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

Hello, ladies and gentlemen. Thank you for standing by, and welcome to 4D Molecular Therapeutics 4D-150 Phase I/II for Wet AMD Interim Clinical Data Conference Call. [Operator Instructions] As a reminder, today's call is being recorded. With that, I will hand the call over to August Moretti, Chief Financial Officer, who will make introductory comments.

Thank you, operator, and welcome, everyone, to 4D Molecular Therapeutics' 4D-150 Phase I/II for Wet AMD Interim Clinical Data Conference Call. A press release describing the interim results from our Phase I/II clinical trial of 4D-150 in patients with wet AMD is accessible in the Investors section of the 4D Molecular Therapeutics website. And a recording of this webcast will be accessible on our website after completion of the call. With me today are Dr. David Kirn, our Co-Founder and Chief Executive Officer; and Dr. Arshad Khanani, Managing Partner and Director of Clinical Research at Sierra Eye Associates and Clinical Associate Professor at University of Nevada, Reno. Dr. Khanani is a principal investigator on the 4D-150 Phase I/II clinical trial. As a reminder, on this call, we will be making forward-looking statements regarding our clinical data from our 4D-150 Phase I/II clinical trial, product development plans and research activities. These statements are subject to risks and uncertainties that may cause actual results to materially differ from those forecasted. A description of these risks can be found in the Risk Factors sections of our most recent Form 10-K and Form 10-Q, which are on file with the SEC. We will reference a slide presentation during the call today. Shortly after the call, we will post the presentation to the Investors section of our website. With that, I'd like to turn the call over to Dr. David Kirn. David?

