Good morning, and welcome to Editas Medicine's Fourth Quarter and Full Year 2023 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, Corporate Communications and Investor Relations at Editas Medicine.

Thank you, Maria. Good morning, everyone, and welcome to our fourth quarter and full year 2023 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 in 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 the 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.

Thanks, Cristi, and good morning, everyone. Thank you for joining us today on Editas's fourth quarter and full year 2023 earnings call. I am joined today by four other members of the Editas executive team, our Chief Medical Officer, Baisong Mei; our Chief Financial Officer, Erick Lucera; our Chief Scientific Officer, Linda Burkly; and our Chief Commercial and Strategy Officer, Caren Deardorf. We are pleased with Editas' momentum and progress in the fourth quarter and all of 2023. In early 2023, we shared our vision and the three pillars of our strategy to position Editas as a leader in in vivo programs for gene editing and hemoglobinopathies. The first of these pillars is to drive reni-cel, formerly known as EDIT-301, toward BLA and commercialization. The second is to strengthen, reorganize, and focus our discovery organization to build an in vivo editing pipeline. And the third is to increase business development activities with a particular focus on monetizing our very strong IP. So how did we do last year? Well, we achieved a lot. First, we accelerated the clinical development of reni-cel, exceeding our enrollment goal of 20 patients and sharing clinical updates from our RUBY and EdiTHAL studies in June and December of 2023. Those accumulating data have strengthened our belief that reni-cel is a potentially competitive medicine with a differentiated profile characterized by the correction of anemia at normal physiologic ranges of hemoglobin. Second, we strengthened our in vivo discovery capabilities and organization and hired a new Chief Scientific Officer, Linda Burkly, who brings three decades of experience in successfully inventing, developing, and moving new human medicine forward. And third, we increased our business development activities and monetized our IP, leveraging our robust IP portfolio. A critical example was our granting Vertex a non-exclusive license for our Cas9 IP in a focused way to enable the launch. Finally, we strengthened our senior leadership team with people who have a proven track record in bringing new medicine through development to approval and commercialization. So how are we executing against these strategies and these objectives? Well, let's start with reni-cel. First, on enrollment, we have now enrolled 40 sickle cell and 9 beta-thalassemia patients in our RUBY and EdiTHAL studies respectively, and enrollment continues at a good pace. Second, on dosing, we have dosed 18 RUBY patients and 7 EdiTHAL patients, and we have multiple patients scheduled for dosing in the coming month. Patient screening and demand in both studies continue to remain robust. Third, on clinical data, we remain on track to present a substantive clinical data set of sickle cell patients with considerable clinical follow-up in the RUBY study in the middle of 2024, with a further update by year-end 2024. On the regulatory front, we have engaged with the FDA regarding the RUBY sickle cell trial. The FDA agrees that RUBY is a single Phase 1, 2, 3 study and has aligned with us on the study design. Our discussions with the FDA will continue as RUBY and EdiTHAL progress and will be enhanced by our RMAT designation for severe sickle cell disease. Baisong will share further details regarding the development of reni-cel in his remarks, as well as recap the RUBY and EdiTHAL takeaways and clinical data that we provided in December and share more information on the adolescent cohort. Now, let's turn to in vivo and our pipeline development, where we strengthened our in vivo discovery capabilities in 2023 and began lead discovery work on in vivo therapeutic targets in hematopoietic stem cells and other tissues. As we announced earlier this year, we aim to establish in vivo preclinical proof-of-concept for an undisclosed indication this year. Linda and her team are leveraging key capabilities that we have in-house and she looks forward to sharing more at a future date. Regarding our hemoglobinopathies focus, after a thorough evaluation of the development landscape, we have decided not to pursue internal development of a milder conditioning regimen. We believe standalone milder conditioning regimens will be widely available once FDA approves, and therefore, we have determined that research, clinical development and regulatory investment in hemoglobinopathies can be better deployed for our continued development of in vivo HSE medicines. Turning to business development, in the fourth quarter, we announced a licensed agreement with Vertex Pharmaceuticals. Editas provided Vertex a non-exclusive license for Editas Medicine's Cas9 gene editing technology for ex vivo gene editing medicines targeting the BCL11A gene in the field of sickle cell disease and beta-thalassemia, including Vertex's CASGEVY. And the upfront and contingent payments pursuant to this agreement extended our cash runway into 2026. This and other agreements, the strength of our patents and the number of companies developing CRISPR/Cas9 medicine reaffirm our confidence that our IP portfolio of foundational U.S. and international patents covering Cas9 use in human medicine are a source of meaningful value. So what are our objectives for 2024? For reni-cel, we will provide a clinical update from the RUBY trial for severe sickle cell disease and the EdiTHAL trial for transfusion-dependent beta thalassemia in mid-2024 and by year-end 2024. We will complete adult cohort enrollment and initiate the adolescent cohort in RUBY, which we've already initiated, and continue enrollment in EdiTHAL. For our in vivo pipeline, we will establish in vivo preclinical proof-of-concept for an undisclosed indication, and for PD, we will leverage our robust IP portfolio and business development to drive value and complement core gene editing technology capabilities. We are energized by our progress and execution in 2023. With our sharpened strategic focus, our world-class scientists and employees, and our keen drive in execution, we continue to build momentum to progress our strategy to deliver differentiated editing medicines to patients with serious genetic diseases. Now, I will turn the call over to Baisong, our Chief Medical Officer.

