4D Molecular Therapeutics, Inc. (FDMT) May 19, 2026 Conference Transcript

Lisa 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 Sims, who's the chief commercial and business officer, and Christian Humer, who is the chief financial officer. Chris, Christian, thanks so much for joining us today. How are you both doing?

Great. It's great to be here. Thanks for the opportunity.

Great.

Thank you for having us. It's been a good day.

Well, it's great to have you both here. So, 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 two to three years. So, you know, with all the progress, what do you think remains the biggest misconceptions about the story? And what are investors missing?

I can start with that. And Christian, feel free to add an additional color. So 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. And 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. So 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 application is always on board 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. And 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. But admittedly, 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. Then 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 want to 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 4150 certainly differentiates on safety. We hope to prove that certainly in our phase three program, which, as you referenced, has been enrolling at a very high pace. And 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. And so, 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?

Yeah, there's nothing of note that's unique to our conversations with the FDA. We acknowledge the volatility, but 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 three program is very traditionally designed. So 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 the BISOM, ILEAS, and so on. So I don't think there's anything that's overly unique or unusual about how we've developed 4D150 in our Phase III program. So I think that is conducive to pretty up-the-middle FDA interactions. The 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. And we have regulatory alignment from both the FDA, EMA, and Japan for a single DME trial. So we plan to do a single trial globally. We'll do it in partnership with Atsuka, which is our partner for Asia Pacific. And 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 going to get the update in the third quarter, but should we expect this trial design to follow what we have seen in the past with other programs?

Yeah, I don't 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, but 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. So 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 three data set has applicability to clinic usage. So again, while we haven't got the final details of our phase three DME study ready to be shared, I think you should expect that it'll also be very, I think, standard and traditional in its approach, similar to how we've done Forefront 1 and Forefront 2 for AMD.

Should there be some similarities with the Forefront trials, maybe in terms of the rescue criteria or steroid use?

Yeah, we don't know, 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, but certainly I think it'd be somewhat similar to what we have in the wet AMD trial. And 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 Forefront One and what we've seen in other phase three DMV programs from, you know, Roast Genentech or Generon and so on.

Got it. Got it. That's hopeful. 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. And, you know, these drugs are safe and they improve vision and the branded market has really grown into the largest area of ophthalmology therapeutics. So 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?

Yeah, it's a great question. And it's amazing, actually, as you mentioned that. We're about 20 years since, I think, the introduction of Plucentus. So for 20 years, the treatment of these diseases has been done through a needle in the eye at some frequency. And of course, that creates a whole host of treatment burden challenges and a needle in the eye is it's fairly a rote standard procedure retina docs do it multiple times a day but you have to think that that treatment paradigm is due for a different approach um and we think we can we can deliver that um so you know and you mentioned these therapies uh help patients gain vision and that's correct. You see in all these phase three programs upon initiation of therapy, depends on what the patient's baseline vision was, but on average, a patient, a wet AMD patient is going to gain five to seven or so letters on average at the start of a trial. But 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've stayed on therapy for two, three, or even up to five years, more likely than not, you've actually lost that vision that you gained initially. And you actually see this. In real-world data, you gain that five to seven letters. But over time, that vision slowly erodes. And in fact, many patients, when you get into year two and three, actually have worse vision than they had when they were initiated on therapy. And 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. And sometimes there's anatomical issues like fibrosis or atrophy that may show up, which has an effect on vision. But what we also know, and we've seen this in a number of data sets, is that the constant regular suppression of VEGF has resulted in patients holding on to that vision for the long term. So 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. So you know that if you are constantly controlling the disease with VEGF therapy, patients can hold on to that vision. And we've also seen that data, by the way, with a drug that Genentech has called Susvima, which is an implant, which does the same thing. It controls VEGF continuously. It's always there. It's always on. and you see as a result of that, patients hold on to that vision long-term. Our view is that with a 4150, 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. So in many ways, we think we can produce sustainable-like long-term vision outcomes, but not have to do it through an invasive implant type of approach.

Got it. And, 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. And we're also going to get our first pivotal gene therapy readout as well later in the year for a subretinal approach. So how might all these readouts, you know, as the data comes in, how is this going to shape your strategy, your commercial strategy for 4150, which is going to start to read out later or beginning in first half 2027 with forefront one?

Yeah, it's a very dynamic space, as you just referenced. The next 12 months is going to be pretty exciting. And I think a lot of those readouts are going to be informative. I think a couple things I would say. First of all, all of these programs, certainly the TKIs, are looking to extend durability, as are we, right? They're looking to add another week or two of durability because treatment burden is an issue. and we know it's an issue when we've seen medicines like Vibaismo or ILEA-HD, which extends durability by a week or two, come to market. We all know the commercial success that have resulted in that. So 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 three program. I think the difference 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 two. we're looking to establish a backbone for retina that for patients holds the promise of months and likely years for many patients. I've never needed 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, 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. And so 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. And, you know, the branded wet A&B 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 4150 capture?

