For episode 34, we sit down with Bruno Gagnon, SVP of Global Clinical Operations at Opthea. Learn about how Opthea is working to better the quality of life for those suffering impaired vison by improving visual acuity with their novel therapeutic agent. First In Human is a biotech-focused podcast that interviews industry leaders and investors to learn about their journey to in-human clinical trials. Presented by Vial, a tech-enabled CRO, hosted by Simon Burns, CEO & Co-Founder & guest host Co-Founder, Andrew Brackin. Episodes launch weekly on Tuesdays.
Amy Del Medico: [00:00:00] Hi everybody. I’m Amy Del Medico and I’m Vice President of Ophthalmology at Vial. Vial is a technology enabled CRO. I’ve worked in the industry for the last twenty years. I’m here today speaking with Bruno Gagnon, who is SVP of Global Clinical Operations at Opthea. Bruno, would you like to introduce yourself?
Bruno Gagnon: Absolutely. Thank you, Amy. It’s a pleasure to be here. That’s correct, I’m heading up the Clinical Operations group globally for Opthea, which is an ophthalmology company. Glad to be here.
Amy Del Medico: Thank you very much. Bruno, you have over thirty years of experience working in clinical operations. I know you’ve worked at a number of different pharmaceutical companies. How has your approach evolved over this time, and what have been some of the key learnings that you have?
Bruno Gagnon: I’ve been in the Bay Area now for over twenty years. My approach has evolved. In the beginning, I was focusing a lot on processes, SOPs and hiring people at companies such as Chiron, Fibrogen, BioMarin, and most recently at Bridge Bio. I have seen companies of different sizes and I’ve done a lot of work in small biotech and startups. Building infrastructure is not always the most important in the startup environment. I realized the key is to have the maximum impact in a short amount of time, because often the small companies live and die based on data.
Making phase advances is very important. Go to that Phase 2B, for example, and make sure that you have your proof of concept will allow you to raise money and eventually get to that phase three. In the way I work, there’s always, especially in small companies, a heavy outsourcing component. You have to have really good talent in the office. Then to put the right balance between what you outsource, and what you do in house, right? Because you’re going to need an important component that will be zero oversight, and go-to results focused on everything to make that phase advance.
It’s always a non-regrettable move to put emphasis on quality, because even if you go fast and there are some mistakes being made along the way, you may have to redo the work. Typically spending more time on the front end, the planning period is always important. You can never plan too much in advance. You can never hire great people too early. That’s never happened in my career, where I said, “Oh, I wish I would have hired that great person, later.” You always feel that you need the people to be able to support you. I call it hiring ahead of the curve. It’s very important.
Amy Del Medico: I like that. You can never hire great people too early. That’s fantastic. What led you to join Opthea, and what particularly excites you about Opthea’s mission?
Bruno Gagnon: When you look at the next company you want to work at like a biotech company, in most clinical operations, leaders will probably look at similar factors, but you want to have great technology, or great science. At Opthea, we have a novel therapeutic agent. That’s exciting. Is there an unmet medical need? Sometimes there are great molecules, but the disease area can already be saturated.
The third thing is the people, because nowadays, you’re not choosing an office because of the- the parking lot or they have beer in the fridge. Most people work remote, or go to the office once or twice a week. It’s not so much like the work environment in a sense, a physical environment, but the people. The people are always very important. For me, with Opthea, I had all that. It’s the only company working on improving visual acuity for retinal disease. All other drugs that are being developed right now will be looking at durability, which means that existing drugs that are great, the companies are trying to make them last longer, which is great, it’s also important. But we have a drug with a novel mechanism of action.
There’s definitely a clear unmet medical need, which is age-related macular degeneration, wet AMD. I was excited when I saw that. It’s still a young company with this potential to make a really big difference to disrupt what is happening right now in the field of wet AMD.
Amy Del Medico: It’s exciting to work for a company that’s taking a slightly different approach. I think that makes it really appealing to come and work with. I certainly feel that way about Vial, as well, with our sort of technology enabled solutions. It’s making a huge difference.
How do you think your experience has prepared you for your current role at Opthea? Have you come across any challenges that surprise you, that perhaps you weren’t anticipating?
Bruno Gagnon: There are always surprises. Not having surprises by itself would be a surprise, but when I arrived, in fact, keep in mind, I didn’t come with deep ophthalmology experience, so then it’s always a little bit of the first challenge is that I need to learn the therapeutic area, and the acronyms and all that. But, the fact that I had a lot of startup experience, I also didn’t mention in the beginning, but I also did a number of years of independent consulting after my BioMarin days. I did a lot of small companies where you come in and there’s not necessarily any kind of processes yet.
