About Ocular Therapeutix

Ocular Therapeutix, Inc. operates as a biopharmaceutical company. The company focuses on the formulation, development, and commercialization of innovative therapies for diseases and conditions of the eye using its proprietary bioresorbable hydrogel-based formulation technology. The company’s products and product candidates in clinical development incorporate therapeutic agents that have previously received regulatory approval from the U.S. Food and Drug Administration, or FDA, including small molecules, into the company’s proprietary bioresorbable hydrogel-based formulation technology in the company’s internal drug development activities, with the goal of providing local programmed release to tailor the duration and amount of drug to be delivered to the eye. The company’s local programmed-release drug delivery technology has the potential to enable the treatment of conditions and diseases of both the front and the back of the eye and can be administered through a range of different modalities, including intravitreal implants, intracameral implants and intracanalicular inserts. The company is commercializing DEXTENZA, an intracanalicular insert for the treatment of both post-surgical ocular inflammation and pain and ocular itching associated with allergic conjunctivitis, in the United States. The company also has product candidates in preclinical and clinical development: OTX-TKI, an axitinib intravitreal implant being developed for the treatment of wet age-related macular degeneration, or wet AMD, diabetic retinopathy and other retinal diseases; OTX-TIC, a travoprost intracameral implant being developed for the reduction of intraocular pressure, or IOP, in patients with primary open-angle glaucoma or ocular hypertension; OTX-DED, a dexamethasone intracanalicular insert being developed for the short-term treatment of the signs and symptoms of dry eye disease; OTX-CSI, a cyclosporine intracanalicular insert being developed for the chronic treatment of dry eye disease; A complement inhibitor program in preclinical development for the treatment of dry age-related macular degeneration, or dry AMD; and A gene delivery program in preclinical development using the company’s hydrogel technology to control the release of vectors, such as adeno-associated virus , or AAV, to ocular tissues for the treatment of inherited and acquired ocular diseases, including dry or wet AMD. The company focuses on some of the largest markets in ophthalmology. The company holds worldwide exclusive commercial rights to the core technology underlying all of the company’s product candidates in development and has not granted commercial rights to any marketing partners other than a license agreement and collaboration with AffaMed for the development and commercialization of DEXTENZA and OTX-TIC in the geographies agreed to between the parties. Strategy The company’s strategy is to continue to build upon its experience in commercializing ophthalmology products that can be administered primarily in the surgical and/or office settings and to continue to develop a clinical pipeline of innovative ophthalmology products that address large areas of unmet need. The key tactics of the company’s strategy are to grow DEXTENZA revenues primarily through sales for the treatment of ocular inflammation and pain following ophthalmic surgery; advance the company’s clinical development programs; leverage its commercial infrastructure for additional ophthalmology products for both the surgical and office settings; continue to develop experience and expertise with buy-and-bill products; apply the company’s local programmed-release hydrogel-based formulation technology to create additional proprietary solutions for additional ophthalmic diseases and conditions; and address rest-of-world commercial opportunities through licensing and collaboration agreements. The Ocular Therapeutix Approach Hydrogel-Based Formulation Technology The company applies its expertise with an established bioresorbable hydrogel-based formulation technology to the development of products for local programmed-release of known, FDA-approved therapeutic agents for a variety of ophthalmic diseases and conditions and to ophthalmic wound closure. The company’s bioresorbable hydrogel-based formulation technology is based on the use of a proprietary form of PEG. The company’s technical capabilities include a deep understanding of the polymer chemistry of PEG-based hydrogels and the design of the highly specialized manufacturing processes required to achieve a reliable, preservative-free and pure product. The company tailors the hydrogel to act as a vehicle for local programmed-release drug delivery to the eye and as an ocular tissue sealant. The company creates its hydrogels by cross-linking PEG molecules to form a network that resembles a three-dimensional mesh on a molecular level. The company’s PEG molecules are branched, with four to eight branches or arms. Each arm bears a reactive site on its end. The company’s cross-linking chemistry uses a second molecule with four arms, bearing complimentary reactive sites on each end, such that when combined with the PEG molecules, a network spontaneously forms. When swollen with water, this molecular network forms a hydrogel. The company designs these hydrogels to slowly degrade in the presence of water, a process called hydrolysis, by inserting a biodegradable linkage between the PEG molecule and the cross-linked molecule. By appropriately selecting the number of arms of the PEG molecule and the biodegradable linkage, the company can design hydrogels with varying mechanical properties and bioresorption rates. Because the body has an abundance of water at a constant temperature and pH level, hydrolysis provides a predictable and reproducible degradation rate. The company’s technology