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

Ladies and gentlemen, thank you for standing by, and welcome to 4D Molecular Therapeutics webcast presentation of interim data for 4D 150 24-week Landmark Analysis From PRISM Phase II Population Extension Cohort in Broad Wet AMD. As a reminder, today's call is being recorded. With that, I will hand the call over to Uneek Mehra, Chief Financial and Business Officer, who will make introductory comments.

Thank you, operator. And thank you, everyone, for joining our webcast this morning. We issued a press release describing the 4D-150 PRISM interim results for our population extension cohort earlier today and the recording of this webcast will be accessible in the Investors section of the 4DMT website after the completion of this call. We remind you here, we may be making forward-looking statements. For further details, you can visit our website. With me today are Dr. David Kirn, our Co-Founder and Chief Executive Officer, who will provide introductory remarks; Dr. Bob Kim, our Chief Medical Officer, who will review the program summary and next steps; and Dr. Arshad Khanani from Sierra Eye Associates and a lead principal investigator on the 4D-150 PRISM clinical trial who will discuss the data. The PRISM interim data for the population extension cohort was presented earlier this morning by Dr. Raj Maturi, a principal investigator in the PRISM study at the ASRS Annual Scientific Meeting in Stockholm, Sweden. With that, I would like to turn the call over to our CEO, David Kirn. David?

