Good morning, and welcome to Editas Medicine’s Third Quarter 2021 Conference Call. All participants are now in a listen-only mode. There will be a question-and-answer session at the end of this call. Please be advised this call is being recorded at the Company's request. I would now like to turn the call over to Ron Moldaver, Investor Relations at Editas Medicine.

Thank you, Melissa. Good morning, everyone, and welcome to our third quarter 2021 conference call. Earlier this morning, we issued a press release providing our financial results and recent corporate updates. A replay of today's call will be available on the Investors section of our website, approximately 2 hours after its completion. After our prepared remarks, we will open the call for Q&A. As a reminder, various remarks that we make during this call 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 and 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. Now, I will turn the call over to our Chief Executive Officer, Jim Mullen.

Thanks, Ron, and good morning, everyone. I am joined today by several members of the Editas executive team, including Mark Shearman, our Chief Scientific Officer; Lisa Michaels, our Chief Medical Officer; and Michelle Robertson, our Chief Financial Officer. I want to start off by providing some highlights from the third quarter, including some important milestones for Editas. In our first-ever clinical data readout, we announced positive initial data from our ongoing Phase 1/2 BRILLANCE trial of EDIT-101 for the treatment of LCA10, including clinical evidence of gene editing and potential early clinical benefit. We are dosing patients in the adult high-dose cohort and enrolling patients in the first of two pediatric cohorts of that trial. The RUBY study of EDIT-301 for sickle cell diseases is enrolling patients and we expect to begin dosing in the first half of 2022. The pre-IND work for EDIT-301 in transfusion-dependent beta thalassemia is progressing and we remain on track to file the IND before year-end. In our cell therapy platform, Bristol-Myers Squibb opted into a fourth alpha-beta T-cell program this quarter, further advancing our successful collaboration. We presented data on our SLEEK technology platform demonstrating high efficiency multi-transgene knock-in across multiple cell types, which we believe can enable improved CAR-T and CAR-NK cell therapies for solid tumors. At the upcoming SITC and ASH Conferences, we will present data showing improved tumor-killing ability through multiplex gene editing using SLEEK and our iNK program. Finally, we have appointed Emma Reeve and Bernadette Connaughton to our Board of Directors. Both Emma and Bernadette are highly accomplished biopharma executives and we look forward to their contributions to Editas. This quarter showcased a critical advancement for our clinical programs. The initial safety and efficacy data for the BRILLIANCE trial was an important milestone for patients with LCA10 and marked a key step in Editas' mission of providing life-changing gene editing medicines to patients. These early data provide proof-of-concept for our in vivo gene editing platform and help strengthen our foundational technology with the clinical evidence to progress our broader pipelines. We made excellent progress this year with our programs and platform technologies and will continue an aggressive pace to deliver against our long-term objectives. With that, let me turn the call over to Lisa to review our clinical programs.

