Good morning. Welcome to Editas Medicine's fourth quarter and full year 2022 conference call. All participants are now in listen-only mode. There will be a question and answer session at the end of this call. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Cristi Barnett, investor relations for Editas Medicine. Thank you, Sherry. Good morning, everyone, and welcome to our fourth quarter and full year 2022 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 two 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, 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. Now, I will turn the call over to our CEO, Gilmore O'Neill. Thank you, Ron, and good morning, everyone. I am joined today by two other members of the Editas executive team, Baisong Mei, our Chief Medical Officer, and Michelle Robertson, our Chief Financial Officer. Last year was a landmark year in Editas Medicine's history as our team demonstrated two clinical proof of concepts in patients using both in vivo and ex vivo therapeutic approaches. In November, we announced data demonstrating human proof of concept for our in vivo EDIT-101 AAV-delivered Cas9 therapy for LCA-10, an inherited retinal disease. However, due to the limited addressable population, we made the tough decision to pause patient enrollment in our BRILLIANCE trial. In December, we shared very encouraging initial data from the RUBY phase 1/2 clinical study of our ex vivo autologous EDIT-301 therapy in severe sickle cell disease. The readout provided human proof of concept, demonstrating that EDIT-301 could safely drive expression of fetal hemoglobin to clinically meaningful levels and correct anemia in sickle cell disease patients. The study continues to progress. As we move into 2023, we will build on these successes as we continue to drive towards our goal of delivering life-saving medicines to patients with previously untreatable or undertreated diseases. As many of you know, last month, we shared our strategy to position Editas as a leader in in vivo programmable gene editing. There are three underlying pillars of our strategy, which I will recap here. First, we have sharpened our discovery focus to in vivo administered genome editing medicines while continuing to develop EDIT-301 for severe sickle cell disease and transfusion-dependent beta- thalassemia, or TDT. We continue to support our partnered cell therapy programs but are no longer discovering or developing standalone cell therapies, and we have divested our iNK cell franchise to Shoreline Biosciences last month. Additionally, we terminated our AAV IRD program or platform and are seeking to divest those assets. Our sharpened discovery focus allowed us to concentrate our talent, which reduced our headcount by approximately 20% and extended our cash runway into 2025. Turning to our second strategic pillar, we are strengthening our discovery engine and technological capabilities. We have split our research division into separate technology and drug discovery groups, enhancing the capabilities of each. Under our new target selection criteria, we will select therapeutic targets that will allow our genome editing approach to differentiate maximally from the current standard of care for serious diseases. Our goal here is to build a robust pipeline of assets that maximize the probability of technical, regulatory, and commercial success. Our new technology group, under the leadership of Chief Technology Officer Bruce Eaton, will focus on targeted delivery and enhancing our gene editing toolbox to enable targeted gene repair. Furthering innovation in our technology platform is a key component to achieving our goals via both internal clinical execution and external business development. Bruce is a biotech veteran who, in addition to his new role, will continue as Chief Business Officer to spearhead our PD objectives. Within our drug discovery group, we have begun lead discovery work on in vivo therapeutic targets in hematopoietic stem cell, or HSCs, and other tissues. Our search for a new CSO who will head up our drug discovery group continues to progress, and I look forward to updating you on this search and our in vivo work in the future. Finally, our third strategic pillar is an increased and expanded approach to business development. Going forward, we will pursue the right combination of gene editing and targeted delivery tools through internal development and the in-licensing of complementary technologies in order to expedite our drug discovery and clinical execution objectives. In tandem, we will continue to leverage our IP portfolio to drive potential out-licensing and partnership discussions. Moving to our development plans under the new strategy, as we shared last month, we are pursuing a leadership position in HSC therapeutics for hemoglobinopathies by taking three actions. First, we have reallocated investment resources to accelerate the clinical development of EDIT-301 for the treatment of sickle cell and beta thalassemia. The