Cue Biopharma, a clinical-stage biopharmaceutical company targeting transformative therapies for immune-mediated diseases, announced positive topline results from the Phase 2 clinical trial of CUE-221 (UB-221) conducted in China by Genesis Life Sciences, a related company of Ascendant Health Limited (Ascendant). The trial enrolled 145 participants with moderate to severe chronic spontaneous urticaria (CSU), a disease resulting in chronic hives, that remained inadequately controlled despite treatment with H1 antihistamines.

“We are excited to share these positive results which we believe establish CUE-221 as a potential best therapeutic option for patients suffering with chronic spontaneous urticaria,” said Shao-Lee Lin, M.D., Ph.D., President and Chief Executive Officer of Cue Biopharma. “These findings reinforce our enthusiasm for the precision engineered, unique dual mechanism of action of CUE-221, reflecting science that is truly differentiated. Based on the strength of these data, we are working toward the rapid initiation of a Phase 2b/3 study in CSU and continuing to advance a planned Phase 2 study in food allergy. We thank the patients, investigators, and study staff, all of whom made these results possible. We look forward to presenting the complete data set including PK and IgE analyses from this 36-week study at an upcoming scientific meeting.”

Phase 2 CSU Study Topline Results
The Phase 2 multicenter, randomized, double-blind, placebo and active comparator-controlled study was conducted in China and included a 16-week treatment period with a 20-week follow-up period post-treatment. Patients were randomized in a 2:2:2:1:1 ratio across five treatment groups to either subcutaneously deliver CUE-221 at 4 mg/kg, 2 mg/kg, or 1 mg/kg Q4W, or placebo Q4W, or omalizumab 300 mg Q4W. The primary endpoint was the proportion of patients who achieved HSS7=0 at week 12. A key secondary endpoint assessed complete response, defined as the proportion of patients who achieved UAS7=0 at week 12. The study was designed to test superiority over placebo. Omalizumab was included to enable comparative efficacy without planned statistical testing.

The primary endpoint of percentage of patients with HSS7=0 at week 12 was dose-responsive and met at all dose levels. The key secondary endpoint of percentage of patients with UAS7=0 at week 12 was dose responsive and met statistical significance at the 4 mg/kg highest dose level.

Demographics and baseline disease characteristics were generally well balanced across treatment groups. CUE-221 demonstrated a favorable safety profile. There were no treatment-related serious adverse events and no cases of hypersensitivity reactions including anaphylaxis. Injection site reactions (ISR) were infrequent, only one ISR was > grade 1, and none led to study discontinuation.

“The results of the Phase 2 CUE-221 study in patients with CSU are particularly notable,” said Dale Umetsu, M.D., Ph.D., Clinical Professor of Medicine and former Chief of the Allergy and Immunology Division, Stanford University, Clinical Professor of Pediatrics, University of California, San Francisco and prior Global Lead for XOLAIR development. “First, the results after 12 weeks of treatment, after three doses, appear to indicate that CUE-221 was better than XOLAIR for CSU at all dose levels tested. Moreover, there was persistent improvement with the 4 mg/kg dose at week 28, which was 12 weeks off treatment, significantly better than that off of standard XOLAIR dosing. Finally, the safety data analyzed so far, show no major safety issues, which is not unexpected from an anti-IgE mAb.”

Dr. Umetsu added, “These results suggest that CUE-221, like XOLAIR is designed to prevent IgE from binding to FceR1 but unlike XOLAIR, allows IgE to bind to CD23, may represent a critical advancement over XOLAIR. The results support that the effects of CUE-221 on IgE function could result in substantial efficacy in CSU that persists for several months, even after dosing ends. Since XOLAIR has represented the clear standard for all other CSU therapies, the possibility that CUE-221 may represent a clear improvement above that of XOLAIR is most impressive. That improvement in efficacy may be directly relevant for food allergy, another area where XOLAIR currently prevails as the standard-of-care.“

“I am very pleased to see these outstanding results from the UB-221 Phase 2 CSU trial,” said Tse-Wen Chang, Ph.D., innovator of XOLAIR as well as UB-221 and an international expert in IgE biology. “The UB-221 data provide clear clinical evidence validating the molecule’s design to not only directly neutralize IgE, but also to create a next-generation approach to eliminate the production of new IgE over time. This fundamental difference in biological mechanism that is now clinically evident cannot be reached by giving higher doses or more potent IgE neutralization. Having invented several novel IgE-targeting molecules that ultimately led to the creation of UB-221, I am encouraged by these emerging data and the potential for this approach to offer a meaningfully different path toward a functional treatment for IgE-mediated diseases.”