barzolvolimab (CDX-0159) / Celldex - LARVOL DELTA

New and Emerging Biologics and Jak Inhibitors for the Treatment of Prurigo Nodularis: A Narrative Review. (PubMed, Medicina (Kaunas)) - "Among new treatment options, dupilumab, an IL-4 receptor antagonist, and nemolizumab, an IL-31 receptor inhibitor, demonstrated significant efficacy in reducing pruritus and lesion severity in PN patients. Other promising monoclonal antibodies include vixarelimab (OSMRβ inhibitor) and barzolvolimab (KIT inhibitor). Small molecules such as JAK inhibitors (upadacitinib, povorcitinib) also show potential by modulating inflammatory pathways...Emerging biologics and small molecules represent a transformative approach for PN management, offering targeted therapies that address underlying immunological and neurological mechanisms. Ongoing research and long-term studies are crucial to optimizing treatment strategies and improving patient outcomes."

Journal • Review • Dermatology • Immunology • Prurigo Nodularis • Pruritus • IL4

Treatment with Barzolvolimab Leads to Sustained Improvement in Angioedema in Chronic Spontaneous Urticaria (CSU) patients: Results from 52 Weeks of Treatment (EAACI 2025) - No abstract available

Clinical • Immunology

EvolvE: A Study of CDX-0159 in Patients With Eosinophilic Esophagitis (clinicaltrials.gov) - P2 | N=86 | Active, not recruiting | Sponsor: Celldex Therapeutics | Trial completion date: Aug 2025 ➔ Dec 2025 | Trial primary completion date: Mar 2025 ➔ Jun 2025

Trial completion date • Trial primary completion date • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

EvolvE: A Study of CDX-0159 in Patients With Eosinophilic Esophagitis (clinicaltrials.gov) - P2 | N=86 | Active, not recruiting | Sponsor: Celldex Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

A Phase 2 Study of CDX-0159 in Patients With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P2 | N=208 | Completed | Sponsor: Celldex Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Celldex a new overweight at Morgan Stanley on urticaria candidate (MSN News) - "Morgan Stanley has initiated Celldex Therapeutics...at overweight saying that barzolvolimab (barzol), its asset for chronic urticaria (CU), is poised to become a major revenue generator in a decade...Analyst Judah Frommer said that barzol is an anti-KIT monoclonal antibody that helps to reduce mast cells....He projects barzol revenue of $1.3B in 2035."

Sales projection • Chronic Spontaneous Urticaria

Update on the Treatment of Chronic Spontaneous Urticaria. (PubMed, Drugs) - "About 70% of patients with antihistamine-refractory CSU do not reach complete control with omalizumab, the second-line treatment...Several emerging treatments can address these unmet needs including Bruton tyrosine kinase inhibitors, e.g., remibrutinib and rilzabrutinib; anti-KIT monoclonal antibodies, e.g., barzolvolimab; and anti-cytokine therapies, e.g., dupilumab...The most common adverse events were injection site reactions for dupilumab (12%), respiratory tract infections (11%), headache (6%), and petechiae (4%) for remibrutinib and changes in hair color (14%), neutropenia / decreased neutrophil count (9%) and skin hypopigmentation (1%) for barzolvolimab. This review provides an update on the current state of development of treatments for CSU."

Journal • Cardiovascular • Chronic Spontaneous Urticaria • Dermatology • Hematological Disorders • Immunology • Infectious Disease • Neutropenia • Pain • Respiratory Diseases • Urticaria

INTRAEPITHELIAL MAST CELLS ARE ELEVATED IN ACTIVE EOSINOPHILIC ESOPHAGITIS AND CORRELATE WITH EOSINOPHILS: BASELINE DATA FROM A RANDOMIZED CONTROLLED TRIAL OF BARZOLVOLIMAB (DDW 2025) - No abstract available

Clinical • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

Phase 2 CIndU trial disease control and quality of life measurements (12 week analysis) (GlobeNewswire) - P2 | N=196 | NCT05405660 | Sponsor: Celldex Therapeutics | "The data were presented by Martin Metz, M.D., Deputy Director, Head of Translational Research at Charité - Universitätsmedizin Berlin in poster presentations...as part of the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting 2025....Up to 53% of patients with ColdU and 58% of patients with SD achieved complete response (negative provocation test)—first large randomized, placebo-controlled study to demonstrate clinical benefit in patients with CIndU; Marked and rapid improvement in urticaria control (UCT) and quality of life (DLQI) in patients with ColdU and SD; sustained through the 12-week period; Up to 60% of patients reported that CIndU symptoms no longer had an impact on their quality of life at Week 12; Up to 69% of patients reported well-controlled urticaria based on UCT at Week 12."