Thanks, Augie. Today, we're reporting interim clinical data from the ongoing 4D-150 Phase I/II clinical trial in patients with wet AMD. 4D-150 is our genetic medicine designed for the intravitreal treatment of wet AMD. These are also the data from the third clinical trial using our proprietary intravitreal-delivered R100 vector invented at 4DMT through Therapeutic Vector Evolution. Prior to giving some background on the program and the clinical data details, I'd like to first run through the key takeaways for today. The PRISM clinical trial targets wet AMD patients requiring frequent anti-VEGF injections. Last week, we announced that the Phase I dose exploration stage of this Phase I/II trial has been fully enrolled, with all 3 dose levels now cleared for safety. 15 patients have been enrolled to date in 3 dose cohorts of 5 patients each. We will discuss results from Cohort 1 patients today. The mean annualized anti-VEGF injection rate prior to 4D-150 treatment was approximately 11 in this cohort, indicating that these are high-need patients requiring frequent injections. These 5 patients received a single intravitreal dose of 4D-150 of 3E10 vg per eye, a far lower dose than is used in other gene therapy programs for wet AMD. The clinical data takeaways for Cohort 1 are as follows. Data to date demonstrated that 4D-150 at this dose was safe and well tolerated with no SAEs or DLTs. No 4D-150 related clinically significant adverse events were reported with no clinically significant intraocular inflammation, no endophthalmitis, no retinal vasculitis, no retinal artery occlusion, no choroidal effusions and no hypotony were reported. In all 3 patients for whom we have available aqueous humor aflibercept levels, aflibercept concentrations were detected that were in a therapeutically active range. Clinically meaningful anti-VEGF activity has been demonstrated to date in these high-need patients with wet AMD. Intravitreal 4D-150 was associated with a significant reduction in anti-VEGF injection rate. Following intravitreal 4D-150, the annualized anti-VEGF injection rate was reduced by 96.7%. 80% of patients have remained anti-VEGF injection free, meaning they have not required any supplemental aflibercept injections to date. Next steps in this clinical trial include initiation of the Phase II dose expansion portion of the trial, in which we will randomize 50 wet AMD patients to 1 of 2 dose levels of 4D-150 versus aflibercept. While the advent of anti-VEGF therapy has been a milestone in the management of wet AMD and DME, the need for frequent injections creates compliance challenges and suboptimal injection frequency, leading to poor real-world visual acuity outcomes, particularly in those patients with the heaviest treatment needs. Reducing the need for frequent injections is therefore a major unmet medical need, and 4D-150 was developed to address this unmet need. 4D-150 is a novel synthetic AAV-derived vector that is customized for efficient delivery to the retina by a single routine intravitreal injection. Rather than relying on a nonspecific naturally occurring AAV vector, we applied a Nobel prize-winning technology called directed evolution to invent our customized AAV capsid R100 through directed evolution in primates. We refer to our vector invention platform as Therapeutic Vector Evolution. We start our design process for every disease target on the whiteboard where we design the optimal target vector profile for that disease or set of diseases. Our target vector profile for this sector included intravitreal injection and subsequent penetration through the internal limiting membrane to reach and transduce cells within the retina. Next, we use our massive synthetic AAV-derived capsid library as a starting material for our competitive selection process. We have approximately 1 billion different synthetic capsid vector sequences in our library. We then perform sequential in vivo selection rounds in nonhuman primates following intravitreal delivery to isolate the vector that best matched our target vector profile, which we designated R100. Our genetic medicine 4D-150 is comprised of the R100 capsid and a dual payload cassette. To our knowledge, this is the first genetic medicine to deliver 2 different transgene payloads. These payloads express both aflibercept and the VEGF-C RNAi. This dual transgene payload therefore inhibits 4 angiogenic factors that drive the disease: VEGF-A, B, C and placental growth factor. While major biologics for the eye are dosed by routine intravitreal injection, conventional wild-type AAV vector gene therapy has not been feasible with intravitreal injection. The figure on the top left illustrates the limitations of conventional AAV following intravitreal injection. When delivered by this route, the internal limiting membrane and other components on the surface of the retina act as a barrier to penetration, and vector does not efficiently reach nor transduce retinal cells. On the right is an in-life image from a primate retina 26 weeks following intravitreal injection of R100, expressing the reporter gene GFP. Transgene protein expression, shown in light blue, is diffused and highly intense across all regions of the retina, including the macula. Our intravitreal genetic medicine 4D-150 is highly differentiated from other therapeutic approaches in wet AMD including gene therapy product candidates that utilize wild-type conventional AAV or mouse-evolved AAV vectors. Both 4D-150 and traditional gene therapy approaches have the design advantage of long-term expression and efficacy after a single dose in marked contrast to repeated dosing required with standard agents such as aflibercept. In contrast, however, 4D-150 is the only product candidate to utilize both intravitreal delivery and a dual transgene payload that enables the inhibition of all 4 known VEGF family molecules driving the disease. In contrast to ADVM-022 specifically, 4D-150 has 4 points of differentiation to date. 4D-150 utilizes an intravitreal vector that was invented through directed evolution in primates. 4D-150 inhibits all 4 molecular drivers of wet AMD and DME. 4D-150 has not been associated with hypotony to date, and it has not been associated with chronic intraocular inflammation to date. 4D-150 has a unique biodistribution profile, with the highest aflibercept concentrations being detected within the retina and choroid. This is in marked contrast to ADVM-022. With the intravitreal administration of a biologic like aflibercept, the highest concentrations are observed in the vitreous with lower concentrations in the aqueous humor and the retina and choroid, as illustrated in the figure on the left. In the center panel, we've plotted published preclinical data on aflibercept concentration in primate eye tissues after intravitreal injection of ADVM-022. The tissue distribution profile shows that vitreous and retina/choroid concentrations are roughly equivalent. On the right, we see data from our preclinical study of 4D-150 administered by intravitreal injection in nonhuman primates. In marked contrast to ADVM-022, aflibercept concentrations are highest in the retina and the choroid, followed by the vitreous and lowest in the aqueous humor, as would be expected based on aflibercept expression primarily from the retina and the choroid. 4D-150 therefore is highly efficient at driving aflibercept expression within the retina and choroid precisely in the tissues that are critical to clinical efficacy. We carried out a preclinical efficacy study with 4D-150 in a primate model of wet AMD. In the retinal laser-induced CNV model, we treated animals with intravitreal 4D-150 at doses of 1E11, 3E11 and 1E12 vgs per eye with 7 animals per group. The primary end point in this model was the percentage of laser spot that became severe Grade IV CNV lesions. 4D-150 resulted in complete suppression of 100% of all CNV lesions at all 3 doses tested for all groups and at both time points. In terms of safety, no adverse findings were reported through 6 months of follow-up. The lowest dose evaluated, which was 1E11 vg per eye, was efficacious and equivalent to the high dose, so lower doses are likely to be efficacious and should be explored in clinical trials, as you'll see in a moment. These results demonstrated the potential safety and efficacy of intravitreal 4D-150 in wet AMD and DME at relatively low doses. Now I'd like to turn the presentation over to Dr. Khanani. Arshad?