enables it to make hydrogels that can bioresorb over days, weeks or months. The company selects the active pharmaceutical ingredients for its local programmed-release drug delivery product candidates based on criteria the company has developed through its extensive experience with hydrogel-based technologies. The company considers the following selection criteria: prior approval by the FDA for the targeted ophthalmic indication, except for the company’s OTX-TKI program in which the active pharmaceutical ingredient, axitinib, is not approved for an ophthalmic indication; expiration of relevant patent protection prior to or within the company’s anticipated development timeline; high potency to minimize required drug load in the intracanalicular insert, intracameral implant or intravitreal implant; availability from a qualified supplier; and compatibility with the company’s drug delivery system. The company’s intracanalicular insert, intracameral implant and intravitreal implant products and product candidates may offer a range of favorable attributes as compared to eye drops and immediate release back-of-the-eye injections, including: Improved Patient Compliance: The company’s inserts and implants are placed by a healthcare professional and are designed to provide local programmed-release of drug to the ocular surface, intracameral space or intravitreal space. Because patients are not responsible for self-administration of the drug and the inserts and implants dissipate over time and do not require removal for acute conditions or frequent removal for chronic conditions, the company’s inserts and implants address the problem of patient compliance. Ease of Administration: The company has designed its inserts and implants to provide the entire course of medication with a single administration by a healthcare professional for acute conditions or for months for chronic conditions. This avoids the need for frequent administration, reducing the patient’s treatment burden and the likelihood of potential complications that could result if doses are missed. Local Programmed-release of Drug: The company has designed its inserts and implants to deliver drug in a programmed fashion in order to avoid the peak and valley dosing and related side effects and spikes in IOP associated with eye drops, as well as current standard of care injections for the back of the eye. Programmed-release dosing may improve the therapeutic profile of the active pharmaceutical ingredient because it eliminates periods of little or no drug presence between eye drop or back of the eye injection administrations. Further, the company is designing its products and product candidates so that their drug release profiles can be tailored or programmed to match the treatment needs of the disease. For example, steroids for ophthalmic purposes generally require administration over four weeks, with tapered dosing over this period. In contrast, PGAs require administration in a steady fashion over the duration of treatment. The company’s inserts and implants are designed to fully dissipate and can be removed if necessary by a healthcare professional. Avoidance of Preservative Side Effects: The company’s inserts and implants do not involve the use of preservatives, such as BAK, which have been linked to side effects, including burning, stinging, hyperemia, irritation, eye dryness and, less frequently, conjunctivitis or corneal damage. Intracanalicular Inserts The company’s intracanalicular inserts, including DEXTENZA, OTX-DED, and OTX-CSI, are designed to be inserted into the patient’s punctum by a healthcare professional and to release drug to the surface of the eye to address diseases, including ocular inflammation and pain following ophthalmic surgery, ocular itching associated with allergic conjunctivitis, and dry eye disease. The company’s intracanalicular inserts utilize its proprietary hydrogel-based formulation technology and are embedded with an active drug. Following insertion through the punctum, the company’s inserts swell in tear fluid to fill the vertical canaliculus, which secures the inserts in place. Over time, the inserts liquefy and are cleared through the nasolacrimal duct. If necessary due to excessive tearing, discomfort or improper placement, a healthcare professional can remove an intracanalicular insert by a process of pushing the soft insert back through the punctum. Intracameral Implants The company is engaged in the clinical development of the company’s hydrogel administered via intracameral injection to address glaucoma. Intracameral implants refer to biodegradable or bioresorbable implants placed into the anterior chamber or front of the eye for the treatment of ocular conditions. The implants are designed to be held in place by currents and gravity present in the anterior chamber of an eye. In the case of OTX-TIC, the implant is designed to infuse with liquid, settle into the inferior angle of the eye and demonstrate little to no movement. The implants are preferably polymeric, biodegradable and provide sustained release of at least one therapeutic agent to both the trabecular meshwork and associated ocular tissue and the fluids within the anterior chamber of an eye. Intravitreal Implants The company is engaged in the clinical development of its hydrogel administered via intravitreal injection to address the large and growing markets for diseases and conditions of the back of the eye. The company’s intravitreal implant product candidates, such as OTX-TKI, consist of a PEG-based hydrogel suspension, which contains embedded micronized particles of active drug. The company designs the intravitreal implant to be injected and retained in the vitreous humor to provide local programmed-release intravitreal delivery of anti-VEGF compounds. Retinal Disease Programs OTX-TKI (Axitinib Intravitreal