Conference Transcript - FDMT 2026-06-09

Operator

Okay, well, thank you, everyone, for joining us. We are here with FDMT, Christian Humer, CFO, and Chris Sims, CCO and CVO. Maybe you could start with an overview of your directed evolution gene therapy platform, your pipeline progress, and your 12-month catalyst path.

David Kirn, CEO

Yeah, hey, it's great to be here. Thanks for the opportunity. I'm happy to start with that, and Christian can fill the details in our catalysts that are coming up over the next 12 months. So first of all, 4DMT, we're a next-generation gene therapy company, platform company. We have a number of programs in development, but the program that's taken the majority of our focus right now is a program, we call it 4D150, and that's a gene therapy that we're studying for the treatment of wet AMD. So our wet AMD Forefront 1 and Forefront 2 Phase 3 trials are underway right now. So that's our leading program. We hope to start our trial for DME, so diabetic macular edema, the second largest indication in retinal disease later this year with 4D150 as well. And we have other programs in cystic fibrosis, but the 4D150 is the primary focus for us right now, considering where we are with phase three. And with that, Christian, you want to speak more to the catalysts that are coming up?

Kristian Humer, CFO

So in terms of catalysts, the big catalysts are next year, kind of first half of next year, there'll be Phase 3, Forefront 1 data. And second half of next year will be Forefront 2 data. This year, we'll have kind of by the middle of the year, we'll have a two-year duration update for our PRISM trial, kind of our Phase 1, 2 trial in wet AMD. and two-year duration data for our DME Phase II sometime second half of this year. And we endeavor to provide an update on our cystic fibrosis program 7-10 by the end of the year.

Operator

Okay. So multiple leadership changes at the FDA. You guys as a gene therapy company go through CBER. How are you thinking of your positioning in this current environment?

David Kirn, CEO

Yeah, so no doubt there's been a lot of change. I'll tell you that our interactions with the FDA have been pretty standard. We've been very productive, so nothing that's come up in any of those interactions that would cause us to have any view that's different than what we've been operating with. We also think the fact that our Phase III program, our Phase III trial designs, are fairly standard in their design. If you look at how we've designed Forefront 1 and Forefront 2, It's a very similar design to how other new agents in this space have been studied and approved. So the Babismo design, the ILEA HD design, and even other pivotal programs going back many years ago, we follow a very similar type of trial design as that. And we think that design is conducive to a very productive regulatory path forward with the FDA and the European regulators as well.

Operator

Yeah. So starting with wet AMD, you enrolled faster than expected and upsized your North American phase three trial. Maybe speak to the expectations for enrollment for your global trial and whether this could be upsized as well. And overall, what this says about the physician

David Kirn, CEO

enthusiasm for gene therapy in the eye. Yeah, I love that question for a couple of reasons, So first of all, yes, to your point, we started out just over a year ago with initiating our first phase three trial, so Forefront One. And at that time, we estimated that it would take about 18 months to enroll at the time an end size of 400. What happened instead is we actually ended up rolling over 500 patients, and enrollment finished in Forefront One in just under 12 months. So we finished enrollment in March of this year. So faster enrollment as well as with an increased end size. And we've already said publicly Forefront 2, we think it's enrolling at a similar pace as Forefront 1. And the difference is that it's a global trial. And the end size, we also will increase that as well. So we expect that to, the official end size is 480, and we're likely to over-enroll that, similar to what we did with Forefront 1. And as the commercial guy who's launched a couple of drugs in the space, when you're trying to prepare for commercialization and you hear all the feedback and you do the modeling and what the opportunity is, and we think it's certainly very significant, one of the things that can be a good proxy, we believe, is pace and enthusiasm for a phase three program. So for me to see that level of physician and patient enthusiasm that helped drive that Forefront One enrollment time period, it's very encouraging. We think it points to it's a good proxy for what we think the unmet need is and how we can possibly solve for it.

Operator

Yeah, that makes sense. So you have a non-fioriority margin that you have to hit at these studies, but based off of your discussions with physicians, what do you really need to show in this data set for this to become practice-changing as a foundational therapy?

