• Peer‑reviewed publication in ACS Chemical Neuroscience reveals that zalsupindole (DLX‑001), a first‑in‑class non‑hallucinogenic neuroplastogen, engages serotonergic receptors to drive rapid structural and functional neuroplasticity in the cortex that lasts after the drug has been cleared from the body.
  
  
  
  
• Side‑by‑side comparisons show that zalsupindole produces dendritic spine growth and functional plasticity comparable to, or exceeding that of ketamine, psilocybin, and DMT without inducing hallucinations or dissociation.
  
  

• Receptor profiling demonstrates high selectivity for serotonergic targets supporting a favorable safety profile consistent with Phase 1 data.

Delix Therapeutics, a clinical‑stage neuroscience company developing non‑hallucinogenic neuroplastogens for the treatment of serious neuropsychiatric and neurodegenerative disorders, announced that the peer‑reviewed manuscript “Zalsupindole is a non‑dissociative, non‑hallucinogenic neuroplastogen with therapeutic effects comparable to ketamine and psychedelics” has been published in ACS Chemical Neuroscience. The in‑depth study, authored by Delix scientists and co-founder David E. Olson, PhD, provides additional pharmacological profiling and mechanistic details about Delix’s lead candidate zalsupindole (DLX‑001). This first‑in‑class analog of 5‑MeO‑DMT produces robust structural and functional neuroplasticity without the hallucinogenic, psychotomimetic, or dissociative effects associated with first‑generation psychoplastogens.

In preclinical assays, zalsupindole promoted cortical neuritogenesis in vitro, increased dendritic spine density in vivo, and enhanced measures of functional plasticity to a similar or greater extent than ketamine, psilocybin and DMT. Pharmacokinetic studies revealed that zalsupindole is highly brain‑penetrant, distributes rapidly, and is cleared quickly. Receptor profiling demonstrated that zalsupindole is a low‑potency partial agonist at 5‑HT₂A/C receptors and exhibits high selectivity for serotonergic targets while antagonizing 5‑HT₂B receptors. These characteristics contribute to its robust neuroplasticity‑promoting effects and support a favorable cardiovascular safety profile as has been seen in clinical studies.

“At Delix, we believe that promoting neuroplasticity to repair dysfunctional neural circuits is the key to treating a broad range of neuropsychiatric conditions,” said David E. Olson, PhD, co‑founder and Chief Innovation Officer of Delix Therapeutics. “By systematically comparing zalsupindole with clinically effective, first-generation psychoplastogens such as ketamine, psilocybin, and DMT, we have shown that our compound produces the same rapid and sustained structural and functional plasticity without inducing hallucinations or dissociation. The data described in this paper provide a clear path toward developing safe, effective, and scalable neuroplastogen therapeutics for people who need them.”

Delix’s neuroplasticity platform has generated thousands of non‑hallucinogenic plasticity‑promoting compounds. The publication follows encouraging clinical results: in a Phase 1 study in healthy volunteers, zalsupindole demonstrated a favorable safety and tolerability profile with no serious adverse events or psychotomimetic, hallucinatory or dissociative effects while EEG biomarkers demonstrated CNS exposure and activity relevant to neuroplasticity. Delix is currently completing a Phase 1b study in patients with major depressive disorder (MDD).

“Delix is honored that ACS Chemical Neuroscience has chosen to publish this important characterization of the first novel neuroplastogen to advance to the clinic and patients,” said Mark Rus, CEO of Delix Therapeutics. “By deepening our understanding of neuroplasticity, the serotonergic system, and sharing that with the field, we are driving forward the evidence that non‑hallucinogenic neuroplastogens can provide the robust rapid efficacy of psychedelics and other first generation plastogens, but at a completely different scale.”

In addition to this ACS Chemical Neuroscience publication, Delix's research has been widely published in scientific journals including Science, Cell, Nature, Molecular Psychiatry, Frontiers in Psychiatry, and the Journal of Medicinal Chemistry, among others. The Company was also recognized in Chemical & Engineering News' Top 10 Start-ups to Watch, named to Nature Biotechnology's list of leading spinouts, and included in Fierce Biotech's prestigious "Fierce 15" list.

About Zalsupindole (DLX‑001)

Zalsupindole (DLX-001) is a novel, non‑hallucinogenic, non-dissociative isotryptamine neuroplastogen currently being evaluated for the treatment of Major Depressive Disorder (MDD). Preclinical data has demonstrated that DLX-001 increases dendritic spine density on neurons in the prefrontal cortex and has rapid and enduring antidepressant-like effects in animal models after a single dose. Recent Phase 1 data has 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 1b 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 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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