4D Molecular Therapeutics, Inc. (FDMT) Earnings Call Transcript & Summary

I would imagine. Yes, very much so. I mean, I think the big takeaway is it's consistent right prior to what we shared at ASRS was a 2-year update and we had previously shared an 18-month update so it was an incremental six months and now we've shared 2 years of data across all those Phase 2 populations that we reference, some more severe patients that were getting in 10 injections a year to patients that were broad or more recently diagnosed. And I think what we see is largely throughout those different time periods, now out to 2 years, a very consistent safety profile, and importantly, a very consistent level of efficacy as measured by the retention of vision, which is super important, obviously, but also the continued treatment burden. We see those numbers in the 70, 80, 90% range, and we've seen that continuously now out to 2 years. So that's very validating. A question that often comes up from retina docs when they think about a gene therapy modality, to no surprise, is, you know, what will this look like long term? And the more we can show data out to 2, 3 years, maybe potentially even more, potentially, it gives them increased confidence of how they think about it when they consider this in a commercial setting for their patients.

Okay. And I guess speaking of the potential commercial opportunity for 4D-150, you know, we touched on the powering for Forefront, but, you know, beyond success from a regulatory perspective, I guess, what's the feedback you get, you know, whether it's from payers, prescribers, patients of, you know, what is a compelling profile for 4D-150? Is it, you know, a stat-sig benefit in Forefront? Is there more to the profile they'd like to see?

Yes, so I'll tell you, when we share the PRISM data that I just referenced, that 2 years of data, you're seeing the maintenance of vision, you're seeing safety, that's very consistent, and you're seeing overall treatment burden reduction rates, again, between 70% and 90%. That profile is immensely compelling to all of the stakeholders that you just referenced. In fact, doctors will tell you that it doesn't need to be the treatment burden reduction rates in that range. They still have a very compelling profile. And keep in mind, Vabysmo has been a pretty significant commercial success with reducing treatment burden by, we model like 20%. We don't think we're going to be anywhere in that range. So we think that's that's highly compelling across all of all of those stakeholders to have a very very strong target product profile in the commercial setting and and we have we haven't officially engaged with payers, but we have done a lot of market research with payers, sharing their profile, getting their reaction. And payers in the U.S. is largely Medicare Advantage providers, plans, being in a heavy Medicare patient population. Quick plug, we will have an investor day focused on a lot of commercial topics on the 21st of October. Oh, great. Where a lot of this commercial content that we're talking about we'll go into with more detail and share some of our internal work and research to help the broader investor community give hopefully a better appreciation for the commercial opportunity. Okay.

Great. Maybe just a bit deeper on treatment burden, and I think this is something that investors maybe struggle with from time to time in terms of cross-trial comparisons. Just remind us of the rescue criteria in Forefront. You know, we tend to see some variability across trials in that regard. So what informed your decision on the rescue criteria here? And again, just remind it what it looks like.

You want me to take that one, David? I guess I can take that one and give you a little break. Yeah, so when we, you know, when you think about the trial design, it's all about what patients go in. We thought we'd optimize that, then kind of the treatment, and then the endpoints. And in terms of the supplemental injection criteria, we wanted to make sure that we really protected that BCVA primary endpoint. And so we tightened them up a little bit from what we've been doing in Phase 1, 2. At the same time, we'd refine the patient population so we think at the end of the day it's a wash and we'll probably end up back in that same kind of 80 to 85% range that we've been in and all the other studies. And so we feel really good about the fact that we have, we believe, protected the BCVA primary endpoint, but also we'll have a robust treatment burden reduction.

Okay. Great. And we talked about it a bit earlier, but safety, obviously, a particular focus in wet AMD and other retina studies as well. But I guess just on the prophylactic steroid regimen, it seems like you are controlling inflammation risk fairly well. Just remind us of that regimen. Can you give us a summary? sense of how that's been received in the Phase 3 program? And is there any cushion embedded within that regimen to the point where in the real world, if that's the regimen you're using, if a patient misses a dose, would you have raised concerns of IOI?

