Good morning, everyone, and thank you for joining the EDIT-101 clinical update webinar. This webinar is being recorded and can be accessed in the future through the same link or through the investor section of the company's website. After the webinar, the call will be open to Q&A. To ask a question, please click the Raise Hand feature in the webinar portal. As a reminder, various remarks that we make during this presentation about the company's future expectations, plans, and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent annual report on Form 10-K, which is on file with the SEC, as updated by our subsequent filings. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Except as required by law, we specifically disclaim any obligation to update or revise any forward-looking statements, even if our views change. This webinar will be presented by Editas Medicine CEO, Gilmore O'Neill, and our Chief Medical Officer, Baisong Mei. I'd now like to turn the call over to Gilmore for opening comments. Thank you, Ron, and good morning, everyone. We have shared before that one important objective of the EDIT-101 BRILLIANCE study is to identify a population of LCA10 patients who have a clinically meaningful response to EDIT-101 and can be identified by baseline characteristics so that we can pre-select patients that have a high probability of clinical response in future studies. For this analysis, we defined a clinical responder as a person who had a consistent, clinically meaningful improvement in BCVA and positive clinical responses in at least two of the following three additional endpoints, Full-Field Stimulus Test or FST, visual navigation course, or the visual function quality of life, VFQ, a patient-reported outcome. Before handing over to Baisong, here are the key takeaways. EDIT-101 was well-tolerated with a favorable safety profile. We believe that the BRILLIANCE study has demonstrated proof of concept of clinically meaningful CEP290 editing by EDIT-101 because three out of 14 treated subjects met the responder threshold, having experienced clinically meaningful improvement in visual acuity measured by BCVA and having demonstrated consistent improvements in two additional endpoints. Having demonstrated POC, can we pre-select patients more likely to experience a clinical benefit from EDIT-101? Looking at the baseline characteristics of the treatment responder patients, two of the three responders were homozygous for IVS26 mutations. That is two out of two or 100% of the homozygous patients treated. Now, this is a small number of subjects as you might expect in a phase I study of a rare disease. Nevertheless, we believe that we have identified homozygosity as a baseline parameter that will allow pre-selection of patients most likely to experience clinically meaningful response in a registration study. Looking beyond genotype and homozygosity, we were not able to identify any additional baseline characteristics in the three responders that could be used to pre-select additional patients with a high probability of clinical response for future clinical studies. Baisong, our Chief Medical Officer, will now take you through the ENLIGHTEN Natural History Study and BRILLIANCE studies and show the data that lead these conclusions. Baisong. Thank you, Gilmore. LCA10 is a rare inherited retinal disease characterized by profound visual impairment starting in early childhood. Currently, it's without treatment. LCA10 is caused by mutations in the CEP290 protein in photoreceptor cells, resulting in significant field and central vision loss. The most prevalent mutation is the IVS26 mutation, which affects about 1,500 patients in the United States. About 20% of IVS26 mutation patients are homozygous for this mutation with an estimated 300 patients in the United States. EDIT-101 deletes the IVS26 mutation and restores expression of full-length functional CEP290 protein. The EDIT-101 clinical program, including two studies in IVS26 LCA10 patients. The first was the ENLIGHTEN Natural History study, and then the second is the phase 1/2 BRILLIANCE study. The Natural History Study was a 12-month prospective study designed to characterize the clinical course of LCA10 and to understand the behavior of multiple endpoints to determine a threshold of statistically meaningful change. The data from the Natural History Study have been used to contextualize the data interpretation of the BRILLIANCE study. The BRILLIANCE study was designed to evaluate the safety and tolerability of EDIT-101 in participants with LCA10, and to evaluate the efficacy of EDIT-101 on endpoints of visual function and visual quality of life, and to identify a segment of patient population based on baseline characteristics in clinical responders. Which will allow us to select patients with high probability of responding to EDIT-101 treatment in a future phase three registration study. The BRILLIANCE study includes adult low, mid, and high-dose cohorts, and pediatric mid and high-dose cohorts. The study inclusion criteria allow the enrollment