positive initial data from our RUBY phase 1/2 clinical study was a key driver of our decision to invest more heavily into EDIT-301. Second, and third, by leveraging our unique and differentiated approach of 301, we are investing to develop milder forms of patient preconditioning, as well as develop an in vivo approach for editing hematopoietic stem cells, or HSCs, both of which should reduce the burden and improve the journey for patients who currently live with sickle cell diseases and TDT. Beyond hemoglobinopathies, our discovery and development efforts will be focused on in vivo administered genome editing medicines in other tissues. Turning to the clinic. Since we shared our strategy update last month, we have completed review of the safety data from the Sentinel patients of the RUBY trial for sickle cell disease and have begun parallel dosing of additional patients. We remain on track to provide an update on the RUBY clinical data mid-year and dose 20 total patients by year-end, an ambitious but certainly attainable goal. On EDIT-301 for TDT, we remain on track to dose the first patient in our EdiTHAL phase 1/2 trial this quarter and provide an update from this trial by year-end. Taking a step back, I am confident in our strategy and we remain keenly focused on execution. We are building upon the momentum from our clinical readout milestones during the fourth quarter and our recently announced deal with Shoreline. We look forward to updating you on our progress and execution of our new strategy throughout the year. I will turn the call over to Bais ong, our Chief Medical Officer. Thank you, Guillermo. Good morning, everyone. As Guillermo mentioned, last December, we presented initial data from the RUBY trial of EDIT-301 for the first two patients with the severe sickle cell disease. That data for the first patient who had five months of follow-up showed clinically significant improvement across all hematological parameters. These preliminary data suggest that Editas has a product candidate that can potentially give robust clinical benefit to patients with severe sickle cell disease and has the potential for clinical differentiation in the long term. Specifically, that patient had increased fetal hemoglobin fraction of 45.4% five months after EDIT-301 infusion, above the 30% fetal hemoglobin threshold where sickle cell patients may have no symptoms. We were also pleased to see that the patient's total hemoglobin increased by more than 4 gram per deciliter to 16.4 gram per deciliter, well into the normal range of male patients. Finally, the distribution of fetal hemoglobin was highly pancellular, with 96% F-cells. The mean corpuscular fetal hemoglobin, or the fetal hemoglobin concentration per red blood cells, increased to 13.8 picogram per red cells, exceeding 10 picogram threshold considered clinically meaningful, as empirical evidence indicates those level will prevent that red blood cell from sickling. As we have previously highlighted, EDIT-301 utilize a unique mechanism of action that edits the promoter sequence of the gamma-globin genes to disrupt binding of BCL11A suppressor, mimicking the natural mechanism of hereditary persistence of fetal hemoglobin. The editing is done by a high-fidelity, highly specific engineered AsCas12a enzyme. In turn, this provides a high, sustained level of fetal hemoglobin in a manner that can be independent of erythropoietic stress, resulting in reduced sickling and the vaso-occlusive events in sickle cell patients, and resolving anemia and transfusion dependence in beta thalassemia patients. Since launching the initial data, we have completed our safety review of Sentinel patients from the RUBY trial for sickle cell disease. We're pleased to share that we continue to see a favorable safety profile. After completing sequential dosing of the first two patients, we have commenced parallel patient dosing, meaning that we can now dosing multiple patients simultaneously. We remain on track to dose 20 total sickle cell patients by year-end. Our initial clinical data were very encouraging, consistent with preclinical data. We're confident we'll see replication of similar results in subsequent patients. We have said before that sickle cell disease is characterized by more than just vessel occlusive events. It can result in other severe symptoms such as anemia, fatigue, hemolysis, stroke, and other organ damage. As we continue to monitor patients over time, we see potential for differentiation via longer-term improvement in symptoms and more durable treatment. Since joining Editas last year, I and the rest of management team has been focused on sharpening our clinical execution. We are very pleased with the momentum of EDIT-301 in both the RUBY and EdiTHAL studies. Look forward to updating you as those trials progress. I will turn the call over to Michelle, our Chief Financial Officer, to review our financials. Thank you, Baisong, 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 fourth