Walter, biotech analyst here at RBC Capital Markets. Thanks for joining us at RBC's 2026 Global Healthcare Conference. This session, we have 4D Molecular Therapeutics, and we have the pleasure of hosting Chris Simms, who's the Chief Commercial and Business Officer, and Kristian Humer, who is the Chief Financial Officer. Chris, Kristian, thanks so much for joining us today. How are you both doing? Doing great. It's great to be here. Thanks for the opportunity. Thank you for having us. It's been a good day. Well, it's great to have you both here. Team, maybe a big picture question for you. You know, FDMT has made really tremendous progress over the last four years, launching two pivotal studies for wet AMD. You're on the verge of launching a pivotal study for DME. You have an enviable cash position and potential to transition to a commercial stage company within maybe the next 2 to 3 years. You know, with all the progress, what do you think remains the biggest misconceptions about the story, and what are investors missing? Yeah, I can start with that, and Kristian, feel free to add additional color. I think there's a couple of things. First of all, I think we're setting out to reset a treatment paradigm and do something that hasn't been done before. I think whenever you're endeavoring to do something that's bold in that nature, it's sometimes hard to fully appreciate the potential until you see it. I think that's very true for us. We're trying to evolve the treatment paradigm for retinal disease, notably AMD and DME, from this bolus therapeutic process where patients are treated on some frequency of, you know, 4, 8, 12 weeks, to a backbone for retina treatment paradigm, where you have a safe, efficacious, always onboard treatment that's then supplemented as required. That's a big change from what I think the market has experienced in the past, and I think that inherently creates some challenges with how does that play out in the market. The other part of that is the market itself has become more cluttered, right? It's a highly competitive space today. There's lots of other assets in development. We think our profile is uniquely positioned to make a real meaningful difference and to reset the treatment paradigm, certainly with a lifelong, safe, efficacious backbone therapy in place. Admittedly, like in a space where there's lots of other treatment alternatives in a bolus nature available, sometimes it's challenging at this stage to see what the true commercial potential of that is. We believe highly in the commercial value. There's the other part, Lisa, that I think will get proven with time, but a function of being a gene therapy is that you are sometimes, you know, burdened with some of the gene therapy challenges of the past, right? People hear gene therapy, they wanna see the evidence of safety in the real world, and we're working through that. What we're really proud of, though, is that in the clinical development that we've done so far, we believe our molecule 4D-150 certainly differentiates on safety. We hope to prove that certainly in our Phase III program, which as you referenced has been enrolling at a very high pace. I think, you know, through our development program and ultimately commercialization, we'll show what the real opportunity is for a treatment like this. Thanks for that Chris. Well, I do have another big picture question on regulatory. You know, we're experiencing some volatility right now with the FDA as the commissioner has stepped down recently. You know, given you're in pivotal stage, and you are still developing the pivotal for the DME study. Is there any risk to your communication with the FDA given all the volatility that's going on? There's nothing of note that's unique to our conversations with the FDA. We acknowledge the volatility, we would say that our interactions have been very productive. Nothing that's come up that would give us any concern. Again, I think part of that relates back to while we are gene therapy, we're not a gene therapy for a rare disease. Our Phase III program is very traditionally designed. If you look at our phase III program for wet AMD, the design is similar to what you've seen in other pivotal programs like VABYSMO, EYLEA, and so on. I don't think there's anything that's overly unique or unusual about how we've developed 4D-150 in our Phase III program. I think that is conducive to pretty up the middle FDA interactions. The only other thing I would say, you referenced our plans to start our DME trial, so we hope to start that in the third quarter of this year. Very excited about the opportunity there, by the way, in DME, a huge unmet need. We have regulatory alignment from both the FDA, EMA, and Japan for a single DME trial. We plan to do a single trial globally. We'll do it in partnership with Otsuka, which is our partner for Asia-Pacific. Again, our regulatory interactions for that trial continue to be very productive and nothing new or different in those interactions that would cause us any change to what we've assumed previously. Well, Chris, since you bring up the DME study, maybe let's dive into that a little bit more. What is your latest thinking here on the trial design? I know we're gonna get the update in the third quarter, should we expect, you know, this trial design to follow what we have seen in the past with other programs? Yeah. I think we will share the more specific details on trial design in a couple of months as we get closer to the initiation of that trial. I think for investors, you could assume that you can look at what we've done historically with our trial design for wet AMD and assume we'll take the same approach and philosophy as we go into DME. We believe designing trials for a pivotal program need to be done in a way where the data that's produced obviously allows you to get regulatory approval, but also the data that's produced is conducive to a physician looking at that data and translating it to in-clinic usage. We don't always see that in some recent trial designs. We think that's important to design it in a way where that Phase III