Thank you, Gilmore. Good morning, everyone. Let's talk about reni-cel, which is in clinical development for severe sickle cell disease and transfusion-dependent beta-thalassemia. As of today, in the RUBY trial for sickle cell disease, we have enrolled 40 patients and dosed 18 patients. We have multiple patients scheduled for dosing in the coming month. We're also pleased to announce that we have initiated the adolescent cohort in the RUBY study, which is one of our 2024 objectives. The interest and demand are high, and adolescent patients have already started screening. In the EdiTHAL trial for transfusion-dependent beta-thalassemia, to date, we have enrolled nine patients and dosed seven patients. As I shared earlier, I continue to visit our RUBY and EdiTHAL clinical trial sites and continuously speak with investigators. I appreciate the enthusiasm and support from the investigators and study size. I’m pleased with the momentum of reni-cel in patient recruitment, apheresis, editing, and dosing in both studies. I’m excited to hear from the investigators that patients dosed with reni-cel have already seen positive changes in their lives. As Gilmore mentioned, we have aligned with FDA that RUBY clinical trial is now considered a Phase 1, 2, 3 trial for BLA findings. We have also aligned with FDA on the study design and endpoints, and the FDA has agreed to our activation of the adolescent cohort. We look forward to future discussions with the FDA and continued collaboration. Turning to clinical data, in December 2023, we shared safety and efficacy data from 17 patients, 11 RUBY patients, and six EdiTHAL patients. Once again, the data confirmed observations from our prior clinical readouts, including reni-cel driving early and robust correction of anemia to a normal physiological range of total hemoglobin in sickle cell patients. Reni-cel drove robust and sustained increases in fetal hemoglobin in excess of 40%. All RUBY sickle cell patients have remained free of vaso-occlusive events following reni-cel treatment. Reni-cel treated sickle cell and beta-thalassemia patients have shown successful engraftment and have stopped red blood cell transfusion. The safety profile of reni-cel observed today is consistent with myeloablative busulfan conditioning and autologous hematopoietic stem cell transplant. In addition, the trajectory of the correction of anemia and expression of fetal hemoglobin is consistent across reni-cel treated sickle cell disease patients and beta-thalassemia patients at the same follow-up time points. These data reinforce our belief that we have a competitive product that is potentially differentiated from other treatments with rapid correction of anemia. Thanks to the deliberate choice that our discovery group has made early in the program. As we have previously stated, the choice of CRISPR enzyme and the target to edit for increased hemoglobin, fetal hemoglobin expression matters. Reni-cel uses our proprietary AsCas12a enzyme to edit the HBG12 promoter. AsCas12a increases efficiency of editing and significantly reduces off-target editing when compared to other CRISPR nucleuses, including Cas9. Editing the HBG12 promoter in human CD34 positive cells not only maximizes red blood cell protection but also maintains normal proliferative capacity and improves red blood cell health compared to the editing of BCL11A. We look for differentiation in three categories of outcome in clinical trials: hematological parameters and organ function, and patient-reported outcome or quality of life. Based on the clinical data thus far, we believe that sustained normal levels of total hemoglobin could be a potential point of differentiation for reni-cel. As a reminder, a sustained normal total hemoglobin level is an important clinical outcome for patients, as the correction of anemia can significantly improve quality of life and ameliorate organ damage. We look forward to sharing additional updates, including RUBY and EdiTHAL clinical trial data with more patients and a longer follow-up period in mid-year and additional data by year-end. Now I will turn the call over to Erick, our Chief Financial Officer.