Thank you, David. Here is the design of the Phase I/II PRISM clinical trial of intravitreal dual transgene gene therapy with 4D-150 for patients with wet AMD. The objectives of the trial are to evaluate the safety, tolerability and efficacy of 4D-150 in patients with wet AMD requiring frequent anti-VEGF injections. This trial has 2 phases. The first is the open-label dose exploration phase which involved a standard 3+3 design with optional addition of 2 more patients for a potential total of 5 patients per cohort. The second stage is the dose expansion phase in which 50 patients are randomized to 1 of the 2 doses of 4D-150 or aflibercept in a 2:2:1 ratio. Key eligibility criteria are listed here. As a reminder, these are previously treated patients requiring at least 6 prior anti-VEGF injections within the last 12 months in the study eye and documented response to anti-VEGF therapy during the 12-month period. The primary end point is safety and tolerability of 4D-150. Key secondary end points include the need for supplemental aflibercept injection and aqueous humor aflibercept concentration. Topical steroid prophylaxis was initiated 3 days prior to receiving 4D-150 on day 1 and tapered over 20 weeks. These patients received no oral or intravitreal or subtenon steroids. After the first month, patients were followed every 4 weeks, and the need for supplemental aflibercept was assessed at each visit using prespecified best-corrected visual acuity and optical coherence tomography criteria. Enrollment is now complete in the dose exploration phase, and all 3 dose levels were cleared for safety without dose-limiting toxicity by an independent data safety monitoring committee. 15 patients were enrolled in 3 cohorts of 5 patients each in this stage. Cohort 1 received the highest dose of 3E10 and is the group for which we have the longest follow-up and whose interim results we will share with you today. Of note, based on the high degree of clinical activity and therapeutic aflibercept concentrations in Cohort 1 patients, we elected to explore whether lower doses of 1E10 and 6E9 could achieve similar results. Here, you can see the baseline characteristic and follow-up for patients in Cohort 1. Of note, these are high-need patients with wet AMD requiring frequent anti-VEGF injections. These patients required a mean of approximately 11 injections in the preceding 12 months. Patients have now been powered post treatment for up to 10 months. Data to date demonstrated that 4D-150 at this dose was safe and well tolerated. No DLTs or SAEs were reported. No clinically significant adverse events were reported with no clinically significant intraocular inflammation, no endophthalmitis, no retinal vasculitis, no retinal artery occlusion, no choroidal effusions and no hypotony reported. AAV gene therapies for wet AMD have been associated with intraocular inflammation and pigment changes in multiple programs. The field has seen long-standing clinically significant intraocular inflammation especially with intravitreal delivery. Recently, intraocular inflammation has also been reported with supracolloidal delivery. The field has also seen subretinal pigmentary changes with subretinal delivery. As a reminder, transduction and transgene expression with intravitreal 4D-150 are targeted to the retina and not the front of the eye. In addition, the dose in this Cohort 1 with 4D-150 was relatively low. Other AAV candidates for wet AMD have used doses that were 7- to 30-fold higher. We therefore hypothesized that 4D-150 might be associated with less intraocular inflammation versus other AAV candidates. Hence, as stated, only topical steroid prophylaxis was used in the PRISM trial. In this trial, patients' eyes were examined at week 2 and 4 and then every 4 weeks thereafter. Investigators assess patients' eyes for inflammatory cells, flare and haze in the aqueous and vitreous chambers. 39 interior chamber exams are represented in this table. As shown, interior chamber exam results were almost uniformly normal. A single patient had isolated 2-plus pigmented cells at a single time point. Of note, this patient did not maintain the protocol defined to find position following intravitreal injection. The pigmented cell finding resolved by the next time point during continued topical corticosteroid treatment. No flare was reported at any time point. No nonpigmented cells were detected at any time point. 39 vitreous chamber exams are represented in this table. As shown, vitreous exam results were almost uniformly normal. A single patient had [ trace mix ] cells at a single time point. This finding resolved by the next time point. No haze was reported at any time point. No nonpigmented cells were detected at any other time point. Aflibercept concentrations were assessed in the aqueous humor at 12 weeks following intravitreal 4D-150. As a reminder, based on the primate data with 4D-150, retina/choroid tissue concentrations are predicted to be higher than aqueous humor concentrations. 3 patient samples have been evaluated to date. All 3 patients had levels of aflibercept that were in the expected therapeutic range. Aflibercept data from all 15 patients in the 3 dose exploration cohorts will be reported at a future medical meeting. To date, in Cohort 1, intravitreal 4D-150 was associated with a significant reduction in anti-VEGF injection frequency. Cohort 1 patients had a reduction in annualized rate of anti-VEGF treatment of 96.7%. On the left is the anti-VEGF history for each patient during the 12 months prior to trial in gene pool Cohort 1. Circles represent anti-VEGF treatment. Different colors represent specific anti-VEGF treatment agents. As you can see, these patients were heavy users of anti-VEGF treatment with a mean annualized injection rate of approximately 11. On the right are the study visits, represented as circles. Following treatment with a single injection of 4D-150, patients were evaluated for the need for supplemental aflibercept injection at visits every 4 weeks based on strict prespecified BCVA and OCT criteria. Aflibercept treatment was indicated if any of the following criteria were met: loss of 10 or more letters from baseline BCVA attributed to intraretinal or subretinal fluid, increase from baseline in central subcu thickness of 75 or greater microns confirmed by a reading center or a new vision-threatening hemorrhage. The white circles on the right indicate visits, and this supplemental aflibercept injection was not required and therefore not given. We can see here that to date, only 1 patient met the prespecified criteria at one time point and received a supplemental aflibercept injection. So to reiterate, to date, Cohort 1 patients had a reduction in annualized rates of anti-VEGF treatment of 96.7%. 4 out of 5 or 80% of patients were supplemental aflibercept injection free. Injection free follow-up to date has been 40, 36, 32 and 16 weeks. Now I would like to hand the presentation back over to Dr. Kirn. David?

