ART27.13 Phase II: Novel Oral Cannabinoid Enters Uncharted Territory Against Generic-Dominated Glaucoma Market

Artelo Doses First Patient in Phase II Glaucoma Study

Artelo Biosciences has initiated its Phase II DREAM study, dosing the first patient with ART27.13 for glaucoma or ocular hypertension. The study, sponsored by Belfast Health and Social Care Trust and funded by Glaucoma UK and HSC R&D, aims to evaluate if orally administered ART27.13, a synthetic cannabinoid, can effectively influence intraocular pressure by targeting cannabinoid receptors in eye tissue. This peripherally selective design is intended to mitigate CNS adverse effects commonly associated with other cannabinoid treatments for this indication. Initial results are anticipated later this year.

• ART27.13 is an orally administered, peripherally selective synthetic cannabinoid receptor agonist and dual cannabinoid agonist. Initially developed by AstraZeneca, this benzimidazole derivative has undergone seven prior clinical studies involving over 280 participants, demonstrating its established safety profile.
• The Phase II DREAM study is designed to assess ART27.13's ability to influence intraocular pressure via cannabinoid receptors in eye tissue. It is sponsored by the Belfast Health and Social Care Trust, with research operations managed by the Northern Ireland Clinical Trials Unit, and receives funding from Glaucoma UK and the Health and Social Care research and development (HSC R&D) division.
• The study holds potential to validate the role of an orally active cannabinoid in managing intraocular pressure, specifically leveraging ART27.13's peripherally selective design to overcome CNS adverse effects observed with other cannabinoid therapies. Artelo Biosciences anticipates announcing initial results from the DREAM study later in the current year.

Addressing the Unmet Needs in Glaucoma Treatment

Current glaucoma management remains constrained by a fundamental overreliance on intraocular pressure (IOP) reduction as the primary therapeutic target, despite growing recognition that the disease's pathophysiology extends well beyond elevated IOP. No curative therapies exist, and glaucoma continues to be the second leading cause of blindness worldwide — underscoring the critical gap between available interventions and true disease control.

• IOP-centric paradigm with limited scope: IOP reduction remains the only clinically validated treatment modality, yet elevated IOP is no longer considered a defining diagnostic criterion for glaucoma. A subset of patients shows disease progression independent of IOP elevation, highlighting the inadequacy of therapies — pharmacological, laser, or surgical — that address only this single parameter.

• Failure to prevent progressive neurodegeneration: Existing IOP-lowering treatments frequently fail to halt the progressive loss of retinal ganglion cells (RGCs) and their axons that characterizes glaucomatous optic neuropathy. No approved therapy currently targets RGC neuroprotection, axonal repair, or restoration of structural and functional connectivity.

• Preservative-related ocular surface toxicity: Chronic topical hypotensive agents commonly formulated with benzalkonium chloride (BAC) are associated with conjunctival inflammation and fibrosis, tear film instability, corneal cytotoxicity, trabecular meshwork cell apoptosis, anterior chamber inflammation, cataract development, and macular edema. Ocular surface disease resulting from preservative exposure can directly impair IOP-lowering efficacy and negatively affect patient adherence and compliance.

• Surgical risk and corneal compromise: Glaucoma surgical interventions carry meaningful risks of corneal endothelial damage. Clinical data indicate endothelial cell loss of approximately 9.6% at 12 months following trabeculectomy, reflecting the potential for lasting iatrogenic corneal injury.

• Unaddressed multifactorial etiology: The complex, multifactorial nature of glaucoma creates an urgent need for novel therapeutic strategies focused on preventing or retarding RGC death and facilitating axonal repair — areas where current treatment options remain essentially absent.

The Evolving Landscape of Glaucoma Therapies

The treatment landscape for glaucoma has undergone substantial transformation over the past five years, driven by landmark trial data across laser therapy, surgical innovation, and drug delivery. The LiGHT trial's six-year data have been particularly influential, establishing selective laser trabeculoplasty (SLT) as a viable first-line therapy rather than an adjunctive intervention. At six years, 69.8% of eyes in the SLT arm remained at or below target intraocular pressure (IOP) without medical or surgical escalation, and disease progression was significantly less frequent compared to topical therapy (19.6% vs. 26.8%, P = 0.006). The SLT arm also required markedly fewer trabeculectomies (13 vs. 32 eyes, P < 0.001) and cataract surgeries (57 vs. 95 eyes, P = 0.03) over the same period, with no serious laser-related adverse events recorded. These findings directly address the longstanding challenge of medication non-adherence by reducing dependence on daily topical regimens.

Minimally invasive glaucoma surgery (MIGS) has matured considerably, with longer-term efficacy and safety data now informing device selection. Five-year results from the HORIZON trial demonstrated that the Hydrus Microstent combined with cataract surgery achieved IOP ≤18 mmHg without medications in 49.5% of eyes versus 33.8% with cataract surgery alone (P = 0.003), with 66% of the Hydrus group remaining medication-free compared to 46% of controls (P < 0.001) and a lower cumulative risk of incisional glaucoma surgery (2.4% vs. 6.2%, P = 0.027). Comparative safety analyses across device classes have, however, revealed important distinctions in corneal endothelial impact. While the iStent inject showed no significant differences in endothelial cell density versus controls through five years, the Hydrus demonstrated greater endothelial cell loss (20.8% vs. 10.6%, P = 0.01), and the CyPass showed the highest rates (27.2% vs. 10.0%, P = 0.02), with seven eyes developing associated complications — findings that have meaningfully influenced post-market device positioning.

Sustained-release and novel topical pharmacotherapies represent a third pillar of this evolving landscape. Two intracameral implants have received FDA approval: a biodegradable bimatoprost implant offering continuous drug release for four to six months — with IOP-lowering effects persisting up to two years in 25% of patients — and a non-biodegradable travoprost implant providing medication delivery over 36 months, with 81% of patients remaining medication-free. Real-world data from 118 eyes confirmed meaningful IOP reduction following bimatoprost sustained-release implantation (18.5 ± 5.7 mmHg vs. 16.0 ± 5.4 mmHg, P < 0.01) alongside a significant decrease in concomitant medication burden (2.1 ± 1.4 vs. 1.2 ± 1.2, P < 0.01). Complementing these advances, three novel topical agents have entered the market — latanoprostene bunod 0.024%, netarsudil 0.02%, and the fixed combination of netarsudil-latanoprost — each targeting distinct outflow pathways. Latanoprostene bunod, a nitric oxide-donating prostaglandin analog acting on both trabecular and uveoscleral routes, demonstrated a mean IOP reduction of 2.5 ± 3.3 mmHg (P < 0.0001) at a mean follow-up of approximately 236 days, with pressure decreasing by ≥2 mmHg in 60% of treated eyes. Collectively, these developments signal a clear strategic shift toward therapies that reduce the daily medication burden, improve long-term disease control, and broaden individualised management options for this chronic condition.