I was lucky because there were already people there that had been working on the design of the phase studies, like phase two and three. Great scientific knowledge, so they were able to guide me. But my deep CRO management experience helped me also, because as I said earlier, we count on our CRO and vendor partners. Making sure that you could put the right emphasis on the focus, where do you put the expectations from the sponsor, and all of that?
Another success factor, and for me, maybe one of my core strengths is developing powerful relationships with healthcare providers, investigators, and study coordinators. Small [00:05:00] companies don’t have a lot to compete with the large companies who have drugs on the market, they have huge groups, and a presence. They are household names in this field.
People don’t necessarily need to know us, or they don’t know our drug yet, or our drug candidate. You have to go out there and meet with them, make a name for yourself, and make sure that they keep your trial and the company you’re working for top of mind. In my experience, building relationships helped a lot, because even though I was new in the field, I was able to quickly make a mark.
And to the last part of your question, in terms of surprise. I was happily surprised that the retina community was so welcoming. At the very first meeting I went to, people were walking me around, making introductions, and very quickly I felt at home, learning from them. I go there very humble, I tell them I’m here to learn from you.
I’m not trying to go and say, “Let me explain to you our trial. Of course, I know my trial very well. But they know the disease. Down to entry level or early career study coordinators, or, KOL and people in the middle, like new physicians who want to develop their career, when I meet with them, I always ask them, “Tell me how you work. What are the barriers of success for our trial, or for trials in general, in the field of retina.” I’m learning from them, and that was a good finding for me.
Amy Del Medico: It’s a very small and extremely busy community, isn’t it, retina? You’re absolutely right, building those relationships is key. I’m going to change the focus a little bit, now. We’ve touched on this, but I wondered if you could dive a bit more into the mechanism of action of OPC302, and, perhaps, how it differentiates from both emerging therapies, and those that are already established.
Bruno Gagnon: As many people may know, existing treatments for wet AMD work very well. They are called anti-VEGF A, and for example, Ranibizumab, which is Lucentis, and Aflibercept, which is Eylea. They have revolutionized the treatment of wet AMD. Anti-VEGF injections are now the standard of care, there is no doubt about it. However, we know that they are not sufficient. More than 40% of patients on these therapies still do not achieve meaningful vision gain. About 25% will have further vision loss, despite being on these drugs.
In fact, the majority of patients end up not being able to do daily life activities, such as driving, cooking, or reading. Our compound, our molecule is called OPT302, it’s a novel therapeutic agent. What it does, it inhibits the angiogenic signaling through VEGFR 2 and 3 receptors. It blocks, or we can even say it traps the light in VEGF C and D and prevents them from activating VEGF 2 and 3 receptors, with that it provides broader inhibition of the angiogenesis process, and it prevents leakage from existing blood vessels. It blocks the formation of new blood vessels in the eye, and prevents leakage from existing blood vessels.
The results from our phase 2B trials were very strong. The goal of the phase three is to demonstrate that OPT302, in combination with any anti-VEGF A, has the potential to achieve superior vision gain. Or, more visual acuity, in this case, compared to monotherapy. In other words, OPT302 plus the standard of care would be superior than the standard of care, alone.
Amy Del Medico: Are you able to discuss the status of Coast and Shore, how are they going, and if there are any particular milestones that you’d like to talk about?
Bruno Gagnon: I’m happy to. Obviously, this is my day to day life, it’s my passion. So I have two phase three clinical trials ongoing and recruiting. Shore is our drug on top of Lucentis. Coast is our drug on top of Eylea. They are global studies in twenty-five to thirty countries. We are making excellent progress in recruitment. Every week we enroll patients. It’s moving steadily. We expect to complete enrollment by as early as the end of December 2023. So, we’re probably in the last stretch.
Based on the study design, because it’s an efficacy study with primary endpoint being visual acuity would be at 12 months. You can imagine last patient, last visit, being by the end of 2024. Top line results would be shortly after that in a question of a few weeks. We have an experienced team in operations. Looking at the data, we’re working on techniques such as, clean as you go, rolling log, and we want to decrease the time from last patient in to the top line.
I want to be able to count it in days from the moment where we say, last patient out, when are we gonna have our top line results? It should be pretty fast. But right now, the focus is on enrollment, it’s on quality of the data. We’re very excited about the way this is going now.
