Good morning, welcome to Editas Medicine's First Quarter 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 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, Camilla. Good morning, everyone, and welcome to our first quarter 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 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, Cristi, and good morning, everyone. Thank you for joining us today on Editas's first quarter earnings call. 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. As many of you know, in early January, we shared our strategy to position Editas as a leader in in vivo programmable gene editing and hemoglobinopathies. During the first quarter, we successfully executed this strategy, driving to our goal of delivering life-changing medicines to patients with previously untreatable or undertreated diseases. We are increasing our momentum in driving our ex vivo EDIT-301 program as we pursue a leadership position in hematopoietic stem cell medicines for hemoglobinopathy. As a quick recap, there are three underlying pillars to our new strategy.
First, while continuing to develop EDIT-301 for severe sickle cell disease and transfusion-dependent beta thalassemia, or TDT, we have sharpened our discovery focus to in vivo-administered genome editing medicines. As part of that refocusing effort, we previously announced that we had divested our iNK cell franchise to Shoreline Biosciences in January. Second, we are strengthening our discovery engine and technological capabilities. We have divided our research division into separate technology and drug discovery groups, enhancing the capabilities of each and implementing our new target selection criteria. Finally, our third strategic pillar is an increased and expanded approach to business development. In tandem, we will continue to deleverage our IP portfolio to drive out-licensing and partnership discussions. How have we executed against our new strategy in the first quarter?
We have increased our investment in our EDIT-301 program after reviewing promising initial RUBY phase I/II study data that indicated that we have a competitive and potentially differentiated program to treat sickle cell anemia and TDT. Additionally, we are investing to develop an in vivo approach for editing hematopoietic stem cells for the treatment of sickle cell disease and TDT, leveraging the unique and differentiated approach of EDIT-301, that we have already seen a PoC for in humans. We continue to ramp up enrollment and dosing of patients in the RUBY trial for sickle cell disease and are on track to have dosed 20 total patients by the end of 2023.
We are also excited to share that the FDA recently granted Orphan Drug Designation to EDIT-301 for the treatment of sickle cell disease. We are pleased to announce that in June, we will provide a RUBY clinical data update in an oral presentation at the European Hematology Association, or EHA, Congress. In our company-sponsored webinar, Baisong will share further details regarding our June data readout and our enrollment progress in his remarks. On EDIT-301 for TDT, we are pleased to share that we dosed the first patient in our EdiTHAL phase I/II trial in the first quarter. The patient has successfully engrafted neutrophils and platelets. Enrollment continues to progress. We remain on track to provide initial clinical data from the EdiTHAL trial by year-end.
Moving to in vivo, earlier this year, our drug discovery group began lead discovery work on in vivo therapeutic targets in HSCs, or hematopoietic stem cells, and other tissues. As a reminder, 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. The target selection criteria will work to ensure targets are selected that maximize the probability of technical, regulatory, and commercial success. Our search for a new CSO to lead this drug discovery group continues to progress. I look forward to updating you on this search and our in vivo work in the future. Turning to our intellectual property position.
Since the founding of Editas, we have placed substantial importance in securing robust intellectual property protections covering our cutting-edge scientific discoveries and gene editing advancements to enable the development of novel transformative medicines for patients in need. It is important to note that we have a large portfolio of foundational U.S. and international patents covering CRISPR Cas9 in human therapeutics, only some of which are subject to interference proceedings, and we are confident that our IP portfolio will provide meaningful value in the future. We are the exclusive licensee of Harvard University's and Broad Institute's Cas9 patent estates, and Editas is uniquely positioned to issue exclusive and non-exclusive licenses for Cas9 to any company seeking to use these enzymes to make human medicines, including in vivo and ex vivo therapeutic applications.
Our unique position as the exclusive licensee of this patent estate ensures that we are the party responsible for any licensing discussions as CRISPR Cas9 products enter the market, which given the size of the U.S. patient market and the number of companies vying to develop CRISPR Cas9 medicines, is a substantial position. With our newly sharpened strategic focus, our world-class scientists and employees, and our keen attention to execution, we continue to build upon the momentum from our clinical readout milestones during the fourth quarter of 2022. We look forward to updating you on our progress and on the execution of our new strategy throughout the year. I will turn the call over to Baisong Mei, our Chief Medical Officer. Baisong Mei.