Thank you, Dr. Khanani. Today, we've shared data from our wet AMD product candidate 4D-150 to review 4D-150 as a highly differentiated intravitreal and dual transgene genetic medicine comprising of primate-evolved AAV derived vector invented at 4DMT through our Therapeutic Vector Evolution platform. In a single product, 4D-150 inhibits all 4 VEGF family molecules that drive wet AMD and DME. 4D-150 is the only genetic medicine in clinical development for wet AMD with either a dual transgene payload or a primate-evolved low-dose intravitreal vector. In summary, the PRISM clinical trial targets wet AMD patients requiring frequent anti-VEGF injections. We've announced that the Phase I dose exploration stage of this trial has been fully enrolled, with all 3 dose levels now cleared for safety by the independent DSMV (sic) [ DSMC ]. 15 patients have been enrolled to date in 3 dose cohorts of 5 patients each. The clinical data takeaways for Cohort 1 are as follows. Cohort 1 patients received an intravitreal 4D-150 dose of 3E10 vg per eye, a substantially lower dose and has been advanced in other gene therapy programs for wet AMD. Prior AAV gene therapy products have utilized doses that were approximately 7- to 30-fold higher than this Cohort 1 dose level. A simple and well-tolerated topical-only corticosteroid regimen was used in this trial. To date, 4D-150 was safe and well tolerated. No clinically significant adverse events were reported, and no clinically significant intraocular inflammation or any hypotony were reported. In the 3 patients for whom we have available aqueous humor data, aflibercept concentrations were in the expected therapeutic range. Clinically meaningful anti-VEGF activity has been demonstrated to date in these high-need patients with wet AMD. To reiterate, prior to 4D-150 treatment, patients had a mean annualized anti-VEGF treatment rate of approximately 11. Following intravitreal 4D-150, the annualized anti-VEGF injection rate was reduced by 96.7%. 80% of patients have not required supplemental aflibercept injections to date. So what are the implications of these findings? These clinical results, should they be confirmed with additional patients and more follow-up, validate the tolerability and clinical activity of the 4D-150 product. These clinical data also support the validation of the R100 vector for intravitreal delivery, an expression of other transgenes for large market ophthalmologic diseases. Finally, these clinical data further validate our Therapeutic Vector Evolution platform. Of note, the intravitreal vector R100 represents 1 of 3 therapeutic area vectors that we have invented and taken into clinical trials. All 3 vectors have demonstrated initial safety, tolerability, delivery, transgene expression and clinical activity. Regarding next steps, we expect to release additional clinical data from all 3 dose cohorts on this trial in Q2 of 2023. We also plan to initiate the Phase II dose expansion portion of the trial in Q1 of 2023. In this phase, we plan to randomize 50 wet AMD patients to 1 of 2 dose levels of 4D-150 versus aflibercept. Based on data to date, we expect these dose levels to be in the range of 3E10 to 1E10 vgs per eye. Finally, we are actively developing additional preclinical pipeline product candidates for other large market diseases leveraging our R100 intravitreal vector in a modular fashion. And so with that, thank you for your attention. And thank you to the investigators, the clinical trial staff and to the patients on our clinical trial. We now welcome your questions. Operator?