of LCA10 patients with homozygous or compound heterozygous IVS 26 mutation. The protocol also allows the recruitment of patients ages 3 and older. Key endpoints including safety and tolerability, and efficacy and quality of life-related endpoints, which I will cover later. To date, we have enrolled a total of 14 participants, 12 adults between 18-63 years old, and 2 pediatric participants at age 9 and 14 years old. 2 of the 14 participants are homozygous, and the remaining 12 participants are compound heterozygous. As you can see, participants have a broad range of BCVA and FST without a clear correlation to patient age. 2 participants are enrolled in adult low-dose cohort, 5 each in adult mid and high-dose cohort, and 2 pediatric participants in mid-dose cohort. Among the 14 participants, 11 had at least six months follow-up period. Seven of them had at least 12 months of follow-up. Three participants had three months of follow-up. During the follow-up period, EDIT-101 demonstrated a favorable safety profile. EDIT-101 was generally well-tolerated across all cohorts, and no dose-limiting toxicity or drug-related SAE or ocular SAE were observed across cohorts. The majority of AE were mild or moderate, which accounts for 90% of all AEs. Half of all AE were related to surgical procedures and are a recognized complication of subretinal injection. Seven of the 14 participants, 50% of them, reported no ocular AE related to EDIT-101. One patient reported a related ocular grade three AE at six months, a non-serious vision impairment, which is improving. This participant enrolled in the Natural History Study, during which the same eye experienced a similar vision fluctuation. Now we turn to the key endpoint used in our analysis of BRILLIANCE study. For the BCVA, a decrease in measurement indicates clinical improvement, and an improvement from baseline of 0.3 logMAR is accepted as clinically meaningful. For FST, a decrease in the score indicates improvement, and our natural history study demonstrated that an improvement of 0.6 is outside the range of noise and is statistically meaningful based on test and retest data. For visual function navigation, or VFN, an increased score indicates improvement, and our natural history study demonstrated that an improvement of 3 is statistically meaningful. Finally, for the patient-reported outcome, visual function quality of life, or VFQ endpoint, an increased score indicates improvement, and an improvement of 4 points has been determined to be clinically meaningful. As a result, the BRILLIANCE study responders are defined as meeting the threshold of clinically meaningful change for BCVA and meaningful improvement in two other endpoints. Now I will discuss the summary of efficacy for BRILLIANCE study. Among the 14 participants in the study, several participants showed improvement in one or more of the four endpoints, as highlighted in the blue cells on the screen. Now, as I mentioned earlier, we define the positive response to EDIT-101 treatment as clinically meaningful improvement in BCVA and consistent improvement in at least two of the three other endpoints: patient-reported outcome VFQ, VFN, and FST. Indeed, three participants, as highlighted by orange box on the screen, met this definition of a clinical responder. Looking at the baseline characteristics of the treatment responders, two of the three responders were homozygous IVS26 mutation. These patients are identified there, pink identifier on the left. That is two of the two or 100% of the homozygous participants treated were responders. Looking beyond genotype and specifically homozygosity, we were not able to identify additional baseline characteristics that could be used to pre-select patients with a higher probability of clinical response in future studies. Whereas homozygosity is the only baseline parameter that can predict a clinical response based on the current data. These slides show some details of the results from the two homozygous patients. Please note that solid lines represent data from the treated eye, and the dotted line represents data from the contralateral untreated eye. During the 12-month follow-up period, the 54-year-old homozygous patient, whose data are presented in the four-panel in the top row, showed that a clinically meaningful BCVA response of 1.3 logMAR at month 12, sorry, a meaningful improvement in visual function navigation and the visual function quality of life, VFQ, over the course of 12 months. The FST also showed trend improvement for four lights of all three colors. This participant had a knee injury at month 12 visit, which the investigator felt might have confounded her performance in the visual function navigation course. In summary, this subject showed consistent and a directionally positive response in three of the four endpoints and meet the definition of a responder. During the three-month follow-up period, the 14-year-old pediatric homozygote, homozygous participant, whose data are presented in the four-panel in the bottom row, showed that clinically