Thank you, Gilmore. Good morning, everyone. Let's start with EDIT-301 RUBY study for severe sickle cell disease. As Gilmore mentioned, we continue to enroll and dose patients in the RUBY study. We have activated 20 study sites and enrolled 19 patients, almost double the number of patients enrolled from three months ago. As we previously shared, we began parallel dosing of patients earlier this year. We are on track to provide an update on the RUBY clinical data both next month and year-end, as well as to dose 20 total patients by year-end. Turning to clinical data, I'm excited that we will present RUBY clinical data as an oral presentation at the European Hematology Association, or EHA Congress, and at our company-sponsored webinar in June.
The dataset will including safety and efficacy data from multiple patients, including 10 months data from the first patient treated and six months data from the second patient treated, including total hemoglobin, fetal hemoglobin. We'll also share data on safety, neutrophil, and platelet engraftment, and vessel occlusion event, or VOE, from the first four patients. As a reminder, last December, we present initial data from the first two patients treated in the RUBY trial. The first patient, who had five months of follow-up after treatment with EDIT-301, showed clinically significant improvements across all hematological parameters and then no VOEs. Specifically, that patient had an increase of fetal hemoglobin fraction to 45.4% five months after EDIT-301 infusion, and the correction of anemia with total hemoglobin level well into the normal range at 16.4 grams per deciliter.
These initial clinical data indicated that EDIT-301 provides patients with high and sustained level of fetal hemoglobin and normal level of total hemoglobin. This clinical observation is consistent with preclinical data, which has demonstrated that targeting of gamma-globin promoter enables increases of fetal hemoglobin independent of erythropoietic stress. Given the unique gene editing approach and the mechanism of action by EDIT-301, supported by preclinical data and initial clinical data, we continue to believe that EDIT-301 can potentially provide robust clinical benefit to patients with severe sickle cell disease and potentially provide clinical differentiation in the long term. 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 end organ damage. We believe sustained normal level of total hemoglobin could be a potential point of differentiation for EDIT-301.
Turning to EDIT-301/reni-cel phase I/II trial for transfusion-dependent thalassemia. As Gilmore mentioned earlier, we dosed our first patient in Q1, and the patient has successful neutrophil and platelet engraftment. We remain on track to provide initial clinical data from the reni-cel trial by year-end. As we have done for the RUBY study, we are also taking multiple measures to accelerate the development of EDIT-301 for TDT and have strong positive momentum. We have enrolled multiple patients who have completed apheresis and have their CD34 positive cells edited or are in the process of apheresis. Recently, I have been traveling around the country visiting our RUBY and reni-cel clinical trial sites. I very much appreciate the enthusiasm and the support from the investigators and study sites. I'm pleased with the momentum of EDIT-301 in patient recruitment, apheresis, editing, and dosing in both studies.
I'm excited to hear from investigators that patients dosed with EDIT-301 have already seen positive changes in their lives. We look forward to sharing additional updates as the year progresses i ncluding RUBY study data next month and at year-end, sharing initial clinical data from EdiTHAL study by year-end. Now I will turn the call over to Michelle, our Chief Financial Officer, to review our financials.
Thank you, Baisong , 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 first quarter of 2023. I'll take this opportunity to briefly review a few items. Our cash equivalents, and marketable securities as of March 31st were $402 million, compared to $437 million as of December 31st, 2022. We expect our existing cash equivalents, and marketable securities to fund our operating expenses and capital expenditures into 2025. Revenue for the first quarter of 2023 was $9.9 million compared to $6.8 million for the same period last year. The increase is related to the previously announced sale of our oncology assets to Shoreline Biosciences and related licenses, which was completed in January 2023.
G&A expenses for the quarter were $23 million, compared with $19.5 million for the first quarter of 2022. The $3.5 million increase is primarily attributable to increased professional services expenses to support product development activity, partially offset by a decrease in stock compensation expense. R&D expenses this quarter were $38 million, which is flat compared to the first quarter of 2022. This reflects a decrease in expenses following the strategic reprioritization of our portfolio, offset by increased investment to accelerate the development of EDIT-301. This reallocation of capital is in line with our strategic priorities.
Overall, Editas remains in a strong financial position, and our sharp and discovery focus allowed us to concentrate our talent and extend our cash runway into 2025, which provide ample resources to support our continued progress in both of our EDIT-301 trials, 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. It has been almost one year since I joined Editas. In this time, the company has demonstrated two clinical proof of concepts, including a proof of concept for EDIT-301, which has the potential to be a competitive and differentiated product for the treatment of sickle cell disease and transfusion-dependent beta thalassemia. In addition, as I stated in my opening remarks, we've taken a number of tangible steps to reshape the company around our new strategy, which we shared in early January and have begun executing on that strategy. This is just the beginning. We look forward to continuing our transformation and sharing our progress with you. As a reminder, our strategic objectives for the year include providing clinical updates from the EDIT-301 RUBY study in June and end of 2023.
