Ocular Therapeutix
Overview
Ocular Therapeutix (OCUL) is a biopharmaceutical company focused on the development and commercialization of innovative therapies for diseases and conditions of the eye using its proprietary hydrogel platform technology. Its bioresorbable hydrogel-based drug product candidates are designed to provide extended delivery of therapeutic agents to the eye. Its lead product candidates are DEXTENZA (dexamethasone insert), for the treatment of post-surgical ocular inflammation and pain, allergic conjunctivitis and dry eye disease, and OTX-TP, for the treatment of glaucoma and ocular hypertension, which are extended-delivery, drug-eluting inserts that are placed into the canaliculus through a natural opening called the punctum located in the inner portion of the eyelid near the nose. Its intracanalicular inserts combine its hydrogel technology with U.S. Food and Drug Administration, or FDA, approved therapeutic agents with the goal of providing extended delivery of drug to the eye. Ocular also has a preclinical product development candidate that is injected into the front of the eye intracamerally for the treatment of glaucoma. Ocular also has an intravitreal hydrogel depot which is in preclinical development for the treatment of diseases and conditions of the back of the eye including wet age-related macular degeneration, or wet AMD. Its initial development efforts are focused on the use of its hydrogel depot in combination with anti-angiogenic drugs, such as protein-based anti-VEGF drugs, or small molecule drugs, such as tyrosine kinase inhibitors, or TKIs. Its intravitreal depot is designed to be delivered via intravitreal injection to release therapeutic agents, such as antibodies to vascular endothelial growth factor, or VEGF, over a sustained period. Ocular has entered into a collaboration with Regeneron Pharmaceuticals, Inc., or Regeneron, for the development and potential commercialization of products containing its extended-delivery hydrogel depot in combination with Regeneron’s large molecule VEGF-targeting compounds, with the initial focus on the VEGF trap aflibercept, currently marketed under the brand name Eylea. In addition to its ongoing product development, Ocular currently market its first commercial product, ReSure Sealant, a hydrogel-based ophthalmic wound sealant approved by the FDA to seal corneal incisions following cataract surgery. ReSure Sealant is the first and only surgical sealant to be approved by the FDA for ophthalmic use.1
DEXTENZA
Ocular's most advanced product candidate, DEXTENZA, incorporates the FDA-approved corticosteroid dexamethasone as an active pharmaceutical ingredient into a hydrogel-based drug-eluting insert for intracanalicular use. In September 2015, Ocular submitted to the FDA a New Drug Application, or NDA, for DEXTENZA for the treatment of post-surgical ocular pain. In July 2016, Ocular received a Complete Response Letter, or CRL, from the FDA regarding its NDA for DEXTENZA. This CRL pertained to deficiencies in manufacturing process and controls identified during a pre-NDA approval inspection of its manufacturing facility. In January 2017, Ocular resubmitted its NDA. Following a re-inspection of manufacturing operations by the FDA which was completed in May 2017, Ocular received an FDA Form 483 containing inspectional observations focused on procedures for manufacturing processes and analytical testing related to the manufacture of drug product for commercial production. In July 2017, Ocular received a CRL from the FDA regarding its NDA for DEXTENZA for the treatment of post-surgical ocular pain. This 2017 CRL refers to deficiencies in manufacturing processes and analytical testing related to manufacturing of drug product identified during the pre-NDA approval inspection and states that the FDA has determined that it cannot approve the NDA in its present form. Ocular has corresponded with the FDA regarding these inspectional observations and are working to resolve the issues that have been identified, including the presence of particulate matter in certain manufactured lots of DEXTENZA. Following up on its initial response to the Form 483 in May 2017, the company continue to provide the FDA with updates on its corrective actions in an effort to close out the Form 483 deficiencies. Subject to the closing out of the Form 483, including process qualification which the company believe will require consistently producing commercial lots, the company plan to resubmit its NDA for DEXTENZA for the treatment of post-surgical ocular pain. Adequate resolution of the outstanding Form 483 inspectional observations with the FDA New England District Office is a prerequisite to the approval of the NDA for DEXTENZA, although the final decision as to the adequacy of its manufacturing processes is made by the FDA’s Center for Drug Evaluation and Research, or CDER, with input from CDER’s Office of Process and Facilities, as part of the NDA review process.
