Good morning, everyone. I'm Lisa Walter, Senior Biotech Analyst here at RBC Capital Markets. Thanks for joining us at RBC's Inaugural Ophthalmology Conference. This morning, we are lucky to have practically the entire management team from gene therapy pioneers, 4D Molecular Therapeutics. Please welcome David Kirn, CEO and co-founder; Robert Kim, CMO; Chris Simms, Chief Commercial Officer; Dhaval Desai, Chief Development Officer; and Carlos Quezada Ruiz, the Therapeutic Area Head of Development and Ophthalmology Team. Welcome to the conference. Thanks for having us. Pleasure to be here. David, I believe you'd like to kick things off with a few slides to walk us through what 4D is working on currently. Yeah, absolutely. We'd love to start with some opening slides to orient the audience, and then we are looking forward to Q&A. Perfect. Let's start with the slides then. David. David, are you back with us? You were frozen for a second. Oh, I'm sorry. Okay. No, I'm with you 100%. If you could advance the slide. Okay, perfect. Okay. First of all, you know, we're thrilled to be a phase III company. 4D has worked tirelessly for a decade to bring innovative gene therapies to patients that solve the problems with traditional AAV gene therapy. That is improved delivery, reduced dose, and excellent safety profile. We've achieved that, we believe, with 4D-150. This is for wet AMD. We have initiated the 4FRONT-1 clinical trial and opened enrollment at multiple sites. We announced this a couple of weeks ago. Next slide. This is a summary of 4D-150. This is a phase III therapeutic, which can be disruptive, we believe, for the global market for retinal vascular diseases, and really has the potential to improve patient outcomes and address the number one need that patients have, which is reduced injection frequency and treatment burden. First of all, we're addressing a multi-billion dollar annual opportunity. This is a $17 billion a year market, and it's growing. This is in marked contrast to other gene therapies that go after rare diseases. Our product addresses the primary clinical unmet need. In every survey that you look at, including the ASRS surveys, patients want multi-year durability and reduced treatment burden. We can provide that. We believe this can be really a foundational backbone therapy that reduces patients' VEGF levels significantly, and patients can end up getting no further injections or a significant treatment burden reduction with an injection or two a year. We have a strong safety profile to date, very predictable, and a very routine topical eye drop regimen to control any issues. Patients are happy to take this, and we've seen a great safety profile with that, as you'll see in a minute. Again, importantly, the primary therapeutic that we're producing in the retina is Aflibercept, which is the standard of care for these diseases and has been in over 60 million eyes safely to date. We're building on that safety profile and efficacy profile. With this product, we have an ease of clinical and commercial adoption. We believe this can fit seamlessly into clinical practice flows, and we think there are strong incentives financially for physicians to use this product, given their current buy-and-bill reimbursement model. Chris will speak to this shortly. We do expect top-line data from the wet AMD programs, both 4FRONT-1 and 4FRONT-2, in the second half of 2027, well before our expected cash runway. Next. Let's get into the global market. Chris will speak to this more later, but I can address this. Next slide. Here you see year over year the growth of the anti-VEGF injectable markets with intravitreal injection. You can see that in this started with dark blue and Lucentis, and you can see now Eylea dominates this market, which is what we're expressing from 4D-150. We also see Vabysmo with a very small incremental reduction in treatment burden versus Eylea of about 20%, is having a very successful launch. Here we can see that with each incremental reduction in treatment burden, massive commercial opportunity. Next slide. This is what we were talking about. Lucentis, which was led by Robert Kim, who's part of our team, the development of that was the first approved anti-VEGF, and then a 32% reduction in treatment burden with Eylea, which was a couple of weeks, led to blockbuster status. Then by extending that another couple of weeks with Vabysmo, about a 23% reduction in treatment burden, that's translating to blockbuster status. You can see these small incremental gains in duration of effect and reductions in treatment burden can have massive financial benefits. Next. Let's talk about the unmet need in these patients. Currently, patients get repeat bolus therapy, which leads to very high peak levels in the vitreous and then a rapid decline. Patients are going up and down seesaw. You can see in the middle here a representation of that on the central retinal thickness, that's CST. You can see it going up and down in this cartoon. We've seen this in our randomized clinical trial as well, that repeat burdensome bolus injections lead to oscillations. Many patients are untreated at this frequency. The result is loss of vision over time with fibrosis and atrophy. Next. We can see 4D-150, given its ability to express aflibercept, the leading product in this