Celldex Therapeutics(CLDX)2024-11-06 21:06Clinical Development - Barzolvolimab (CDX-0159) is currently in Phase 3 studies for chronic spontaneous urticaria (CSU), with a Phase 2 study achieving primary efficacy endpoints and demonstrating a statistically significant mean change from baseline to week 12[75]. - The company initiated a Phase 2 study in prurigo nodularis (PN) in April 2024, following positive data from a Phase 1b study reported in November 2023[90]. - A Phase 2 study in eosinophilic esophagitis (EoE) was initiated in June 2023, with enrollment ongoing[76]. - The company plans to initiate a Phase 2 study for atopic dermatitis (AD) by the end of 2024, targeting patients who have received prior biologics[76]. - The company initiated two Phase 3 studies of barzolvolimab in Chronic Spontaneous Urticaria (CSU) in July 2024, enrolling approximately 915 patients per trial across 250 sites in about 40 countries[113]. - In a Phase 1b trial for Cold Urticaria (ColdU) and Symptomatic Dermographism (SD), a complete response was achieved in 95% (n=19/20) of patients treated with a single dose of 3 mg/kg barzolvolimab[118]. - In a Phase 2 study for Chronic Inducible Urticaria (CIndU), 196 patients were randomized to receive barzolvolimab at either 150 mg every 4 weeks or 300 mg every 8 weeks, with the primary endpoint being the percentage of patients with a negative provocation test at week 12[128]. - The company has expanded clinical development of barzolvolimab into Prurigo Nodularis (PN), a chronic skin disease with an estimated 154,000 patients in the U.S. who have undergone treatment in the last 12 months[134]. Financial Performance - The total research and development expenses for the nine months ended September 30, 2024, amounted to 87.6 million for the same period in 2023, reflecting a year-over-year increase of approximately 33%[86]. - The total revenues for the three months ended September 30, 2024, were 1.517 million in the same period in 2023[151]. - Research and development expenses increased by 31% to 34.535 million in the prior year[151]. - The net loss for the three months ended September 30, 2024, was 38.260 million in the same period in 2023[152]. - Revenue from product development and licensing agreements for the three months ended September 30, 2024, was 2.8 million for the same period in 2023[161]. - Investment and other income increased by 236% to 2.979 million in the prior year[151]. - Investment and other income, net, for the nine months ended September 30, 2024, increased by 28.3 million compared to 338.8 million in research and development expenses over the past five years through December 31, 2023[86]. - Product development expenses for the nine months ended September 30, 2024, rose by 64.7 million compared to 6.2 million, or 28%, totaling 22.1 million for the same period in 2023[167]. Cash Flow and Financing - Net cash used in operating activities was 74.8 million for the same period in 2023[174]. - Net cash used in investing activities was 65.4 million for the same period in 2023[176]. - Net cash provided by financing activities was 1.1 million for the same period in 2023[177]. - In March 2024, the company issued 9,798,000 shares of common stock, resulting in net proceeds of $432.3 million after deducting underwriting fees and offering expenses[178]. Clinical Efficacy and Safety - Barzolvolimab demonstrated a mean reduction from baseline in weekly urticaria activity score (UAS7) of 67% at week 12 for both the 1.5 mg/kg and 3.0 mg/kg dose groups, and 82% for the 4.5 mg/kg dose group[94]. - At week 12, complete response (UAS7=0) was achieved by 57% of patients in the 1.5 mg/kg group, 44% in the 3.0 mg/kg group, and 67% in the 4.5 mg/kg group[95]. - Well-controlled disease (UCT≥12) at week 12 was reported in 75% of the 1.5 mg/kg group, 63% of the 3.0 mg/kg group, and 89% of the 4.5 mg/kg group[96]. - At week 12, barzolvolimab achieved a statistically significant mean change from baseline in UAS7 compared to placebo across all dose levels, with a mean difference of -13.41 for 300 mg Q8W[105]. - 71% of patients treated with barzolvolimab 150 mg Q4W and 52% treated with 300 mg Q8W had a complete response (UAS7=0) at week 52[110]. - 74% of patients treated with barzolvolimab 150 mg Q4W and 68% treated with 300 mg Q8W had well-controlled disease (UAS7<6) at week 52[111]. - Barzolvolimab was well tolerated, with most adverse events being mild to moderate; common events included hair color changes (9%) and neutropenia (8%)[100]. - Approximately 72% of patients had angioedema at baseline, with significant improvements in angioedema activity score (AAS7) observed across all doses at week 12[108]. - Patients in the 300 mg cohort experienced angioedema-free days 77% of the time over the 12-week period[108]. - The studies confirmed that serum tryptase level is a robust pharmacodynamic biomarker for assessing mast cell burden and clinical activity in inducible urticaria[122]. - The Phase 1b study of barzolvolimab showed a 57% reduction in Worst Itch Numerical Rating Scale (WI-NRS) at week 8 for the 3.0 mg/kg dose, compared to 25% for placebo[137]. - At week 8, 29% of patients in the 3.0 mg/kg group achieved clear or almost clear skin according to Investigator Global Assessment (IGA), with no patients in the 1.5 mg/kg or placebo groups achieving this[138]. Future Outlook - The ongoing clinical trials and development programs are subject to various uncertainties, including regulatory approvals and the ability to raise sufficient capital for continued operations[72]. - The company expects revenue to decrease over the next twelve months primarily due to a decrease in services under contract manufacturing and research agreements[153]. - The company anticipates that cash used in operating activities will increase over the next twelve months due to expanded development of barzolvolimab[174]. - The company plans to initiate a Phase 1 study of CDX-622, a bispecific antibody, in healthy volunteers by the end of 2024[147]. - The company successfully scaled up the barzolvolimab manufacturing process to produce larger cGMP batches in support of late-stage trials[144].