RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--Evecxia Therapeutics, Inc., the leader in serotonin synthesis amplification to treat brain disorders, today announced the absence of toxicity findings associated with the co-administration of EVX-101 in conjunction with the first-line antidepressant fluoxetine in nonclinical GLP toxicology studies. These favorable results support the safety profile of the lead drug candidate, EVX‑101, in a planned Phase 2 clinical trial in patients with major depressive disorder inadequately responding to first‑line antidepressant therapy.
EVX‑101 is being developed as an adjunctive treatment for depression when first-line SSRI/SNRI antidepressants alone are inadequate. EVX‑101 is a patented gastroretentive sustained-release tablet formulation of 5‑hydroxytrytophan (5‑HTP), the natural immediate precursor of serotonin, and low-dose carbidopa, a peripheral L-aromatic amino acid decarboxylase inhibitor. In EVX-101, the 5-HTP dose is fixed, while the amount of carbidopa is varied to control the level of 5-HTP plasma exposure.
The nonclinical GLP toxicology program was designed to assess the pharmacokinetics and systemic toxicity of oral administration of EVX-101 in conjunction with an SSRI for up to 3 months in rats and pigs. EVX‑101 tablets were administered twice daily to pigs, similar to the intended administration in humans. A formulation containing 5‑HTP and variable carbidopa amounts prepared in rodent diet was offered ad libitum to rats to simulate EVX-101 administration. Fluoxetine administration was initiated several weeks before EVX-101 initiation to model the future clinical scenario where EVX-101 will be administered adjunctively to ongoing SSRI/SNRI. Fluoxetine administration was continued for the duration of EVX-101 administration.
Oral adjunctive EVX-101 for 3 months was well tolerated in both species. There were no safety findings at any parameter, even at 5‑HTP plasma levels exceeding 2000 ng/mL, 20-fold greater than the anticipated human therapeutic plasma level of about 100 ng/mL. Safety endpoints included detailed clinical observations, body weight, ophthalmic examinations, clinical pathology (serum chemistry, hematology, and urinalysis), organ weights, macroscopic organ appearance, and microscopic tissue examinations, in accordance with FDA guidance.
The absence of toxicological findings in the nonclinical GLP studies are consistent with the favorable historical safety profile of 5‑HTP administration across more than 100 human clinical studies conducted over the past six decades. The findings are also consistent with the absence of safety findings of concern in two Phase 1 clinical trials of EVX-101 and one Phase 1 clinical trial of EVX-301 (IV 5-HTP formulation) in conjunction with a first-line antidepressant, conducted by Evecxia to date. Hence, the totality of safety data suggest that serotonin synthesis amplification with adjunctive EVX-101 could have good safety during human therapy.
“Evecxia has made great strides to advance EVX‑101 through two Phase 1 trials, which produced excellent safety, acceptable tolerability, and evidence of brain serotonin target engagement. The results from our nonclinical GLP toxicology studies strongly support our mission to bring safer and potentially more effective treatments to patients suffering from disabling neuropsychiatric disorders. We look forward to advancing EVX-101 into Phase 2 trials,” said Dr. Jacob Jacobsen, CEO and co-founder of Evecxia.
About Evecxia Therapeutics
Evecxia’s mission is to help patients suffering from disabling neuropsychiatric conditions for which current therapies are inadequate. Evecxia is the first company dedicated to realizing the therapeutic potential of amplifying serotonin synthesis to treat brain disorders. Serotonin synthesis amplification is distinct from targeting serotonin transporters (e.g., SSRIs) and receptors (e.g., psilocybin). Evecxia deploys 5-hydroxytryptophan (5-HTP), the natural serotonin precursor, delivered via proprietary drug delivery technologies to achieve sustained serotonin synthesis amplification. Evecxia has two Phase 2 clinical-stage drug candidates in development. EVX‑101 is being developed as an adjunctive treatment for depression when first-line SSRI/SNRI antidepressants alone are inadequate. EVX-301 is being developed as a rescue therapy for acute suicidal crisis.
For additional information about Evecxia, please visit www.evecxia.com.