This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk16: Good morning and 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 Christy Barnett, Corporate Communications and Investor Relations at Editas Medicine.
spk02: 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 investor 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, Gilmour O'Meal.
spk09: Gilmour O'Meal Thank you, Christy, and good morning, everyone. Thank you for joining us today on EDItas' first quarter earnings call. I am joined today by two other members of the EDItas executive team, Baesong Mai, our chief medical officer, and Michelle Robertson, our chief financial officer. As many of you know, in early January, we shared our strategy 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 EDIT301 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 EDIT301 for severe sickle cell disease and transfusion-dependent beta thalassemia, or TDT, We have sharpened our discovery focus to in vivo administer 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 leverage our IP portfolio to drive out licensing and partnership discussions. So, 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 1-2 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 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 EDIT31 for the treatment of sickle cell disease, and 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, and in our company-sponsored webinar. Baesong will share further details regarding our June data readout and our enrollment progress in his remarks. On EDIT301 for TDT, we are pleased to share that we dosed the first patient in our EDITHAL Phase 1-2 trial in the first quarter, and that the patient has successfully engrafted neutrophils and platelets. Enrollment continues to progress, and 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, and 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 US 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 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 US 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. Now, I will turn the call over to Baesong, our Chief Medical Officer. Baesong.
spk06: Thank you, Guillermo. Good morning, everyone. Let's start with 8301, 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 the year end. as well as to dose 20 total patients by year end. Turning to clinical data, I'm excited that we will present RUBI clinical data as an oral presentation at the European Hematology Association, or eHeart Congress, and at our company-sponsored webinar in June. The dataset will include safety and efficacy data for multiple patients, including 10-month data from the first patient treated and six months data from the second patient treated, including total hemoglobin, fetal hemoglobin. We will also share data on safety, neutrophil and platelet engraftment, and vaso-occlusive event, or VOE, from the first four patients. As a reminder, last December, we presented initial data from the first two patients treated in the RUBI trial. The first patient, who had five months of follow-up after treatment with LE301, showed clinically significant improvements across all hematological parameters and no VOEs. Specifically, the patient had an increase of fetal hemoglobin fraction to 45.4 percent five months after N301 infusion and the correction of anemia with total hemoglobin level well into the normal range at 16.4 grams a deciliter. initial clinical data indicated that AD301 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 have demonstrated that targeting of gamma-globin promoter enables increases of fetal hemoglobin independent of erythropoietic stress. Given the unique gene editing approach and the measures of action by EDDI301, supported by preclinical data and initial clinical data, we continue to believe that EDDI301 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 AD301. Turning to AD301, ADI-Cell Phase 1-2 Trial for Transfusion-Dependent Velocirrhizemia. As Guillermo 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 EDI-301 trial by year end. As we have done for the Ruby study, we are also taking multiple measures to accelerate the development of EDI-301 for TDT and have strong positive momentum. We have enrolled multiple patients who have completed a phrasis and have their CD34 positive cells edited, or are in the process of phrasis. Recently, I have been traveling around the country, visiting our Ruby and Edithell 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 83.1 in patient recruitment, aphasis, editing, and dosing in both studies. I'm excited to hear from investigators that patients dosed with 8301 have already seen positive changes in their lives. We look forward to sharing additional updates as the year progresses, including Ruby study data next month and at year end, and sharing initial clinical data from EDITHEL study by year end. Now I will turn the call over to Michelle, our Chief Financial Officer, to review our financials.
spk03: Thank you, Besan, 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 first quarter of 2023. I'll take this opportunity to briefly review a few items. Our cash, cash equivalents, and mock book securities as of March 31st were $402 million compared to $437 million as of December 31st 2022. We expect our existing cash, 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 to $6.8 million in 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 was $23 million, compared with $19.5 million for the first quarter of 2022. The $3.5 million increase is primarily attributable to increasing professional services expenses to support business development activities, partially offset by a decrease in stock compensation expenses. 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, EDIT has remained in a strong financial position, and our sharpened discovery focus allowed us to concentrate our talent and extend our cash runway into 2025, which provides ample resources to support our continued progress in both of our EDIT 301 trials as well as advancing our research efforts in hemoglobinopathy and other in-devo discovery. With that, I will hand the call back to Gilmar.
spk09: 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. And 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 3.1 Edithal trial for TDT by the end of 2023, dosing 20 total patients in our EDIT 3.1 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, and finally, leveraging our robust IP portfolio and business development activities to drive value and complement for 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 and we're happy to answer questions. Thank you.
