4D Molecular Therapeutics Inc at Chardan Genetic Medicines Conference Transcript

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

Question: Geulah Livshits - Chardan Capital Markets LLC - Analyst : To begin with, can you give us a high-level overview of 4D Molecular and it's AAV platform, and also talk about your key catalysts for the year? Either of you can jump in on this. Uneek Mehra - 4D Molecular Therapeutics, Inc. - Chief Financial and Business Officer, Principal Accounting Officer, & Assistant Secretary Yes, sure. Good afternoon and thank you for having us. It's an exciting conference. So 4D Molecular Therapeutics. It's an exciting stage in time for the platform. Our mission is to continue to unlock the full potential of genetic medicines for millions of patients across both large and small market diseases. We are harnessing the power of directed evolution to invent and develop novel AAV capsids. And these are basically customized for any therapeutic area that we are looking to solve. We are right now in the clinic with three of these novel vectors, which is A100 in terms of aerosol, which is for pulmonary -- A101 for pulmonary, R100 for ophthalmology, and C102 for cardiology. All three are clinically validated vectors, and they're serving those three therapeutic areas. So it's an exciting time. We have a lot of interesting milestones that are also coming up. So for example, let's go down the list. In terms of our ophthalmology program for wet AMD and DME, we have our Phase 2 readout that will come up early in 2024. In terms of our Phase 2 trial for wet AMD across 50 patients, this is building on the first phase that we have already published for 15 patients across three doses: 3E10, 1E10, and 6E9. We will also be presenting an update in terms of our discussions with the FDA on pivotal-stage trial for wet AMD. That will also happen next quarter, and we will update that early in 2024. Now coming on to DME, we have an update in terms of the first patient got enrolled in our dose-confirmation study, and then we'll be providing an update in 2024. We will also be updating in the next quarter on our program for geographic atrophy, which is again a large market opportunity. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 02, 2023 / 6:30PM, FDMT.OQ - 4D Molecular Therapeutics Inc at Chardan Genetic Medicines Conference In terms of cystic fibrosis in the pulmonary program, we will be providing an update at the North American Cystic Fibrosis Conference, which is in November, in terms of Cohort 2 of patient data, building on the first cohort of three patients that we already shared with. And finally, we will be providing an update on our cardiology program for Fabry disease that's coming up in the next quarter. So a lot of data readouts, exciting stage for the company right now. I'll just summarize to say it's three novel AAVs that are in the clinic, that are clinically validated, and that's what we think sets for the [4D] path right now.

Question: Geulah Livshits - Chardan Capital Markets LLC - Analyst : And can you help us frame expectations for the update that you'll give in November? Uneek Mehra - 4D Molecular Therapeutics, Inc. - Chief Financial and Business Officer, Principal Accounting Officer, & Assistant Secretary Yes, I can do that. It's -- basically, we follow from the last update we gave in November at the North American Cystic Fibrosis, where we presented biopsy data and safety data on Cohort 1. We will be following a similar track where we'll be presenting the same for Cohort 2, which is up three to six patients coming up. So expect to hear about the biopsy and those three patients -- three to six patients as well as the safety data on those. Plus, we will be rounding up the Cohort 1 follow-up because we had shared 9 to 12 months of follow-up for three patients in which two were nine months, one was 12. We'll be rounding that off to give a full picture on the 12-month safety follow up for the Cohort 1. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 02, 2023 / 6:30PM, FDMT.OQ - 4D Molecular Therapeutics Inc at Chardan Genetic Medicines Conference

Question: Geulah Livshits - Chardan Capital Markets LLC - Analyst : Got it. And in terms of the development path in cystic fibrosis, modulators have set some precedent regarding the development path and the approval endpoints. But gene therapy approach might have different considerations. So what are some scenarios for pivotal endpoints for the modulator-ineligible population? And what kind of effect sizes would you be looking for based on what we've seen in the past in this space?

Question: Geulah Livshits - Chardan Capital Markets LLC - Analyst : And as you think about expansion to potentially the modulator-eligible population, how do you envision that development path? And what proportion of that population do you think might be good candidates for gene therapy, even though they're technically eligible from modulators? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 02, 2023 / 6:30PM, FDMT.OQ - 4D Molecular Therapeutics Inc at Chardan Genetic Medicines Conference Uneek Mehra - 4D Molecular Therapeutics, Inc. - Chief Financial and Business Officer, Principal Accounting Officer, & Assistant Secretary I think there's anywhere published work again between 5% to 10% of the modulator eligibles as well who are not responding. So I think when we look at sort of a combination development plan, we believe there could be synergistic effect. Given what Julian just mentioned, if the thinning of the mucus potentially lower dose of our therapy, it could also work. And those are the development paths that we are evaluating with modulators.

