Delix Announces DLX-001 Demonstrates Evidence of CNS Penetration and Brain Activity Without Psychotomimetic, Dissociative, or Hallucinogenic Effects in Ongoing Phase 1 Trial

2024-05-13

临床1期ASCO会议临床结果

Preclinical Pro DLX-001 Promotes Robust Neuroplastic Effects with Rapid and Durable Antidepressant Effects Novel Neuroplastogen Continues to Be Well-Tolerated After Single and Multidose Administration Data Presented at SOBP and ASCP Annual Meetings BEDFORD, Mass.--(BUSINESS WIRE)-- Delix Therapeutics, a clinical-stage neuroscience company developing novel neuroplasticity-promoting therapeutics for psychiatric and neurological disorders, today announced additional data from an ongoing Phase 1 trial evaluating DLX-001, a novel neuroplastogen, demonstrating evidence of brain activity in healthy volunteers without producing psychotomimetic, dissociative or hallucinogenic effects. The Company also announced preclinical data showing the effects of DLX-001 on antidepressant, structural, and functional plasticity assays. These data were presented at the 2024 Society of Biological Psychiatry (SOBP) Annual Meeting from May 9-11 in Austin, Texas and will also be presented at the 2024 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting from May 28–31 in Miami Beach, Florida. “Building on interim results presented at ACNP in December, we are encouraged by DLX-001’s favorable safety and tolerability pro date, as well as time- and dose-dependent effects observed on quantitative EEG,” said Aaron Koenig, MD, Chief Medical Officer of Delix Therapeutics. “These results, coupled with a continued lack of hallucinogenic, psychotomimetic, or dissociative effects as we approach the end of this first-in-human study, reinforce our belief that DLX-001 has the potential to address significant unmet needs for patients suffering from MDD and related disorders.” DLX-001, A Novel Neuroplastogen, Produces Rapid Time- and Dose-Dependent Increases in Delta and Theta Power on Quantitative EEG (qEEG) Lead Author: Aaron Koenig, M.D. Session Date: Thursday, May 9 Session Time: 5:30-7:30pm CT A three-part Phase 1 study will enroll over 100 healthy volunteers at the Center for Human Drug Research (CHDR) in The Netherlands, with the primary objectives of assessing safety, pharmacokinetics (PK), and markers of brain activity. Part A is a randomized, double-blind, placebo-controlled single ascending dose (SAD) study of DLX-001. Part B is an open-label crossover design study to investigate the effect of food on the PK of DLX-001. Part C is a randomized, double-blind, placebo-controlled multiple ascending dose (MAD) study in which participants receive multiple oral doses of either DLX-001 or placebo over 7 days. Key Findings DLX-001 has demonstrated a favorable safety and tolerability pro date, with no serious adverse events. No psychotomimetic, hallucinatory, or dissociative effects have been observed, as reflected by no change over time on a robust battery of assessments. Time and dose-dependent changes measured by resting-state quantitative electroencephalography (qEEG), paired with consistently measurable concentrations of compound in the cerebrospinal fluid (CSF), support brain penetration and the presence of target engagement with DLX-001. The qEEG pattern of DLX-001 in healthy volunteers is characterized by increases in slow wave (delta and theta) activity consistent with the pattern observed with ketamine and Electro-Convulsive Therapy (ECT). The maximum tolerated dose for DLX-001 has not yet been reached, and the study remains in progress. Along with these additional Phase 1 data, Delix presented preclinical data characterizing DLX-001’s neuroplastic and therapeutic effects, including comparative data marking the beneficial efficacy of DLX-001 against ketamine, psilocybin, DMT, and differentiating from these compounds due to a lack of hallucinogenic liability. Preclinical Pharmacology of DLX-001, a Novel Non-Hallucinogenic Neuroplastogen With the Potential for Treating Neuropsychiatric Diseases Lead Author: Kurt Rasmussen, Ph.D. Session Date: Saturday, May 11 Session Time: 12:30–2:30pm CT DLX-001 was examined in a series of in vitro, ex vivo, and in vivo assays relevant to neuroplasticity and major depressive disorder (MDD). Key Findings In PK studies, DLX-001 was shown to be orally bioavailable and brain penetrant. In vitro studies demonstrate robust increases in neurite length and branching, increasing neuronal complexity. Ex vivo, DLX-001 demonstrated robust effects on both structural and functional neuroplasticity after a single dose. The magnitude of these effects was on par with first generation compounds including ketamine, psilocybin, and DMT and were seen at doses relevant to the behavioral effects of each of these compounds. DLX-001 exhibited both rapid—within 24-hours, and enduring—up to 14 days, antidepressant-like activity after a single dose in multiple behavioral models. In studies relevant to cardiotoxicity and hallucinations, no signal was identified for DLX-001. About DLX-001 DLX-001 is a novel, non-hallucinogenic, and non-dissociative isotryptamine neuroplastogen currently undergoing initial human testing to treat those diagnosed with major depressive disorder (MDD) and other associated neuropsychiatric conditions. Preclinical data show that in efficacious doses, DLX-001 increased dendritic spine density in rat brain PFC layer-V pyramidal neurons and had rapid and enduring antidepressant-like effects after a single dose. Recent phase 1 data found DLX-001 to be well tolerated, with no serious adverse events reported and robust signs of target engagement. In addition, researchers did not observe significant abnormalities among crucial safety indicators, including vital signs, electrocardiogram (ECG) readings, and laboratory analysis. 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 phenotypic drug discovery engine to generate distinct compounds, Delix seeks to bring to market a pipeline of neuroplastogens that will be the faster, stronger, and more effective therapies 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 will serve several unmet needs and enhance the psychiatric treatment paradigm for patients and providers.