space, consistently, constitutively in a sustained way, 24 hours a day, what we can get is a more stabilized CST, a more stabilized retina. We have adherence by design with this approach. Patients, if they miss a dose or two, they're still protected. The result of that should be better visual outcomes at the end of the day. What we have a chance to offer patients is a much better quality of life with less burden and improved visual outcomes in the long run. Next. Okay, what have we seen with 4D-150 today? First of all, we've explored this product in a very broad range of wet AMD patients in contrast to many programs to date. We've looked at the most severe patients on the far left, patients who are really failing standard of care. They've had disease for many, many years. They still have a thickened retina, intraretinal fluid. Kind of the most severe recalcitrant population there. When we compare the injection frequency, the supplemental injections after 4D-150 versus what patients had previously been getting, which was about over 10 injections per year, we see an 83% reduction in that treatment burden. Now, remember, Vabysmo was a blockbuster with about 20% improvement. We're talking about 80% improvement here, which is a game changer. How did we do in a broader population? That's our phase IIb population in the middle. You can see those patients typically would have had six injections over the course of a year with Eylea. We see that these patients only had a single injection on average, which again is an 83% reduction. When we look at the more recently diagnosed patients who have not had retinal damage from their disease, so it's a healthier retina for us to transduce, we see a 94% injection burden reduction with patients on average only getting 0.3 injections. This is a game changer. This is not achievable with Vabysmo or any other agents on the market. Next slide. Let's talk about safety. Safety is critical in a large market disease. Again, we're leveraging the safety profile of Eylea, which has been in over 60 million eyes. Let's see how our safety profile looks to date. Next slide. You can see here, we've had no serious related adverse events, no hypotony, no endophthalmitis. A lot of the issues you worry about with other gene therapies in the retina, we have not seen to date in 71 patients at the 3E10 dose, which is our go-forward phase III and commercial dose. We've really only had two episodes of very mild transient vitreous cells, and that's less than 3%. A remarkable safety profile to date. Importantly, patients have been comfortable taking their topical steroid drops, and they've gotten off the drops very quickly and on schedule in all but one case where a physician elected to continue dosing. Otherwise, 99% have completed that steroid taper on schedule. Next. We call this the sea of green. This is data from SPECTRA. This is our DME study. Now, remember, DME, a number of other gene therapies, are unable to treat DME because of the concern of toxicity. We haven't seen those toxicities. Given the vector that we evolved using Nobel Prize-winning technology, this enables us to treat this disease safely in a way that other AAVs just have not been able to do. In this graph, which you see, each row is a patient. You can see the top patients in the dark next to the dark blue box. That's a 3E10 dose. We're looking at anterior chamber cells on the left, vitreous on the right. You can see at that high dose, every box is green. What does that mean? It means we saw no cells. The physician saw no cells at any of those time points. When we look at the lower dose level, we see the same thing as well at the 1E10 dose level. Really remarkable, consistent safety and lack of concerning inflammation, lack of hypotony or front of the eye toxicities, which have really stopped, halted other programs in this space. This space is now wide open for 4D-150. Next slide. Okay, let's talk about commercial adoption. I'll keep this quick because I want Chris to speak to this later. Next slide. To remind you again, this is a single intravitreal injection, routinely fits into clinical practice flow, no special storage or handling. It fits right into the way that these clinics work today. Payers, we think, are going to like this approach because of the adherence by design. We're covering patients 24 hours a day, seven days a week with this therapy. Patients are going to be adherent by definition. We are expecting a significant reduction in treatment burden, which should lead to patient freedom from frequent visits, improved quality of life for them and their caregivers. We talked about the preservation of vision, which will benefit patients and have a socioeconomic benefit. Again, importantly, when we think about pricing and commercialization, we have very low cost of goods, well under $1,000 per dose. We have significant pricing flexibility. In the clinic, again, we believe we can fit seamlessly into the clinical practice flow. There will be financial benefits of getting that cash upfront to the physician and open up other slots in their clinic for other procedures that can also improve patient outcomes and their economic benefit. Next slide. Okay, top-line data. Let's talk about the 4FRONT phase III program. This is the study design. Our team can answer any questions on this in the future, but this