spk16: 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 1 on your telephone keypad. A confirmation tone will indicate that your line is in the question queue. You may press star 2 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.
spk17: One moment, please, while we poll for questions. Thank you.
spk16: And our first question comes from June Lee with Truist Securities. Please proceed with your question.
spk13: Hi. Thanks for taking our questions. Novartis recently terminated their supercell 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 strategies should continue to work when Novartis fails? And I will follow up. Thank you.
spk09: Thanks very much, June. 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 that it is that in our initial POC readout at the end of last year, we actually saw very robust data with 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 now 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 of fetal hemoglobin. I think we believe that all those factors point towards a key difference and differentiation. And indeed, our preclinical data and our clinical data have actually supported that hypothesis.
spk13: Great. So can you remind me if you have any data preclinically comparing the entity with the same region using Cas9 versus AS Cas12 that you're using and what the differences in output may be?
spk04: Sorry, Jun.
spk13: Yeah, so I mean, comparing CAS9, which is what I think Novartis used, and ASCAS12A, which is what you're using, you get a different outcome if you were to target the same lesion in terms of getting deletions or indels.
spk06: Jun, I think you're a little bit back down, but let me try. This is a base song. Let me try to see whether I understand correctly. Sorry, background noise. So I think your question to say compared to Novartis and do we have a comparison between Cas9 and Cas12a and also the region just Guillermo mentioned. Is that your question?
spk13: Yeah. No, actually, if you target the same region either with Cas9 or Cas12a, what differences in outcome do you get?
spk06: Yeah. Let me just go in it, please. 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. So without too many specifics, but we recovered a large region of the promoter in the HBG192. And we find out that blended to the region we selected, which Gilmour just mentioned, is consistent to the clinical observation for these HBFH. And then we also compared the Cas9 with Cas12, and we found the difference between Cas9 and Cas12. Does that answer your question?
spk13: Yeah, no, absolutely. Your impaired data says it. But we're just curious what was driving that difference. Thank you so much. I'll hop back on to you.
spk06: Thank you.
spk16: Thank you. Our next question is from Samantha Semenkal with Citi. Please proceed with your question.
spk15: Hi, good morning, and 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.
spk09: Thanks, Samantha. I just have a base song update.
spk06: She'll give you detail there. It is a normal oral presentation that's being accepted.
spk15: Okay, got it. Thank you for that. And then I also wanted to clarify, I heard you mention, obviously, we'll have updated data for the first and second patients. And then I heard you, I think, say four patients. So will it be six patients total that will get data on VOE, or is it, or VOCs, or is it four patients total?
spk06: Total will be four patients at the eHeart presentation.
spk15: Got it. Okay. And then, you know, when you're making that cutoff for those incremental additional two patients, what level of follow-up was the cutoff there? So I'm just curious. Is it a couple months or is it one month? Any information you could provide would be helpful.
spk06: Yeah. For this next two patients, we'll have two months or more.
spk15: Perfect. Thank you so much for taking the question.
spk09: Thank you. Just in thought of one other thing, I think it's important to understand that obviously we will, because the abstract, which will be published later, was based on data cut earlier, we would like to be presenting more data than in the abstract at the EHA Congress.
spk06: Yeah. Thanks, Guillermo. And just kind of also follow up on that. The abstract will be available on May 11th.
spk16: Thank you. Next question is from Dagon Ha with Stiefel. Please proceed.
spk04: Hey, great. Thanks so much for taking the question and look forward to the data update next month. So I guess I was just kind of wondering about your strategy going forward. So 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. But curious, is delivery tech or less burdensome conditioning a stronger emphasis in your lineup or is it advancing new programs? And if it's the latter, I guess, would you continue to do other ex vivo HSC or is it more of an in vivo? And in that case, would you also think about other organs? And I've got a follow up.
spk09: Yeah, thanks very much, Jagan. We are, you know, the large part of our discovery focus is actually on in vivo HSC. 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 the point of view of HSCs, if you reduce the problem of in vivo to sort of three elements, 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 target of that specific HBG12 promoter. And so that reduces it to an 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.
spk04: Got it. Thanks so much. And then second question, I just wanted to follow up on Bezong'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? And 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.
spk06: 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. And so actually the benefit for us is those investigators have a lot of experience in this field.
spk09: I think, you know, just building on Baesong'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. And I can go into more details on that. But I think a very important point, and 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. And 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.
spk16: Thank you. Our next question comes from Steve Seedhouse with Raymond James. Please proceed with your question.
