting Poster Abstracts, Neuropsychopharmacology 2024;49(S1) — Neuropsychopharmacology (Springer Nature) / American College of Neuropsychopharmacology
  6. Meyer R, Koenig A, Nijhuis J, Tiessen R, Gillie D, Stam M, Dunbar J, Olson D, Salinas E. P231. A Phase Ib study to evaluate the pharmacodynamics, safety, and tolerability of the novel neuroplastogen Zalsupindole (DLX-001), dosed daily and intermittently in participants with major depressive disorder. ACNP 64th Annual Meeting Poster Abstracts, Neuropsychopharmacology 2026;51(S1) — Neuropsychopharmacology (Springer Nature) / American College of Neuropsychopharmacology
  7. Salfiti M, Kyriazis M, Mikellides G. Zalsupindole: A Non-Hallucinogenic Psychoplastogen Advancing Psychedelic-Inspired Therapeutics. ACS Chem Neurosci. 2026;17(2):382-391 — structured review covering receptor selectivity, ketanserin blockade, absence of 5-HT2B agonism, and the 2-360 mg Phase 1 dose range — ACS Chemical Neuroscience (American Chemical Society) / PubMed