Skye Bioscience, Inc.

CBeyond Extension Study Design and Interim Data Summary

The blinded extension of the CBeyond study for combination cohorts was opened in May 2025 for participants assigned to either nimacimab plus semaglutide or placebo plus semaglutide arms. Eligible patients completed 26 weeks of treatment and were precluded from being off therapy for longer than 4 weeks. In total, 19 participants in the combination cohorts who completed week 26 were eligible for and elected to enroll in the extension study. The extension continued in a blinded manner for an additional 26 weeks, maintaining their original treatment assignment (10 nimacimab plus semaglutide; 9 placebo plus semaglutide). An additional 22 participants completed week 26 and were either ineligible for the extension or chose not to join the extension study and continued for 13 weeks on post-treatment follow-up (11 nimacimab plus semaglutide; 11 placebo plus semaglutide).

Of the 10 participants in the nimacimab plus semaglutide arm who joined the extension study, the mean weight loss at 26 weeks was 14.4%. Seven (7) participants completed the additional 26 weeks of treatment and lost an additional 7.9% of weight, resulting in a mean weight loss of 22.3% after 52 weeks of treatment with no weight loss plateau observed. The combination therapy continued to demonstrate safety and was well tolerated at the tested doses. No serious adverse events or adverse events of special interest were reported during the extension period.

Of the 9 participants in the placebo plus semaglutide arm that joined the extension study, mean weight loss at 26 weeks was 13.9%. Seven (7) participants completed treatment of the additional 26 weeks and lost an additional 5.8% of weight during the extension period, resulting in a mean weight loss of 19.7% after 52 weeks of treatment.

In October 2025, Skye reported top-line 26-week data from CBeyond showing that the nimacimab and semaglutide combination cohort achieved clinically meaningful weight loss compared with semaglutide alone (-13.2% vs -10.25%, p=0.0372, mITT), with no plateau observed.