Editas Medicine (NASDAQ:EDIT), a leader in gene editing technology, has reported significant advancements and robust financial results in its fourth quarter and full year 2023 earnings call.
The company highlighted the success of its lead gene-editing candidate, reni-cel, and its strategic focus on in vivo gene editing and hemoglobinopathies. With a strong financial position, Editas Medicine (ticker: EDIT) is poised to continue its clinical and research developments into 2024.
Key Takeaways
- Editas Medicine has exceeded enrollment goals for reni-cel and presented positive clinical data.
- The company has selected the AsCas12a enzyme for the reni-cel program, showing increased efficiency.
- Financials are strong with $427 million in cash reserves as of December 31, 2023, and expected funding until 2026.
- Revenue for Q4 2023 was $60 million, largely from a licensing agreement with Vertex Pharmaceuticals (NASDAQ:VRTX).
- Clinical updates, including a substantial data set, are expected in the middle of the year.
- The company is confident in its FDA engagement and manufacturing scale-up.
Company Outlook
- Editas Medicine aims to provide additional clinical updates and complete enrollment in the adult cohort for reni-cel.
- The initiation of the adolescent cohort for reni-cel is scheduled.
- Preclinical proof-of-concept for an undisclosed indication in the in vivo pipeline is to be established.
- Business development efforts will leverage the company's intellectual property portfolio.
Bearish Highlights
- The market for gene editing is developing but may take time to mature fully.
Bullish Highlights
- Editas Medicine has strengthened its in vivo discovery capabilities and increased business development activities.
- The company has ongoing engagement with the FDA and is confident in their oversight of off-target editing.
- There is optimism about the CMMI pilot and government interest.
Misses
- There were no significant misses reported in the earnings call.
Q&A Highlights
- The company is focused on high conviction targets that offer differentiation from the standard of care.
- Editas Medicine is keen on partnering for global commercialization, with a current focus on North America.
- They addressed a case of erythrocytosis, confirming it was not related to the treatment.
Editas Medicine has demonstrated a strong commitment to advancing its gene-editing technologies, particularly its reni-cel program. The company's strategic focus on high-impact clinical outcomes, such as hematological parameters, organ function, and patient-reported outcomes, positions it as a pioneer in the field. With a healthy financial outlook and ongoing clinical trials, Editas Medicine is set to make further strides in the gene-editing market, while maintaining a strong partnership with Vertex Pharmaceuticals and engaging proactively with regulatory bodies. The anticipated clinical updates and preclinical proof-of-concept data are eagerly awaited by stakeholders as Editas Medicine continues to optimize its processes and enhance patient experiences in clinical settings.
InvestingPro Insights
Editas Medicine's (ticker: EDIT) recent earnings call underscores a solid financial foundation and a commitment to advancing gene-editing therapies. Delving into the company's financial health and market performance offers additional insights for investors.
InvestingPro Data metrics reveal a market capitalization of $822.88 million, which reflects investor confidence in the company's potential despite its challenges. The revenue growth is particularly striking, with a 296.32% increase over the last twelve months as of Q4 2023, indicating that the company is expanding its financial base rapidly. However, the gross profit margin at -127.4% suggests that Editas is investing heavily in its research and development efforts, which is common for companies in the biotechnology industry focusing on groundbreaking therapies.
The InvestingPro Tips highlight two critical aspects of Editas Medicine's current situation. Firstly, the company holds more cash than debt on its balance sheet, which is a reassuring sign for investors worried about financial sustainability. This aligns with the reported $427 million in cash reserves as of December 31, 2023. Secondly, the strong return over the last month, with a 39.34% price total return, underscores a recent surge in investor optimism, possibly related to the positive clinical data and strategic advancements mentioned in the earnings call.
For investors seeking a deeper analysis, there are additional InvestingPro Tips available on the platform. By using the coupon code PRONEWS24, investors can get an additional 10% off a yearly or biyearly Pro and Pro+ subscription, providing access to a comprehensive set of insights that could further inform investment decisions.
With Editas Medicine's strategic focus and financial health, coupled with the insights from InvestingPro, stakeholders have a well-rounded view of the company's position in the dynamic gene-editing market.
Full transcript - Editas Medicine (EDIT) Q4 2023:
Operator: Good morning, and welcome to Editas Medicine's Fourth Quarter and Full Year 2023 Conference Call. All participants are now in listen-only mode. There will be a question-and-answer session at the end of this call. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Cristi Barnett, Corporate Communications and Investor Relations at Editas Medicine.