data set has applicability to clinic usage. Again, while we haven't got the final details of our Phase III DME study ready to be shared, I think you should expect that it'll also be very standard and traditional in its approach, similar to how we've done 4FRONT-1 and 4FRONT-2 for AMD. Should there be some similarities with the 4FRONT trials, maybe in terms of rescue criteria or steroid use? We haven't shared the exact rescue criteria, but I think certainly, rescue criteria will be applied. The exact specifics are not ready to be shared just yet. Certainly, I think it'd be somewhat similar to what we have in the wet AMD trial. Yes, we'll most likely have a prophylactic steroid regimen as well. The details of that again to be shared, but I wouldn't expect anything all that significantly different from both what we've done in 4FRONT-1 and what we've seen in other Phase III DME programs from, you know, Roche, Genentech, or Regeneron. Got it. That's helpful. Well, maybe let's just talk about the larger retina landscape for a second. You know, for the last 20 years, this market for wet AMD and DME included, has really been dominated by intravitreal delivery of these anti-VEGF biologics. You know, these drugs are safe, and they improve vision, and the branded market has really grown into the largest area of ophthalmology therapeutics. Where does the unmet need lie for wet AMD, and does it differ for a disease like DME, which affects a bit of a different patient population? It's a great question. It's amazing, actually, as you mentioned, that we're about 20 years since, I think, the introduction of LUCENTIS. For 20 years, the treatment of these diseases has been done through a needle in the eye at some frequency. Of course, that creates a whole host of treatment burden challenges. A needle in the eye, it's fairly a rote standard procedure. Retina docs do it multiple times a day. You have to think that that treatment paradigm is due for a different approach. We think we can deliver that. You know, and you mentioned these therapies help patients gain vision, and that's correct. You see in all these Phase III programs upon initiation of therapy, depends on what the patient's baseline vision was. On average, a patient, a wet AMD patient is gonna gain five to seven or so letters on average at the start of a trial. What's really interesting and what's really unfortunate is despite these medicines being highly efficacious, real-world data would suggest that even if you stayed on therapy for 2, 3, or even up to 5 years, more likely than not, you've actually lost that vision that you gained initially. You actually see this. With real-world data, you gain that five to seven letters, but over time, that vision slowly erodes. In fact, many patients, when you get into year 2 and 3, actually have worse vision than they had when they were initiated on therapy. There's a couple of reasons for that. One is a lot of these patients can be undertreated. Sometimes there's lapse in therapy. This is where the treatment burden issue comes to life. Sometimes there's anatomical issues like fibrosis or atrophy that may show up, which has an effect on vision. What we also know, and we've seen this in a number of datasets, is that the constant regular suppression of VEGF has resulted in patients holding on to that vision for the long term. There's been studies done where LUCENTIS is dosed monthly, and amazingly, that vision gain that I referenced happens, and the retaining of that vision is flat for many years. You know that if you are constantly controlling the disease with VEGF therapy, patients can hold on to that vision. We've also seen that data, by the way, with a drug that Genentech has called Susvimo, which is an implant which does the same thing. It controls VEGF continuously. It's always there. It's always on. You see as a result of that, patients hold on to that vision long term. Our view is that with a 4D-150, a gene therapy approach, is that you can do that. You can hold on to that vision for many years, but you do it obviously through a biological approach. In many ways, we think we can produce Susvimo-like long-term vision outcomes but not have to do it through a invasive implant type of approach. Got it. You know, Chris, to me, 2026 is really a kind of a landmark year for wet AMD in terms of development of new therapeutics. We're having or we already had a pivotal readout in one of the long-acting TKIs. We're expecting more in the latter half of the year. We're also going to get our first pivotal gene therapy re-readout as well later in the year for a subretinal approach. How might all these readouts, you know, as the data comes in, how is this gonna shape your strategy, your commercial strategy for 4D-150, which is gonna start to read out later or beginning in 1st half 2027 with 4FRONT-1? Yeah. It's a very dynamic space, as you just referenced. The next 12 months is gonna be pretty exciting, and I think a lot of those readouts are gonna be informative. I think a couple things I would say. First of all of these programs, certainly the TKIs, are looking to extend durability, as are we, right? They're looking to add another week or 2 of durability because treatment burden is an issue, and we know it's an issue when we've seen Medicines like VABYSMO or EYLEA HD, which extends durability by a week or 2, come to market. We all know the commercial success that have resulted in that. We know durability matters. Those agents are trying to extend durability a little bit further as well, and I think there's a market for that should they prove to be successful in their Phase III program. I think the difference between- for us versus the TKIs or any other bolus therapy that's in development is that we're not trying to extend durability by a week or 2. We're looking to establish a backbone for retina that, for patients, holds the promise of months and likely years for many patients of never needing another bolus injection again, and that's a whole different category we believe, and a whole different value proposition for patients and providers and also for