Thank you, Uneek, and thank you, everyone, for joining us. This is an exciting moment today for 4DMT, for ophthalmologists and for their patients with wet AMD. The data we'll be reviewing today confirms and expands 4D-150's potential as a pipeline in a product with multiple potential multibillion-dollar ophthalmology market opportunities, including wet AMD, DME and diabetic retinopathy. This data also confirms our strong conviction in the 4D-150 Phase III program in wet AMD. Thank you to all the patients, clinicians and the entire 4DMT team for your efforts to get us where we are today. Here are the key highlights for today or 4D-150. First, we're delighted to report that 4D-150 continues to be safe and well tolerated in both wet AMD and DME. A key strength for this program and testament to our powerful platform technology and product development. Second, 4D-150 demonstrated strong clinical activity in a broad wet AMD disease activity population, which is representative of our planned Phase III and commercial populations. Third, 4D-150 has demonstrated durable clinical activity from Phase 1 long-term follow-up. Finally, the results we'll share today confirm our conviction in our planned wet AMD Phase III program commencing in Q1 2025. I'll now review the key takeaways of the PRISM Phase II population extension 24-week landmark data. In population extension, we enrolled a total of 45 patients with wet AMD including 30 at the high dose of 3E10 vgs, which is our planned Phase III dose, plus 15 at the low 1E10 vg dose. 4D-150 was safe and well tolerated overall. At the high dose, specifically, none of the 30 patients experienced inflammation in the anterior chamber of the eye, and none had significant inflammation in the vitreous. All patients completed their local prophylactic steroid regimen on schedule and remained off steroids. These safety results are consistent with what we previously reported in the severe disease population in our dose expansion cohort. Strong clinical activity was demonstrated and a dose response in favor of the high dose versus the low dose was evident. We demonstrated a robust reduction in patients' anti-VEGF injection treatment burden. Overall, high-dose patients had an 89% overall reduction in annualized injection frequency. 93% of patients received either 0 or 1 injection and 77% were injection free. BCVA improved by 4.2 letters relative to baseline at week 24 in the high-dose arm. And this was 5.7 letters higher than in the low dose control arm. CST results showed sustained anatomic control that was greater than the low dose and without fluctuations overall. We believe these positive results reinforce the potential of our planned Phase III program. We have now more than doubled the patient safety database at the planned Phase III dose level. And we've confirmed robust clinical activity with key efficacy endpoints in our planned Phase III population. We are now finalizing the few remaining details of our Phase III study design, which we plan to share in September and we remain on track to initiate the first study in Q1 2025. We show here that standard of care bolus anti-VEGF therapies, unfortunately, do not preserve long-term vision in the real world. You can see there is a consistent loss of vision each year, demonstrating the remaining high unmet medical need in these patients. So why do patients still lose vision with standard of care treatment? Here, we describe 3 major limitations, all of which can contribute to vision loss over time. First, current anti-VEGF treatments have limited durability, which leads to suboptimal compliance and undertreatment. Second, bolus intravitreal injection agents result in oscillating peak trough anti-VEGF concentrations that lead to damaging fluctuations in CST. Third, VEGF-C is a driver of wet AMD and can lead to persistent disease activity in patients treated with VEGF-A inhibitors, and this target is not addressed by any of the currently approved agents. As shown here, 4D-150 was designed to address all 3 of these limitations. Our approach is to deliver a single intravitreal injection resulting in durable steady-state anti-VEGF levels within the retina and choroid and to inhibit all 4 VEGF family members that drive the disease. Thus, 4D-150 has the potential to transform the treatment paradigm and to preserve vision over many years. Innovation and treatment of wet AMD has been incremental. With durability improvements of several weeks over standard dose EYLEA demonstrated by new agents such as VABYSMO and high-dose EYLEA. The resulting reduction in injection burden is approximately 20% to 30%. With these relatively modest improvements, these second-generation products are predicted to reach peak worldwide annual sales of over $11 billion across all retinal disease indications. SUSVIMO is designed to reduce injection burden over the course of roughly 6 months after surgical implantation. In contrast, 4D-150 has the potential for multiyear durability and even greater reductions in overall injection burden versus second-generation agents. Our target reduction in patients' injection burden is at least 80% with sustained benefit over at least 3 to 5 years. We believe this represents a compelling target product profile for both patients and caregivers. Wet AMD is a multibillion-dollar revenue opportunity. By 2035, we expect wet AMD to be an approximately $10 billion market annually in the U.S. alone. We estimate that each 1% of market share for 4D-150 could translate into $300 million to $500 million in revenue, assuming we price with at least 3 to 5 years of benefit. Thus, we believe 4D-150 clearly has blockbuster potential in this indication alone in the U.S. We predict market adoption of 4D-150 in parallel across 3 key patient segments. First, the high treatment burden patients representing approximately 20% of the overall population. Second, logistically and/or compliance challenge patients who have difficulty getting to the clinic for repeated injections representing another 20%. And finally, the remaining 60% of the overall wet AMD population. So wet AMD is only the beginning. We believe our promising wet AMD clinical results to date have clear read-through to our ongoing 4D-150 clinical trial in DME or diabetic macular edema. These markets encompass approximately 3.4 million patients in the U.S. alone. In addition, future opportunities with 4D-150 include moderate to severe non-proliferative diabetic retinopathy or NPDR. Finally, we're leveraging the same proprietary R100 vector and manufacturing platform used in 4D-150 for the 4D-175 product candidate for geographic atrophy patients. These 2 markets encompass an additional 4.2 million addressable patients in the U.S. The promising safety and efficacy data generated with 4D-150 to date with a single intravitreal injection, has driven significant momentum in both investigator and patient interest. Enrollment rates have accelerated between its sequential cohorts in our PRISM inspector clinical trials. We believe that this momentum will continue into Phase III enrollment and commercial uptake with this compelling product profile. Here, we show the breakdown of patient numbers treated with 4D-150 to date in all 4 wet AMD cohorts in PRISM and a fifth cohort of DME patients in SPECTRA. 139 patients have been treated in total to date and 80 have been treated at the highest dose of 3E10 vgs per eye, our planned Phase III and commercial dose. We started development in the wet AMD patients with the highest disease severity and treatment burden in both Phase I and the Phase II dose expansion cohort. As planned, following safety and efficacy data in this population, we then moved into a broad patient population that is representative of our planned Phase III population. Finally, based on this wet AMD data, we initiated clinical development in DME patients with broad disease activity in parallel to maximize our steroid prophylaxis options for potential commercialization. We have enrolled wet AMD patients with both severe and broad disease activity into an alternate ocular steroid regimens cohort. Of note, no oral or systemic steroids were included in any regimen. We plan to use our current topical Durezol eye drop regimen in Phase III. I'd now like to hand the presentation over to Bob Kim to summarize the PRISM clinical trial design and baseline characteristics for the population extension cohort. Bob?