Thank you, Baisong, and good morning, everyone. I'm happy to be speaking with you, and I'd like to refer you to our press release issued earlier today for a summary of financial results for the fourth quarter and full year 2023. I'll take this opportunity to briefly review a few items for the fourth quarter. Our cash, cash equivalents, and marketable securities as of December 31 were $427 million compared to $446 million as of September 30, 2023. We expect our existing cash, cash equivalents, and marketable securities together with the near-term annual license fees and contingent upfront payment payable under our license agreement with Vertex to fund our operating expenses and capital expenditures into 2026. Revenue for the fourth quarter of 2023 was $60 million, which primarily relates to revenue recognized under our license agreement with Vertex, which, as Gilmore referenced earlier on this call, we announced in December of 2023. R&D expenses this quarter increased by $18 million to $70 million from the fourth quarter of 2022. The increase reflects additional sublicense expenses offset by the decrease in R&D spend resulting from our reprioritization and targeted focus on our reni-cel program. G&A expenses for the fourth quarter of 2023 were $14 million, which decreased from $18 million for the fourth quarter of 2022. The decrease in expense is primarily attributable to reduced patent and legal costs. Overall, Editas remains in a strong financial position bolstered by our sharpened discovery focus, new capital rates, and our recent out-licensing deals. Our cash runway into 2026 provides ample resources to support our continued progress in the RUBY and EdiTHAL clinical trials for reni-cel, continued commercial manufacturing preparation, and the advancement of our discovery and research efforts. With that, I'll hand the call back to Gilmore.

Thank you, Erick. We are very proud of our progress in 2023 and look forward to accelerating the momentum into 2024 as we continue to evolve from a development-stage technology platform company into a commercial-stage gene editing company. We look forward to continuing our transformation and sharing our progress with you. As a reminder, our 2024 strategic objectives include, for reni-cel, we will provide a clinical update from the reni-cel RUBY trial for severe sickle cell disease and the EdiTHAL trial for transfusion-dependent beta-thalassemia in mid-2024 and year-end 2024. We will complete adult cohort enrollment, and we've already initiated the adolescent cohort in RUBY, and will continue enrollment in EdiTHAL. For our in vivo pipeline, we will establish in vivo preclinical proof-of-concept for an undisclosed indication. For PD, we will leverage our robust IP portfolio and business development to drive value and complement core gene editing technology capabilities. As always, it must be said that we could not achieve our objectives without the support of our patients, caregivers, investigators, employees, corporate partners, and you. Thanks very much for your interest in Editas, and we're happy to answer questions. Thank you.

Our first question comes from Joon Lee with Truist Securities. Please proceed with your question.

Hi. Good morning, and congrats on the quarter. I'm sorry for my voice. My question is that could you please elaborate on the hemolysis markers that you're tracking and tell us how they will relate to patient-reported outcomes such as quality of life? Thank you.