Thank you, Jim. I'll start with a recap of our recent data for the BRILLIANCE trial for EDIT-101 for the treatment of LCA10. To give some quick background, CEP290 associated retinal degeneration or LCA10 is a rare inherited disorder affecting about three out of every 100,000 children. It’s autosomal recessive, which means that to be impactful, the person has to inherit two copies of the defective gene, one from each parent. If you can repair at least one of these copies, you can potentially treat the disease. Despite being rare, it is the most common cause of early onset inherited retinal degeneration. The loss of vision is caused by early loss of photoreceptors in the eye. Patients are usually diagnosed during infancy and early childhood, with the majority of vision loss occurring in the first decade. However, even in adults, there remains a small area of preserved anatomy in the central part of the retina. This provides the opportunity for gene correction. When Editas first started the EDIT-101 program, it was the first time that any company had attempted gene editing in the human body. The BRILLANCE trial was designed primarily as a safety study, with the purpose of identifying the highest tolerated dose for subsequent study. At September's Retinal Degeneration Symposium, we shared safety data on two patients treated at the first and lowest dose cohorts, and four patients treated in the middle dose cohort as of the data cutoff date in August 4th. All observed adverse events were mild to moderate, and the majority of these reported events were directly attributable to the surgical procedure. Importantly, no detectable immune responses against the Cas enzyme were observed. This is great news, and the results are comparable for the two dose cohorts. Our non-clinical data suggests that we expect a greater number of photoreceptors to be effectively edited at each consecutive dose level. The safety observed has allowed us confidence to start treatment subjects in the highest planned dose cohort and to start enrolling the pediatric dose cohort with the middle-dose pediatric cohort. We expect that EDIT-101 will have a differentiated safety profile, as it is administered as a single one-time injection directly to the part of the retina where the photoreceptors are preserved. This targeted approach treats only those cells, thereby limiting any potential effects on the structures of the eye. Although the primary endpoint of the study is safety, there are multiple exploratory endpoints focused on efficacy. Preliminary findings were presented for the five patients who had at least three months follow-up after treatment. This included two patients in the low-dose cohort and three in the mid-dose cohort. The three-month mark was selected as the earliest time point where we might expect to pick up some sign of editing for several reasons. Based on the injection procedure, there needs to be time for the retina to heal and for maximal editing to occur. Additionally, it takes time for the dysfunctional CEP290 protein to be replaced by newly-generated functional protein. Three months is really when the clock starts, and it may take longer for the brain to respond to the new signals. One of the challenges of treating an ocular disease is that we don't have a direct way of measuring how much of the normal CEP290 protein is being made in the eye or a direct way to determine how many cells were edited. Therefore, we're dependent on surrogate measures of efficacy, such as full-field light sensitivity threshold testing, best-corrected visual acuity, and improvement in an individual's ability to navigate standardized navigation courses with varying levels of difficulty. At least one positive change in any of these procedures suggests that a biological effect has occurred on how the treated photoreceptors in the eye register light. For this reason, we were very pleased to document meaningful changes from baseline in one or more measures in two mid-dose subjects, in whom we have the longest follow-up. The changes indicate biological activity. Most excitingly, in at least one subject in the mid-dose cohort, there is a clinically meaningful change in best-corrected visual acuity and a real change in her ability to maneuver through obstacles at different levels of light. These are approvable clinical endpoints. As for the other patients treated in the mid-dose cohort, it may have been too early to draw conclusions, which is why we continue to follow them. In the meantime, we are eager to see whether the study can produce similar or stronger responses in the subjects who are now being treated in the high-dose group. We've been very pleased with the safety we have observed so far and the initial signals that effective editing has occurred. This is illustrated by clinically meaningful changes in the mid-dose cohort and in those subjects with the longest follow-up. Consequently, the BRILLIANCE study is moving forward. We continue to progress the adult high-dose and the pediatric mid-dose cohorts, and expect to complete dosing of these two cohorts in the first half of next year. Now, turning to our ex vivo programs, specifically EDIT-301 for sickle cell disease and transfusion-dependent beta thalassemia. We believe that EDIT-301 has the potential to be a leading gene editing medicine based on its highly efficient editing and specificity, which we expect to result in optimized safety and efficacy. By demonstrating robust and sustained fetal hemoglobin expression, with both short and long-term safety, we aim to have a differentiated medicine to treat sickle cell disease and beta-thalassemia that will hopefully lead to longer lifespans and better quality of life for these patients. Currently, we are enrolling patients in the RUBY study for the treatment of sickle cell disease. In this program, we are using our engineered Cas12a enzyme to target a region in the beta globin locus. We believe this to be a potentially safer target for gene editing because several different mutations or polymorphisms that are not associated with human disease occur at this site. More specifically, the Editas approach mimics naturally occurring mutations associated with a condition called hereditary persistence of fetal hemoglobin, which we know prevents sickle cell disease. We've demonstrated excellent pre-clinical data that support the benefits of editing the beta globin locus and our Cas12a enzyme, and we're also very excited to be advancing that program to the clinic. As mentioned, patient screening and enrollment is moving forward for EDIT-301 in sickle cell disease. We have patients who are currently undergoing cell harvesting cycles as a requisite to editing their own stem cells, and we look forward to dosing the first patient in the first half of next year. On EDIT-301 for transfusion-dependent beta-thalassemia, we will be presenting data at the American Society of Hematology Conference next month. Preclinical data will demonstrate that edited CD34 cells showed significant improvement in erythroid maturation and health, along with increased total hemoglobin content. This reinforces our belief that our therapeutic strategy has great potential for beta-thalassemia in addition to sickle cell disease. We remain on track to file our investigational new drug application for EDIT-301 with beta-thalassemia by year-end. And with that, I'd like to turn things over to Mark to run through our pipeline and our gene editing technology.