Implant) The company’s product candidate OTX-TKI is a preformed, bioresorbable hydrogel fiber implant incorporating axitinib, a small molecule TKI with anti-angiogenic properties delivered by intravitreal injection and designed for a duration of six months or longer. The company is conducting a Phase 1 clinical trial in Australia and a Phase 1 clinical trial in the United States to evaluate OTX-TKI for the treatment of wet AMD. The company’s initial implants have delivered anti-VEGF compounds in vitro over a targeted nine to twelve month period, which could make it possible to reduce patients’ treatment burden by reducing the frequency of the current monthly or bi-monthly intravitreal injection regimen for wet AMD. The company is also conducting a Phase 1 clinical trial in the United States to evaluate OTX-TKI for the treatment of DR. Axitinib is well suited for use with the company’s platform given its high potency, multi-target capability, and compatibility with a hydrogel vehicle. In the absence of a sophisticated drug delivery system, TKIs have been difficult to deliver to the eye for acceptable time frames at therapeutic levels without causing local and systemic toxicity due to low drug solubility and very short half-lives in solution. The company’s local programmed-release drug delivery technology gives the company potential advantages in this regard. The company has conducted two Phase 1 trials of OTX-TKI for the treatment of wet AMD, with different formulations of axitinib. The company intends to move forward into pivotal trials with the company’s single 600 µg axitinib implant formulation of OTX-TKI for both the treatment of wet AMD and the treatment of diabetic retinopathy. As the company has previously disclosed, it is also developing a second formulation of OTX-TKI that could be used in future trials of retinal indications. Wet Age-Related Macular Degeneration (wet AMD) Phase 1 Clinical Trial (Australia) The company is conducting an open-label, multi-center, proof-of-concept, dose-escalation Phase 1 clinical trial of OTX-TKI for the treatment of patients with wet AMD caused by excessive blood vessel growth in the back of the eye due to VEGF. This Phase 1 clinical trial is designed to evaluate the safety, durability and tolerability of OTX-TKI. The Phase 1 clinical trial was submitted to the Therapeutic Goods Administration, Australia’s regulatory authority for therapeutic goods, in July 2018 and is being conducted at multiple sites in Australia. The company’s Phase 1 clinical trial of OTX-TKI in Australia is consisted of four cohorts consisting of subjects with pre-existing intraretinal and/or subretinal fluid: a lower dose cohort of 200 µg with six subjects; a higher dose cohort of 400 µg with seven subjects; a third cohort with two parallel arms, one arm of six subjects receiving a concomitant anti-VEGF injection with 400 µg of OTX-TKI and the other arm of six subjects receiving a 600 µg of OTX-TKI with no anti-VEGF injection; and a fourth cohort with two parallel arms, one arm of six subjects receiving a 600 µg single implant of OTX-TKI and the other arm of six subjects receiving a 600 µg single implant of OTX-TKI with anti-VEGF injection. In this trial, the company is evaluating whether OTX-TKI can reduce existing fluid levels. This trial’s enrollment is complete. The company plans to continue to follow subjects at least until their respective seventeen-month anniversaries of initial dosing, in accordance with the clinical trial protocol. In the Phase 1 clinical trial of OTX-TKI, the company is evaluating biological activity by measuring central subfield thickness, or CSFT, using spectral domain optical coherence tomography, or OCT, and following visual acuity over time as measured by Best Corrected Visual Acuity, or BCVA. In February 2022, interim data as of January 11, 2022 from this Phase 1 clinical trial of OTX-TKI was presented at the Angiogenesis, Exudation and Degeneration Virtual Symposium. In subjects with subretinal and/or intraretinal fluid due to wet AMD, OTX-TKI was observed to be generally well tolerated. In addition, the OTX-TKI implants in cohort 1 (single implant) were observed to have biodegraded in all subjects within nine to 10.5 months of injection. It has also been observed in the trial that the implants were able to be adequately monitored and that there was limited to no movement of the implant in the anterior segment of the eye. Phase 1 Clinical Trial (the United States) In July 2021, the company announced that it had dosed the first patient in a prospective, multi-center, randomized, controlled Phase 1 clinical trial in the United States under an exploratory investigational new drug, or eIND, application to evaluate a single implant 600 µg dose of OTX-TKI with an anti-VEGF injection in comparison with a 2 mg dose of aflibercept. The population the company is studying in this U.S.-based clinical trial is different than the population the company is studying in its ongoing Phase 1 clinical trial of OTX-TKI in Australia. In this trial, the company is evaluating how long the company is able to maintain subjects who have been previously treated with anti-VEGF therapy without the need for retreatment. In February 2023, the company announced interim 10-month data from the ongoing Phase 1 clinical trial of OTX-TKI in the United States at the Angiogenesis, Exudation, and Degeneration 2023 Annual Meeting. Regulatory Pathway The company is in active discussions with the FDA regarding the regulatory pathway for OTX-TKI for the treatment of wet AMD and potential future clinical trial requirements. Subject to those discussions and obtaining the necessary financing, which could be provided through a strategic alliance, the company intends to be prepared to initiate a pivotal clinical trial for the treatment of wet AMD in the third quarter of 2023. If the company was to obtain favorable results from two pivotal clinical trials, the company expects that it would submit an NDA under Section 505(b)(2) of the FDCA. Diabetic Retinopathy (DR) Phase 1 Clinical Trial Given the company’s belief in the potential applicability of OTX-TKI to other retinal diseases, the company initiated a Phase 1 U.S.