Hi, everyone. Thanks for joining us here at the Bank of America Healthcare conference. My name is Daniel Giraldo. I'm one of the biotech analysts here at the bank. Our next presenting company is 4D Molecular Therapeutics, and I think the company has a few slides. David, if you want to go ahead and start, and then we'll do a short Q&A after.
All right. Thanks, Daniel. Thanks for having us. I'm David Kirn, co-founder and CEO of 4D Molecular Therapeutics. 4D-150 is our lead product candidate. This is currently in phase III development in wet AMD. Forefront One is well underway with over 50 clinical trial sites activated today. There is great momentum there. This is the first known genetic medicine to receive RMAT designation for both wet AMD and DME. 4D-150, phase III therapeutic, is designed to disrupt the global market for retinal vascular diseases and improve patient outcomes. We'll walk through each of these items on the slides. First of all, this is addressing a $17 billion anti-VEGF market, and this is growing significantly. We're expressing aflibercept from our product, which is the market leader. This is just showing the growth of the branded anti-VEGF market over time as the population ages.
This is a massive and growing market. Importantly, you can see in dark blue at the top there on the far right, the rapid uptake of Vabysmo, which is driven by about a two-week improvement in durability. This is in marked contrast to what we provide, which is multi-year durability. I think this is evidence that new agents with improvements in durability can become blockbusters very quickly. This is looking at durability improvements over time in the field. You see going from Lucentis to Eylea, the durability is on the order of a little bit over a month. Going from Eylea to Vabysmo is again a month or two. Yet each of these products has been a blockbuster as they have entered the market. You can see Vabysmo is reducing injection burden by about 23%.
Our data to date says we can do about 85%-95% reduction. This is a backbone therapy with multi-year durability. This is really addressing the key unmet need in this space, which is durability. This is the number one thing that patients want. When you ask them what novel mechanisms are you most interested in, gene therapy is at the top. This is what we see with standard of care. In the middle there, you see the repeat bolus injections with the central subfield thickness of the retina expanding and contracting over and over again. That leads to vision loss over time. In contrast, for 4D-150, where we're getting sustained expression of aflibercept 24 hours a day, seven days a week, you see a nice stabilization of CST. The belief is that will result in better long-term vision outcomes.
This is data from our phase I to PRISM study, where we've treated and studied a very broad range of patients, probably more broad than anyone has done in development to date. What we see on the far left is in the most extreme patients, the highest need recalcitrant patients, we see an ability to reduce injection burden by about 83%. Again, just for context, Vabysmo, 23% in front line, this is 83% in the hardest to treat. When we move all the way to the right and we look at recently diagnosed patients in our phase II study, we see that we can reduce the injection burden by about over 90% at 94%. Really broad activity across a broad range of patients. Safety is critical in a large market opportunity like this with existing therapies. We've been thrilled to date with our safety.
We think this comes from the fact that we innovated and invented a novel vector that is easy to inject intravitreally with little or no inflammation. You can see overall no serious adverse events. Importantly, about a 3% mild transient rate of cells in the eye, very similar to what we see with Eylea, the market leader. Skip over that slide. Ease of clinical and commercial optimization here. Chris will speak a little bit to this, our Chief Commercial Officer. Importantly, this is a single IVT intravitreal injection, seamlessly fits into the clinic flow, routine storage conditions, routine shipping conditions, and really an optimal therapeutic for the buy and bill model that makes these practices so lucrative. We think we are actually going to help them to make more money and fit seamlessly into their practice flow. This is a lot of what we are talking about.
We believe payers are going to like this because patients have fewer visits, fewer complications of their disease. That is going to save them money. Again, they'll be paying money upfront for long-term durable benefit. We have very low cost of goods on the order of $500. We have a lot of pricing flexibility here. Again, we've already spoken to how this fits seamlessly into the clinic and will free up space for them to make more money on other patients and other treatments. Finally, we're in phase III. We expect to have top-line data from our wet AMD pivotal trials, both of those phase III in the second half of 2027. This is the design.
I think what's important here in the interest of time is just to emphasize that this was designed by some of the most experienced key opinion leaders and experts in the field, as well as top industry leaders who are responsible for approval of six of the top seven retina agents out there. It is very carefully designed to be a non-inferiority win on best corrected visual acuity or BCVA and to show a very significant reduction in injection burden for patients on the treatment arm of 4D-150 in comparison to aflibercept. Again, we've talked about these timelines. We hope to beat these timelines and bring this in even faster than the 15 months that we've signaled externally.
Finally, in addition to 4D-150 for wet AMD, we also have very promising data for diabetic macular edema with this agent and have approval from FDA to do a single approval study for that. We are looking to advance that. We also have an active program of 4D-710 for cystic fibrosis lung disease, where we are seeing some really outstanding clinical activity. We look to update that in the second half of this year. Thank you.
All right. Great. Thanks, David. Thanks for that introduction. I thought maybe we could start with just some general questions on the macro. This is something we've been asking all of our companies just because it's become very topical with all the recent changes we've been seeing impacting the biotech industry. Maybe to start, can you comment on sort of your recent interactions with FDA? Have you noticed any changes? Do you expect to have any significant interactions with them now that your phase III trials are underway? Do you have any thoughts on how their view on gene therapies could change over the next few years?
Let me just start on that. We haven't noticed any changes to date. The people we're interacting with at FDA for the cystic fibrosis program have not changed. We recently received RMAT designation for DME with 4D-150. There's incredible progress there. I think importantly, these questions around endpoints, this is not a problem for our programs. I mean, we're using BCVA, which is the gold standard functional endpoint. For cystic fibrosis, we're looking at lung function through FEV1 and lung clearance index, both of which are tried and true and not surrogates. I think we're well positioned.
