Eupraxia Pharmaceuticals Reports Positive Nine-Month Tissue Health and Symptom Data from Highest Dose Cohort in RESOLVE Trial

Eupraxia's EP-104GI Shows Robust 36-Week Efficacy in EoE Trial

Eupraxia Pharmaceuticals announced positive 36-week tissue health and symptom data from the highest dose cohort (Cohort 9, n=3) of its ongoing Phase 1b/2a RESOLVE trial for EP-104GI in eosinophilic esophagitis (EoE). Patients in Cohort 9 demonstrated robust and sustained improvements in both tissue health and symptom response compared to baseline, with 66% maintaining clinical remission in symptoms at week 36. The drug, EP-104GI, continued to be well tolerated across all 31 patients treated in the study, with over 230 patient-months of follow-up and no drug-related Serious Adverse Events reported.

• Tissue health outcomes in Cohort 9 (20 x 8 mg dose) at week 36 showed significant improvements, with EoEHSS Stage and Grade reductions of 90% and 88% respectively. This included improvements in both inflammatory and architectural components. Additionally, a 72% reduction in Peak Eosinophil Count (PEC) from baseline was observed, marking the largest reduction among all dose cohorts.
• Clinical remission and symptom response were robust, with an average 3-point reduction in the Straumann Dysphagia Index (SDI) from baseline in Cohort 9 at week 36, which is defined as clinical remission. Notably, 2 of 3 patients (66%) maintained clinical remission from week 8 through week 36, demonstrating a durable response.
• EP-104GI exhibited an excellent safety and tolerability profile across all dose levels. Over 230 patient-months of follow-up across 31 patients reported no drug-related Serious Adverse Events (SAEs). Crucially, there were no cases of oropharyngeal candidiasis, a common adverse event with oral steroids, nor any instances of adrenal insufficiency or glucose derangement, even in a patient with type II diabetes.

Sustained Tissue Health and Symptom Response with EP-104GI in EoE

Recent clinical investigations in eosinophilic esophagitis demonstrate significant advances in both biologic and conventional therapies. The cendakimab Phase 3 trial (NCT04753697) evaluated this high-affinity IL-13 monoclonal antibody in 430 patients aged 12 to 75 years, utilizing two dosing regimens: 360 mg once weekly for 48 weeks or 360 mg once weekly for 24 weeks followed by every-other-week dosing. At week 24, cendakimab demonstrated superior efficacy compared to placebo, with a reduction in dysphagia days of -6.1 versus -4.2 days (P<0.001) and histologic response rates of 28.6% versus 2.2% (P<0.001). Endoscopic severity improvements were also significant, with effects maintained through week 48. Safety analysis revealed adverse events in 83.8-84.6% of cendakimab-treated patients versus 73.4% with placebo, though the profile was not dose-limiting.

Dupilumab's efficacy profile has been further refined through two pivotal Phase 3 studies. The LIBERTY EoE TREET study (NCT03633617) demonstrated improved outcomes with subcutaneous dupilumab 300 mg weekly versus placebo in adults and adolescents aged ≥12 years, while the EoE KIDS study (NCT04394351) established efficacy using weight-tiered dosing in children aged ≥1 to <12 years. Population pharmacokinetic modeling identified alternative regimens optimized for specific weight ranges, including 200 mg every 3 weeks for patients weighing ≥5 to <15 kg. Meta-analysis data encompassing 8 randomized controlled trials with 865 participants confirmed that monoclonal antibodies significantly reduced peak eosinophil counts (MD: -59.17; 95% CI: -88.88 to -29.45), with dupilumab demonstrating the strongest efficacy among six evaluated antibodies and adverse event profiles comparable to placebo.

Topical corticosteroid therapy remains a cornerstone treatment, with updated meta-analysis of budesonide demonstrating robust efficacy across 11 randomized controlled trials involving 1,089 participants. Budesonide significantly improved histologic remission (RR: 26.85; 95% CI: 13.72-52.56; P<0.00001), reduced peak eosinophil counts (SMD: -1.08; 95% CI: -1.40 to 0.77; P<0.00001), and enhanced clinical response rates (RR: 1.58; 95% CI: 1.03-2.42; P=0.04). However, fibrosis scores showed no significant improvement (P=0.48), highlighting limitations in reversing structural changes. Safety analysis revealed overall adverse events comparable to placebo (RR: 1.01; 95% CI: 0.82-1.24), though infections were more frequent (RR: 2.14; 95% CI: 1.20-3.80; P=0.009), primarily localized oropharyngeal candidiasis rarely requiring discontinuation. Transient cortisol suppression was observed (SMD: -0.41; 95% CI: -0.66 to 0.16; P=0.001), warranting long-term adrenal monitoring considerations.