Cristi Barnett: Thank you, Maria. Good morning, everyone, and welcome to our fourth quarter and full year 2023 conference call. Earlier this morning, we issued a press release providing our financial results and recent corporate updates. A replay of today's call will be available in the Investors section of our website approximately two hours after its completion. After our prepared remarks, we will open the call for Q&A. As a reminder, various remarks that we make during this call about the company's future expectations, plans and prospects constitute forward-looking statements for the purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent Annual Report on Form 10-K, which is on file with the SEC as updated by our subsequent filings. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Except as required by law, we specifically disclaim any obligation to update or revise any forward-looking statements, even if our views change. Now, I will turn the call over to our CEO, Gilmore O'Neill.
Gilmore O'Neill: Thanks, Cristi, and good morning, everyone. Thank you for joining us today on Editas's fourth quarter and full year 2023 earnings call. I am joined today by four other members of the Editas executive team, our Chief Medical Officer, Baisong Mei; our Chief Financial Officer, Erick Lucera; our Chief Scientific Officer, Linda Burkly; and our Chief Commercial and Strategy Officer, Caren Deardorf. We are pleased with Editas' momentum and progress in the fourth quarter and all of 2023. In early 2023, we shared our vision and the three pillars of our strategy to position Editas as a leader in in vivo program for gene editing and hemoglobinopathies. The first of these pillars, to drive reni-cel, formerly known as EDIT-301, toward BLA and commercialization. The second, to strengthen, reorganize, and focus our discovery organization to build an in vivo editing pipeline. And the third, to increase business development activities with a particular focus on monetizing our very strong IP. So how did we do last year? Well, we achieved a lot. First, we accelerated the clinical development of Reni-cel, exceeding our enrollment goal of 20 patients and sharing clinical updates from our RUBY and EdiTHAL studies in June and in December of 2023. And those accumulating data have strengthened our belief that reni-cel is a competitive potential medicine with a differentiated profile characterized by correction of anemia at normal physiologic ranges of hemoglobin. Second, we strengthened our in vivo discovery capabilities and organization and hired a new Chief Scientific Officer, Linda Burkly, who brings three decades of experience in successfully inventing, developing, and moving new human medicine forward. And third, we increased our business development activities and monetized our IP, leveraging our robust IP portfolio. A critic example was our granting Vertex a non-exclusive license for our Cas9 IP in a focused way to enable the [XSL] launch. Finally, we strengthened our senior leadership team with people who have a proven track record in bringing new medicine through development to approval and commercialization. So how are we executed against these strategies and these objectives? Well, let's start with Reni-cel. First, on enrollment, we have now enrolled 40 sickle cell and 9 beta thalassemia patients in our RUBY and EdiTHAL studies respectively, and enrollment continues at a good pace. Second, on dosing, we have dosed 18 RUBY patients and 7 EdiTHAL patients, and we have multiple patients scheduled for dosing in the coming month. Patient screening and demand in both studies continue to remain robust. Third, on clinical data, we remain on track to present a substantive clinical data set of sickle cell patients with considerable clinical follow-up in the RUBY study in the middle of 2024, with a further update by year-end 2024. On the regulatory front, we have engaged with the FDA regarding the RUBY sickle cell trial. The FDA agrees that RUBY is a single Phase 1, 2, 3 study and has aligned with us on the study design. Our discussions with the FDA will continue as RUBY and EdiTHAL progress and will be enhanced by our RMAT designation for severe sickle cell disease. Baisong will share further details regarding the development of reni-cel in his remarks, as well as recap the RUBY and EdiTHAL takeaways and clinical data that we provided in December and share more information on the adolescent cohort. Now, let's turn to in vivo and our pipeline development, where we strengthened our in vivo discovery capabilities in 2023 and began lead discovery work on in vivo therapeutic targets in hematopoietic stem cells and other tissues. As we announced earlier this year, we aim to establish in vivo preclinical proof-of-concept for an undisclosed indication this year. Linda and her team are leveraging key capabilities that we have in-house and she looks forward to sharing more at a future date. Regarding our hemoglobinopathies focus, after a thorough evaluation of the development landscape, we have decided not to pursue internal development of a milder conditioning regime. We believe standalone milder conditioning regimens will be widely available once FDA approves and therefore we have determined that research, clinical development and regulatory investment in hemoglobinopathies can be better deployed for our continued development of in vivo HSE medicines. Turning to business development. In the fourth quarter, we announced a licensed agreement with Vertex Pharmaceuticals. Editas provided Vertex a non-exclusive license for Editas Medicine's Cas9 gene editing technology for ex vivo gene editing medicines targeting the BCL11A gene in the field of sickle cell disease and beta thalassemia, including Vertex's CASGEVY. And the upfront and contingent payments pursuant to this agreement extended our cash runway into 2026. This and other agreements, the strength of our patents and the number of companies developing CRISPR/Cas9 medicine reaffirm our confidence that our IP portfolio of foundational U.S. and international patents covering Cas9 use in human medicine are a source of meaningful value. So what are our objectives for 2024? For reni-cel, we will provide a clinical update from the RUBY trial for severe sickle cell disease and the EdiTHAL trial for transfusion-dependent beta thalassemia in mid-2024 and by year-end 2024. We will complete adult cohort enrollment and initiate the adolescent cohort in RUBY, which we've already initiated, and continue enrollment in EdiTHAL. For our in vivo pipeline, we will establish in vivo preclinical proof-of-concept for an undisclosed indication, and for PD, we will leverage our robust IP portfolio and business development to drive value and complement core gene editing technology capabilities. We are energized by our progress and execution in 2023. With our sharpened strategic focus, our world-class scientists and employees, and our keen drive in execution, we continue to build momentum to progress our strategy to deliver differentiated editing medicines to patients with serious genetic diseases. Now, I will turn the call over to Baisong, our Chief Medical Officer.