David Kirn, CEO

Yeah, so, I mean, first things first, right? You have to hit your primary end point. So for us, that's non-inferiority and vision at week 52. And you also have to have a profile that's safe, which makes perfect sense when you consider that this therapy area has lots of efficacious and fairly safe agents available today. So you need to show, you know, safety and efficacy in that regard. From a paradigm-shifting perspective, what we think we can deliver is what we've seen through our Phase 2 program, which is treatment-free rates in the 50% range, depending upon the population of patients at Week 52, and overall treatment burden reduction rates, 80-plus percent. And we think that's highly meaningful for a couple of reasons. Well, first of all, when you look at how this entire anti-VEGF space has evolved over the last 20 years, it started out with Lucentis back in 2006, and ILEA launched. And Lucentis was an on-label four-week drug. ILEA was approved for use every eight weeks. And advances since then have come in incremental advances in durability measured by a week or two. So Vibizmo is a 16-week medicine, but not all patients are at 16 weeks. So you get a sense that these incremental advances in duration have yielded significant commercial value, both medicines like the Beismar worth over $4 billion, I think, in the current year. But the benefit from a treatment burden reduction standpoint was a week or two. We think we can affect that by orders of magnitude in the 50% of patients being treatment-free or over 80% of treatment burden reduction that patients will benefit from. So that treatment effect is definitely a paradigm shift versus everything that's been done before. So that's what we aspire to with a backbone for retina approach, which is how we coin it. We are uniquely positioned in a space that's highly competitive but also has still a very high unmet need in terms of reducing treatment burden.

Operator

Yeah. And when you think about executing on the operational aspects of the trial, especially around managing sorts of confounding factors such as cataracts or the potential for investigators' discretion on supplemental injections, how are you making sure that you have kind of those aspects in check?

David Kirn, CEO

yeah so on the on the cataract question first well first of all you would expect that any you know incidence of cataracts would be observed in both arms assuming both treatment arms are balanced and just as a reminder for your audience our trial design has you know half of patients being randomized to 4150 and the other half of patients being randomized to on label ilea and both arms will get a prophylactic steroid regimen so if a patient develops a cataract, we have a protocol that allows for that cataract to get removed, and then the patient should stay in the trial. As far as supplemental treatments are concerned, we have very well defined and we think very reasonable criteria that would trigger a supplemental treatment. Those criteria were developed with, you know, world experts in retina, and there is no physician discretion. So if there's a flag for supplemental injection that would get elevated to a, we have a committee that would look at that and verify that it meets the criteria, but there is no option for a physician to, you know, exercise their own discretion. It has to meet the criteria and go

Operator

through that process. In terms of commercial positioning, there are also TKI programs that have reported data and are emerging in this space. How would you characterize the positioning of those agents versus a gene therapy, and what do you expect their durability will be in real-world

David Kirn, CEO

practice? Yeah, so like I mentioned earlier, the entire space has evolved by incremental advances in durability, and that's meaningful, which, you know, that's actually been a good thing for patients, and you can understand it, right? If you tell a patient that you're getting six or seven needles in the eye in a given year, and you can reduce that by one or two, most patients would be very attracted to that. We think of TKIs and other bolus type of therapies in development as trying to advance an incremental benefit in that regard. So there's interesting science beyond the TKIs that are in development, but all of them are trying to squeeze out another increment of durability. That's not our positioning. We're not trying to advance incrementally. We're trying to set a whole treatment paradigm, which is why we call it a backbone for retina. We actually think of a treatment paradigm where we think the majority of patients could be considered to have a onboard 4D150 that's constantly managing and controlling the disease for the rest of that patient's life. And for some patients, because it is a very dynamic disease that may need occasional supplementation, there is a wide number of different options that a doctor can choose from, and TKIs and other things in development could fill that need for supplementation when and if needed. But our positioning, we think, is very clear. It's a backbone type of approach. We're not a bolus therapy like those other agents, and we think, you know, that has very significant clinical meaning, both for our practice and certainly for patients. Yeah, and noting that TKI did recently

Operator

report data from a superiority trial, maybe could you remind us of the rationale and why you chose non-inferiority and how that reads through to pair dynamics if launched?

