Cue Biopharma’s CUE-221 Hits Phase II Goals, Shows Durable CSU Response

Key Points

• CUE-221 met its Phase II efficacy endpoints in moderate-to-severe chronic spontaneous urticaria, with all dose groups significantly improving complete hive resolution versus placebo and the 4 mg/kg dose also meeting the key UAS7 secondary endpoint.
• The 4 mg/kg group showed potentially meaningful durability: about 60% of patients remained hive-free at week 28, compared with 24% in the omalizumab arm, although comparisons with omalizumab were not preplanned and should be interpreted cautiously.
• CUE-221 was generally well tolerated, with no treatment-related serious adverse events, anaphylaxis or deaths. Cue Biopharma plans to advance the program into a Phase IIb/III CSU trial and study it in food allergy.

Cue Biopharma NASDAQ: CUE reported positive top-line results from a Phase II trial of CUE-221 in patients with moderate-to-severe chronic spontaneous urticaria, or CSU, whose disease was inadequately controlled with H1 antihistamines.

The randomized, double-blind, placebo-controlled study evaluated subcutaneous CUE-221 at doses of 1 mg/kg, 2 mg/kg and 4 mg/kg, administered every four weeks. The trial also included an omalizumab arm at its registered dose and a placebo group. The primary endpoint was assessed at week 12, while patients were followed for 20 weeks after their final dose at week 16.

Primary and Secondary Endpoints Met

According to Cue Biopharma, all CUE-221 dose groups achieved statistically significant improvements over placebo on the primary endpoint: complete resolution of hives, measured as a Hives Severity Score over seven days, or HSS7, of zero at week 12. The company said the results were dose-responsive, with the high-dose group producing a p-value below 0.005 versus placebo.

The key secondary endpoint, complete response on the Urticaria Activity Score over seven days, or UAS7=0, was also met in the 4 mg/kg group, with a statistically significant difference compared with placebo. The company also reported statistically significant changes from baseline in UAS7 across all CUE-221 dose groups at week 12.

“The study demonstrated robust, durable, and dose-responsive clinical effects,” President and Chief Executive Officer Shao-Lee Lin said during the call. Lin said the findings reinforce the company’s view that CUE-221 could offer differentiated benefit in IgE-mediated diseases.

Durability Findings After Dosing Ended

Cue Biopharma emphasized results observed after the week 12 primary analysis. The rate of complete hive resolution continued to increase through week 22, six weeks after the final treatment administration, across CUE-221 dose groups.

At week 28, or 12 weeks after the last dose, approximately 60% of patients in the 4 mg/kg CUE-221 group continued to have complete resolution of hives, compared with 24% of patients in the omalizumab group, according to the company. Cue Biopharma said a post hoc Fisher’s exact test found the difference between the high-dose CUE-221 group and omalizumab to be statistically significant.

Chief Medical Officer and Head of Research and Development Dominic Borie said both products are expected to have half-lives of roughly two to three weeks, meaning patients were several half-lives beyond their final doses at week 28. He said the durability observed in the high-dose CUE-221 group could reflect a biological effect beyond IgE neutralization.

The omalizumab arm was included for comparative efficacy and safety purposes, but the company noted that no formal statistical testing against omalizumab had been planned. Cue Biopharma also cautioned that cross-trial comparisons presented in its materials were illustrative and not direct efficacy comparisons.

Dual-Mechanism Design

CUE-221 was designed to block IgE binding to the high-affinity receptor involved in allergic-cell degranulation while preserving the ability of IgE complexes to bind the low-affinity CD23 receptor on B cells. Borie said CD23 binding can initiate a negative-feedback mechanism that reduces new IgE synthesis.

In company-presented preclinical data, CUE-221-IgE complexes bound CD23, whereas omalizumab-IgE complexes did not. Cue Biopharma said CUE-221 also reduced IgE synthesis at messenger RNA and protein levels in its studies.

Lin said the company intends to further analyze pharmacokinetic, IgE and immunogenicity data, including anti-drug antibody results, and expects to present those analyses at a future scientific meeting. Those data were not available at the time of the call.

Safety and Next Steps

Cue Biopharma said CUE-221 was generally well tolerated. There were no treatment-related serious adverse events, no cases of anaphylaxis and no deaths reported in the study. One treatment-related adverse event of special interest, a Grade 2 injection-site reaction, was reported.

Two treatment-related adverse events led to study discontinuation: one case of worsening urticaria and one case of insomnia, the company said.

The company plans to advance CUE-221 into a Phase IIb/III CSU study and also intends to conduct a Phase II study in food allergy. Lin said the next CSU trial will further examine pharmacokinetics, IgE levels and clinical responses, potentially including dosing approaches such as induction and maintenance regimens. Final dose selection, the possible use of an active comparator and study timing have not yet been determined.

“We are working towards the initiation of a Phase IIb/III study in CSU, in addition to our planned Phase II study in food allergy,” Lin said.

About Cue Biopharma (NASDAQ:CUE)

Cue Biopharma, Inc is a clinical-stage biotechnology company developing therapeutics that selectively activate and regulate antigen-specific T cells inside the body. Its approach is designed to direct the immune system toward cancer cells while potentially reducing the broad immune activation and toxicity associated with conventional immunotherapies.

The company's proprietary Immuno-STAT (Selective Targeting of Antigens for Remodeling of T cells) platform uses biologic molecules that combine peptide-major histocompatibility complex components with immune-modulating signals.

This instant news alert was generated by narrative science technology and financial data from MarketBeat in order to provide readers with the fastest reporting and unbiased coverage. Please send any questions or comments about this story to contact@marketbeat.com.