Baisong Mei: Thank you, Gilmore. Good morning, everyone. Let's talk about reni-cel, which is on the clinical development for severe sickle cell disease and transfusion-dependent beta thalassemia. As of today, in the RUBY trial for sickle cell disease, we have enrolled 40 patients and dosed18 patients. We have multiple patients scheduled for dosing in the coming month. We're also pleased to announce that we have initiated adolescent cohort in the RUBY study, which is one of our 2024 objectives. The interest and demand are high, and adolescent patients have already started screening. In the EdiTHAL trial for transfusion-dependent beta thalassemia, to date, we have enrolled nine patients and dosed seven patients. As I shared earlier, I continue to visit our RUBY and EdiTHAL clinical trial sites and continuously speak with investigators. I appreciate the enthusiasm and support from the investigators and study size. I'm pleased with the momentum of reni-cel in patient recruitment, apheresis, editing, and dosing in both studies. I'm excited to hear from the investigators that patients dosed with reni-cel have already seen positive changes in their lives. As Gilmore mentioned, we have aligned with FDA that RUBY clinical trial is now considered a Phase 1, 2, 3 trial for BLA finding. We have also aligned with FDA on the study design and endpoints, and the FDA has agreed to our activation of adolescent cohort. We look forward to future discussion with FDA and continued collaboration. Turning to clinical data, in December 2023, we shared safety and efficacy data from 17 patients, 11 RUBY patients, 6 EdiTHAL patients. Once again, the data confirmed observation from our prior clinical readouts, including reni-cel driving early and robust correction of anemia to a normal physiological range of total hemoglobin in sickle cell patients. Reni-cel drove robust and sustained increase in fetal hemoglobin in excess of 40%. All RUBY sickle cell patients have remained free of vaso-occlusive events following reni-cel treatment. Reni-cel treated sickle cell and beta-thalassemia patients have shown successful engraftment, have stopped red blood cell transfusion. And the safety profile of reni-cel observed today is consistent with myeloablative busulfan conditioning and autologous hemopoetic stem cell transplant. In addition, the trajectory of the correction of anemia and expression of fetal hemoglobin is consistent across reni-cel treated sickle cell disease patients and beta-thalassemia patients at the same follow-up time points. These data reinforce our belief that we have a competitive product and the product potentially differentiated from other treatments with rapid correction of anemia. Thanks to the deliberate choice that our discovery group has made early in the program. As we have previously stated, the choice of CRISPR enzyme and the target to edit for increased hemoglobin, fetal hemoglobin expression matters. Reni-cel uses our proprietary AsCas12a enzyme to edit HBG12 promoter. AsCas12a increases efficiency of editing and significantly reduced off-target editing when compared to other CRISPR nucleus, including Cas9. Editing HBG12 promoter in human CD34 positive cells, resulting in greater red blood cell protection, normal proliferative capacity and improved red blood cell health when compared to editing of BCL11A. We look for differentiation in three categories of outcome in clinical trials. Hematological parameter and organ function and patient reported outcome or quality of life. Based on the clinical data thus far, we believe that sustained normal level of total hemoglobin could be a potential point of differentiation for reni-cel. As a reminder, a sustained normal total hemoglobin level is an important clinical outcome for patients. As the correction of anemia can significantly improve quality of life and ameliorate organ damage. We look forward to sharing additional updates, including RUBY and EdiTHAL clinical trial data with more patients and longer follow-up period in mid-year and additional data by year-end. Now I will turn the call over to Erick, our Chief Financial Officer.
