Skye Bioscience Reports Topline 26-Week Phase 2a CBeyond Results for Nimacimab in Obesity

Skye Bioscience Reports Topline 26-Week Phase 2a CBeyond Results for Nimacimab in Obesity

By, Admin 8 October 2025

Skye Bioscience, Inc., a clinical-stage biotech focused on novel therapies for obesity and metabolic disorders, announced topline data from its 26-week Phase 2a CBeyond study evaluating nimacimab, a peripherally-restricted CB1 inhibitor antibody.

Key Highlights

  • Monotherapy Arm: Nimacimab 200 mg weekly did not meet the primary weight loss endpoint compared to placebo (-1.52% vs. -0.26%, mITT). Pharmacokinetic analysis suggested suboptimal exposure, informing higher-dose strategies for future trials.
  • Combination Therapy: Nimacimab 200 mg plus semaglutide (Wegovy) showed clinically meaningful additional weight loss versus semaglutide alone (-13.2% vs. -10.25%, p=0.0372, mITT) with no plateau observed at 26 weeks.
  • Responder Rates:
    - >5% weight loss: 100% in combination arm vs. 85% with semaglutide alone
    - >10% weight loss: 67% vs. 50%
  • Body Composition: Combination therapy improved lean mass to fat mass ratio compared with placebo (0.26 vs. 0.02, p<0.0001) and semaglutide alone (0.26 vs. 0.13, p=0.0126).
  • Safety and Tolerability:
    - Nimacimab showed a favourable safety profile, with placebo-like tolerability.
    - No increase in gastrointestinal (GI) or neuropsychiatric adverse events was observed with monotherapy or combination therapy.
    - Overall discontinuation rate: 27%; only 3.7% due to adverse events.

Expert Commentary

"The combination of a CB1 inhibitor with a GLP-1 therapy is the first clinical demonstration of additional meaningful weight loss beyond a GLP-1 alone. Importantly, this was achieved without neuropsychiatric or additive GI side effects, warranting further evaluation of nimacimab."

  • Dr. Louis Aronne, clinical advisor to Skye.

"GI side effects remain a key cause of therapy discontinuation. Nimacimab did not increase GI events while enhancing weight loss, supporting exploration of higher dosing,"

  • Dr. Sean Wharton, clinical advisor to Skye.

Study Design

  • Population: 136 adults with overweight or obesity (mean BMI ~36.8 kg/m²), randomized 2:2:1:1 across four arms (nimacimab, placebo, nimacimab + semaglutide, placebo + semaglutide)
  • Duration: 26-week double-blind treatment, with a 26-week extension ongoing
  • Endpoints: Efficacy, safety, pharmacokinetics, and exploratory endpoints

Participants completing the primary phase could enroll in a 26-week extension, with monotherapy patients receiving nimacimab 300 mg weekly and combination-arm patients continuing blinded treatment with semaglutide. Skye expects extension study data in Q1 2026.

About Nimacimab

Nimacimab is a first-in-class, peripherally-restricted monoclonal antibody targeting the CB1 receptor. Unlike prior CB1 inhibitors, it avoids central nervous system penetration, minimizing neuropsychiatric side effects. Nimacimab can act independently of GLP-1 pathways and has shown additive effects in combination with incretin-based therapies.

Next Steps

  • Skye plans to evaluate higher dosing strategies for nimacimab based on pharmacokinetic insights and preclinical data.
  • Detailed 26-week CBeyond results will be presented at ObesityWeek in November 2025.
  • Ongoing extension study will assess durability, safety, and potential weight regain.

Skye Bioscience continues to advance its mission to unlock new therapeutic pathways for metabolic health, leveraging biologic targets with strong human proof of mechanism to develop differentiated, first-in-class therapies.

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