quarter and full year 2022. I'll take this opportunity to briefly review a few items. Our cash equivalents, and marketable securities as of December 31st were $437 million compared to $620 million as of December 31st, 2021. We expect our existing cash equivalents, and marketable securities to fund our operating expenses and capital investments into 2025. Revenue for 2022 was approximately $20 million compared to $26 million in 2021. This decrease is mostly driven by a decrease in revenue recognized related to our collaboration agreement with BMS. G&A expenses decreased year-over-year from $76 million in 2021 to $71 million in 2022. The decrease was the net from an increase in strategy-related expenses, offset by a decrease in legal and stock-based compensation expenses. R&D expenses increased from $143 million in 2021 to more $175 million in 2022. The $32 million increase was principally driven by manufacturing and clinical-related costs incurred to advance EDIT-301, as well as a one-time charge incurred in connection with pausing enrollment in the BRILLIANCE trial. Overall, Editas remains in a strong financial position. As Gilmore said, our sharpened discovery and development strategy extends our cash runway into 2025. This provides ample resources to support our continued trials of EDIT-301, as well as advancing our research efforts in hemoglobinopathies and other in vivo discovery. With that, I will hand the call back to Gilmore. Thank you, Michelle. In the almost eight months since I joined Editas, the company has demonstrated two clinical POCs, one of which has the potential to be a competitive and indeed differentiated product. In addition, we have developed and shared our new strategy, reallocated resources to accelerate the clinical development of EDIT-301, begun discovery of in vivo editing of HSCs and other tissues, executed our goal to divest stand-alone cellular therapy business with our Shoreline deal, and are building up an already robust gene editing toolbox through the internal development or external business development of new and complementary technologies. This is just the beginning. Looking into 2023, we look forward to executing on our strategy, continuing our transformation, and sharing our progress with you. As a reminder, our strategic objectives for the year include hiring a new CSO with specific expertise aligned to our vision, refocusing our discovery group, advancing discovery of in vivo editing of HSCs and other tissues. On the development side, we plan to execute on the following in 2023: providing clinical updates from the EDIT-301 RUBY study in mid-2023 and the end of 2023, which will include longer-term data from the initial two patients that were dosed last year, as well as data from additional patients from the ongoing RUBY trial. In addition, dosing 20 total patients in our EDIT-301 RUBY program by year-end, dosing the first patient in the EDIT-301 EdiTHAL trial for TDT this quarter, and finally, providing early data in the EDIT-301 EdiTHAL trial for TDT by year-end. Thank you very much for your interest in Editas. We are happy to answer questions now. Thank you. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question comes from Joon Lee with Truist Securities. Please proceed. Hi. Good morning. This is Mehdi on for Joon. I have two related questions. Do you expect or already have takers for ASCas12a and SLEEK technology? On ASCas12a, on the Nature Communications paper 2021, IDT mentioned that they have a patent on the mutations made for Cas12 Ultra. How similar or different is the ASCas12a that you're using from Cas12 Ultra? Thank you. Well, Mehdi, I may have to ask you to pose your first question. I couldn't actually hear it. Oh, sorry. Do you expect or do you already have some other takers for AsCas12a and SLEEK technology? Oh, thank you, Mehdi. Well, what I would say is that the most recent agreement or deal that we have done was with Shoreline, in which we gave them an exclusive license to our SLEEK knock-in technology for iNK and their oncology derived or driven iMACs platform, and an additional non-exclusive license for AsCas12a. That was in addition to obviously selling the EDIT-202 asset. I think that's where we are on AsCas12a and SLEEK as an example of licensing. With regard to your second question around the IP, we actually have a very comfortable state that gives us the freedom to operate, and there are no interferences or other disputes around IP for AsCas12a. Thank you very much. Our next question is from Samantha Semenkow with Citi. Please proceed. Good morning. Thanks for taking our questions. First question, I'm wondering what experience or expertise you're looking for specifically in your next CSO, and if there's any expectation you could give us for when they could be appointed. Thanks very much, Samantha. We're looking for a number of the different qualities and capabilities in our future CSO. We are looking for somebody who has experience in developing and bringing