Yes, certainly. So the regimen is a 20-week taper of Durezol, so it starts out I think four times per day and then it graduates down a drop a day every month thereafter. So to your point, we think 20 weeks is probably way more than enough. It's designed out of an abundance of caution. But should in the real world patients not be precise in their adherence to that 20-week taper, we think there's room built within that to still provide I think a cushion around safety for sure. And, you know, it's a good question. We, you know, would there be, in the clinical trial setting, some patients that were hesitant and what patients told us loud and clear is taking a topical drop, which many of, which are very used to doing themselves, right, for different, you know, other conditions, was a very small price to pay for the potential benefit of saving, you know, significant amount of potential future needles in the eye and the possibility of preserving vision. So we have picked up on literally zero concern through our Phase 3 program on a patient having any hesitancy because of a topical steroid taper at the beginning of the, you know, being put on 4D-150.

Okay, great. And then we're not asking you to front run your own commercial day five weeks from now, but, you know, assuming success in Phase 3 and commercialization, I guess, can you give us kind of, you know, some initial thoughts on what a launch could look like, what a commercial build out could look like? in terms of a field force? Are there particular areas of the market you might initially focus on?

Yeah, for sure. So I'm glad to go into it now, even if it preempts the conversation on the 21st. It's always good to say it is a few times. My background, by the way, is I've been in retina and the commercial side for nearly 14 years now, and I've done commercial leadership roles in large pharma companies, like Genentech, Roche. I was on Lucentis for a while. I was at Novartis. I launched a drug called Beovu and built the team there from scratch. But I was also at Eyevie, and I built the retina team to commercial. So I've done it in a small company setting and a large company setting. The commercial footprint in both of those scenarios is largely the same. And that's roughly 2,500 to 3,000 injecting ophthalmologists. The vast majority of those are retina specialists in the U.S. Yes. Interestingly, about 1,200 to 1,300 of those, so roughly half, account for north of 85% of all those treatments. So there's a big bolus at the beginning, and there's a long tail. The reason that's important to share for your audience is that that has a direct connection to what type of commercial footprint do you need to scale an audience of that size. And the reality is you probably need 60 to 80 or so field-based employees in both clinical sales and reimbursement support and a total commercial footprint 100 to 120 or so. That I think is a common size regardless of the size whether you're commercializing a large company setting or a small company. So that's very scalable and doable for us. We know the approach there. I've done it a couple of times and we don't need a partner to do that and do it in a way where we are, we can be competitive against much larger companies or established players, even though we're a smaller organization. So we plan and are likely to prepare accordingly to that. Okay.

And you touched on it a little bit earlier, but I guess it's kind of, you know, the economic model of some of these high volume retina specialist practices, I guess, how could a gene therapy fit into a typical or maybe fairly established workflow? What are the considerations for retina specialists as you start talking to them about that?

Yes, very important, I think, as many of your audience members, I'm sure, are aware. You're aware that retina clinics today largely fit within a Medicare buy-and-bill model. So these medicines that they inject today are purchased from a distributor. The clinic then and assumes the responsibility for claiming reimbursement once they inject these patients. And they've, I think, largely built pretty robust practices around that, and they make a gross profit as a part of that treatment paradigm. So I think it's important to understand for 4D-150 is, actually, the answer is somewhat embedded in your question in that we do fit into that pretty seamlessly. We're intravitreal administered, so it's a needle in the eye. It's just the same as Eylea, Vabysmo, and all the other established anti-VEGFs are administered. So we're not a surgical procedure. We think everything about the distribution system is likely to mirror what clinics use today for anti-VEGF therapy. The storage requirements, all those things are pretty consistent. And so from that standpoint, I think we seamlessly integrate into the product acquisition, storage, administration pieces of the process. Then the other side of this is, well, they make money today, and if we reduce treatments by, call it 80%, the knee-jerk reaction is, are you not therefore reducing the economics of a clinic by 80%? And I think what we remind folks is that today the economics of a practice is driven by the price of the medicine, right? get a percentage of that price as reimbursement. So while we it's premature to say what our price will be, clearly it's going to be higher than a single IVT injection of bolus anti-VEGF. So you'll get reimbursement of a higher price point. You'll also get that reimbursement up front. And the other component where economically we think we can make a positive impact for practices is today a lot of patients are lost to follow up, right? We've seen data that as early as 18 months, 40% of patients that started on anti-VEGF therapy have fallen off for a variety of reasons. when that happens, the clinic is not capturing the value of those patients. Right. if we were to price for multi-years worth of value, generally we often think about at least five years, then you would capture the value of that patient or those patients that otherwise would have been lost to follow up. So all that put together, we actually think, to summarize, we fit seamlessly into the current process and we think the economics of a 4D-150 gene therapy could actually be better than what they currently have today, albeit it's calculated a little bit differently.

