Opthea, a public company listed on the Australian Stock Exchange, is developing OPT-302, a novel therapy for wet age-related macular degeneration (AMD). The company’s lead compound targets two alternative members of the vascular endothelial growth factor (VEGF) family, VEGF-C and VEGF-D, through a “trap” mechanism. Currently approved anti-VEGF treatments, Lucentis and EYLEA, target VEGF-A. Long-term single-agent therapy with VEGF-A inhibitors is associated with a sub-optimal response in both visual acuity and persistent retinal fluid. VEGF-C levels in the retina increase with AMD disease severity, and VEGF-C is up-regulated when VEGF-A is inhibited.
Megan Baldwin, CEO and managing director, explained that VEGF-C and D work as important mediators of neovascular function as they induce angiogenesis as well as vascular permeability, and can also mediate non-neovascular functions as well, such as inflammation. Ophthea developing OPT-302 as a combination therapy with the existing anti-VEGF-A agents in order to mediate a more complete blockade of this very important VEGF receptor family. But we’re also potentially complementary to other novel therapies that are currently in development as well.”
A Phase I/IIa trial is being conducted at 14 clinical sites in the US, with ongoing recruitment into the Phase IIa dose expansion cohort. In the 20-patient Phase I study, OPT-302 was administered in combination with Lucentis or as monotherapy, in difficult-to-treat sub-responsive patients plus some treatment-naive patients. OPT-302 was safe and well tolerated in this study, and 16 of 19 evaluable patients maintained or gained vision from baseline to week 12, with no patient losing more than 3 letters. Improved outcomes in patients that were sub-responsive to prior anti-VEGF-A therapy suggest incremental benefit of VEGF-C and VEGF-D inhibition.
Opthea is actively accruing into Phase IIa and is planning to advance OPT-302 combination therapy into a Phase IIb randomized controlled clinical trial in 2017.
Megan Baldwin, PhD
Dr Megan Baldwin is CEO/Managing Director of Opthea Limited and has over 19 years of experience in preclinical and clinical development of therapies for cancer and eye diseases.