Delix Announces DLX-001 Demonstrates Evidence of CNS Penetration and Brain Activity Without Psychotomimetic, Dissociative, or Hallucinogenic Effects in Ongoing Phase 1 Trial
May 13 2024 - 7:00AM
Business Wire
Preclinical Profile Shows 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
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
profile to 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
profile to 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.
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Investor Relations: Retsina Meyer, PhD Delix Therapeutics
invest@delixtherapeutics.com
Media Relations: Robert Stanislaro FTI Consulting
delix@fticonsulting.com