Erick Lucera: Thank you, Baisong, and good morning, everyone. I'm happy to be speaking with you and I'd like to refer you to our press release issued earlier today for a summary of financial results for the fourth quarter and full year 2023, and I'll take this opportunity to briefly review a few items for the fourth quarter. Our cash, cash equivalents, and marketable securities as of December 31 were $427 million compared to $446 million as of September 30, 2023. We expect our existing cash, cash equivalents, and marketable securities together with the near-term annual license fees and contingent up-front payment payable under our license agreement with Vertex to fund our operating expenses and capital expenditures into 2026. Revenue for the fourth quarter of 2023 was $60 million, which primarily relates to revenue recognized under our license agreement with Vertex, which as Gilmore referenced earlier on this call, we announced in December of 2023. R&D expenses this quarter increased by $18 million to $70 million from the fourth quarter of 2022. The increase reflects additional sub-license expenses offset by the decrease in R&D spend resulting from our reprioritization and targeted focus on our reni-cel program. G&A expenses for the fourth quarter of 2023 were $14 million, which decreased from $18 million for the fourth quarter of 2022. The decrease in expense is primarily attributable to reduced patent and legal costs. Overall, Editas remains in a strong financial position bolstered by our sharpened discovery focus, June capital rates, and our recent out-licensing deals. Our cash runway into 2026 provides ample resources to support our continued progress in the RUBY and EdiTHAL clinical trials at reni-cel, continued commercial manufacturing preparation, and the advancement of our discovery and research efforts. With that, I'll hand the call back to Gilmore.
Gilmore O'Neill: Thank you, Erikc. We are very proud of our progress in 2023 and look forward to accelerating the momentum into 2024 as we continue to evolve from a development-stage technology platform company into a commercial state gene editing company. We look forward to continuing our transformation and sharing our progress with you. As a reminder, our 2024 strategic objectives include, for reni-cel, we will provide a clinical update from the reni-cel RUBY trial for severe sickle cell disease and the EdiTHAL trial for transfusion-dependent beta thalassemia in mid-2024 and year-end 2024. We will complete adult cohort enrollment, and we already initiated the adolescent cohort in RUBY, and will continue enrollment in EdiTHAL. For our in vivo pipeline, we will establish in vivo preclinical proof-of-concept for an undisclosed indication. And for PD, we will leverage our robust IP portfolio and business development to drive value and complement core gene editing technology capabilities. As always, it must be said that we could not achieve our objectives without the support of our patients, caregivers, investigators, employees, corporate partners, and you. Thanks very much for your interest in Editas, and we're happy to answer questions. Thank you.
Operator: [Operator Instructions] Our first question comes from Joon Lee with Truist Securities. Please proceed with your question.
Joon Lee: Hi. Good morning, and congrats on the quarter. I'm sorry for my voice. My question is that, could you please elaborate on the hemolysis markers that you're tracking and tell us how they will relate to patient-reported outcomes such as quality of life? Thank you.
Gilmore O'Neill: Thanks very much, Joon. I hope that your voice gets better. I'm going to pass that question over to Baisong.
Baisong Mei: Thanks for the question, Joon. For the hemolysis marker, we look into multiple markers for indicating for hemolysis including reticulocyte, LDH, bilirubin, among others. For the patient-reported outcome, we use several instruments to measure that clinical outcome and quality of life. They're related to the general PRO instrument as well as sickle cell specific instrument.
Joon Lee: Thank you.
Operator: Our next question comes from Samantha Semenkow with Citi. Please proceed with your question.
Samantha Semenkow: Hi. Good morning. Thanks very much for taking the question. Can you share just any additional insights into your FDA conversation as you aligned on the RUBY trial specifically in terms of the number of patients you'll need and the amount of follow-up you'll need to file a potential BLA?
Gilmore O'Neill: I'm going to have Baisong to address that question.
Baisong Mei: Thank you for the question. We aligned with the FDA about the RUBY trial to be a Phase 1, 2, 3 trial to support BLA including endpoint, sample size, and study design. We are continuing to have engagement with the FDA about the BOA data package and the follow-up. We'll have a further discussion with the FDA.
Samantha Semenkow: Got it. Thank you.
Operator: Our next question comes from Brian Cheng with JPMorgan. Please proceed with your question.
Brian Cheng: Hi, guys. Thanks for taking our questions this morning. Can you just give us a sense of what does a Phase 1, 2, 3 designation for RUBY really mean from a timeline perspective? And on the potential differentiation, I think based on your talk about investigators' feedback so far, I'm curious if you can also talk about just feedback that you've been hearing from investigators. Are they seeing potential differentiation this early on? Thank you.
Gilmore O'Neill: Thanks very much, Brian. I think there were three parts to your question. What is a Phase 1, 2, 3 and its impact on the BLA path? What was the investigator feedback on differentiation? And were they seeing signs or what were the things that they might be seeing in patients at this point? What I'll do is just address the first part and then ask Baisong to follow-up on the other two. So with regard to Phase 1, 2, 3, I think the key point here is that it is a single. We've agreed that there's a single Phase 1, 2, 3 study. We have important agreement on what the outcomes are and the size of the study. And what that basically means is that we remain on track and are more confident about being on track to a BLA. I think it's worth calling out that the Vertex study was also the study that was used for their BLA application was designated a Phase 1, 2, 3 before or prior to that BLA. So I hope that actually helps from the point of view of our path to BLA. And I think just mentioning Vertex, it's just worth calling out that we sort of have a benchmark based on the BLA filing from last year with regard to the size of the filing that was originally used for that approval. Baisong?