drugs into the clinic. We are looking for expertise and the ability to work with complex genomics groups. Actually also looking for somebody who has, you know, significant and important collaborative leadership capabilities for working with Baisong, our Chief Medical Officer, with Bruce Eaton, our Chief Technology Officer, and the executive team, to help us in, you know, driving the selection of future therapeutic targets and target tissues in which we will combine a number of elements, including the technology and the probability of technical success, as well as the probabilities of clinical, regulatory, and commercial success. And with regard to the timing, I'm happy with the progress we're making. We are talking to very interesting candidates. But the timing will really depend on making sure that we choose the best CSO for the organization. What I will tell you is that I am very happy with the leadership that we have in our discovery group, which is driving forward on our strategy in the interim. Thank you. Great. Thank you very much. Our next question is from Dae Gon Ha with Stifel. Please proceed. Hey, good morning. Thanks for taking our questions. Clarification question and then one from me. On the clarification, dosing 20 patients into RUBY by year-end 2023, do you think that's sufficient to kinda move forward, whether it's for regulatory filing or the pivotal trial? The question on BD, when it comes to milder conditioning, just wanted to get your preliminary thoughts on where you think the direction is for potential differentiation for you guys. If it pertains to CD-117, can you perhaps speak to what areas of differentiation you can actually contemplate here, given the Jasper and Magenta updates? Thanks. Yes. Thanks very much, Dae Gon. With regard to the 20, we actually believe that that is actually going to generate a lot of very important clinical data. With regard to the regulatory needs, that will be a matter of discussion and agreement with the FDA and other regulatory agencies. And that's just something that we are, you know, planning over the coming year. With regard to the milder conditioning and differentiation, I think there are a number of ways of looking at that. I think the key thing about milder conditioning is that it actually significantly broadens the eligible patient population. current conditioning is an extremely severe therapeutic intervention, and many patients are precluded from using it just owing to significant comorbidities, which unfortunately result from the long-term complications of their disease. Milder conditioning per se doesn't have to be differentiated to actually substantially broaden the patient population that could benefit from these therapies. I think that's an important piece when you actually think about CD-117. With regard to other approaches, that is something that we are actively exploring, and we'll be able to share more as we advance on how we think that differentiates beyond the sort of the general and broad benefit to patients' eligibility through the development of milder conditioning. Great. Thanks for the updates. Our next question is from Phil Nadeau with Cowen and Company. Please proceed. Good morning. Congrats on the progress. Thanks for taking our questions. First, a couple on EDIT-301. In terms of the mid-year update in the RUBY trial, do you have a preliminary sense as to the number of patients in follow-up that'll be in that look? On EDIT-301 in TDT, can you remind us, is the design similar to RUBY in that the first two patients will be sequential dosing before moving to parallel dosing? Thanks, Phil. I'm gonna ask our Chief Medical Officer, Bei Song, to answer those two questions. Thank you. Thank you, Phil, for the question. Regarding your first question, in the middle year of data release, we will not share the number of patients this time, but what we can share is that we will share the longer-term data for the two patients dosed last year and the additional data for multiple patients dosed this year. We have been not only dose the sequential dosing the sentinel patient, but also started dosing the parallel dosing for the additional patients. In addition to that, we have enrolled multiple patients, some of them already being CD34 cells being edited and others in the process of apheresis. We are very confident and pleased with the progress of the RUBY trial progress. For your second question, can you repeat again? Yeah. Sorry. In terms of, EDIT-301 in thalassemia, is the design the same as the RUBY trial in that the first two patients will be dosed sequentially before you can move on to parallel dosing? Yeah. We will, we will have sentinel patients, and we will share more details when we have more of the data. Great. Two follow-up questions. In terms of the prior question, the mild preconditioning, do you have a sense when Editas could move that into the clinic, when you could begin testing a milder preconditioning regimen? Second, in terms of business