Pipeline

EVX-101

Evecxia Therapeutics is developing EVX-101 as an adjunctive (add-on augmentation) therapy for patients with depression responding inadequately to first-line SSRI/SNRI antidepressants monotherapy. EVX-101 is a proprietary, oral tablet, gastroretentive, slow-release formulation of 5-HTP and low-dose carbidopa. EVX-101 uses a novel embodiment of a validated gastroretentive drug delivery technology, used in 8 FDA-approved drug products. The gastroretentive technology ensures delivery of 5-HTP and carbidopa over about 8h to the site of 5-HTP absorption, the upper intestine. The low-dose carbidopa protects 5-HTP against first-pass metabolism (degradation) over the intestinal wall, manyfold increasing the oral bioavailability of 5-HTP.

When added to existing SSRI/SNRI first-line antidepressant therapy, adjunctive EVX-101 will amplify serotonin neurotransmission beyond the antidepressant effect, which clinical data suggest will augment the antidepressant response in patients inadequately treated by antidepressant monotherapy.

EVX-101 can be taken by the patient at home, with breakfast and dinner. EVX-101 is expected to be free of abuse potential and therefore not considered a controlled substance by the US Drug Enforcement Agency.

EVX-101, adjunctive or as monotherapy, could have therapeutic relevance in additional important unmet needs in Psychiatry e.g. OCD, and in other disorders of the brain.

EVX-101 is protected by a portfolio of issued and pending patents, in the US as well as all major overseas markets.

EVX-101 Phase 1 Trials

Evecxia has successfully completed two Phase 1 clinical trials of EVX-101

A Phase 1a trial was an open-label trial in healthy volunteers to evaluate the 5-HTP bioavailability and PK profile following EVX-101 administration. The trial aim was to optimize 5-HTP/carbidopa doses and the EVX-101 formulation composition. Adverse events were mild or moderate with no safety signals. There were no serious adverse events.

A Phase 1 trial was a double-blind, placebo-controlled, single ascending dose (SAD), multiple ascending dose (MAD) titration trial in healthy subjects receiving an SSRI (escitalopram) at steady state to evaluate safety, tolerability, 5-HTP pharmacokinetics, and neuroendocrine target engagement when EVX-101 was administered adjunctively to an SSRI. Four carbidopa dose levels (0.3125 mg to 2.5 mg per tablet) with fixed dose 5-HTP (250 mg per tablet) were evaluated. All four carbidopa dose levels produced 5-HTP exposure in or above the anticipated therapeutic range, estimated at C_Average ~100 ng/ml. Carbidopa enhanced 5-HTP bioavailability with a clear dose-response relationship. Neuroendocrine biomarker data suggested robust target engagement, i.e., elevation of brain extracellular serotonin beyond the SSRI effect, across several carbidopa dose levels. Adverse events were mild or moderate with no safety signals. There were no serious adverse events.

These Phase 1 data strongly support EVX-101 as an adjunctive antidepressant candidate. A Phase 2 study of adjunctive EVX-101 in depression patients with inadequate response to first-line antidepressants is expected to commence enrollment in Q1/2024.

EVX-301

Evecxia Therapeutics is developing EVX-301 as a rescue therapy for patients hospitalized for acute suicidal ideation crisis. EVX-301 is a proprietary intravenous up to 24h infusion of 5-HTP. EVX-301 is designed to quickly and optimally amplify brain extracellular serotonin and hence serotonin neurotransmission. Convergent clinical data suggest this will impart an anti-suicidal effect, comprised of improved mood, sociability, and calmness, and reduced aggression and impulsivity.

The patient will receive EVX-301 in the clinic or hospital. Evecxia expects that EVX-301 can be a stand-alone therapy or be the first step in a novel treatment algorithm, the second step being transfer to maintenance suicide ideation prevention therapy with EVX-101.

EVX-301 Phase 1 Study

Evecxia has successfully completed a Phase 1 clinical trial of EVX-301

This Phase 1 trial was a double-blind, placebo-controlled, single ascending dose (SAD) trial in healthy subjects receiving an SSRI (escitalopram) at steady state to evaluate safety, tolerability, 5-HTP pharmacokinetics, and neuroendocrine target engagement when EVX-301 was administered adjunctively to an SSRI.
 
EVX-301 dose-dependently increased 5-HTP plasma exposure with minimal variation between subjects. Importantly, adjunctive EVX-301 could achieve clinical target 5-HTP plasma exposure, C_Average ~100 ng/ml, within hours, with no adverse events, and with neuroendocrine biomarker data suggesting robust target engagement, i.e., elevation of brain extracellular serotonin beyond the SSRI effect. Adverse events at higher doses were mild or moderate, with minimal safety signals detected.
 
These Phase 1 data support EVX-301 as a rescue therapy for acute suicidal ideation crisis. A Phase 2a trial of adjunctive EVX-301 in depression patients with inadequate response to first-line antidepressants and ongoing suicidal ideation is expected to commence enrollment in Q3/2023.