Thanks very much, Joon. I hope that your voice gets better. I'm going to pass that question over to Baisong.

Thanks for the question, Joon. For the hemolysis marker, we look into multiple markers indicating hemolysis including reticulocyte, LDH, and bilirubin, among others. For the patient-reported outcome, we use several instruments to measure clinical outcomes and quality of life. They're related to the general PRO instrument as well as a sickle cell-specific instrument.

Thank you.

Our next question comes from Samantha Semenkow with Citi. Please proceed with your question.

Hi. Good morning. Thanks very much for taking the question. Can you share just any additional insights into your FDA conversation as you aligned on the RUBY trial specifically in terms of the number of patients you'll need and the amount of follow-up you'll need to file a potential BLA?

I'm going to have Baisong address that question.

Thank you for the question. We aligned with the FDA about the RUBY trial to be a Phase 1, 2, 3 trial to support BLA, including endpoints, sample size, and study design. We are continuing to have engagement with the FDA about the BLA data package and the follow-up, and we'll have further discussions with the FDA.

Got it. Thank you.

Our next question comes from Brian Cheng with JPMorgan. Please proceed with your question.

Hi, guys. Thanks for taking our questions this morning. Can you just give us a sense of what does a Phase 1, 2, 3 designation for RUBY really mean from a timeline perspective? And on the potential differentiation, I think based on your talk about investigators' feedback so far, I'm curious if you can also talk about just feedback that you've been hearing from investigators. Are they seeing potential differentiation this early on? Thank you.

Thanks very much, Brian. I think there were three parts to your question: What is a Phase 1, 2, 3, and its impact on the BLA path? What was the investigator feedback on differentiation? And were they seeing signs or what were the things that they might be seeing in patients at this point? I'll address the first part and then ask Baisong to follow up on the other two. With regard to Phase 1, 2, 3, I think the key point here is that it is a single study. We've agreed that there's a single Phase 1, 2, 3 study. We have important agreement on what the outcomes are and the size of the study. What that basically means is that we remain on track and are more confident about being on track to a BLA. It's worth calling out that the Vertex study was also the study that was used for their BLA application was designated a Phase 1, 2, 3 before that BLA. I hope that actually helps from the point of view of our path to BLA. Just mentioning Vertex, it's worth calling out that we have a benchmark based on the BLA filing from last year with regard to the size of the filing that was originally used for that approval. Baisong?

So Brian, regarding differentiation and investigator feedback, we have had quite a bit of engagement with the investigator and their observations of their patients as well as to see the data. They're very pleased to see the correction of anemia. The hematologists very much appreciate that the level of total hemoglobin is able to correct the anemia, and they see their patients are less fatigued and have more energy. There’s feedback from the investigators that the total globulin level, as published, also impacts end-organ function. So those are the directions that we're also looking for.

One other thing I'd just like to quote regarding the Phase 1, 2, 3. The important thing is that the RUBY study has been converted from a Phase 1 to a Phase 1, 2, 3, which allows a seamless transition to that study to support the BLA. I hope that's helpful.

Just to add on Gilmore's point, we can use all the patient data from the study to support the BLA.

Our next question comes from Greg Harrison with Bank of America. Please proceed with your question.

Hi, good morning. Thanks for taking the question. Now that there is a gene editing treatment approved in sickle cell, what are your latest thoughts on how reni-cel would fit in the space? And what have you learned from the early launch by the competitor?

Thanks very much, Greg. I'm going to ask Caren to address that question.