-based clinical trial to evaluate OTX-TKI for the treatment of DR in the fourth quarter of 2022 and dosed the company’s first patient in February 2023. The company is conducting the Phase 1 clinical trial initially under an eIND. The trial is designed to include approximately 21 subjects with diabetic retinopathy secondary to type 1 or type 2 diabetes who had not had an anti-VEGF injection in the prior 12 months or DME in the prior six months, randomized 2:1 to either a single 600 µg implant of OTX-TKI or sham control across approximately 10 sites. The company anticipates disclosing topline results as early as the fourth quarter of 2023. Regulatory Pathway The company is in active discussions with the FDA regarding the clinical development of OTX-TKI. Assuming positive topline data results from the Phase 1 clinical trial, the finalization of the design of the company’s clinical development program reflecting of the company’s ongoing discussions with the FDA, and additional financing to fund the trials, the company could be in a position to initiate its first pivotal trial of OTX-TKI for the treatment of DR as early as the first quarter of 2024 and a second pivotal trial shortly thereafter. If the company was to obtain favorable results from these two pivotal clinical trials, the company expects that it would submit an NDA under Section 505(b)(2) of the FDCA. Glaucoma Program OTX-TIC (Travoprost Intracameral Implant) The company’s product candidate OTX-TIC is a bioresorbable hydrogel implant incorporating travoprost, an FDA-approved prostaglandin analog designed to lower elevated IOP, that is designed to be administered by a physician as an intracameral injection with an initial target duration of drug release of four to six months with a single treatment. Phase 1 Clinical Development The company submitted an IND for OTX-TIC in February 2018 and has completed a prospective, multi-center, open-label, dose-escalation, proof-of-concept Phase 1 clinical trial of OTX-TIC in the United States that the company initiated in the second quarter of 2018 for the treatment of subjects with moderate to severe glaucoma or ocular hypertension. The clinical trial is designed to evaluate the safety, biological activity, durability and tolerability of OTX-TIC in subjects with controlled open-angle glaucoma or ocular hypertension. In February 2022, at the Glaucoma 360 virtual meeting, the company presented interim results from all four subject cohorts in the Phase 1 clinical trial. Phase 2 Clinical Trial The company is conducting a U.S.-based Phase 2 prospective, multi-center, randomized, controlled clinical trial evaluating the safety, tolerability and efficacy of OTX-TIC for the treatment of patients with primary open-angle glaucoma or ocular hypertension. The company initiated the Phase 2 clinical trial in the fourth quarter of 2021 and dosed the first subject in the first quarter of 2022. The company expects that the Phase 2 clinical trial will consist of approximately 86 patients: approximately 35 patients in the OTX-TIC 26 µg treatment arm, 35 patients in the DURYSTA arm and approximately 16 patients that were previously enrolled in the OTX-TIC 5 µg treatment arm. Enrollment is ongoing. The company plans to provide topline data from the trial in the fourth quarter of 2023. Regulatory Pathway If the company’s Phase 2 clinical trial is successful and subject to obtaining the necessary financing, the company would then be required to successfully complete two well-controlled pivotal clinical trials conducted under an IND to obtain marketing approval from the FDA. If the company was to obtain favorable results from these two pivotal clinical trials, the company expects that it would submit an NDA to the FDA for marketing approval of OTX-TIC under Section 505(b)(2) of the FDCA. Ocular Surface Disease Programs The company is engaged in the development of formulations of the company’s hydrogel administered via intracanalicular inserts to address large markets for diseases and conditions of the surface of the eye. The company’s initial development efforts are focused on the use of the company’s extended-delivery hydrogel in combination with well-known and well-understood drugs (corticosteroids and cyclosporine) for the treatment of dry eye disease, allergic conjunctivitis and inflammation and pain following ophthalmic surgery. Dry Eye Disease Program OTX-DED (Dexamethasone Intracanalicular Insert) The company’s product candidate OTX-DED incorporates the FDA-approved corticosteroid dexamethasone as a preservative-free active pharmaceutical ingredient in a hydrogel, drug-eluting intracanalicular insert. OTX-DED incorporates the same active drug as DEXTENZA but includes a lower dose of the drug, is administered in the office setting as a smaller insert and is designed to release dexamethasone over a period of two to three weeks, compared with up to thirty days in the case of DEXTENZA. Phase 2 Clinical Trial The company submitted an IND in November 2020 for OTX-DED. In February 2021, the company initiated a U.S.