[Operator Instructions] Your first question comes from the line of Salveen Richter with Goldman Sachs.

Congratulations on the data. Just a couple of questions here. One is, what gives you confidence that the results will be durable over time? And help us understand how long it would take to be cleared or to pass the hurdle on safety in terms of your work here. And then secondly, how do you expect these results to translate in terms of BCVA and CST? And will these measures be presented at next data updates?

Well, Salveen, and thanks for the question. So in terms of durability, one of the exciting things about gene therapy in the eye is that expression from the retina has been very, very durable with other programs. So we know that Luxturna, we've seen efficacy out to a decade or more in that program. We've seen other wet AMD programs report stable aflibercept concentrations in the eye over time. And certainly, in primates, we've gone out well over a year and seen stable anti-VEGF expression. So we do think that the eye is a particularly stable tissue. The retina in that expression will be durable. Certainly, it's something we'll continue to follow over time. In terms of safety, we're very pleased by the safety profile to date and lack of clinically significant inflammation. Certainly, we wouldn't be comfortable releasing these data until we had a number of patients out in that sort of 6- to 10-month time frame because we want to make sure that we don't see any safety concerns in that time frame, which we haven't. We'll certainly continue to follow up patients long term, but one would think that within this time frame, if there were any significant safety concerns, they would have risen. And I think you might have had a third question?

With regard to translation to BCVA and CST and when we may get the update.

Sure. Yes. So we expect to give a full update of the entire study, all 3 cohorts in dose exploration in Q2 of next year. So we look forward to sharing that data. At that point, patients will have anywhere from 7 to 15 months of follow-up, so it should be a robust data set. And we can also at that time look at the dose response relationship. Certainly, these data to date show that BCVA and OCT were maintained. There's no significant worsening. That's why we only had one supplemental aflibercept injection. But in that data set, we'll also report on whether we can show improvement from baseline on other anti-VEGF therapies.

Your next question is from the line of Nalin Tejavibulya with Jefferies.