Yes, great. Thanks for your question. What we've been hearing from the various stakeholders in this space is a lot of interest and some really good initial momentum. I think we are also hearing that across all of the groups such as stakeholders, patients, families, transplant centers, and payers. There's just a lot of work that needs to happen, and I think you all are picking up on that. But it's starting and it's happening. The way we see it is very encouraging. It's going to take time, and we really believe that the fast follower of reni-cel is going to be timed very well. It gives us time to continue to collect data that is meaningful and differentiated, to understand where centers may be struggling, and where else we can optimize our vein-to-vein processes to deliver a product that's differentiated not just in efficacy and safety, but also in our operational aspects. So we see the market developing in a very robust way. We just think it's going to take a little bit of time. So we're very pleased with initial interest and certainly the ongoing interest in our clinical studies, and look forward to talking more with you about it.

Great. That's helpful. Thanks so much.

Our next question comes from Mani Foroohar with Leerink. Please proceed with your question.

Great. Thanks for taking the question. You talked a little bit about improvements in vein-to-vein time as an incremental source of differentiation independent of clinical data. Can you walk through how you think of the timing on which we might see that show up in terms of CapEx investment, in terms of clinical trial execution, etc.? Where we're going to start to see data points that could de-risk that part of your advantage in the eyes of investors?

Yes. Thanks for the question. This is Baisong. We are in the clinical trial stage. We're already trying to optimize all the processes from vein-to-vein, as you mentioned. We amended our protocol and work with our experts in apheresis, for example, to help with the sites in the apheresis cycle and support to prepare the patients. So the experience we gather now will help for our future commercial launch. I'll pass that to Caren.

Yes. To add, as we continue to engage in our clinical sites and expand our outreach to other centers, we'll have the opportunity to really understand how the process is working and how we can make the introduction and products like reni-cel as seamless as possible, ensuring that we do the advanced work and fit into their existing processes. We're always looking for opportunities across just, again, the efficiency and timing, and we'll certainly be able to talk more as we get closer.

Our next question comes from Terence Flynn with Morgan Stanley. Please proceed with your question.

Great. Thank you, team. This is Max Skor on for Terrence Flynn. Can you provide an update on the CRISPR-Cas9 appeal case and whether you expect an oral argument in the first half of 2024? Thank you.

Thanks very much, Max. The Court of Appeals, Federal Circuit has yet to schedule that oral hearing. It should be sometime this year, and once we have that scheduling, we can update you on that.

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

Thank you for taking my questions. So if I heard it correctly, Gilmore, you mentioned that the FDA and I think both of you mentioned a single study, and the FDA agrees on the single study, also the number of patients. I'm not sure if they agree on the duration of the study for the RUBY trial. I’m wondering if we think about the CRISPR trial, vertex trial, it's about 45 to 50 patients. Is that aligned with that number? And what is the duration that the FDA requires? And related questions, how many active sites do you have now? And what is your goal of total sites for the pivotal study?

Thanks very much, Gina, for your question. Before I answer, let me clarify something. We're not talking about a separate study. Essentially, the RUBY study, which is ongoing with its sites activated, is the Phase 1, 2, 3 study. That will be used for BLA, and that is the agreement we have with the agency.

I know we had already expanded the number of sites previously to a number that would support the full study, right? That was a very thoughtful approach to ensure that we had a good, strong number of sites with geographic coverage.

We have activated over 20 sites, and we have already enrolled 40 patients. Those sites for the adolescent cohort have overlap between the adult and adolescent from the same study sites. We are also activating a few more sites specifically for pediatric patients.

Our next question comes from Dae Gon Ha with Stifel. Please proceed with your question.

Good morning, guys. Thanks for taking our questions. I apologize. It's actually a two-part question. But just to clarify on the reni-cel progress in RUBY. If I heard you correctly, 18 dosed, I thought the prior conversation was 20 dosed by January. So can you talk about sort of the dropouts there? What was the reason behind that? And then another clarification on the FDA side, when you talk about differentiation, have you guys actually engaged them on the angle you're taking on the differentiation, whether total hemoglobin or end-organ function? How are they perceiving that in terms of the conversation? Thanks so much.