Amy Del Medico: I can’t wait to see what the results are next year. COVID-19 had a huge impact on clinical studies across all therapeutic areas. How did it impact recruitment for your studies? Has it changed the way you have worked since then?
Bruno Gagnon: COVID has changed the way I work. Just for context, I started with Opthea last year, so the pandemic had stabilized a little bit. When Opthea started, it was right in the middle of the pandemic and even lockdown. The huge challenge there was, as you can imagine, starting a trial around that time, everybody in the industry faced challenges of startup, because you had contracts, IRVs, and regulatory authorities. A lot of [00:10:00] those were delayed. This was a challenging start.
On top of that, you think about, as I mentioned earlier, site and personal engagement. That was a lot harder, because anything from an investigator meeting from SIVs to CRO kickoff meetings everything was done online. We can do online meetings, but it’s not the same. If you do a study in twenty-five countries, and you have no chance to go to any of those, it’s hard. So the study had started in a challenging environment, like many people.
Another area, we all appreciate in the COVID era, is staff turnover. Not just like CRO staff, and our own staff, but at the site level. Many people, at the site level, decided to go work somewhere, or work from home. Even investigators would say, “I would love to do your study, but I don’t have the personnel to run it. We are overwhelmed, I cannot take it.” Site selection was affected. Now, I was at a different company during COVID and we faced the same things.
But how are we doing things differently now? We appreciate that many things can be done remote, we can do a lot more, like remote monitoring, and training. We adapt to this, but I want to go back to the importance of human contact. It’s not enough, and if you have zero choice, then of course we can support the patients, give them transportation, and deliver drugs at their home. But, some trials, let’s say, a drug that needs to be injected, you cannot do this from home. Patients still need to be able to go to the site.
We need to figure out ways to support the patients, in any environment like that. Since our challenging start, we’ve overcome that. We’ve doubled down on site engagement. The core of our strategy is to meet with people, develop relationships, train and retrain. We talk about lessons learned. We have what I call the principle of cross pollination. We do investigator meetings, or study coordinator meetings, in person, it’s a workshop style, and we work with them on finding solutions. We take these and we bring them to the next meeting. And then what we learn from one meeting gets presented at the next meeting. We go to conferences, and have oral presentations, just to make sure that Opthea is present in the community.
Recently, as of a few months ago, we built an MSL group. I have MSLs reporting in to me now. They are in the field visiting doctors. They support even study coordinators for our phase three study. We’re using the MSL as a way to do site engagement, and have similar roles, also in other countries. We feel this is an important way that we can distinguish ourselves from the other companies who have clinical trials on there. Even if, technically, there is no competition for our patients in the study, but there’s competition for the attention, and for the workload of the study coordinator. We feel being out there, and present, and supporting them, we will help focus their time on our study, when it’s appropriate.
Amy Del Medico: Thanks, Bruno. COVID’s taught us a lot I think, but you can’t beat that face to face, it’s just so nice to see people in the flesh. Lastly, what is Opthea’s long term goals for advancing retinal disease treatment?
Bruno Gagnon: As I said, our trials are designed to demonstrate superiority in the OPT302 plus standard of care compared to monotherapy alone. Our goal is to increase visual acuity outcomes. The first thing is we need to get it demonstrated in a well powered phase three pivotal trial. From that, you make angiogenic drug approval, and a label that would be broad enough that people could use OPT302 with any anti-VEGF therapy.
After that, we will look at other indications in retina, like GME, diabetic retinopathy, and RVO. We’re focused on patients, we want to make sure where are the needs. Where are the areas where patients need it? And the doctors, we want to give them tools.
Our trials are designed to demonstrate superiority in the OPT302 plus standard of care, compared to monotherapy regarding visual acuity outcomes. Once we can demonstrate that in wet AMD, we’re planning to continue to explore other indications. We feel we have one of the most innovative drug treatments in retinal disease, but other diseases that are characterized by venous growth and edema, we feel that we can address that. The first step is to demonstrate in wet AMD, because this is our well-powered study, then you are able to look at potentially other areas.
We expect the doctors may want to use this earlier than later with some of their more severe patients. It will be left at the discretion of the doctors how they use OPT302 for the label, obviously, but how they can play a little bit with it, based on the patients that they are treating themselves. You can start early with combination therapy, or you can wait until the patient would deteriorate, but we just hope that they will have a great understanding of the mechanism of action, and how they can improve visual acuity by adding anti-VEGF C and D on top of what they’re already using.
Amy Del Medico: Thank you so much, it’s been so interesting talking to you today.
Bruno Gagnon: Thank you, Amy. It was a pleasure.