Summary of Celldex Therapeutics Conference Call Company Overview - **Company**: Celldex Therapeutics (NasdaqCM:CLDX) - **Date**: November 13, 2025 - **Key Speakers**: Anthony Marucci (CEO), Tibor Keler (CSO), Diane Young (CMO) Key Points Industry and Product Focus - The discussion primarily revolves around Celldex's ongoing clinical trials and data related to their drug Barzolvolimab, particularly in the context of Chronic Spontaneous Urticaria (CSU), Prurigo Nodularis (PN), and Atopic Dermatitis (AD) [3][4][34] Clinical Data Highlights - **CSU Phase Two Data**: - A 76-week phase two study showed a **41% complete response rate** seven months after stopping Barzolvolimab, indicating a durable remission [3][4] - This response rate is comparable to Xolair and higher than Dupixent, suggesting significant efficacy [3][4] - **Competitor Comparison**: - Xolair's effects diminish within weeks after cessation, while Ruxolitinib's long-term effects remain unclear. Dupixent shows modest efficacy [4][5] - **Mast Cell Dynamics**: - Data indicates that mast cells return to normal levels after treatment, but the long-term effects on disease modification are still being evaluated [6] Future Studies and Trials - **OLE (Open Label Extension)**: - The OLE is designed to gather additional follow-up data and explore retreatment options post-approval [7][8] - **Upcoming Trials**: - Ongoing phase two studies for PN and AD are expected to yield results in the second half of 2026. The PN trial involves 120 patients and focuses on itch reduction and lesion healing [17][21][34] - **CDX-622 Development**: - CDX-622, a bispecific targeting mast cells and TSLP, is in phase one trials with promising pharmacokinetics and no immunogenicity observed [28][29] Market Position and Strategy - **Competitive Landscape**: - Celldex aims to position Barzolvolimab as a competitive option against existing treatments like Dupixent, focusing on improving itch reduction and lesion healing [19][20] - **Pipeline Expansion**: - The company is considering various indications for CDX-622, including severe asthma and food allergies, based on ongoing data [31][32] Upcoming Catalysts - Key upcoming milestones include: - Phase three study initiation for cold urticaria and symptomatic dermographism by the end of 2025 - Phase two readouts for cold urticaria and symptomatic dermographism in Q1 2026 - Completion of CSU phase three accrual by summer 2026 - Data releases for AD and PN in the second half of 2026 [34][36] Enrollment and Study Progress - Enrollment for the ongoing EMBARK studies is proceeding well, with expectations to complete by summer 2026 [36][37] Additional Insights - The discussion emphasizes the importance of understanding mast cell roles in various conditions, which could lead to innovative treatment strategies and improved patient outcomes [20][22]

Core Insights - Celldex announced new data showing the efficacy of barzolvolimab in treating chronic spontaneous urticaria (CSU), demonstrating significant improvement regardless of baseline immunoglobulin E (IgE) levels [1][3][5] Group 1: Study Results - The Phase 2 study of barzolvolimab met its primary endpoint, showing a significant improvement in UAS7 (weekly urticaria activity score) compared to placebo at 12 weeks across all dose groups [5][9] - Complete response rates (UAS7=0) were observed in up to 51% of patients at 12 weeks, increasing to 71% at 52 weeks, with 41% of patients reporting a complete response at 76 weeks [5][8] - The study demonstrated similar efficacy in patients with low (<40) and normal/high (>40) IgE levels, reinforcing the role of mast cells in CSU [8][9] Group 2: Mechanism and Treatment Potential - Barzolvolimab targets mast cells by binding to the receptor tyrosine kinase KIT, inhibiting its activity, which is crucial for mast cell function and survival [1][7] - The drug shows promise as a treatment for all patients with moderate to severe CSU, particularly those with low IgE levels who typically respond poorly to existing therapies [3][8] Group 3: Ongoing Research and Development - Celldex is currently enrolling patients in a global Phase 3 program for barzolvolimab, consisting of two trials designed to establish its efficacy and safety in adult patients with CSU who remain symptomatic despite H1 antihistamine treatment [6][10] - The ongoing studies also include patients who have not responded to biologic treatments, indicating a broad potential application for barzolvolimab [6][10] Group 4: Background on CSU - Chronic spontaneous urticaria (CSU) is characterized by hives or wheals lasting for 6 weeks or longer without identifiable triggers, often leading to significant patient discomfort and reduced quality of life [11] - Current therapies provide only symptomatic relief for some patients, highlighting the need for more effective treatments like barzolvolimab [11]