Thank you, Lisa. I'll start off with an important advance in our editing platform that we call SLEEK, which we presented at the Cold Spring Harbor Conference in August. We are really excited about this proprietary technology. SLEEK is short for Selection by Essential-gene Exon Knock-in. It's a technology that was developed at Editas utilizing the AsCas12a nuclease to selectively and at high-efficiency integrate transgenes into a specific locus. Essentially, the technique allows us to achieve high-efficiency knock-in with a variety of different cell types while also installing robust transgene expression. We've published data on iPSCs, T-cells, and NK cells, and believe the knock-in rates are the highest in the gene editing field across these cell types. In addition to the high editing efficiency from AsCas12a, we utilize a selection process where only those cells that have been successfully edited survive. The rates of transgene expression in the final cell population are extremely high. Furthermore, we can fine-tune expression levels of transgenes by knocking in at different essential genes, which could be an important attribute of next-generation cell therapy medicines. We think this is a really powerful technology that is far superior to other modes of integration that we've seen published. We've deployed this in our iNK program, as well as in our collaboration on the alpha-beta T-cell program with Bristol Myers Squibb. It's something that we've been working on for some time that can open up a lot of possibilities for more effective and safer cell therapy. Also related to our platform, we recently presented at the TIDES Oligonucleotides and Peptide Therapeutics Conference about the advantages of our AsCas12a nuclease. Additionally, we described some of our process and analytical chemistry capabilities for guide RNA synthesis. With the completion of our Boulder, Colorado GMP manufacturing facility, we remain confident that our in-house guide RNA development will translate into high fidelity and quality manufacturing for our next-generation enzyme. Our iPSC program utilizes both the AsCas12a nuclease and SLEEK technology. One important goal is to customize an iNK cell that addresses some of the current limitations of this class of therapy, specifically around persistence. We're using a combination of knockout and knock-in technologies to introduce a series of edits. For example, we've knocked-out TGF-beta receptor 2 to overcome resistance and enhance persistence. At the upcoming conferences, we'll be presenting additional data indicating some of our knockout strategies. We're building on the various strengths we have to produce a customized iNK cell that we believe will be superior across multiple tumor cell killing mechanisms, as well as persistence and potentially also targeting, which reinforces our view that it's an exciting allogeneic approach for a potential wide range of solid tumors. On the knockout side, at the upcoming conference, we will present data demonstrating that using SLEEK to knock-in genes for CD16 expression greatly improved tumor killing, thereby enhancing antibody-dependent cell-mediated cytotoxicity via iNK cells. This is important data as it provides evidence for the potential of our iNK program as it advances towards the clinic. At ASH, we'll also demonstrate that a double knockout in iNK cells at both SHIP and TGF-beta receptor-2 promotes high levels of cytotoxicity and enhanced in vivo tumor killing in preclinical models compared to unedited iNK cells. Furthermore, we'll show that cryopreservation of these iNK cells had no impact on their tumor-killing ability, which is an important property for eventual off-the-shelf cell-based medicines. We also believe this to be a much safer approach to developing next-generation cell therapies because through our iPSC clone selection process, we specifically avoid potential cell abnormalities. After gene editing iPSCs, we screen and select single clones that are fully characterized, including detailed sequencing and cytogenetic analysis. By doing this, we eliminate clones with chromosomal abnormalities. The selected engineered clones only contain the desired allelic edit, ensuring a pure final population of iPSCs. These clones have highly characterized genomes, allowing us to create a massive cell bank that is stable and infinitely renewable, from which we differentiate the edited iPSCs into edited iNK cells. The iNK cells will be fully characterized and analyzed with a well-developed analytical asset panel to confirm their genomic profile. This process and the preclinical data we've observed may address some critical barriers to allogeneic NK cell therapy for solid tumors. We are eager to move this program towards the clinic. Lastly, in our partner cell therapy program, we're excited that Bristol Myers Squibb has opted into a fourth Alpha Beta T-cell Program as part of our ongoing collaboration. Over the last year, one of these programs has progressed to the development candidate phase. This has been a very productive collaboration and we look forward to future programs. With that, I'd like to turn it over to Michelle to review our financial results.

