Seelos Therapeutics, Inc. announced top line data demonstrating clinically meaningful treatment effects across multiple endpoints and a well-tolerated safety profile from the double-blind, placebo-controlled cohort (Part 2) of its Phase II study of SLS-002 (intranasal racemic ketamine) for Acute Suicidal Ideation and Behavior (ASIB) in adults with Major Depressive Disorder (MDD). SLS-002 versus placebo demonstrated early and persistent reductions in symptoms of depression as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). The graph presents results from the mixed model for repeated measures (MMRM) analysis of change from baseline in MADRS total score.

Target enrollment of this study was 220 patients, however, due to financial constraints, only 147 patients diagnosed with MDD requiring psychiatric hospitalization due to significant risk of suicide were randomized. The data from the 147 subjects (67% of target enrollment) were evaluated using the protocol-defined methods of analysis. Due to the limited sample size, the study did not meet the pre-defined primary endpoint (MADRS ANCOVA at 24 hours post dosing).

However, assuming the same treatment difference and standard deviation, analyses showed that the study would have achieved statistical significance for the primary endpoint, had the study reached full enrollment (220 patients). Detailed Summary of Key Efficacy Endpoints: MADRS results at 4 hours after dosing demonstrated a statistically significant change relative to placebo (p <0.001, 5.9 point LS mean treatment difference); MADRS results at 24 hours after dosing utilizing 2-way ANCOVA3 with baseline MADRS as a covariate (the pre-defined primary endpoint/analysis) demonstrated clinically meaningful results, but did not achieve statistical significance under the methodology used (p=0.069, 3.3 point LS mean treatment difference); MADRS results at 24 hours after dosing utilizing an exploratory ANOVA (t-test) analysis demonstrated statistically significant change relative to placebo (p=0.049, 3.6 point mean treatment difference); MADRS results at Day 16 demonstrated a statistically significant change relative to placebo (p=0.012, 4.4 point LS mean treatment difference) ? demonstrating persistence of effect; Meaningful results further supported by (proportion of SLS-002 subjects versus placebo, respectively): MADRS Response Rate, defined as = 50% reduction from baseline, at Day 16 (75.7% versus 47.9%) p<0.001; MADRS Remission Rate, defined as a total score = 12, at Day 16 (62.2% versus 32.9%) p<0.001; MADRS at end of 2-week safety follow up (Day 29/30) revealed continued improvement, demonstrating no evidence of return of symptoms. Clinically meaningful reduction in acute suicidality was demonstrated with SLS-002 over placebo.

Both groups continued to improve over time. Sheehan-Suicidality Tracking Scale (S-STS) Total Score: (Mean baseline total scores were 21.4 for SLS-002 and 21.0 for placebo): 4 hour change from baseline was -15.1 for SLS-002 and -12.0 for placebo (p=0.022); 24 hour change from baseline was -15.5 for SLS-002 and -12.1 for placebo (p=0.008); Clinical Global Impression of Severity for Suicidal Ideation and Behavior (CGIS-S/IB)5: (Mean baseline scores were 4.0 for both SLS-002 and placebo): 4 hour change from baseline was -1.5 for SLS-002 and -1.1 for placebo (p=0.011); 24 hour change from baseline was -1.7 for SLS-002 and -1.4 for placebo (p=0.102); Detailed Summary of Safety Results: SLS-002 was well-tolerated with no new or unique safety signals identified and there were no deaths reported in the study. At least one treatment-emergent adverse event was reported in 52.7% of subjects treated with SLS-002 versus 39.7% treated with placebo; the majority of adverse events were mild or moderate and transient in nature.

The most common treatment-emergent adverse events (=5% and >placebo) were dizziness (18.9% versus 2.7%), euphoric mood (6.8% versus 0%) and suicidal ideation (5.4% versus 2.7%). There were 5 serious adverse events (3 with SLS-002, 2 with placebo), all for suicidality, all judged unrelated to the study drug, and all resolved. Specific scales were utilized to measure the three most common known adverse events associated with ketamine treatments, which are dissociation, hemodynamic effects and sedation.

The data below support that SLS-002 may reduce the frequency and severity of these most common effects compared to what is reported with other ketamine treatments. Clinician-Administered Dissociative States Scale (CADSS): At no point did the placebo-adjusted mean change from pre-dose baseline exceed the threshold of clinically meaningful dissociation (>4); Placebo-adjusted mean change from pre-dose baseline (at 40 minutes ? correlating roughly with maximum plasma concentrations) = 3.9 after first dose and 1.8 at 1 hour post first dose; Placebo-adjusted mean change from pre-dose baseline 2.5 on Day 4 (at 40 minutes) after second dose and 1.4 on Day 8 (at 40 minutes) after third dose.

Hemodynamic Effects: 6 subjects who received SLS-002 had an adverse event reported of either increased blood pressure or hypertension, all events were mild (except 1 moderate), all were transient and resolved; In review of mean vital sign data for SLS-002, minimal changes were observed; Systolic blood pressure at Baseline was 122.7 mmHg, with maximum mean values of 126.7 mmHg on days 1 and 11 (1 hour post dose); Diastolic blood pressure at Baseline was 77.7 mmHg, with maximum mean values of 81.1 mmHg on Day 8 (1 hour post dose). Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S): Maximum sedation (MOAA/S score < 5) occurred approximately 15 minutes after dosing on day 1 (placebo adjusted % of subjects 25.5%) with attenuation over time.