EyePoint Pharmaceuticals Stock

EyePoint Pharmaceuticals, Inc. engages in developing and commercializing innovative therapeutics to help improve the lives of patients with serious eye disorders.

The company's pipeline leverages its proprietary Durasert technology (Durasert) for sustained intraocular drug delivery, including delivery of EYP-1901, an investigational sustained delivery intravitreal treatment in Phase 2 clinical trials. The proven Durasert drug delivery platform has been safely administered to thousands of patients' eyes across four U.S. FDA approved products, including YUTIQ for the treatment of posterior segment uveitis, which is marketed by the company.

EYP-1901 is an investigational product and the company’s lead pipeline program deploying a bioerodible Durasert insert of vorolanib, a selective and patented tyrosine kinase inhibitor (TKI), that potentially brings a new mechanism of action and treatment paradigm for serious eye diseases beyond existing anti-vascular endothelial growth factor (VEGF) large molecule therapies. EYP-1901 is in Phase 2 clinical trials as a sustained delivery treatment for wet age-related macular degeneration (wet AMD), the leading cause of vision loss among people 50 years of age and older in the United States, and non-proliferative diabetic retinopathy (NPDR), a largely untreated disease due to limitations of available therapies. The company expects to initiate a Phase 2 clinical trial in diabetic macular edema (DME) in late 2023 or early 2024.

In 2022, the company reported positive twelve-month safety and efficacy data in a Phase 1 clinical trial of EYP-1901 (DAVIO), delivering the active drug vorolanib. Vorolanib acts through intracellular binding of all VEGF receptors thereby blocking all VEGF isoforms. Vorolanib has also demonstrated encouraging neuroprotection data in preclinical in-vivo studies potentially bringing an additional treatment benefit.

In wet AMD, EYP-1901 is being developed as a sustained delivery maintenance therapy as a six-month treatment. Data from the DAVIO clinical trial demonstrated that 53% of patients went six-months without needing a supplemental anti-VEGF injection and the treatment burden across all cohorts was reduced by 75% through six-months. For NPDR, EYP-1901 has the potential as a once-yearly treatment option.

The company’s commercial product, YUTIQ, is a once every three-year treatment for chronic non-infectious uveitis affecting the posterior segment of the eye that utilizes a non-erodible formulation of Durasert. YUTIQ was launched in the U.S. in 2019 and the company has focused on its use by both uveitis and retinal specialist physicians.

The company continues to evaluate potential product candidates through internal discovery efforts, research collaborations and in-licensing arrangements to build its pipeline.

Strategy

The key elements of the company’s strategy are to advance EYP-1901 through Phase 3 clinical development for wet AMD, NPDR and DME; advance EYP-1901 into clinical trials in additional indications, potentially, including Myopic Choroidal Neovascularization (CNV) and retinal vein occlusion (RVO); expand product pipeline through in-license, partnership or acquisition with initial focus on molecules that can be delivered using its Durasert technology; and Leverage its drug delivery technologies through research collaborations and out-licenses with other pharmaceutical and biopharmaceutical companies, institutions and other organizations.

Product Candidates

EYP-1901 for wet AMD, NPDR and DME

EYP-1901 is an investigational product deploying a bioerodible Durasert insert of vorolanib, a selective and patent protected TKI, that potentially brings a new mechanism of action and treatment paradigm for serious eye diseases beyond existing anti-VEGF large molecule ligand blocking therapies. The company has reported positive safety and efficacy data for EYP-1901 in its Phase 1 DAVIO clinical trial and it is developing EYP-1901 in Phase 2 clinical trials for wet AMD and NPDR. A Phase 2 clinical trial in DME is anticipated to initiate in late 2023 or early 2024.

Vorolanib acts through intracellular binding of all VEGF receptors thereby blocking all VEGF isoforms, the main driver of the proliferation of blood vessels that are the hallmark of wet AMD and other retinal diseases. In addition to the safety and efficacy demonstrated in the DAVIO clinical trial, vorolanib has also demonstrated encouraging neuroprotection data in preclinical in-vivo studies potentially bringing an additional treatment benefit. Prior to in-licensing by EyePoint, vorolanib was previously studied in Phase 1 and 2 clinical trials as an orally delivered therapy for the treatment of wet AMD and data from these trials demonstrated a positive clinical signal and no ocular toxicity.

Clinical Development

The Phase 1 DAVIO clinical trial was a dose escalation trial that enrolled 17 wet AMD patients across four separate doses. In November 2021, the company reported positive interim six-month safety and efficacy data for the DAVIO clinical trial. In July 2022, the company updated the results of the DAVIO clinical trial through 12-months reporting continued positive safety and efficacy results.

