barzolvolimab (CDX-0159) / Celldex - LARVOL DELTA

A Study of Barzolvolimab in Patients With Prurigo Nodularis (clinicaltrials.gov) - P2 | N=140 | Active, not recruiting | Sponsor: Celldex Therapeutics | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2026 ➔ Mar 2027 | Trial primary completion date: Jan 2026 ➔ Jun 2026

Enrollment closed • Trial completion date • Trial primary completion date • Immunology • Prurigo Nodularis

A Study to Investigate Efficacy, Safety and Tolerability of Barzolvolimab Versus Placebo in Adults With Cold Induced Urticaria and Symptomatic Dermographism Inadequately Controlled by H1-antihistamines (EMBARQ - ColdU and SD) (clinicaltrials.gov) - P3 | N=240 | Recruiting | Sponsor: Celldex Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Dermatology • Immunology • Urticaria

Emerging IgE and non-IgE targeted therapies for chronic urticaria. (PubMed, Ann Allergy Asthma Immunol) - "Dupilumab received FDA approval for antihistamine refractory chronic spontaneous urticaria (CSU) supporting the targeting of type-2 cytokines, IL-4 and IL-13, in this disease. Bruton's tyrosine kinase (BTK) inhibitors show promise, with remibrutinib receiving FDA approval and demonstrating significant reductions in UAS7 in Phase 3 trials. c-Kit (c-Kit or KIT) inhibition with barzolvolimab shows robust efficacy with sustained effects post-treatment...Although some programs have been discontinued due to safety concerns or lack of efficacy such as fenebrutinib (BTK inhibitor), THB001 (c-Kit inhibitor), EP262 (MRGPRX2 antagonist), tezepelumab (anti- TSLP), as well as lirentelimab and AK006 (Siglec-targeting agents), these studies have informed many of the other positive studies. In summary, over the last year, we have seen the CU pipeline mature with multiple Phase 3 programs and new approvals representing diverse mechanisms of action. Nevertheless, significant..."

Journal • Review • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria • IL13 • IL4 • TSLP

Celldex Initiates Global Registrational Phase 3 Program of Barzolvolimab in Cold Urticaria and Symptomatic Dermographism (GlobeNewswire) - "EMBARQ-ColdU and SD is designed to establish the efficacy and safety of barzolvolimab in adult participants with ColdU and SD who remain symptomatic despite H1 antihistamine treatment...The randomized, double-blind, placebo-controlled, parallel group Phase 3 study will recruit participants from approximately 75 clinical trial sites across 7 countries."

Trial status • Dermatology • Urticaria

EMBARQ: A Study of CDX-0159 in Patients With Cold Induced Urticaria and Symptomatic Dermographism (clinicaltrials.gov) - P3 | N=240 | Not yet recruiting | Sponsor: Celldex Therapeutics

New P3 trial • Dermatology • Immunology • Urticaria

Long-term Efficacy and Safety Extension (LTE) Study of Barzolvolimab in Participants With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P3 | N=1370 | Recruiting | Sponsor: Celldex Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Long-term Efficacy and Safety Extension (LTE) Study of Barzolvolimab in Participants With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P3 | N=1370 | Not yet recruiting | Sponsor: Celldex Therapeutics

New P3 trial • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

…Company’s Phase 2 study in ColdU and SD (GlobeNewswire) - "Patients were followed for up to 24 weeks after treatment completion and patients with returning or continuing symptoms were given the option to enter an open label extension (OLE) during this follow up period. Consistent with the clinical endpoint results at Week 20, placebo-treated patients entered the OLE at a faster rate compared to barzolvolimab-treated patients. The study was recently completed and data from the OLE are expected to be presented in Q1 2026."

P2 data • Trial status • Immunology • Urticaria

Barzolvolimab - KIT Inhibitor Program:…Additional Indications (GlobeNewswire) - "(i) Enrollment continues in the Phase 2 study in prurigo nodularis (PN)....Initial data from this study are expected to be presented in 2H 2026; (ii) Enrollment is ongoing in the Phase 2 study in atopic dermatitis (AD)....Initial data from this study are expected to be presented in 2H 2026."