Congratulations on the results. I have 2 quick questions, please. So with the safety profile seen, can you talk us through your decision to lower the dose as opposed to pushing forward to a higher dose to potentially achieve greater durability? And the second question is what -- can you talk us through your confidence level in not seeing adverse events in DME as competitors have seen?

Thank you for the question, Nalin. I really appreciate it. In terms of the rationale to drop dose, the way we've approached this, which has been consistent with FDA guidance, is that we start our trials in the dose exploration phase at doses that we think will be therapeutically active based on our data in primates. And so that was the case here. Based on our modeling in primate eye in terms of aflibercept concentrations and efficacy in the laser-induced retinal model, we thought this would be a highly active dose. Now in terms of -- and I think that's obviously been confirmed in this Cohort 1 of patients. We certainly could go up, and that's something we could explore in the future, but we also feel that anything we can do to get the dose down in these patients, given that this is a large market disease, high incident rate, if we're successful, we're going to be treating a large number of patients. Anything we could do to get the dose down and maximize safety, we wanted to explore. So that was really the rationale. We felt that the clinical activity was very promising in terms of over 95% reduction in annualized anti-VEGF injections and also that the aflibercept concentrations were actually above where we had predicted they might be based on primates. So given the totality of the data, we elected to take advantage of the study design which allowed for reduce doses to explore whether we could maintain that efficacy at even lower doses. And I think your second question was relating to DME. So that's a population where other programs have shown some inflammation and hypotony. Importantly, those were at doses that are 20-fold higher than we're at today. And we certainly hope we can see clinical activity at even lower doses from where we are today. So I think given that therapeutic index, that large window of 20-fold or more and the lack of any significant safety concerns or inflammation or hypotony, we're confident that we can move into the DME population. And we're having conversations with FDA around DME. And as soon as we have clarity on the timing of that program, we'll share that publicly.

Your next question is from the line of Mani Foroohar with SVB Securities.

Congrats on the data. You mentioned the patients are receiving topical-only corticosteroid therapy. How should we think about more structural metrics from a product profile perspective, timing that patients could roll off topical steroid therapy? I'm just looking down the road towards what you might -- how you might structure a pivotal trial, how you might eventually aim for what a label might look like so that physicians can gain the benefit of single administration here rather than 2-, 4-week follow-ups and, I don't know, that doesn't make a lot of sense. So where is your avenue? And how do you think about that in terms of your pivotal study design?

Well, thanks, Mani, for the question. We're pleased with the safety profile that we've seen with this all topical regimen over the course -- tapering over the course of about 4 months. We'll continue to reevaluate that over time and see whether we could shorten that in some patients. Right now, we're pleased to have just a consistent 40-week -- excuse me, a 4-month tapered steroid regimen, it's all topical. And that's something we'll certainly discuss with the FDA and with other investigators prior to Phase III. Dr. Khanani, would you like to comment on the use of the all topical regimen and how we might evolve that over time?

Yes, absolutely, David. So I think the main thing is that topical is the least invasive, where we're not sticking the needle inside or around the eye. And in terms of the steroids, it also probably has the best safety profile in terms of intraocular pressure increase in cataract formation. So the goal is to see if we can just do a topical prophylaxis. And then once the programs go forward, there's always could be consideration of other modalities of prophylaxis. And once the treatment hits the market, then I think physicians make decisions based on what patients can do and cannot do, so other modalities can be implemented. But I think if we are not seeing inflammation with topical steroid that gives us confidence that this is very, very safe at this point. And then, of course, this idea that David said, which is very meaningful in gene therapy, is to make sure that we are in the right dose range. We don't want to be on the top of the dose range where we can see DLTs and other things there. We have a very, very low dose, and we have not seen any inflammation. And the vector is designed to transduce the retina instead of the front of the eye. So all those things combined, I think, we thought the topical would be enough, and that's what seems to be the case.

That makes sense, Dr. Khanani. And as we go to lower doses, would you contemplate a steroid-free approach? Or do you think sticking with the topical approach is the right answer? Or is there not a path towards steroid-free regimen?