-based, randomized, double-masked, vehicle-controlled, multi-center Phase 2 clinical trial evaluating two different-strength formulations of OTX-DED (0.2 mg and 0.3 mg of dexamethasone) versus a hydrogel implant in a total of 166 subjects with dry eye disease, with more than 50 subjects per arm. The subjects were followed for approximately two months after randomization. This trial was designed to assess the safety and efficacy of these two formulations of OTX-DED for the short-term treatment of signs and symptoms of dry eye disease. The company announced the topline Phase 2 clinical results in December 2021. The clinical trial achieved its pre-specified primary endpoint. Regulatory Pathway Based on the data from the Phase 2 clinical trial, the company intends to conduct a small trial in connection with its efforts to develop an appropriate placebo comparator that may be used in both the OTX-DED and OTX-CSI programs. Specifically, the company intends to evaluate the performance of OTX-DED versus placebo inserts, namely fast-dissolving, biodegradable collagen plugs, and no inserts at all, to explain the placebo performance seen in the Phase 2 clinical trials evaluating both OTX-DED and OTX-CSI in which the vehicle hydrogel placebo insert or placebo comparator vehicle remained in the canaliculus longer than anticipated, performing more like an active comparator than a placebo. The company expects to begin this trial in the first half of 2023. If the company determines to advance the program, the company could advance the program to pivotal trials subject to a discussion with the FDA. The company would then be required to successfully complete two well-controlled Phase 3 clinical trials conducted under an IND to obtain marketing approval from the FDA. If the company’s development efforts are successful, the company expects that it would submit an NDA under Section 505(b)(2) of the FDCA. OTX-CSI (Cyclosporine Intracanalicular Insert) OTX-CSI incorporates the FDA-approved immunomodulator cyclosporine as a preservative-free active pharmaceutical ingredient into a hydrogel, drug-eluting, intracanalicular insert. The product candidate is designed for subjects suffering from moderate to severe dry eye and to be administered by a physician as a bioresorbable intracanalicular insert. OTX-CSI is designed to release cyclosporine to the ocular surface for approximately three to four months in order to increase tear production for the chronic treatment of dry eye disease. Phase 1 Clinical Development The company submitted an IND for OTX-CSI in the United States in December 2019 and initiated a Phase 1 clinical trial in the first quarter of 2020. The Phase 1 clinical trial was a U.S.-based, open-label, single-center trial that included five subjects (ten eyes) who were followed for approximately four months. The study was designed to evaluate the safety, tolerability and durability of OTX-CSI and assess the biological activity by measuring signs and symptoms of dry eye disease over this time period. On October 8, 2020, the company announced topline data from its Phase 1 clinical trial evaluating OTX-CSI in the chronic treatment of dry eye disease. All subjects completed the 16-week study period with no drop-outs. There were no serious adverse effects reported. The inserts were observed to be well-tolerated, and there were no adverse events of stinging, irritation, blurred vision or tearing reported or observed. Phase 2 Clinical Development In September 2020, the company dosed the first subjects in a U.S.-based, randomized, double-masked, multi-center, vehicle-controlled Phase 2 clinical trial designed to assess the safety, tolerability and durability and to evaluate the efficacy of OTX-CSI in the chronic treatment of dry eye disease. The company announced topline results from the company’s Phase 2 clinical trial in October 2021. In the Phase 2 clinical trial, OTX-CSI was administered to 147 subjects with dry eye disease at 15 sites in the United States. Regulatory Pathway The company is continuing formulation work to extend the durability of the OTX-CSI insert and select the most appropriate formulations to move forward. If the company determines to advance the program, the company could advance the program to pivotal trials subject to discussions with the FDA. The company would then be required to successfully complete two well-controlled pivotal clinical trials conducted under an IND to obtain marketing approval from the FDA. If the company’s development efforts are successful, the company expects that the company would submit an NDA under Section 505(b)(2) of the FDCA. Additional Potential Areas for Growth The company continues to leverage the potential of the company’s hydrogel platform to explore areas for growth with a focus on formulating, developing and commercializing innovative therapies for diseases and conditions of the eye. Complement Inhibitor: In June 2021, the company entered into an agreement with Mosaic Biosciences, Inc., or Mosaic, to identify new targets and discover novel therapeutic agents aimed at the treatment of dry AMD. The company’s collaboration with Mosaic has yielded lead compounds that Mosaic has humanized and is now optimizing for the company’s preclinical complement inhibitor program. Product candidates with these compounds have the potential for targeted dosing of every three to four months. Companies actively pursuing treatments for GA through the inhibition of the complement system include Apellis Pharmaceuticals, Inc. and Iveric bio, Inc. Apellis’ Syfovre received marketing approval from the FDA in February of 2023. In February 2023, Iveric Bio, Inc. also announced that the FDA had accepted the company’s NDA for avacincaptad pegol for filing and established a PDUFA target action date in August 2023. The company is aware that several other companies are actively developing product candidates for the treatment of GA, including Annexon Biosciences, Inc. Novartis Ionis (in collaboration with Roche/Genentech), AstraZeneca, The Janssen Pharmaceutical Companies of Johnson & Johnson (after acquisition from Hemera Biosciences), Alkeus Pharmaceuticals, Inc., Lineage Cell Therapeutics, Inc. (in collaboration with Roche/Genentech), and Regenerative Patch Technologies, LLC. Gene Delivery