payers. So that's how we differentiate. We think it's great for patients and providers that you have a broad list of bolus supplemental therapeutics to choose from should you need to supplement. And then as far as the other gene therapies in development, we think we also differentiate from those as well. Clearly, we have our delivery is intravitreal, which is highly important. It allows you to seamlessly integrate into a retina practice. It's a pretty standard procedure compared to other programs that have a surgical or subretinal approach, and that can be, I think, pretty prohibitive for a retina clinic to adopt just based upon the time it would take to deliver that other medicine. We think we're uniquely positioned. We think our delivery, our safety data, and certainly our efficacy data that we've generated thus far, supports that. Got it. That's very helpful, Chris. You know, the branded wet AMD market is worth about $10 billion today. The DME market, the branded market is worth about $4 billion. That's a $14 billion market between those two indications. What slice of that could 4D-150 capture? That's Yeah, that's a great question. That's and growing, right? Growing. We actually project that the global anti-VEGF market, kind of in our launch horizon, could actually be valued as high as $20 billion as the population ages. I'll tell you, we ask this question to physicians a lot based upon our target product profile. We get numbers that I think are very encouraging. We don't think of 4D-150 as being a niche type of product. We actually think if we generate the data we expect to in phase III, that backbone therapy approach should be considered for the majority of patients. The feedback that we get from physicians when we take them through our profile and the data that we've generated, I ask a question that's similar but a little bit different, which is, "Based upon all the wet AMD patients that you have in your clinic, what patient do you think you would not consider for a therapy like this?" What we get is, you know, there's a handful of patients that are seemingly controlled with 2 or 3 injections per year, and that's the group that physicians are likely to not consider 4D-150 for, at least initially. We think that represents maybe 10% of the overall AMD population. The majority of patients need, you know, on average, the number of injections about 6-7 per year, with many patients needing 8-10, if not more. We think there's a segment where we're likely to be used less, but the overall population, we think over 90% at least physicians would consider us for those patients based upon their treatment burden need. Of course, there's lots of other factors that will come into play, insurance and so on, and coverage, but that's how we view the opportunity. Very, very helpful. Chris, maybe on pricing, I think many investors are used to hearing these multi-million-dollar price tags for gene therapies. Of course, these are typically gene therapies that are developed for rare diseases. Wet AMD, DME, these are not rare diseases whatsoever. How are you thinking about pricing gene therapy for an ocular indication where there's already a large established market with price points that are also already established? Yeah, of course. I love that question because it gives us a chance to also distinguish between what you just referenced, which is sometimes a gene therapy. You hear gene therapy, and you instantly think small patient population, gotta charge $3 million to have a business case. That's not us at all, right? There's, I think, over 600,000 patients in the U.S. alone that are on anti-VEGF therapy in any given year. About, I think, 100,000-150,000 of those are new to treatment in that year. You have a fairly high incident rate that continuously brings you in a, I think, a nice bolus of patients that are considered for treatment. Of course, that's just a function of the aging population. Those things have to be considered when you think about things like pricing. While it's way too early to say what we think our price will be because it's gonna be determined by a number of factors, our Phase III data, the market, and so on, I can tell you that we will not be in the million-dollar price range. In fact, I'd be surprised if we were higher than $100,000. Where we fall ultimately, we'll make that decision once we get further along in our preparation process. The only other point I would make, we've said this publicly before, because of the volume and because of our expertise in manufacturing, again, we're delivering a relatively low dose at 3E10. We think we can deliver a cost of goods profile, which is probably less than $1,000. That gives us a lot of room to be competitive and potentially disruptive in a large category as it relates to our pricing decision. Well, I think that is very different in terms of what happens with gene therapy and rare disease. It is. It's very helpful to kind of get your thinking around it. I do wanna touch on the opportunity outside of the United States since this is part of your strategy. You know, you have this partnership with Otsuka on the Japan APAC region. E.U. obviously, the anti-VEGFs are sold widely there. How are you thinking about the opportunity for 4D-150 in those regions? First, just to reiterate the obvious, I guess U.S. is priority number one. We think that would be our first launch market, and that's how we're planning our commercialization strategy. That said, our development program has been intentionally designed to allow for global, what we think is global approval. So 4FRONT-1, the first Phase III trial that completed enrollment at the end of March, that's a U.S., North America, no, U.S. and Canada trial. 4FRONT-2 is a global trial, we have sites in the U.S. and Asia-Pacific, South America, and in Europe. 4FRONT-2 also has a little bit of a different patient population. 