The company initiated a randomized controlled Phase 2 clinical trial for EYP-1901 for wet AMD (DAVIO 2) and top-line data is anticipated in the fourth quarter of 2023. This trial is expected to enroll approximately 144 patients across three arms consisted of two separate doses of EYP-1901 with an aflibercept control. In addition, a Phase 2 clinical trial in NPDR (PAVIA) was initiated in the third quarter of 2022, following the initiation of the Phase 2 wet AMD trial. The PAVIA trial is expected to enroll approximately 105 patients across three arms consisted of two separate doses of EYP-1901 and a sham control.

Intellectual Property

In February 2020, the company entered into an Exclusive License Agreement with Equinox Science, LLC (Equinox), pursuant to which Equinox granted it an exclusive, sublicensable, royalty-bearing right and license to certain patents and other Equinox intellectual property to research, develop, make, have made, use, sell, offer for sale and import the compound vorolanib and any pharmaceutical products comprising the compound for the prevention or treatment of wet AMD, diabetic retinopathy (DR) and RVO (the Original Field) using its proprietary localized delivery technologies, in each case, throughout the world except China, Hong Kong, Taiwan and Macau (the Territory). In May 2022, the company entered into Amendment 1 to the Equinox License Agreement, pursuant to which the Original Field was expanded to cover the prevention or treatment of ophthalmology indications using the company’s proprietary localized delivery technologies.

In May 2022, the company entered into an Exclusive License Agreement (the Betta License Agreement) with Betta Pharmaceuticals Co., Ltd. (Betta), an affiliate of Equinox. Under the Betta License Agreement, the company granted to Betta an exclusive, sublicensable, royalty-bearing license under certain of the company’s intellectual property to develop, use (but not make or have made), sell, offer for sale and import the company’s product candidate, EYP-1901, an investigational sustained delivery intravitreal anti-VEGF treatment that combines a bioerodible formulation of the company’s proprietary sustained-release technology with the compound vorolanib (the Licensed Product), in the field of ophthalmology (the Betta Field) in the Greater Area of China, including China, the Hong Kong Special Administrative Region, the Macau Special Administrative Region, and Taiwan (the Betta Territory). The company retained rights under the company’s intellectual property to, among other things, conduct clinical trials on the Licensed Product in the Betta Field in the Betta Territory.

Commercial Products

YUTIQ

YUTIQ (fluocinolone acetonide intravitreal implant or FA 0.18 mg) for intravitreal injection, was approved by the FDA in October 2018 and the company commercially launched YUTIQ in the U.S. in February 2019. YUTIQ is indicated for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye. YUTIQ is a once every three-year treatment utilizing a non-erodible formulation of the company’s proprietary Durasert technology that is administered during a physician office visit.

In addition to commercialization of YUTIQ in the U.S., the company has licensed regulatory, reimbursement and distribution rights to the product to Alimera for Europe, Middle East, and Africa (EMEA) under its ILUVIEN tradename and clinical development, regulatory, reimbursement and distribution rights to Durasert FA to Ocumension Therapeutics (Ocumension) for Mainland China, Hong Kong, Macau, Taiwan, South Korea and other jurisdictions across Southeast Asia.

Recent Clinical Development Highlights

CALM real world registry study is ongoing and collecting real world data on YUTIQ for the Treatment of Chronic Non-Infectious Uveitis Affecting the Posterior Segment. There were two initial baseline posters presented at the American Society of Retina Specialists (ASRS) and Retina Society conferences in 2021. At present, data for 188 eyes of 122 patients have been logged in the registry. Various posters with follow-up data will be presented at ARVO 2023 Meeting and at the ASRS 2023 meeting. Additional data will be analyzed and presented or published as the study continues and the data are analyzed.

In the second quarter of 2022, the company dosed the first patient in a Phase 4 Study, the SYNCRONICITY study, of YUTIQ (fluocinolone acetonide intravitreal implant) 0.18 mg for the treatment of Chronic Non-Infectious Posterior Segment Uveitis. This is a 2-year, prospective, open-label, uncontrolled, safety and efficacy study. As of January 2023, 25% patient recruitment has been attained, as the clinical trial continues, data will be presented or published and when appropriate data are analyzed.

Intellectual Property

The company owns the rights for YUTIQ in the U.S. and all foreign jurisdictions and have licensed these rights in EMEA and Mainland China, Hong Kong, Macau and Taiwan. In August 2020, the company expanded the out-license agreement with Ocumension to include South Korea and other jurisdictions across Southeast Asia. The company has patent rights for YUTIQ in the U.S. through at least August 2027 and internationally through dates ranging from October 2024 to May 2027.

