First in Class Mitochondrially targeted antioxidants with transcriptional modulator capabilities and their implication in the diseases of the eye

Dry Eye Disease (DED) affects 20% of the global adult population, with higher rates in developed countries like the USA. It significantly impacts quality of life, productivity, increases healthcare costs, and can lead to vision loss if untreated. Current therapies are incapable of addressing chronic DED as they cannot be used long-term due to their toxicity. Our innovative First-In-Class mitochondrial technology targets the root cause of DED by addressing oxidative stress and mitochondrial dysfunction, which induces Meibomian Gland Dysfunction (MGD), a predominant cause of DED. Due to its unique mechanism of action, our drug candidate is safe for long-term use and offers a broader therapeutic window. This noninvasive treatment promises to revolutionize eye care and provide a sustainable solution to this widespread health challenge. Our proprietary small molecule lead candidate exhibits dose dependent free radical scavenging potential with calculated IC50 of 2.1µM and was found to protect various ocular cell lines against oxidative stress. It was found to be highly efficacious in reducing Benzalkonium chloride induced dry eye, tissue damage and vascularization in mice model of dry eye. An ophthalmic safety study suggests that an acute TID dose of our candidate as eye drops up to 30 µg/eye (total dose of 90 µg/eye/day) was well tolerated in New Zealand White rabbits. We have secured our invention by the filing of patent applications in the USA (US2021163159081), China (CN2280008594), India (IN202317001652), Canada (CA3205099A1), EU (EP22767950.3), Brazil (BR 1120230181097), Australia (AUS 2022234307) and Japan (JP2023-555226) for compounds, compositions, and their method of use. The novelty of our invention is confirmed by a written opinion from USPTO and an enhanced freedom to operate searches by qualified patent attorneys. DED is a multifactorial indication; therefore, in proposed SBIR phase I, our proposed studies entail In vivo characterization of lead candidates in desiccating stress/scopolamine (DSS) model of DED in mice working through varied etiologies. We also propose to evaluate the toxicity of our lead in repeated dose 7-day rabbit model of toxicity with PK parameters and local biodistribution in eye tissues of rabbits. Successful completion of proposed studies will be followed by submission of a phase-II SBIR to conduct a set of IND-enabling pre-clinical studies, manufacturing process scaleup and development, and analytical method validation, GLP toxicity studies with recovery group. Setup of in-house eCTD software interface and electronic submission gateway (ESG) with FDA and relevant certifications of personnel and workstation infrastructure will also be included in the SBIR phase-II application. We have assembled an experienced team consisting of chemists, drug discovery and bench to bedside drug product development experts, pharmacologists, ocular pharmacokinetics, toxicologists, ophthalmologists, regulatory experts, and industry partners. We are confident of successfully completing the proposed work.