4D Molecular Therapeutics, Inc. (FDMT) May 13, 2026 Conference Transcript

Hi, everyone. Welcome back to the Bank of America Healthcare Conference. My name is Daniel Gualdo. I'm one of the biotech analysts here at B of A. Our next presenting company is 4D Molecular Therapeutics. Some members from the management team here. So welcome, guys. Thank you for joining us. Maybe we can start with a couple of introductions from your side, and then, you know, you can give us a high-level overview of the company. And I know you have some catalysts coming up, especially 2027 is going to be a big year for the company. So maybe you can start with that. So, David, maybe if you want to start.

Yeah, thanks, Daniel, for having us. I'm Dave Kern, co-founder, president, and CEO. Thanks, Daniel. Chris Sims, chief commercial and business officer. Christian Humor, CFO. So I can give the high-level overview of the company. So 4D Molecular Therapeutics is really a leader in next-generation AV gene therapy. We're a platform and product company with a lead asset 4150 in Phase 3 for wet AMD and soon to be in Phase 3 for diabetic macular edema as well. We believe we really have the opportunity to be best-in-class, highly durable backbone therapy for these neovascular diseases of the retina. So we're thrilled to be in phase three. The enrollment's been extremely rapid, probably double what we expected going into it, showing a lot of enthusiasm from patients and physicians. There have been a number of surveys that have come out that show that physicians in this field are most excited about 4150 and gene therapy writ large. So I think we have a real opportunity here. Catalysts this year are we have a two-year follow-up on a broad population of what A&B patients with 4150. Phase two, that's mid-year. And then second half of the year will be a DME two-year update. And then next year will be the first phase three readout, and the second phase three readout will be in the second half.

Okay, great. Great. So maybe let's just start with a high-level question. You know, the wet AMD market is becoming increasingly competitive. There's a lot of new products coming out, a lot of innovation there. You mentioned some of the surveys. You know, what are you hearing from physicians in terms of what the unmet need is right now for the treatment of wet AMD? And, you know, how do you think 4D150 could be differentiated in that market?

Yeah, I'll kick it off and then hand it over to Chris, our chief commercial officer, who's done a lot of work in this area, and I think it's very promising for us. But I think at a high level, the way we view this is there's a lot of noise and a lot of competition for incremental improvements in bolus anti-vegotherapies, and that's great. But we're fundamentally in a completely different category. You know, what we're looking at with the way AAV gene therapy works in the retina, it's likely lifelong therapy, continuous expression every day of the rest of the patient's life, which we think really will translate into markedly improved quality of life, major reductions in treatment burden. Some patients may never get another treatment and should also translate into better visual outcomes over time. And Chris can really speak to, I think, you know, what's what's driving patients and physicians interest. Yeah, happy to.

So, you know, you take a little bit of a step back and you're familiar with the category. It's a large space valued at roughly 17 billion dollars globally today with existing bolus anti-VEGF therapies. And we expect that to continue to grow largely driven by an aging patient population. And these existing therapies are actually pretty efficacious. They do a good job of improving the patient's vision. The challenge is getting in and staying on therapy at a frequency that allows a patient to maintain that vision. And, of course, the process of administering the medicine being a needle, an injection in the eye on some frequency is burdensome beyond the other factors of getting to the clinic and so on. So the unmet need, to your question, has been the same unmet need for years. You go back and look at surveys 10, 15 years ago. You ask doctors, hey, what's the biggest unmet need? It's always been we need agents that are more durable. More durable means that we can reduce the treatment burden for patients. We can reduce the complexities of delivering these treatments in our office. And not only have they said that, we've seen innovation prove that to be real. So you look at the latest bolus therapy launches, Vibisnil, Ileah HD. All of those assets have extended durability by a week or two. So meaningful, certainly for a patient, maybe takes an injection per year out of their normal routine, but incremental. But despite that incrementality, those agents have become multi-blockbuster within a couple of years. I mean, the BISMO is the greatest example of that. So I think with our approach, we ask the question of if an incremental benefit like that can be of commercial value measured into four plus billion dollars in terms of top line revenue globally, what could do the commercial value be if an agent like 4150 that we're not looking to extend durability by a week or two? We think for a lot of patients, it would be the last injection they'll ever need. And for others, we're looking at durability improvements that are measured in months or years. So it's a completely different paradigm. So we think we are uniquely positioned to, like, really address this durability question in a way that hasn't been done before. Oh, and in addition to that, we think we could actually help the patient maintain their vision over the rest of their lives. And that's pretty, pretty significant when you think about, you know, you go on to these therapies for the benefit of keeping your vision. A lot of these therapies don't allow you to keep your vision because you get undertreated just because, again, of the challenges of administration. So if you can not only reduce treatment burden by 80 plus percent, but also say to a patient you've got a good chance of holding on to your vision for the rest of your life, that's a completely different ballgame and a completely different treatment paradigm.