Program: The company has a preclinical program using its hydrogel technology to control the release of vectors, such as AAV to ocular tissues for the treatment of inherited and acquired ocular diseases, including dry or wet AMD. The company’s hydrogel formulation technology may be uniquely suited to deliver a gene therapy safely, effectively and efficiently with a longer duration of effect. Companies actively pursuing gene therapy to address ocular diseases and conditions of the eye include Adverum Biotechnologies, GenSight, REGENXBIO, and Spark Therapeutics. Commercial Portfolio Post-Surgical Ocular Inflammation and Pain DEXTENZA (Dexamethasone Intracanalicular Insert) DEXTENZA incorporates the FDA-approved corticosteroid dexamethasone as a preservative-free active pharmaceutical ingredient into a hydrogel, drug-eluting intracanalicular insert. Following FDA approval, the company commercially launched DEXTENZA for the treatment of post-surgical inflammation and pain in July 2019. DEXTENZA is the first FDA-approved intracanalicular insert delivering dexamethasone to treat post-surgical ocular inflammation and pain for up to 30 days with a single administration. The company selected dexamethasone as the active pharmaceutical ingredient for DEXTENZA because it is approved by the FDA and has a long history of ophthalmic use; is available on a generic basis; is highly potent and is typically prescribed for prevention of ocular inflammation and pain following ocular surgery; is available from multiple qualified suppliers; and has physical properties that are well suited for incorporation within the company’s hydrogel technology. The dexamethasone drug particles embedded within the company’s DEXTENZA intracanalicular insert gradually erode and release the drug in a programmed fashion until the drug is depleted. As the dexamethasone drug particles erode and the hydrogel degrades by hydrolysis, the intracanalicular insert softens, liquefies and is cleared through the nasolacrimal duct. The company provides the DEXTENZA drug product in a preservative-free formulation in a sterile, single use package. Investigator-Initiated Trials The company has received proposals for, and are supporting, several investigator-initiated trials evaluating DEXTENZA in different clinical situations. To date, third-party clinical investigators have initiated over 45 trials to study the use of DEXTENZA in cataract surgery, other ophthalmic surgeries and other potential indications. Over 25 of the trials have completed enrollment, and the remaining trials are actively enrolling and treated subjects are being followed. Post-Approval Studies In September 2020, the company announced that it had dosed the first pediatric subjects in a U.S.-based, randomized, multicenter Phase 3 clinical trial evaluating DEXTENZA for the treatment of post-surgical ocular inflammation and pain in children following cataract surgery. This clinical trial is a post-approval requirement of the FDA in accordance with the Pediatric Research Equity Act of 2003, in connection with the FDA’s prior approval of DEXTENZA for the treatment of inflammation and pain following ophthalmic surgery in adults. The company intends to enroll approximately 60 subjects in this clinical trial. It is designed to evaluate the safety and biological activity of DEXTENZA compared to an active control, prednisolone acetate suspension eye drops, for the treatment of inflammation and pain following ocular surgery for pediatric cataract in children between zero and three years of age. The primary endpoint is the absence of pain at day eight post-treatment as measured by a FLACC (Face, Legs, Activity, Cry, Consolability) score of zero. Enrollment is ongoing. The FDA has agreed that this Phase 3 clinical trial evaluating DEXTENZA for the treatment of post-surgical ocular inflammation and pain in children following cataract surgery may also satisfy the post-approval requirement for a pediatric trial as it relates to indication ocular itching associated with allergic conjunctivitis. Foreign Approvals Outside the United States, the company continues to assess whether to seek regulatory approval for DEXTENZA in markets, such as the European Union, Australia and Japan based on the market opportunity, particularly pricing, and the requirements for marketing approval. Given the company’s prioritization of the clinical development of its sustained-release product candidates and the company’s planned commercialization efforts for its initial intracanalicular insert product candidates in the United States, the company will need to engage third parties to assist the company in the approval process. The company has entered into a license agreement and collaboration with AffaMed for the development and commercialization of DEXTENZA, along with OTX-TIC, in specified Asian markets. In January 2022, AffaMed dosed its first subject in a study conducted in China evaluating the safety and efficacy of DEXTENZA for the treatment of ocular inflammation and pain post-cataract surgery. This prospective, single-arm, real-world trial is designed to assess the safety and efficacy of DEXTENZA for the treatment of ocular inflammation and pain following cataract surgery in approximately 120 patients at the Bo’ao Super Hospital. In April 2022, AffaMed announced that DEXTENZA has been approved in Macau, China for the treatment of ocular inflammation and pain following ophthalmic surgery. The company does not expect that DEXTENZA sales in Macau will result in material revenues to the company. The company retains the right to develop and commercialize DEXTENZA in all other global markets. From time to time, the company may consider additional arrangements with other companies to address markets outside of the United States. If the company or its collaborators obtain regulatory approval to