Skye Bioscience Showcases New Synthetic Cannabinoid Library for Ocular Disease Treatment at ARVO 2024

Skye Bioscience, Inc., a clinical-stage biotechnology company listed on Nasdaq as SKYE, recently showcased new research in a poster presentation at the ARVO 2024 Annual Meeting. The poster, titled "Development and screening of a novel library of synthetic endocannabinoid agonists and inhibitors to advance a potential therapy to treat dry eye disease and chronic ocular pain," highlighted their innovative approach to finding new therapeutic candidates for ocular conditions.

Punit Dhillon, the CEO and Chairman of Skye, emphasized that the endocannabinoid system (ECS) offers unique prospects for addressing unmet medical needs through new mechanisms of action. He noted that the presentation at ARVO demonstrated Skye's progress in developing and screening a novel library of synthetic agonists and inhibitors, which could address conditions like dry eye disease (DED) and chronic ocular pain.

The key highlights from the presentation included a biological ECS screening program aimed at pathways relevant to DED and chronic ocular pain. Through this program, three synthetic cannabinoid-based compounds were identified for further pharmaceutical development. The approach taken in this study has the potential to provide a new class of therapeutics with unique mechanisms of action for a variety of ocular diseases.

Chris Twitty, PhD, the Chief Scientific Officer of Skye, explained the company's strategy to develop advanced pharmaceutical drugs that modulate the ECS to positively impact ocular pathologies. The study involved evaluating a novel synthetic cannabinoid-based library with biologically relevant cell types, targets, and pathways. This evaluation enabled the identification of candidate molecules suitable for treating DED and chronic ocular pain. Specifically, cannabinerol and two non-electrophilic indolic adducts of cannabidiolquinone and cannabigeroquinone were selected for further investigation and pharmaceutical development.

The study utilized a rigorous in-vitro screening platform focused on cannabinoid biology within the context of ocular diseases. A library of 98 synthetic cannabinoid-based molecules was scrutinized for their potential to treat ocular conditions. Immortalized human ocular cell lines and stable modified HEK cells were employed to measure the activation or inhibition of specific cannabinoid receptors, including CB1, CB2, GPR55, and TRPV1. The compounds were initially screened for relevant biological activity, resulting in 38 compounds being further scored based on their EC50/IC50 metrics for signaling pathways like CB1/2, TRPV1, PPARg, and NF-kB, as well as their inhibition of ROS and HIF-1a in human epithelial and endothelial cells. Chemical and developability attributes of these compounds were also assessed, leading to the selection of three lead candidate molecules.

Skye Bioscience is focused on harnessing the potential of the ECS to develop treatments for diseases characterized by metabolic, inflammatory, and fibrotic processes. Supported by leading life science venture investors, Skye aims to develop first-in-class therapeutics with significant clinical and commercial differentiation. One of their key products, Nimacimab, a negative allosteric modulating antibody that inhibits peripheral CB1, demonstrated a favorable safety and tolerability profile in a Phase 1 study. The company plans a Phase 2 clinical trial in mid-2024 to compare monotherapy and combination arms of Nimacimab and a GLP-1R agonist in the context of obesity. Additionally, enrollment for a Phase 2 clinical trial of SBI-100 Ophthalmic Emulsion, a CB1 agonist for glaucoma and ocular hypertension, is complete, with topline data expected in the second quarter of 2024.

Skye Bioscience continues to pursue the development of innovative cannabinoid-derived therapeutics, targeting a range of unmet medical needs with novel mechanisms of action.