Celldex Presents Histology Data from Phase 2 Study of Barzolvolimab in EoE Supporting Potential of Mast Depleting Agent in this Difficult to Treat Disease
- Phase 2 study is fully enrolled, with results expected in 2H 2025
- Histology data supports the therapeutic potential of barzolvolimab in EoE treatment
- Strong correlation found between mast cells and eosinophils in patient biopsies, validating the treatment approach
- None.
Insights
Celldex's Phase 2 data supports scientific premise that depleting mast cells could effectively treat eosinophilic esophagitis, with results expected 2H 2025.
The histology data presented by Celldex provides encouraging scientific validation for barzolvolimab's mechanism in eosinophilic esophagitis (EoE). The key finding - that high numbers of intraepithelial mast cells correlate with eosinophil counts in active EoE patients - strengthens the rationale for targeting mast cells with this c-KIT antibody.
What makes this particularly compelling is that mast cells persist in patients who don't respond to conventional therapies like topical corticosteroids, even when eosinophil counts decrease. This suggests barzolvolimab could address a critical gap in current treatment approaches by depleting these inflammatory cells that contribute to ongoing symptoms.
The Phase 2 EvolvE study design appears robust, enrolling 151 participants with a primary endpoint of reduction in peak esophageal mast cell count at 12 weeks. The secondary endpoints logically examine both eosinophil reduction and symptom improvement via the dysphagia symptom questionnaire.
For Celldex's pipeline strategy, this represents continued expansion of barzolvolimab beyond its initial applications in dermatological conditions. The company is building a cohesive platform around mast cell depletion across multiple inflammatory diseases, potentially increasing the overall value proposition of this asset.
Importantly, while this data supports the scientific premise, we await the actual efficacy results in the second half of 2025 to determine whether the mast cell depletion translates to clinical benefit in this difficult-to-treat condition.
Baseline data confirms high mast cell presence in EoE correlating with eosinophil counts, supporting barzolvolimab's potential therapeutic mechanism.
The histology findings presented at DDW 2025 reveal important immunological insights about eosinophilic esophagitis. The demonstration that intraepithelial mast cells are elevated across all esophageal segments in active EoE patients establishes a crucial baseline for understanding treatment potential.
The correlation between CD117+ or tryptase+ mast cells and eosinophils is particularly significant from an immunological perspective. This relationship suggests these cell types work in concert to drive the inflammatory cascade characteristic of EoE. Current treatments primarily target eosinophils, which explains why some patients experience incomplete resolution of symptoms despite reduced eosinophil counts - the mast cells remain active.
Mechanistically, barzolvolimab targets c-KIT (CD117), which is essential for mast cell survival and function. It has previously demonstrated the ability to deplete cutaneous mast cells in other conditions. The scientific question now is whether similar depletion will occur in esophageal tissue and whether this translates to symptom improvement.
The endorsement from Dr. Dellon, a recognized authority in esophageal diseases, adds weight to this approach. His observation that "eosinophilic esophagitis involves more than just eosinophils" aligns with the evolving understanding of this condition's complex immunopathology.
This data provides the immunological foundation for the ongoing clinical trial, but the true test will come when we see if mast cell depletion correlates with symptom improvement when full results are released later this year.
Phase 2 study fully enrolled; data expected in 2H 2025
HAMPTON, N.J., May 05, 2025 (GLOBE NEWSWIRE) -- Celldex announced today the presentation of histology data from the Company’s ongoing Phase 2 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 2 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 specimens1-11, are important sources of inflammatory cytokines2,9 and are associated with disease features of EoE including histological abnormalities and pain5,7,12,13,14. Mast cells persist in patients who are refractory to topical corticosteroid therapy, even when eosinophils regress13. The Phase 2 “EvolvE” study is designed to test the hypothesis that barzolvolimab, a monoclonal antibody (mAb) against c-KIT previously shown to deplete cutaneous mast cells15, will deplete esophageal mast cells and lead to clinical improvement in EoE.
Phase 2 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.
- 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.
- Patients are currently completing treatment and the follow up phase on study; clinical data from the study is expected to be presented in the second half of 2025.