Great. There's a few competitors in the gene therapy space for wet AMD. How do you view your product compared to those? Where do you think is your edge in this market?

Well, we think we're the best, which shouldn't be surprising. But actually, we think there's actually very good data behind that statement. First of all, I don't think there's any doubt that an intravitreal product has massive commercial advantages over a subretinal product. So subretinal surgery is just, it's great for proof of concept, but for commercialization, it's really a non-starter. So we have major advantages over the AbbVie Regenexx product since we're intravitreal. And then I think our safety profile has really shined and differentiated us from the Advirum Lilly product to the point where they're not even in DME. They can't go in because of the blinding events they had.

DME is a major opportunity for us in addition to what AMD and DR. For what it's worth, our doctor checks also indicate physicians think your product has the best profile so far. So you mentioned you have a tier update coming up for the broad patient population. Can you maybe remind us what you've shown so far? I think the last update was 18 months. What should we expect to see in two years? And you've also shown data for different patient populations. Maybe you can talk about kind of like the evolution of the patients you've treated and what you've seen in terms of efficacy there.

Sure. So in wet AMD, you know, our team has done a phenomenal job of really having a very robust phase one and phase two program to really set us up for success in phase three. So we started in the hardest to treat patient population, one of the hardest to treat populations I've studied. And that was sort of on average, eight to 10 injections a year, still failing therapy. And in that population out to two years, we showed nearly an 80% treatment burden reduction compared to what they'd been getting. using patients as their own control. So that's huge. And then when we moved into a broad population, we showed about, again, an 80% reduction out through a year and a half. And when we looked at the patients that most closely mirror our phase three population, we had a 90% treatment burden reduction through a year and a half with over 70% of patients injection-free through a year and a half. Most importantly, though, given this is a large market and there are effective therapies, is our safety has been extremely favorable. So we look very, very closely every several weeks for any evidence of inflammation in the eye. The most we can find is about 3% of patients might have a single time point where they have a few trace cells that we see in the eye, but nothing clinically significant. So it's been really phenomenal. And that's just during the first few months after treatment. After six months, we just don't see anything. So the safety has been really phenomenal. So that's sort of what we've shown today. So we would expect the two-year update for the broad population and recently diagnosed population would be more of the same, you know, more safety and just more stability of the treatment burn reduction over time.

Great. What do you think is the profile that physicians are looking for for this type of product? You know, you've reported data for injection freedom over time, but you've also shown, you know, significant treatment burden reduction. You know, where do you think physicians will be comfortable using a gene therapy product? You know, is it, you know, just significant treatment burden reduction? Is it injection freedom that they're looking for?

Well, I think Chris has probably interviewed more physicians on this than anybody in the world. So leave it to him.