market and sell DEXTENZA in international markets, the company expects to utilize a variety of types of collaboration, distribution and other marketing arrangements with one or more third parties to commercialize DEXTENZA. Allergic Conjunctivitis DEXTENZA (Dexamethasone Ophthalmic Insert) for the Treatment of Ocular Itching Associated with Allergic Conjunctivitis In October 2021, the FDA approved the company’s sNDA, for DEXTENZA to include the treatment of ocular itching associated with allergic conjunctivitis as an additional indication. With the approval, DEXTENZA became the first, FDA-approved, physician-administered intracanalicular insert capable of delivering a preservative-free drug for the treatment of ocular itching associated with allergic conjunctivitis with a single administration for up to 30 days. DEXTENZA for the treatment of ocular itching associated with allergic conjunctivitis also represents the company’s first indication approved to be administered in a physician’s office during a routine, non-surgical appointment. The company commercially launched DEXTENZA for the treatment of ocular itching associated with allergic conjunctivitis in the first quarter of 2022 utilizing a small, dedicated and highly focused sales force of four key account managers and two field reimbursement managers that called exclusively on the offices of ophthalmologists and optometrists. In the fourth quarter of 2022, the company redeployed this small sales force to join the DEXTENZA sales force focused on the ophthalmic surgery market, specifically cataract surgery, in ambulatory surgery centers, or ASCs, and hospital outpatient departments, or HOPDs. Prevention of Wound Leaks Following Cataract Surgery ReSure Sealant ReSure Sealant is a topical liquid hydrogel that creates a temporary, adherent, soft and lubricious sealant to prevent post-surgical leakage from clear corneal incisions that are made during cataract surgery. The FDA granted marketing approval for ReSure Sealant in January 2014 and the company commercially launched ReSure Sealant in the United States in February 2014. As of the fourth quarter of 2021, the company suspended the production of ReSure Sealant in order to focus the company’s manufacturing resources on the commercialization of DEXTENZA. ReSure Sealant is not commercially available in the United States. AffaMed License Agreement In October 2020, the company entered into a license agreement and collaboration with AffaMed Therapeutics Limited, or AffaMed, for the development and commercialization of DEXTENZA and OTX-TIC in mainland China, Taiwan, Hong Kong, Macau, South Korea, and the countries of the Association of Southeast Asian Nations. In return, the company agreed to grant AffaMed exclusive rights to develop and commercialize DEXTENZA for the treatment of post-surgical inflammation and pain following ophthalmic surgery and ocular itching in patients with allergic conjunctivitis, and OTX-TIC for the reduction of elevated IOP in patients with primary open-angle glaucoma or ocular hypertension in specified Asian markets. The company retains the right to develop and commercialize DEXTENZA and OTX-TIC in all other global markets. In January 2022, AffaMed announced that it had dosed its first patient in a real-world setting study conducted in China evaluating the safety and efficacy of DEXTENZA (0.4mg dexamethasone ophthalmic insert) for the treatment of ocular inflammation and pain post-cataract surgery. This prospective, single-arm, real-world trial is designed to assess the safety and efficacy of DEXTENZA for the treatment of ocular inflammation and pain following cataract surgery in approximately 120 patients at the Bo’ao Super Hospital. In April 2022, AffaMed announced that DEXTENZA has been approved in Macau, China for the treatment of ocular inflammation and pain following ophthalmic surgery. The company does not expect that DEXTENZA sales in Macau will result in material revenues to the company. Sales, Marketing and Distribution The company generally expects to retain commercial rights in the United States to any of its product candidates for which the company may receive marketing approvals and which the company can successfully commercialize. In general, if the company receives approval to market any of the company’s product candidates in the United States, the company plans to then evaluate the regulatory approval requirements and commercial potential for any such product candidate in Europe, Japan and other selected geographies. If the company decides to commercialize the company’s products outside of the United States, the company expects to utilize a variety of types of collaboration, distribution and other marketing arrangements with one or more third parties to commercialize any product of the company that receives marketing approval. The company sells DEXTENZA in the United States to a network of specialty distributors, who then resell DEXTENZA to ASCs and HOPDs. The company has built a highly targeted, key account sales force of KAMs, or key account managers, regional directors, and FRMs or field reimbursement managers that focus on the ASCs and their affiliates responsible for the largest volumes of cataract surgery in the United States, with an initial emphasis on the approximately two million cataract procedures performed annually under Medicare Part B. With the approval of DEXTENZA for the indication of ocular itching associated with allergic conjunctivitis, the company launched a commercial effort in the first half of 2022 with four KAMs and two FRMs dedicated to selling DEXTENZA to the offices of ophthalmologists and optometrists, where the vast majority of prescriptions for allergies are written. Intellectual Property As of March 1, 2023, patents and/or patent applications pending owned by the company, were 95 pending applications: 