As anyone who has had an eye injury, or even a small foreign object in the eye, knows-the cornea and surrounding structures are exquisitely sensitive to physical trauma. Ocular pain can be agonizing, paralyzing and extremely distressing to both the affected person, and particularly in the case of pediatric cases, family members who may feel powerless to help. Surprisingly, even emergency response personnel and specialized ophthalmologists are also largely ill equipped to manage acute or chronic eye-pain, as there are no appropriate analgesic options available for clinical use. While this is a problem for both affected adults (including armed forces personnel) and children, this grant submission will focus on the development of specific formulations of Sarentis compounds developed for managing acute and sub- acute eye pain. We will outline the scope of the clinical problem, describe the current medications available for pain relief, and then give the scientific and pre-clinical rationle for the development of these unique neuropeptide compounds with highly favorable pain control and toxicity profiles. This application seeks funds to develop the necessary delivery vehicles and formulation, with the desirable properties of agent delivery, product stability, lack of irritation, shelf life, and overall clinical acceptability. Success in this will open the door to definitive toxicology and clinical trial studies, followed by commercialization.
Eye pain: By far the most the most frequent cause of serious eye pain is trauma, caused by a variety of situations. Remarkably, there are no good ways to manage eye pain today, a situation that can be literally excruciating to children with eye injury and their often frantic parents. The Sarentis small-molecule-based pharmaceuticals described below represent a completely new approach to ophthalmic pain relief that can be used to manage pain associated with eye emergencies and routine injuries. In contrast, conventional analgesic drugs given by mouth or by IV are largely ineffective for treating severe corneal pain, as the cornea is avascular and equilibrates slowly and inefficiently with compounds in circulation. Existing topical (local) anesthetics like lidocaine are highly effective in eliminatin pain. However, and unfortunately, they are highly toxic to corneal cells and can be used only briefly during surgery or emergency care. Consequently, there are no truly successful acute or long-term therapies for eye pain currently available. In fact, there is not one word on the topic i the AMA Pediatric Pain Management CME document 1. Importantly, and unlike other agents, the Sarentis peptides applied topically do not impair the healing process. Impaired healing can lead to delayed wound closure, infections, scarring, hazing in the corneal, inflammation and potential loss of vision. Because of their lack of toxicity, the Sarentis peptides can be applied repeatedly to provide extended periods of pain control. This potential to relieve human (and animal) suffering and the lack of existing commercial alternatives suggest that Sarentis is well positioned to successfully address an unmet, significant, global need. Substantial basic and preclinical data support the potential utility of the neuropeptide approach. The next essential step is to develop appropriate formulations and delivery vehicles to take these compounds ahead to definitive toxicology and Phase I clinical trials.