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Investors sent Celldex’s share price down by 18% to $19.72 in premarket trading.\n Celldex has stopped development of barzolvolimab in eosinophilic esophagitis (EoE) despite meeting its primary endpoint in a phase 2 trial. The biotech showed the candidate depletes mast cells in the gastrointestinal tract, but that positive finding was overshadowed by the antibody\'s failure to improve clinical outcomes.EoE is a chronic inflammatory condition of the esophagus characterized by the infiltration of eosinophils and mast cells, two types of white blood cells. Yet, efforts to treat the condition by targeting white blood cells have floundered. Allakos’ lirentelimab reduced eosinophils in a phase 2/3 trial but showed no significant effect on a dysphagia scale that assessed patients’ ability to swallow food, a key symptom of EoE.Now, Celldex has suffered a similar setback. The biotech randomized 65 patients to receive the anti-KIT antibody barzolvolimab or placebo. After 12 weeks, mucosal mast cell levels in the gastrointestinal tract had fallen significantly in the barzolvolimab cohort compared to placebo, achieving the trial’s primary endpoint. Previously, Celldex had shown the antibody can deplete cutaneous mast cells.Yet, the mucosal mast cell primary endpoint was just one of two key areas of focus for Celldex. The biotech also wanted to show that depleting mast cells improves symptoms, as Celldex CEO Anthony Marucci explained on a Tuesday call with investors to discuss the data.“We have repeatedly said that we needed to not only see profound impact of cell depletion, but we also [needed] a reduction of dysphagia scores that would be clinically meaningful and compare favorably to the current standard of care,” Marucci said. “These results did not meet our internal hurdle rate, and we will not advance development in this indication.” Scores on the Dysphagia Symptom Questionnaire were no better for patients on barzolvolimab than placebo, the biotech reported. Equally, Celldex saw no significant improvement in endoscopic scoring of EoE-related inflammation and fibrosis in the treatment group. After Celldex reported the trial findings and program discontinuation, investors sent the biotech’s share price down by 18% to $19.72 in premarket trading.Celldex is continuing to test barzolvolimab in two phase 3 trials in chronic spontaneous urticaria as well as in phase 2 studies in atopic dermatitis and prurigo nodularis. The biotech advanced in those settings on the strength of evidence that barzolvolimab depletes cutaneous mast cells. The discovery in the EoE trial that barzolvolimab also depletes mucosal mast cells could open up other indications for KIT inhibitors.  The EoE trial suggests Celldex could expand beyond skin conditions to target gastrointestinal conditions where mast cells play a role. One possibility is that Celldex will apply its bispecific approach, rather than barzolvolimab, to gastrointestinal indications. Engaging two targets may unlock diseases where depleting mast cells is beneficial but insufficient to significantly improve clinical outcomes.  The failures of Allakos and Celldex in EoE have thinned the field of late-stage programs in this indication. Amgen and AstraZeneca are still in the running, with a phase 3 trial of the partners’ anti-TSLP antibody Tezspire now fully enrolled. Tezspire reduces blood eosinophil counts but works in severe asthma patients irrespective of their starting levels of the white blood cells.