Small Pharma Inc. announced that SPL026, intravenous N,N-Dimethyltryptamine (“DMT”), with supportive therapy for the treatment of Major Depressive Disorder (“MDD”) met the primary endpoint in its Phase IIa clinical trial, demonstrating a statistically significant and clinically relevant reduction in depressive symptoms at two-weeks post-dose, as compared to placebo. Further analysis of key secondary endpoints demonstrated a rapid and durable antidepressant effect to 12-weeks. The trial investigated the efficacy and safety of intravenous (“IV”) SPL026, with supportive therapy, in 34 patients with moderate/severe MDD.

Participants who entered the trial on pharmacological antidepressant medication were withdrawn from their treatment prior to dosing. Patients were dosed with a short IV infusion of 21.5mg of SPL026, resulting in a 20 to 30-minute psychedelic experience. The dose was selected as a result of data analysis from the Company's Phase I study confirming that it was well tolerated and delivered a consistent psychedelic experience in healthy volunteers.

The two-staged Phase IIa study included a blinded, randomized, placebo-controlled phase, where the primary endpoint was to assess the efficacy of a single dose of SPL026 with supportive therapy (N=17) versus placebo with therapy (N=17) at two-weeks post-dose. All study participants were subsequently enrolled into an open-label phase of the study where they received a single dose of SPL026 with supportive therapy, and were followed-up for a further 12-weeks in study. This open-label trial design enabled the assessment of durability of antidepressant effect, as well as the comparative efficacy and safety of a one versus two dose regimen of SPL026.

Efficacy was assessed using the Montgomery-Asberg Depression Rating scale (“MADRS”) to measure any potential change in patients' depression from baseline. MADRS was assessed by independent raters who were not present at dosing and were blinded to the overall treatment. The Phase IIa study met the primary endpoint demonstrating a statistically significant and clinically relevant reduction in depressive symptoms two-weeks following a dose of SPL026 with supportive therapy, compared to placebo, demonstrating a -7.4 point difference in MADRS (p=0.02).

Analysis of key secondary endpoints demonstrated a rapid onset of antidepressant effect one-week post-dose, with a statistically significant difference in MADRS score between the active and placebo groups of -10.8 (p=0.002). Across the 12-week open-label phase, patients who received at least one active dose of SPL026 with supportive therapy reported a durable improvement in depression symptoms. No apparent difference in antidepressant effect was observed between a one and two dose regimen of SPL026. The total mean reduction in MADRS from baseline after a single dose of SPL026 was –15.4 at 12-weeks.

Rapid onset of antidepressant effect: Primary endpoint met with a statistically significant -7.4 point difference between SPL026 and placebo (p=0.02) at two-weeks post-dose, as measured by MADRS change from baseline. Statistically significant -10.8 point difference between SPL026 and placebo (p=0.002) at one-week post-dose, as measured by MADRS change from baseline. Clinically meaningful difference in response rates of SPL026 at week one and week two, 44% and 35%, respectively.

Clinically meaningful difference in remission rates of SPL026 at week one and week two of 44% and 29%, respectively. Durability of antidepressant effect: Durability was measured by a change in MADRS from the original baseline of the study, at one, two, four and 12-weeks after the open-label dose of SPL026. Durable improvement in depression symptoms from baseline in groups receiving at least one dose of SPL026 observed to 12-weeks following the open-label dose.

No apparent differences identified in antidepressant effect between a one and two dose regimen of SPL026. Treatment group receiving an open-label dose of SPL026 following placebo showed: Total change in MADRS from baseline of -10.6 and -15.4 at one and 12-weeks post open-label dose. Durable response rate from week 1 (43%) to week 12 (50%) post dose.

Durable remission rate from week 1 (43%) to week 12 (57%) post dose. Safety and tolerability: SPL026 was well tolerated by all patients receiving an active dose. No drug-related serious adverse events reported, including no reported suicidal ideation or behaviour.

Adverse events (“AEs”) deemed possibly related to treatment in the blinded phase: 19 in the SPL026 group. 4 in the placebo group. All were deemed mild or moderate in severity.

24 AEs deemed possibly related to treatment in the open-label phase. Majority of drug-related AEs (80%) resolved during the dosing visit. No clinically significant safety concerns in any treatment group, including with vital signs, electrocardiogram (ECG) or clinical laboratory findings.

The detailed results of the Phase IIa trial are expected to be presented at upcoming scientific meetings and published in a peer-reviewed journal.