Ocular has completed three Phase 3 clinical trials of DEXTENZA for the treatment of post-surgical ocular inflammation and pain. The data from two of these three completed Phase 3 clinical trials and a prior Phase 2 clinical trial are being used to support its NDA for post-surgical ocular pain. Subject to receiving approval for the pain indication pursuant to its NDA, the company plan to submit an NDA supplement, or sNDA, for DEXTENZA for the treatment of post-surgical ocular inflammation. Ocular has also completed two Phase 3 clinical trials of DEXTENZA for the treatment of allergic conjunctivitis. In October 2015, the company announced topline results of its first Phase 3 clinical trial for allergic conjunctivitis, and in June 2016 the company announced topline results of its second Phase 3 clinical trial for this indication. Finally, DEXTENZA is in Phase 2 clinical development for the treatment of dry eye disease. Ocular announced topline results from Phase 2 clinical trial for this indication in December 2015. Ocular is assessing its plans for its dry eye program going forward and may focus future efforts on an intracanalicular insert containing an immunosuppressant drug.
OTX-TP
Ocular's second product candidate, OTX-TP, incorporates travoprost, an FDA-approved prostaglandin analog that reduces elevated intraocular pressure, or IOP, as its active pharmaceutical ingredient, into a hydrogel-based drug-eluting intracanalicular insert. OTX-TP is being developed as a treatment for glaucoma and ocular hypertension. The company reported topline results from a Phase 2b clinical trial for this indication in October 2015. The company completed an End-of-Phase 2 review with the FDA in April 2016 and initiated the first of two Phase 3 clinical trials of OTX-TP in September 2016. Ocular expect topline efficacy data from the first Phase 3 clinical trial in the second half of 2018. Ocular plan to initiate the second Phase 3 clinical trial in 2017.
Intracameral Glaucoma (OTX-TIC) Product Candidate
Ocular is conducting preclinical development of OTX-TIC, its product candidate, for the treatment of patients with moderate to severe glaucoma and ocular hypertension. OTX-TIC (extended-delivery travoprost) is a bioresorbable hydrogel insert incorporating travoprost that is designed to be an intracameral injection into the anterior chamber of the eye with an initial target duration of drug release of three to four months. Preclinical studies to date have demonstrated clinically meaningful intraocular pressure lowering and good pharmacokinetics in the aqueous humor. Ocular expect to initiate a pilot clinical study outside the United States in 2017 to assess safety and obtain initial efficacy data. The study is expected to be a prospective, single-center, randomized, double-masked, sham-controlled study to evaluate the safety, efficacy and tolerability of OTX-TIC compared to topical travoprost (eye drops) in up to 20 patients with open-angle glaucoma or ocular hypertension. If the results from this trial are promising, the company plan to advance to a Phase 2 clinical development program in the United States.
Back-of-the-Eye Programs
In addition to DEXTENZA and OTX-TP, the company IS engaged in the preclinical development of its hydrogel depot administered via intravitreal injection to address the large and growing markets for diseases and conditions of the back of the eye. Its initial development efforts are focused on the use of its extended-delivery hydrogel depot in combination with anti-angiogenic drugs, such as protein-based anti-VEGF drugs or small molecule drugs, such as TKIs, for the treatment of retinal diseases such as wet AMD, retinal vein occlusion and diabetic macular edema. Its initial goal for these programs is to provide extended delivery of a protein-based large molecule or small molecule TKI drug targeting VEGF and other targets over a four to six month period following administration of a bioresorbable hydrogel incorporating the drug by an injection into the vitreous humor, thereby reducing the frequency of the current monthly or bi-monthly intravitreal injection regimen for wet AMD and other retinal diseases and potentially providing a more consistent uniform release of drug over the treatment period.