Providing clinical data from EDIT-301 EdiTHAL trial for TDT by the end of 2023. Dosing 20 total patients in our EDIT-301 RUBY study by year-end. Hiring a new CSO with specific expertise aligned to our vision. Advancing discovery of in vivo editing of hematopoietic stem cells and other tissues. Finally, leveraging our robust IP portfolio and business development activities to drive value and complement core gene editing technology capabilities. I thank all the patients, investigators, and our employees who are helping to drive our strategy forward. Thank you very much for your interest in Editas, we're happy to answer questions. Thank you.
Thank you. At this time, we will be conducting a question and answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate that 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. One moment please while we pull for questions. Thank you. Our first question comes from Joon Lee with Truist Securities. Please proceed with your question.
Hi. Thanks for taking our questions. You know, Novartis recently terminated their sickle cell disease program after treating a couple of patients who showed no benefit. Given your editing strategy is similar to what Novartis did, can you point to some differences why your promoter editing strategy should continue to work when Novartis failed? I have a follow-up. Thank you.
Thanks very much, Joon. Yes, we did actually see that event some weeks or months ago. I think there are some elements that are critical. I think the first thing to point out is that in our initial POC readout at the end of last year, we actually saw very robust data with an increase in total hemoglobin.
Early increase in total hemoglobin, as well as a robust fetal hemoglobin expression, completely consistent with the preclinical data that were generated in testing our preclinical and our clinical hypotheses that our unique approach of combining an AsCas12a effector CRISPR enzyme with the targeting of a different region of the HBG1/2 promoter, which is much closer, in fact, actually encompasses the area in which we see deletions or mutations associated with Hereditary Persistence Fetal Hemoglobin. I think we believe that all those factors point towards a key difference and differentiation. Indeed, our preclinical data and our clinical data have actually supported that hypothesis.
Great. you know, can you remind me if you had any data preclinically, you know, comparing the editing on, the same region using Cas9 versus As Cas12 that you're using, what the difference is in outcome may be?
Sorry, Joon.
Do you use some amount of, y eah. I mean, comparing Cas9, which is what I think Novartis used, and AsCas12a, which is what you're using, do you get a different outcome if you were to target the same region in terms of getting deletions or indels?
Yeah, Joon, I think you're a little bit breakdown, but let me try. This is Baisong, and let me try and see whether I understand correctly. Just background noise. I think your question to say compared to Novartis and do we have a comparison between Cas9 and Cas12a and also the region, just Gilmore mentioned. Is that your question?
Yeah. No, actually, if you target the same region either with Cas9 or Cas12a, what differences in outcome do you get?
Yeah. Let me just kind of in it. We did the comparison. We did from clinical perspective, we scanned a large region of the promoter region to identify which area to do the editing. Without too many specifics, but we cover the large region of the promoter in the HBG / 2. We find out that latitude, the region we selected, which Gilmore just mentioned, is consistent to the clinical observation for these HPFH. We also compare the Cas9 with Cas12, and we find the difference between Cas9 and Cas12. Does that answer your question?
Yeah, no, absolutely. Your impaired data says it, we're just curious what was driving that difference. Thank you so much. I'll hop back on the queue.
Thank you.
Thank you. Our next question is from Samantha Semenkow with Citi. Please proceed with your question.
Hi. Good morning. Thanks for taking the question. Just a couple for me. For the presentation at EHA, is that a late-breaking presentation? I just wanted to clarify.
Thanks, Samantha. I just have, based on updates, she'll give you detail there.
It is a normal oral presentation, that, being accepted.
Okay. Got it. Thank you for that. I also wanted to clarify, I heard you mention obviously we'll have the updated data for the first and second patients. I heard you, I think, say four patients. Will it be six patients total that will get data on VOE or is it, or VOCs or is it four patients total?
Total will be four patients at the EHA presentation.
Got it. Okay. Then, you know, when you're making that cutoff for those, incremental additional two patients, what level of follow-up was the cutoff there? I'm just curious, is it a couple of months or is it one month? Any information you could provide would be helpful.
Yeah. For this next two patient, we have two months or more.
Perfect. Thank you so much for taking the question.
Thank you.
Just in follow-up, one other thing I think is important to understand that obviously we will, because the abstract, which will be published later, was based on data cut earlier, we will actually be presenting more data than in the abstract, at the EHA Congress.
Yeah. Thanks, Gilmore. Just can also follow up on that. The abstract will be available on May eleventh.
Thank you. Next question is from Dae Gon Ha with Stifel. Please proceed.