Yeah, it's a great question. So first of all, safety has to be established, right? And I think to David's point, we think we really differentiate on our profile as it relates to safety, no doubt. But that's in a category where you have effective and safe medicines available. I launched a drug called B of U at Novartis several years ago, highly efficacious, highly potent, maybe even more so than it should have been in hindsight, but it had a safety issue, which caused it to be a challenge from a commercial perspective. So you've got to have safety. And we think our profile would support that. As far as the treatment burden, injection-free numbers, doctors don't say it has to be X percent. There's no binary cutoff point. It has to be meaningful. It's got to be, for a gene therapy, a significant step change from the incrementality that they're getting with high-dose products or TKIs. But there's no magical number. What I'll tell you is that when we take them through the profile that we've seen through the PRISM data, which David just alluded to, so you see basically like in the broad population, injection-free rates of about 70% at a year and a half, overall treatment burden reduction rates in the 80%, 90% range across a broader population, they're blown away by that. We don't believe commercially it has to be at that level to be a strong commercial success. But if our phase three data and profile comes out in that range, then that would be a significant change, leap change forward for physicians and patients for sure. Okay, great.

You mentioned there's potential for this being a one-time treatment. But, you know, realistically, that might not be the case for everyone. You know, what sort of durability do you think physicians would like to see? And, you know, maybe how are you thinking about potential redosing over time?

So for redosing, we don't think it's going to be necessary. You know, the retinas are very, very stable tissue. So other AV gene therapies have shown stability out through 10 years or more. And it's an elderly population. So it's probably lifelong treatment. So we don't think they're going to need injections, say, my, A big opportunity for us commercially and to help patients is about 40% will get wet EMD in the other eye. And so I expect if they have great success in this eye, they're going to want it in the other eye almost by definition. So that's another 40% on top of the initial population. So I think it's a huge opportunity. And then maybe, Chris, you can speak to the other part of the question.

Yeah. So, you know, there's no, physicians don't say it has to last X amount of time. I think they just look at, you know, what is the treatment burden reduction that we're showing? I think practically, we're going to have to show long-term data over time to continue to prove that one continues to be efficacious in years out. And there's no biological reason that we think would prevent that from being the case. um so i think that'll come i think long-term safety is going to be important as well but you know for for the purpose of modeling and i'll throw out numbers that we use just to model what the market opportunity and ultimately we'll probably have to use that for figuring out things like pricing we we look at a three to five year window for amd from a modeling perspective but again that that's not to say that's how long we think the drug lasts but that's often the window that patients are on therapy in the real world today in that range on the outside of their durability of treatment, so much by the fact that in AMD you have an older patient population. So that's just some of the variables that we use when we think about, you know, length and treatment durability.

Okay, great.

Maybe we can talk about the phase three program. So you have two trials ongoing. You recently announced you completed randomization in in Forefront 1, the North America trial, you know, what do you think drove kind of the accelerated enrollment in the trial? And, you know, do you think that's going to boost enrollment in Forefront 2 as well now that you've completed the first trial?

Yeah, the second question, yes, absolutely. And we're seeing that. We're seeing the same level of excitement and enrollment momentum. I think what drove the enrollment in the first study, Forefront One, bodes very, very well for commercialization, and that is high end met need in the opinion of the patients. So they really, really want something that's much more durable, if not lifelong benefit. And then physicians, it's the data. You know, they look at our data and say, wow, it's intravitreal. It fits seamlessly into my practice, and they're getting safety profile that's not unlike a flippercept and you know the treatment burden reduction is remarkable and so I think it's really a combination of unmet need and in our data and again Chris has had a lot of those conversations and probably add some color to that yeah I not a whole lot I mean we did something that I think is pretty obvious in hindsight but we went out to all the clinical trial sites with a pretty robust phase two data set and said hey before you start up in phase three Let us just make you aware of what we've seen so far as we've taken this asset through development from phase one to phase two.