Enrollment status • P2 data • Atopic Dermatitis • Prurigo Nodularis

Celldex Presents Additional Positive Data Demonstrating Barzolvolimab’s Ability to Drive Rapid, Profound and Durable Complete Urticaria Control in Phase 2 Chronic Spontaneous Urticaria (CSU) Study (GlobeNewswire) - "Barzolvolimab treatment demonstrated rapid and profound improvement in urticaria control with sustained efficacy, including after the completion of active therapy, in patients with CSU refractory to antihistamines; Significant improvements in urticaria control test over seven days (UCT7) scores were observed. UCT7 evaluates symptoms, quality of life, treatment adequacy and overall disease control within the past week. Patients on barzolvolimab experienced up to an 8.6 point improvement (mean) from baseline UCT7 scores compared to only 2.5 points for placebo at Week 12. This improvement deepened for patients on barzolvolimab to up 10.0 points at Week 52....At Week 52, 71% of patients achieved complete disease control (UCT7=16) and 86% of patients achieved well-controlled disease..."

P2 data • Chronic Spontaneous Urticaria

Celldex…announced today new data demonstrating sustained efficacy and a well tolerated safety profile over a 20 week treatment period for barzolvolimab in two of the most common forms of chronic inducible urticaria (CIndU)—cold urticaria (ColdU) and symptomatic dermographism (SD). (GlobeNewswire) - "Patients on study (n=196) had poorly controlled disease on initial provocation testing (ColdU—mean baseline critical temperature threshold of approximately 19°C or 66°F on TempTest; SD—average baseline critical friction thresholds of 3.6 out of 4 pins on FricTest)...Barzolvolimab was well tolerated with a favorable safety profile over the 20 week treatment period consistent with previous studies."

P2 data • Urticaria

Phase 3 study in ColdU and SD to initiate in December 2025 (GlobeNewswire)

New P3 trial • Immunology • Urticaria

CDX0159-07: A Study of CDX-0159 in Patients With Chronic Inducible Urticaria (clinicaltrials.gov) - P2 | N=196 | Completed | Sponsor: Celldex Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Dermatology • Immunology • Urticaria

Sustained Efficacy and Safety of Barzolvolimab in ClndU (ACAAI 2025) - P2 | "The 20-week blinded period confirmed efficacy previously observed in week 12. This Phase 2 trial represents the first large, placebo-controlled study to show positive outcomes in CIndU, supporting advancement to Phase 3 development."

Clinical • Dermatology • Immunology • Urticaria

Barzolvolimab Improves Urticaria Control On and Off Treatment in Chronic Spontaneous Urticaria (ACAAI 2025) - P2 | "Well-controlled urticaria was still present at 28 weeks following the last dose of barzolvolimab in 59.4% and 53.6% of patients, respectively. Conclusion Long-term barzolvolimab treatment resulted in marked improvement in urticaria control with sustained off-treatment efficacy in patients with CSU refractory to antihistamines."

Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

The Role of Mast Cells in the Pathophysiology of Chronic Prurigo. (PubMed, J Invest Dermatol) - "The promising therapeutic effects of the tyrosine kinase KIT antibody barzolvolimab in an early-stage clinical trial have highlighted the crucial role of mast cells in the pathophysiology of CPG. This review discusses the important bidirectional crosstalk between mast cells and skin nerves, inflammatory cells, keratinocytes, and fibroblasts for initiating and maintaining the itch signal in CPG. In addition, we review mast cell-targeted treatments in CPG and explore future directions."

Journal • Review

Addressing the Unmet Need in Chronic Spontaneous Urticaria: A Network Meta-Analysis of Novel and Established Therapies (EADV 2025) - "Interventions: Oral agents: Cyclosporine, fenebrutinib, hydroxychloroquine, methotrexate, remibrutinib. Subcutaneous agents: Barzolvolimab, benralizumab, dupilumab, ligelizumab, omalizumab, quilizumab, tezepelumab...Efficacy: i. All treatments except benralizumab, methotrexate, and quilizumab significantly improved UAS7, ISS7, HSS7, and DLQI vs. placebo... 1. Barzolvolimab is the most effective therapy for symptom control (UAS7/HSS7/ISS7). 2."

Retrospective data • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Barzolvolimab Treatment Improves Urticaria Activity in Patients with Chronic Spontaneous Urticaria Regardless of Baseline IgE Levels (EADV 2025) - P2 | "We previously reported that barzolvolimab demonstrated statistically significant and clinically meaningful improvement in weekly Urticaria Activity Score (UAS7) at 12 weeks, with deepening of response over 52 weeks in antihistamine-refractory CSU patients (NCT05368285), including patients who received prior omalizumab. Barzolvolimab at 150mg Q4W and 300mg Q8W demonstrated similar clinically meaningful benefits in UAS7 and UAS7=0 in CSU patients regardless of baseline total IgE level, consistent with its mechanism of action."

