4D Molecular Therapeutics Inc To Discuss Interim Data Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Jonathan Miller - Evercore Inc - Analyst : Hi guys, thanks for taking my question and congrats on all the data. I guess just high level for me, the patient level data that you gave today does highlight how variable both patient journey and monitoring can be even for outcomes like LCI, which is clearly a more sensitive measure. So could you talk a little bit about the Phase II strategy, what we should be expecting in terms of the homogeneity of patients there and what we should be expecting about the number of patients needed to get reliable measures for LCI and FEV1 in the Phase II? And then just secondly, why is expression decrease over time not proportional with dose? It seems like the 2.5E14 dose is somehow more durable than 5E14, at least based on the one slide that you showed. Just curious about that, too.

Question: Ryan McElroy - Leerink Partners LLC - Analyst : Hey guys, you have Ryan on for Mani. Congrats on the update. Maybe just between the expression and the clinical data, we obviously saw some wide error bars. Can you just talk about any correlation you're seeing at this Phase II dose between those 2? And then maybe just one on the regulatory front. LSEG STREETEVENTS | www.lseg.com | Contact Us consent of LSEG. 'LSEG' and the LSEG logo are registered trademarks of LSEG and its affiliated companies. DECEMBER 17, 2025 / 1:00PM, FDMT.OQ - 4D Molecular Therapeutics Inc To Discuss Interim Data Can you just talk about any of your initial conversations that you've had with the FDA and where they stand on this FEV1 versus LCI debate as an endpoint moving forward? And do we plan to get more clarity on that in the second half of next year? Thanks for taking our question.

Question: Gena Wang - Barclays Services Corp - Analyst : So I think, David, we had a debate in the past regarding this approach. So when I look at the data, I know you're using ORKAMBI, we are discussing about the AOCI as a potential approvable endpoint. But the bottom line is FEV1, we already follow this 12 months to 15 months. If we see like such a modest FEV1 benefit, and we have to try to understand better of the AOCI, which ORKAMBI actually is a fair comparison. It's such a modest clinical benefit. I can foresee this will phase out very quickly. We have a much better drug already coming to the picture. So here, my question is, is that really the -- do you think that this is really viable moving forward? And then also, I know you do have a very good funding from others so that you do not spend too much money from your own in terms of investment moving this forward. So maybe like just give us a sense how much that will cost going to the next stage.

Question: Gena Wang - Barclays Services Corp - Analyst : I have a quick follow-up regarding -- I think you said enrollment criteria, 40 to less than 100 for FEV1. Wouldn't that be too wide a range that cover two different -- too many different types of a patient population. We do know Alyftrek did not show superiority on FEV1 versus the -- sorry, I'm blanking out the previous triple combo -- but it did show -- yes, that's right. So like because one part of the reason is FEV1, you basically -- you could reach the peak depends on what kind of baseline you enroll. So that could be a very important data point to think about it. And then the other important data point that everyone is checking is the sweat chloride. Have you thought about that as well? Jennifer Taylor-Cousar So to answer your second question first, so sweat chloride is impacted by systemically administered therapy, so I would not expect to be actually affected by an inhaled therapy. So we won't measure sweat chloride for this administration because we're just administering to the lungs. It's not getting into the other tissues as we've shown previously from the nonhuman primate models. In terms of your first question, we're using the standard range of FEV1 that we use in most of our trials in cystic fibrosis. So yes, there is a range, but we want this drug to work for people in that range. Over 100, it's very hard to show a difference in FEV1. But in that range of 40 to less than 100, we have been able to show it with multiple different therapies, even if you go back to the days of Pulmozyme, for example, or the inhaled antibiotics. So we think that's a reasonable range to also have enough participants to enroll the study.

Question: Tommie Reerink - Goldman Sachs Group Inc - Analyst : Thanks so much for taking our question. This is Tommie on for Salveen and congrats on the progress. We were wondering if you could just give us a bit more color on your redosing strategy and how that factors into your future development? And if there's anything that you can update us on a potential accelerated path here?

Question: Daniel Giraldo - Bofa Merrill Lynch Asset Holdings Inc - Analyst : Hey guys, good morning. Thank you for taking our question and congrats on the update. I was just wondering if you could speak a little more on the LCI as an endpoint for adults. And maybe you talked about how it's been used for pediatric patients and maybe milder disease, but how well do you think it is measuring clinical benefit in more advanced or severe patients? LSEG STREETEVENTS | www.lseg.com | Contact Us consent of LSEG. 'LSEG' and the LSEG logo are registered trademarks of LSEG and its affiliated companies. DECEMBER 17, 2025 / 1:00PM, FDMT.OQ - 4D Molecular Therapeutics Inc To Discuss Interim Data And how are you going to take that into account for the enrollment criteria for the next patients? Is there going to be sort of range you're looking to enroll in terms of the LCI for that next cohort? And maybe more long term, how are you thinking about developing this program fully? Or is this something you would consider partnering after you acquire more data next year?