And we share with them what the results were. We share with them what we saw in terms of safety. And I mean, that's just, I think, putting a little bit more evidence around. We've got a really good drug and it's and it is unique and it's different than what you've been, I think, used to before. And I think that created enthusiasm for them to talk to their patients about it. And then what's really, I think, amazing and encouraging for us is we're starting now to get a better sense as to what patients think. And some of that we get through the physician conversation, and they parlay how patients react when they present them with a gene therapy and a clinical trial option in a world where you have a lot of other therapies to choose from. And by the way, you're presenting that to naive patients. And the patient enthusiasm has been off the charts. So I think that combined with a highly engaged, a great drug, a highly engaged physician audience, a great team to kind of roll it out and really strong patient enthusiasm for a profile like this is, I think, the four reasons why we saw the pace of involvement.

Great. And Daniel, let me just expand on that for just a minute. I think it's remarkable to think where we came from with gene therapy initially was people thought this is a dangerous therapy. It's going to be a million dollars a dose. You know, boy, it's got to be curative. You can only go into rare diseases where it's fatal. We flipped that on its head and we said, no, if you actually innovate and we used a Nobel Prize winning technology to innovate and create a new vector that had the features we want, we can flip that on its head and take this into large market, high incident rate diseases. No one thought that was possible. And yet here, after five short years in the clinic, we're enrolling at record speed, not only in a large market indication in patients who are in their 70s and 80s for the most part. It's in patients who are treatment naive, like frontline therapy. So nobody thought that was possible. It's really remarkable, I think, what the team and the product has accomplished.

Great. So, safety, like you mentioned, has been a big point of focus for these programs. Can you maybe remind us what you have seen so far? Has anything changed, like, I guess on a blinded, you know, basis in the Phase III trials? And I know you have a seroate regimen as part of the trial. You know, how do you think that will play out in the real world when patients are not part of the clinical trial? Yeah, that's a great question.

So, just starting from fundamentals. Again, because we came in and we said we're going to innovate and invent and optimize capsid that's the features we want, our dose levels are lower, our inflammation is much lower, if any. And it set us up for success. So the fact that we're seeing no significant inflammation or toxicity is not by chance. It's not luck. It was by design. And we took years to innovate, where others just kind of took existing vectors, threw it in the clinic, and hoped for the best. So, you know, we take great pride in that, that we're seeing exactly what we expected to see. In terms of the safety, we've now reported, you know, treatment of over 400 patients with 4150, which is, again, a remarkable accomplishment. And we haven't reported any serious adverse events or significant toxicity. You know, we've had, again, less than 3% kind of trace to one plus cells that could be detected maybe at one time point and then are gone by the next time point. So not clinically meaningful whatsoever. Again, a remarkable outcome. So that's that's the safety profile. And while we're not giving formal safety updates, we do watch the safety of every single patient on our phase three in a mask fashion. But, you know, we're we're you know, we certainly haven't seen anything that changes our thesis that this is going to be very safe and effective. And we do have a DSMC that also reviews the data every six months who, again, would tell us if there was a problem. The steroid regimen is probably overkill, to be honest. It's about 20 weeks of topical steroid drops. You know, each month you reduce the number of drops until you're basically on de minimis drops by the end. Compliance seems to be very good, but even if it's not, it's probably overkill. overkill, so patients probably can miss some doses. But we haven't, I don't think we've heard of a single patient from the sites who said, I'm not going on this because of eye drops, because what they're trading is a jab in the eye, and then blurry vision and pain for three days versus some drops. They'll do that trade-off all day, every day.

Great. And so we have the first readout coming out in the first half of next year. You know, what do you think would be good data there? What do you think is needed for commercial success? Chris, you want to speak to that?

I would go back, I think, to the comment I made earlier, where, again, this is not an absolute binary kind of pivot point. So, clearly, you've got to meet your primary endpoint. You've got to demonstrate safety that we think needs to be kind of in the range of where a standard of care is currently. We feel good about both of those based upon how the trials have been designed and the performance of the drug as we've seen it through development thus far. And then when it comes to the treatment burden effect, the injection-free, honestly, if it's in the range of what we've seen through PRISM, I think we have a massive home run. We'll see where the data falls. We actually think there's reasons why, based upon, again, the design and the patient selection for phase three, that it may actually could be better than that. Because, again, if you look at our efficacies and results that we've shown through PRISM, you look at patients that were more recently diagnosed, you do see a proportional benefit in terms of treatment burden reduction to those patients. And it makes sense biologically. You have healthier retinas. You're transducing retinal cells. So, therefore, it would make sense that you'd probably get more expression and more of a treatment effect. And then in our phase three, we'd have a completely, at least in forefront one, a naive patient population. So there's a scenario where you actually see, I think, a potential improvement versus what the treatment burden and injection free rates were from phase two. But even if that's not the case, if we're in that range of phase two, we're in a really good spot for commercial success, I believe.

