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DLX-001 offers potential for a range of conditions, according to Retsina Meyer, head of corporate strategy at Delix. “The aperture for indications for psychoplastogens is broad and is even broader for our non-hallucinogenic compounds of this class,” Meyer said. DLX-001 holds promise for conditions where cortical dendritic/synaptic atrophy plays a role in the pathology. Such atrophy is involved in conditions ranging from major depressive disorder (MDD), schizophrenia, Parkinson’s disease and substance abuse. Meyer highlights MDD as the company’s initial focus for DLX-001 although other mood disorders could be potential candidates in the future. “Additional mood and anxiety indications could also benefit from DLX-001 or another Delix neuroplastogen compound,” she said.
Clinical trial design and endpoints
Delix plans on enrolling roughly 100 healthy volunteers, aiming to determine the safety, pharmacokinetics, psychometric functions and markers of brain activity and synaptic plasticity. Specific endpoints include safety profile evaluation, measurement of drug concentration in blood, assessment of cognitive and emotional functions and neuroimaging studies to evaluate brain activity changes. The Center for Human Drug Research (CHDR) in the Netherlands will oversee the research.
The company ultimately plans to see how DLX-001 stacks up against current treatments, such as SSRIs and other psychoplastogens, which also encompass drugs ranging from ketamine to psilocybin.
“Unlike most current antidepressants such as SSRIs, DLX-001 has rapid and enduring effects on cortical structural neuroplasticity, which will translate into rapid and enduring antidepressant effects,” Meyer said. The company’s preclinical and molecular work suggests that DLX-001 will be neither hallucinogenic, like the first-gen serotonergic psychoplastogens, nor dissociative as is found in the glutamatergic psychoplastogens such as the dissociative anesthetic ketamine.
Exploring the safety profile of Delix Therapeutics’ psychoplastogen DLX-001
Based on its preclinical and molecular research, Delix does not expect DLX-001 to be hallucinogenic like first-generation serotonergic psychoplastogens or dissociative like glutamatergic psychoplastogens such as ketamine.
The company expects DLX-001 to potentially have a better safety profile than first- and second-generation psychoplastogens. Some researchers have noted that psychedelics could have cardiovascular risks, given that they are partial agonists at the 5HT2b serotonin receptor, which could theoretically pose a risk for cardiac valvulopathy. Scientists, however, have not yet demonstrated a direct link between classic psychedelics and this condition, which involves a thickening of the heart valves. One notable example of a 5HT2b agonist linked with cardiac valvuopathy is the fenfluramine/phentermine combination (fen/phen). Comparing classic psychedelics to fen/phen is difficult, however, given differences in drug classes, mechanisms of action and doses. However, some researchers are cautious about the potential cardiovascular risks associated with psychedelics, which are partial agonists at the 5HT2b serotonin receptor
Delix also is optimistic that DLX-001 will not have the same list of contraindications such as neuropsychiatric or cognitive comorbidities, family mental health, or heart issues. “DLX-001 is expected to be dosed intermittently – i.e., not daily – which would make potential drug-drug interactions clinically manageable,” Meyer said.
“We anticipate full results of the totality of this sequential ascending dose study in 1Q2024,” Meyer said. “The next studies will be in depressed patients and will include a Phase1b Pharmacodymanic study and a Phase2 Proof of Concept study.”
Filed Under: clinical trials, Drug Discovery, Psychiatric/psychotropic drugs