References: 1Tappata et al. Allergy 2018; 2Aceves et al. JACI 2010; 3Abonia et al. JACI 2010; 4Colombo et al. WJGPT 2013; 5Dellon et al. AJG 2011; 6Lomazi et al. Arq Gast 2017; 7Zhang et al. JACI 2024; 8Kleuskens et al. Muc Imm 2023; 9Ben-Baruch Morgenstern et al. JACI 2022; 10Dunn et al. JACI 2020; 11Kirsch et al. JPGN 2007;12Alvarado et al. Allergy 2023;13Bolton et al. AMJ 2020; 14Zhang et al. Allergy 2022;15Terhorst-Molawi et al. Allergy 2023.
About Eosinophilic Esophagitis (EOE):
EoE, the most common type of eosinophilic gastrointestinal disease, is a chronic inflammatory disease of the esophagus characterized by the infiltration of eosinophils. This chronic inflammation can result in trouble swallowing, chest pain, vomiting and impaction of food in the esophagus – a medical emergency. Currently, there are limited treatment options for EoE. Several studies have suggested that mast cells may be an important driver in the disease. Given the lack of effective therapies for EoE and barzolvolimab’s potential as a mast cell depleting agent, Celldex believes EoE is an important indication for study. For additional information on the Phase 2 EvolvE study of barzolvolimab in EOE (NCT05774184), please visit clinicaltrials.gov.
About Barzolvolimab
Barzolvolimab is a humanized monoclonal antibody that binds the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity. KIT is expressed in a variety of cells, including mast cells, which mediate inflammatory responses such as hypersensitivity and allergic reactions. KIT signaling controls the differentiation, tissue recruitment, survival and activity of mast cells. In certain inflammatory diseases, such as chronic urticaria, mast cell activation plays a central role in the onset and progression of the disease. Barzolvolimab is currently being studied in chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU), prurigo nodularis (PN), eosinophilic esophagitis (EOE) and atopic dermatitis (AD), with additional indications planned for the future.
About Celldex Therapeutics, Inc.
Celldex is a clinical stage biotechnology company leading the science at the intersection of mast cell biology and the development of transformative therapeutics for patients. Our pipeline includes antibody-based therapeutics which have the ability to engage the human immune system and/or directly affect critical pathways to improve the lives of patients with severe inflammatory, allergic, autoimmune and other devastating diseases. Visit www.celldex.com.
Forward Looking Statement
This release contains "forward-looking statements" made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements are typically preceded by words such as "believes," "expects," "anticipates," "intends," "will," "may," "should," or similar expressions. These forward-looking statements reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct or that those goals will be achieved, and you should be aware that actual results could differ materially from those contained in the forward-looking statements. Forward-looking statements are subject to a number of risks and uncertainties, including, but not limited to, our ability to successfully complete research and further development and commercialization of Company drug candidates, including barzolvolimab (also referred to as CDX-0159), in current or future indications; the uncertainties inherent in clinical testing and accruing patients for clinical trials; our limited experience in bringing programs through Phase 3 clinical trials; our ability to manage and successfully complete multiple clinical trials and the research and development efforts for our multiple products at varying stages of development; the availability, cost, delivery and quality of clinical materials produced by our own manufacturing facility or supplied by contract manufacturers, who may be our sole source of supply; the timing, cost and uncertainty of obtaining regulatory approvals; the failure of the market for the Company's programs to continue to develop; our ability to protect the Company's intellectual property; the loss of any executive officers or key personnel or consultants; competition; changes in the regulatory landscape or the imposition of regulations that affect the Company's products; our ability to continue to obtain capital to meet our long-term liquidity needs on acceptable terms, or at all, including the additional capital which will be necessary to complete the clinical trials that we have initiated or plan to initiate; and other factors listed under "Risk Factors" in our annual report on Form 10-K and quarterly reports on Form 10-Q.
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Company Contact
Sarah Cavanaugh
Senior Vice President, Corporate Affairs & Administration
(508) 864-8337
scavanaugh@celldex.com
Patrick Till
Meru Advisors
(484) 788-8560
ptill@meruadvisors.com
FAQ
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