Hey, great. Thanks for so much for taking the question, look forward to the data update next month. I guess I was just kind of wondering about your strategy going forward. Maybe if you can kind of walk us through how you're thinking about next programs or priorities beyond EDIT-301. I think, Gilmore, you mentioned in vivo HSC editing. Curious, is delivery tech or less burdensome conditioning a stronger emphasis in your lineup, or is it advancing new programs? If it's the latter, I guess, would you continue to do other ex vivo HSC, or is it more of an in vivo? In that case, would you also think about other organs? I've got a follow-up.
Yeah. Thanks very much, Dae Gon. We are, you know, the large part of our discovery focus is actually on in vivo. I think that was a very important part and pivot of our strategy because we believe that it maximizes our ability to exploit the powerful technology that we have available to us. From a point of view of HSCs, if you reduce the problem of in vivo to sort three elements, you know, selecting a robust effector molecule or enzyme, CRISPR enzyme, selecting a good target, and then delivery, we believe that we have solved two of those problems with very robust human data in the use of our Cas12a CRISPR enzyme and the targeter of that specific HBG1/2 promoter.
That reduces it to a in vivo delivery problem. As I said in my earlier remarks, our discovery group is actually working in that, and we look forward to updating more at an appropriate time in the future. I will say that we are looking actually also beyond HSCs to other tissues, and again, we'll give further updates in the future.
Got it. Thanks so much. Second question, I just wanted to follow up on Baisong's commentary during prepared remarks. As you were going into the field and kind of gauging physicians' take on EDIT-301, you expressed or you commented on their high enthusiasm. Wondering if you could comment, I guess, what proportion of those docs you visited are also looking to administer CTX001? I guess, have there been any kind of gauge or ascertainment from your part as to what their sort of motivation would be in taking CTX001? Like, are they lining up patients right now for CTX001? What kind of sentiment do you have? Are there any reservations on that approach? Any thoughts on that would be helpful. Thanks so much.
Yeah. Thanks for that question. Yes, I visited quite a few number of study sites. Actually, many of them are being participating in the previous gene editing trials, so they are very enthusiastic about the approach we're taking, including the different targeting region for editing and the different enzyme to do. Actually the benefit for us is these investigators have a lot of experience in this field.
Yeah. I think you know, just, you know, building on Baisong's remarks, you know, as you're obviously looking out towards the evolution of the market, against the background of enthusiasm for our investigators and indeed the patients, with the increase in our acceleration enrollment, you know, we anticipate that in the future that the vast majority of patients will be awaiting dosing at the time of our launch. I can go into more details on that. I think a very important point, I think something that has really resonated with the investigators, is that our initial clinical data were very encouraging, as presented in December, consistent with our preclinical data.
We're actually very confident that we will see replication in subsequent patients as we continue to monitor them through the execution of the 301 studies.
Great. Thanks for taking our questions.
Thank you. Our next question comes from Steve Seedhouse with Raymond James. Please proceed with your question.
Good morning. Thanks so much. My question actually requires a bit of a prelude, so I hope everyone can bear it for a moment. You made a comment on globin locus editing increasing fetal hemoglobin independent of erythropoietic stress. As you know, the ICER, recent ICER report on Exa-Cel uncovered an ongoing phlebotomy, at least one in sickle cell, and some of the earlier data releases for that program, and thalassemia indicated phlebotomy use there as well. That just stopped being reported at some moment, so it's not clear how prevalent phlebotomy use is for Exa-cel. This is all important because there was data at ASH years ago, as I'm sure you also know, indicating BCL11A editing cooperates with phlebotomy in primates to accentuate F-cells and ultimately HBF levels, probably because of the stress erythropoiesis causes.
All of that said, I'm curious if you agree that phlebotomy is potentially confounding fetal hemoglobin data for BCL11A approaches, and if you know what is the impact specifically for your editing approach at the HBG1/2 locus, what has phlebotomy use been like in your study, and if you think this is all potentially a competitive advantage for you? Thanks.
Steve, thank you very much for your question. From our own clinical data, preclinical data and also published data you're probably referring to, for the BCL11A targeting approach, it did require some stimulation for the erythropoietic stress to increase the fetal hemoglobin, sufficient fetal hemoglobin expression. That's actually the reason we choosing the target we are treating now, and we actually did take a longer time to get all the targets from preclinical study perspective, and that's been validated by other other publications. Regarding specific clinical data, for the BCL11 approach, I have not seen formal publication, so I would waiting for them to publish their data and see where we have a better understanding.
I would not comment on their data unless they're published.