Thank you, Mark, and good morning, everyone. I'd like to refer you to our press release issued earlier today for a summary of our financial results for the third quarter. I'll take this opportunity to briefly review a few items. Revenue for the first 9 months of this year is $13.1 million, compared to $79 million for the same period last year. During 2020, we recognized $71 million in revenue in connection with our agreement with Allergan, $63 million of which was earned during the third quarter of 2020 as a result of recognizing the remaining deferred revenue balance associated with this agreement when we regained control of our ocular program last summer. Comparing the first 9 months of this year to last year, total operating expenses increased by approximately $60 million. This is related to an increase in stock-based compensation of $18 million, $9 million in success payments due under certain of our institutional licenses, as well as an increase in expenses to support our clinical programs. These increases were offset by a $3.4 million tax credit reported as a gain in operating expense during the period and a decrease of $9.5 million in profit R&D that was reported in 2020 in connection with the Allergan transaction, and 2020 license expenses that did not recur in 2021. Comparing the third quarter of 2021 with the same period last year, total operating expenses decreased by approximately $8 million. This was primarily related to expenses recorded in 2020 in connection with the Allergan transaction that totaled approximately $9 million, as well as expenses that were incurred in 2020 in connection with in-licensing agreements. During the third quarter of 2021, the Company had an increase of $4 million in stock-based compensation compared to the same period last year, which was fully offset by decreases in legal patent fees and the tax credit reported as a gain in operating expense during the quarter. Editas continues to maintain a strong balance sheet and cash position, which as of September 30th, totaled $657 million compared to $698 million at the end of Q2. This capital will allow us to continue progress on our clinical programs and further develop our pipeline, as well as our internal manufacturing capabilities. We anticipate that this current cash position will fund our operations well into 2023. With that, I will hand it back to Jim.

Thank you, Michelle. This has been a strong quarter for Editas. We presented the first clinical data for the Company validating our in vivo gene editing platform. We made substantial progress in our other pipeline programs, moving them towards the clinic. We've made fundamental advances in our platform technologies, including our best-in-class engineered AsCas12a enzyme and our innovative SLEEK platform to deliver what we believe to be unprecedented gene editing knock-in rates. We built our manufacturing capabilities to support our multiple clinical programs, brought together a world-class leadership team that is capable of executing on the tremendous opportunities we have for our technological platform, and we have the financial resources to deliver on these opportunities. I believe there's never been a better opportunity to deliver innovative new genomic medicines to patients. That is at the heart of everything we do and what motivates us to push forward on our programs and technological innovation. We thank you all for your interest and support. With that, we'll open it up to questions and answers.

Thank you. We will now begin the question-and-answer session. Our first question comes from Cory Kasimov with JPMorgan. Please go ahead with your question.