Thanks very much, Dae Gon. First, we are actually very happy with our dosing, 18 patients dosed. That puts us on track for a substantial data set in the middle of the year without dropouts. I just want to clarify that. We have scheduled multiple patients for dosing in the coming months. Regarding differentiation and our conversations with the FDA, we have highlighted our potential differentiation and the mechanistic differences behind that, but I think it's too soon to comment on where the FDA stands regarding our discussions on that.

Our next question is from Debjit Chattopadhyay with Guggenheim. Please proceed with your question.

Good morning. This is Ry Forseth from Debjit's team. Did the alignment with the FDA include any feedback on off-target editing, profiling, akin to the AdCom's criticism around CASGEVY's characterization for the breadth of genetic diversity? Our second question is, regarding the yet-to-be disclosed progress; are you going to offer proof-of-concept? I mean, what characteristics of this program are you most excited about? The market size, the opportunity for first-in-class, the specific editing chemistry, etc.?

Thanks very much, Debjit. Let me pass the first question to Baisong.

Yes. We have continuous engagement with the FDA. The engagement is scientifically driven, to understand the science of our molecule, the data we have, and how the patient will manage it. We have continuous interaction that is collaborative in nature. We were gratified by what we heard from the AdCom discussion, because our confidence in the robustness of our off-target editing oversight package was validated. Our off-target editing data package is comprehensive; we are using our engineered AsCas12a enzyme, which is high fidelity and efficiency. Importantly, the off-target editing is not detectable across a genome-wide screen compared to Cas9. Regarding in vivo characteristics, we focus on selecting targets based on their potential for critical differentiation from the current standard of care, including probability of technical, regulatory, and commercial success.

Thanks for the rundown.

Our next question comes from Phil Nadeau with TD Cowen. Please proceed with your question.

Good morning. Thanks for taking my question. Our question is on manufacturing. Can you remind us where you are in the scale of process in commercial, manufacturing scale process? And in your discussions with the FDA, have you agreed upon the CMC package? In particular, is there a requirement for patients in RUBY to be dosed with the commercial material? Thanks.

Thanks very much for your question. From a CMC point of view, we are in a very good place. We have had discussions with the FDA and are progressing well. We are building our commercial capacity, which will be ready for the demand that will exist at the time of our launch, and is ready for supporting demand beyond that launch. We are making excellent progress in support of our BLA to ensure we are BLA ready and inspection ready at that time.

Our next question comes from Jay Olson with Oppenheimer & Co. Please proceed with your question.

Oh, hi, congrats on all the progress and thank you for providing this update. Our question is about your in vivo program. Can you talk about how and when you plan to share preclinical proof-of-concept? Since it seems like there's two undisclosed targets in your corporate deck, are you planning to share preclinical proof-of-concept for both programs? Any thoughts you could share on your choice for editing tool and delivery tool? Thank you.

Thanks very much. From the in vivo pipeline point of view regarding how and when, we're excited to be on track towards POC this year. We'll be able to share more on the timing, whether it be at a scientific forum or some other forum to share the data. We have a focus on driving towards a POC for in vivo this year. Our editing tool is our proprietary AsCas12a editor, which we favor for its high fidelity, high efficiency, and advantages for quality, etc. We have robust editing data in human cells from our reni-cel program, and we focus on non-viral delivery via nanoparticles.

Super helpful. Thank you so much.

Our next question comes from Yanan Zhu with Wells Fargo. Please proceed with your question.

Great. Thanks for taking our questions. We're just wondering about the mid-year readout from the RUBY trial. I think you have 18 patients dosed to date. Are you going to report data on these 18 patients plus any additional patients dosed with a certain amount of follow-up at the time of readout? It seems like this is a much bigger number compared to the last readout. So I was just wondering your confidence level of continuing to show the total hemoglobin normalization kind of goal in this mid-year readout. Thank you.