spk01: 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 urethra poetic stress. And as you know, the recent ICER report on XSL uncovered an ongoing phlebotomy, at least one in sickle cell. And some of the earlier data releases for that program in thalassemia indicated phlebotomy use there as well. But that just stopped being reported at some moment. So it's not clear how prevalent phlebotomy use is for excess cell. And 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 HB F levels, probably because of the stress erythropoiesis it causes. So 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 HPG1,2 locus, what has phlebotomy use been like in your study, and if you think this is all potentially a competitive advantage for you. Thanks.
spk06: Steve, thank you very much for your question. So, from our own clinical data, preclinical data, and also published clinical data, you're probably referring to, for the BCL11A targeting approach, it did require some stimulation for the stress to increase the fetal loading, sufficient fetal loading expression. And so, that's actually the reason We're choosing the target that we are choosing 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 publications. And 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. So I would not comment on their data unless I publish.
spk09: However, 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 erythroiesis, as we hypothesized based on the known biology and our non-clinical data, that our approach is not dependent on stress erythroiesis.
spk16: Thank you. Our next question is from Yanan Zhu with Wells Fargo. Please proceed with your question.
spk10: Hi. Thanks for taking our questions. Maybe to continue the discussion a little bit from the prior question, Gilmour, you mentioned that the total hemoglobin for the first patient is quite robust and in the normal range. The percent of fetal hemoglobin appears to be very much in line with competitor gene editing product. So 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? And along that line, to continue a little further and to perhaps looking into what we could expect from patient number two at IHA, I was just wondering, could you remind us the baseline hemoglobin for patient number two, and what is the normal range for the female patient, which is obviously the second patient. Thank you.
spk06: Thank you. So thanks for your question. So I will start with answering your first part of the question regarding the... fetal hemoglobin versus the number of red blood cells and all these. So what we see is actually robust erythropoiesis for these patients we observed. So their hemoglobin level is contributed by both the hemoglobin per cell as well as the number of red blood cells. And you can see that we actually do see the increase also on both ends of that. And then also I 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. So that's kind of all in that. And then regarding the second patient, and we will present the data very soon, so I will not comment on the specifics of the patient 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. So there's some difference in that, too.
spk09: Great. I think one other thing, you know, you asked a question about what was the baseline hemoglobin of the patient one. And 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, comprised at 3.5 gram per deciliter increase.
spk06: Yeah. Maybe I'll just add a little bit of nuance on that baseline for sickle cell patients especially for gene editing trial. And because the patient, when they prepare for a phoresis and conditioning, and they usually have blood transfusion. So the baseline actually we have, it's not the lowest level we recorded. We just set up a time of the visited two as the baseline. So actually it's confounded. It could be many different reasons for the baseline on that too. That's just a new nuance. 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 is just an example about the baseline, maybe a little bit more confusing.
spk10: 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.
spk09: Thanks very much, Yanan. We designed Our discovery group and scientists designed and selected the combination of Cas12A with the specific targeting of the HPG1-2 promoter using a set of empirical experiments to determine what was the best approach to driving not just fetal hormone 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. And those empirical experiments really determined that approaching or directly targeting the HBG1-2 promoter would be better. And that was the original design hypothesis. The nonclinical data, preclinical data actually supported that, showing robust erythroid output in comparison to other approaches, as well as robust fetal hemoglobin expression. And 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. And so, obviously, it is, we haven't seen enough data in our Edifal patient. 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.
spk10: Great. Thanks for all the answers.
spk17: Thank you. Our next question is from Phil Nadeau with TD Cowen.
spk16: Please proceed with your question.
spk05: Good morning. This is for Phil. Thanks for taking my question. On the program, have you met with the FDA to gain better visibility on the regulatory path? And then a second question on the TPP program. For the year-end update, will that include only the Sentinel patients that you initially dose, or will you disclose additional patients? And if you will be disclosing additional patients, are you planning on reporting when you switch from central dosing to parallel dosing? Thank you.
spk09: So I think what I'll do is ask Baesong to, I've actually, I'll keep track of the questions, Baesong. It might ask you just to ask, you know, the question on the FDA and the regulatory interactions that are planned.
spk06: Yeah. Thanks for your question. So we certainly have a lot of engagement with FDA, as you see that recently we have the offering direct designation. And 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 that data can be supporting registration. And we will have further engagement with the agency to align on the total registration package for the BLA submission, which is also planned. And your second part of the question is about the Betafil data. So we are moving really along with the Betafil study, and we expect that we will have data by year end more than Sentinel patient. And so, we're looking forward to sharing the data by the year end.