Okay. Great. Maybe as you get closer to commercialization, how are you thinking about manufacturing? There is a lot of talk in terms of potential tariffs to the biotech industry. How are you thinking about that? What is your plan for manufacturing at this point?
Want to speak to that?
Sure. Yeah. I mean, currently our manufacturing is all in-house. I think as we get closer to commercialization, we'll look to outsource and tech transfer that to the right third party. All of that we would expect would occur inside the U.S. If there are tariff effects on supply chain, we don't necessarily believe that we would have exposure there.
Okay. Great. David, you mentioned you have some readouts coming out later this year. I think you'll have two-year data and 18-month data for 4D-150 and wet AMD. I guess, can you maybe set expectations for that? What should we be looking to see for those data? What do you think are going to be sort of the key learnings from that?
I think there's great data with AAV in the retina from other programs showing anywhere from 5 to 10+ years of durability. We would expect to see the same. We have very little, if any, inflammation. We would expect very durable expression. We would expect to see that. We expect to see then consistent reduction in treatment burden over time. It's not to say that every single patient is going to be injection-free. A patient may, every year or two, need a bolus in marked contrast to, on average, 8-10 a year. We expect to see good long-term safety and good long-term injection burden reduction that does not drop off over time, that is consistent over time.
How are you thinking about sort of the balance between injection burden reduction and injection freedom, which is something that I think has been a focus for investors for previous readouts you've had? What do you think is the importance for those two different endpoints? How do you think physicians might look at those two different things when they're thinking about choosing this therapy for their patients?
Yeah. The physicians that we talk to, and Chris can speak to this as well, and patients, injection-free never comes up. These patients are getting dosed every four to eight weeks in the eye. If you can say, "I can decrease that by 80%-90% your need for that," they're like, "That's a win. I don't need perfection." That doesn't come up with them. It's an investor-specific thing. If I had to guess where it comes from, I would guess it comes from the fact that they assume gene therapy is going to be dangerous, which ours is not. They assume gene therapy is going to be very, very expensive, which ours is not. Very different situation. Chris has had hundreds of these conversations. You want to take it away?
Yeah. No, not much more to add. Listen, if you can be injection-free, of course, that's ideal. No one would say no to that. We think certainly we believe our data would show that some patients would certainly well fall into that category. Some patients are going to need occasional supplemental therapy. The good news is that there's a great number of really efficacious supplemental therapies that are out there that physicians are very well accustomed to. We have those options. I think it's really important, and we see this already in our phase II data, that even if you do need a supplemental therapy bolus injection following 4D-150, it doesn't mean that you now need them at the same frequency that you would have otherwise. It may be, we think it would be occasional.
That treatment burden reduction that you see in year one, we think that proportional rate would extend long-term over time. Certainly, patients will still need monitoring. They'll still need to see their physician. There's a big difference from a patient perspective, at least, between going into the office for a monitoring and an assessment versus going in for an injection.
Got it. How are you thinking about sort of the competitive profile of 4D-150 as it relates to other gene therapies in development for wet AMD and also other long-acting treatments or TKI inserts that we're expecting to go into and enter the market in the next few years?
Yeah. I mean, as David's shown, as you all know, it's a large market that's growing. We actually estimate by the time we get to our launch window, the value of the market globally is well over $20 billion. It's got room to accommodate a lot of different, I think, assets with different profiles. We think our profile stands up and is really differentiated from a number of perspectives. First of all, relative to TKIs, TKIs seem to show an efficacy. I think the question remains as to how efficacious they will be in a harder-to-treat patient population, which, by the way, every time you launch a new medicine in this space, the first patients you're going to get used upon is patients that have a high treatment burden, which makes perfect sense, right?
As a physician, you're going to consider patients that have the highest treatment need as the patients to be considered for new therapies. I think there's a question there. We believe that should they be successful in phase III, there's room for them in this space. We think of, listen, long-acting bolus injections today like Vabysmo will get certain portions of patients out to three or four months. If you're an asset that's going for a six-month profile, we see them as in the same category of each other. Our goal with 4D-150 is not to add an extra month or two to durability. Our goal is to actually set a new standard where many patients have months, if not years, of durability. We think that's a completely different paradigm versus some of those assets in development.
Got it. Can you maybe talk about sort of your expectations for initial uptake just based on your conversations you've had with physicians? You've shown data in sort of more severe patients. You've also shown data in more mild to moderate patients. Where do you think 4D-150 could be used initially? How do you see that evolving over time as physicians get more comfortable with the profile?
Yeah, for sure. Good question. First of all, I think a good proxy for interest and uptake is enrollment in our trials. We see that in our phase II trials, enrollment was quite strong. We would expect that would continue as we get further a few months out with phase III already starting last month. The first patients that are going to get considered for these therapeutics are the patients I mentioned earlier, these patients that are on 8, 9, potentially 10 injections per year with current standard of care. I think all new assets that are approved are going to get first tested with that patient profile. What makes us feel really good and confident is that we actually have really good data that we showed earlier with that exact patient profile, our phase I, phase II-A patient profile.
We're hard to treat patients with an average injection rate of over 10 per year. We think we'll perform well with that patient population. As the launch progresses, I think expanding it to consider patients that are maybe of lesser treatment need or more naive in their diagnosis is probably where we would see the adoption grow.
Great. All right. I think with that, we're out of time.