Study details formulation that offers enhanced IOP reduction

Skye Bioscience Inc. this week announced the release of preclinical data¹ demonstrating stronger and longer-lasting reduction of intraocular pressure (IOP) when Skye’s proprietary molecule, SBI-100, is formulated as a nanoemulsion containing the mucoadhesive agent Carbopol 940.

In a news release, Skye, in collaboration with investigators at the University of Mississippi, previously published preclinical data² demonstrating SBI-100 formulated as a nanoemulsion (THC-VHS-NE) achieved greater reduction of intraocular pressure in non-pigmented rabbits than both latanoprost and timilol, the current first and second line treatments for glaucoma, respectively. The current study was undertaken to determine if the inclusion of a mucoadhesive agent could prolong the intensity and duration of action of the THC-VHS-NE formulation through increased residence time or penetration, or both, to potentially achieve once- or twice- a day dosing.

According to the release, in this study sponsored by Skye, researchers at the University of Mississippi compared the reduction of IOP in normotensive rabbits with a single treatment of THC-VHS-NEC (SBI-100 formulated as a nanoemulsion with Carbopol 940) compared to latanoprost, the commercial standard of care; THC-NEC (native THC formulated as a nanoemulsion with Carbopol 940); and THC-VHS-NE (SBI-100 formulated as just a nanoemulsion). When comparing each treatment group, THC-VHS-NEC, Skye’s SBI-100 ophthalmic emulsion, demonstrated the greatest intensity and duration of IOP-lowering.

Punit Dhillon, CEO and chairman of Skye, noted in the news release that the company has been working aggressively to optimize a formulation of SBI-100 to advance toward a first in-human study, which is planned to start this quarter.

“We previously reported strong preclinical results that highlighted the superior IOP-lowering of our unique molecule formulated as just a nanoemulsion compared to other established commercial glaucoma drugs,” Dhillon said in the release. “This further evolution of our formulation, generating even more robust results, gives us strong conviction as we step into the clinic with SBI-100 ophthalmic emulsion.”

Dhillon added that the company’s goal with this program is to advance a new class of glaucoma treatment with a once or twice a day dosing regimen.

“Positive, prior third-party research relevant to our molecule and this preclinical work informed our selection of the best formulation of SBI-100 for this application,” Dhillon concluded.

In comparison to THC-VHS-NE, THC-NEC and commercial latanoprost, THC-VHS-NEC (SBI-100 ophthalmic emulsion) exhibited a prolonged duration of action. THC-NEC and THC-VHS-NE formulations respectively produced an average maximum drop in IOP of 3.7 mm Hg at 60 minutes and 4.8 mm Hg at 150 minutes, while the IOP-lowering effect lasted for 240 and 360 minutes, respectively, in the treated eye. In contrast, SBI-100 ophthalmic emulsion lowered IOP by 4.5 mmHg at 60 min and maintained this drop for at least 480 min in the treated eye.

A significant difference (p < 0.05) in IOP-lowering was also observed between SBI-100 Ophthalmic Emulsion and commercial latanoprost ophthalmic solution. The average maximum drop in IOP with SBI-100 ophthalmic emulsion (THC-VHS-NEC) of 4.5 mm Hg at 60 minutes was almost twice that obtained with commercial latanoprost ophthalmic solution (2.3 mm Hg) at 60 minutes.

Moreover, latanoprost maintained IOP 10% below baseline for only 360 minutes, whereas SBI-100 ophthalmic emulsion maintained the IOP- lowering effect for at least 480 min (p < 0.05).

References

1 Sweeney, C., Dudhipala, N., Thakkar, R., et al. Impact of mucoadhesive agent inclusion on the intraocular pressure lowering profile of Δ9-tetrahydrocannabinol-valine-hemisuccinate loaded nanoemulsions in New Zealand white rabbits. Int’l Journal of Pharmaceitics. Published March 25, 2022. https://doi.org/10.1016/j-ijpharm.2022.121564

2 Sweeney, C., Dudhipala, N., Thakkar, R. et al. Effect of surfactant concentration and sterilization process on intraocular pressure–lowering activity of Δ9-tetrahydrocannabinol-valine-hemisuccinate (NB1111) nanoemulsions. Drug Deliv. and Transl. Res. 11, 2096–2107 (2021). https://doi.org/10.1007/s13346-020-00871-9