Great. There's been a lot of talk, especially in ophthalmology, about the potential for approvals based on a single trial. So, you know, have you had those conversations with FDA? Do you think there's a path forward there to apply with just four-front one?

So we've not specifically had that conversation around wet AMD. We have for DME, diabetic macular edema, and we have alignment with both the U.S. FDA and EMA in Europe to do a single filing for DME. So that's definitely our plan. I think for wet AMD, there's probably a path. But the reality is also is because we were doing good drug development and de-risking things, we have two studies that are pretty close to each other. You know, readout for forefront one is going to be first half next year, forefront two second half. So how much do we really gain versus the benefit of having, you know, filing on both, both in Europe, U.S. and in Europe and Japan? And so, you know, we're still looking at that, but I think we're really well positioned even with just filing off two studies right now. Makes sense. That's our base case.

How are you thinking about the commercial strategy now that you're getting closer to pivotal data? And, you know, how do you think this type of product would fit into the buy and build model of retinal praxis? Would it be any different from like any of the other currently approved therapies?

The ways that it's different is better. So, but most of it is, I mean, so it's buy and build. The distribution model, we think it's the same as currently exists. It's, again, supported by the fact that it's an inter-visual delivery, and that's really important. When we, I recently had the opportunity to share our product profile and our development plans with a group of practice managers, which run some of the largest retina clinics in the country. They loved it. They were blown away by the profile. They're like, this is really IBT. They can store it at the same temperature as our current, I guess. Like, that's massive. So I think commercially that bodes well for us. The buy and build model, we think we'll fit within that because it's largely a Medicare Part B, an office administration product. And I actually think the economics, this comes up a lot when it comes to retina phlegmics. People are aware that physicians make profit on these medicines because of the buy and build model. And the retina community, I think, has largely perfected that business model with, you know, bolus therapies and how they create economics through that. But the dynamics of our medicine is going to be priced higher, of course, because the value that we reflect over long-term treatment burden reduction, the value of getting reimbursed up front is of significance to them. The value of capturing patients on a therapy that accounts for what likely multiple years of treatment versus a lot of patients fall off current therapies within a year, year and a half. So that's incremental value. So we think there's an economic story that actually improves the buy-and-build economics for a retina clinic with our profile. So, yeah, I'm pretty excited about that. And I think there's a great, I think, overlap of value for physicians and their clinics, clearly value for patients and the treatment burden reduction and the potential to hold on to their vision. And I also think there's a value story that will be interesting for payers as well, notably when you can show the reduction of treatment burden and the value and the preservation of vision for years. So we think we've got some unique elements that position us really strongly there commercially.

Great. You recently announced, I guess last year, you announced the partnership with Otsuka for commercial realization in Asia Pacific. You know, how are you thinking about the rest of the world? Are you going to do it yourself? Do you think it would make sense to find another partner for Europe or other regions? I assume you speak to that.

Yeah, happy to. I think we're keeping all options on the table, honestly. So we have said consistently and continue to believe that 4D150 creates value for all patients globally. And when it comes to Europe and basically ex-US, excluding Asia-Pac, which Hatsuka has, we're going to keep options at the table. So we'll look at a partnership opportunity if the terms and the details of that are right. If the factors there are not available to us or the terms aren't what we think are the right set of terms, then we reserve the option to commercialize ourselves. And by the way, that's one of the unique things about retina. You can do that. You don't need to be a large top 10 pharma to commercialize in this space. I've done it twice. I did it at Novartis, and I did it at Iveric with the launch of a GA drug. Same customer base. And the amount of commercial investment pre-launch, the size of the team, was the same in both dynamics. Small biotech, large top five pharma. So we can take on that commercialization challenge ourselves if that's what we think is strategically the best option for us.