meaningful improvement in his BCVA of 0.6, of 0.7 logMAR. A meaningful FST improvement for lights of all three colors, and a meaningful improvement in children VFQ. His VFN score also showed trend improvement. We did notice that this participant had improvement in his BCVA and visual function navigation endpoint in both the treated eye and nontreated contralateral eye. We and the investigator and the steering committee members discussed this data in detail, and it was struck nevertheless by the overall consistency of improvement in the treated eyes for all four key visual endpoints, thus giving us confidence in our conclusion that this patient meets the definition of a responder. Such challenges on results of untreated contralateral eyes have been reported in other LCA trials before. It is also worth noting that regulators tend to favor using treated patients as control rather than untreated contralateral eyes owing to such challenges in pivotal trials. In summary, EDIT-101 was well-tolerated with a favorable safety profile. We believe that BRILLIANCE study has demonstrated proof of concept clinically meaningful CEP290 editing by EDIT-101 because three out of 14 treated subjects met the responder threshold, have experienced clinically meaningful improvement in visual acuity measured by BCVA, and having demonstrated consistent improvement in two additional endpoints. Two of two homozygous participants are among the three responders. As I mentioned earlier, based on current data, the homozygous patients are the only population that can be predicted as responders. I will now turn the call back to our CEO, Gilmore O'Neill, for his concluding remarks. Thank you, Baisong. As you can see, BRILLIANCE demonstrates compelling evidence of clinically meaningful EDIT-101-driven genome editing in the retina of LCA10 patients with an IVS26 mutation. Now, we have previously stated that in order to move forward to a registration study, Editas needs to see both consistent effects on a number of clinical outcomes in treated patients and a meaningful treatment benefit for a commercially viable patient segment. The BRILLIANCE data show that the only patient segment that we can predict to have a clinically meaningful response is homozygous for the IVS26 mutation. This segment of the already small population of patients with LCA10 is estimated to comprise only 300 patients in the U.S. The size of the population does not make it viable for Editas to advance this program alone. However, because patients are at the very center of our mission, we will therefore seek a partner to continue the development of this program. In the meantime, we will pause further enrollment in the BRILLIANCE study, but of course, we will continue the follow-up of all patients who have been already dosed. Additional learnings from the BRILLIANCE study include the demonstration of a satisfactory safety profile for CRISPR nuclease delivery by AAV to the retina, variability of disease phenotype and severity not simply predicted by age, and the translational challenges in determining the baseline characteristics most likely to predict a clinical benefit. In addition, looking forward, Baisong and I, since our arrival in the middle of this year, are implementing the use of new therapeutic target selection criteria that use translational, clinical, and commercial factors to maximize the probabilities of technical, regulatory, and commercial success for our pipeline. Clinical execution is a top priority for us. We look forward to sharing more details around the criteria and our strategic plans in the coming months. We want to thank all the patients, their families, PIs, clinical sites, and employees who have worked on this project and look forward to updating you in the future should we identify a partner to take EDIT-101 forward. Thank you, Gilmore. We will now proceed to the Q&A portion of the webinar. As a reminder, to ask a question, please select the Raise Hand feature at the bottom of your webinar portal. You will be prompted to unmute your line before asking your question. First question comes from Joon Lee at Truist Securities. Joon, you may now unmute and ask your question. Hi, this is Mandy for Joon, and sorry for my bad voice. The question would be how you would make this treatment viable for a compound heterozygous. Is it improvement of editing efficiency and cutting out the deletion or the delivery to the right cells? Thank you. Thank you very much. I believe your question, for me, I think what you're trying to ask is, are there alterations to the program or the molecular design that would improve or provide potential benefit to compound heterozygous patients? I think the best answer to give you on this is that when we look at the current data set with the construct that we have, which essentially targets the editing out of the deep intronic IVS 26 cryptic splicing site, the only patients that we can see that would have a baseline characteristic that would allow us to pre-select a patient population for a registration or future