Thank you, David. Today, we'll be sharing a 24-week landmark analysis for all 45 patients from the population extension cohort based on a data cutoff date of June 24, 2024. This is the design of the Phase II portion of the PRISM clinical trial evaluating safety and clinical activity of 4D-150 at the 3E10 and 1E10 dose levels. With the dose expansion cohort shown on the left, as we reported in February, and the population extension cohort shown on the right. As discussed, the population extension cohort includes patients with broader disease activity than a dose expansion, which focused on the most severe and highest treatment burden patients. The inclusion criteria for population extension are shown on the bottom right. Patients must have received 1 to 6 prior anti-VEGF injections in the past 12 months with at least 1 injection in the last 12 weeks. Screening BCVA had to be between 34 and 83 letters. Here, we show a figure that compares the population extension and dose expansion cohorts. Retinal CST is shown on the X-axis reflecting disease severity. And the actual number of injections that patients received in the last 12 months is on the Y-axis, which reflects patients treatment burden. In February, we reported Phase II dose expansion cohort data. These patients had a mean CST of 440 microns and 10 actual injections in the prior 12 months as shown in the upper right. These patients had severe disease activity and a high treatment burden. In contrast, the population extension cohort enrolled patients with broad disease severity and treatment burden with a mean CST of 330 microns and an average of 4.4 actual injections in the prior 12 months. The patients in this cohort are representative of the planned Phase III population. This is the clinical trial design for the population extension cohort. All patients received aflibercept on week minus 1 before receiving 4D-150 on day 0. Patients then received intravitreal 4D-150 at either the high dose of 3E10 or the low dose of 1E10. As is done in some other gene therapy studies, another aflibercept injection was given on week 4, to ensure anti-VEGF coverage during the 4D-150 transgene expression ramp-up phase of approximately 8 to 12 weeks. Consistent with other pivotal gene therapy studies in wet AMD, this week 4 dose will also be used in our Phase III trials. Patients initiated a prophylactic ocular steroid regimen involving only local administration. Study endpoints included safety and tolerability, annualized anti-VEGF injection rate, proportion of patients requiring supplemental aflibercept injections and change from baseline in BCVA and CST. The criteria for supplemental aflibercept injections are shown on the right and are the same as were used in the dose expansion cohort. This table outlines the key baseline characteristics of the 45 patients enrolled with 30 in the 3E10 arm and 15 in the 1E10 arm. All patients were previously treated. Overall, the arms were well balanced. Mean BCVA was 72 letters at baseline or roughly 20, 40 still on equivalent. Patients had a mean CST of 329 microns indicating active disease and as mentioned earlier, the mean number of actual anti-VEGF injections in the prior 12 months was 4.4. I'd now like to hand the presentation over to Dr. Arshad Khanani, Lead Investigator of the PRISM clinical trial to present the data. Arshad?