Sales and Marketing

YUTIQ was granted a permanent and specific J-code by the Centers for Medicare & Medicaid Services (CMS), effective October 1, 2019. Approximately 20 Key Account Managers (KAMs) are dedicated to calling on uveitis and retinal specialists across the U.S. as of February 28, 2023.

DEXYCU

DEXYCU (dexamethasone intraocular suspension) 9%, for intraocular administration, was approved by the FDA in February 2018 for the treatment of post-operative ocular inflammation and commercially launched in the U.S. in March 2019 with a primary focus on its use immediately following cataract surgery. DEXYCU is administered as a single dose directly into the surgical site at the end of ocular surgery and is the first long-acting intraocular product approved by the FDA for the treatment of post-operative inflammation. DEXYCU utilizes the company’s proprietary Verisome drug-delivery technology, which allows for a single intraocular injection that releases dexamethasone, a corticosteroid, for up to 22 days.

Clinical Development Highlights

Retrospective study data were presented at the Association for Research in Vision and Ophthalmology (ARVO) and American Society of Cataract and Refractive Surgery (ASCRS) 2021. This completed study was a multicenter retrospective study of real-world data from use of DEXYCU. ARVO 2021 data from this study highlighted real world data in patients with a history of glaucoma treated with DEXYCU for inflammation control following cataract surgery. Anti-inflammatory efficacy, as measured by anterior chamber cell (ACC) count clearing and safety with regard to intraocular pressure (IOP) elevation were similar in patients with glaucoma to the full study population.

Intellectual Property

The company owns the worldwide rights to all indications for DEXYCU and in January 2020 the company out-licensed clinical development, regulatory, reimbursement and distribution rights to Ocumension for the product in Mainland China, Hong Kong, Macau and Taiwan. In August 2020, the company expanded the out-license agreement with Ocumension to include South Korea and other jurisdictions across Southeast Asia.

Sales and Marketing

Effective January 1, 2022, the company’s commercial alliance partner, ImprimisRx, assumed responsibility for all sales and marketing activities for DEXYCU in the U.S. and absorbed the majority of its DEXYCU commercial organization. The company continued to recognize net product revenue and maintained manufacturing and distribution responsibilities for DEXYCU along with non-sales related regulatory compliance. The company paid ImprimisRx a commission based on the net sales of DEXYCU and retained all commercial rights and the New Drug Application (NDA) for DEXYCU. ImprimisRx utilized their internal sales representatives and their numerous indirect representatives to promote DEXYCU to their existing cataract surgery customers. The contract with ImprimisRx was terminated on December 31, 2022.

Manufacturing

Manufacturing of the company’s clinical trial materials (CTM) and of its commercial products is subject to these Current Good Manufacturing Practice (cGMPs) which govern record-keeping, manufacturing processes and controls, personnel, quality control and quality assurance, among other activities.

EYP-1901

The company sources the active pharmaceutical ingredient (API) vorolanib from Betta Pharmaceuticals and various raw materials and components for both EYP-1901 and its injector from third-party vendors. The company’s agreements with Betta Pharmaceuticals and these third parties include confidentiality and intellectual property provisions to protect its proprietary rights related to EYP-1901.

The U.S. Sales and Marketing

As of February 28, 2023, the company has 20 KAMs deployed across the U.S. responsible for the sale of YUTIQ. In addition to the company’s KAMs, it has an experienced sales and marketing leadership team that has extensive commercialization experience with ophthalmic products at previous companies.

Effective January 1, 2022, the company’s commercial alliance partner, ImprimisRx, assumed responsibility for all sales and marketing activities for DEXYCU in the U.S. and absorbed the majority of its DEXYCU commercial organization. The company’s partnership with ImprimisRx ended on December 31, 2022 and DEXYCU marketing responsibilities returned to EyePoint and it has minimized those activities in 2023 due to the elimination of separate pass-through reimbursement by CMS.

The U.S. Product Distribution Channel

The company has established a distribution channel in the United States for the commercialization of YUTIQ and DEXYCU that provides physicians with several options for ordering its products. This includes agreements with a nationally recognized third-party logistics provider (3PL), several distributors and a specialty pharmacy provider for physicians who prefer to use a traditional buy-and-bill model. The 3PL provides fee-based services related to logistics, warehousing, order fulfilment, invoicing, returns and accounts receivable management.

FDA Approved Products Licensed to Others

ILUVIEN for DME

ILUVIEN is an injectable, sustained-release micro-insert based on the company’s Durasert technology platform and delivers 0.19 mg of FA to the back of the eye for the treatment of DME. The ILUVIEN micro-insert is substantially the same micro-insert as YUTIQ.

The company originally licensed its Durasert proprietary insert technology to Alimera for use in ILUVIEN for the treatment of all ocular diseases (excluding uveitis). In July 2017, the company entered into the Amended Alimera Agreement, pursuant to which it expanded the license to Alimera to its proprietary Durasert sustained-release drug delivery technology platform to include uveitis, including chronic non-infectious uveitis affecting the posterior segment of the eye, in the EMEA and converted the net profit share arrangement for each licensed product (including ILUVIEN) under the original collaboration agreement with Alimera (the Prior Alimera Agreement) to a sales-based royalty on a calendar quarter basis commencing July 1, 2017, with payments from Alimera due 60 days following the end of each calendar quarter.

Retisert for Chronic Non-Infectious Uveitis Affecting The Posterior Segment of The Eye

Retisert is a sustained-release non-erodible implant based on the company’s Durasert technology platform for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye. Retisert is licensed to Bausch & Lomb, with which the company co-developed the product. Retisert is approved in the U.S., Bausch & Lomb sells the product and paid sales-based royalties to the company. The patent with which Retisert is marketed expired in March 2019. As such, pursuant to the company’s agreement with Bausch & Lomb, payment of sales-based royalties concluded at the end of March 2019 following patent expiration.

Intellectual Property

The company owns or licenses patents in the U.S. and other countries. For example, the company owns and/or licenses the U.S. and foreign patents and patent applications for its DURASERT technology and its VERISOME technology. In addition, the company owns the U.S. and foreign patents and patent applications covering other technologies, such as devices used to administer some of its products.

The U.S. patents that were previously listed in the USFDA Orange Book for Retisert expired in March 2019. The latest expiring patent listed in the USFDA Orange Book covering ILUVIEN and YUTIQ expires in August 2027 in the U.S. and in October 2024 in the EU, although extensions have been obtained or applied for through May 2027 in various EU countries. The U.S. patent covering the YUTIQ injector and administration with this injector expires in January 2028.

The last of the previously issued patents covering DEXYCU expire in July 2023, but additional patents have issued in the U.S. that will cover DEXYCU until at least May 2034, and to the injection dosing guides until June of 2039.

The last expiring patent covering the vorolanib compound licensed to the company by Equinox Science and used in EYP-1901 expires in September 2037, but EyePoint has filed an additional patent application for EYP-1901 that, if issued, would extend coverage of EYP-1901 until at least 2041. In addition, EyePoint has filed additional patent applications for technology relating to EYP-1901, that, if issued, could expire in 2043, and for a new injector designed for administration of DURASERT, that, if issued, could expire in 2042.

The acquired Aerpio patent portfolio includes more than 300 U.S. or ex-U.S. patents and pending applications that claim compositions of matter, pharmaceutical formulations and methods of use covering both small molecule and mono and bi-specific antibody inhibitors of the protein tyrosine phosphatase (VE-PTP). Some of the antibodies covered include both VE-PTP and VEGF binding domains. VE-PTP is a negative Tie2 regulator that, when inhibited, can activate the Tie2 pathway leading to downstream signaling that promotes vascular health, stability and decreases vascular permeability and inflammation associated with a number of posterior segment eye diseases. The potential expiration dates of the patents and applications in this portfolio range from 2027 to 2041.

DEXYCU, YUTIQ, and Durasert are the company’s trademarks. Verisome is a trademark owned by Ramscor, Inc. and exclusively licensed to the company.

Government Regulation

The company is subject to extensive regulation by the U.S. Food and Drug Administration (FDA) and other federal, state, and local regulatory agencies. The Federal Food, Drug and Cosmetic Act (the FD&C Act), and FDA’s implementing regulations set forth, among other things, requirements for the testing, development, manufacture, quality control, safety, effectiveness, approval, labeling, storage, record-keeping, reporting, distribution, import, export, advertising and promotion of the company’s products and product candidates.

Customers

For the year ended December 31, 2022, revenues from ASD Specialty Healthcare LLC and McKesson Specialty Care Distribution LLC accounted for 51.1% and 39.5% of total revenues, respectively.

Research and Development

The company’s research and development expenses were $49.6 million for 2022.

History

The company was incorporated in 1987. The company was formerly known as pSivida Corp. and changed its name to EyePoint Pharmaceuticals, Inc. in 2018.