That's a great question. And growing, right? So 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. So 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 4D150 as being a niche type of product. We actually think if we generate the data we expect to in phase three, that backbone therapy approach should be considered for the majority of patients. I actually, 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, Like, what patient do you think you would not consider for a therapy like this? And what we get is, you know, there's a handful of patients that are seemingly controlled with two or three injections per year. And that's the group that physicians are likely to not consider 4D154, at least initially. And we think that represents maybe 10% of the overall AMD population. The majority of patients need, you know, on average, the number of injections is about six to seven per year, with many patients needing eight to ten, if not more. So we think there's a segment where we're likely to be used less, but the overall population, we think over 90 percent, at least physicians, would consider us for those patients based upon their treatment burden need. And 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. And 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. so 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 and i 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 got to charge three million dollars 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. And about, I think, 100,000 to 150,000 of those are new to treatment in that year. So you have a fairly high incident rate that continuously brings you in, I think, a nice bolus of patients that are considered for treatment. And, of course, that's just a function of the aging population. So those things have to be considered when you think about things like pricing. So while it's way too early to say what we think our price will be, because it's going to be determined by a number of factors, our phase three 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, and we're delivering a relatively low dose at 310, we think we can deliver a cost of goods profile, which is probably less than $1,000. So 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 So it's very helpful to kind of get your thinking around it. And I do want to touch on the opportunity outside of the United States, since this is part of your strategy. You know, you have this partnership with Atsuka on the Japan, APAC region, EU, obviously, the anti-VEGFs are sold widely there. So how are you thinking about the opportunity for 4150 in those regions?

Well, yeah, so first, just to reiterate the obvious, I guess, U.S. is priority number one, and 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, Forefront 1, the first phase 3 trial that completed enrollment at the end of March, that's a U.S., North America, U.S. and Canada trial. Forefront 2 is a global trial. So we have sites in the U.S., in Asia Pacific, South America, and in Europe. And Forefront 2 also has a little bit of a different patient population. So Forefront 1 is entirely treatment naive, and Forefront 2 is a blend of naive and experienced patients. That experienced patient population is in direct response to an EU regulatory requirement. Those patients could have been diagnosed in the prior six months. So we've designed our pivotal program for global adoption. So I do think the European market is of interest. Certainly Asia Pacific is a market of interest as well, which is why Atsuka was motivated to do the partnership with us that they've done. So we believe there's an opportunity globally and certainly like the top five 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. And 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 US-only need. That patient need exists globally, unfortunately, in this disease. And you can make the argument that But 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. So 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. And on the forefront trial, these are your two pivotal studies that are ongoing. You know, Chris, these are non-inferiority trials, and they have a rescue criteria in them. And the rescue criteria is relatively strict. If the patient loses five letters and has, I believe, a 50 micron or greater increase in CST is your criteria, they would get a supplementary injection of anti-VEGF. So 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 de-risked the phase three program as much as we can, while also maintaining its relevance in terms of the data that it will present. You know, you never want to say that things are guaranteed. That's just not the nature of the business that we find ourselves in. But, 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 approved to make sure that whatever we choose to be the retreatment criteria is relevant and physicians would look at that and say that represents something that's meaningful to how I treat my patients. But yeah, I think we've tried to do as much as we can to de-risk the program. You never know until you know and you turn that data card over. It's the nature of being in this business, but we think we're as de-risked as you can be and looking forward to seeing those results in the first half of next year.

So some of the secondary endpoints of this trial, I think, are going to be a lot of interest, like reduction in injection burden. Is there a bar you have in mind that would really facilitate commercial adoption of a gene therapy?

So yes, 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 one percentage below or above that number defines success and the reality is it's not that so I'll refer to I think the conversations we have with retina docs and we take them through our program and we show them our phase two data which we show treatment free rates 50 to 70 percent depending on the population overall treatment burden reduction 80 to 90 percent range I'll guarantee you anything from our phase three 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? And the first time we did it eight months ago, we tested a 60 percent, I'm sorry, no, a 70 percent treatment free rate did a 90% treatment burden reduction, and then we did it a month ago and we tested a 50%, so a lower treatment-free rate and 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 two data sets. So I guess it just proves that there's no magical number per se, but again, I think if we're in that range of 50% treatment-free, 80-plus percent 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 of catalysts coming up. We're supposed to see two-year follow-up from PRISM and the broad and recently diagnosed patient population. What should we expect to see here in that date?

So that's a continuation. So we've already shared 18-month data on that patient population. So our expectation is just more of the same. We think that data would, it should just represent the same overall treatment burden kind of reduction rate just out to a longer time period. And hopefully, of course, the continuation is safe.

Got it. And 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.

Okay.

Okay, got it.

Well, I think we're a bit out of time, but Christian, maybe a question for you since we have you here. Can you maybe just remind us of the cash position and the runway and what the runway is expected to cover in terms of your clinical programs?

Happy to. So as of the end of Q1, we had $558 million in cash. We are guiding to cash runway into the second half of 2026, or 2028. And what it doesn't include that cash runway is basically the commitment to the commercial build out that we would need to do post full front one day.

got it very helpful christian well chris christian 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