is standard design. It's a BCVA vision non-inferiority study. We're comparing standard Aflibercept to 4D-150, followed by supplemental Aflibercept injections as needed. We think this is very well designed by our expert team, who's been involved in the development and commercialization of six of the seven major products in retina. They know what they're doing, and we also have an outstanding advisory board, and they've set the study design in a way to make sure that we win on BCVA and that we also have a significant reduction in treatment burden versus the Aflibercept arm. We are enriching patients in this study for success. Again, we're focusing those patients who are diagnosed within the last six months, and we're requiring that they show a significant response to Aflibercept before being randomized. We're making sure that whoever gets on in the study has a relatively newly diagnosed disease, a viable retina, and that they respond very well to the Aflibercept that we'll be producing. Next slide. Primary endpoint will be BCVA non-inferiority at 52 weeks. Again, you can see the supplemental injection criteria here, which were very expertly designed and will be implemented expertly. Next slide. This is the timeline. Again, we're thrilled to be in phase III and 4FRONT-1 Expect to be fully randomized in 2026 and have top-line data in the second half of 2027. We will give enrollment updates periodically to show progress towards this goal, and we'll refine those timelines as we get more data. 4FRONT-2 is poised to start in Q3 and also have top-line data readouts in 2027. 4FRONT-1 is North America only, and then 4FRONT-2 is a global study. We also have a cystic fibrosis program, 4D-710, that we're very excited about addressing a very high unmet need population in CF initially, which is modulator-ineligible and intolerant patients. We expect to have data in the second half of this year from that phase I study and feedback from the FDA on potential accelerated approval paths in that indication. We expect to broaden out to all patients with CF lung disease after this initial focus on the highest need patients. We do have a cash runway that takes us into 2028. We're funded out beyond the readout from 4FRONT-1 and 4FRONT-2, which puts us in an excellent position given current market conditions. Next slide. Okay, thank you. I hope that was helpful and look forward to your questions. You can go back. Yeah, thank you. Thanks, David. Thanks so much for walking us through 4D and the data and the phase III trial design and some of the upcoming milestones here. More of a big picture question for you to start off, you know, one that is on top of investors' minds. What impact will CBER head Peter Marks' departure have on gene therapy development? Is this going to be negative across the board for all gene therapies? Is this issue impact going to be more indication specific? Or is it just too early to know how impactful this is going to be to companies like yourselves that fall under the CBER category? Yeah, it's a great question, Lisa, and obviously very topical. First of all, we have incredible respect for Peter Marks. He's done great things for patients, we believe, and for the industry. We also have tremendous respect for our FDA colleagues. They've been great partners with us. We do have RMAT designation with them and PRIME in the European Union. We have had a great relationship. We expect that to continue. We think for a large market disease like wet AMD, this is a very tried and true path we're following. This is nothing new or innovative. This is very straightforward. We do not believe it's going to have any impact on our lead indications with 4D-150 in wet AMD and DME. We expect to continue on the path we're on. Again, we hope for kind of rare diseases where Peter's been very innovative. We hope that the current FDA staff will continue his innovative and open-minded approach. Thanks, David. Maybe I have a question for Chris here since we did not quite touch on the commercial landscape in the presentation. You know, Chris, where do things stand right now with the current wet AMD treatment landscape? How might things evolve with the entry of biosimilars, long-acting TKIs? We also have three gene therapies, yourself included, entering to late-stage development. Is there going to be room for all modalities beyond the monoclonal antibodies? Yeah, great question, Lisa. It's good to see you. The short answer is we think definitely so. It's a large market, as David pointed to earlier, globally, I think over $17 billion and growing, which is part of the reason why I think you start to see so much interest from all these other different modalities and approaches. The other thing I think it's really important to keep in mind is all of these modalities are trying to solve for the biggest unmet need in retina, which is the need to reduce treatment burden. We see this from patients. We see this from physicians quite consistently. We think over time, the profile that can best reduce that treatment burden and provide benefit to patients and that profile that can also provide capacity relief to the retina clinics is a profile that's likely to be the most successful. Again, time and again, the PAT survey and other surveys have validated that the number of unmet need is the reduction of treatment