OC-01 Nasal Spray for Treatment of the Signs and Symptoms of Dry Eye Disease

Dry Eye Disease

Dry Eye Disease (DED) is a multifactorial chronic disease of the ocular surface characterized by a loss of homeostasis of the tear film, resulting in pain, visual impairment, tear film hyperosmolarity and instability, inflammation, and corneal wounding. Patients with DED are also more susceptible to eye infections and damage to the surface of the eye (cornea). DED is characterized by a reduction in tear volume, rapid breakup of the tear film, and/or an increase in the evaporative properties of the tear film layer. DED affects daily life, including reading and driving at night and has been associated with depression and migraines. Underlying DED can limit patients’ ability to tolerate contact lenses and impacts patient satisfaction with post-op cataract and refractive patients. Despite the large prevalence of dry eye and the burden of the disease, there remains a significant unmet need for effective therapies.

Normal Tear Film Production

Human tear film is a complex mixture of more than 1,500 different proteins, including antibodies and numerous classes of lipids and mucins that are responsible for forming the primary refracting surface of the cornea, as well as, protecting and moisturizing the cornea.

The LFU, which is controlled by the parasympathetic nervous system, is comprised of Meibomian glands, lacrimal glands, and goblet cells that are responsible for producing the three layers that comprise healthy tear film. The National Eye Institute defines healthy tear film as “a complex mixture of fatty oils, water, mucus, and more than 1,500 different proteins that keep the surface of the eye smooth and protected from the environment, irritants, and infectious pathogens.” The outermost layer of tear film is a lipid layer produced by the Meibomian glands that keeps tear film from evaporating too quickly. The lacrimal glands produce the aqueous layer, which comprises the bulk of tear volume and flow. This middle layer is not just water – it contains thousands of proteins, enzymes, antibodies and growth factors that are cytoprotective, anti-inflammatory, and anti-microbial. The aqueous layer nourishes the cornea and the conjunctiva, the mucous membrane that covers the entire front of the eye and the inside of the eyelids. Finally, the innermost mucin layer is produced by goblet cells and binds water from the aqueous layer to ensure that the eye remains wet. The LFU receives stimulus from the trigeminal nerve, which has sensory nerve endings in the nasal cavity.

LFU

OC-01

Our lead product candidate, OC-01, a highly selective nicotinic acetylcholine receptor (nAChR) agonist, is being developed as a preservative free nasal spray to treat the signs and symptoms of dry eye disease. The parasympathetic nervous system, the “rest and digest” system of the body, controls tear film homeostasis partially via the trigeminal nerve which is accessible within the nose. Administered as a preservative-free nasal spray, OC-01’s novel mechanism of action activates the trigeminal parasympathetic pathway to promote natural tear film production. We believe that increasing tear film volume and re-establishing tear film homeostasis will address the fundamental characteristic of DED, regardless of etiology, and has the potential to treat a broad population of patients throughout the dry eye continuum. Based on OC-01’s safety and efficacy results to date, combined with its rapid onset of action, we believe OC-01 has the potential to become the standard of care and redefine how dry eye disease is treated for millions of patients.

How it Works

To activate the LFU, we are targeting a class of receptors called nicotinic acetylcholine receptors (nAChR) that are located on the trigeminal nerve and readily accessible within the anterior nasal cavity. OC-01 is a highly selective nAChR agonist. Administered as a preservative-free nasal spray, OC-01’s novel mechanism of action stimulates the trigeminal parasympathetic pathway to activate natural tear film production.

Our Pipeline

Leveraging our nAChR domain expertise, we continue to explore the development of OC-01 for a number of potential indications and uses associated with and beyond DED including dry eye associated with contact lens intolerance, and ocular surface preparation for refractive surgeries. We have also developed and studied OC-02 (simpanicline), in two Phase 2b clinical trials for DED. We believe that targeting the parasympathetic nervous system through the use of locally administered cholinergic agonists has the potential to treat a wide range of diseases and disorders.