Baisong Mei: So Brian, for the differentiation and investigator feedback wise, so we actually have quite a bit of engagement with the investigator and from their own observation of their patients as well as to see the data, they're very pleased to see the correction of anemia. And the hematologist that very much appreciate that the level of total hemoglobin be able to correct the anemia and they see their patient is less fatigued and they have more energy and they just, they're direct observation. And then also they told us that total globulin level as published also impacted the end organ function. So those are the direction that we're also looking for.
Gilmore O'Neill: And one other thing I'd just like to quote just with regard to the Phase 1, 2, 3, I think the important thing is that the RUBY study has been, we've agreed with the FDA it's converted from a Phase 1 to a Phase 1, 2 , 3 which allows, because it's a single study, a seamless transition to that study to support BLA. I hope that's helpful.
Baisong Mei: Just to add on Gilmore's point, what Gilmore means is also to say we'd be able to use all the patient data from the study to support the BLA.
Brian Cheng: Great, thanks guys.
Operator: Our next question comes from Greg Harrison with Bank of America. Please proceed with your question.
Greg Harrison: Hi, good morning. Thanks for taking the question. Now that there is a gene editing treatment approved in sickle cell, what are your latest thoughts on how reni-cel would fit in the space? And what have you learned from the early launch by the competitor?
Baisong Mei: Thanks very much, Greg. I'm going to ask Caren to address that question.
Caren Deardorf: Yes, great. Thanks for your question. What we've been hearing from the various stakeholders in this space is a lot of interest and some really good initial momentum. I think we are also hearing that across all of the groups so your stakeholders, your patients, families, your centers which are transplant, maybe gene therapy centers, your qualified centers as well as your payers. There's just a lot of work that needs to happen and I think you all are picking up on that. But it's starting and it's happening. So I think it's the balance of saying there's tremendous interest even from the government in the CMMI pilot that CMS has kicked off. So the way we see it as it is very encouraging. It's going to take time and we really believe that the fast follower of reni-cel is going to be timed very well. It gives us time to be able to continue to collect data that is meaningful, differentiated, to understand where centers may be struggling, where else we can optimize our vein-to-vein profits to deliver a product that's differentiated not just in efficacy and safety perhaps but also in our operational aspects. So we see the market developing in a very robust way. We just think it's going to take a little bit of time. So we're very pleased with initial interest, certainly the ongoing interest in our clinical studies and look forward to talking more with you about it.
Greg Harrison: Great. That's helpful. Thanks so much.
Operator: Our next question comes from Mani Foroohar with Leerink. Please proceed with your question.
Mani Foroohar: Great. Thanks for taking the question. You talked a little bit about improvements in vein-to-vein time as an incremental source of differentiation and independent of clinical data. Can you walk through how you guys think of the timing on which we might see that show up in terms of CapEx investment, in terms of clinical trial execution, et cetera? Like where we're going to start to see data points that could de-risk that part of your advantage in the eyes of investors?
Baisong Mei: Yes. Thanks for the question. This is Baisong. Thank you, Mani. We are in the clinical trial stage, right. We're already trying to optimize all the process from vein-to-vein, as you mentioned. So we amend our protocol and work with our expert in free treats, for example, and to help with the sites in the free treat cycle and help with sites to prepare the patients and provide support. So that's kind of the experience we gather now will help for our future commercial launch. I'll pass that to Caren on that.
Caren Deardorf: Yes. And just to add, as we continue to be very engaged in our clinical sites and expanding our outreach to other centers, we'll have the opportunity to really understand how the process is working, how we make the introduction and the products like reni-cel as seamless as possible, do the advanced work, fit into their existing processes. But we're always looking at opportunities across just, again, the efficiency, the timing, and we'll certainly be able to talk more as we get closer.
Mani Foroohar: Great. That's helpful.
Operator: Our next question comes from Terence Flynn with Morgan Stanley. Please proceed with your question.
Max Skor: Great. Thank you, team. This is Max Skor on for Terrence Flynn. Can you provide an update on CRISPR-Cas9 appeal case and whether you expect an oral argument in the first half of 2024? Thank you.
Gilmore O'Neill: Thanks very much, Max. We have the Court of Appeals, Federal Circuit has yet to schedule that oral hearing. It should be sometime this year. And once we have that scheduling, we can update you on that.
Max Skor: Great. Thank you.
Operator: Our next question comes from Gena Wang with Barclays. Please proceed with your question.
