Skye Bioscience (SKYE) Study Update summary

Study design and population

• Phase 2a CBeyond trial evaluated nimacimab as monotherapy and in combination with semaglutide for obesity over 26 weeks, with a 13-week follow-up and an optional 26-week extension; 136 adults with overweight or obesity and at least one comorbidity were enrolled, mostly female, mean age 45.6 years, BMI ~36.8.

• Participants were randomized across four arms: nimacimab 200 mg, placebo, nimacimab 200 mg plus semaglutide, or placebo plus semaglutide, dosed weekly.

• The primary endpoint was percent change in body weight at 26 weeks, analyzed using mITT and per protocol populations.

• Extension study for an additional 26 weeks is ongoing, with nimacimab monotherapy increased to 300 mg.

Efficacy results

• Nimacimab monotherapy at 200 mg did not meet the primary endpoint, with placebo-adjusted weight loss of -1.26% (p=0.2699, mITT) and -1.33% (p=0.2878, PP) at 26 weeks.

• Combination of nimacimab and semaglutide showed greater placebo-adjusted weight loss than semaglutide alone: -12.94% (mITT), -14.29% (PP) vs -9.99% (mITT), -10.8% (PP), with p=0.0372 (mITT) and p=0.0178 (PP).

• 100% of combination arm participants lost at least 5% of weight, and 67% lost at least 10%.

• Improved lean to fat mass ratio was observed in the combination arm (0.26 vs 0.13, p=0.0126), with 76% of weight lost as fat.

• No weight loss plateau observed at 26 weeks in the combination arm, suggesting potential for further loss.

Pharmacokinetics and dose response

• Most patients had lower than expected nimacimab exposure at 200 mg, potentially limiting monotherapy efficacy; higher drug exposure correlated with greater weight loss (r = -0.62, p = 0.006).

• Preclinical models suggest current dosing is at the low end of the efficacy curve; higher doses (600–1,000 mg) are being considered.

• Anti-drug antibodies did not appear to drive nimacimab clearance.

• Compliance and dosing variability are being investigated as contributors to suboptimal exposure.