S891 Results From Dose Escalation Cohorts 1-6 of RESOLVE, an Ongoing Phase 1b/2a Study of EP-104GI (Long-Acting Fluticasone Propionate Injectable Suspension) for Eosinophilic Esophagitis

Introduction: Eosinophilic esophagitis (EoE) is characterized by inflammation, eosinophil influx, and esophageal remodeling. Current therapies for EoE are not always effective and have potential side effects. EP-104GI is a long-acting fluticasone propionate (FP) injectable suspension of coated FP crystals that release at a pre-defined rate via diffusion at the injection site. RESOLVE (NCT05608681) is a Phase 1b/2a, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, feasibility, pharmacokinetics, and efficacy of EP-104GI in adults with EoE. Methods: A single administration EP-104GI is injected at multiple sites in the esophagus. Dose escalations increase the dose per injection site and/or number of sites. Esophageal biopsies are collected at baseline, weeks 4, 12, and 36. Assessments include EoE Histologic Scoring System (EoEHSS), peak eosinophil count (PEC), and patient-reported Straumann Dysphagia Index (SDI). Results: Previously reported data from cohorts 1-2 (total doses 4-8 mg) showed decreases in SDI for all patients, which were maintained to week 24 where follow-up data are available. A decrease in mean PEC was observed for all patients in Cohort 2. Cohorts 3-6 (total doses 20-64 mg) showed symptom (SDI) reductions at week 12 for 11/12 patients; the majority maintained to week 24. Mean PEC declined for 10/12 participants at week 12, including 1 patient in Cohort 5 who achieved PEC ≤6 at all biopsy sites, representing complete histological remission. Cohorts 5 and beyond are followed for 36 weeks post-dose; symptom and histological responses have extended to week 36 for Cohort 5. For all in Cohort 6, PEC was reduced by 59 to 91% and SDI peak reductions were up to 6 points (0-9 scale) by week 12. Mean EoEHSS stage reduction was 66% or 0.40 points (composite score of 0-1) and mean EoEHSS grade reduction was 65% or 0.38 points. Plasma FP levels increased with dose and were stable at <25 pg/mL after the initial peak. Treatment-emergent adverse events were mild to moderate, most unlikely related to EP-104GI. Serum glucose and cortisol were stable post-dose with no gastrointestinal candidiasis or adrenal suppression. Conclusion: EP-104GI injection has been feasible and safe. Higher doses yield improved patient-reported symptom scores and favorable histology results, without the occurrence of corticosteroid-related side effects.