study would be patients who are homozygous for the IVS 26. We haven't looked at or considered a different strategy from a therapeutic point of view because the nature of the construct as we have built it today. I hope that answers your question. Next question comes from Matthew Harrison at Morgan Stanley. Matt, you may proceed. Great. Good morning. Thanks for taking the question. I just wanted to ask about how you think about investments in some of the other genetic eye disease programs that you have in the pipeline, just given today's data and either, you know, somewhat similar to the prior question, thoughts on the construct and things you might wanna do differently in those other programs or just how you think about the investment in those programs given the commercial opportunity. Thanks very much. Thanks very much, Matt. I think the key things, the takeaways or sort of the read-throughs we have is that we are seeing a very satisfactory safety profile for AAV-delivered CRISPR nucleases to the retina, which is a first. The second is that we have seen POC for editing. That actually reads through to the IRDs. It is worth pointing out that when you look at our other preclinical programs, for example, EDIT-103, we have demonstrated higher editing efficiency, which would actually build on what we've seen today. I think finally, from a commercial viability point of view, the way we look at commercial viability and, you know, Baisong Mei, myself, and members of the leadership team bring a substantial experience, indeed, between Baisong Mei and myself, a track record for 10 approvals and drugs we brought to market. We are looking at a commercially viable population through multiple factors which include not just the size of the population, but the unmet need, the complexity of the therapy and how it interacts with the existing medical therapeutic landscape, as well as ascertaining. Those just to name out a few. I think the answer to the construct we have today and what will we change, I think I've answered that in the previous question. I think the key points, I think when you look beyond 101 is that, for example, our 103 construct uses a dual vector approach that has in addition a different and more robust editing efficiency in our preclinical data. Our next question comes from Gena Wang at Barclays. Gena, you may proceed. Thank you for taking my question. Also kind of follow the first two questions. Also, you know, Gilmore, you also mentioned, you know, what is the read-through to the other programs, you know. Maybe if you can talk a little bit more for other eye indications, how you will select or prioritize the remaining programs with this now become deprioritized. Also another question is how much cost saving you have, you know, now with the reprioritized development path. Thanks very much, Gena, for your question. When I think about the read-through to other retinal programs, I think I've actually addressed that. One thing I did leave out when we talked about 103, when I talk about the editing efficiency, is the use of a different promoter and the fact that it uses a single guide, which actually those two things together are probably what's driving the efficiency of the editing that we see relative to 101. I think the good news is that we have a proof of concept determined by, you know, a very rigorous test of selection criteria. With regard to prioritizing, I was just mentioning that, based on myself, you know, joining in the midyear, with a view to really moving this organization into a commercial therapeutics company while, you know, building its technology. We have outlined and are applying a new set of target selection criteria informed by factors coming from biology, translational biology, clinical and commercial factors to maximize the probability of technical, regulatory, and commercial success. These we are applying with our executive team as we evaluate our strategy and pipeline going forward and look forward to sharing that with you in the coming months. I think with regard to savings, we will actually be sharing that with you in the coming months in the context of our evaluation of our strategy and pipeline. Thank you. Our next question comes from Phil Nadeau at TD Cowen. Good morning. Thanks for taking our questions. Just a couple from us. First, maybe ask the other questions in a different way. Why do you think the compound heterozygous patients didn't respond when initially you were optimistic they would? Do you think the threshold for the number of alleles or cells that need to be edited is higher? Was the efficiency in the eye somewhat less than would have been predicted by preclinical studies? That's the first question. Second, a clarifying question. You mentioned on the pediatric patient that the contralateral eye also seemed to have some improvements. That didn't refer to the BCVA. Is that correct? It seemed like from the chart, BCVA was only measured in the treated eye, and that was the only one that improved. Thanks. Yeah. Thanks very much, Phil, for your question. Why