The trial delivered POC that active compound 5-HTP at target plasma exposure (i) enters the brain, (ii) elevates biomarkers of serotonin synthesis, and (iii) elevates biomarkers of serotonin activity beyond the SSRI/SNRI effect
The data corroborate the 5-HTP plasma exposure target of ~100 ng/mL and de-risk Phase 2 development
RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--Evecxia Therapeutics, Inc.—a clinical-stage neuroscience company developing a novel class of Serotonin Synthesis Amplification therapies—today announced positive data from a Phase 1b PK/PD trial for brain serotonin target engagement in depression patients on selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) therapy.
Phase 1b Target Engagement Trial
Design: N=18 depression patients on SSRI/SNRI therapy were administered adjunctive placebo (N=6) or EVX-301 (IV 5-HTP, N=12) at a dose (1 mg/kg/24h) previously reported to produce a CAverage of ~100 ng/mL plasma 5-HTP in humans, the putative therapeutic 5-HTP exposure target, with rapid onset (hours). Cerebrospinal fluid (CSF) 5-HTP, 5-HIAA (serotonin metabolite), and serotonin were determined at baseline and after placebo/EVX-301. Changes in serum cortisol, a validated neuroendocrine biomarker of brain synaptic serotonin release, and 5-HTP PK were included as ancillary measures.
Results: EVX-301 elevated all CSF biomarkers and the serum cortisol biomarker, together indicating brain serotonin synthesis amplification and elevation of serotonin activity beyond the SSRI/SNRI effect. Taken together, the data corroborate the 5-HTP exposure target for Evecxia’s drug candidates, EVX-101 and EVX-301. Adjunctive EVX-301 was generally well tolerated; adverse events were mostly mild or moderate and consistent with elevation of brain serotonin activity.
Trial site: The trial was conducted at PARC Clinical Research, Adelaide, Australia.
“The Phase 1b PK/PD target engagement data further de-risk Phase 2 development of Evecxia’s drug candidates, including lead candidate EVX-101,” said Jacob Jacobsen, PhD, Chief Executive Officer and Co-founder of Evecxia Therapeutics. “EVX-101 is backed by Evecxia’s comprehensive data package and decades of peer-reviewed published clinical data, addresses multiple unmet needs in psychiatry, and would slot seamlessly into existing psychiatric care and reimbursement infrastructure, globally. EVX-101 Phase 2 initiation in OCD is targeted for 1H 2027.”
About EVX-101
EVX-101 is an oral, gastro-retentive, sustained-release tablet formulation of 5-HTP (the natural immediate precursor to serotonin) and low-dose carbidopa (multiplies 5-HTP’s bioavailability). In Phase 1, EVX-101, as an adjunctive to SSRI therapy, transformed 5-HTP’s PK profile and demonstrated favorable safety and tolerability. EVX-101 is the first drug candidate realizing the therapeutic potential of Serotonin Synthesis Amplification, a pharmacology risk-mitigated by decades of clinical data (J Clin Psychopharmacol 2026 46(4):462-475, Full text, Podcast). Lead indication for EVX-101 is obsessive compulsive disorder (OCD) responding inadequately to SSRI therapy — a chronic, severe indication, with no FDA-approved drugs, affecting an estimated 2 million US patients.
About EVX-301
EVX-301 is a proprietary intravenous infusion of 5-HTP designed to rapidly increase 5-HTP plasma exposure and produce fast-onset brain Serotonin Synthesis Amplification. EVX-301 is being positioned as rescue therapy for patients hospitalized with suicidal ideation.
About Evecxia Therapeutics
Evecxia is the first company dedicated to realizing the therapeutic potential of Serotonin Synthesis Amplification—building a stronger, more resilient brain serotonin system—to treat psychiatric indications. Evecxia’s lead candidate EVX-101 is being developed as next-line oral adjunctive (add-on) therapy for OCD and depression patients for whom monotherapy with first-line serotonin reuptake inhibitor antidepressants (e.g., SSRIs such as Prozac®) yields inadequate therapeutic relief.
Contacts
Jacob Jacobsen, PhD, CEO
Evecxia Therapeutics, Inc.
info@evecxia.com