David Kirn, CEO

Well, we chose our approach because we think the data that would get generated from our approach is most meaningful to physicians and their patients. It's how drugs have been developed in this space. It's how the data that comes out of these programs physicians use to translate to how they would incorporate it into their clinic. And some other designs, I think, are interesting, certainly from a headline perspective, but may not be as applicable to the clinical setting. So that's what drove our design. We wanted to make sure that we generated a data set that, one, obviously, allowed us to have a shot at approval, show that the medicine worked in a meaningful way and solved an unmet need, and show that the data that would come from our pivotal program could be translated by a physician to their clinic for application to their patients. And in addition to that, as you just referenced, we will need to show that we can generate value for payers, right? There's multiple stakeholders in this space, and it's a complicated set of variables, but you have to think through all the stakeholders that are ultimately going to be important for the success of your medicine. So payers are a big part of that, both U.S. payers and ex-U.S. payers, which is one of the other reasons why our Forefront 1 and 2 program, we think of it as a global program. Forefront 2 is being run around the world. We have sites in the U.S., in Europe, in South America, and in Asia, because we think the unmet need that we're solving for or trying to solve for around significant reduction of treatment burden, it's a global issue. In fact, if you look at other countries around the world where access to retinal care may not be as accessible as it might be in the U.S. or in the Western world, what we could solve for with an always-on constant gene therapy could actually be more significant in countries where that access to care is more limited. So our design was done with keeping all of those variables in mind. The last thing I'll mention, which I think could be really interesting in terms of what we can show in a future state, is the ability to preserve vision. So it's really interesting in this space. These therapies, these bolus therapies that exist today, are highly efficacious, right? You get diagnosed, and it's very common. You see this in data sets that patients within the first couple of treatments will gain five to ten letters of vision. and for that patient, that's incredibly meaningful. It's actually life-changing in many respects. Unfortunately, if you look at a lot of data in the real world, despite gaining that vision initially, a lot of those patients, if not the majority, over time will lose that vision, even if they're staying on therapy. And one of the big reasons for that is for a variety of factors, patients tend to get undertreated in the real world. So that vision gain happens. They hold on to it for a while, and then you get out a year maybe beyond that for some patients, and a lot of those patients have lost that vision. In fact, a lot of those patients, their vision will eventually go below where they started. But there's also really good data that shows that if you have constant VEGF suppression, you see this in a data set from CISVIMO, the Port Delivery System from Genentech, or even other studies where, like, Lucentis was dosed monthly regardless of disease activity. you actually see that vision game be maintained for years. We think, based on our modality, we have the potential to show that as well, which is very exciting. So you can imagine telling a patient that, hey, you have the potential that this might be the last injection you'll ever need. And in addition to that, there's a potential that that vision that you care the most about, not only can we give some of that vision back to you, but there's a high likelihood that you can hold on to that for years to come. And we think the combination of those two elements is incredibly compelling for all stakeholders, payers, and physicians. And back to the first part of your question, we designed our trial to hopefully show that.

Operator

So at launch, do you expect a dynamic where you'll have advanced patients as the early adopters and then shift over time to earlier stage? And maybe can you characterize what the treatment goals are for each of these populations?

David Kirn, CEO

Yeah, it's a great question. What AMD patients, DME patients, are highly variable, right? You get a distribution curve like you do in many diseases. So you get some patients that may only need two or three injections per year to manage their disease. You get some that almost need monthly injections. And then you get the standard distribution curve in the middle where the average is six or seven or so per year. But your point is spot on. Upon launch of new medicines in this space, I saw this when I launched a drug called BioView at Novartis several years ago, and I think we say this with new launches from Babismo and ILEA HD, that the patients that are treated first are the patients with the highest need, which makes sense. Those are the patients that are most interested and motivated by trying something new. So you get tested on patients that are often getting 9, 10-plus injections per year almost on a monthly cadence. We feel really good about that challenge that we anticipate getting in the commercial setting because we've generated pretty robust data on patients that look just like that. In fact, if you look at our severe patient population from our Phase II PRISM trial, which is data that we've shared now out to two years, you will see that those patients were historically getting an average 10.2 injections in the year prior to going on to 40, 150. And up to two years, we've shown a treatment burden reduction where they were on pace to get just over 20, if you take that 10 and assume, you know, two years of treatment. And on 40, 150, the average number of supplemental injections was four. So about an 80% treatment burden reduction up to two years on a patient population that was getting injected almost monthly. So if that's the type of patients that we get tested on in the commercial setting, we think we can show a very significant treatment burden impact on patients that are arguably the hardest to treat. That's a test that we think all new agents launched in this space are going to get tested with, regardless of whether you're a TKI or other bolus therapy that's in development. That's the patients that doctors are going to be most motivated to try your new drug on out of the gate. And I think how you do with that patient population is going to be pretty informative as to how the rest of your commercial launch goes.

Operator

Yeah. On pricing, a high price naturally is attractive for buy and bill purposes, but also may have some payer dynamics to watch. How are you thinking of balancing between those two aspects?