the compound heterozygotes? I think the issue here is that we certainly saw one compound heterozygote patient actually met our, you know, our rigorous definition of a clinical responder. I think there are a number of hypotheses that would actually drive this. I think you touched on one, which is around the efficiency of editing one versus two potential targets. I think the second centers around observations that the IVS26 cryptic splice site may actually be read through and indeed, published work looking at expression in fibroblasts for CEP290 IVS26 homozygous patients do demonstrate higher levels around the order of 50% expression of a full-length CEP290 protein. That's the first question. I think you asked about the contralateral improvement in pediatrics. In fact, you see 1 line. The dotted line represents the contralateral eye sitting, they're basically on top of 1 another. That's why you didn't see it. However, I do want to make a couple of comments about that. A contralateral eye moving on BCVA is actually not without precedent. It has been seen in multiple clinical trials of retinal therapeutics, both for acquired disease as well as congenital disease. Indeed, as Baisong said, it was observed even with the early development of ProQR Therapeutics. I would call out that early 1, because that's where 1 eye was treated and the other not. It is for, I think, those reasons and with also many possible complex physiological explanations why it was observed. This is the reason why FDA and other regulators tend to favor using as controls untreated patients as opposed to an untreated eye in the same patient as the treated eye. This is an observation that may be for. I think the final point I'd like to make is that, notwithstanding this observation, if you looked at the data, you can actually appreciate that because of our requirement to have three out of four consistent and directionally positive movements to call a responder, we feel confident that this patient is a responder. I think, you know, the fact that we see not only that, but within that, the patient-reported outcome actually also being consistent is all very supportive of that observation, that conclusion. Our next question comes from Liisa Bayko at Evercore. Liisa, you may proceed. Oops, sorry about that. Can you explain just sort of mechanistically why you think you're getting, this particular mutation seems to be, I think, having the majority of the benefit? If you could, you know, is there some rationale there biologically? Well, yes, Lisa, thanks very much for your question. I apologize if we didn't make it clear in the presentation. A subset, a subgroup of LCA 10 patients have an IVS26 mutation, and about 1,500 patients, you know, a subset of 1,500 patients estimated in the LCA 10 population carry the IVS26 intronic mutation. This is deep intronic mutation, which creates a cryptic splice site. That is the target of the editing therapeutic EDIT-101. The intent of the therapeutic is to actually remove, either delete or potentially invert, the segment of the intron carrying that mutation. That's why that mutation is important. I think I've already said that, you know, in the context of the patient population who all had to carry at least one IVS26 containing allele as well as another mutation, be it IVS26, homozygous therefore, or another disease-associated allele. We found that in this study, which was designed to do a number of things, but one key objective was to identify a responder population that could be pre-selected based on baseline characteristics for future studies. We found that the homozygous patients with IVS26 mutation were responders and would be easily identified. Our next question comes from Jay Olson at Oppenheimer. Jay, you may unmute and ask the question. Oh, hey. Thank you for taking the questions. Can you talk about how you're learning from 101 to help you better predict for your new patient population in the optimized program? Sorry. Jay, you're very muffled, but I believe that your question you asked was, can you see or are there learnings from this 101 experience that would inform the selection of patients in other inherited retinal disease trials? Let me attempt to answer that question. I hope that's the right question. Yeah. Yeah. Okay, great. Thanks, Jay, for confirming. I mean, I think key thing is two key learnings. A very important learning obviously is that we actually have demonstrated that we can safely deliver CRISPR nuclease to the retina using AAV. That is actually a very important step. In addition, we have found that we can, with the EDIT-101 construct, edit and do clinically meaningful editing in patients. In this case, it was approximately 20% of the patients, and we can pre-identify going forward a patient population most likely to respond. I think it's important to say that the EDIT-103 from an efficiency point of view, has a higher editing efficiency, and there are other issues which I won't revisit just now. With regard to would you design studies differently, I think the