burden. We think we're very well positioned in that regard with a profile, as David went through, that's both safe and efficacious and I think leading or showing leading levels of treatment burden reduction. We think we're well positioned to win in that competitive environment. The last thing that I'll add, and I think it's really important, is the fact that we can seamlessly fit into a retina practice flow. We think our profile allows for that. We also believe it'll fit seamlessly into the existing buy-and-bill reimbursement model that retina practices have optimized. I think those are key things that help differentiate us and will set us up for success as the market potentially becomes more competitive as we see these programs read out over the coming years. Thanks, thanks, Chris. And thanks for sharing that you think the product could fit in seamlessly with the current retina practices. You know, one strong view that we get from some investors is that it's going to be difficult to uproot the current treatment paradigm of chronic regular injections simply because there's a financial incentive for doctors to inject patients frequently and often. Gene therapies, you know, with potential for a long-lasting effect, that this is going to be too disruptive to the retina clinic business model. What is your pushback to that? I love that question. Yeah, yeah, yeah. Go ahead, David. To Chris and Carlos, yeah, I'll just say, I mean, at a high level, look at the data. You know, if that was the case, why did physicians move to Eylea dramatically from Lucentis? They would have stayed at Q4 Lucentis, but they did not. They went to Eylea. Why is Vabysmo having a tremendous launch with only a 20% reduction in treatment burden? Because that is what patients want, and physicians understand that. I think the data, the evidence is unequivocal. These will be adopted, and there is evidence to say that. Chris, over to you. Yeah, no, spot on. First of all, the financial component of the buy-and-bill model is clearly there, and it's important. I think it's inherent in how that model is designed. To David's point, if it was solely about maximizing financial benefit, most physicians could treat Q4 Lucentis, right? For years, the community has tried to alleviate the treatment burden reduction by adopting PRN or treatment extend type of protocols. That's important. To David's point, listen, we think the best science will ultimately win, regardless of the financial components to it. Even with that said, we don't believe we will have a disadvantage on the financial elements of the buy-and-bill model for a couple of key reasons. One is today, the financial kind of reimbursement happens in tandem with bolus therapies, right? Every six, eight, twelve weeks, whatever the schedule is, we'll likely price our medicine at a commensurate level to treatment burden reduction. The cash flow component of when you get reimbursed for a medicine like ours is accelerated. I think the timing of cash flow is a really important factor. Maybe some education on those dynamics required, but we can certainly do that. We're well equipped and knowledgeable about the space to educate physicians on that element. The last thing I'll add is a lot of patients today on bolus therapy, sometimes modeled as high as 40-50% over time, fall off of therapy, right? They're no longer adherent for a number of reasons. That, in essence, is also a potential financial opportunity that's lost when those patients don't stay on therapy. By design, because we have adherence by design, we capture the value of that patient flow upfront. I think those elements and the fact that it fits seamlessly into the buy-and-bill model, we do not believe we will have a disadvantage when it comes to the financial kind of elements of the practice. Carlos, anything you would add there? Thank you, Chris, and thank you, Lisa. No, I definitely agree with everything that has been said, you know, but I, you know, again, this really reminds me about when all this intravitreal anti-VEGF market actually started. There was a lot of challenges, and people could not believe actually that doing intravitreal injections was actually going to be even possible and would fit in the clinic flow of retina specialists back in the day. Here we are with a multibillion market opportunity, as David mentioned at the beginning. I definitely think that the retina community is a very innovative community. I think that, you know, this is going to be embraced, as Chris mentioned, for all of the reasons that he highlighted. I'm definitely looking forward because most importantly, as physicians, we're trained to do the right things for patients, and this is the right thing for patients. Got it. Thanks, Carlos, Chris, and David. I guess maybe what I'm hearing is could long-acting treatments, could a gene therapy essentially allow retina clinics to capture more patients, but you're just going to have fewer injections in individual patients. Is that how we should think about it? I think what we do is we financially benefit them by bringing up that cash upfront, making sure they get it on day one, which is an advantage. The fact that patients drop off over time, they'll still have been reimbursed for these patients for five years or whatever we agree with payers. There is a big financial