Gena Wang: Thank you for taking my questions. So if I heard it correctly, Gilmore, you mentioned that the FDA and I think both of you may be mentioned single study, FDA agree on the single study, also number of a patient. I'm not sure if they agree on the duration of the study for RUBY trial. So wondering, if we think about the CRISPR trial, vertex trial, it's about 45 to 50 patients. Is that aligned with that numbers? And what is the duration that FDA require? And related questions, how many active sites you have now? And what is your goal of total sites for the pivotal study?
Gilmore O'Neill: Thanks very much, Gina, for your question. Before I, let me just address a couple of things from the point of view of the study design. I think, first of all, the benchmark that was set by the BLA with Vertex approval by the FDA for exa-cel is actually very good benchmark against, which we're operating. And that is certainly informed our discussions with the FDA. We were actually very pleased with the discussion with the FDA, and we believe that it actually really puts us on a track that lines up with the benchmark And as a result, when we actually talk about having enrolled our 40 patients, how we've initiated the adolescent enrollment and so on, we believe we're actually on a very good track for - to BLA. With regard to the number of active sites, I actually want to clarify something. We're not talking about a separate study. Essentially, the RUBY study, which is ongoing with its sites activated, is the Phase 1, 2, 3 study. That will be used for BLA, and that is the agreement that we have with the agency.
Gena Wang: Okay. Sorry. The reason I'm asking more thinking about in the future commercial perspective, if you have already established the active sites for your clinical trial, and it's very easy to transition this to commercial once drug-approved in the future?
Gilmore O'Neill: Yes, I understand that and appreciate that clarification. And certainly, we agree with that principle. I can take it, Caren, if you want to add to that.
Caren Deardorf: No, no. I mean I know we - had already expanded the number of sites previously to get to a number that would support the full study, right, based on. So that was a very thoughtful approach to ensure that we had a good, strong number of sites with geographic coverage.
Baisong Mei: Yes. Maybe I can add a bunch. We already share we have activated over 20 sites. And so we got over 20 sites who are already enrolled 40 patients. And we already, those sites for adolescent cohort that you have the overlap between the adult and adolescent from the same study sites. And we are also activating a few more sites that specifically for pediatric patients.
Gena Wang: Thank you very much.
Operator: Our next question comes from Dae Gon Ha with Stifel. Please proceed with your question.
Dae Gon Ha: Good morning, guys. Thanks for taking our question. I apologize. It's actually a two-part question. But just to clarify on the reni-cel progress in RUBY, if I heard you correct 18-dosed, I thought the prior conversation was 20-dosed by January. So can you talk about sort of the dropouts there? What was the reason behind that? And then another clarification on the FDA side, when you talk about differentiation, have you guys actually engaged them on the angle you're taking on the differentiation, whether total hemoglobin, or end organ function? How are they perceiving that in terms of the conversation? Thanks so much.
Gilmore O'Neill: Thanks very much, Dae Gon. First of all, I think we're actually very happy with where we are with our dosing, 18 patients dosed. And that really has us on track with that dosing pace to get us on track for a presentation of a substantial data set in the middle of the year. And actually, with regard to our driving towards BLA. We have not had dropouts. So I just want to be sure that there's no confusion about that. And I think the final thing is that, you know, Baisong and myself with our clinical development experience, and particularly when you're dealing with complex therapeutics like that, you're going to get some waves, ups and downs and waves of not just enrollment, but dosing, particularly around scheduling, around holiday periods, et cetera. So as they saw and also said we have many more patients scheduled for dosing in the coming months. And as I say, remain on track for a substantive data set in the middle of the year. With regard to differentiation and our conversations with the FDA, we have actually highlighted our potential differentiation, the mechanistic differences behind that, et cetera. But I think it's too soon to comment on where the FDA and where our discussions with the FDA are on that.
Dae Gon Ha: Great. Thank you very much.
Operator: Our next question is from Debjit Chattopadhyay with Guggenheim. Please proceed with your question.
Ry Forseth: Good morning. This is Ry Forseth from Debjit's team. Did the alignment with the FDA include any feedback on off-target editing, profiling akin to sort of the AdCom's criticism around CASGEVY's characterization for the breadth of genetic diversity? And our second question is, so the yet to be disclosed progress are you going to offer proof-of-concept I mean what characteristics of this program are you most excited about? The market size, the opportunity for first-in-class, the specific editing chemistry, et cetera?
Gilmore O'Neill: Thanks very much, Debjit. So let me actually pass the first question to Baisong.