key thing here is that the phase 1 BRILLIANCE study did exactly what it was designed to do. It was designed not only to determine and look at a dose range for maximum tolerated dose determination, which it has done. It was determined or designed to identify proof of concept. It was also asked to identify the outcome measures and their behavior in this patient population. It was designed to see if there were objective characteristics at baseline that would allow you going forward to pre-select a responder patient population. I think actually those are kind of the lessons that we learned to carry forward. I think it's important to understand that there are elements in rare diseases where one must actually do the important exploratory elements of design that we carried out for this program. Great. Thank you. That's very helpful. Maybe if I could ask one follow-up. Have you discussed these data with the FDA and feedback have you received? Yeah, sorry, Jay, for interrupting. I'm going to actually hold the next question just for a second. You were very muffled again. I think you said, have you discussed this with the FDA, and what was their feedback? Yes. Is that correct? Yes. Okay. Yes. We have not had a detailed discussion with the FDA, but obviously, throughout the course of the study, you know, we're continuously updating with data. Okay, great. Thank you. Maybe one final question. Can you just provide some color around the characteristics of the ideal partner you would be looking for to collaborate on the 101 program going forward? Yes, Jay, and congratulations, you're completely clear on this one. We can hear you very well. Yes. Obviously, we are looking for a partner who has an interest and expertise in retinal diseases and a genetic gene therapy in retinal disease, and who has a particular interest and a business model that will work in the context of a really ultra-rare population. All right. Super helpful. Thank you for taking all the questions. Thanks, Jay. The next question comes from Joel Beatty at Baird. Joel, you may now unmute and ask your question. Great. Thanks. I guess first for the severe ocular adverse events, what's your assessment on whether or not it was related to drug? Thanks, Joel. This is Baisong. Thanks for your question. We have had detailed discussions with the investigator and IDMC about this case. We did see the fluctuation of the visual function, and this patient is recovering with all the detailed analysis data, including OCT imaging, baseline characteristics. As I mentioned also, this patient was in natural history study, and the IDMC also reviewed the data. The conclusion was we can continue to dose the patient as we planned. There was no concern of specific about this case. All right. Thank you. One follow-up question. Related to efficacy and the finding that the efficacy seemed to be limited to homozygous patients, how does this match up with the preclinical data on this agent? Thanks very much, Joel, for that. The preclinical data and models did not predict this, and largely because the preclinical data we're looking at and basically the animal models used in the preclinical data were really designed to look at the splicing or rather the editing efficiency. The actual animal model does not actually manifest the phenotype with this IVS 26 mutation inserted into the murine gene. This was not predicted by the preclinical data. I think the key thing was that the study was designed to recruit a diverse group of patients and actually represented with a very good representation of the genetic epidemiology disease. Thank you. Our next question comes from Madhu Kumar at Goldman Sachs. Madhu, you may now unmute and ask your question. Thank you. This is Omari in for Madhu. The first question is, how does the zygosity influence the decision-making framework for future ocular indications? Second, how does EDIT-101 decision affect cash run rate? Thanks very much for the two questions. I think the first question is how does the observation of homozygosity for the IVS26 mutation influence our view of other diseases? It really informs that if you want to go into the specifics, when we look at the 103, we're looking at autosomal dominant allele-driven disease. That should not actually impact that. I think that's, you know, kind of the key answer to you. I think that's the key point to your question. From the point of view of the cash runway, there is clearly a potential saving. We will be sharing, you know, more details, you know, in the coming months. Thank you. Our next question comes from Yanan Zhu at Wells Fargo. Yanan, you may now unmute and ask your question. Thanks. Perhaps two questions. One is on the confidence level that the homozygous patients population is indeed a responding population, given that the pediatric patient only had a three-month follow-up. What's your confidence level that the efficacy you observed could persist in future time points? The other question is, you know, obviously, you know, I'm wondering about this because this response in this