barzolvolimab (CDX-0159) / Celldex - LARVOL DELTA

Barzolvolimab: “47% - 56% barzolvolimab patients had well controlled disease at week 76”; Chronic spontaneous urticaria (Celldex) - EAACI 2025

P2 data • Chronic Spontaneous Urticaria • Immunology

Celldex Presents Data Demonstrating Profound Long Term Improvement in Angioedema in Barzolvolimab Phase 2 Study in Chronic Spontaneous Urticaria at EAACI 2025 (GlobeNewswire) - P2 | N=208 | NCT05368285 | Sponsor: Celldex Therapeutics | "Summary of Key Findings: Patients on study had severe CSU. Over 70% of patients had a weekly urticaria activity score (UAS7) greater than 28 at baseline and reported very high rates of angioedema at baseline; Barzolvolimab demonstrated rapid, robust and durable improvements in angioedema symptoms over the treatment period. At Week 52, an 86% mean reduction from baseline was reported for 150 mg Q4W arm and an 82% reduction was reported for the 300 mg Q8W; Up to 77% of patients treated with barzolvolimab who had angioedema at baseline were angioedema free (AAS7=0) at Week 52; Patients treated with barzolvolimab were angioedema free up to 72% of the time over the 52 week treatment period; Up to 87% of patients reported clinically meaningful improvement (>8 point) in AAS7 at Week 52."

P2 data • Chronic Spontaneous Urticaria

Sustained Disease Control Following Withdrawal of Barzolvolimab in Patients with Chronic Spontaneous Urticaria (EAACI 2025) - P2 | "Barzolvolimab was well tolerated with a favorable safety profile. These results support the ongoing Phase 3 studies in patients with CSU refractory to antihistamines."

Clinical • Late-breaking abstract • Immunology

Treatment with Barzolvolimab Leads to Sustained Improvement in Angioedema in Chronic Spontaneous Urticaria (CSU) patients: Results from 52 Weeks of Treatment (EAACI 2025) - P2 | "We previously reported that barzolvolimab (an anti-KIT monoclonal antibody that depletes MCs) demonstrated statistically significant and clinically meaningful improvement in angioedema activity score (AAS)7 at Week 12 in patients with antihistamine refractory CSU, including patients who previously received omalizumab. Conclusion Barzolvolimab treatment demonstrated clinically meaningful and sustained improvement in CSU symptoms, including angioedema through week 52, in patients with antihistamine refractory CSU. These results combined with a favorable safety profile support the ongoing Phase 3 studies in CSU."

Clinical • Immunology

Celldex Presents Unprecedented 76 Week Results from Barzolvolimab Phase 2 Study in Chronic Spontaneous Urticaria at EAACI Congress 2025 (GlobeNewswire) - P2 | N=208 | NCT05368285 | Sponsor: Celldex Therapeutics | "The data are being presented in a late breaking oral presentation (#100227) at the EAACI Congress 2025....Rapid, profound improvements in UAS7...were reported as early as one week after dosing. Barzolvolimab achieved the primary efficacy endpoint, a statistically significant mean change from baseline to Week 12 in UAS7...compared to placebo, at all dose levels. These improvements were sustained or deepened at Week 52 and continued to Week 76. UAS7 mean change from baseline at Week 76 was -20.42 for patients treated with 150 mg Q4W and -21.10 for patients treated with 300 mg Q8W. 41% of patients treated with barzolvolimab 150 mg Q4W and 35% of patients treated with 300 mg Q8W had a complete response (no itch/hives; UAS7=0) at Week 76. 56% of patients treated with barzolvolimab 150 mg Q4W and 47% of patients treated with 300 mg Q8W had a complete response (no itch/hives; UAS7=0) at Week 76."

