Late-stage Pre-clinical Development and GMP Production of a First-in-Class Extended Release IOP-lowering Formulation

Glaucoma is a multifactorial, polygenetic disease that is the leading cause of irreversible blindness worldwide. Trends predict that by 2040, ~112 million people worldwide will have glaucoma, and many of those will be legally blind. Several risk factors are known for this disease, with elevated intraocular pressure (IOP) and fluctuations in IOP being the only modifiable risk factors linked to the development and progression of visual field loss. Because of the critical role played by IOP, the current standard of care for adult-onset glaucoma includes treatment with IOP-lowering medications that are delivered topically as eye drops. Unfortunately, notwithstanding the convenience of instilling eye drops at home, patient adherence is a major challenge making it essential that topical dosage forms be engineered to mitigate side effects and eliminate IOP fluctuations. A market-based comparison has identified multiple issues with current glaucoma medications, the most significant of which are: 1) limited options for different drug classes/mechanisms of action that are needed when tolerance to treatment develops; 2) lack of sustained IOP-lowering action, thus requiring many patients to apply eye drops 2-3 times daily to avoid IOP fluctuations, which are now known to be highly deleterious; and 3) side effects¾intolerable orbital and systemic discomfort and hyperemia, iris pigmentation changes¾that contribute to poor patient compliance. We have identified a new druggable target for the treatment of glaucoma, as well as a highly promising drug and formulation to address all the above listed pain points and unmet needs. Previous support from NIH SBIR Phase 1 and R24 awards to the OculoTherapy team allowed us to make excellent progress on the optimization of a novel, topical IOP-lowering formulation, which addresses all the major limitations listed above. Our formulation is engineered to be bioadhesive with extended-release properties. In addition, it is well-tolerated, based on the outcomes of a non-GLP 7-day repeat-escalating dose exploratory toxicity study. Moreover, IOP fluctuations are eliminated, beginning with the first topical application, and the effectiveness has not waned after 8 months of daily dosing. The active pharmaceutical ingredient ¾pregabalin (PRG)¾represents a new IOP-lowering drug class and provides an additional therapeutic option when current treatments fail. Because PRG is a safe and efficacious drug, our regulatory strategy is streamlined. Our patent portfolio is robust and relies of composition of matter and use patents. Importantly, via a June 2023 Type-B pre-IND meeting with the FDA, OculoTherapy obtained agreement for our regulatory strategy, plan and pathway to IND and NDA approvals. Specifically, because of the extensive systemic safety data that is available on PRG, the FDA has agreed to allow OculoTherapy to pursue a 505(b)(2) regulatory pathway, which will save both time and cost. This Phase II SBIR application was crafted specifically to perform the IND-enabling studies required by the FDA prior to submission of our first-in-human Phase IIa IND application, a critical step to establish our PRG-ME as a therapeutic agent for glaucoma.