Celldex Therapeutics(US:CLDX)2025-11-10 21:06Clinical Trials and Efficacy - Barzolvolimab (CDX-0159) achieved the primary efficacy endpoint in the Phase 2 study for Chronic Spontaneous Urticaria (CSU), showing a statistically significant mean change from baseline to Week 12 compared to placebo[67]. - In the CSU study, over 40% of patients continued to experience a profound, sustained complete response at 76 weeks after treatment with barzolvolimab[67]. - The Phase 2 study for Cold Urticaria and Symptomatic Dermographism achieved its primary efficacy endpoint, with all secondary endpoints also met and statistically significant[67]. - Barzolvolimab demonstrated rapid and durable responses in patients with moderate to severe Chronic Spontaneous Urticaria (CSU), with a mean reduction in baseline UAS7 of 82% at Week 12 for the 4.5 mg/kg dose group[86]. - In a Phase 2 study, barzolvolimab achieved a statistically significant mean change from baseline to Week 12 in UAS7 compared to placebo across all dose levels, with a mean change of -23.87 for the 300 mg Q8W group[92]. - 71% of patients treated with barzolvolimab 150 mg Q4W and 52% of patients treated with 300 mg Q8W had a complete response (UAS7=0) at Week 52[96]. - Approximately 72% of patients on study had angioedema at baseline, with barzolvolimab demonstrating significant improvements in AAS7 across all doses at Week 12[95]. - At Week 12, 37.5% of patients in the 300 mg Q8W group achieved complete control (UAS7=0), compared to 6.4% in the placebo group[92]. - Barzolvolimab's mechanism of action demonstrated strong improvement in UAS7 independent of prior omalizumab treatment status, benefiting even omalizumab-refractory patients[93]. - At Week 52, barzolvolimab demonstrated an 86% mean reduction in angioedema symptoms for the 150 mg Q4W arm and an 82% reduction for the 300 mg Q8W arm[97]. - 77% of patients treated with barzolvolimab were angioedema free (AAS7=0) at Week 52, with patients being angioedema free up to 72% of the time during the treatment period[97]. - In the Phase 2 CSU study, at Week 76, the UAS7 mean change from baseline was -20.42 for the 150 mg Q4W group and -21.10 for the 300 mg Q8W group[100]. - 41% of patients on 150 mg Q4W and 35% on 300 mg Q8W achieved a complete response (UAS7=0) at Week 76[100]. - A complete response was achieved in 95% of patients with ColdU and SD treated with a single dose of 3 mg/kg, with a median duration of complete response of 77+ days[105]. - At Week 12, 53.1% of patients treated with 300 mg barzolvolimab achieved a negative provocation test for Cold Urticaria, compared to 12.5% in the placebo group, with a p-value of 0.0011[111]. - In the same study, 75% of patients receiving 300 mg barzolvolimab had a complete or partial response per provocation test, versus 31.3% in the placebo group, with a p-value of 0.0006[111]. - By Week 20, 66% of Cold Urticaria patients and 49% of Symptomatic Dermographism patients achieved a complete response with barzolvolimab, compared to 16% and 10% in the placebo groups, respectively[118]. Research and Development Expenses - Total research and development expenses for the nine months ended September 30, 2025, were $169.7 million, compared to $116.6 million for the same period in 2024, reflecting a 45.5% increase[80]. - The Barzolvolimab/Anti-KIT Program incurred $134.0 million in R&D expenses for the nine months ended September 30, 2025, up from $88.6 million in the same period of 2024[80]. - The company incurred an aggregate of $459.7 million in research and development expenses over the past five years through December 31, 2024[79]. - Research and development expenses increased by 39% to $62.93 million for the three months ended September 30, 2025, compared to $45.26 million in 2024, driven by barzolvolimab-related costs[139]. - Research and development expenses for the nine months ended September 30, 2025, rose by 46% to $169.74 million, up from $116.61 million in 2024, reflecting increased investment in barzolvolimab[149]. - Research and development expenses increased by $43.3 million (67%) to $108.1 million for the nine months ended September 30, 2025, primarily due to higher clinical trial and contract manufacturing expenses for barzolvolimab[155]. Financial Performance - Total revenues for the three months ended September 30, 2025, were $3.19 million, a decrease of 100% compared to the same period in 2024, primarily due to a $3.19 million drop in contracts and grants revenue[139]. - The net loss for the three months ended September 30, 2025, was $67.04 million, a 59% increase from the net loss of $42.12 million in the same period in 2024[140]. - For the nine months ended September 30, 2025, total revenues were $1.42 million, a decrease of 76% compared to $5.85 million in 2024, with a significant drop in contracts and grants revenue[149]. - The company incurred a loss of $177.4 million for the nine months ended September 30, 2025[160]. Clinical Development Initiatives - The company initiated a Phase 2 study in Prurigo Nodularis (PN) in April 2024, with positive data reported from a Phase 1b study in November 2023[73]. - The company is developing CDX-622, a bispecific antibody targeting TSLP and SCF, with a Phase 1a dose-escalation study initiated in November 2024[73]. - The company plans to initiate a global Phase 3 study in Cold Urticaria and Symptomatic Dermographism in December 2025, based on positive results from earlier studies[114]. - A Phase 2 study for Atopic Dermatitis has been initiated, evaluating the efficacy of barzolvolimab in approximately 120 patients, with initial data expected in the second half of 2026[124][127]. - The company has expanded clinical development of barzolvolimab into Prurigo Nodularis, targeting a significant unmet need with an estimated 154,000 patients in the U.S. having undergone treatment in the last year[115]. - Enrollment is ongoing for the Phase 2 subcutaneous study in Prurigo Nodularis, which will include approximately 120 patients and is designed to evaluate the clinical effect of barzolvolimab on itch response[123]. - The company discontinued the development of barzolvolimab for eosinophilic esophagitis (EoE) based on Phase 2 study results, which showed no improvement in EoE symptoms despite meeting the primary endpoint of mast cell depletion[128]. Safety and Tolerability - Barzolvolimab was well tolerated, with most adverse events being mild to moderate; common events included hair color changes (9%) and neutropenia (8%) without a clear association with infections[94]. - The Phase 1b study included 45 patients with moderate to severe CSU, assessing safety and pharmacokinetics of barzolvolimab[84]. - Barzolvolimab was well tolerated with a favorable safety profile, and no new safety signals were identified during the follow-up period[100]. - Barzolvolimab demonstrated a favorable safety profile, with 18% of patients experiencing hair color changes and 12% experiencing neutropenia, both primarily grade 1 adverse events[112][118]. Cash Flow and Financial Position - Cash, cash equivalents, and marketable securities totaled $583.2 million as of September 30, 2025, sufficient to meet estimated working capital requirements through 2027[160]. - Net cash used in operating activities was $147.0 million for the nine months ended September 30, 2025, compared to $125.3 million for the same period in 2024, reflecting increased research and development and general administrative expenses[162]. - Net cash provided by investing activities was $153.6 million for the nine months ended September 30, 2025, compared to net cash used of $314.2 million for the same period in 2024, primarily due to net sales and maturities of marketable securities[165]. - Net cash provided by financing activities decreased to $1.0 million for the nine months ended September 30, 2025, down from $441.1 million in the same period in 2024, due to reduced net proceeds from stock issuances[166]. - Investment and other income decreased by $3.43 million for the three months ended September 30, 2025, primarily due to lower cash and investment balances[148]. - Investment and other income, net decreased by $5.5 million for the nine months ended September 30, 2025, primarily due to lower cash and investment balances[157].