Understanding the RESOLVE Trial Design and Key Endpoints

Recent clinical trials in eosinophilic esophagitis have established standardized design parameters and endpoint measures that reflect both histologic improvement and symptomatic relief. The most significant trials include the MESSINA trial for benralizumab, phase 3 studies for cendakimab and dupilumab (LIBERTY EoE TREET), and pediatric studies, all demonstrating convergence toward consistent primary endpoints of histologic response (≤6 eosinophils per high-power field) and dysphagia symptom improvement.

Addressing Unmet Needs in Eosinophilic Esophagitis Treatment Landscape

Recent research has identified significant gaps in eosinophilic esophagitis management, with approximately one-third of patients remaining inadequately controlled despite current therapeutic options. The literature reveals both treatment-related challenges and specific patient populations requiring targeted interventions.

• Treatment-refractory patients represent a major unmet need, with real-world remission rates below 50% regardless of treatment modality, significantly lower than short-term clinical trial results

• Severe and fibrostenotic EoE patients who do not respond to standard therapies (PPIs, topical corticosteroids, dietary elimination) and would not qualify for most clinical trials require specialized approaches

• Pediatric populations with early-onset disease, particularly those diagnosed before age 2 years who may need combination therapies including off-label biologic use despite not meeting standard indication criteria

• Patients with psychiatric comorbidities show increased psychotropic drug use (13.8% vs 7.1% in matched controls), with women, older patients, and those with lower educational levels at higher risk

• Non-adherent patient populations where over half demonstrate imperfect medication adherence and approximately 20% receive no therapy, contributing to suboptimal outcomes

• Patients experiencing diagnostic delays who face an average 3.4-year delay from symptom onset to diagnosis, with many lacking appropriate follow-up endoscopy (19.0%) despite available care

• Individuals requiring non-invasive monitoring solutions as current endoscopic assessments create barriers to optimal disease management and treatment response evaluation

EP-104GI: Sustained Efficacy and Safety Signal a New Era in EoE Treatment

The recent announcement regarding EP-104GI in eosinophilic esophagitis (EoE) offers a compelling glimpse into the future of managing this chronic, immune-mediated esophageal condition. With positive 36-week data from its Phase 1b/2a RESOLVE trial, Eupraxia Pharmaceuticals is signaling a potential advancement in a therapeutic area that continues to seek more effective and durable solutions. EoE, characterized by debilitating dysphagia and the risk of progressive esophageal remodeling and fibrostenosis, necessitates long-term, well-tolerated treatments.

Current therapeutic mainstays, including proton pump inhibitors, dietary modifications, and swallowed topical corticosteroids (STCs) like fluticasone propionate and budesonide, have demonstrated efficacy in inducing histological remission and improving symptoms. However, challenges persist, particularly concerning the consistency of drug delivery, patient adherence, and the potential for localized adverse events. The sustained improvements in both tissue health and symptom response observed with EP-104GI over 36 weeks are therefore highly encouraging. Achieving clinical remission in symptoms for a substantial portion of patients in the highest dose cohort suggests a robust and lasting anti-inflammatory effect, which is critical for a disease that requires ongoing management to prevent structural damage.

The safety profile reported for EP-104GI is equally significant. With no drug-related Serious Adverse Events across a considerable patient-month follow-up, the drug appears to be well tolerated. This is a crucial factor for a chronic condition where patients require continuous therapy, and it could differentiate EP-104GI from systemic corticosteroids, which are known for widespread adverse effects, and even from some topical agents that can lead to local complications.

However, it is important to contextualize these promising early-stage results. The data, while strong, originates from a small cohort within a Phase 1b/2a study. Larger, randomized controlled trials will be essential to confirm these findings across a broader and more diverse patient population, and to fully characterize the long-term safety profile, including any potential localized adverse events. The competitive landscape for EoE is also dynamic, with novel corticosteroid formulations and emerging biologic agents targeting specific inflammatory pathways. For EP-104GI to carve out a significant market position, it will need to demonstrate clear advantages in efficacy, safety, or patient convenience compared to these evolving treatment options. Should these positive trends continue through later-stage development, EP-104GI could represent a valuable new tool for clinicians, offering a sustained and well-tolerated option to improve outcomes for patients living with EoE.