Question: Geulah Livshits - Chardan Capital Markets LLC - Analyst : Got it. Maybe let's move over to the ocular portfolio. You talked a little bit about how you're planning to put out data in 2024 for your wet AMD and diabetic macular edema programs. Can you expand a little bit on the elements of the clinical profile thus far that give you confidence in the Phase 2 readout for wet AMD and also more generally read across to the DME program?

Question: Geulah Livshits - Chardan Capital Markets LLC - Analyst : So for an indication like this where there are some available therapies, safety obviously becomes an important component there. Can you remind us of what steroid regimen you're using and talk about how that plays into the profile that you're seeing? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 02, 2023 / 6:30PM, FDMT.OQ - 4D Molecular Therapeutics Inc at Chardan Genetic Medicines Conference Uneek Mehra - 4D Molecular Therapeutics, Inc. - Chief Financial and Business Officer, Principal Accounting Officer, & Assistant Secretary We're currently using a 20-week topical taper, the steroid we're using, durezol, here. And I think it has served us well, both in the Phase 1 and what we have seen and we've announced in July until that point in the Phase 2 as well with the 50 patients. So we feel pretty happy with that. We will likely be optimizing the steroids, not from any other sort of a treatment perspective, but because durezol is not available in Europe. So we have to figure out how do we translate that in Europe. But right now, we feel pretty good with the regimen that we have.

Question: Geulah Livshits - Chardan Capital Markets LLC - Analyst : Got it. And you did recently add a population extension cohort. Can you explain a little bit about the rationale there and discuss how your trial populations in Phase 1 and 2 compare with the overall wet AMD population in terms of the disease severity and treatment burden?

Question: Geulah Livshits - Chardan Capital Markets LLC - Analyst : Okay. When we think about these variables that affect commercialization and Phase 3 design, as we've talked about already, this is a space where there are several treatments on the market and additional regimens that are emerging that could potentially extend the intervals between dosing. So that, in some ways, translates to evolving unmet need. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 02, 2023 / 6:30PM, FDMT.OQ - 4D Molecular Therapeutics Inc at Chardan Genetic Medicines Conference So can you talk a little bit about how your conversations with clinicians and others in this space, how you're thinking about that evolving unmet need? And what does that emergence of newer regimens mean for issues like Phase 3 design, like a control arm and things like that?

Question: Geulah Livshits - Chardan Capital Markets LLC - Analyst : Got it. Maybe sticking with the ocular theme but moving on to geographic atrophy, you mentioned that you're also advancing a program there. There are a few different early stage programs that are looking at different complement pathway genes that are being explored in this indication. So what gives you confidence in this specific approach that you guys are advancing with your individual capsid? Uneek Mehra - 4D Molecular Therapeutics, Inc. - Chief Financial and Business Officer, Principal Accounting Officer, & Assistant Secretary Yes. So first and foremost, I think our 4D-175, again, consistent with all the other capsids, a novel capsid we feel pretty comfortable about. We also made publicly the announcement that we in-licensed the factor format -- the complement factor format with the short-form version of that. And we believe that since it probably manifests itself in about 75% of the patients in GA that that's an ideal target for us combined with our capsid. So more details to come as we announce that program, but we feel that this combination of the capsid and the gene construct could be really helpful. It is a significantly large patient population, as you know, and that would be our third large disease as we move just in the [optic] space.

Question: Geulah Livshits - Chardan Capital Markets LLC - Analyst : And those are things that you might update on when you provide your update on the program later this year? Great. So jumping back to your cystic fibrosis program since we do have a minute, I did want to ask, there are several other modalities that are now in the clinic or in development for modulator-ineligible cystic fibrosis or mRNA approaches or other viral vectors. And then there's some early pre-clinical work on the genome-editing front. So as we think about these different flavors of genetic medicines, approaches, what do you see as the major advantage of your program and strategy here? Uneek Mehra - 4D Molecular Therapeutics, Inc. - Chief Financial and Business Officer, Principal Accounting Officer, & Assistant Secretary I think, fundamentally, it boils down to delivery, right? I think we believe we have, with the gene expression that we are seeing now in the Cohort 1, 92% to 99%. I mean, that delivery -- yes, there are other modalities in gene editing, but at the end of the day, they still have to deliver and get through the lung. We have seen our particular -- not only the gene expression, but then you measure it across all types of cells in the lung. Whether it's the secretory cells, the basal cells, the ciliated cells, we are seeing consistent reproducible expression there, and that gives us conviction that this modality will be quite differentiated.

Question: Geulah Livshits - Chardan Capital Markets LLC - Analyst : Yes, I think we're starting to see it being built here. Julian, anything to add on that front?

Question: Geulah Livshits - Chardan Capital Markets LLC - Analyst : Fantastic. Any questions from the audience? Otherwise, I think that will bring us to the end of our session. So I'd like to thank you both for your participation and for the fantastic discussion. Uneek Mehra - 4D Molecular Therapeutics, Inc. - Chief Financial and Business Officer, Principal Accounting Officer, & Assistant Secretary Thank you so much.