• SBI-100 Ophthalmic Emulsion, a CB1 agonist/activator delivered as a topical eye drop, was developed to treat patients with elevated intraocular pressure
• Phase 2 study evaluating efficacy and safety using two concentrations of SBI-100 OE vs. placebo, dosing twice a day for 14 days
• Analysis of IOP data from 50% of patients enrolled in Phase 2 study to be performed in Q1 2024

“Skye’s clinical pipeline targets the endocannabinoid system, which has seen growing development and M&A attention. We are advancing the next generation of investigational drugs targeting the endocannabinoid system’s CB1 receptor,” said Punit Dhillon, Skye’s CEO and Chairman. “Key opinion leaders have indicated that there is a need for an alternative class of glaucoma medicine to serve patients that fail approved treatments and that potentially offers an improved safety profile. SBI-100 OE represents an opportunity to develop a first-in-class alternative with differentiated therapeutic characteristics. Following our encouraging Phase 1 results, we look forward to assessing initial Phase 2 IOP results in Q1 2024.”

SBI-100 Ophthalmic Emulsion Phase 2 Study Design

• Double-masked, randomized, placebo-controlled study treating approximately 54 patients with elevated intraocular pressure (between 21mmHg and 36mmHg) diagnosed with POAG or OHT.
• Primary endpoints: assess change in diurnal IOP vs placebo, and ocular and systemic safety.
• Secondary endpoints: assess ocular hypotensive efficacy at individual time points and application comfort.
• Dosing: 0.5% or 1.0% concentrations of SBI-100 OE, or placebo.
• Patients will be treated with one drop in each eye, twice a day, in the morning and the evening (about 12 hours apart), for 14 days.
• Description of Phase 2 study on ClinicalTrials.gov: NCT06144918

“We have long been aware of THC’s ability to lower intraocular pressure, however, the true capabilities were confounded by the psychotropic effects of inhaled/ingested delivery. Localized ocular delivery via topical drop enables optimal evaluation with less risk of the systemic (psychotropic) effect, allowing for concise assessment of the IOP lowering potential,” said Dr. David Wirta, MD, a principal investigator of this study. “This Phase 2 study provides an avenue to confirm IOP-lowering ability and advance the potential for SBI-100 OE in treating ophthalmic disorders. We are excited to be apart of the evolution of SBI-100’s capabilities within the ophthalmic realm.”

SBI-100 OE Phase 1 Trial Results

In October 2023, Skye reported data from its first clinical study of SBI-100 OE, with the following highlights:

• SBI-100 OE was deemed safe, well-tolerated, and no serious adverse events were reported (drug related and non-drug related).
• No participants dropped out due to SBI-100. Reported adverse events were consistent with topically applied eye treatments.
• Discomfort/pain after drop instillation was the most commonly reported adverse event, but was transient and resolved in less than 15 minutes.
• SBI-100 was detected in the blood, consistent with exposure dose concentration, however, none of the active ingredient (THC) and minimum amounts of the psychoactive metabolite (11-OH-THC) were detected. The lack of detection supports minimal systemic side effects.
• Low rate of hyperaemia (red eyes) of 8.4% compared to other leading classes of glaucoma drugs.
• Mean reduction of intraocular pressure of 23.9% in subset of healthy volunteers with higher baseline IOP (>17 mm Hg)

SBI-100 OE

SBI-100 OE is a synthetic THC prodrug which can cross the corneal membrane, where it is converted into tetrahydrocannabinol ("THC"). This active form of SBI-100 OE is able to bind and activate CB1 receptors in key ocular tissues, which may help to lower intraocular pressure in patients suffering from glaucoma and ocular hypertension.

Past studies have shown that activation of the CB1 receptor using THC is able to notably reduce intraocular pressure, but not without psychotropic and other side effects. SBI-100 OE’s novel molecular structure and proprietary nanoemulsion eyedrop formulation was designed to enable topical delivery and enhance bioavailability of a CB1 agonist in ocular tissue. In preclinical studies involving three different species, SBI-100 OE lowered IOP to a level and duration that compared favorably to the standard of care for treating glaucoma. Skye’s Phase 1 study of SBI-100 OE showed that the drug was safe and well-tolerated, with no psychotropic effects, and provided an encouraging preliminary indication of IOP-lowering in a subset of healthy volunteers with higher baseline IOP.