development, you mentioned you were looking to bring complementary technologies in-house. Could you give us some sense of what complementary technologies you think you need? Thank you. Yeah. Thanks very much, Phil. With regard to the milder preconditioning, we will actually talk more about that in the future at an appropriate time when we have some more details that we feel able to share with you. With regard to the complementary technologies, just in general, we are looking across the two elements of advanced technology that will be important to driving our in vivo focus. Those around targeted delivery, and obviously, additional, targeted editing approaches. Again, we will be able to share more details about that in the future. Perfect. Thanks for taking our questions. Thanks very much, Phil. Our next question is from Eric Schmidt with Cantor Fitzgerald. Please proceed. Hi, everyone. Good morning. Thanks for taking the questions. Congrats on all the progress here. My first question is on the in vivo pipeline. I know that the first two target indications are currently undisclosed, but it looks like the initial discovery efforts are going towards the in vivo editing of stem cells. Could you highlight the reasons why you chose this as the initial area of focus and why it could be advantageous to target these cells rather than an organ like the liver, where methods of delivering gene editors are more established? Then for my second question, for the goal of dosing 20 patients by year-end in the sickle cell trial, are there any important limitations in manufacturing capacity or beds available that would limit the number of patients that you can dose in parallel? You know, I guess what I'm really trying to understand here is if patient dosing is likely to be evenly distributed over the year or if it could be weighted more towards the back half of the year. Thanks very much, Ric, for those questions. Let me turn to the in vivo pipeline question. While we did talk about in vivo HSCs, indeed, we are looking at other tissues which we have not disclosed. The reason that we actually talk about HSCs is that, you know, are several, one of which is that it aligns with a key focus of our active pipeline. It builds on the success of our EDIT-301. Essentially, we have somewhat simplified the calculus by having a human-validated enzyme or effector enzyme in AsCas12a and a humanly validated target in the HBG1/2 promoter, which enables us to really focus largely or predominantly on the target delivery. I will say, however, that we actually are looking at other tissues, but we haven't disclosed those yet. Turning to your second questions with regards to, you know, limitations, we have actually substantially invested and reallocated capital with our new strategy to CMC and do not have limitations there to both editing and supporting parallel dosing. Indeed, you know, Baisong could probably tell you more about the enthusiasm in the community following our data disclosure and our plans for the year. Yeah. Yes. Sure. Yes. Ric, yes, that's a very good question. As Gilmore mentioned, we really beefed up our CMC capacity. As we discussed before, we actually have a strong CMC team internally be able to handle all those handle the internal CMC manufacturing capacities and working with partners. We have patient recruitment. We really see a strong momentum over the last several years. We are very pleased to that, to see the number of patients being enrolled, being, you know, in screening as well as the prospective patients we have in there. We are very confident we'll be able to achieve the goal to do 20 patients by year-end. I think when you said previous years, I mean, I think you meant previous months and weeks. Several, last several months is what I meant. Yes. Yes. Thank you. A lot of enthusiasm and excitement from patients and investigators when we disclose the initial 301 data in December. Thanks very much. Great. Thank you. Thanks. Our next question is from Joel Beatty with Baird. Please proceed. Hi. Thank you so much for taking the questions. It's Jack Allen dialing in for Joel. We were hoping you could provide an update as it relates to the IP dynamics surrounding CRISPR/Cas9 and your IP there, in light of the February 22 decision by the USPTO. I ask as your competitor, CRISPR Therapeutics and for Vertex Pharmaceuticals, is looking to commercialize CTX001 as a Cas9-based therapy for sickle cell and beta thal in late 2023, early 2024. I was wondering if you had any thoughts as it relates to the time course of potential, I guess, settlements or any litigation surrounding IP of that Cas9 portfolio. Thank you so much. Thanks very much, Jack, for the question. Obviously we were very happy that the Broad's IP was upheld by the PTAB last February. I think the key thing is that this is a very exciting time, and we're delighted for patients. This is an exciting time because we're looking potentially at the first approval for a CRISPR-based medicine for