4D Molecular Therapeutics, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Everyone I've got to go.

Perfect. First of all, thank you, Josh, for having us. Really appreciate it. 4D, in terms of pipeline, we have our lead program, 4D-150, is in phase III for wet AMD. Our two phase III trials have fully enrolled. We're guiding to the first phase III trial to read out in Q2 of next year, and the second phase III trial to read out in the second half of next year. We will announce, towards the end of the month, the initiation of a phase III trial in DME, the next indication for 4D-150. We have a long program in 4D-710, where we'll provide an operational update towards the end of the year. That's a program in CF. From a cash perspective, we've got around $458 million in cash as of 6/30 this year, with cash runway into the second half of 2028.

I can start with that. I think the first, maybe overstating the obvious, that I would point to is 4D-150 in our program scientifically couldn't be more different than I think the programs you referenced. We're gene therapy that expresses aflibercept. I think a key takeaway, again, stating the obvious most likely is that EYLEA is a really good drug. It performs well. The efficacy has been proven. It's been standard of care for well over a decade now, and I think the bar for success when you have a comparator of EYLEA is pretty high. We feel good about our chances. In essence, we express aflibercept, so that is EYLEA.

It's the reason why we chose that as a protein to express with 4D-150, and we believe the data we've shown so far has shown strong progress, certainly as it relates to treatment burden reduction versus on-label EYLEA and the ability to preserve vision long term. That may not be a total surprise, but I think it's becoming evident as you see the data come through from some of these other programs, that the bar for efficacy and safety is high and as it should be.

Yeah. Great question. Our phase III program is 4FRONT-1 and 4FRONT-2, right? 4FRONT-1 is the first trial that is North America, so U.S. primarily with some sites in Canada as well. Before I get to, I think, the core of your question, maybe take a little bit of a step back and just remind the audience a little bit around just the history of this space and what's driven the evolution of this space. As many of you likely know, treating wet AMD has been done through bolus needles in the eye or intravitreal injections. Years ago, that started with LUCENTIS being a 4-week drug, at least per label, and then EYLEA comes out and says it's an 8-week drug, and it extends that durability a little bit further. What we've seen since then is largely an attempt to increase that durability in increments.

You saw VABYSMO, which we think extended durability maybe by a couple of weeks, reduced maybe an average of an injection per year, and similar with EYLEA HD. What we endeavor to do is to not extend that durability or reduce that treatment burden by an increment of 15%, 20% is to do more of a paradigm change through a modality like an always-on continuous backbone therapy like 4D-150. As you referenced, Josh, what we've shown in our PRISM data, at least in wet AMD so far, is we've shown across a broad range of patients, so patients that historically were getting over 10 injections per year, so a pretty severe largely patient population, to patients that were more recently diagnosed, that we've shown treatment burden reduction rates in that 80-plus or so percent range.

A little bit of variability in that depending on the patient population, but generally, that's what we've demonstrated with the ability to preserve vision in concert with that significant reduction in treatment burden. We certainly believe that if we show that in our phase III program, we have a huge opportunity to change the treatment paradigm, and we think that translates to commercial success.

To your question about how we've adapted the Phase III program, we looked at some of the results from the Phase II program. What we saw is that as patients were more recently diagnosed, so patients diagnosed in the last 6 months, that treatment burden effect that I referenced was more pronounced with those patients. Patients that were on therapy 4 or 5 years, we showed up to 2 years of treatment burden reduction rate in the mid-70s or so range. When you look at patients that were diagnosed within the prior 6 months, and then they went on 4D-150, we've now shown data up to 2 years in that patient population, and you see treatment burden reduction rates as measured by what you would have gotten on on-label EYLEA, full disclosure, in the mid-80s range. So a more pronounced effect.

When we went into our Phase III program, we said, "How do we enhance for a patient population that's likely to have a higher level of response?" We think in a more recently or newly diagnosed patient population is likely to do that for us. Our 4FRONT-1 trial is entirely treatment-naive. 4FRONT-2 has a blend of treatment-naive in some patients that were previously treated, and that satisfies a European regulatory requirement. That's an important change. Important, though, to recognize all of the Phase III pivotal programs for retinal disease, A and B, primarily, you look at any of the approved medicines, they've all been studied in a naive patient population. We're not breaking precedent with our design.