Ongoing phase II data announced of barzolvolimab in eosinophilic esophagitis (EoE)..- Celldex

Celldex announced  the presentation of histology data from the Company’s ongoing Phase II study of barzolvolimab in eosinophilic esophagitis (EoE). Biopsies taken during screening demonstrate the presence of high numbers of intraepithelial mast cells in participants with active EoE and correlate with eosinophil counts, supporting the hypothesis that treating EoE with barzolvolimab—a mast cell depleting agent—could provide promising therapeutic benefit. The data were discussed in a poster presentation at the Digestive Disease Week (DDW) 2025 conference in San Diego today. Celldex announced in February 2025 that enrollment to the Phase II study is complete and that clinical results are expected in the second half of 2025.

“These data continue to add to a growing body of literature suggesting that eosinophilic esophagitis involves more than just eosinophils and that mast cells play an important role in the disease process,” said Evan S. Dellon, MD, MPH, Professor of Medicine and Director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina School of Medicine and the lead author of the poster. “This is further supported by previous findings that mast cells are present in the biopsy tissue of some patients who continue to suffer from EoE even after eosinophils have been depleted. Barzolvolimab has been shown to deplete cutaneous mast cells and we believe it will likely also deplete esophageal mast cells, which could lead to clinical improvement in EoE—an indication that sorely needs additional effective treatment options. I look forward to seeing the clinical data from the study later this year.”

EoE is the most common type of eosinophilic gastrointestinal disease, a chronic inflammatory disease of the esophagus characterized by the infiltration of eosinophils. Chronic inflammation can result in trouble swallowing, chest pain, vomiting and impaction of food in the esophagus – a medical emergency. Several studies have suggested that mast cells may be an important driver in the disease. Mast cells are present and activated in the esophageal epithelium of EoE biopsy specimens,  are important sources of inflammatory cytokines  and are associated with disease features of EoE including histological abnormalities and pain . Mast cells persist in patients who are refractory to topical corticosteroid therapy, even when eosinophils regress. The Phase II “EvolvE” study is designed to test the hypothesis that barzolvolimab, a monoclonal antibody (mAb) against c-KIT previously shown to deplete cutaneous mast cells, will deplete esophageal mast cells and lead to clinical improvement in EoE.

Phase II EvolvE presentation details: “Intraepithelial Mast Cells are Elevated in Active Eosinophilic Esophagitis and Correlate with Eosinophils: Baseline Data from a Randomized Controlled Trial of Barzolvolimab”; poster #Mo1345; Ongoing 28-week, randomized, double-blind, placebo controlled study evaluating 300 mg of barzolvolimab or placebo administered every 4 weeks in participants with known EoE. Eligible participants have at least 15 eosinophils per high power field (hpf) in 2 of 3 segments of the esophagus and at least 4 dysphagia days in the 2 weeks prior to baseline (dysphagia symptom questionnaire [DSQ] score ≥ 8). Primary endpoint is reduction in peak esophageal epithelial mast cell count (PMC) cell at 12 weeks, with key secondary endpoints of reduction in peak eosinophil count (PEC) and reduction in DSQ at 12 weeks. Pinch biopsies from 151 screened participants were obtained at screening from three different esophageal segments (proximal, middle, distal). Screening histology data from this trial demonstrate that high numbers of intraepithelial mast cells are present in participants with active EoE and correlate with eosinophil counts:
Intraepithelial mast cells (Tryptase and CD117 positive) and eosinophil counts per hpf from screening biopsies were enumerated by IHC and H&E staining. Similar numbers of cells were observed across the three biopsy sites, with a trend towards greater numbers in the distal esophagus. Participants who failed screening due to low eosinophil counts also tended to have lower tryptase+ and CD117+ mast cell counts.
 Pearson correlations show a strong association between both CD117+ or tryptase+ total and peak mast cells and eosinophils, as well as between CD117+ and tryptase+ total and peak mast cells