ROPANICANT (SUVN-911), AN α4β2 NACHR ANTAGONIST: A PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY, EVALUATING THE EFFICACY AND SAFETY OF ROPANICANT IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER (MDD)

Ropanicant (SUVN-911) is a potent and selective α4β2 nicotinic acetylcholine receptor (nAChR) antagonist and has demonstrated more than 100 fold selectivity against over 70 receptors which include closely related α3β4 nAChR receptors, GPCRs, ion channels, enzymes, peptides, steroids, second messengers, growth factors, and prostaglandins. Ropanicant showed good oral bioavailability in preclinical species (rats, mice and dogs). Good oral exposures and increased cortical serotonin and norepinephrine levels translated into robust antidepressant like effects in animal models of depression. It showed faster onset of antidepressant activity, procognitive activity, and did not induce sexual dysfunctions in animal models thus, addresses major limitations of the currently used antidepressants. Non-clinical safety of ropanicant has been established in battery of safety pharmacology, general toxicity, embryo-fetal developmental and genotoxicity studies. Ropanicant was well tolerated and safe up to the highest tested dose of 60 mg single dose and 45 mg once daily (qd) for 14 days in healthy subjects. An open-label parallel-group Phase 2a study evaluated the safety and efficacy of Ropanicant in patients with moderate to severe MDD patients across multiple centers in the USA (NCT06126497). A total of 41 patients were randomized to receive Ropanicant either 45 mg qd, 30 mg twice a day (bid), or 45 mg bid in a ratio of 1:1:1, for duration of 14 days. Of the 41 randomized patients, 14 received Ropanicant 45 mg qd, 14 received 30 mg bid, and 13 received 45 mg bid. On Day 14, the Montgomery-Asberg Depression Rating Scale (MADRS) total score had changed significantly from baseline for the 30 mg bid group (-12.7), followed by the 45 mg qd (-10.5), and 45 mg bid (-10.4) groups. Day 14 MADRS total score showed a statistically significant improvement from baseline (p < 0.0001) across Ropanicant treatment arms. Ropanicant was found to be safe and well tolerated in patients with moderate to severe MDD across tested doses. The highly statistically significant improvement in the MADRS total score suggested potential treatment benefits of Ropanicant in MDD patients. Currently, a Phase 2b, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial is ongoing (NCT06836063). The study is evaluating the efficacy and safety of Ropanicant 30 and 45 mg bid compared to placebo bid. The primary objective of the study is to evaluate the efficacy of Ropanicant compared to placebo in reducing the depressive symptoms. The secondary objectives are efficacy of ropanicant compared to placebo based on clinician reported outcome, functional impairment, and safety. The primary endpoint is the change from baseline in MADRS total score at Day 43 (Week 6). The study is planned to randomize 195 patients in a 1:1:1 ratio to receive either 30 or 45 mg bid of Ropanicant or placebo bid (65 per treatment group) for a duration of 6 weeks. Topline data readout is expected in May 2026. Demographics and baseline characteristics of enrolled subjects will be presented at the conference.