P2 data • Urticaria

Phase 2 CSU trial disease control and quality of life measurements (52 week analysis) (GlobeNewswire) - P2 | N=208 | NCT05368285 | Sponsor: Celldex Therapeutics | "The data were presented...as part of the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting 2025....Up to 71% of patients with CSU achieved complete response (UAS7 = 0) at Week 52—the highest rate of complete response observed in a well-controlled study; Rapid and sustained improvement in urticaria control (UCT) and quality of life (DLQI) observed in patients with CSU refractory to antihistamines; Up to 82% of patients reported that CSU symptoms no longer had an impact on their quality of life at Week 52; Up to 95% of patients reported meaningful improvement in quality of life based on DLQI at Week 52; Up to 95% of patients reported meaningful improvement in quality of life based on DLQI at Week 52; Up to 82% of patients reported well-controlled urticaria based on UCT, and approximately half of patients reported complete control at Week 52."

P2 data • Chronic Spontaneous Urticaria

Barzolvolimab - KIT Inhibitor Program (GlobeNewswire) - "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 approximately 120 patients with moderate to severe PN who had inadequate response to prescription topical medications, or for whom topical medications are medically inadvisable, including patients who received prior biologics; A Phase 2 study in atopic dermatitis (AD) was initiated in December 2024 and enrollment is ongoing. This randomized, double-blind, placebo-controlled, parallel group study is evaluating the efficacy and safety profile of barzolvolimab in approximately 120 patients with moderate to severe AD."

Enrollment status • Atopic Dermatitis • Prurigo Nodularis

Barzolvolimab - KIT Inhibitor Program (GlobeNewswire) - "The Company is currently planning a global Phase 3 program in chronic inducible urticaria (CIndU), which is expected to initiate in 2025...Phase 2 study in CSU...The Company anticipates presenting 76 week data (52 weeks of treatment; 24 weeks of follow up post treatment) from the study in 2025...Phase 2 study in CIndU....Company anticipates presenting data through week 44 in 2025 (20 weeks of treatment; 24 weeks of follow up post treatment; patients with returning symptoms can enter open label extension during follow up period)."

New P3 trial • P2 data • Chronic Spontaneous Urticaria • Urticaria

Barzolvolimab - KIT Inhibitor Program (GlobeNewswire) - "A Phase 2 study in eosinophilic esophagitis (EoE) is fully accrued. This randomized, double-blind, placebo-controlled, parallel group study is evaluating the efficacy and safety profile of barzolvolimab in patients with active EoE. Data from this study is expected in 2025."

Enrollment closed • P2 data • Eosinophilic Esophagitis

Barzolvolimab Improves Urticaria Control and Quality of Life in Patients with Chronic Spontaneous Urticaria: 52-Week Data (AAAAI-WAO 2025) - P2 | "At 52 weeks, the mean CFB in DLQI was -14.2 (7.3) and -15.0 (8.5), respectively. Conclusions Barzolvolimab treatment for up to 52 weeks resulted in marked and sustained improvement in urticaria control and quality of life in patients with CSU refractory to antihistamines."

Clinical • HEOR • Late-breaking abstract • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Treatment with Barzolvolimab Improves Urticaria Control and Quality of Life in Patients with Chronic Inducible Urticaria: Phase 2 12 Week Results (AAAAI-WAO 2025) - P2 | "Conclusions Barzolvolimab treatment resulted in clinically meaningful improvement in urticaria control and quality of life in ColdU and SD. These results support advancing to Phase 3 registrational studies."

Clinical • HEOR • P2 data • Dermatology • Immunology • Urticaria

A Study of Barzolvolimab in Patients with Atopic Dermatitis (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Celldex Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Celldex Initiates Phase 2 Study of Barzolvolimab in Atopic Dermatitis (GlobeNewswire) - "Celldex Therapeutics, Inc...announced that the Company has initiated a Phase 2 study of barzolvolimab in atopic dermatitis (AD) and that the study is actively enrolling patients...'We’re pleased to end this year with the advancement of barzolvolimab into its fifth indication and look forward to an exciting year ahead in 2025 with multiple upcoming data readouts.'....The randomized, double-blind, placebo-controlled Phase 2 study is evaluating the efficacy and safety profile of subcutaneous barzolvolimab in patients with moderate to severe atopic dermatitis. Approximately 120 patients will be randomly assigned on a 1:1:1 ratio to receive subcutaneous injections of barzolvolimab at either 150 or 300 mg or placebo every 4 weeks after an initial loading dose of 450 mg or placebo during a 16-week placebo-controlled treatment phase."

Clinical data • Trial status • Atopic Dermatitis

A Phase 2 Study of CDX-0159 in Patients With Atopic Dermatitis (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Celldex Therapeutics

New P2 trial • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Therapies for Chronic Spontaneous Urticaria: Present and Future Developments. (PubMed, Pharmaceuticals (Basel)) - "If symptoms persist despite this adjustment, the next step involves the use of omalizumab, a monoclonal anti-IgE antibody, which has shown efficacy in the majority of cases. However, a subset of patients remains refractory, necessitating alternative treatments such as immunosuppressive agents like cyclosporine or azathioprine...Among them, significant attention is being given to drugs that block Bruton's tyrosine kinase (BTK), such as remibrutinib, which reduces mast cell activation. Therapies like dupilumab, which target the interleukin-4 (IL-4) and IL-13 pathways, are also under investigation. Additionally, molecules targeting the Mas-related G protein-coupled receptor X2 (MRGPRX2), and those inhibiting the tyrosine kinase receptor Kit, such as barzolvolimab, show promise in clinical studies...Further research is essential to better elucidate the pathophysiology of CSU and optimize treatment protocols to achieve long-term benefits in managing this condition...."