Core Insights - Celldex announced new data showing rapid and strong efficacy of barzolvolimab in treating chronic spontaneous urticaria (CSU), regardless of baseline immunoglobulin E (IgE) levels [1][3][8] Study Results - The Phase 2 study of barzolvolimab met its primary endpoint, showing significant improvement in UAS7 (weekly urticaria activity score) compared to placebo at 12 weeks across all dose groups [5][9] - At 12 weeks, up to 51% of patients achieved a complete response (UAS7=0), which increased to 71% at 52 weeks; 41% of patients reported a complete response at 76 weeks [5][8] - The study demonstrated a well-tolerated safety profile throughout the treatment period [5] Mechanism of Action - Barzolvolimab targets mast cells by binding to the receptor tyrosine kinase KIT, inhibiting its activity, which is crucial for mast cell function and survival [1][7] - The data reinforces the role of mast cells as key drivers of CSU, indicating that barzolvolimab could be a meaningful treatment for all patients, including those with low IgE levels [3][8] Ongoing Research - Celldex is currently enrolling patients in a global Phase 3 Program for barzolvolimab, consisting of two trials designed to establish its efficacy and safety in adult patients with CSU who remain symptomatic despite H1 antihistamine treatment [6][10] About Chronic Spontaneous Urticaria (CSU) - CSU is characterized by hives or wheals lasting 6 weeks or longer without identifiable triggers, often resulting from mast cell activation [11]

Group 1 - The article is authored by Terry Chrisomalis, who operates the Biotech Analysis Central pharmaceutical service on Seeking Alpha Marketplace, offering a two-week free trial for new subscribers [1] - Biotech Analysis Central provides a library of over 600 biotech investing articles, a model portfolio of more than 10 small and mid-cap stocks, and various analysis and news reports to assist healthcare investors [2] Group 2 - The service is priced at $49 per month, with a yearly plan available at a discounted rate of $399, representing a 33.50% discount [1] - The analyst has no current stock or derivative positions in any mentioned companies and does not plan to initiate any within the next 72 hours [3]

Efficacy of Barzolvolimab - At Week 52, 71% of patients receiving 150 mg Q4W of barzolvolimab achieved a complete response in CSU, demonstrating the highest rate of complete response observed in a well-controlled study[16] - At Week 12, 51% of patients on the 150 mg Q4W dosage achieved complete response, compared to only 6% in the placebo group[16] - 7 months post-treatment (Week 76), 41% of patients in the 150 mg Q4W group sustained a complete response[16] - At Week 76, 47%-56% of barzolvolimab patients had well controlled disease[50] Safety and Tolerability - Barzolvolimab demonstrates a well-tolerated, long-term safety profile in Phase 2 trials[25] - Most adverse events are mild (Grade 1), KIT-mediated effects and reversible during follow-up period[27] - Localized hair color changes/lightening occurred in 48 patients through 52 weeks of treatment, with >90% already resolved at study closure[36] - Small areas of hypo-pigmentation occurred in 30 patients through 52 weeks of treatment, with >70% already resolved at study closure[36] Impact on Quality of Life - 92% of patients report moderate to high impact from CSU on their daily life[11] - At Week 76, 40%-48% of patients on barzolvolimab reported CSU had no impact (0-1) on their quality of life[53] - At Week 52, 82% of patients on the 150 mg Q4W dosage reported CSU had no impact (0-1) on their quality of life[57]