4FRONT-1 is entirely treatment naive, 4FRONT-2 is a blend of naive and experienced patients. That experienced patient population is in direct response to a E.U. regulatory requirement. Those patients could have been diagnosed in the prior 6 months. We've designed our pivotal program for global adoption. I do think the European market is of interest. Certainly, Asia-Pacific is a, is a market of interest as well, which is why Otsuka was motivated to do the partnership with us that they've done. We, we believe there's an opportunity globally, and certainly, like the top 5 European countries would be on that list. When and how we go about that is still strategy that needs to be developed, but it's within our model to assume significant value there. The last thing I would say about that is the patient need that we think we solve for, again, a therapy that's constantly on treating the disease 24/7 because the disease is constantly on, that patient need is not a U.S.-only need. That patient need exists globally, unfortunately, in this disease. You could make the argument that in certain countries where access to care like access to a retina doc is not as easy as it may be in countries like the U.S. or Canada, that having a therapy that you can administer to a patient that may not be able to get back in to see you for months from that point in time could actually solve a pretty significant need in those markets. I think our value proposition and our story and what we can ultimately deliver in terms of ongoing treatment and the potential to preserve vision would be of interest to a number of, I think, European countries and payers. Got it. That's super helpful. On the 4FRONT trial, these are your two pivotal studies that are ongoing. You know, Chris, these are non-inferiority trials. They have a rescue criteria in them. The rescue criteria are relatively strict. If a patient loses five letters and has, I believe, a 50-micron greater increase in CST as your rescue criteria, they will get a supplementary injection of anti-VEGF. Under that umbrella, how could a non-inferiority study when you get rescued possibly fail? How could it not possibly meet the primary endpoint? Well, we think we've derisked the Phase III program as much as we can while also maintaining its relevance in terms of the data that it will present. You know, you never wanna say that things are guaranteed. That's just not the nature of the business that we find ourselves in. You know, the criteria we think are reasonably designed. We did that in collaboration with world experts in retina. We did that by looking at similar criteria from other drugs that have been re-approved to make sure that whatever we choose to be the retreatment criteria is relevant, and physicians will look at that and say, "That represents something that's meaningful to how I treat my patients." Yeah, I think, you know, we've tried to do as much as we can to derisk the program. You never know until you know, and you turn that data card over. It's the nature of being in this business. We think we're as derisked as you can be, and looking forward to seeing those results in the first half of next year. Some of the secondary endpoints of this trial, I think, are going to be a lot of interest, like reduction in injection burden. Yeah. Is there a bar you have in mind that would really facilitate commercial adoption of a gene therapy? Yes. It's a great, it's a great question. It comes up a lot. I guess where I hesitate a little bit in the answer is because sometimes if you give a number, you think that, you know, 1% below or above that number defines success. The reality is it's not that. I'll refer to, I think, the conversations we have with retina docs when we take them through our program, and we show them our Phase II data, which we show treatment-free rates 50%-70% depending on the population, overall treatment burden reduction 80%-90% range. I'll guarantee you anything from our phase III program that comes within that realm of treatment burden reduction would be a huge out of the park home run by far. I don't think it has to be in that range. Physicians will tell you that. The last point I'll share with you, Lisa, on that question is we did market research asking doctors around, "Hey, how many patients would you use a product like this in?" The first time we did it 8 months ago, we tested a 60% sorry about that, 70% treatment-free rate and a 90% treatment burden reduction. Then we did it 1 month ago, and we tested a 50%, so a lower treatment-free rate, and an an 80% treatment burden reduction. The percentage of patients that doctors would say they would choose the product for was exactly the same in those 2 data sets. I guess it just proves that there's no, like, magical number per say. Again, I think if we're in that range of 50% treatment free, 80%+ treatment burden reduction at week 52, then, we think that's a huge success. Got it. Well, Chris, maybe just in the last minute or so we have here, you have a couple catalysts coming up. We're supposed to see two-year follow-up from PRISM in the broad and recently diagnosed patient population. What should we expect to see here in the update? That's a continuation. We've already shared 18-month data on that patient population. We think it should just represent the same overall treatment burden kind of reduction rate just out to a longer time period. Hopefully, of course, the continuation of safety. Got it. We're also expecting to share an update from the DME SPECTRA trial as well, correct? That's correct. That's coming up in the back half of this year as well. Okay. Okay. Got it. Well, I think we're a bit out of time. Kristian, maybe a question for you since we have you here. Can you maybe just remind us of the cash position and the runway? Sure What the runway is expected to cover in terms of your clinical programs? Happy to. As of the end of Q1, we had $558 million in cash. We are guiding to cash runway into the second half of 2026, 2028. What it doesn't include, that cash runway, is basically the commitment to the commercial build-out that we would need to do post 4FRONT-1 data. Got it. Very helpful, Kristian. Awesome. Well, Chris, Kristian, thank you so much for joining me today. I hope you enjoy the rest of your day. Thank you. Pleasure. Thank you for having us.