Thanks, Bob. I would like to start by summarizing the safety profile from 4D-150 in this cohort. Safety is a priority for any new treatment in wet AMD, 4D-150 was safe and well tolerated with no 4D-150 related serious adverse event. There were no cases of hypotony, endophthalmitis, vasculitis, choroidal effusions or retinal artery occlusions, in 30 patients treated with 3E10, no significant inflammation was reported. All 30 patients completed the prophylactic steroid regimen on schedule and non-resumed steroid treatment. This slide summarizes the safety results from comprehensive ophthalmic examinations completed at every visit to look for cells in the anterior chamber and vitreous. Cells were graded according to the standard SUN and NEI scores. Each row represents a patient, each column represents a visit, and each box represents the SUN and NEI score from that visit. As seen with all of the dark green boxes, 4D-150 was very well tolerated. At the 3E10 dose level plan for Phase III, no clinically significant or recurring intraocular inflammation was observed in any of the 30 patients. Specifically, no inflammation was detected in the anterior chamber in all 30 patients and none was detected in vitreous in 29 of 30 patients. A single patient had trade cells detected that did not require treatment. At the lower 1E10 dose, 14 of 15 patients had no inflammation, a single case of mild to moderate inflammatory cells was noted in a patient. This patient also had trade cells in the vitreous of the non-injected eye as well. This patient improved rapidly on a topical Durezol taper. This outlier case represents approximately 2% of all patients in this study, whereas 98% of study patients had no significant inflammation. Here are the swim lane plots for individual patients from both dose groups. During both the pre-enrollment anti-VEGF injections on the left and the supplemental anti-VEGF injections on the right for both treatment arms. At week 24, the annualized anti-VEGF injection rate in the 3E10 dose arm was reduced by 89%. 93% of patients received either no injection or only a single supplemental injection. Finally, 77% of these 30 patients remain completely injection free. The low dose demonstrated clear biological activity as well with a similarly strong reduction in overall treatment burden. Our dose response was suggested when looking at the injection free rate of 77% at the high dose versus 60% at the low dose. These data highlight the efficacy potential of a single intravitreal injection of 4D-150 in wet AMD patients representative of the planned Phase III population. Here on the BCVA results, as seen in the dark blue solid line for all patients on the 3E10 dose, mean visual acuity improved by 4.2 letters from baseline. The dash blue line shows BCVA results from the subgroup of 3E10 patients who were supplemental injection free. The BCVA in these patients improved by 4.7 letters from baseline. Our dose response was observed between the high dose of 3E10 and the low dose of 1E10. The mean change in BCVA from baseline was 5.7 letters higher in the 3E10 arm versus the 1E10 arm. As a reminder, these are previously anti-VEGF-treated patients with broad disease activity. This slide shows the CST as measured by OCT. A measure of disease activity and response to treatment in wet AMD, as shown with the dark blue line, the 3E10 dose level was associated with sustained and greater anatomic control versus the low dose with the CST reduction of 9.2 microns from baseline. As shown with the dash blue line, the CST results from the 77% of patients who remain injection free on the 3E10 dose, their CSTs improved by 32 microns from baseline. No CST fluctuations were observed. Consistent and sustained disease control was demonstrated without supplemental aflibercept injections in these patients. Arises the reduction in treatment burden at the 3E10 dose across the severe patient population from dose expansion and the broad disease population from population extension described today. The data show up consistent anti-VEGF treatment reduction across both patient populations. An 89% reduction in mean annualized injection rate was achieved in both populations. 93% of patients achieved 0 or 1 supplemental injection in the broad population versus 84% in the severe population. And finally, 77% of patients in the broad population were supplemental injection-free versus 63% in the severe population. This consistent and reproducible data across 2 study cohorts confirmed 4D-150's potential to significantly decrease treatment burden regardless of disease activity. Here, we have a case study from the population extension cohort of a patient treated with the 3E10 dose, who has been supplemental injection-free through 24 weeks. This patient received 4 anti-VEGF injections in the prior 6 months and missed the day 28 per protocol injection. As shown on the lower left, this patient BCVA was consistently improved throughout 24 weeks. And by week 24, the BCVA was improved by 6 letters. OCT images of the patient are displayed at the top of the slide and associated CST results are shown in the lower right. The same CST control and improvement can be seen through week 24. These BCVA and CST results confirm strong and sustained disease control after a single injection of 4D-150 without any supplemental anti-VEGF injection. Here, we have an update from the Phase I stage of PRISM, which is now in long-term follow-up. We previously presented three heavily pretreated patients in the 3E10 dose who are injection free through 1.5 to 2 years. Of note, these patients received 11 to 12 injections in 12 months prior to receiving 4D-150 and all 3 patients remain injection-free for 2 to 2.5 years. Mean BCVA has remained stable and mean CST was improved and sustained without fluctuations. This highlights the emerging long-term sustained benefits of 4D-150 at the Phase III dose. Importantly, 4D-150 continues to be safe and well tolerated across all 139 patients dosed to date in both PRISM and SPECTRA clinical trials. This includes follow-up in 22 DME patients through up to 36 weeks, and there has been no inflammation observed. All patients have completed their topical prophylactic Durezol regimen on schedule and did not resume. 51 patients have been treated at the planned wet AMD Phase III dose and topical Durezol prophylactic regimen had no significant inflammation. Hypotony, retinal vasculitis, choroidal effusions, retinal artery occlusion with up to 2.5 years of follow-up and no recurrent inflammation post steroid taper has been observed. This safety profile is highly promising for Phase III development and our patients in the real world. We are pleased to report that we have seen no 4D-150 related hypotony, endophthalmitis, vasculitis, choroidal effusions or retinal artery occlusions across all patients. I will now hand it back over to David to discuss next steps.

Thanks, Arshad. The exciting results we shared today validate the potential of 4D-150 to be a highly disruptive product in the broad population of wet AMD and the overall retinal diseases market. Here, we review our Phase III pivotal trial design and registrational planning in wet AMD. We will be running two Phase III non-inferiority trials based on BCVA, evaluating 4D-150 at the 3E10 vg per eye dose level versus a control arm of aflibercept 2 milligrams every 8 weeks. The non-inferiority margin for FDA and EMA is 4.5 and 4 letters, respectively. We expect each study to enroll approximately 450 patients or approximately 225 patients per arm. The population extension cohort characteristics and treatment regimen discussed today are representative of our planned Phase III design. We have received both RMAT designation from the FDA and PRIME designation from the EMA for 4D-150 in wet AMD. These designations enable increased collaboration between the two agencies and an opportunity for expedited product development. To our knowledge, we are the only ophthalmology product candidate to ever receive both designations, which differentiates us from our competitors in this market and enables us for global commercial readiness. We plan to provide an update on our finalized Phase III pivotal study protocols this September. We remain on track to initiate our first Phase III pivotal trial in Q1 2025. In summary, 4D-150 achieved all of our objectives in this population extension cohort and program update, including safety, efficacy and long-term durability. These results confirm our conviction in our planned wet AMD Phase III program. In addition to Phase III plans, we also look forward to sharing 52-week wet AMD data from both PRISM dose expansion and population extension cohorts in February 2025 and 24-week DME data from Part 1 of SPECTRA in Q4 of 2024. Our balance sheet remains strong to fund the Phase III program with $589 million of cash as of the end of Q1 2024 and with runway into the first half of 2027. Before I open up the call to questions, I'd like to take a moment to thank the entire 4DMT team for their remarkable innovation, execution and dedication. I'd also like to deeply thank our investigators, clinical trial staff, patients and their families. Thank you. And I'm happy to now open the call to questions. Operator?

