Novel, Non-InvasiveImaging of Eosinophil-Related Inflammation Throughout the Esophagus in Patients withEosinophilic Esophagitis

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ABSTRACT Eosinophilic Esophagitis (EoE) is a chronic inflammatory disease of the esophagus, characterized by eosinophil infiltration into the esophagus, resulting in pain, dysphagia and, if untreated, eventual esophageal fibrosis and stricture. EoE prevalence in the U.S. is approximately 57/100,000 including patients of all ages, and current evidence suggests that the overall prevalence of EoE continues to increase.. There is a great unmet medical need for a new EoE diagnostic method. The current standard-of-care method involves endoscopy plus biopsies of the esophagus which are difficult, costly, and invasive, creating barriers to both diagnosis and ongoing disease management. As a result, EoE tends to be underdiagnosed and patients’ symptoms and disease less optimally managed. NDX33-o is a novel, non-invasive medical imaging agent that is optimal for identifying eosinophilic inflammation in EoE patients and can be used to image and diagnose patients with EoE in a less invasive manner and with a higher accuracy than today’s current approach. Preliminary clinical results, in a limited number of patients have shown that NDX33-o can detect areas of inflammation in esophagi of EoE patients supporting NDX33-o as a novel detection method for EoE. This project will assess NDX33-o detection of EoE in a larger number of EoE patients. Phase 1 of the project will focus on planning activities for the clinical trial that will be conducted in phase 2. In Phase 1, NexEos Diagnostics, Inc. will complete all planning activities including development of manufacturing methods for a NDX33-o kit for use in the radiopharmacy. NexEos will also seek IND approval from the FDA for the administration of NDX33-o to human participants in the Phase 2 clinical study. After receiving IND approval, Phase 2 of the project will be initiated with a clinical study of 180 patients suffering from EoE symptoms or dysphagia who will be enrolled at the University of Utah. All participants will receive the same treatment – they will first be diagnosed by oral administration of NDX33-o and medical imaging followed several days later, by diagnosis with the current standard-of-care, endoscopy and biopsy. NDX33-o will be evaluated for its accuracy and sensitivity for detecting EoE compared to standard-of-care. Moreover, the safety profile of NDX33-o will be evaluated in all administered patients. Successful completion of the proposed clinical trial will significantly contribute to the development of NDX33-o as an imaging marker for eosinophil-related inflammation in EoE patients, and subsequently for the potential diagnosis of other human eosinophil-associated diseases.