Great. Hey, good morning. This is Thomas on for Cory. Thanks for taking the question. I guess maybe just on EDIT-101, can you talk about how we should be thinking about the cadence of potential updates from here, including longer-term follow-up from the adult low and mid-dose cohorts and then also data from the new cohorts? I'm curious specifically if you can comment on what kind of duration of follow-up you'll be looking for to share these data updates. Thank you.

I’m going to keep it fairly short and to the point. One of the important things for us this year in terms of being able to share data was the fact that it had been such a long period of time from when the study had started, and we felt it was important for us to be able to communicate and update on the trial. We were very happy with the safety that we observed, as well as the clinical signs suggesting that editing had occurred. In terms of our next planned update, that's going to be primarily data-driven. The trial is continuing to enroll participants in the pediatric and high-dose adult cohorts. The timing of delivery will be based on our ability to provide longer-term safety data on the mid-dose cohort, as well as some preliminary efficacy data in the high-dose cohort, at which point we'd like to have at least three months of data on all the patients in that cohort before we move forward.

Okay. Thank you.

Thank you. Our next question comes from the line of Joon Lee with Truist Securities. Please proceed with your question.

Hi. Good morning. This is Mehdi for Joon. My question is related to EDIT-301. Specifically, we want to know what kind of specific experiments you do to define the inversion or deletion rate in the locus and if you have compared that to the same rates if you would have done that with Cas9 enzyme. Thank you.

Yeah. I'll take that. We did a lot of experimental work preclinically to define the on-target edit. This included extensive sequencing. We had known ahead of time that the activity was pretty much limited to on-target editing as opposed to any off-target editing. Across both normal as well as sickle and CDC cells, the profile was very consistent, which appears to be a property of that combination of the guides in the AsCas12a. We do not have comparable datasets with Cas9 and Cas12a. We've focused on the use of Cas12a, which given what we're trying to achieve with this approach, is to disrupt the binding of BCL11A, which was the most appropriate usage to do that.

Thank you.

Thank you. Our next question comes from the line of Phil Nadeau with Cowen and Company. Please proceed with your question.

Good morning. Thanks for taking our question. I guess, the one on EDIT-101 to start, which patient population do you think is most appropriate for future development in pivotal studies? Would you move forward in both pediatric and adult patients, or would pediatric patients be more appropriate given their disease state?

At this point in time, there's no reason to consider not going forward with both adult and pediatric patients. So far, we are seeing some clinically meaningful endpoints in the adults. In the pediatric patients, we expect to see at least as good a benefit, if not more. I don't see a reason to limit the patient population at this point.

Got it. One follow-up question on chromosomal abnormalities. You mentioned what you do to assay for them in the iPSC program itself. What are you doing in, say, the 301 program? Do you feel like you have to change your release assays given what was seen by another gene editing company recently, or do you feel that your assays would pick it up in all the programs?

I think the short answer is no. We have no intention to change the assays that we've applied to this program. We’ve thoroughly analyzed the changes at the editing site. As we've expressed, we have no evidence of any chromosomal abnormalities created by this editing event.

Perfect. Thanks for taking our questions.

Thank you. Our next question comes from the line of Yanan Zhu with Wells Fargo. Please proceed with your question.

Hi, thanks for taking my questions. First, regarding BRILLIANCE, could you let us know if there's a chance of seeing data by the end of this year? Additionally, concerning the changes in endpoints on OCT as evidence of gene editing, when do you anticipate those changes might be observable? Thank you.

To the first question regarding the timeline for data, the patients are basically seen every three months after they've passed the initial safety evaluations at the very beginning of the trial. This limits the intervals in which we can provide updates. The second question is related to OCT. One of the challenges with these patients, especially very early on, is that they have significant nystagmus, so it’s very difficult for their eyes to remain still enough for the OCT imaging. To measure those changes, you need achievable landmarks in the eye for comparison. We are following OCT in these patients as best as we’re technically able to do so.

Got it. Follow-up on the iNK program. Do you think in the first iteration of the candidate, would you implement some kind of IL-15 receptor ligand engineering for persistence? Thank you.

