PERTH, Australia – On the heels of positive phase IIb data, Melbourne-based Opthea Ltd. announced a private placement of AU$50 million (US$33.87 million) from institutional investors in Australia and the U.K. to advance lead candidate OPT-302 to phase III trials in wet age-related macular degeneration (AMD).
The funds will be used to manufacture clinical-grade OPT-302 and for two concurrent phase III pivotal trials.
Two phase III registrational studies are required for registration in the U.S. and EU as well as other regulatory agencies, Opthea CEO Megan Baldwin told BioWorld.
Opthea announced positive phase IIb results in August that demonstrated that OPT-302 combination therapy met the primary endpoint of superiority in mean visual acuity gain at 24 weeks compared to Lucentis (ranibizumab, Roche Holding AG/Novartis AG) monotherapy in treatment-naïve patients with AMD.
OPT-302 is a soluble form of VEGFR-3 or “trap” molecule that blocks the activity of VEGF-C and VEGF-D, which cause blood vessels to grow and leak.
“We intend to run the trials concurrently and independently across global trial sites. Running two separate studies provides more statistical power for phase III data, and this is a preferred approach than running only one larger phase III clinical study,” she said, noting that the company anticipates beginning the studies in the second half of 2020.
Opthea has not yet discussed the program with the FDA, Baldwin said, noting that the end-of-phase II meeting with the agency is scheduled for the first half of 2020.
“We plan on opening a number of sites in the U.S., which is consistent with how our phase IIb study was conducted,” she said.
About half of patients receiving VEGF-A therapies for wet AMD are considered nonresponders, Baldwin said, noting that OPT-302 blocks VEGF-C and VEGF-D that cause vessels to grow and leak and are hallmarks of wet AMD disease progression. Approved therapies such as Lucentis and Eylea (aflibercept, Regeneron Pharmaceuticals Inc./Bayer AG) inhibit VEGF-A, and Opthea will position its therapy as an additive benefit to existing therapies.
Combination therapy of OPT-302 and a VEGF-A inhibitor achieves more complete blockage of members of the VEGF family, blocking mechanisms contributing to suboptimal responses to selective VEGF-A inhibitors and has the potential to improve vision outcomes by more completely inhibiting the pathways involved in disease progression.
Exploring strategic options
The placement was priced at AU$2.65 per new share, representing a 5.9% discount to the 15-day value-weighted average price (VWAP) and a 3% discount to the closing price of AU$2.73 on Nov. 29. A total of 18.9 million fully paid ordinary shares will be issued under the placement, representing about 7.5% of current issued capital. New shares issued will have the same terms and rank equally with Opthea’s existing fully paid ordinary shares.“This financing allows the company to trigger several activities that allow the phase III clinical development program to progress according to our timeline, including manufacture of clinical-grade OPT-302 for trials, regulatory interactions and phase III planning,” Baldwin said.
“The financing will see the company’s operations funded into the first half of 2021, which means we are in a strong financial position to explore strategic opportunities and clinical activities.”
Opthea is developing OPT-302 for use in combination with inhibitors of VEGF-A and has reported outcomes from an international, multicenter, prospective, sham-controlled, double-masked, superiority study that enrolled 366 treatment-naïve patients with wet AMD.
“We’ve shown vision gain over and above what patients currently have available, and small gains in patients who lose vision makes a massive difference in patients’ lives,” Baldwin said.
The phase IIb, randomized, double-blinded, sham-controlled trial recruited 366 patients with wet AMD who were allocated to two intravitreal doses of OPT-302 (0.5 mg and 2 mg), administered monthly in combination with 0.5 mg Lucentis over 24 weeks, vs. a control group that received standard of care 0.5 mg Lucentis administered monthly.
The higher-dose OPT-302 combination treatment showed improvements across multiple secondary endpoints: 45% gained 15 or more letters from baseline to week 24, compared to 40.5% of patients in the Lucentis control group. The proportion of patients gaining 10 or more letters was also greater, at 70% vs. 57.8%, respectively. Stable vision was achieved in 99.2% with the higher-dose OPT-302 combination treatment, compared to 96.7% of the Lucentis control group.
“We are the only drug that has demonstrated significant efficacy above standard of care. A number of other drugs have failed, including big pharma companies, but the reality is, if you can change the efficacy of a drug, you can drive the most benefit,” she said.
Baldwin said she anticipates reporting top-line data from its ongoing phase IIa trial of OPT-302 in patients with persistent diabetic macular edema in early 2020.
Opthea’s stock on Australia’s Securities Exchange (ASX:OPT) gained 138% following the phase IIb news in August when its shares were trading at AU$2.06. Opthea shares have steadily risen and were trading at AU$3.16 by market close Monday.