David Kirn, CEO

Yeah, it's kind of like Goldilocks, right? Not too hot, not too cold. There are a lot of variables you have to think about. So very familiar with all the dynamics that go into pricing. There's a practice economics piece, which you alluded to, based on the price of the drug, that's how physicians make profit. There's also the consideration of, there's a societal consideration, there's a payer consideration, there's a patient out-of-pocket consideration. So there's lots of things that go into the mix. and as we said today we have no idea what the pricing will be we'll make those decisions when we're further along in our development program but what I will tell you is that philosophically, because part of pricing as well it's a math exercise but it's also a bit of a philosophy exercise as to what you think you're trying we truly believe that 4D150 can be a backbone therapy for patients with retinal disease it's hard to have the aspiration and vision and then price it in a way where you limit access to the 10 or 12% of patients that can truly afford it so that's going to be important to us when we make those decisions practice economics will certainly be important to us as well and we'll make those decisions when we have phase 3 data and we have a better view of the landscape the good thing that I'm excited about is that we don't, despite being a gene therapy sometimes that comes with the assumption or the connotation that your pricing must be well in the six figures, your cost of goods must be exorbitantly high, which is often the case for other gene therapies and sometimes in more systemic settings. Our cost of goods is less than $1,000. So when we have to make that pricing decision, we have a lot of pricing flexibility. And at the end of the day, I think we'll price it in a way where we consider all of those variables and make the best decision that hopefully satisfies the needs of all of the stakeholders and patients to physicians and payers and, of course, for investors and owners of the company.

Operator

And in this population, we have Medicare Part B, fee-for-service, and Medicare Advantage. Maybe if you can discuss the split between those two and how coverage and out-of-pocket differs.

David Kirn, CEO

Yeah, so absolutely right. What AMD, we think 90% to 95% of patients are covered on some sort of a Medicare arrangement and then 5 or so percent are still on the commercial plan. In the Medicare population, for rough estimates, it's kind of half fee-for-service, half Medicare Advantage. Medicare Advantage portion could have a variety of different constructs and designs. The patient out-of-pocket can vary. Sometimes it's more driven by having a deductible up front that they have to kind of burn through before the out-of-pocket goes down, but it can often depend upon how that individual Medicare Advantage plan has constructed the design for that particular patient. And what you typically find in the MedAdvantage space is you have, as opposed to being on or off formulary, that's not really how it works. It's more of you have stepped through other types of things that you have to get through in order to get access to sometimes more expensive medicines that exist today. I would expect some version of that to exist for us as well. All of that's manageable. All of those are things that you would normally expect to see. Medicare fee-for-service is very different. It's direct reimbursement from CMS through one of their MACs. And, you know, typically the design of the plan there is the drug is covered by 80% of the cost of the medicine is covered. and most patients have supplemental insurance for that out-of-pocket 20%, so their out-of-pocket would be very minimal. So that's usually a fairly more accessible payer segment for a patient to be in. For patients that don't have the supplemental insurance for that 20% out-of-pocket, it can be more limited in terms of what they can afford. It varies by patient, of course, but I think you hear even evidence of that today if a patient wants to go on a branded anti-VEGF drug and they don't have supplemental insurance for that 20%, 20% of a $2,000 anti-VEGF today is about $400. So for some patients, that's tolerable. For some, it's not. So that's something that we'll certainly have to consider.

Operator

And do you factor dosing the second eye into your projections?

David Kirn, CEO

We certainly do. Yeah, we estimate about 40% of patients with wet AMD have bilateral disease. So our development program, we have a planned contralateral eye study that we'll run to provide, hopefully, a label that supports dosing in the fellow eye.

Operator

So turning to DME, you have alignment on a single phase three trial. Any experience that you can leverage from your wet AMD trials to hear?

David Kirn, CEO

Yeah, a lot. So we're very excited about starting our DME trial. We hope to initiate that in the back half of this year. I actually think DME could, DME is the second largest indication, as you know, in this space today after wet AMD. But it's largely underpenetrated in terms of the market potential for a bunch of reasons. Younger patients, patients aren't necessarily as adherent to therapy as you would see with a wet AMD population. So I actually think that a gene therapy like 4D150 that solves the adherence challenge by design, right, once it's there, it's always there and helping to treat the disease, could actually unlock the diabetic macular edema market in a way that it's even more significant than it exists today. So we're thrilled about the opportunity in DME. As you mentioned, we have regulatory alignment from both the FDA and EMA for a single global trial. We're planning to start that trial in the back half of this year in partnership with Otsuka, which we have an Asia-Pac relationship with. And, yeah, I think a super, super exciting opportunity and an exciting follow-on development for us after wet AMD and we've learned a lot to your question about how we could execute against that in fact you know the fact that we have pretty wide awareness right now within the retina community at the 4150 profile we have a really strong network of clinical trial sites I think all those things will be conducive to starting the trial fairly quickly and hopefully we would see enrollment that's similar to what we've seen with AMD we think the physician enthusiasm certainly is