That would be a logical approach based on the track that others have taken. I think you'll have to wait for the details, which we will present at the ASH conference.

Great. Thank you.

Thank you. Our next question comes from the line of Dae Gon Ha with Stifel. Please proceed with your question.

Hi. Good morning. Thanks for taking my questions. First question is for Mark. Regarding BRILLIANCE, with the pediatric group going into the mid-dose and potentially higher, I wanted to get your take on one of the gene therapy companies that recently reported that they tested the same dose in adults which was safe, but did see some inflammation in pediatric patients after about a month. Can you talk to the AV safety as it pertains to pediatrics using the same dose? I know it's immune-privileged, but any thoughts on that? I've got a follow-up.

Right now, it's too soon to determine if the finding you're referencing will be recapitulated across other gene therapy programs. We're focused on continuing enrollment, particularly in the adult high-dose, as well as initiating the pediatric dose in a very careful step-wise manner and will track the tolerability of the vector in this patient population. That's all I can say right now.

Great, thanks for that. The second question is about EDIT-301 with RUBY. One of your colleagues here in Cambridge just announced this morning that they cleared the IND for a competing program also targeting HBG1 and 2, promotor region. Can you talk about how you plan to adjust your strategy on the protocol side to possibly accelerate patient enrollment as well as get treatment going in the first half of the year as opposed to the latter half?

We cannot necessarily accelerate because the treatment of the first patient is safety-driven, and we need to show that they have had meaningful engraftment from the treatment. However, we do have multiple patients in the pipeline with the goal that once we achieve that safety mark, we want to start enrolling ongoing patients much more rapidly.

Okay. Great. Thanks for taking our questions.

Thank you. Our next question comes from the line of Jay Olson with Oppenheimer. Please proceed with your question.

Thank you for the update. Can you talk about the timeline and factors gating EDIT-102 to enter the clinic and anything that you've learned from EDIT-101 that can be applied to that program?

We haven't given any specific guidance on EDIT-102 other than that we are continuing to iterate and improve upon the editing efficiency for that program, and our intention is to present the results of those improvements at scientific conferences in the coming years.

Okay, thank you. As a follow-up for EDIT-301 in sickle cell disease, I think you mentioned the target enrollment is 40 patients. How long do you think it will take to enroll 40 patients? Also, do you know how long you’ll need to follow those patients before filing?

Essentially, this is a well-trodden path. What we're doing is not necessarily different than what our competitors have done in the same space. But in general, the primary goal of getting to these patients is first to demonstrate a graftment. As I've already mentioned, the plan is to be able to start moving more patients in tandem and in parallel moving forward. At the moment, we're not having any issues related to enrollment. It's actually quite strong.

Great. Thanks for taking the questions.

Thank you. Our next question comes from the line of Luca Issi with RBC Capital Markets. Please proceed with your question.

Thanks so much for taking my questions. Congrats on the progress. I have two questions: one on BRILLIANCE and one on strategy, a little bit bigger picture. So maybe in BRILLIANCE, I think the data at the Retinal Degeneration meeting showed serum antibodies against AAV-5 at the 10th to the 4th and 10th to the 5th levels. I'm wondering if you can expand a bit more on what gives you confidence that such levels are low enough, and do not prevent you from either redosing or dosing the fellow eye. Then maybe a bigger strategy question. We've seen one of your competitors breaking up the company, spinning off the oncology pipeline into a new company and focusing on rare genetic diseases. I’m wondering what your take is on that decision and if it's something you're contemplating.

Regarding antibodies, certainly the levels we've seen do not give us any concern about, one, correlation with any immune response and, two, there is no issue with potential redosing in the same manner or even dosing at the follow-up eye. That's based on a very extensive non-human primate series of studies that were published. We're not concerned about that profile.