[Operator Instructions] Our first question today comes from Salveen Richter.

Congratulations on the data. A couple of questions from us here. One is, were there any baseline characteristics associated with achieving injection-free status versus not? Could you give us a little bit more clarity here on the CST side as well? And then just speak to -- for the Phase III study, what items are left to gain alignment on? And could you confirm that you'll evaluate 1, not 2 4D-150 dose levels and whether there's any ongoing work on dosing fellow eye or evaluating higher doses.

This is Dave Kirn, CEO of 4D. So you had a question about baseline predictive factors for injection free status. So again, 77% of the high dose were injection free. We've been thrilled that a broad range of patients, even very severe patients in terms of CST and number of prior injections have been able to respond and achieve long-term injection-free status. So as of today, there's nothing that predicts for patients who won't be able to achieve injection-free status, but that's something we'll continue to study over time. In terms of the CST details, we're thrilled again with these results. So as we said in the introduction, patients still lose vision with wet AMD on standard of care. We believe that's due to this oscillation or fluctuation in the retina that comes from that intermittent bolus therapy. What we've been able to show in the prior study cohort dose expansion and now in this population today was a rock solid CST, particularly in those 77% of patients who are injection free. We really don't see any change from 12 weeks after any sort of bolus aflibercept loading doses done and out to '24. So on 4D-150 alone, that CST is rock stable and there's no evidence of fluctuations. We think that's going to translate into BCVA benefit. And in fact, on this study, we saw a pretty remarkable 4.7 letter improvement in the injection-free patients in terms of their BCVA. With regards to Phase III, we've made great progress there with the FDA and the EMA under these special designations that we have of PRIME and RMAT and we're getting down to the final details, and we will release the final study design in September. I would say the open details there around the precise enrollment criteria, things like that. But the primary endpoint of BCVA and secondary endpoints, the overall patient population, the dosing regimen, the steroid regimen, all of that is locked in. So we're -- this data today really increases our conviction in that plan and that program. And then you had a question about confirming a single dose level, and we can confirm that in both of these cohorts, in PRISM, we saw a nice dose response favoring the 3E10 dose. So we are now confirming that we're taking 1 dose level into Phase III, and that will be the 3E10 dose level. Before we move on, I'd like to turn to Arshad and see if you have anything to add to Salveen's questions.

So I think for me, this data set is super important because on your question about CST, if you remember in the dose expansion, we were looking at patients who are super high need, difficult to treat to established biological activity. So as a clinician, we want to make sure that, obviously, gene therapy number one is safe. And number two is efficacious. And in that cohort, we have patients with significant fluid over 6 injections in 12 months, CST greater than 325 and a lot of fluid at a very high actual treatment or in history. And there, we saw great efficacy in terms of injection free and minimizing the number of injections and stable anatomy, as David was saying. So this data on broad patient population which by the way, includes some high-need patients also. So this is not a patient population that's completely dry with the very low CST. This is around 320 to 330 in terms of CST to your question. So these are also active patients, but some of them were relatively fresh and others were longer because what happens when you go from Phase II to Phase III is you get a broad patient population. And for me, as the lead investigator, always goal is to derisk the pivotal program. So adding this forward gives us the confidence that you have patients who are high need, patients who are lower need, patients who are chronic, patients who are fresh, if we can have activity in those patients, then essentially derisks the Phase III program. And I think this data set really highlights that. And of course, you're going to get patients who are not all super high need, but you're going to be able to have better numbers in terms of injection free and others. So I think this kind of confirms that there's great biological activity. There's maintenance of CST that is minimization or no fluctuations. And of course, for me, as a clinician, the biggest thing is safety and the safety profile here we are seeing is very consistent with what we have seen in the past. So I think this kind of makes a really good pathway or having this in Phase III program in the near future and hopefully available for our patients.