spk05: Oh, I see. And you, more than a second question. So, are you planning to disclose when you get approved to continue parallel voting before then?
spk09: 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.
spk20: Got it. Thank you.
spk16: Thank you. Our next question comes from Rick Bankowski with Cantor Fitzgerald. Please proceed with your question.
spk18: Hey, good morning, and 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, so do you have any sense of how many patients' worth of data you will need for a registration or filing?
spk06: Thank you for the question. So, we certainly think that, you know, with the gene editing approach that we have we will be able to generate a substantial amount of data. And the specifics on the number of patients to be able to use for such registration, we need to align with the regulatory agencies that we are planning to discuss with FDA.
spk18: Okay, got it. And 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?
spk03: It's a combination of both the Shoreline and then some other small, like, sub-license revenue.
spk20: You got it. Thanks for taking the questions. Thank you.
spk16: Thank you. Our next question is from Rich Law with Credit Suisse. Please proceed with your question.
spk08: Good morning, and thanks for taking my question. I have a couple questions for you guys. So with the appeal litigation pending, what does it mean for companies such as CRISPR and Vertex that already filed a BIA for XSL that utilize CRISPR-Cas9 from your IP perspective? They don't have a license from you or the bro and could potentially launch the product before we know the outcome of the appeal. So any insight here would be helpful. And then I have a follow-up question.
spk09: 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'll 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 products in development using CAS9 for the application of human therapeutics. And looking forward, we are happy to grant licenses to enable delivery of this technology to patients and believe that we should recognize significant value around that.
spk20: Okay, great. Thanks.
spk08: So in terms of granting license, so we're not going to know the appeal decision likely before the BLA and also potentially the launch. Like, how do you sort of think about that?
spk09: Well, I think that 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 appeals case. And we actually believe that it actually covers products in development. And so what I think I want people to really understand is that that appeals case is around interference on some of our IPS statement, not all. Okay, got it.
spk08: And then just one more question from me. So you're seeing some next-gen STD therapies already in development with new conditioning agents. So 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?
spk09: So 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 either are close to approval. I think it really might very much depends on the nature of the conditioning As we look out at our execution obviously something we've looked at closely and one of the important things is to balance both the reduction of toxicities with engraftment efficacy and I think we all see that it's a very important path to increasing eligibility for 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, and so 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 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.
spk20: Thanks
spk17: Thank you.
spk16: Our next question is from Debjit Chattotadjie with Guggenheim. Please proceed with your question.
spk07: Good morning, everyone. This is Rai Forseth for Debjit. I just want to build off of the conditioning discussion and sort of get an 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? And 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.
spk09: Yeah. Thanks very much, Jeb Sheed. I think I'll start and then I will have a based on 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. And I think, as I said earlier, we believe that this is a problem that we can focus on, where we can focus on delivery, where, certainly in humans, we believe we have solved two of the three 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. And I think you asked more importantly, or in follow-up, a question about the, for example, CD117, and I'll ask Daesang just to talk about that. Yeah. Yeah, thanks.
spk06: Thank you. Thanks for your question. I can say that we have looked into these model condition in very deep, looking at the space as well as the internal efforts-wise. And there were generally probably two approaches. One is that CD117 antibody and in that direction. And the other one is actually doing the cell modification together with gene editing. So the latter approach is still in infancy, if I may say. And the previous approach with antibody have many different exercise on that. So I think we are very closely monitoring this space and understand these. And I also want to mention that the model conditioning is successful, is not going to be only successful for sickle cell transplant, it's going to be successful for leukemia and many different gene, the therapeutic areas. So we are actually very much looking into this space.
spk20: Thanks for the insight.
spk17: Thank you. Our next question is from Madhu Kumar with, Goldman Sachs. Please proceed with your question.
spk12: Hey, this is Rob. Thanks for taking our question. We were just wondering how should we think about forward optics, particularly R&D, given our robust recruitment into Ruby, and how long we will spend around cell editing and transplants versus follow-up?
spk09: I'm sorry, Rob. I actually had great difficulty hearing your question. Could you just repeat it, please?
spk12: Sure. We were just wondering how we should be thinking about forward OPEX, particularly spending in regard to transfusions versus follow-up.
spk09: Okay. So I think you're asking, if I'm a bit clear, you're asking about forward-looking OPEX around the execution of the Ruby study. Is that correct? Okay, Michelle.
spk03: Yeah, so 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 both on the Ruby trial and the TBT trial. We don't expect an enormous increase quarter over quarter, but as we do dose more patients, obviously our R&D spend will go up, but not substantially.