It is worth pointing out that, you know, in our early disclosure, we actually noticed a combination of very robust normalization or correction of anemia in our first patient in December, and that was associated with a robust fetal hemoglobin expression, suggesting that indeed stress erythropoiesis, as we hypothesized based on the known biology and our non-clinical data, that our approach is not dependent on stress erythropoiesis.
Thank you. Our next question is from Yanan Zhu with Wells Fargo. Please proceed with your question.
Hi, thanks for taking our questions. Maybe to continue the discussion a little bit from the prior question. Gilmore, you mentioned that the total hemoglobin for the first patient is quite robust and in a normal range.
The percent fetal hemoglobin appears to be very much in line with a competitor gene editing product. I was wondering, is the greater total hemoglobin reported for that patient, is that due to the total number of red blood cells? Could that potentially be a reason, or could it be related to the baseline level of hemoglobin in that patient? Along that line, to continue a little further, and to perhaps looking into what we could expect from patient two at EHA, I was just wondering, could you remind us the baseline total baseline hemoglobin for patient two, and what is the normal range for the female patient, which obviously is the second patient? Thank you.
Thanks. Yeah, thanks for your question, Yanan. I will start with answer to your first part of the question regarding the fetal hemoglobin versus the number of red blood cells and all these. What we see is actually robust erythropoiesis for this patient we observed. Their hemoglobin level is contributed by both the hemoglobin per cell as well as the number of red blood cells. You can see that we actually do see the increase also on both end of that. Also want to mention that even though we also have, like, around 45% of fetal hemoglobin, and because of the total hemoglobin level is high, and the total amount of fetal hemoglobin is also high.
That's kind of on that. Then regarding the second patient, we will present the data very soon, so I will not comment on the specifics of the patient's data, but I can mention that of course, the male and female normal hemoglobin level are different. Usually for male is around 13.5 to up to 18 gram per deciliter. For female is around 12 to 14, depending on the reference lab. There's some difference in there too.
Great. I think one of the thing, Yanan, you asked a question about, what was the baseline hemoglobin of the patient one. I think what we can say is that the hemoglobin or the total hemoglobin increase that we saw occur very rapidly, just within the first few months of dosing, with, you know, comprise a 3.5 g per dL increase.
Yeah. Maybe I just add a little bit nuance on that baseline for sickle cell patient is fairly during 14 editing trial. Because the patient, when they prepare for apheresis and conditioning, they usually have blood transfusion. The baseline actually we have is not the lowest level we recorded. We just set up a time of the visit two as a baseline. Actually it's compounded. It could be many different reason for the baseline on that too. That's just a new nuance.
It's lower.
It's actually, you know, it's lower than. It's around a little bit over 10 gram per deciliter when we actually on our record for this patient. This just example, about the baseline, maybe a little bit more confusing.
Very, very nice. Thank you for all the explanation. Maybe a quick follow-up. Do you expect this to be also a differentiator for TDT and perhaps maybe at a greater level of significance because anemia is a major manifestation of that disease? Thank you.
Thanks very much, Yanan. We designed our discovery group and scientists designed and selected the combination of Cas12a with the specific targeting of the HBG1/2 promoter, using a set of empirical experiments to determine what was the best approach to driving not just fetal hemoglobin expression, but robust erythroid output that would be or red cell output for the bone marrow that would be independent of stress erythropoiesis or anemia. Those empirical experiments really determined that approaching or directly targeting the HBG1-2 promoter would be better. That was the original design hypothesis. The non-clinical data, preclinical data actually supported that, showing a, you know, robust erythroid output in comparison to other approaches, as well as robust fetal hemoglobin expression.
Indeed, that is what we have seen, you know, as we disclosed in our first sharing of the data or cut of the data from our RUBY study. Obviously, We haven't seen enough data in our EdiTHAL patient, but what I can say is that RUBY has certainly demonstrated data that are consistent with both the preclinical data, which were supportive of the original biological and therapeutic hypotheses.
Great. Thanks for all the answers.
Thank you. Our next question is from Phil Nadeau with TD Cowen. Please proceed with your que-
Good morning. This is Ernie Rodriguez for Phil. Thanks for taking my question. On the sickle cell program, have you met with the FDA to gain better visibility on the regulatory path? A second question on the TDT program. For the year-end update, would that include only the Sentinel patients that you initially dosed, or will you disclose additional patients? If you will be disclosing additional patients, are you planning on reporting when you switch from central dosing to parallel dosing? Thank you.
I think what I'll do is ask Baisong to. I actually keep track of the questions, Baisong. If I'd ask you just to ask, you know.
Sure.
