INNOVATION IN RETINA: Opthea’s Promising Therapy for Retinal Diseases

CEO Megan Baldwin is well prepared to lead.


Although it is based in Melbourne, Australia, biotech company Opthea wanted it known from early on that its development strategy would be relevant globally. As such, the company made several key strategic decisions. First, it conducted the early-stage trial for its OPT-302 drug for retinal disease at US clinical sites under FDA regulations. It also sought to attract specialist US and European health care investors, and stayed in close contact with knowledge leaders in the worldwide retina community.

“Being based in Australia, in many ways the easier path may be to conduct trials only in Australia or Asia,” says Megan Baldwin, PhD, Opthea’s CEO. “While that can be a viable approach, we recognized early on the benefits of approaching our development program with a long-term global view, similar to that of our US and European counterparts.”

Opthea CEO Megan Baldwin, PhD


Opthea recently took a giant step in terms of creating a global footprint with the release of across-the-board positive data from its 12-week, 51-patient phase 1/2a study that evaluated OPT-302, its fusion protein “trap” therapy in the treatment of wet AMD. The drug was investigated as both monotherapy and in combination (two injections given 30 minutes apart) with ranibizumab (Lucentis; Genentech). The results were so impressive in both mono- and in combination therapy that Opthea was able to quickly consummate an oversubscribed $45 million (Australian dollars) offering to fund 3 additional clinical trials and keep the company fully funded until 2021.

The studies will encompass a 350-patient phase 2b trial for treatment-naïve wet AMD patients, a smaller phase 2a trial for previously treated wet AMD patients, and a phase 2a trial for patients with DME.

The science behind OPT-302, Opthea’s only current investigational drug candidate, is in some ways familiar. It is based on foundational research at the University of Helsinki and the Ludwig Institute for Cancer Research in Melbourne (both now Opthea shareholders), which formed a basis for continued internal development and optimization of the drug at Opthea.

“As a fusion protein with a ‘trap’ mechanism of action, OPT-302 bears some similarities to aflibercept (Eylea; Regeneron), but Eylea targets VEGF-A and our drug targets VEGF-C and VEGF-D that are novel members of the VEGF family,” says Dr. Baldwin.

Thus, a major part of the potential appeal of intravitreally injected OPT-302 is that used in combination with one of the currently approved anti-VEGF-A drugs, it could inhibit VEGF-A, -C, and -D, in what lead investigator Pravin U. Dugel, MD, calls a “pan-VEGF” approach.

The phase 1/2a trial, though early-stage, demonstrated that OPT-302 was well tolerated following 3 monthly intravitreal injections in both treatment-naïve and previously treated patients who are considered “difficult to treat” and have demonstrated a suboptimal response to prior anti-VEGF-A therapy. Monthly OPT-302 also demonstrated clinical activity in all patient groups investigated, with improvements in visual acuity and reductions in subretinal fluid over the 12-week trial.

Dr. Baldwin said the decision to begin a 90-patient trial in DME later this year was based on the reduction of retinal thickness and subretinal fluid achieved in the phase 1/2a trial.

“We know that reducing fluid is a key to combating DME, which presents an opportunity for OPT-302 for that indication,” she says. “We are also interested in other indications beyond wet AMD and DME. RVO is one of them. Overall, we have sound science and think that OPT-302 has the potential to be a game changer.”


When Dr. Baldwin joined the company in 2008, Opthea’s focus was on oncology and potential cancer treatments. However, company researchers soon began to see that their therapeutic concepts also applied to retinal disease, a relationship that had previously been explored by the Folkman Lab at Harvard. By 2014, after further preclinical research and some corporate restructuring, Opthea became fully committed to developing treatments for wet AMD and other retinal indications — with Dr. Baldwin ascending to the posts of CEO and managing director.

Being at the head of a company focused on biologic treatments for retinal disease was a perfect fit for Dr. Baldwin, who had spent 5 years at Genentech, first as a researcher working with the team of Napoleone Ferrara, MD, who discovered VEGF-A, and 2 years gathering valuable business experience in market planning on the company’s commercial side. Her time at Genentech provided her with a set of skills well suited to an entrepreneur.

“My time at Genentech was definitely a key part of my career,” she says. “I began with a scientific background (a PhD in medicine from the University of Melbourne) and was able to broaden my experience in the commercial realm. But even with that experience, you have to deal with the fact that a smaller biotech is fundamentally different than a large company like a Genentech.”


Dr. Baldwin has found that, in her case, the gender-based glass ceiling has not been an impediment to career advancement, but she recognizes that she is fortunate to have had key mentors and supportive environments to guide her career.

“As women CEOs we are outnumbered,” she laughs. “But I try not to think about it very much. I focus on the job at hand; advancement should be based upon job performance. I do have younger female colleagues knocking on my door asking for career advice, but it’s mainly about how they can successfully translate a scientific background to the commercial realm.”


Dr. Baldwin believes that making the translation from scientific skills to business skills is an aspect of the Australian biotech industry that is becoming increasingly recognized as critical for the success of the sector.

“Melbourne has great capability in academic research but the biotech community here is smaller than in the US, with many focused on early-stage research,” she notes. “There are several university and government programs that have been established over recent years to facilitate the effective transition of early-stage research into translational medicine and commercial opportunities, but there is still more work to do in that area.” RP