Baisong Mei: Yes. Well, we have continuous engagement with FDA. So we are looking, the engagement is scientifically driven, is to understand the science of our molecule, the data we have, and then how the patient will manage it. And we have a whole range of engagement with FDA, from preclinical, CMC, to clinical. So because, as Gilmore mentioned, we have an armed response destination, and we have a lot of leverage and a lot of opportunity to actually engage with FDA. So we are very happy with the collaborative nature of the engagement. And can I just add to that is that, as we said before, when we actually watched the AdCom discussion, we were very gratified, by what we heard and saw, because our confidence, both in the comprehensive nature of our off-target editing, oversight package, was actually very robust relative to the discussion of the AdCom. And frankly, our off-target editing data package is actually very good, and not surprisingly, because we are using our own engineered AsCas12a enzyme, which is a high fidelity, as well as high efficiency enzyme. And it's worth saying that in our hands and in the hands of others, off-target editing is not detectable across a genome wide screen as opposed Cas9. So feel very good about that. And then with regard to the in vivo characteristics, I think I just want to say, as I said before, that the key things, or factors that we are focusing on is to select a set of targets that are high conviction based on their potential for critical differentiation from the current standard of care. And it actually does include a number of variables, including the probability of technical success, as well as regulatory success and commercial success.
Ry Forseth: Thanks for the rundown.
Baisong Mei: Thank you.
Operator: Our next question comes from Phil Nadeau with TD Cowen. Please proceed with your question.
Phil Nadeau: Good morning. Thanks for taking our question. Our question is on manufacturing. Can you remind us where you are in the scale of process in commercial, manufacturing scale process? And in your discussions with the FDA, have you agreed upon CMC package? And in particular, is there a requirement for patients in RUBY to be dosed with the commercial material? Thanks.
Gilmore O'Neill: Thanks very much for your question. From a CMC point of view, we actually are in a very good place. We have, as you know, had discussions with the FDA and are actually progressing very well along that line. We actually are, as we have our building, our commercial capacity, and obviously that capacity will be ready for the demand that will exist at the time of our launch and is ready for supporting demand beyond that launch. And then with regard to the processes, I would say we're making excellent progress there in support of our BLA so that we would be BLA ready and inspection ready at that time.
Phil Nadeau: Thank you.
Operator: Our next question comes from Jay Olson with Oppenheimer & Co. Please proceed with your question.
Jay Olson: Oh, hi, congrats on all the progress and thank you for providing this update. Our question is about your In vivo program. Can you talk about how and when you're planning to share preclinical proof-of-concept? And since it seems like there's two undisclosed targets in your corporate deck, are you planning to share preclinical proof-of-concept for both programs? And also, any thoughts you could share on your choice for editing tool and delivery tool? Thank you.
Gilmore O'Neill: Thanks very much. So from the in vivo pipeline point of view with regard to the how and the when, we're excited to be on track towards POC this year for an in vivo preclinical POC. And we're going to be able to share more and look forward to sharing more later in the year about the forum and the timing, whether it be a scientific forum or some other forum in which we would share the data. And we haven't made a determination yet about that. And as I say, our focus is on driving towards a POC for in vivo this year. Oh, sorry. With regard to the editing tools, well, we have, I think, been very clear that we are focusing on our AsCas12a editor. And we are really focused on that, because for a number of reasons. First, it's our proprietary enzyme that we have selected going forward, because of its high fidelity and high efficiency, because of the benefits of it using a smaller guide and the advantages for quality, et cetera, in the manufacturing. And then finally, because we have human proof-of-concept, we have very exciting, robust editing data in human cells from AsCas12a from our reni-cel essel program. So all of those are the reasons why we're favoring and using that editing tool. And in regards to delivery, we are using a non-viral, focusing on non-viral delivery and nanoparticles.
Jay Olson: Super helpful. Thank you so much.
Gilmore O'Neill: Thank you.
Operator: Our next question comes from Yanan Zhu with Wells Fargo. Please proceed with your question.
Yanan Zhu: Great. Thanks for taking our questions. We're just wondering about the mid-year readout from the RUBY trial. I think you have 18 patients dosed to-date. Are you going to report data on these 18 patients plus any additional patient dosed with a certain amount of follow-up at the time of readout? And also, it seems like this is a much bigger number, compared with the last readout. So I was just wondering your confidence level of continuing to show the total hemoglobin normalization - kind of goal in this mid-year readout? Thank you.
Gilmore O'Neill: Thank you, Yanan. Before passing to Baisong on some of the details, I agree with you. Yes, this is a much bigger number of patients that we have dosed. And our confidence, as we've said, has increased with the accumulation of data that are continuing and repeatedly show that not only are we achieving robust fetal hemoglobin expression in excess of 40%, which is well above the - 30% threshold that natural history would tell us is relevant. But we actually also see that consistent correction of anemia normal physiologic range in all men and all women treated and followed past four months to-date. And yes, we're excited about the mid-year disclosure. But with that, I'm going to pass it to Baisong to give you a little more detail.
Baisong Mei: Yes. Thanks, Yanan. I mean, your understanding is absolutely correct. We already dosed 18 patients and we'll continue to dose patients in the coming months. So the data set will be 18 patients plus more that, we're going to be dosing before the middle of the year. And as you can see, we publish the data in ASH and some patients already over a year. Then this patient will have continued to monitor for those patients longer for a period. And then we have 18 patients dosed now. And by the middle of the year, and this will have this patient, 18 patients, we'll have three or five months more data by the time we release that. That's why we describe as really very meaningful substantive data we will be able to share the middle of the year. As exactly you mentioned, this data set is pretty strong.