Okay, great. And maybe just specifically on competition within windings. IMD gene therapy, right? Like, different routes of administration, I guess. You know, how are you thinking about... It seems like there's just a huge TAM available to kind of everybody that might be pursuing a new modality here, but just how you're thinking about learnings from the competitive landscape.

Yeah, for sure. I think, listen, there's a huge market. The unmet need is real. So I think there's room for lots of different players. We think we're uniquely positioned against, I think, anything else in development. I think our positioning versus bolus therapeutics that are in development, be it a TKI or other anti-VEGF type of modalities is clear. We're a continuous backbone therapy. And versus other gene therapies, you know, the Regenex program has shown, I think, very compelling data so far, certainly from an efficacy and safety standpoint. It does require a subretinal surgery to deliver that medicine. And we think that in a commercial setting could have significant barriers to adoption just because that will take time and will be disruptive to a practice flow. And of course, if you don't have to do a surgery to deliver your medicine because you have a safe interventional therapy available, then we think we would be the preferred choice in that situation for sure. therapy program that uh, it's been advanced by Adverum, which was acquired by Lilly. Intravitreal as well expresses Aflibercept like we do, but I think many of your audience would know there's been a history there with safety concerns that we, you know, you alluded to earlier. So how that profile looks through its development program, I think we're going remains a big question of interest for the community.

Okay. Just in the last couple of minutes, I want to make sure we touch on DME. What should we be looking for in terms of, I think we'll get to your SPECTRA data, and then we should start thinking about design of Phase 3. What would you tell us to focus on as DME moves forward?

Sure, so on DME it's an excellent market as Chris can tell you. It's probably two-thirds the size of the wet AMD market and maybe even higher on that need there and those patient populations tend to be less compliant. So Phase 3 design will look a lot like the wet AMD study in terms of primary endpoint BCVA, well-powered. Details shortly on on the study design but again again, run in with five bolus injections, which is typical of DME studies, reloading, five loading doses, and then response to Aflibercept during that phase. So it's going to look a lot like the other, the wet AMD study. We do have approval in Europe, U.S., Europe, and Japan for a single study there, given the robustness of our data. We do have RMAT designation for that in the U.S. RMAT, excuse me, is in Europe and then the data the 2-year data will be essentially similar data to what we've shown before which is basically it's only nine patients at the high dose so it's a which is important in this, so we hope to show ongoing safety of 2 years and injection burden reduction with very strict injection criteria in that, which will be different in Phase 3. So stay tuned there, but, you know, we expect to announce initiation of that study this quarter. Okay.

Great. And then just quickly, I want to make sure we touch on 710 and in CF, status of the program. You know, we're going to get a program update back after this year. What should we be looking for there as well?

Yes, so it'll be a program update in terms of expectations around total patients to be enrolled in different patient populations and dose levels. Again, we're moving into patients who are on modulators as well as patients who have no modulators available. Optimizing the dose, optimizing the endpoints. We'll then have a conversation with FDA. So I think in Q4, we'll simply be updating the program operationally and saying here's what you can expect in '27 in terms of timing and nature of those decisions. data and regulatory updates next year. Okay, great. And just rounding out the questions, cash runway, what's funded, what we've spoken about, for what we consider funding, for what we consider funded. Thank you for giving me a couple of minutes.

We have $431 million in cash, in cash equivalents as of June 30, with cash runway into the second half of 2028. In terms of what the cash runway includes, it does not include commitments that are or do post Forefront 1. That's something that's gated post due date of the Forefront 1 data that we expect in Q2.

Alright, super helpful.

I think we will shut it down there, but thank you for being here. Thank you for listening, guys. It's great to have you. Thank you. This live transcript is auto-generated without human intervention or review.