The question on the FDA and the regulatory interactions that are planned.
Yeah. Thanks for your question. We certainly have a lot of engagement with FDA, as you see that recently we have the Orphan Drug Designation. From the registration perspective, we previously announced that we actually have the alignment on the potency assay with FDA, which FDA will consider this efficacy data can be supporting registration. We will have further engagement with the agency to align on the total registration package for the BLA submission, which is also planned. Your second part of the question is about the beta cell data. We are moving really along with the EDIT cell study, and we expect that we will have data by year-end, more than Sentinel patient.
We're looking forward to share the data by the year-end.
Okay. I see. You, more than Sentinel patient. Are you planning to disclose when you get approved to continue parallel dosing before then?
Okay. What we are actually planning to do is, you know, I think the key thing is we're on track to get the data for readout at the end of the year, for that initial readout at the end of the year. We haven't determined if we're actually going to share that, but I think the important point is that we are well on track to disclose good initial data for the end of the year.
Got it. Thank you.
Thank you. Our next question comes from Rick Bienkowski with Cantor Fitzgerald. Please proceed with your question.
Hey, good morning, congrats on all the progress. I guess I'll expand a bit on the last question on the path towards registration for EDIT-301. 20 patients is a pretty substantial cohort size in sickle cell disease. Do you have any sense of how many patients worth of data you will need for a registrational filing?
Thank you for that question. We, we certainly, you know, with the gene editing approach, we will be able to generate substantial amount of data. The specifics on the number of patients to be able to use for such registration, we need to align with the regulatory agencies. We are planning to discuss with FDA.
Okay, got it. I just have another quick one. I was hoping for a little bit more granularity on the collaborative revenues for the quarter. Were all of the $9.9 million in revenue attributable to the Shoreline transaction, or are there some other revenues attributable to other partnerships in there?
It's a combination of both the Shoreline and then some other, small, like, sub-license revenue.
You got it. Thanks for taking the questions.
Thank you.
Thank you. Our next question is from Rich Law with Credit Suisse. Please proceed with your question.
Good morning, and thanks for taking my question. I have a couple questions for you guys. With the appeal litigation pending, what does it mean for companies such as CRISPR and Vertex that already filed a BLA for Exa-cel that utilize CRISPR Cas9 from your IP perspective? They don't have a license from you or the Broad Institute and could potentially launch the product before we know the outcome of the appeal. Any insight here would be helpful. I have a follow-up question.
Okay. Thanks very much, Rich. I think the key thing is that we sort of anticipate the judgment in the early to mid 2024. We are confident that we prevail as we have before, largely because what are under discussion is the application of the law and not about new facts, and it's the application of the law by PTAB. Now setting aside that interference, I think the important thing is to say that we have a portfolio of IP not subject to any interference that actually covers, you know, products in development, using Cas9 for the application of human therapeutics.
You know, looking forward, we are, you know, happy to grant licenses to enable delivery of this technology to patients, and, you know, believe that we should recognize significant value around that.
Okay, great. Thanks. In terms of granting license, we're not gonna know the appeal decision likely before the BLA and also potentially the launch. Like, how do you sort of think about that?
Well, I think there are a number of important points to make. I think the first, again, is just to remind that the appeal applies to some of our Cas9 in human therapeutics IP estate, but not all. I think it's important to emphasize that we have Cas9 or IP around Cas9 use in human therapeutics that is not subject to any interference and therefore is not subject to that appeal's case. We actually believe that it actually covers products in development. What I think I want people to really understand is that that appeals case is around interference on some of our IP estate, but not all.
Okay, got it. Just one more question from me. You're seeing some next-gen SCD therapies already in development with new conditioning agents. If they don't succeed, it doesn't seem like the shelf life for these first-gen therapies will last too long. Any thoughts about this?
Just to be clear, I understand your question. You're actually questioning if the evolution of new conditioning would actually change the landscape for the products that are close to approval. I think it really might very much depends on the nature of the conditioning. As we look out at total execution, obviously something we've looked at closely, one of the important things is to balance both the reduction of toxicities with engraft and efficacy. I think we all see that it's a very important path to increasing eligibility for patients because more patients will be able to tolerate a non-genotoxic, less toxic conditioning regime. Many of the regimes or some of the approaches are not actually editing dependent.
They are actually... What we actually believe is that the evolution of milder conditioning could actually expand and grow the size of the eligible patient population for all. I think the important thing obviously also is that we are looking beyond not just conditioning, but looking to in vivo editing as part of our strategy. For the very simple reason that we believe that in vivo editing will further increase the eligibility of the patient population for treatment.