population at least demonstrates gene editing could be effective if editing efficiency is sufficient. The second question is on the endpoint. I'm wondering your bar, the bar you set, BCVA plus at least two out of the three other endpoints. Is that decision made with input from regulators? For example, you know, could you choose the quality of life as the primary, which seems like there are more responding patients or BCVA with only one other endpoint? How did you come to this conclusion and whether that applies to other ocular programs? Yeah, thank you. Thanks for, you know, your question. With regard to our confidence, we actually are confident that the homozygosity for IVS26 is a predictor and would be a good predictor for pre-selecting patients with a high probability of clinical response. We're not saying it's 100%, but we're actually saying that it allows pre-selection of a patient population with a high probability. Why? Well, we have two out of two, 100% of the homozygous patients treated versus one out of 12 for the compound heterozygous. That actually represents two-thirds of the responders we saw. You're correct. We have three months of follow-up for the homozygous pediatric patients. I think, you know, the durability question, obviously, it remains, and we would continue to follow that patient and treat the patient. However, because the target is one of editing, we see this as a permanent and durable. It's not like expressing a transgene. This is a permanent, what's the word we're looking for, edit that we see. I think that really is why we are confident of what we're observing here. With regard to the rigor of the definition of a responder, this is where, you know, Baisong and myself bring our experience and track record of bringing medicine through approval and to market. Our desire to ensure that we move medicines forward that have not only a high probability of technical success, but also a high degree and level of probability of regulatory and commercial success. The high bar actually felt very reasonable considering the novelty of the therapy and our desire to be absolutely sure that we can pre-select and predict benefits going forward. We did not discuss that specifically with regulators but believe that the bar here should be high. From the point of view, the quality of life is a primary outcome. I'm pleased that you call that out because, you know, this we felt was certainly compelling data for supporting the observations that we made across the other three endpoints. I think it is important to say that to date, the regulators, you know, for ophthalmology have not approved based on a quality of life or patient-reported outcome as a primary. I think it's a strong supportive, and that'll be a matter of certainly debate and discussion or negotiation with regulators. We believe that using this rigorous threshold for defining a responder leaves no doubt about the fact of the observation and our conclusion that we've seen proof of concept of clinically meaningful editing. Right. Thank you. A few more. The last bit of the question on whether other ocular programs will adopt a similar bar. We would actually be applying a similar bar. What I would say is that, you know, it's important to consider that in the context of Usher syndrome, our preclinical 103 program, it's a different mechanism of disease, and the patient population is different. Also the efficacy or the efficiency of editing is higher. Great. Thanks for taking the question. Our next question comes from Mani Foroohar at SVB. You may now unmute and ask your question. Taking the question, I guess a broader one, since a lot of the previous analysts have dug into the nuances of this program. You talked a little about how you think about market opportunity, how you think about a threshold for appropriately sized market. I guess I'll start with a two-parter, the first part being, even if the response had not been larger than this to the homozygous patients, what was your original rationale why this market was large enough to be viable in pursuing whole hog, not even limited to homozygous? Secondarily, just I wanna understand your philosophy on market opportunity. Sickle cell, beta thalassemia, etc., other applications of your technology, how do you think about market opportunity in a world where you guys are just six, seven, etc., to market? I have a quick follow-up. Yeah. Thanks very much, Mike, for your question. I think there were two parts to the question. One was, how are we thinking or how did we come to determine that the LCA10 population will be commercially viable? I think there are a couple of points to make. First of all, the LCA10 population and specifically the IVS26 allele subpopulation comprises approximately 1,500 patients with relatively good ascertainment. I think the original rationale was that that was actually a reasonable population, a commercially viable type patient population. Nevertheless, when we actually look at the data and find that in fact the IVS26 homozygous are the ones or the patient