Company: SUPN
Filing Date: 2025-02-25
Form Type: 10-K
Source: 0001356576-25-000017
Chunk: 605

Company: SUPERNUS PHARMACEUTICALS, INC.
Filing Date: 2025-02-25
Form: 10-K
Item: Item 1
Chunk 605
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. A single administration of SPN-820 rapidly (on within one hour) and transiently (off within seven hours) enhances intracellular mTORC1 signaling in the prefrontal cortex of animals, restores levels of synaptic proteins, reducing depressive-like behaviors in a brain-derived neurotrophic factor "BDNF"-dependent manner. The rapid and transient enhancement of mTORC1 signaling in the prefrontal cortex is required for anti-depressant effects in preclinical animal models. The intracellular mechanism of SPN-820, and the lack of binding to cell surface receptors, suggests the potential for a differentiated safety profile.

A Phase 1 trial demonstrated early proof of concept in which a single dose of SPN-820 showed a rapid and sustained improvement in core symptoms, with favorable safety and tolerability in patients with treatment resistant depression. We believe the novel mechanism of action (MOA) in depression may improve symptoms of depression in patients who have failed other 

8

agents. 

We completed a Phase 2a multi-center open label study in 40 subjects with Major Depressive Disorder (MDD) in the fourth quarter of 2024. The data were based on 40 enrolled subjects, of which 38 completed the ten-day treatment period. The primary objective of the study was to assess efficacy in MDD, as well as the onset of efficacy. The Phase 2a study demonstrated rapid and substantial decrease in depressive symptoms, and 80% decrease in suicidal ideation. SPN-820 was well-tolerated during the study with few adverse events reported by the subjects. In addition, the data demonstrated a rapid Montgomery–Asberg Depression Rating Scale (MADRS) response rate (≥50% reduction) and remission (MADRS ≤10), reaching 50.0% and 35.0% of subjects, respectively, at 4 hours, with additional improvement to 84.2% and 63.2% of participants by Day 10.  

In February 2025, we reported topline results from the Phase 2b study of SPN-820. The Phase 2b study of SPN-820 in adults with treatment-resistant depression did not demonstrate a statistically significant improvement on the primary endpoint of change from baseline in the MADRS total score to Week 4 (SPN-820 [LS mean ± Standard Error]: -12.3 ± 0.96 vs. placebo: -11.9 ± 0.96; p = not significant