Thank you, Yanan. Before passing it to Baisong on some details, I agree with you, this is a much bigger number of patients we have dosed. Our confidence has increased with the accumulation of data that show robust fetal hemoglobin expression in excess of 40%, well above the 30% threshold that natural history indicates is relevant. We are excited about the mid-year disclosure. I will pass it to Baisong for a bit more detail.

Yes. Your understanding is correct. We have dosed 18 patients and will continue to dose patients in the coming months. So the data set will consist of 18 patients plus more that we're going to be dosing before the middle of the year. We have published data in ASH, and some patients have been monitored for over a year. Those patients will continue to be monitored, and by the middle of the year, the 18 patients will have three to five months more follow-up data by the time we release that. That's why we describe it as meaningful substantive data to share by the middle of the year. This data set is quite strong.

Yes. We're also talking about follow-ups from an efficacy point of view at between three and 18 plus months. Now, with the total patients, we're building a data set that's robust not just in count but also in follow-up time, which increases confidence in durability.

Our next question comes from Luca Issi with RBC Capital. Please proceed with your question.

Oh, great. Thanks so much for taking my question. Congrats on all the progress. Maybe Baisong, any update on the grade 2 polycythemia case that was potentially related to reni-cel? I remember the poster at ASH noted the causality of the AEs was being investigated pending additional lab tests. Just wondering if you have any update on that one. Also, any update on partnering sickle cell disease ex-U.S.?

Baisong will take that first question. Regarding partnering, we are keen that a partner with a global footprint could help us with a global commercialization and development. We see that as an upside, but right now, our focus is on driving our sickle cell and thalassemia programs here in North America. Partnering will be something we look for in the future as upside.

Yes. That specific patient had a transient elevation of total hemoglobin, which we reported in ASH. It has remained normal for over six months. The patient’s hematological parameters, including total hemoglobin, continue to stay normal. The investigator conducted further investigation of the patient data and concluded that this event is not related to sickle or the reni-cel treatment.

Got it. Thanks so much.

Our next question comes from Steve Seedhouse with Raymond James. Please proceed with your question.

Hi. Good morning. This is Timur Ivannikov on for Steve Seedhouse. We just had a clarification question on your PRO tools in RUBY. To what extent are you going to be using the same tools that Vertex and CRISPR used before like EQ, VAS, FACT-G, and BMT? To what extent do you think of including new tools? On the issue of not being able to do a clean cross-trial comparison possibly?

Yes. Thank you for the question. As I mentioned, we use tools from two ends: one is a more general quality of life tool, and the other is a sickle cell-specific tool. The specific tools we are using are focused on evaluating key complaints from sickle cell patients, such as fatigue and pain.

We are using multiple instruments. Some were used by Vertex, and we have additional instruments in our PRO armamentarium and are actively collecting them in the RUBY Phase 1, 2, 3 trial as we speak.

Our next question comes from Jack Allen with Baird. Please proceed with your question.

Great. Thanks so much for taking the question and congratulations on the progress. I want to touch a little bit on the patient experience with reni-cel. Have you provided any disclosures around the number of apheresis cycles required to receive reni-cel, and I was wondering if the higher editing efficiency of AsCas12a allows for a shorter number of apheresis cycles? After treatment, what are you seeing related to time to neutrophil engraftment? How do you think that compares to some of the competing products in the space? Thanks so much.

Thanks very much, Jack. I’ll ask Baisong to discuss the clinical experience with apheresis and other elements of the patient experience, as well as address neutrophil engraftment, which we have been pleased with.

Thank you, Jack. Apheresis is a very important part of the patient experience. As I mentioned earlier, since I joined, I have been working with the team and experts. We amended the protocol and optimized the apheresis process, so now we are pleased with the number of cycles that patients go through; we see improvements. In terms of engraftment, as we disclosed at ASH, all patients have achieved engraftment within 30 days. So we are very happy about that, and we continue to see similar data as we follow through the protocol for our studies. Thank you very much.

We have reached the end of our question-and-answer session. This concludes today's conference. Thank you for your participation. You may disconnect your lines at this time.