Operator

as high there as it is in AMD. How much of an issue really is capacity constraints within these clinics? And does this come up as a reason for prescribing gene therapy versus other reasons

David Kirn, CEO

such as economics? It's a, love that question. So it does. Listen, the reality is there is more demand for the services of retina specialists today than there's often retina specialists available to meet that demand. That can vary by geography. Some geographical areas, that's more pronounced than others. But it's also projected, that divergence of supply versus demand is projected to increase over time. You have a continuing aging patient population, and the number of new retina specialists that are being trained and put into practice is not keeping up with that. So we think the timing of 40-150 could really be interesting in that regard, where you could significantly not just alleviate treatment burden for the patient, but you could help create capacity room for the clinic as well. And listen, the clinics are becoming more competitive and more complex, right? I was on Lucentis years ago when it was Lucentis, ILEA, and off-label Avastin. That's largely the drugs that physicians had to choose from. And today you have biosimilars, you have new agents. You have GA drugs that launched Iservay. So there's lots of other things that have created complexity in these retina clinics. So anything that can offer a simplifying solution the way we think 4D150 can, can help solve, we think, be a big part of the solution around capacity. And most doctors recognize that. And for doctors that don't seem to recognize that because they may not be paying attention or measuring that, I would encourage your audience to talk to a practice manager in that clinic because those are the folks that are often managing the back office, the patient flow, the scheduling, and so on, and they would tell you pretty quickly that there's definitely a challenge with capacity and they're looking for real innovation to help solve for that. An incremental durability of a week or two from a bolus new therapy doesn't really solve for that unmet need. We think we can.

Operator

And are there any other indications that you're interested in pursuing with 4D150 and in that context, how are you thinking of phasing spend as you go into these large market opportunities?

David Kirn, CEO

Yeah, we've talked about whether it makes sense to consider diabetic retinopathy after diabetic macular edema. We haven't made a final decision on that, but I think there's lots of physician feedback that would suggest that that's something we should consider. And as far as thinking about prioritizing phasing spend, maybe Christian, you want to speak to that?

Kristian Humer, CFO

Look, I think there it's very clear. So we're laser-focused on the execution of wet AMD and DME. That's kind of the phase three trials that are ongoing. But we're acutely aware kind of the potential value of our platform. I think at these current share prices, probably investment in our platform is going to be moderate. But over the medium to long term, You know, we believe there's significant value there in our platform.

Operator

So touching on cystic fibrosis, you plan to provide an update in the second half of this year. What could that contain, and how are you thinking of forward pass, accelerate approval versus phase three?

Kristian Humer, CFO

Look, we reported in last December kind of what we believe is a super interesting kind of ALI signal of our vector and cystic fibrosis with our 710 program. What we want to do kind of with the next update is really provide the kind of 12 patients' worth of data with 9 to 12 months of duration. i think that's what we'll guide to in in the update that's coming kind of second half of this

Operator

year great maybe in our last few minutes you can touch on um the cash runway your assumptions factored into that and um on partnership strategy clearly your platform has broad utility how are you thinking about out licensing on the forward absolutely uh so from from a cash perspective

Kristian Humer, CFO

As of the end of Q1, we had $458 million in cash and cash equivalents and are going to a cash runway into the second half of 2028. What that doesn't include is the ramp-up in commercial spend that would happen post-FourFrontOne data. That's something that we can commit to once we have that data in hand. um in terms of partnership uh look i think as as chris mentioned here in i mean we we require kind of an 80 to 100 sales force to execute commercially here in the u.s on any of our retina programs we think we can do that by ourselves um we want to make sure we maximize value for our shareholders it. In terms of ex-US, I think those rights for us are strategically and economically important. I think we're going to be really careful kind of how we approach that from a partnership perspective. And if need be, we can go at a line, for sure.

Operator

Okay. And just in our last minute, you touched on this a bit with cogs and pricing of gene therapy but is there anything else that you would want investors to understand about your story and

Kristian Humer, CFO

your strategy? Look I think we covered a lot. To summarize again I think this is a we're doing something that's never been done with a gene therapy before. We're going after a very large market with wet AMD and DME that we can execute on by ourselves and I think if touch on wood if if we're right in what we want to do it has the potential to treat to really change the treatment paradigm of these patients and how these patients are being treated today okay well with that thank

Operator

you very much for joining us and we look forward to seeing all the progress thank you so much thank

Kristian Humer, CFO

Thank you for having us.