Megan Baldwin, PhD, MAICD, is the CEO and managing director of Opthea Limited, a clinical stage biopharmaceutical company, based in Melbourne, Australia with a growing US presence. Opthea is developing OPT-302, a novel biologic inhibitor of VEGF-C and VEGF-D, for use in combination with VEGF-A inhibitors for the treatment of wet AMD and diabetic macular edema (DME). Dr. Baldwin has more than 20 years of experience focusing on angiogenesis and therapeutic strategies for cancer and ophthalmic indications.

Ophthalmology Management: Opthea’s lead product candidate is OPT-302. Can you discuss the need for this treatment and how it works?

Megan Baldwin: Opthea’s research with retinal ophthalmologists and retinal specialists indicated that physicians currently have limited treatment options for wet AMD and that those current standard-of-care therapies do not address limitations in clinical efficacy that are observed in many patients. We recognized the urgency in advancing OPT-302 for the treatment of wet AMD so that physicians have an additional treatment option in their everyday practice and importantly, one with the potential to improve vision outcomes in their patients.

OPT-302 is given via an injection into the eye and is designed to target the mechanisms and the biology that lead to wet AMD. It works by blocking two members of the vascular endothelial growth factor family, VEGF-C and VEGF-D, which stimulate angiogenesis and vascular permeability independently of VEGF-A and are upregulated when VEGF-A is suppressed. The OPT-302 molecule mops up those VEGF-C and VEGF-D signals, and that has a downstream effect to reduce lesion development and shrink the network of vessels that can occur in wet AMD.

OPT-302 has also been shown to decrease swelling and have a greater drying impact at the back of the eye. These anatomical changes may also contribute to a functional improvement in visual acuity in patients. Opthea has demonstrated this in our large Phase 2b clinical trial and has shown activity of OPT-302 in early-stage clinical trials as well. We are also looking to confirm these data in the larger registrational Phase 3 program, which we hope will lead to approval of the product globally, but initially in the United States, Europe and Asia Pacific.

OM: Can you discuss the recent OPT-302 trials?

MB: We conducted a large Phase 2b clinical trial in treatment-naïve, wet AMD patients. A total of 366 patients were recruited into the study, which was conducted across 10 countries. The objective was to investigate if adding OPT-302 to standard of care ranibizumab therapy resulted in better clinical outcomes, including visual acuity. We asked the question, if we add OPT-302 to ranibizumab, will we see improved visual acuity outcomes after a 6-month dosing period?

We tested two doses of OPT-302 — a lower dose as well as the dose of 2 mg, which we have taken forward into our Phase 3 clinical trials. We hit the primary endpoint of the Phase 2b clinical trial, in that visual acuity was significantly better in those patients who received the 2.0-mg OPT-302 treatment together with the standard of care compared to patients who received ranibizumab alone.

Our Phase 3 registrational program is being conducted across 30 countries and includes two Phase 3 clinical trials (ShORe and COAST) that are being run concurrently. Both Phase 3 trials are double-masked, sham-controlled studies that enroll treatment-naïve patients and assess the efficacy and safety of 2.0-mg OPT-302 in combination with anti-VEGF-A therapy (either ranibizumab in ShORe or aflibercept in COAST) compared to standard of care anti-VEGF-A monotherapy.

To understand the durability of OPT-302 treatment effect with less frequent dosing, each trial will compare the clinical efficacy of 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.

OM: What other developments are in the pipeline for the US?

MB: We see the opportunity to expand the clinical development program with OPT-302 into other retinal eye diseases, and we’ve already conducted a trial of OPT-302 in diabetic macular edema. We’ve shown some very promising results that this is a molecule that may also have efficacy across a broad range of retinal eye diseases. OM