Core Insights - Skye Bioscience, Inc. will host a virtual KOL event on September 4, 2025, to discuss the upcoming topline results from the Phase 2a CBeyond™ trial of nimacimab, a first-in-class peripheral CB1 antibody for obesity [1][2] - The event aims to provide clarity on what constitutes success in the proof-of-concept study, focusing on safety, tolerability, and new preclinical insights related to nimacimab [2][7] Company Overview - Skye Bioscience is a clinical-stage biotechnology company focused on developing new therapeutic pathways for obesity and metabolic health disorders [1][8] - The company is conducting a Phase 2a clinical trial for nimacimab, which is designed to inhibit peripheral CB1 and is also assessing its combination with a GLP-1R agonist [8] KOL Event Highlights - The event will feature discussions with leading obesity experts, including Skye's CEO, Punit Dhillon, who will address the significance of safety and tolerability benchmarks in the obesity treatment landscape [2][7] - Key opinion leaders participating include Dr. Kevin Cannon, Dr. Sean Wharton, and Dr. Marcus Goncalves, who bring extensive experience in metabolic health and obesity research [3][4][6] Research Focus - The event will cover the mechanism and potential role of peripheral CB1 inhibition as a differentiated anti-obesity therapeutic pathway [7] - Newly generated preclinical data with nimacimab will be highlighted, contributing to the understanding of its potential advancement into Phase 2b development [2][7]

Core Insights - The model presented by Skye Bioscience indicates that central inhibition of CB1 is not necessary for weight loss, emphasizing the importance of peripheral CB1 inhibition for efficacy [1][3] - Nimacimab, an anti-CB1 inhibiting antibody, shows superior peripheral restriction compared to small molecule-based CB1 inhibitors like monlunabant and rimonabant, which penetrate the brain more [1][3] - The therapeutic index of nimacimab is potentially more favorable due to its minimal brain exposure while maintaining effective peripheral inhibition [1][3] Company Overview - Skye Bioscience is a clinical-stage biotechnology company focused on developing new therapeutic pathways for obesity and metabolic health disorders [5] - The company is conducting a Phase 2 clinical trial for nimacimab, which is a negative allosteric modulating antibody that inhibits CB1 peripherally [6] - Skye aims to differentiate its therapeutics through biologic targets with substantial human proof of mechanism [5] Clinical Findings - The model developed utilized published clinical pharmacokinetic and potency data from other CB1 inhibitors, demonstrating that central inhibition alone does not lead to significant weight loss [2][4] - Phase 2 data for monlunabant showed that all doses achieved significant peripheral inhibition, resulting in similar weight loss outcomes [2] - Nimacimab's Phase 2 dose achieves peripheral CB1 engagement at over seven times the inhibition threshold while remaining significantly below this threshold in the brain [4] Safety and Efficacy - The model provides insights into the therapeutic index of different CB1 inhibitors, indicating that increased central inhibition correlates with neuropsychiatric adverse events [3][4] - Nimacimab has been shown to be virtually undetectable in the brain, which is a challenge faced by small molecule CB1 inhibitors [3][4]