Journal • Review • Cardiovascular • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria • BTK • IL13 • IL4

Celldex Announces Barzolvolimab Met All Primary and Secondary Endpoints with High Statistical Significance in Positive Phase 2 Study in Chronic Inducible Urticaria (GlobeNewswire) - P2 | N=196 | NCT05405660 | Sponsor: Celldex Therapeutics | "The data were presented in a late breaking oral presentation at the American College of Allergy, Asthma & Immunology's Annual Scientific Meeting....'We...look forward to initiating Phase 3 development in inducible urticaria in 2025'....90% (n=173) of patients on study completed the study through 12 weeks (discontinuation rate of 8% barzolvolimab compared to 14% placebo)....Patients experienced rapid disease improvement as early as two weeks (the first assessment) after receiving the initial dose of barzolvolimab as demonstrated by reductions in critical temperature and friction thresholds resulting in hives and rapid reduction in itch at the time of provocation testing (WI-NRSprovo). Barzolvolimab was well tolerated with a favorable safety profile consistent with prior studies."

Late-breaking abstract • New P3 trial • P2 data • Urticaria

Celldex Announces Upcoming Late Breaking Oral Presentation of 12 Week Results from Barzolvolimab Phase 2 Study in Chronic Inducible Urticaria at ACAAI 2024 (GlobeNewswire) - "Celldex Therapeutics...announced today that 12 week results from the Company’s Phase 2 clinical trial of barzolvolimab in two of the most common forms of chronic inducible urticaria (CIndU)-cold urticaria (ColdU) and symptomatic dermographism (SD)-will be presented in a late breaking oral presentation at the American College of Allergy, Asthma & Immunology's (ACAAI) Annual Scientific Meeting being held in Boston October 24-28, 2024."

Late-breaking abstract • P2 data • Urticaria

Distinguished Industry & Late-breaking Oral Abstracts - Session 1 (ACAAI 2024) - "Learning Objectives Objective 1: Discuss lebrikizumab’s efficacy up to 52 weeks among patients with atopic dermatitis with or without atopic comorbidities. Observe that participants with hereditary angioedema treated with a single dose of NTLA-2002 in Phase 2 of a Phase 1/2 study saw robust, sustained reductions in attacks and plasma kallikrein levels, with no new safety signals...To educate on the efficacy and safety of Dupilumab in a randomized, placebo-controlled, double-blind 24-week phase 3 trial compared dupilumab to placebo treatment in omalizumab-naive patients with symptomatic CSU despite standard-of-care H1-antihistamines treatment (up to 4-fold approved dose)...Understand the efficacy and safety profile for barzolvolimab from the first large, randomized placebo-controlled study to achieve a successful outcome for chronic inducible urticaria. This data allows advancement of the program to registrational studies."

Late-breaking abstract • Allergic Rhinitis • Atopic Dermatitis • Cardiovascular • Chronic Spontaneous Urticaria • Complement-mediated Rare Disorders • Conjunctivitis • Dermatitis • Dermatology • Hereditary Angioedema • Immunology • Inflammation • Ocular Infections • Ocular Inflammation • Ophthalmology • Urticaria

Positive Efficacy and Favorable Safety of Barzolvolimab in Chronic Inducible Urticaria: Phase 2 Trial Results (ACAAI 2024) - P2 | "The study met the primary endpoint with unprecedented, clinically meaningful, and statistically significant complete response rates (negative provocation test) in patients with ColdU and SD at 12W. This phase II barzolvolimab study is the first large, ranQomized placebo-controlled study to achieve a successful outcome for CIndU and supports advancing to phase III registrational studies. Asthma, other lower airway disorders"

Clinical • Late-breaking abstract • P2 data • Asthma • Dermatology • Hematological Disorders • Immunology • Neutropenia • Respiratory Diseases • Urticaria

Barzolvolimab: Initiation of P2 trial for atopic dermatitis in the end of 2024 (Celldex) - Corporate Presentation: Data from P2 EvolvE trial (NCT05774184) for eosinophilic esophagitis in 2025

New P2 trial • P2 data • Atopic Dermatitis • Eosinophilic Esophagitis • Immunology

Barzolvolimab: “Barzolvolimab treatment resulted in rapid, profound and durable improvement in UAS7 with a deepening of response over 52 weeks in patients with antihistamine refractory CSU”; Chronic spontaneous urticaria (Celldex) - Corporate Presentation: “Up to 71% of patients achieved complete response”

P2 data • Chronic Spontaneous Urticaria • Immunology