patients with very serious diseases. Obviously we look to a negotiated agreement to enable the continuing advance of the technology, and we will be updating you on the details of that in appropriate time. Thanks so much. Thank you. Our next question is from Jay Olson with Oppenheimer. Please proceed. Hey, thank you for the update, thanks for taking the questions. Can you talk about any feedback that you received from your Independent Data Monitoring Committee in their latest review of the RUBY trial? A second question, as a result of your portfolio reprioritization process, are there any implications for operating expenses or your capital allocation strategy this year? Thank you. Thank you very much. Bais ong, do you want to talk about the IDMC feedback and the release for parallel dosing? Yeah, sure. Thanks, Jay, for the question. Yes, the IDMC has reviewed the data from the two sentinel patients. They agreed for continued and dosing and parallel dosing of the patients. Thanks very much, Bais ong. With regard to the implications for OpEx and capital allocation, I'm gonna just pass that to Michelle. Yeah, great. Hi, Jay. With the refocus strategy, we were able to extend our cash runway into 2025. We don't give out guidance on expenses, but obviously you can back into that, given that our cash balance was $437 million at the end of the year. We'll continue to invest in EDIT-301, both of the clinical trials, continue to invest in CMC and then obviously in our advanced technology and further in vivo platform. Great. Thank you very much. Thanks very much, Michelle. Thanks. Okay. Our next question is from Brian Cheng with J.P. Morgan. Please proceed. Hey, guys. Thanks for taking my call this morning. Gilmore, it looks like your collaboration with Bristol is going fairly well. I'm just curious if you can provide us some color on the collaboration. you know, what were the factors that prompted Bristol to opt in to more programs? Any color on the next steps, and how wide are the indications that the 10 programs are covering? Thank you. Thanks very much, Brian. You know, we're actually very happy with the BMS collaboration. I think one of the things that is driving opt-ins is that I believe that we have been providing very high quality packages around the target nominations. The program or collaboration is focused on alpha-beta T cells for the treatment of oncology and covers a rather broad swath of possibilities, which we haven't actually disclosed publicly, but I think you can infer from the nature of the agreement, the target cell types and the oncology, where there's likely to be. I think more details will be forthcoming as BMS advances the programs. Thanks, Brian. Great. Thank you, Gilmore. Our next question is from Luca Issi with RBC Capital Markets. Please proceed. Great. Thanks so much for taking my question. Congrats on all the progress. I have two quick one. Maybe circling back on a prior question, Baisong, if I may. I think you've spoken in the past about the RUBY trial potentially becoming registrational. Obviously, you're now flagging that you'll have 20 patients by year-end. How many patients, and what is the minimum follow-up that you think is required to actually have a registrational package? Again, any call there will be much appreciated. Then maybe Gilmore for you on LCA-10 and IRD more broadly. Can you just give us an update on what is strategic option that you're exploring in the moment? What will be an ideal partner and ideal deal there? Thanks so much. Thanks, Luca, for your question. Just wanted to clarify, we have ambitious but attainable goal to dose total of 20 patients by year-end. That is separate from the registrational package. As Gilmore mentioned a bit earlier, that for the registrational package, the number of patients required and data package, we will need to actually have a engagement with the regulatory agency to finalize that. It is also worth adding that because we have actually agreement on the potency matrix or assay matrix that all the patients dosed in RUBY will actually provide data that'll be part of marketing application. With regard to your second question on strategic options for our IRD divestiture, we are actually exploring potential divestitures. An ideal partner would be a sponsor interested in rare ocular diseases and potentially with a particular interest in AAV delivery. That's not a complete restriction. A key expertise in rare retinal disorders and their development would be an ideal partner for us. We look forward to being able to update you in the future on the progress we make. Got it. Thanks so much. Our next question is from Greg Harrison with Bank of America. Please proceed. Hey, good morning. Thanks for taking the questions. First, just wanted to ask on expectations for the sickle cell data. You know, I know it's been discussed previously, but just wanted to get your latest thoughts on, you know, what you need to show to really have a competitive profile here in sickle