Small Pharma Inc. announced positive safety, tolerability and efficacy data from its Phase Ib study exploring the interaction between selective serotonin reuptake inhibitors (?SSRIs?) and SPL026, native N, N-dimethyltryptamine (?DMT?), in patients with Major Depressive Disorder (?MDD?). The purpose of this study was to build upon the previously reported Phase I/IIa safety and efficacy profile of SPL026 with support therapy, to assess whether SPL026 can be safely administered with or without SSRIs - the current standard of care for MDD. In the Phase I/IIa SPL026 study, patients were required to be withdrawn from SSRIs, which can be a disruptive experience.

Through the SPL026-SSRI drug interaction study, Small Pharma aimed to address this requirement, which could enable broader patient recruitment on future large-scale studies, and potentially accelerate the clinical development pathway. Additionally, removing the requirement to be withdrawn from SSRIs may facilitate patient access to SPL026 earlier in the MDD treatment journey, if approved. This open-label study investigated the safety, tolerability, pharmacokinetics, pharmacodynamics and exploratory efficacy of a single 27.5 mg intravenous infusion of SPL026, alone or in combination with SSRIs, in 171 patients, together with support therapy.

The test cohort (N=12) (the ?SSRI Cohort?) consisted of patients currently on a stable treatment course of SSRIs, which have been ineffective in fully relieving their depression symptoms. The control cohort (N=5) (the ?Non-SSRI Cohort?) consisted of patients not currently using any pharmacological treatment to treat their depression symptoms. Patients were recruited with moderate-severe MDD as defined by a Hamilton Depression Rating Scale (HAM-D) score of >14. Efficacy was assessed using the Montgomery-Asberg Depression Rating scale (MADRS) to measure any change in patients? depression symptoms from baseline.

Additional exploratory endpoints include the Beck Depression Inventory (BDI) to assess patients? self-reported depression. Key Results: Safety & Tolerability: SPL026 was well-tolerated by all patients in both the SSRI Cohort and Non-SSRI Cohort, with no apparent differences between cohorts.

No drug-related serious adverse events reported. A small number of drug-related adverse events (?AEs?) reported. 8 in SSRI Cohort.

3 in Non-SSRI Cohort. All deemed to be mild or moderate in severity. Majority of drug-related AEs were resolved during the dosing visit.

Exploratory Efficacy. The results reaffirmed the efficacy initially demonstrated in the Phase IIa SPL026 study. However, a marked improvement was observed between the antidepressant effect of SPL026 treatment in the SSRI Cohort compared to the Non-SSRI Cohort.

While the efficacy observed in the Non-SSRI Cohort was comparable to the efficacy data previously observed in the Company?s SPL026 Phase IIa clinical trial, the antidepressant effects observed in the SSRI Cohort were of a greater magnitude, suggesting a potentially enhanced efficacy effect when SPL026 is administered in combination with SSRIs.