incentive, I think, for physicians to use this, actually not the reverse. By having fewer supplemental injections that patients need, fewer treatment, less treatment burden, that will open up those clinic slots, which are currently swamped. That will open up those slots for other patients that they can bill for and that they can treat with GA assets and other things. I think overall, it's going to be a financial win. I think the reason most physicians will do it is mainly because this is what treatment, you know, treatment burden reduction is what patients really, really want and need. Thanks, David. Maybe pivoting gears here, another question that's topical. We recently saw Opthea. This is a company that was developing an anti-VEGF C monoclonal antibody as an add-on to standard of care, Eylea, Lucentis. They recently missed their primary endpoint in a pivotal superiority trial. You know, given 4D-150 is expressing aflibercept, but it also knocks down VEGF C expression with a micro RNA. What read-through is there from Opthea to 4D? Is maybe the pan-VEGF expression not the right way to go? How should we think about this? Yeah, we do not think there is any read-through to us. First of all, the primary mechanism of action for 4D-150, as you said, is aflibercept, which is the market leader and has been in over 60 million eyes. Number one. Number two is the micro RNA or the RNAi that we express to knock down VEGF C. The way we do that, it also boosts aflibercept expression in the eye. We think that there's a significant advantage for that construct that way. We do believe that the VEGF C is a good target. It's just that a superiority study on BCVA, we believe, was a flawed design. Nothing against the people who designed it, but that is a very high-risk approach in contrast to treatment extension, treatment burden reduction, which we think is where you're going to see the benefit of inhibiting VEGF C over time. We'll be doing that. Now, again, the primary mechanism of action is the aflibercept. We know that works, but we believe there will be a subset of patients where that suppression of VEGF C over time will lead to benefit and a reduced development of resistance. Got it. Thanks, David. Maybe just a couple more in the time we have left here. 4FRONT-1, this is underway. This is enrolling. This is a U.S.-based trial. Then 4FRONT-2, this is anticipated to begin enrolling Q3 2025. This is going to be a global study. Both studies are anticipated to read out second half 2027. I guess, is it fair to say, is it fair to assume that the global study might enroll faster than the U.S. study simply because you're going to be tackling more geographies here and that's how you're going to end up having the pivotal top line relatively within the same timeframe? How should we think about that? Yeah, maybe Bob can speak to the design and then Dhaval can speak to the enrollment rates. Yeah. Yeah, so the dynamics of the second study are a bit different because it's global. The regulatory ramp-up actually takes a bit longer, but we anticipate that in part also because the population will include some treatment experienced patients that the actual execution will be faster. It'll have more of a prominent hockey stick dynamic to it. Dhaval? Yeah, thanks, Bob. And Lisa, just comment on kind of the early days of 4FRONT-1. You know, we've seen a lot of enthusiasm and excitement have been out as well as my team kind of talking to the investigators that are participating in the program. We're really encouraged by the activity and the action that we've seen in these early days. We think that's going to carry forward not only to the rest of 4FRONT-1 as more sites become open, but also in 4FRONT-2. I think you're, it's right. It's safe to say that it will, 4FRONT-2 will likely recruit a little bit faster because it has those previously treated patients which are easier to kind of find in practices. In the end, we think both of these will meet or beat our timelines. Got it. Thanks, thanks, Dheval. I do want to touch on the DME program, you know, 4D recently aligned with the FDA that you would only need one pivotal study to go forward with DME. Just curious, when would be the right time to launch this study? I think the time of this study remains to be determined based on the financing environment. We're well funded right now to get out through the primary read on our wet AMD program, which we think puts us in an incredibly strong position. We will want additional financing at the right time in terms to fund the DME study. I will say that that is a remarkable regulatory achievement that we were able to align on a single DME study to get another blockbuster opportunity. That was really led by Carlos and Bob's interaction and respect that they have with the FDA. They proposed it and the FDA was open to it. I think it puts us in an incredibly strong position to have the opportunity to have three total trials to get two blockbuster indications with a highly differentiated product that addresses the number one unmet need in those for those patients. Thanks, thanks, David. We'll leave it there for our time. David, Deval, Bob, Carlos, Chris, thank you so much for joining us this morning. I hope you enjoy the rest of the conference. Have a great day. Thanks, Lisa. Thanks for having us. All right, take care.