Well, maybe I'll start. This is Dave, and then I'll turn it over to Dr. Khanani. But I think it's certainly something we would consider exploring in the future. Right now, we'd like to keep that simple steroid regimen consistent, and so we can compare between dose levels. But I think once we settle on a dose level, that's certainly something we could consider. Dr. Khanani?

Yes. I think as a class, we have seen inflammation with gene therapy. And I think it's good to be -- to have prophylaxis. You recently heard about suprachoroidal programs with that inflammation, with the prophylaxis and they're adding that. So I think a course of topical steroids just when the transgene is expressed and protein is being produced is something to do in the trials because we want to make sure that we don't see any safety events. As David said, it's a large market disease, and we have really good treatments. Currently, of course, they're not durable past 3 or 4 months maximum. So I think the bar is high, so we want to be careful, and we want to make sure that we have a really favorable safety profile of this onetime treatment that can benefit a large number of patients.

[Operator Instructions] Your next question comes from Tazeen Ahmad with Bank of America.

First one for me, I think your original guidance for an update on this program may not have been in some this year. So if that's right, could you just tell us what went faster than expected that allowed you to give us an update now? It's obviously a very encouraging update, and we would look forward to the next one next year. And then secondly, a question for the doctor perhaps, what would you consider to be the ideal scenario here? Is it that patients would go to 0 on aflibercept injections permanently or simply that they reduce the number of injections that they get per year?

So I can take the first one and then turn it over to Dr. Khanani for the second question. So we certainly have come in significantly earlier than our prior guidance on this program. That was really as a result of the very rapid Phase I dose exploration stage enrollment. So we announced enrollment of the first patient early January this year. So we've been averaging on the order of 1.5 patients per month, which is, as you know, very rapid enrollment for a Phase I dose exploration stage given the built-in delays and the need for DSMV meetings in between dose changes. So that was a pleasant surprise that, that went faster than we had hoped and that I think there's a tremendous amount of excitement for an intravitreal approach here, especially one that targets the back of the eye and that it has a dual transgene payload. So I think that's a reflection of the excitement in the program. The other rationale for sharing this data at this time is not only is enrollment complete, but we've also cleared all 3 dose levels for safety, which was the primary end point of the study. And then finally, we felt that while we certainly want to get more patients, more follow-up on the clinical activity side, the signal that we're seeing today is a meaningful one, and we felt that it was important to share. Dr. Khanani, do you want to speak to Tazeen's question regarding the sort of the optimal profile of a product like this?

Absolutely. So I think in terms of gene therapy and in terms of disease, so this is intravitreal, in-clinic gene therapy. So you are able to treat a large patient population. And in terms of efficacy, I think we understand as clinicians that needs are different for each patient. And you -- here, you have seen the data for high-need patients who are requiring frequent injections, almost an injection every 4 to 5 weeks here, you have 11 on average. So we have to have a treatment that can help all patients, whether it's naive, whether it's previously treated, whether it's highest needs like the one in this trial. So in my opinion, it's not unexpected that we will be able to have 50% or greater patients that are injection-free. Now of course, here, you have 80% that are injection free with the follow-up we have presented. But the decrease in treatment burden by 96.7%, in my opinion, if I am seeing a patient in my clinic that is needing injections every 4 to 8 to 12 weeks, and I offer this idea of one-and-done treatment, it's very promising. And that's why the trial enrolled so quickly. Even though it's early stage, dual transgene, low-dose gene therapy, intravitreal, those things are important when you are doing the trial. So I think if we can get greater than 50% injection-free and then 70% or greater reduction in supplemental injections, I think it's going to be clinically meaningful. And of course, this has to come with the favorable safety profile that we have seen so far.

There are no further questions at this time. I would now like to turn the call back to Dr. David Kirn.

Thank you, operator, and thank you, everyone, for your time and attention today. And we look forward to future updates as this program advances. Thank you.

Ladies and gentlemen, thank you for participating. This concludes today's conference call. You may now disconnect.