On the other point, we already have a productive collaboration going, which is gaining momentum with BMS on the oncology side. As I have said previously, we’ve been fairly public about it. On the iNK program, we’re certainly going to entertain another collaboration or an expansion of the collaboration we currently have, so I do think it's an area where a collaboration with an established oncology player is important for success. We will continue to pursue that.

Got it. Thanks so much.

I want to correct something I said earlier. The IL-15 data is actually going to be at SITC, not ASH, so you don't have to wait until December.

Thank you. Our next question comes from the line of Joel Beatty with Baird. Please proceed with your question.

Hi. Thanks for taking the question. For the alpha-beta T cell program partnered with BMS, could you discuss what they based their decision on to opt into the fourth program? Also, could you discuss the timelines for those programs in general for advancing in development?

They looked at good data. We're not at liberty to disclose the details of the programs with them. We don’t have complete visibility into those timelines or the decision-making around those programs.

Okay. Thank you.

Our next question comes from the line of Gena Wang with Barclays. Please proceed with your question.

Thank you for taking my question. I have a couple of parts regarding translocation. First, I'm wondering if you can remind us of the translocation or chromosomal abnormality of age through EDIT-101. And the second, we do have a few approaches with multiplexing, and I know that that will lead to some translocation. Just wondering what is the process in place to monitor translocation and what will be the cutoff for the drug product in terms of product release?

The processes we have in place are extensive; this includes multiple different approaches to sequencing at the intended edited sites to determine the profile of the edits, which includes indels, deletions, reversions, and transactions, among others. The rate of those we determined preclinically is very low, a fraction of a percent. We have not seen anything in the in vitro toxicity essays or in vivo models to indicate any potential latency or cell abnormality to date. As I mentioned for the iNK program, with the interest in reported stem cell editing, we select a single-cell clone which has the exact edits that we want across multiple different constructs; we will only progress a clone that has those and nothing else.

Thank you. Our next question comes from the line of Rick Bienkowski with SVB Leerink. Please proceed with your question.

Hey, good morning, and congrats on all the progress. Looking forward to the post-conference later this week. I have a follow-up from Dagon's question on the pacing of dosing for EDIT-301. Could you say exactly how long the observational period for safety and efficacy will be after the first patient is dosed in the trial? Are there other mechanisms in the trial protocol that could limit the pace of dosing after that initial observational period is complete?

In alignment with regulatory guidance, the first patient needs to engraft. That can happen within 6 weeks to 3 months depending upon the course of events, as well as the second patient showing reproducibility of the process. After that, we have the ability to start enrolling more patients in parallel.

Great. Is there anything else put into the trial protocol after that initial period that could limit dosing?

As soon as we've established reproducibility of the process and the patient's ability to recover and show that they have meaningful endpoints, we proceed.

Great. Thanks for taking our questions.

Thank you. Our next question comes from the line of Madhu Kumar with Goldman Sachs. Please proceed with your question.

Thanks for taking my question. Thinking about the high-dose EDIT-101 data and BRILLIANCE, what do you think you need to see in terms of the kind of visual function endpoints compared to what you've seen so far in the lower-mid-dose that would get you really excited for pursuing the high-dose into a registrational trial?

I'm already excited because we had really great outcomes in one of our patients who is in the mid-dose cohort. She's the one with the longest follow-up at the moment. Her improvements seem to get better with each subsequent follow-up. It's too early to make any real conclusions regarding efficacy in the mid-dose cohort, and that will depend upon continued follow-up with patients in that group. We expect there to be enhanced effectiveness with each additional concentration applied over the area of the phobia. Therefore, as long as everything remains safe, as it has so far, we expect to see meaningful changes from the mid-dose cohort. We are actually excited about our potential product.

Okay. So, just to clarify, if the high-dose profile shows an efficacy profile similar to the mid-dose cohort, that would be sufficient for you to pursue that into registrational development?

Certainly, that's the goal.

Thank you. This concludes our Q&A session and thus concludes our call today. We thank you for your interest and participation. You may now disconnect your lines. Goodbye.