Skye Bioscience (SKYE) investor relations material

Study design and objectives

• Phase 2a randomized, double-blind trial evaluated nimacimab (also referred to as Nimasumab) as monotherapy and in combination with semaglutide in adults with overweight or obesity over 26 weeks, with a primary endpoint of weight loss and additional safety, PK, and body composition assessments.

• Participants were randomized into four arms: nimacimab 200 mg, placebo, nimacimab 200 mg plus semaglutide, or placebo plus semaglutide, with a subsequent extension phase to assess higher dosing and longer-term effects.

• The trial population had a mean BMI of approximately 37, was majority female, and included adults with at least one comorbidity.

• Modified intention-to-treat and per-protocol populations were analyzed.

• The main treatment period was 26 weeks, followed by an ongoing 26-week extension and 13-week follow-up; extension data expected Q1 2026.

Key efficacy results

• Nimacimab monotherapy at 200 mg weekly did not meet the primary endpoint, showing only a 1.26% placebo-adjusted weight loss at 26 weeks (p=0.2699, mITT).

• Combination therapy with semaglutide resulted in greater placebo-adjusted weight loss than semaglutide alone: up to 14.3% at 26 weeks, outperforming semaglutide alone (10.8%), with statistical significance (p=0.0372, mITT).

• 100% of combination arm participants achieved at least 5% weight loss, and 67% achieved at least 10% in per-protocol analysis.

• Combination therapy improved lean-to-fat mass ratio more than semaglutide alone, indicating healthier weight loss.

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

Pharmacokinetics and dose insights

• Drug exposure for nimacimab was lower than predicted at 200 mg, with most participants not reaching steady-state levels.

• PK and exposure-response analyses suggest higher doses are needed for optimal efficacy, with ongoing modeling and preclinical data supporting dose escalation.

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

• Compliance issues and variability in exposure were identified as key factors affecting outcomes.

• Extension study will evaluate nimacimab 300 mg, with results expected in Q1 2026.