Celldex Therapeutics, Inc. announced interim data from the Company's ongoing Phase 1b clinical trial of barzolvolimab in patients with moderate to severe chronic spontaneous urticaria (CSU) refractory to antihistamines. Barzolvolimab is a humanized monoclonal antibody that specifically binds the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity, which is required for mast cell function and survival. CSU is characterized by the occurrence of hives or wheals for 6 weeks or longer without identifiable specific triggers or causes. Data show that multiple doses of barzolvolimab resulted in dose-dependent decreases in itch and hives, as measured through the urticaria activity score over 7 days (UAS7), with a mean UAS7 reduction of 66.6% in all patients in the 1.5 mg/kg dose group (n=8) at week 12 and 75.1% in all patients in the ongoing 3.0 mg/kg dose group (n=9) at week 8 (reflects one dose), demonstrating meaningful symptom improvements for patients. Complete response as measured by UAS7=0 was 57.1% for patients in the 1.5 mg/kg dose group at week 12 and 44.4% for the patients in the 3.0 mg/kg dose group at week 8 (reflects one dose; ongoing). Summary of Data from Ongoing Phase 1b CSU Trial of Barzolvolimab: As of the data cut-off on May 23, 2022, 34 patients with CSU were enrolled and treated [26 barzolvolimab (n=9 in 0.5 mg/kg; n=8 in 1.5 mg/kg; n=9 in 3.0 mg/kg) and 8 placebo]. The 0.5 mg/kg and 1.5 mg/kg cohorts had completed study participation through 24 weeks; 7 of 12 patients in the 3.0 mg/kg cohort had completed week 12; enrollment in the 4.5 mg/kg cohort was ongoing. Adverse events through data cutoff and hematology data through week 12 were included for all dose groups; clinical activity and tryptase data were included through week 12 for 0.5 mg/kg and 1.5 mg/kg, and through week 8 for 3 mg/kg (ongoing; reflecting the administration of only one dose). Interim Clinical Activity Results: Barzolvolimab results in rapid, marked and durable responses in patients with moderate to severe CSU refractory to antihistamines, including patients with prior omalizumab treatment. Mean reduction from baseline in urticaria activity (UAS7) of 66.6% in all patients in the 1.5 mg/kg dose group (n=8) at week 12 and 75.1% in all patients in the 3.0 mg/kg dose group (n=9) at week 8 (reflects one dose; ongoing), demonstrating clinically meaningful symptom improvements for patients. Complete response (UAS7=0) of 57.1% in the 1.5 mg/kg dose group at week 12 and 44.4% at week 8 (reflects one dose; ongoing) in the 3 mg/kg dose group which is a key therapeutic goal. 75% well-controlled disease by Urticaria Control Test (UCT) in the 1.5 mg/kg dose group at week 12 and 83.3% in the 3 mg/kg dose group at week 8 (reflects one dose; ongoing). Patients with prior omalizumab therapy had similar symptom improvement as all patients. All three doses of barzolvolimab markedly improved urticaria symptoms and disease control, with rapid improvement in itch and hives. As predicted, the lowest dose of 0.5 mg/kg resulted in suboptimal clinical activity compared to the higher doses. Rapid onset of responses after initial dosing and sustained durability were observed; onset as early as 1 week after the first dose. Tryptase suppression, indicative of mast cell depletion, paralleled symptom improvement, demonstrating the impact of mast cell depletion on CSU disease activity.