Cue Biopharma (CUE) Study result summary

Study design and objectives

• Phase II randomized, double-blind, placebo-controlled study in adults with moderate to severe chronic spontaneous urticaria (CSU) inadequately controlled by H1 antihistamines, with omalizumab as an active comparator.

• 145 patients were randomized to CUE-221 at 1, 2, or 4 mg/kg, omalizumab, or placebo, with subcutaneous injections every four weeks.

• Primary endpoint: complete resolution of hives (HSS7=0) at week 12; key secondary endpoint: complete response (UAS7=0) at week 12.

• Study included a 16-week treatment period and up to 20-week post-treatment follow-up, with modified intent-to-treat analysis and balanced baseline characteristics.

Efficacy results

• CUE-221 met both primary and key secondary endpoints with robust, dose-responsive, and statistically significant efficacy versus placebo and omalizumab.

• At week 12, 54% (4 mg/kg), 53% (2 mg/kg), and 43% (1 mg/kg) of CUE-221 groups achieved HSS7=0, compared to 11% for placebo and 41% for omalizumab.

• Complete response (UAS7=0) at week 12 was 46% (4 mg/kg), 39% (2 mg/kg), 38% (1 mg/kg), 11% (placebo), and 29% (omalizumab).

• High-dose CUE-221 showed sustained efficacy, with 60% maintaining complete resolution at week 28 versus 24% for omalizumab; peak effect at week 22 (69% HSS7=0 for 4 mg/kg).

• Over 90% of complete responders at week 12 maintained response at week 28 in the high-dose group.

Mechanism of action and biological insights

• CUE-221 is a humanized anti-IgE IgG1 monoclonal antibody engineered for dual mechanism: potent IgE neutralization and preservation of IgE-CD23 interaction, enabling downregulation of new IgE synthesis.

• Unlike omalizumab, CUE-221 does not block IgE-CD23 binding, maintaining negative feedback on IgE production.

• Clinical data support a dual mechanism leading to more durable off-drug responses and potential for disease modification.

• Demonstrated a clinically differentiated efficacy profile compared to omalizumab, suggesting a fundamental biological difference.

• Designed to potentially offer a functional cure for IgE-mediated diseases by eradicating IgE.