Delix: DLX-001 Shows CNS Penetration and Brain Activity Without Psychotomimetic Effects in Phase 1 Trial

Delix Therapeutics, a leading neuroscience company in the clinical stage, is making advancements in the development of innovative therapeutics aimed at promoting neuroplasticity for treating psychiatric and neurological disorders. Recently, the company unveiled promising data from its ongoing Phase 1 trial of DLX-001, a novel neuroplastogen. This trial highlights DLX-001's brain activity in healthy volunteers, devoid of any psychotomimetic, dissociative, or hallucinogenic effects. Additionally, the company presented preclinical data on DLX-001's impressive effects on structural and functional plasticity assays, alongside its antidepressant properties. These findings were showcased at the 2024 Society of Biological Psychiatry (SOBP) Annual Meeting and will also be featured at the upcoming 2024 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting.

Building on previous interim results from the ACNP meeting, the favorable safety and tolerability profile of DLX-001 was emphasized by Dr. Aaron Koenig, the Chief Medical Officer at Delix Therapeutics. He noted the absence of hallucinogenic, psychotomimetic, or dissociative effects, reinforcing the potential of DLX-001 to meet significant unmet needs for patients with major depressive disorder (MDD) and related conditions.

The Phase 1 study of DLX-001 is structured into three parts and involves more than 100 healthy volunteers at the Center for Human Drug Research (CHDR) in The Netherlands. The primary goals are to assess safety, pharmacokinetics (PK), and brain activity markers. Part A is a randomized, double-blind, placebo-controlled single ascending dose (SAD) study. Part B examines the effect of food on DLX-001's PK through an open-label crossover design. Part C is a randomized, double-blind, placebo-controlled multiple ascending dose (MAD) study wherein participants receive multiple doses of DLX-001 or placebo over a week.

Key findings from the study include:
- DLX-001's favorable safety and tolerability without any serious adverse events.
- No observed psychotomimetic, hallucinatory, or dissociative effects.
- Evidence of brain penetration and target engagement demonstrated through time and dose-dependent changes in resting-state quantitative electroencephalography (qEEG) and measurable compound concentrations in cerebrospinal fluid (CSF).
- The qEEG patterns in healthy volunteers, marked by increased delta and theta wave activity, are similar to those observed with ketamine and Electro-Convulsive Therapy (ECT).
- The maximum tolerated dose for DLX-001 hasn't been reached, and the study is ongoing.

Additionally, preclinical studies highlighted DLX-001's neuroplastic and therapeutic effects. In comparative analyses, DLX-001 displayed beneficial efficacy against compounds like ketamine, psilocybin, and DMT, while distinguishing itself with a lack of hallucinogenic liability. Key findings from these preclinical studies include:
- DLX-001's oral bioavailability and brain penetration.
- Robust increases in neurite length, branching, and neuronal complexity in vitro.
- Significant structural and functional neuroplasticity effects ex vivo, comparable to first-generation compounds.
- Rapid and enduring antidepressant-like activity observed in multiple behavioral models.

DLX-001 is a novel, non-hallucinogenic, non-dissociative isotryptamine neuroplastogen being tested for treating major depressive disorder (MDD) and other neuropsychiatric conditions. Initial human testing indicates DLX-001's safety and effectiveness, with no serious adverse events and significant target engagement.

Neuroplastogens, like DLX-001, are a novel class of therapeutics promoting rapid and sustained neuroplasticity, offering fast-acting therapeutic benefits for psychiatric and neurological disorders. Delix Therapeutics is at the forefront of developing these innovative compounds, aiming to revolutionize treatment paradigms for neuropsychiatric conditions and provide effective, outpatient pharmacotherapies to meet unmet clinical needs.