Got it. Very helpful. Thanks.
Thank you. Our next question is from Debjit Chattopadhyay with Guggenheim. Please proceed with your que-
Morning, everyone. This is Ry Forseth in for Debjit. I just want to build off of the conditioning discussion and sort of get a outline of your strategy. Is it sort of bifurcated, kind of exploring both in vivo editing and the opportunity to in-license, assets that would be alternative to busulfan? Can you sort of map that out for us? Just wanted to get your thoughts too, on the ASGCT abstracts, and sort of what you see in the competitive landscape, around conditioning, especially given that a competitor, is kind of moving forward with the, CD117, approach?
Yeah. Thanks very much, Debjit. I think I'll start, and then I will have Baisong comment. From a strategic point of view, we are using a two-pronged strategy. We have directed investments, significant investment, internally, to our discovery of in vivo editing for hematopoietic stem cells. I think as I said earlier, we believe that this is a problem where we can focus on delivery, where certainly in humans, we believe we have solved the 2 of the 3 challenges around the selection of a CRISPR enzyme as well as a target. In parallel, we actually are continuing and have ongoing evaluations of milder conditioning approaches.
I think you asked more, importantly or in follow-up, a question about the, for example, CD117, and I'll ask Baisong just to talk about that.
Yeah. Yeah. Thanks, thank you. Thanks for your question. I can say that we have looked into this mild conditioning in very deep, looking this space as well as internal efforts-wise. There were generally probably two approaches. One is that, a CD117 antibody and in that direction, and the other one is actually doing the cell modification together with the gene editing. The latter approach is in infancy, if I may say, and the previous approach with antibody have many different exercise on that. I think we are very closely monitoring this space and understand these. I also want to mention that the mild conditioning, if successful, is not gonna be only successful for sickle cell transplant.
It's gonna be successful for leukemia and many different, gene, the therapeutic areas. We are actually very much looking into this space.
Thanks for the insight.
Thank you. Our next question is from Madhu Kumar with Goldman Sachs. Please proceed with your question.
Hey, this is Rob on for Madhu. Thanks for taking our question. We were just wondering how should we think about forward OpEx, particularly R&D, given our robust recruitment into RUBY, and how lumpy will spend be around cell editing and transplants versus follow-up?
I'm sorry, Rob. I actually had great difficulty hearing your question. Could you just repeat it, please?
Sure. We are just wondering, how we should be thinking about forward OpEx, particularly spending in regard to, transfusions versus follow-up.
Okay. I think you're asking, if I'm very clear, you're asking about forward-looking OpEx around the execution of the RUBY study. Is that correct? Okay. Michelle?
Rob, I mean, we don't disclose our annual OpEx or our quarterly OpEx, but I can tell you that about half of our spend is in on both the RUBY trial and the TDT trial. We don't expect an enormous increase quarter over quarter. As we do dose more patients, obviously our R&D spend will go up, but not substantially.
Thank you.
Our current, I'll just say one more. Our current cash runway supports our RUBY trial.
Thank you. Our next question is from Greg Harrison with Bank of America. Please proceed with your.. .
Good morning. This is Mary Kate on for Greg. Thanks for taking our question. With 19 patients enrolled in plans for 20 to be dosed by year-end, maybe how many sickle cell patients have been currently treated with EDIT-301? Maybe how could we expect to see this represented in the efficacy readout by the year-end update? Thank you.
Thanks for that question, Mary. We have 19 patients enrolled, and among those, as we just mentioned, forur have been dosed, and we actually have more patients have been completely apheresis, have a CD34 cells edited and ready to schedule dosing. We have other patients who are in the process of apheresis. We are very confident that we will be able to dose 20 patients by the year-end.
Great. Thank you.
Thank you. Our next question is from Luca Issi with RBC Capital Markets. Please proceed with your question.
Oh, great. thanks so much for taking my question. Maybe on beta thalassemia, obviously most patients are in Southern Europe, so wondering if you could comment on what's the plan to capture that market and maybe how you're thinking about some of the key lessons learned from the unsuccessful launch of bluebird bio there. Then maybe on sickle cell disease, wondering if you can comment on pricing. Obviously, the ICO reports is just $1.9 million, so wondering if that is actually aligned with your thinking. Then maybe lastly, on LCA10, any update on partner discussions there? Thanks so much.
Thanks very much, Luca. Obviously, beta thalassemia is a disease that dominates parts of the world, particularly Europe, Southeast Asia, South Asia, amongst others. From a point of view of our forward-looking, we are actually focusing our efforts on North America currently. We have shared in the past that from an upside point of view, we are looking open to partnering, ideally targeting a partner with a large global footprint, who would actually collaborate certainly in sort of ex-U.S. development and commercialization. That's what I would say I can talk about when we look to your point about beta thalassemia outside North America.