population or segment in whom we can with confidence pre-select, that patient population is obviously substantially reduced. That obviously was something that will have to be determined by the phase I study, which was designed to do precisely that, which is to say, what is the size and nature of the patient population that is most likely to respond to this therapy? With regard to overall view of market opportunity and most importantly, the competitive intensity of the space, you know, I think first thing I do is challenge the characterization that our sickle cell EDIT-301 program is 50 or six. It is not. It is much higher up than that. We're obviously looking forward to sharing data about that next month. I think it's also worth pointing out that, you know, what we would hope to share will be that we have a competitive product with the long-term potential for differentiation. In addition, I think it's important to point out that the patient population is actually substantially larger than that in the LCA10 IVS26 homozygous patient population on the orders of tens of thousands. We believe that when we come to market with our EDIT-301 product, the vast majority of the present patient population will not have been yet treated, owing to the challenges of developing that managed care, negotiations, etc. More importantly, as you talk beyond the 301 product and our entire pipeline, I previously shared that, you know, determining what is a commercially viable or attractive patient population comprises an analysis of multiple factors. I outlined a few, including the size of the population, ascertainment, the complexity of the therapy, the unmet need, and as you quite rightly say, obviously competitive intensity is a factor going forward. Great. As a broader follow-up, as you move forward, obviously, like all management teams, you have fiduciary responsibilities to your shareholders, etc. You have to be open-minded about strategic positioning. What data set would you need to see from sickle or beta thalassemia to pursue a restructuring and wind down, pursue a reverse merger strategy? Is your plan to run straight forward as long as you have the capital to pursue it? Well, what I will say is that I don't think I can give a specific answer to that question. I think what I can say is that since my arrival mid-year, I've been working with the executive team to talk about and evaluate our portfolio and strategy. In fact, I feel even more confident in our ability to bring the science to the clinic based on the data we presented today. I look forward to sharing more data again this quarter. Essentially, Editas now will be sharing clinical data from two different programs within its pipeline. I also feel confident that our cash runway is in a very good position for us to move forward with our 301 program as well as our pipeline. I look forward to sharing more details with you in the coming months. Okay. We'll look forward to that. Thanks for taking the question, guys. Thank you very much. Our last question comes from Lisa Walter at RBC. Lisa, you may unmute and ask your question. Hi. Thanks for taking our questions. Can you hear me? Yes, Lisa. Thank you. Perfect. Thank you. Two questions for you. Just wondering, since EDIT-101, you know, you commented that it did have a favorable safety profile with no dose-limiting toxicities, I was wondering if increasing the dose further was a possibility to see if there would potentially be a better response among the heterozygous patients. Second, on the Usher program, you know, given this program has a similar mechanism of action to LCA10 as an exon-splicing approach, how should we think about this program after the results today? Thank you. Yeah. Thanks very much, Lisa, for your question. With regard to the potential for increasing the dose, I think the interesting thing is that we did actually show across the range of low, mid, and high dose a good safety, tolerability profile. One of the limitations to increasing the dose, it sits with a dose at plateau observation, and obviously, one has to be careful about the total dose of AAV delivered to the retina. Right now we are not considering an increase in dose. With regard to your Usher or USH2A, sorry, we actually have been looking at pre-clinically developing enhanced or improved editing efficiency over that seen with 101. Great. Thank you for taking our questions. This concludes the Q&A portion of the webinar. I'd now like to turn the call over back to Gilmore for closing remarks. Thank you all for joining this morning's webinar. Before signing off, I would like to remind you that we will be sharing 301 data update next month and look forward to sharing that with you and spending time with you. Very importantly, I want to thank all the patients, clinical investigators, clinical sites and Editas' employees and researchers for the work in the ENLIGHTEN and BRILLIANCE studies that have actually brought us to, you know, a clear proof of concept and forward planning. With that, I'd like to thank you all, and good morning.