cell. On another note, what else needs to happen with the reorganization and, you know, how close are you to being complete with that? With regard to the sickle cell data, we were very encouraged by the initial clinical data, which were consistent with our preclinical data in demonstrating both impacts, robust effects on fetal hemoglobin and in the resolution of anemia. We are looking forward and confident we'll see replication in subsequent patients for that data set, and look forward to sharing updates in the middle and at the end of this year. With regard to reorganization, we have largely completed that reorganization. I think the critical element of the reorganization that is outstanding is the hiring of our chief scientific officer. I have already talked a little bit about the characteristics, traits, qualities we're looking for in that person leading forward. The good news is that the discovery, development, other, functional, components of the organization, have good, leadership and are already moving forward, in the execution of our new strategy. Great. That's helpful. Thanks for taking the questions. Great. Our next question is from Yanan Zhu with Wells Fargo. Please proceed. Hi, thanks for the questions. Have you dosed the third patient in the sickle cell trial yet? That's the first question. At what point along the data generation process from the sickle cell trial do you plan to reach out and have a discussion with the regulator about the path forward for EDIT-301? Lastly, is the 301's manufacturing process carried out with a commercial grade process, and i.e., would some kind of bridging needed if it is not that kind of a process currently? Thanks. Thanks very much, Yanan. Baisong, do you want just to sort of recapitulate the update? Yeah. Yeah. Thanks for your question, Yanan. I'll get the first two question, and I'll let Gilmore you answer the question about the manufacturing in there too. Yes, Yanan, we actually did dose the third patient and started, as we mentioned, start the parallel dosing for the patients. Regarding the registration of path forward, we will discuss with health authority to finalize the data package required for registration. We'll share more data when the time is appropriate. Thanks very much, Bais ong. With regard to our 301 process, the good news is that, certainly on the potency matrix area, we have actually been very successful in ensuring that the patients that we are currently dosing in RUBY will be able to support a marketing application. With regard to the refinements and agreed final commercial process, that'll be something that we will update you, obviously, at a time that's appropriate and obviously will include, you know, more details. Great. Thanks for the color. Our next question is from Gena Wang with Barclays. Please proceed. Thank you. I have three quick questions. The 1st one is regarding the Shoreline deal. Can you remind us the deal term and the economics, and when do you expect the transaction to be closed? Does your cash guidance take into consideration of the impact from the deal? That's the first question. Thanks, Gena. You're very good. You're going to keep them. That's great. We don't have to track them all. With regard to the Shoreline deal, we didn't actually disclose the numbers in the economics. We did receive an upfront. We are eligible for future development and commercial milestones and royalty payments, you know, with the advance of the assets. Indeed, that those, the impact in the financials is actually included or has been considered. That's, I think, the first question. Okay. Have you already received the payment, or you will receive after transaction, close regarding the Shoreline? We've already- But we- Yeah, we've received the payment, Gena. Yeah. Okay. Fair enough. I actually forgot to answer part of your question, Gena, which is we have closed the deal, we have received the payment. Right. Yes. The payment was. Okay. Received in 2023. Yeah. I see. The cash reported already incorporate that? The cash reported at the end of the year does not yet include that. Okay. The guidance- That will be in our reforecast of our cash runway. Okay, sounds good. The second question, very quick. Just, you know, I know you are committed to present the data EDIT-301 RUBY trial mid-year. What about the end of 2023, you know, especially like ASH, will you also provide some update there and thoughts on the timing and also number of patients? Thanks, Gena. I'm gonna ask Baisong to answer that question, you know, confirm that we are planning to present updates both the middle of this year and at the end of this year. Baisong. Yeah. Thanks, Gena, for the question. Yes, we will plan to have two data release for RUBY study, one in the middle of the year and one near the end of the year. In terms of specific forum, we will share when we have more information. We are not to share the number of patients at this point, but I just mentioned earlier, we really have a strong