I will say that we are happy, very happy with the progress that we're making, with execution here within the United States and North America. With regard to pricing, I think it's very early days yet for us to be talking about pricing. This is something that we would be very happy to discuss, when we're actually closer to approval and launching, and we look forward to future conversation around there. Obviously, we look to the market evolution over that time, but we're going to talk about that closer to launch and approval. Finally, with regard to LCA10, we have, we really have a practice of not really going into details until we have a deal signed and executed.
Maybe just to add one more point.
Thanks so much.
Oh, sorry. Just to add one more point.
Please.
As Gilmore mentioned about pricing, right? Certainly we are very early stage. We're happy to see the community is looking to the value of this gene editing therapy. We are happy to see that the ICO report recently in this space. As Gilmore mentioned, this will be evolving, but we are pleased to see that the entire community recognize the value of the medicine in this field. Thank you. Thanks so much.
Thank you. Our next question is from Jay Olson with Oppenheimer. Please proceed with your question.
Hey, good morning. This is Cheng. I'm on the line for Jay. Thanks for taking the question. Maybe two from us. I'm just wondering if there's a chance where you have a capacity to dose more than 20 patients for the sickle cell disease program this year? Second question is on your ex-U.S. strategy. What's your current thinking and if you are planning to partner that program, what is the best timing to do that? Thank you.
Thanks very much. Do we have capacity to dose more than 20 patients? Yes. One of the important points when we wrote out our strategy was to again sharpen our focus on developing and accelerating EDIT-301, and indeed, we have deployed capital to enable not just the acceleration on the clinical side, but actually also to ensure that we have capacity to edit, or rather CMC capacity to edit and support that clinical acceleration. Indeed, we do have that capacity to dose more than 20 patients. I think your second question was around ex-US and the timing partnership. I think as I said before, we are interested in partnering.
We're looking to a partner with a global footprint that would actually certainly support ex-U.S., you know, particularly on the development and commercialization. With regard to timing, we wouldn't really discuss the timing until we actually have a deal signed and executed.
Okay, thanks.
Thank you. Our next question is from Joel Beatty with Baird. Please proceed with your question.
Hello, this is Benjamin Paluch for Joel. Thanks for taking our question. Looking across other late-stage products in sickle cell and TDT, it appears that datasets of 30 patients could support approval. With the Editas being on track to dose 20 patients by year end, how quickly do you think you'll be able to secure the necessary data to support regulatory approvals? Thank you.
Thanks. Thanks very much, Ben. Baisong .
Yeah. Thanks for the question. As I mentioned earlier, in terms of total number of patients required to support registration and then need to have a required alignment with the regulatory agency. In terms of the progression of the study, we are very positive about the momentum, so we are very optimistic we will be able to dose patients as we planned.
I think the key thing, Ben, is that you know, you've actually identified sort of a benchmark, but obviously what we need to do is, as planned, sit with the regulators and, come to an agreement on what the dataset they would like to see for our programs.
Great. Thank you.
Thank you. Our next question is from Joon Lee with Truist Securities. Please proceed with your question.
Hey, thanks for taking the follow-up question. Sorry for the background noise. I'm at the train station. You know, I had the same question as Steve, but maybe a different way of asking. You know, what percentage of sickle cell patients with hereditary persistence of fetal hemoglobin have mutations along the globin locus versus the BCL11A locus?
Jim, thanks for your question. We do not have all the specifics on your question on that. We know is the mutation, the promoter region directly impacted the fetal globin expression. BCL11A is a transcription factor which impacts multiple different cell units, and that the mutation of the BCL11A will have much different impact from the fetal globin and expression only will have other impacts too. The gene editing mutation is much more complicated issue than the HPFH with the promoter region and mutation for the gamma-globin promoters.
I think another way, Joon, to actually characterize this, you know, because some of the prevalence is a little harder to quantify, but another way of pointing it is really the strength of the signal. The hereditary persistence of fetal hemoglobin and its capacity to substantially mitigate the effects of sickle cell disease and thalassemia were actually determined actually quite some time ago because this phenotypic change actually the phenotype to genotype correlation was actually quite robust and identified actually you know a few decades ago. Whereas the BCL11A was identified really through a GWAS assessment, genome-wide assessment.
Thank you.
Thank you. We have reached the end of the Q&A session. With that, ladies and gentlemen, this concludes today's call. Thank you once again for your participation. You may now disconnect your lines.