And just to clarify, you know, that what wasn't said, but it's definitely our plan, is we will commercialize ourselves in the U.S. And Chris is, you know, the right guy to do that. He's done it, I think, two or three different times with different companies, including Novartis, Genentech, and Iverix, so we're in good hands.

How are you thinking about manufacturing? I think that's a place where, you know, recent gene therapy, you know, filings of, you know, face roadblocks. So, you know, what's your strategy there?

Yeah. So, you know, with complex biologics, it's a real issue, right? And it's probably one of the most common causes of a failed BLA. And, you know, because of that, we invested in CMC very, very early on in the company's evolution. One of the first things we did was build a manufacturing pilot plant. And when we went into the clinic, we said, okay, you know, let's see if we can't manufacture ourself GMP. We were highly successful. We took six different products into the clinic, all internally manufactured, didn't have a single failed lot, never had a trial delayed because of a quality issue with manufacturing. So it's a phenomenal team, all the way up into phase three. And then, of course, you need to do a technology transfer to a commercial facility, which we've achieved already. And then, again, ideally, you'd have at least 50% of the material in one of your phase threes come from the commercial facility, which we are now in the middle of achieving. And then we need to do our qualification batches, which we're in the middle of doing. So I think everything's on schedule. We have a great CDMO who's been a real leader in this space. And so I think between our innovation, RCMC team, plus this commercial CDMO, we're really in a great position.

Great. Maybe in the last couple of minutes, we can talk about DME as well. You know, how are you thinking about that opportunity? And I think you're expecting to initiate your phase three trial soon. You know, what are the gating factors before you can start the trial?

Yeah, I can speak to the practicality. So Q3 is our guidance for starting that study. We're on track for that. We're really excited. I think it's going to be phenomenal excitement there and excellent enrollment mirroring, I think, what we saw on wet AMD. As Chris will tell you in a minute, that probably the unmet need in DME may be even higher. So we're really excited. I think mid-year this year we'll give an update on the final study design after final regulatory interactions. What we've got it to is a BCVA non-inferiority, five loading doses, which is standard in DME, and then a final sample size somewhere in the range of 300 to 400 is where we're currently guiding. And we'll update that soon. And then I think Chris can speak to the real opportunity in DME, which is huge.

Yeah, I mean, as you like, DME is the second largest indication in this polus antivagestia. space today, but it's undertreated and it's underpenetrated in terms of the market value. There's more patients and the challenge with staying on therapy is greater in DME than even in AMD. So when you listen to physicians and they talk about treating DME patients, they think about whether a patient's going to stay on therapy and they worry about whether that patient's going to get lost to follow up. So the benefit of significant treatment burden reduction for a patient that often has a lot of other stuff going on or younger, the burden of getting into the office can be greater. So that benefit is of high significance in the fact that, listen, we by design solve one of the biggest challenges in health care medicine, which is adherence to therapy. Because once you get 40, 150, it's there, it's constant, it's always present. So solving that in a DME patient population is really, really meaningful. So I actually think there's this scenario where in a commercial setting after a couple of years, you actually could see DME be a larger indication because of those factors. than even A&D. So we're pretty excited about that opportunity.

Maybe last question, Christian. What's your current cash runway and what's included in that? I didn't want to leave you out. No, absolutely.

Appreciate it. So as of the end of Q1, we had $458 million in cash and cash equivalents. Cash runway, we're guiding to sometime second half of 2028. um look it it it doesn't include the commercial ramp up yet that's something that uh we anticipate to finance post forefront one great thing with that we're out of time so thanks again for joining us guys thanks for having us to be here thank you