EsoCap Technology
Clinical Development
Lead Indication: Eosinophilic Esophagitis
The lead indication is eosinophilic esophagitis (EoE), a rare and chronic inflammatory disease of the esophagus with no globally approved topical treatment. EoE is increasingly recognized as a chronic, localized, immune-mediated condition, clinically characterized by symptoms related to dysphagia and histologically by eosinophil-dominated inflammation. Common symptoms include difficulty swallowing (dysphagia), food impaction, vomiting, and heartburn. EoE is the leading cause of dysphagia and food impaction in children and young adults.
The only treatment options for the condition are an extremely strict diet, off-label treatment with steroids or proton pump inhibitors, an orodispersible budesonide tablet, which is only available in limited territories, an oral suspension of budesonide, which is only approved in the US for a short duration of treatment, or a monoclonal antibody, approved in the US and Europe ( the latter for steroid-resistant patients).
These treatment options remain suboptimal for the vast majority of affected patients.
ESO-101
EsoCap’s lead product, ESO-101, will ensure a long-lasting topical delivery of mometasone, a well-established safe and highly potent locally acting steroid. It has the potential to establish a new standard of care and majorly improve the lives of affected people.
The ACESO study was a randomized, placebo-controlled, double-blind Phase II study to evaluate the safety, tolerability, and efficacy of ESO-101 in adult patients with active EoE. ESO-101, EsoCap’s lead product candidate, consists of a capsule with a rolled-up, thin mucoadhesive film with the anti-inflammatory corticosteroid mometasone furoate. The study was conducted at 14 medical centers in five European countries and enrolled 43 participants with EoE and a peak eosinophil count of ≥15 eosinophils per high-power field (hpf). Patients were randomized in a 2:1 ratio and treated with ESO-101 or placebo once daily for 28 days.
The ACESO trial met its primary endpoint with a statistically significant reduction of the peak eosinophil count from baseline in histology samples. In the ESO-101 group, the mean reduction was 49.1 ± 88.4 eosinophils/hpf (p=0.0318). In addition, while none of the patients from the placebo group achieved histological remission, 48% and 44% of patients achieved <15 and <6 eosinophils/hpf, respectively, when treated with ESO-101 (p=0.0028 and p=0.0035, respectively). Patients treated with ESO-101 had a significant response in the eosinophilic esophagitis endoscopic reference score (EREFS) scores, indicating promising potential for remodeling effects despite the short treatment duration. A significant improvement of dysphagia symptoms was observed after a 4‑week period with a high placebo response: a benefit of ESO-101 in relieving EoE dysphagia and odynophagia symptoms is expected to be seen in future clinical trials with a longer treatment period.
Importantly, ESO-101 also demonstrated a highly favorable safety and tolerability profile with a notable absence of oral and oropharyngeal as well as esophageal candidiasis, which is commonly observed with topical corticosteroid treatment. Compliance was high, with 100% in the ESO-101 and 93% in the placebo groups. The high level of patient satisfaction with the handling of the study medication underlines the user‑friendliness of the ESO-101 drug-delivery system.
Detailed results of the ACESO Phase II study published in the peer-reviewed medical journal Alimentary Pharmacology & Therapeutics. https://doi.org/10.1111/apt.18443
These results mark an important milestone for EsoCap and represent a substantial value inflection point.
Additional Indications
Further applications with the EsoCap platform technology
EsoCap has successfully integrated small molecules, peptides, an antibody and liposomal encapsulated RNA into its innovative film technology, paving the way for new applications, particularly in reflux, Barrett’s esophagus and oesophageal cancer.
The EsoCap technology enables targeted therapy of the esophageal mucosa and can thus be used to treat or prevent a variety of diseases of the esophagus, such as gastroesophageal reflux disease (GERD).
The EsoCap technology might be suitable to support the natural function of the esophageal sphincter structure through the local and targeted application of active substances and thus prevent pathological reflux. In general, all agents that target the sphincter structure of the esophagus and increase the tone of the lower esophagus are conceivable for this purpose. In connection with the EsoCap system, it should be positively highlighted that the local and long-lasting application of active substances represents a major advantage in the case of particularly potent active substances that usually cannot be used or can only be used to a limited extent by classical oral application due to the critical effect/side-effect profile.
Barrett’s esophagus is often a consequence of gastro-esophageal reflux disease (GERD), caused by the failure of the lower esophageal sphincter over time, leading to acid-induced damage to the esophagus. Under these conditions, the tissue structure of the cells lining the lower esophagus changes. There is a transformation of the squamous epithelium of the terminal esophagus into a specialized intestinal-type cylindrical epithelium with goblet cells. Intestinal metaplasia represents a precancerous condition, which is why Barrett’s esophagus is associated with an increased risk of esophageal cancer.
The prevalence of Barrett’s esophagus is 0.5-10% with a median age of diagnosis of 55-65 years, with men being affected approximately twice as often as women. Treatment approaches to date are based on the patient’s symptoms, the extent of the tissue changes and are accompanied by regular imaging procedures, especially endoscopic controls. The current therapy regime could undergo a fundamental change due to the possibilities of the EsoCap device.