momentum for the RUBY study as well as EdiCel study, and we expect to have multiple patient data for the data release. Okay. Lastly, very quick. In vivo, programs, beyond HSC, what would be your top organ to explore? Thanks very much, Gena. We actually have taken the approach that we will use a sort of a balance of multiple factors in selecting our targets, our therapeutic targets and therefore, ergo, the target tissues. That would be a balance of the state of the technology, the probability of clinical, regulatory and commercial success. We look forward to sharing more specifics on that in the future. Thank you. Thanks very much. Our next question is from Rich Law with Credit Suisse. Please proceed. Good morning. Thanks for taking my question. As you focus on in vivo development, is there any renewed interest in using CRISPR-Cas9 in addition to Cas12 for internal product development, since the Cas9 technology is arguably more mature from the development progress by other companies? I have a follow-up question to that. Thanks very much, Rich. You know, I have to say that our pipeline currently is focused on AS-Cas12a. We believe that the AS-Cas12 enzyme has some significant advantages. We actually also believe that now we have used it in the clinic. Actually, as Bei Song has said, we've already e-edited multiple patients in addition to those already dosed. We actually are building a clinical experience with AS-Cas12a. From the point of view of advantages, we believe that, and actually have data supporting that position, that it has a higher efficiency and essentially higher fidelity with much less off-target editing. It has substantial advantages for moving forward. Right. Okay. A follow-up question to that is there any performance requirement in the licensing agreement that you have with the Broad, that you have to continuously perform product development with the Cas9 technology? I'm not going to go into details, but obviously, like any agreement, there are conditions or requirements to execute. Ours are a mixture around both on our business development and execution. Okay, great. Thank you. Our next question is from Madhu Kumar with Goldman Sachs. Please proceed. Hey, thanks for taking our question. This is Rob on for Madhu. Two quick ones. What venue should we expect the mid-2023 301 update? Is it like medical meeting or company release? How do you think about the regulatory path in in vivo CRISPR in the U.S., given the headwinds we've seen by some of your peers? Thank you. Bei Song, do you wanna take the first question? I'll take the second. We plan to release the RUBY data mid of the year as well as end of the year. The specific revenue we have not decided. We'll share in a later time. Thanks very much, Bei Song. With regard to the regulatory path for in vivo CRISPR, what I would actually say, I'm not gonna comment on others, the regulators. I will say that one of the things that drew me to Editas was the substantial investment and depth of expertise built in both its research analytics as well as its CMC analytics from the point of view of certainly managing risk, et cetera. I actually feel, you know, very good about where we are from that point of view. Obviously, as we move forward, we will engage with regulators, including the FDA, to determine the path to our first in human. Thank you. Thanks very much. Our next question is from Matthew Harrison with Morgan Stanley. Please proceed. Thanks for taking our questions. This is Chris on for Matthew. We have two questions. One is about the SCD filing package. You mentioned a few times that you need to talk to the regulators about that. Do you think it's possible that you could be in a position to file in 2024? The second question is about the BMS collaboration. Is it possible to see an update in 2023? How should we think about any of those programs progressing into the clinic? Thank you. Thanks very much, Chris. I think, let me take both questions regarding the filing package. Certainly, I admire your aggressive, posture there. I think, any question around timing of filings and what is required is really a matter of negotiation with the agencies, and that's only something that we will know as we progress our negotiations with them. With regards to BMS collaboration, we are happy with the collaboration. BMS has actually, received a lot of, nice data from us and actually, nominated, a number of targets. We hope that that will continue to progress. With regard to the specifics of advancing towards the clinic, that really is driven by, and the announcements are driven by, BMS. As I say, we're very excited by the collaboration and delighted to see the progress. Thank you very much. Our final question is from Liisa Bayko with Evercore ISI. Please proceed. Hi. All my questions have been answered. Thanks for taking them in. Thanks. Good. Thanks, Liisa. Thank you. This will conclude today's conference. You may disconnect your lines at this time, and thank you for your participation.