OTX-TKI
OTX-TKI is a preformed, bioresorbable hydrogel fiber depot with anti-angiogenic properties delivered by intravitreal tyrosine kinase inhibitor injection. TKIs have shown promise in the treatment of wet AMD. Currently OTX-TKI is under initial preclinical investigation as a novel extended release drug product candidate. In May 2017, Ocular reported data from preclinical studies evaluating the efficacy, tolerability and pharmacokinetics of its OTX-TKI depot. In this study, the OTX-TKI depot was well-tolerated, and high tissue levels of TKI were maintained for up to 6 months in Dutch belted rabbits. Ocular plan to initiate a Phase 1 clinical trial to assess whether its OTX-TKI depot might deliver TKI to the posterior segment of the human eye for the treatment of VEGF induced retinal leakage for an extended duration later in 2017.
Regeneron Collaboration
In October 2016, the company entered into a strategic collaboration, option and license agreement, or the Collaboration Agreement, with Regeneron for the development and potential commercialization of products containing its extended-delivery hydrogel depot in combination with Regeneron’s large molecule VEGF-targeting compounds for the treatment of retinal diseases, with the initial focus on the VEGF trap aflibercept, currently marketed under the brand name Eylea. The Collaboration Agreement does not cover the development of any products that deliver small molecule drugs, including TKIs, for any target including VEGF, or any products that deliver large molecule drugs other than those that target VEGF proteins. Ocular granted Regeneron an option, or the Option, to enter into an exclusive, worldwide license under its intellectual property to develop and commercialize products containing its extended-delivery hydrogel depot in combination with Regeneron’s large molecule VEGF-targeting compounds, or Licensed Products.
If the Option is exercised, Regeneron will conduct further preclinical development and an initial clinical trial under a collaboration plan. Ocular is obligated to reimburse Regeneron for certain development costs during the period through the completion of the initial clinical trial, subject to a cap of $25 million, which cap may be increased by up to $5 million under certain circumstances. Regeneron will be responsible for funding an initial preclinical tolerability study. Ocular do not expect its funding requirements to be material over the next twelve months. If Regeneron elects to proceed with further development beyond the initial clinical trial, it will be solely responsible for conducting and funding further development and commercialization of product candidates.
Under the terms of the Collaboration Agreement, Regeneron has agreed to pay US $10 million upon exercise of the Option. Ocular is also eligible to receive up to $145 million per Licensed Product upon the achievement of specified development and regulatory milestones, including successful results from the first-in-human clinical trial, $100 million per Licensed Product upon first commercial sale of such Licensed Product and up to $50 million based on the achievement of specified sales milestones for all Licensed Products. In addition, Ocular is entitled to tiered, escalating royalties, in a range from a high-single digit to a low-to-mid teen percentage of net sales of Licensed Products.
ReSure
Following its receipt of FDA approval for ReSure Sealant, Ocular commercially launched this product in the United States in 2014, initially through a network of ophthalmology-focused distributors. In early 2017, Ocular terminated these distributors and hired a contract sales force of four representatives to sell ReSure Sealant. ReSure Sealant is approved to seal corneal incisions following cataract surgery and is the first and only surgical sealant to be approved by the FDA for ophthalmic use. In the pivotal clinical trials that formed the basis for FDA approval, ReSure Sealant provided superior wound closure and a better safety profile than sutured closure.
Additional Potential Areas for Growth
In addition to its focus on developing and commercializing innovative therapies for diseases and conditions of the eye, Ocular is also assessing the future growth potential of the hydrogel platform technology in new areas of the body. In order to properly evaluate and then execute upon any applications beyond the field of ophthalmology, Ocular would need to negotiate and enter into an amendment to its existing license agreement with Incept, LLC, or Incept, or a new license agreement with Incept covering one or more additional such fields of use.