Skye Bioscience (SKYE) Study Update summary

Study design and population

• Phase 2a, randomized, double-blind trial evaluated nimacimab as monotherapy and in combination with semaglutide in 136 adults with overweight or obesity, with a 26-week treatment, 13-week follow-up, and ongoing extension phase.

• Participants were assigned to 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 in mITT and per protocol populations.

• The study population was predominantly female, with a mean BMI of ~36.84 kg/m² and balanced withdrawals across arms.

• An 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) at 26 weeks.

• Combination of nimacimab and semaglutide achieved greater placebo-adjusted weight loss than semaglutide alone: -12.94% (mITT) and -14.29% (PP) at 26 weeks, with a difference of -2.95% (p=0.0372, mITT).

• 100% of combination arm participants lost at least 5% of weight, and 67% lost at least 10%, compared to 85% and 50% for semaglutide alone.

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

• Improvement in lean-to-fat mass ratio was greater with combination therapy (0.26 vs 0.13, p=0.01).

Pharmacokinetics and exposure

• 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), supporting a dose-response relationship.

• Preclinical models suggest current dosing is at the low end of the efficacy curve, indicating higher doses could yield better results.

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

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