Core Insights - Celldex Therapeutics announced that barzolvolimab significantly improves angioedema in chronic spontaneous urticaria (CSU) patients after 52 weeks of treatment [1][2][3] Group 1: Clinical Trial Results - The Phase 2 clinical trial met primary and secondary endpoints at 12 weeks, showing significant decreases in UAS7 scores compared to placebo [2][5] - At Week 52, an 86% mean reduction in angioedema activity was reported for the 150 mg Q4W group, and an 82% reduction for the 300 mg Q8W group [6] - 77% of patients treated with barzolvolimab who had angioedema at baseline were angioedema-free at Week 52 [5][6] Group 2: Patient Impact - The majority of patients with severe CSU experience painful angioedema, which significantly affects their quality of life [3][6] - 87% of patients reported clinically meaningful improvement in angioedema activity scores at Week 52 [6] Group 3: Drug Mechanism and Future Studies - Barzolvolimab is a humanized monoclonal antibody that targets the receptor tyrosine kinase KIT, which is involved in mast cell activation [4] - Celldex is conducting a global Phase 3 program for barzolvolimab in CSU, with enrollment currently underway [8]

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]

Summary of Celldex Therapeutics (CLDX) Conference Call Company Overview - **Company**: Celldex Therapeutics (CLDX) - **Focus**: Development of Barzolumab for chronic spontaneous urticaria (CSU) Key Industry Insights - **Industry**: Biopharmaceuticals, specifically targeting chronic spontaneous urticaria (CSU) - **Current Treatment Landscape**: Existing treatments are inadequate for many patients, highlighting the need for new options Core Findings from the Conference Call 1. **Barzolumab Phase II Study Results**: - Barzolumab shows the highest reported complete response rate in CSU treatment at every time point [7][12][30] - Complete response rates reached 51% at 12 weeks and 71% at 52 weeks, with 41% maintaining a complete response at 76 weeks post-treatment [30][31] - 93% of patients experienced a clinically meaningful reduction in disease burden during the active treatment period [12] 2. **Patient Quality of Life**: - 92% of patients report CSU impacts all aspects of their daily lives, with significant correlations between complete response and improved quality of life [11][36] - 48% of patients reported no impact on their daily quality of life seven months after treatment [35] 3. **Safety Profile**: - Barzolumab has a well-tolerated safety profile with no new safety signals identified during the follow-up period [20][28] - Common adverse events include mild decreases in neutrophil counts and subtle pigmentation changes, which are reversible [21][24] 4. **Market Potential**: - The drug is positioned as a potential first-line treatment for patients with antihistamine-refractory moderate to severe CSU [39] - High excitement among physicians regarding Barzolumab's efficacy and safety profile, which may influence treatment decisions [39] 5. **Ongoing Research and Development**: - Phase III studies are underway, with enrollment expected to complete by summer 2026 [39] - The company is focused on confirming the efficacy and safety of Barzolumab in larger patient populations [39] Additional Important Insights - **Patient Demographics**: The study included patients with severe CSU, with 70% having a UAS7 score greater than 28 at baseline [17] - **Long-term Efficacy**: The sustained response after treatment cessation suggests potential normalization of mast cell activity in patients [44] - **Physician Perspectives**: Physicians are optimistic about the potential for Barzolumab to change treatment paradigms for CSU, particularly for patients who have not responded to existing therapies [42][46] Conclusion - Celldex Therapeutics is making significant strides in the treatment of chronic spontaneous urticaria with Barzolumab, demonstrating promising efficacy and safety data that could redefine treatment standards in this area. The ongoing Phase III studies will be crucial in validating these findings and expanding treatment options for patients suffering from this debilitating condition.

Core Insights - Celldex announced new data showing significant and sustained complete response in chronic spontaneous urticaria (CSU) patients treated with barzolvolimab, with improvements in quality of life observed at 76 weeks post-treatment [1][2][3] Efficacy Data - The Phase 2 study met its primary endpoint, showing a significant improvement in UAS7 (weekly urticaria activity score) compared to placebo at 12 weeks across all dose groups [2][11] - At 12 weeks, up to 51% of patients achieved a complete response (UAS7=0), which increased to 71% at 52 weeks, and 41% maintained this response at 76 weeks [2][6] - 48% of patients reported that CSU no longer impacted their quality of life at 76 weeks, as measured by the Dermatology Life Quality Index (DLQI) [5][6] Safety Profile - Barzolvolimab demonstrated a well-tolerated safety profile throughout the study, with the most common adverse events being mild and reversible [7][3] - No new safety signals were identified, and neutropenia events resolved rapidly without association to infections [7][3] Future Developments - Enrollment for Phase 3 trials of barzolvolimab in CSU is ongoing, with two global Phase 3 trials designed to establish efficacy and safety in patients who remain symptomatic despite antihistamine treatment [12][11] - The company is focused on executing clinical trials to bring this potential new treatment to patients suffering from CSU [8][14]