Late-breaking abstract • P2 data • Chronic Spontaneous Urticaria

Celldex Announces Upcoming Presentations of Barzolvolimab Phase 2 Data in Chronic Spontaneous Urticaria at EAACI 2025 Congress (GlobeNewswire) - "Celldex...announced today that data from the Company’s Phase 2 study of barzolvolimab in chronic spontaneous urticaria will be presented at the EAACI Congress 2025 being held in Glasgow, Scotland. Abstracts will be available on the meeting website Thursday, June 12th at 6:01 pm ET/ Friday, June 13th at 12:01 am CEST. Celldex will host a webcast on Thursday, June 12th at 6:00 pm ET to discuss the data."

P2 data • Chronic Spontaneous Urticaria

Barzolvolimab Demonstrates Rapid Symptom Reduction in Chronic Spontaneous Urticaria (DermatologyTimes) - P1 | N=45 | NCT04538794 | Sponsor: Celldex Therapeutics | "A total of 93.3% (n=42) completed the 12-week treatment phase....Barzolvolimab demonstrated robust and sustained suppression of serum tryptase. Within days of the initial dose, tryptase levels dropped by over 90% in the 1.5 mg/kg and higher-dose cohorts and remained suppressed throughout the 12-week dosing period. Clinically meaningful reductions in disease severity were observed in barzolvolimab-treated patients across all cohorts. By week 12, average UAS7 scores declined substantially, with the 3.0 mg/kg and 4.5 mg/kg groups experiencing reductions of 30 to 35 points compared to baseline. In contrast, placebo-treated patients showed minimal change. A significant proportion of patients receiving 3.0 mg/kg and 4.5 mg/kg barzolvolimab achieved near-complete or complete symptom control. Over 60% of patients in the highest-dose group reached UAS7 scores below 6 by the end of the treatment period."

P1 data • Chronic Spontaneous Urticaria

Depletion of mast cells with barzolvolimab, an anti-KIT antibody, does not affect mast cell progenitors. (PubMed, J Eur Acad Dermatol Venereol) - No abstract available

Journal

Anti-KIT Barzolvolimab for Chronic Spontaneous Urticaria. (PubMed, Allergy) - P1 | "This study supports barzolvolimab as a promising treatment for CSU."

Journal • Cardiovascular • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Celldex Presents Histology Data from Phase 2 Study of Barzolvolimab in EoE Supporting Potential of Mast Depleting Agent in this Difficult to Treat Disease (GlobeNewswire) - P2 | N=86 | EvolvE (NCT05774184) | Sponsor: Celldex Therapeutics | "The data were discussed in a poster presentation at the Digestive Disease Week (DDW) 2025 conference....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....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."

P2 data • Eosinophilic Esophagitis

INTRAEPITHELIAL MAST CELLS ARE ELEVATED IN ACTIVE EOSINOPHILIC ESOPHAGITIS AND CORRELATE WITH EOSINOPHILS: BASELINE DATA FROM A RANDOMIZED CONTROLLED TRIAL OF BARZOLVOLIMAB (DDW 2025) - P2 | "Intraepithelial PMCs are elevated in active EoE and correlate with PEC. PMC may serve as a useful outcome metric of MC depletion with barzolvolimab. This clinical trial will be the first to directly investigate the pathogenic role of MCs in EoE."

Clinical • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Pain • KIT

Celldex Reports First Quarter 2025 Financial Results and Provides Corporate Update (GlobeNewswire) - "The Company is currently planning a global Phase 3 program in chronic inducible urticaria (CIndU), which is expected to initiate in 2025...76 week data, which includes 24-weeks of off-treatment follow-up, from the Phase 2 study in CSU have been accepted for a late breaking oral presentation on Friday, June 13th at 9:12 am BST/10:12 am CEST/4:12 am ET at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2025 being held in Glasgow, Scotland. The Company will host a webcast on Thursday, June 12th at 6:00 pm ET to present the data; 20 week treatment data from the Phase 2 CIndU study will be presented later this year....Research and development (R&D) expenses were $52.6 million in the first quarter of 2025, compared to $31.7 million for the comparable period in 2024. The increase in R&D expenses was primarily due to an increase in barzolvolimab clinical trial, barzolvolimab contract manufacturing and personnel expenses."

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

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

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

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