Gilmore O'Neill: Yes. And we actually, I think, Baisong, I think you said it, but it's worth reemphasizing, we're talking about a range of follow-ups from an efficacy point of view, between three and 18 plus months. So when you're looking at the total patients now, we are now really building not just a data set that is robust in number, but actually robust in follow-up period time, which obviously relevant not just to our hematological and efficacy outcomes, but actually also increasing our confidence in durability.
Yanan Zhu: Great. Thanks. Looking forward to that.
Operator: Our next question comes from Luca Issi with RBC Capital. Please proceed with your question.
Luca Issi: Oh, great. Thanks so much for taking my question. Congrats on all the progress. Maybe Baisong. Any update on the grade 2 polycythemia case that was potentially related to reni-cel? I remember the poster at ASH actually noted the causality of the AEs was being investigated pending additional lab tests. So just wondering if you have any update on that one. And then maybe just quickly, any update on partnering sickle cell disease, ex-U.S.? Thanks so much.
Gilmore O'Neill: So Baisong will take that first question. And you know, with regard to partnering, I will just say that we are keen that a partner with a global footprint could help us with a global commercialization and development. We see that as an upside. But right now, our focus is on driving our sickle cell and thalassemia programs here in North America. And as I say, partnering will be something that we will look to in the future as upside. With regard to the erythrocytosis, Baisong?
Baisong Mei: Yes. Thanks. That specific patient will have a transient elevation of total hemoglobin as we reported in ASH. At the time of ASH reporting, it's already been normal for more than six months. And that continued with the patient hematological parameter including total hemoglobin continues to stay normal. And then the investigator had a further investigation of the patient data. And we reviewed that to. And the patient, the investigator considered this event is not related to the sickle or the reni-cel treatment.
Luca Issi: Got it. Thanks so much.
Operator: Our next question comes from Steve Seedhouse with Raymond James. Please proceed with your question.
Timur Ivannikov: Hi. Good morning. This is Timur Ivannikov, on for Steve Seedhouse. So we just had a clarification question on your PRO tools in RUBY. To what extent are you going to be using the same tools that Vertex and CRISPR used before like [EQ, VAS, FACT-G, BMT]? And to what extent do you think of including new tools? And on the issue being you're not going to be able to do a clean cross-trial comparison potentially here? Thank you.
Baisong Mei: Yes. Thank you for the question. As I mentioned, comment earlier, we use the tool from two ends. One is more general, the quality of life tool as well as the sickle cell specific. And as you mentioned, the specific of the tool we're using, that's the problem for - evaluate the fatigue of the patient, which is important not complain from the sickle cell patient. Just give example wise. And you are very much of - that exactly the direction we were thinking, trying to see, okay, what are the specific instruments be able to detect that major complaint from the sickle cell patient such as fatigue, such as pain, among other things.
Gilmore O'Neill: Yes. So we are actually using a number of instruments. Some were used by Vertex and we have additional instruments in our PRO and armamentarium and they are actually being collected in the RUBY Phase 1, 2, 3 trial as we speak.
Operator: Our next question comes from Jack Allen with Baird. Please proceed with your question.
Jack Allen: Great. Thanks so much for taking the question and congratulations on the progress. I want to touch a little bit on the patient experience with reni-cel. Have you provided any disclosures around the number of apheresis cycles that are required to receive reni-cel and I was wondering if the higher editing efficiency of AsCas12a shorter amount of apheresis cycles. And then on the back end after treatment, what are you seeing as it relates to time to neutrophil engraftment? And how do you think that compares to some of the competing products in the space? Thanks so much.
Gilmore O'Neill: Thanks very much, Jack. I'm actually going to ask Baisong to talk about the clinical experience with apheresis and other elements of the patient experience and honestly touch on neutrophil engraftment with which we have been very pleased to-date?
Baisong Mei: Thank you, Jack. For patient experience, I mean, apheresis is a very important part of that. As I mentioned earlier, since I joined, I work with a team and an expert, we amended the protocol and trying, to optimize the apheresis process. So now, we are very happy with the number of cycles that patient has been going through and we can see that's already improvement from what we had before. In terms of the engraftment, as we disclosed that in ASH, we have all the patients have engraftment within 30 days. So we're very happy about that, and we continue to see the similar data as we follow through the protocol for our studies.
Jack Allen: Great. Thanks a lot for the color.
Baisong Mei: Thank you very much.
Operator: We have reached the end of our question-and-answer session. This concludes today's conference. Thank you for your participation. You may disconnect your lines at this time.
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