And Salveen, you also asked about some of the line study. So that is something that we intend to study as part of a Phase III package, that's something FDA would want to see. We do expect in the commercial setting to treat the control -- the fellow eye, a significant percent of these patient, I think, is up to 40%, will develop the disease in the other eye. So we want to be able to treat those. So we do intend to do that. We have treated the fellow eye in our rare disease program with the same exact vector and manufacturing platform for that product and it was safe and well tolerated. We've also done the same in [indiscernible]. We expect to do that and we expect to be safe and well tolerated and effective.

Next question comes from Tazeen Ahmad.

Congrats on the positive data. David, I just wanted to get some color on that 1 patient that you described as having the case of inflammation in the lower dose. Obviously, it's a low percentage in the relative scheme of things. Can you just provide additional color on the profile of that patient and what might have potentially cause the case of inflammation? And when that case occurred? And can you just compare general rates of inflammation of this sorts to what you see with EYLEA and LUCENTIS? And then I have a follow-up.

I'll kick it off and then turn it over to Arshad. So first of all, this is incredibly rare. It's a single patient out of 139, so less than 1%. You mentioned the EYLEA, the label for EYLEA, I think, has about 2% to 4% of patients can have some inflammation. So again, our profile of 98%, having no significant inflammation compares very favorably to EYLEA. This particular patient, this 2-plus popped up week 24 and the patient was put on a Durezol taper at that point and responded very quickly and is now asymptomatic and doing very well. So incredibly rare and responded well. To reiterate, we had 51 patients to date on the 3E10 plus Durezol regimen, which we're taking into Phase III. And then we had no significant toxicities, no Grade 1, no Grade 2, just 1 patient with trace cells that were not treated. So a very favorable safety profile. In terms of the patient, maybe why this happened, the patient has a complex medical history and background, untreated syphilis in the past and also some misses, week 4 loading dose and had a little bit of a bleed from missing that dose. So it's a complex patient background. We'll continue to study it and see if we can predict this in the future. But I think the bottom line is this is less than 1% of our overall patients. It's very consistent with the EYLEA label and the safety profile has been incredibly compelling to date. Arshad, would you like to add anything on this question?

No, I think as a clinician, safety is a priority. We have intravitreal injections, obviously, that work really well and we have this treatment burden that patients have, or outcomes in the real world. So anything that's going to be adopted broadly in terms of a sustained delivery needs to be very, very safe. So I actually -- as a clinician, I'm always interested in safety. And obviously, it's super important. So this patient, as David said, looking into more history, has complex history and remember this patients have to be on topical drops also for 20 needs. And if they miss 1 appointment for their follow-up, I'm questioning if they also took their drops as instructed. But I think these things happen in terms of patient canvas appointments. And so I think for me, it's the overall data package and data that I'm looking at as a clinician. I just presented the first time results for the RHONE-X study, we use a 4-year follow-up, faricimab study extension study with over 1,400 patients between faricimab and inflammation rate in that trial was between 1% to 2%. So I think if you have a rate that is 1% to 2%, I think that is very reassuring at this stage that this gene therapy is very, very safe. And obviously, you want to make sure that you are looking for those signals, and that's why very detailed examinations were done in the study, looking at anterior chamber, looking vitreous and grading the cells. So I think the bottom line for me is that in this large data set, of 139 patients, the rate is less than 1%. And, this is very reassuring. These are very large numbers that now we have accumulated. And as a clinician, the other thing is that you don't want to restart treatment after tapering off if you have patients having inflammation because you don't want patients on long-term eye drops. So that's the other reassuring thing here is that when you look at the 3E10 dose, all patients completed their prophylaxis on steroid and did not resume. So I think that profile is very meaningful in terms of predictability and adoption in a clinical setting for practicing physicians.

And then I just wanted to get a sense of how you're thinking longer term. You've got a really high percentage of patients that have remained rescue injection free. [indiscernible] indicate that if you can hit a year without needing a rescue injection that would be impressive. And clearly, you're on track to be past that. But in a blue sky scenario, how are you thinking about the need for potential rescue injections from VEGF? And what is your view about looking into the potential of redosing, if redosing is needed several years down the line with your therapy?