IND-enabling Preclinical Development of Sustained Release Inner Ear Delivery of Corticosteroid

PROJECT SUMMARY Autoimmune inner ear disease (AIED) is the name given to describe a disorder where the ear is the target of an overactive immune system, causing symptoms of progressive hearing loss and/or dizziness. Most cases of AIED are accompanied by hearing loss and tinnitus that occur over a course of a few months1,2 that progresses rapidly to the second ear, indicative of AIED.3 There are currently no FDA-approved medications for the treatment of AIED, or any type of inner ear hearing loss. The use of high dose oral or intratympanic injection corticosteroids to suppress immune function is the most common treatment for AIED. However, the use of high doses of corticosteroids leads to significant side effects. In response to this unmet medical need, O-Ray Pharma has developed a lead formulation of sustained-release fluticasone pellets (OR-102) for the treatment of AIED that will provide a consistent low dose of corticosteroid to the cochlea over a period of three months. The pellet is implanted directly into the cochlea and releases steroid at the affected site to protect against hearing loss. The OR-102 formulation has demonstrated its safety, pharmacokinetics (PK), and efficacy in multiple guinea pig studies. To test the safety and preliminary efficacy of OR-102 in a first-in-human clinical trial in AIED-affected patients, O-Ray Pharma has submitted an IND application to the FDA. The FDA provided tacit approval of the majority of the application save for a request to perform an additional animal study and suggestions for additional Chemistry/Manufacturing/Control (CMC) work. In response, there were no clinical holds pertaining to the clinical protocol and the chemistry/manufacturing/controls procedures. Thus, the IND is on clinical hold pending the completion of a Good Laboratory Practices (GLP) compliant toxicity and pharmacokinetics study. This IND correspondence has provided us with a clear framework towards an IND allowance. The Specific Aims of this Direct to Phase II proposal are, therefore, to complete the following IND-enabling activities: 1) Drug product manufacturing in accordance with current Good Manufacturing Practices (cGMP) for animal and human trials; 2) Performance of a GLP-compliant guinea pig study as guided by FDA feedback, 3) Preparation and submission of an IND response. The milestone for the successful completion of this grant will be the granting of an IND approval. The team of investigators at O-Ray is uniquely qualified to perform the work proposed herein, and has expertise in otology, regulatory affairs, and business development. O-Ray’s scientists have successfully developed other therapeutic formulations from concept to FDA approval, including an intraocular sustained- release steroid implant capable of maintaining anti-inflammatory intravitreal drug levels for up to three years from a single implantation. O-Ray’s management has previously out-licensed three drug delivery products to larger pharmaceutical companies upon demonstration of proof-of-concept in the target patient populations.