Clinical • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Barzolvolimab Treatment Improves Urticaria Activity in Patients with Chronic Spontaneous Urticaria Regardless of Baseline IgE Levels (EADV 2025) - No abstract available

Clinical • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Celldex Presents Data Demonstrating Barzolvolimab Improves Chronic Spontaneous Urticaria Independent of Baseline Immunoglobulin E levels in Phase 2 Study at EADV Congress 2025 (GlobeNewswire) - "Barzolvolimab demonstrated rapid and sustained efficacy in patients with CSU with both low (40) IgE levels. Similar improvement in weekly urticaria activity scores (UAS7; mean change from baseline) were observed across both IgE low and IgE normal/high subgroups at Weeks 12 and 52. Similar rates of well-controlled disease (UAS7<6) and complete disease control (both UAS7=0) were also observed across both IgE normal/high and IgE low subgroups at Weeks 12 and 52."

P2 data • Chronic Spontaneous Urticaria

Celldex Reports Results from Phase 2 Study of Barzolvolimab in Eosinophilic Esophagitis (EoE) (GlobeNewswire) - "The primary endpoint of the study, absolute change from baseline to Week 12 in peak esophageal intraepithelial mast cell count was met, but the profound mast cell depletion observed did not result in improvement in EoE symptoms or endoscopic assessment of disease activity compared to placebo....Based on these results, Celldex will not advance development in EoE."

Discontinued • P2 data • Eosinophilic Esophagitis

Celldex Reports Second Quarter 2025 Financial Results and Provides Corporate Update (GlobeNewswire) - "Chronic Urticarias: (i) Phase 3 Development: A global Phase 3 program in chronic spontaneous urticaria (CSU) consisting of two Phase 3 trials (EMBARQ-CSU1 and EMBARQ-CSU2) was initiated in July and enrollment is ongoing....The Company is currently planning a global Phase 3 program in chronic inducible urticaria (CIndU), which is expected to initiate in 2H 2025...; (ii) Phase 2 Development:...20 week treatment data from the Phase 2 CIndU study will be presented later this year. After completing treatment, patients on study are followed for 24 weeks and patients with returning symptoms can enter an open label extension during the follow up period."

New P3 trial • P2 data • Trial status • Urticaria

Additional Indications (GlobeNewswire) - "(i) Enrollment is complete in the Phase 2 study in eosinophilic esophagitis (EoE) and data from this study (12 week analysis) are expected in 2H 2025. This randomized, double-blind, placebo-controlled, parallel group study is evaluating the efficacy and safety profile of barzolvolimab in patients with active EoE; (ii) Enrollment continues in the Phase 2 study in prurigo nodularis (PN). This randomized, double-blind, placebo-controlled, parallel group study is evaluating the efficacy and safety profile of barzolvolimab in patients with moderate to severe PN; (iii) Enrollment is ongoing in the Phase 2 study in atopic dermatitis (AD). This randomized, double-blind, placebo-controlled, parallel group study is evaluating the efficacy and safety profile of barzolvolimab in patients with moderate to severe AD."

Enrollment status • P2 data • Atopic Dermatitis • Eosinophilic Esophagitis • Prurigo Nodularis

Safety and efficacy of barzolvolimab, an anti-KIT monoclonal antibody, in adults with moderate-to-severe prurigo nodularis: A randomized phase 1b intravenous single-dose study. (PubMed, J Am Acad Dermatol) - No abstract available

Journal • P1 data • Dermatology • Immunology • Prurigo Nodularis • Pruritus

Biologic and small molecule therapies in chronic spontaneous urticaria: an update. (PubMed, Curr Opin Allergy Clin Immunol) - "The rapid increase in clinical trials in the field of CSU has already led to a significant improvement in treatment options beyond anti-IgE therapy with omalizumab in Japan and the USA, and further approvals of biologics and small molecules are expected shortly. It is expected that with a wider range of different approved therapeutic approaches, the treatment of CSU will have to be tailored to the urticaria subtype or patient profile in the future."

Journal • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria