About Opthea

Opthea Limited operates as a clinical-stage biopharmaceutical company. The company is developing a novel therapy for the treatment of highly prevalent and progressive retinal diseases. The company is developing its Phase 3-product candidate, Sozinibercept (OPT-302), a biologic designed to inhibit VEGF-C and VEGF-D, to complement VEGF-A inhibitors for the treatment of ophthalmic diseases. As the only biologic inhibitor of VEGF-C and VEGF-D in clinical development for ophthalmology, Sozinibercept (OPT-302) differs from standard of care therapies and when administered in combination with a VEGF-A inhibitor, is designed to achieve broader inhibition of the vascular endothelial growth factor, or VEGF, family and target a mechanism of clinical resistance to improve visual acuity. The company’s lead indication for Sozinibercept (OPT-302) combination therapy is wet AMD, a chronic, progressive disease, and the leading cause of vision loss for individuals over the age of 50. In a 366-patient Phase 2b clinical trial for the treatment of wet AMD, 2.0 mg Sozinibercept (OPT-302), in combination with a standard of care anti-VEGF-A therapy, ranibizumab (Lucentis), met the primary endpoint of a statistically significant superior mean gain in visual acuity over ranibizumab monotherapy at week 24. The company initiated two pivotal Phase 3 clinical trials in treatment-naive patients with age-related macular degeneration (wet AMD) to evaluate the efficacy and safety of Sozinibercept (OPT-302) in combination with anti-VEGF-A therapies compared to anti-VEGF-A monotherapy in March 2021. The company expects to complete patient recruitment in the COAST study in the first calendar quarter of 2024 and in the ShORe study in the second calendar quarter of 2024. In addition to its clinical trials in wet AMD, the company has observed evidence of improved clinical outcomes in a Phase 1b/2a clinical trial of Sozinibercept (OPT-302) in combination with another standard of care anti-VEGF-A therapy, aflibercept (Eylea), in patients with treatment-refractory diabetic macular edema, or DME. The company retains worldwide rights to develop and commercialize Sozinibercept (OPT-302) for the treatment of wet AMD and DME and the novel treatment mechanism of Sozinibercept (OPT-302) has the potential to provide therapeutic benefit for other progressive eye diseases. Sozinibercept (OPT-302) is designed to address a deficiency in the treatment paradigm for wet AMD and other retinal diseases, such as DME, by targeting alternate members of the vascular endothelial growth factor (VEGF) family, namely VEGF-C and VEGF-D, which are not targeted by current standard of care therapies. VEGF-C and VEGF-D function in parallel with VEGF-A to drive neovascularization and vascular leakage, which are key hallmarks of both wet AMD and DME. In addition, treatment with VEGF-A inhibitors leads to upregulation of VEGF-C and VEGF-D to compensate for VEGF-A inhibition, which may represent an important mechanism of clinical resistance to anti-VEGF-A monotherapy. The company is developing Sozinibercept (OPT-302) to be used in combination with standard of care anti-VEGF-A monotherapies to achieve broader inhibition of the VEGF family, with the goal of improving overall efficacy and demonstrating superior vision gains over that which can be achieved by inhibiting VEGF-A alone. In the company’s completed Phase 2b wet AMD clinical trial, 2.0 mg Sozinibercept (OPT-302) in combination with ranibizumab demonstrated a statistically significant superior mean gain in visual acuity at week 24 compared to patients treated with ranibizumab with a sham injection, which it refers to as ranibizumab monotherapy. The trial was an international, multi-center, double-masked trial in 366 treatment-naive patients with wet AMD. In August 2020, the company successfully completed End-of-Phase 2 meetings with the U.S. Food and Drug Administration (FDA), and a Scientific Advice meeting with the European Medicines Agency (EMA). The regulatory engagement provided the company with guidance on its Phase 3 clinical program for Sozinibercept (OPT-302) in wet AMD and associated manufacturing processes that will support the submission of a Biologics License Application in the U.S. and Marketing Authorization Application in Europe. Furthermore, in July 2021, the FDA granted Fast Track designation for Sozinibercept (OPT-302) in combination with anti-VEGF-A therapy for the treatment of patients with wet AMD. The FDA’s Fast Track Designation for Sozinibercept (OPT-302) offers benefits to expedite the Phase 3 clinical program and subsequent potential approval process, including more frequent communication and meetings with the FDA, and a Rolling Review of completed sections of its biologics license application (BLA). The company initiated two concurrent pivotal Phase 3 clinical trials for the treatment of wet AMD in March 2021. These double-masked, sham-controlled Phase 3 clinical trials enrolled treatment-naive patients and assessed the efficacy and safety of 2.0 mg of Sozinibercept (OPT-302) in combination with ranibizumab (Lucentis) (referred to as the ShORe trial) or aflibercept (Eylea) (referred to as the COAST trial), compared to ranibizumab or aflibercept monotherapy in each respective trial. In addition, to understand the durability of Sozinibercept (OPT-302) treatment effect with less frequent dosing, each trial compared the clinical efficacy of Sozinibercept (OPT-302) administered in combination with the applicable VEGF-A inhibitor on an every four-week and every eight-week dosing regimen. Since the first patients were treated in the company’s Phase 3 pivotal program in March 2021, it has continued to activate additional clinical trial sites and recruit patients in the U.S., Europe, and other regions of the world. In August 2021, the first sites opened enrollment in Canada, and in October 2021, the first sites opened enrollment in Europe and the Asia Pacific. In total, the company expected to enroll approximately 990 patients into each trial, with patients recruited from more than 20 countries worldwide. The company’s efforts to advance its Phase 3 clinical trials, including clinical trial activations and trial site engagements, have been challenged in part by the COVID-19 pandemic and administrative delays. The company continues to expect to complete patient recruitment in the COAST study in the first calendar quarter of 2024 and in the ShORe study in the second calendar quarter of 2024. Top-line data is expected to be reported when all patients complete the 52-week treatment period for the primary analysis. If the results at the completion of the primary efficacy phase at week 52 of the Phase 3 clinical trials are favorable, the company intends to submit Biologics License and Marketing Authorization Applications with the FDA and EMA, respectively. In addition to its pivotal Phase 3 clinical trials, the company plans to develop a co-formulation of Sozinibercept (OPT-302) with an approved and/or biosimilar anti-VEGF-A therapy designed to achieve VEGF-A, VEGF-C, and VEGF-D inhibition following the administration of a single intravitreal injection of the co-formulated product. Sozinibercept (OPT-302) is administered as a combination therapy consisting of a sequential injection of Sozinibercept (OPT-302) following intravitreal administration of a VEGF-A inhibitor. The company intends to file an investigative new drug application, or IND, for the co-formulated product in a Phase 1 clinical trial for the treatment of wet AMD. The company is assessing opportunities with multiple third parties to in-license and/or generate a biosimilar anti-VEGF-A therapy, which it intends to co-formulate with Sozinibercept (OPT-302) and advance through non-clinical studies, including IND-enabling safety and tolerability studies. The company intends to file an IND for the co-formulated product in in a Phase 1 clinical trial for the treatment of wet AMD. While the company intends to focus its development efforts on seeking commercialization of Sozinibercept (OPT-302) for the treatment of wet AMD, it is also investigating the therapeutic potential of Sozinibercept (OPT-302) for DME. In the company’s Phase 1b/2a clinical trial of Sozinibercept (OPT-302) in combination with aflibercept in patients with treatment-refractory DME, it observed evidence of improved clinical outcomes following Sozinibercept (OPT-302) combination therapy in this indication. The company may further investigate the efficacy of Sozinibercept (OPT-302) to improve clinical outcomes in patients with polypoidal choroidal vasculopathy, or PCV, a form of wet AMD that is highly prevalent in Asian populations and less responsive to anti-VEGF-A therapy than other wet AMD subtypes. Beyond wet AMD and DME, the company may explore applications of Sozinibercept (OPT-302) in other retinal diseases in which a VEGF-C or VEGF-D inhibitor could have therapeutic potential, such as retinal vein occlusion, or RVO. Strategy The key elements of the company’s strategy are to advance Sozinibercept (OPT-302) through two concurrent Phase 3 trials for the treatment of wet AMD; optimize Sozinibercept (OPT-302) administration and develop a co-formulation to reduce injection burden for patients and provide treatment flexibility; expand clinical development of Sozinibercept (OPT-302) in wet AMD, DME and other retinal diseases; and maximize the commercial potential of Sozinibercept (OPT-302). Pipeline Sozinibercept (OPT-302) The company is developing its Phase 3 product candidate, Sozinibercept (OPT-302), a biologic designed to inhibit VEGF-C and VEGF-D, to complement existing VEGF-A inhibitors, for the treatment of ophthalmic diseases, including wet AMD and DME. Anti-VEGF-A therapies represent the standard of care for wet AMD and other retinal diseases. However, there remains a significant unmet need as many patients do not adequately respond to these treatments. As the only biologic inhibitor of VEGF-C and VEGF-D in clinical development for ophthalmology, Sozinibercept (OPT-302) differs from standard of care VEGF-A inhibitors, and in combination with a VEGF-A inhibitor, is designed to address the sub-optimal clinical responses of anti-VEGF-A monotherapies by achieving broader inhibition of the VEGF family to improve visual acuity over standard of care anti-VEGF-A monotherapies. In 2019, the company completed a 366-patient Phase 2b clinical trial of Sozinibercept (OPT-302) in combination with ranibizumab for the treatment of wet AMD, which met the primary endpoint of a statistically significant superior mean gain in visual acuity over ranibizumab monotherapy at week 24. The company initiated two pivotal Phase 3 clinical trials in treatment-naive patients with wet AMD to evaluate the efficacy and safety of Sozinibercept (OPT-302) in combination with anti-VEGF-A therapy compared to a standard of care monotherapy in March, 2021. The company initiated these two pivotal Phase 3 clinical trials in treatment-naive patients with wet AMD to evaluate the efficacy and safety of Sozinibercept (OPT-302) in combination with anti-VEGF-A therapy compared to anti-VEGF-A monotherapy. The company expects to complete patient recruitment in COAST study in the first calendar quarter of 2024 and in the ShORe study in the second calendar quarter of 2024. In addition, in the company’s Phase 1b/2a clinical trial of Sozinibercept (OPT-302) in combination with aflibercept for the treatment of persistent DME, it observed evidence of clinical activity and improvements in visual acuity outcomes compared to aflibercept monotherapy. Sozinibercept (OPT-302) was observed to be well tolerated across Phase 1 and Phase 2 clinical studies in two disease indications following intravitreal administration of over 1,800 doses of Sozinibercept (OPT-302) to 399 patients either as monotherapy or in combination with standard of care VEGF-A inhibitors. Phase 1/2a Clinical Trial Results in Wet AMD In 2017, the company completed a Phase 1/2a clinical trial of Sozinibercept (OPT-302) for the treatment of wet AMD patients under an investigational new drug, or IND, application accepted by the FDA in 2015. The Phase 1/2a trial was conducted at 14 trial sites in the United States. Phase 2b Clinical Trial Results in Wet AMD Based on the positive results of the Phase 1/2a trial, the company completed an international, multi-center, double-masked Phase 2b clinical trial of Sozinibercept (OPT-302) in combination with ranibizumab in a total of 366 treatment-naive patients in August 2019. Pivotal Phase 3 Clinical Trials in Wet AMD The company initiated two concurrent pivotal Phase 3 clinical trials for the treatment of wet AMD in March 2021. These double-masked, sham-controlled Phase 3 clinical trials enroll treatment-naive patients and assess the efficacy and safety of 2.0 mg of Sozinibercept (OPT-302) in combination with anti-VEGF-A therapy for treatment-naive patients with wet AMD compared to a standard of care anti-VEGF-A monotherapy. In addition, to understand the durability of Sozinibercept (OPT-302) treatment effect with less frequent dosing, each trial compares the clinical efficacy of Sozinibercept (OPT-302) administered in combination with the applicable VEGF-A inhibitor on an every 4-week and every 8-week dosing regimen. The primary endpoint of both trials will be the mean change in visual acuity from baseline at week 52. Patients will continue to be dosed until week 96 to further assess long-term safety at week 100. It expects to complete patient recruitment in the COAST study in the first calendar quarter of 2024 and in the ShORe study in the second calendar quarter of 2024. Top-line data is expected to be reported when all patients complete the 52-week treatment period for the primary analysis. If the results at the completion of the primary efficacy phase at week 52 of the Phase 3 clinical trials are favorable, the company intends to file for marketing approval for Sozinibercept (OPT-302) in 2026 for the treatment of wet AMD in the United States, the European Union, and certain other territories. Phase 1b Clinical Trial of Sozinibercept (OPT-302) in DME In 2018, the company completed a Phase 1b dose-escalation clinical trial of Sozinibercept (OPT-302) in combination with aflibercept in nine patients with persistent DME that were previously treated with anti-VEGF-A therapies. Phase 2a Clinical Trial of Sozinibercept (OPT-302) in DME Based on the positive results of the company’s Phase 1b trial, it reported outcomes from a Phase 2a trial in persistent DME patients refractory to anti-VEGF-A therapy in June 2020. This Phase 2a trial was a randomized, double-masked, dose expansion trial that enrolled patients diagnosed with persistent center-involved DME despite regular administration of prior anti-VEGF-A monotherapy. The Phase 2a trial was conducted at 53 trial sites in the United States, Israel, Australia, and Latvia. Commercial License Arrangement with Selexis SA In October 2013, the company entered into a commercial license agreement, or the Selexis Agreement, with Selexis SA, or Selexis, under which Selexis granted it a non-exclusive, worldwide, sublicensable license under certain patents, know-how and other intellectual property controlled by Selexis to use certain cell lines, deliverables and materials provide by Selexis to manufacture Sozinibercept (OPT-302) and related products and to use, sale and otherwise exploit such products. Intellectual Property As of June 30, 2023, the company had rights to 17 issued U.S. patents, six U.S. patent applications, 64 issued non-U.S. patents, and four pending non-U.S. applications. The company’s issued patents and patent applications began expiring in September 2022 all are projected to expire between September 2022 and November 2034 although its most recent provisional application, when completed, would not expire until 2043. With respect to soluble forms of VEGFR-3, the company owns and has licensed rights to patent families, including issued patents in the United States, Europe, Canada, and Australia, which began expiring in 2022 and are expected to continue expiring until 2031. These patents cover composition of matter and/or method of use claims, including claims directed at the treatment of eye diseases associated with abnormal blood vessel growth, such as wet AMD. With respect to Sozinibercept (OPT-302), the company owns a patent family with two issued U.S. patents, an issued European patent validated in 38 countries and non-U.S. patents granted in Australia, Canada, China, Colombia, Indonesia, Israel, India, South Korea, Mexico, Malaysia, New Zealand, Russia, Singapore, and South Africa. Patent applications are pending in the United States and in Europe, Brazil, Malaysia, and the Philippines. The two issued U.S. patents have claims covering the composition of matter of Sozinibercept (OPT-302) and its use and/or nucleic acids, vectors, and host cells for producing it. These issued patents and pending patent applications, if issued, are expected to expire in 2034, without taking into account any patent term extension. As of June 30, 2023, the company or its subsidiaries had registered and owned ‘Opthea’ as a trademark in ten jurisdictions, including the United States and Europe. Research and Development For the year ended June 30, 2023, the company’s research and development expenses included U.S.$122.1 million. Government Regulation The company’s product candidates and any future biological product candidates it develops must be approved by the FDA through a biologics license application, or BLA, process before they may be legally marketed in the United States. Prior to beginning the first clinical trial with a product candidate in the United States, the company must submit an IND to the FDA. Any products manufactured or distributed by the company pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including among other things, requirements relating to quality control and quality assurance, record-keeping, reporting of adverse experiences, periodic reporting, product sampling and distribution, and advertising and promotion of the product. In the United States, the company’s operations are subject to regulation by various federal, state and local authorities in addition to the FDA, including but not limited to, the Centers for Medicare and Medicaid Services, or CMS other divisions of the U.S. Department of Health and Human Services, or HHS (such as the Office of Inspector General, Office for Civil Rights and the Health Resources and Service Administration), the U.S. Department of Justice, or DOJ, and individual U.S. Attorney offices within the DOJ, and state and local governments. The Foreign Corrupt Practices Act obligates companies whose securities are listed in the United States to comply with accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations. In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservancy and Recovery Act, and the Toxic Substances Control Act, affect the company’s business. History The company was incorporated under the laws of Australia in 1984. It was formerly known as Circadian Technologies Limited and changed its name to Opthea Limited in 2015.