5 pending provisional applications, 11 pending U.S. patent applications, 11 pending World Intellectual Property Organization applications and 68 foreign applications. The following is a summary of patents and patent applications that cover the company’s commercial products and potentially cover its product candidates: OTX-TKI (Axitinib Intravitreal Implant) for Wet AMD, DME and RVO The company owns issued patents in the U.S. that cover this product candidate, with current expiration dates in 2041. Additional U.S. and foreign patent applications are pending. OTX-TIC (Travoprost Intracameral Implant) For Open-Angle Glaucoma Or Ocular Hypertension The company has licenses to pending U.S. applications and certain foreign patent applications pending that potentially cover this product candidate that, if granted, are expected to expire in 2037. The company owns pending patent applications in the U.S., and certain foreign counterparts, with the potential to cover this product candidate that, if granted, are expected to expire in 2041. OTX-CSI (Cyclosporine Intracanalicular Insert) For Dry Eye Disease The company has licenses to the U.S. patents, and certain foreign counterparts, that cover this product candidate, with current expiration dates in 2030. The company owns issued patents and pending patent applications in the U.S. that cover this product candidate with current expiration dates in 2037 and in 2041, and corresponding foreign patent applications that, if granted, are expected to expire in 2041. OTX-DED (Dexamethasone Intracanalicular Insert) For Episodic Dry Eye Disease The company has licenses to the U.S. patents, and certain foreign counterparts, with current expiration dates in 2030. The company owns an issued patent that expires in 2037 that covers this product candidate and a pending patent application in the U.S., and certain foreign counterparts, with the potential to cover this product candidate that, if granted, are expected to expire in 2041. DEXTENZA (Dexamethasone Ophthalmic Insert) 0.4 mg The company has licenses to the U.S. patents, and certain foreign counterparts, with current expiration dates in 2030 that cover this product. The company also owns a U.S. patent that covers this product with a current expiration date in 2037. DEXTENZA (Dexamethasone Ophthalmic Insert) 0.4 mg For Allergic Conjunctivitis The company has licenses to the U.S. patents, and certain foreign counterparts, with current expiration dates in 2030 that cover this product. The company also owns a U.S. patent that covers this product with a current expiration date in 2037 and a pending patent application in the U.S., and certain foreign counterparts, with the potential to cover this product candidate that, if granted, is expected to expire in 2041. ReSure Sealant The company has licenses to two U.S. patents that cover ReSure Sealant. One U.S. patent is expected to expire in 2024 and relating to the process of making and using hydrogel compositions, and one U.S. patent is expected to expire in 2032 and relates to certain features of the ReSure Sealant package. Licenses Incept, LLC In January 2012, the company entered into an amended and restated license agreement, which the company refers to as either the Prior Agreement or Original License, with Incept under which the company holds an exclusive, worldwide, perpetual, irrevocable license under specified patents and technology owned or controlled by Incept to make, have made, use, offer for sale, sell, sublicense, have sublicensed, offer for sublicense and import, products delivered to or around the human eye for diagnostic, therapeutic or prophylactic purposes relating to all human ophthalmic diseases or conditions. This license covers a significant portion of the patent rights and the technology for DEXTENZA, ReSure Sealant and the company’s hydrogel platform technology product candidates. The agreement supersedes an April 2007 license agreement between the company and Incept. AffaMed License Agreement On October 29, 2020, the company entered into a license agreement, or the License Agreement, with AffaMed for the development and commercialization of DEXTENZA regarding ocular inflammation and pain following cataract surgery and allergic conjunctivitis, or collectively, the DEXTENZA Field, and for OTX-TIC, or collectively with DEXTENZA, the AffaMed Licensed Products, regarding open-angle glaucoma and ocular hypertension, or collectively, the TIC Field and, with the DEXTENZA Field, each a Field, in each case in mainland China, Taiwan, Hong Kong, Macau, South Korea, and the countries of the Association of Southeast Asian Nations, or collectively, the Territories. The company retains development and commercialization rights for the AffaMed Licensed Products in the rest of the world. Mosaic Biosciences Agreement In June 2021, the company entered into an agreement with Mosaic to identify new targets and discover novel therapeutic agents aimed at the treatment of dry AMD. The company’s collaboration with Mosaic has yielded lead compounds that Mosaic has humanized and is now optimizing for the company’s preclinical complement inhibitor program for the treatment of dry AMD. The company owns all intellectual property created under this agreement. Government Regulation The company’s clinical trials are regulated by the Federal Policy for the Protection of Human Subjects, known as the Common Rule, which also includes specific privacy-related provisions. Research and Development The company’s research and development expenses were $53.5 million for the year ended December 31, 2022. History The company was founded in 2006. It was incorporated under the laws of the state of Delaware in September 2006 under the name I-Therapeutics, Inc. The company changed its name to I-Therapeutix, Inc. in October 2006 and to Ocular Therapeutix, Inc. in 2009.