spk20: Thank you.
spk03: And our current, I'll just say, our current cash runway supports our Ruby trials.
spk16: Thank you. Our next question is from Greg Harrison with Bank of America. Please proceed with your question.
spk15: Good morning. This is Mary Cadon for Greg. Thanks for taking our question. So 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 EDIT301? And maybe how could we expect to see this represented in the efficacy readout by the year-end update?
spk06: Thank you. Thanks for the question, Mary. So we have 19 patients enrolled, and among those, as we just mentioned, four have been dosed, and we actually have more patients have been completely freezes, have a CD34 cells edited and ready to schedule dosing. And then we have other patients who are in the process of freezes. And so we are very confident that we will be able to dose 20 patients by the end.
spk16: Great. Thank you. Thank you. Our next question is from Luca Isi with RBC Capital Markets. Please proceed with your question.
spk14: Oh, great. Thanks so much for taking my question. Maybe on bisthalassemia, 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. And then maybe on sickle cell disease, wondering if you can comment on pricing. Obviously, the active report suggests $1.9 million, so wondering if that is actually aligned with your thinking. And then maybe lastly, on LCA10, any update on partner discussions there? Thanks so much.
spk09: Thanks very much, Luca. So 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-US development and commercialization. So 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 would 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. And then finally, with regard to LCA 10, we really have a practice of not really going into details until we have a deal signed and executed.
spk06: Maybe just add one more point. Oh, sorry. Just add one more point.
spk19: Please.
spk06: Gilma mentioned about pricing, right? So certainly we are very early stage, and we are happy to see the community is looking to the value of this gene editing therapy, and we are happy to see that the ICER report recently in this space. So we, as Gilma mentioned, this will be evolving, but we are pleased to see that the entire community recognizes the value of the medicine in this field. Thank you.
spk08: Thanks so much.
spk16: Thank you. Our next question is from Jay Olson with Oppenheimer. Please proceed with your question.
spk11: Hey, good morning. This is Cheung on the line for Jay. Thanks for taking the question. Maybe two from us. So I'm just wondering if there's a chance where you have the capacity to dose more than 20 patients for the Segal Cell BD program this year. And the second question is on your ex-US 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.
spk09: Thanks very much. So do we have capacity to dose more than 20 patients? Yes. One of the important points when we rolled out our strategy was to, again, sharpen our focus on developing and accelerating 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 other CMC capacity to edit and support that clinical acceleration. So indeed, we do have that capacity to dose more than 20 patients. And then I think your second question was around XUS 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 XUS, you know, particularly on the development and commercialization. And with regard to timing, we wouldn't really discuss the timing until we actually have a deal signed and executed. Okay, thanks.
spk16: Thank you. Our next question is from Joel Beattie with Baird. Please proceed with your question.
spk19: Hello. This is Benjamin Peluchon for Joel. Thanks for taking our question. Looking across other late-stage products in sickle cell and TDT, it appears that data sets of 30 patients could support approval. So with 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.
spk09: Thanks very much, Ben. Faisal?
spk06: 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 required alignment with the regulatory agency. And 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.
spk09: So I think the key thing, Ben, is that you 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 data set they would like to see for our programs.
spk13: Great, thank you.
spk16: Thank you. Our next question is from June Lee with Truist Securities. Please proceed with your question.
spk13: Hey, thanks for taking the follow-up question. Sorry for the background noise about the transition. I had the same question as Steve, but maybe a different way of asking, what percentage of sickle cell patients with hereditary persistence of hemoglobin have mutations along the globin locus versus the BCL11A locus?
spk06: Jim, thank you for your question. We do not have all the specifics on your question on that, but we know that the mutation in the promoter region directly impacted the fetal global expression. But BCLA is a transcription factor which impacts multiple different cell limits, and that the mutation of the BCLA11A will have much different impact from the fetal hemoglobin and expression only will have other impacts too. So the gene mutation is a much more complicated issue than the SPFH with the promoter region and mutation for the gamma-globin promoters.
spk09: I think another way, Jun, to actually characterize this 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, the phenotype to genotype correlation was actually quite robust and identified actually, you know, a few decades ago, whereas the BC11A was identified really through a GWAS assessment, a genome-wide assessment.
spk13: Thank you.
spk16: Thank you. We have reached the end of the Q&A session. And with that, ladies and gentlemen, this concludes today's call. Thank you once again for your participation. You may now disconnect your lines.
Disclaimer