Editas Medicine - Q1 2024
May 8, 2024
Transcript
Operator (participant)
Good morning, and welcome to the Editas Medicine first quarter 2024 conference call. All participants are now in a listen-only mode. There will be a question and answer session at the end of this call. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Cristi Barnett, Corporate Communications and Investor Relations at Editas Medicine.
Cristi Barnett (Head of Corporate Communications and Investor Relations)
Thank you. Good morning, everyone, and welcome to our first quarter 2024 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 (CEO)
Thanks, Cristi, and good morning, everyone. Thank you for joining us today on Editas' first quarter 2024 earnings call. With me today are four members of the Editas executive team, our Chief Medical Officer, Baisong Mei, our Chief Scientific Officer, Linda Burkly, our Chief Financial Officer, Erick Lucera, and our Chief Commercial and Strategy Officer, Caren Deardorf. We are pleased with Editas' momentum and progress in the first quarter of 2024. Editas' goal is to deliver life-changing medicines to patients with previously untreatable or undertreated genetically determined diseases. Our vision and focus strategy is to position Editas as a leader in in vivo programmable gene editing. Three pillars underpin our strategy. The first of those pillars is to drive reni-cel, an edited cell therapy for hemoglobinopathies, and formerly known as EDIT-301, toward BLA and commercialization.
The second is to build an in vivo editing pipeline, and the third is to increase business development activities with a particular focus on monetizing our very strong intellectual property. At the start of 2024, we announced the following 2024 objectives: 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 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 BD, we will leverage our robust IP portfolio and business development to drive value and complement core gene editing technology capabilities. So how have we executed against this strategy and these objectives in the first quarter?
Let us start with reni-cel. First, on enrollment. We've been very pleased with the growing patient and healthcare provider interest in reni-cel. Indeed, we are delighted to share that we have completed enrollment in the adult cohort of the RUBY clinical trial. Additionally, we have enrolled multiple patients and have more in screening in the adolescent cohort of our RUBY study, which was launched at the beginning of this year. We continue to enroll beta thalassemia patients in our EdiTHAL studies. Dosing continues in both the RUBY and EdiTHAL studies. Second, on clinical data. We remain on track to present a substantive clinical data set of at least 18 sickle cell patients with two-21 months of clinical follow-up in the RUBY study in the middle of 2024, and we will share a further update by year-end.
We are also on track to present clinical data from the EdiTHAL studies of reni-cel in transfusion-dependent beta thalassemia in the middle of 2024, and again by year-end. Baisong Mei will share more reni-cel data later on in this call. On the manufacturing front, I am pleased to share that we have promoted Greg Whitehead to the role of Chief Technology and Quality Officer, leading our technical development, technical operations, and quality departments. Greg has more than 25 years of experience in the biotech industry and extensive cell and gene therapy, clinical and commercial development expertise. Now, let's turn to in vivo and our pipeline development, where we continue to strengthen our in vivo discovery capabilities and continue lead discovery work on in vivo therapeutic targets in hematopoietic stem cells and other tissues.
Importantly, we remain on track to establish in vivo preclinical proof of concept for an undisclosed indication by the end of the year. Our internal development efforts are differentiated by leveraging the indel CRISPR technology we already use to upregulate gamma globin expression through direct editing of the HBG1/2 promoter site in our ex vivo reni-cel program. Our in vivo approach is aimed at functional upregulation of gene expression in genetically defined diseases, with a preliminary focus on rare and orphan patient populations.... In the medium to long term, we intend to expand to more common genetically determined diseases. Linda Burkly, our CSO, will share more details on our in vivo strategy and progress towards building an in vivo pipeline later on in the call. Finally, what is happening in business development?
In March, we signed a two-year extension to the collaboration with Bristol Myers Squibb to research, develop, and commercialize autologous and allogeneic alpha/beta T-cell medicines for the treatment of cancer and autoimmune diseases. We also have options to extend that collaboration for an additional two years. To date, Bristol Myers Squibb has opted into 13 different programs across 11 gene targets to date. two programs are currently in IND-enabling studies, and four programs are in late-stage discovery. In intellectual property, yesterday, oral arguments were held before the U.S. Court of Appeals for the Federal Circuit regarding an appeal of the Patent Trial and Appeal Board's, or PTAB's, previous decision favoring Broad Institute in the U.S. patent interference involving specific patents for CRISPR-Cas9 editing in human cells between the University of California, University of Vienna, and Emmanuelle Charpentier, or CVC, and the Broad.
We expect a decision on the case in the second half of 2024. Erick will share more BD and IP details later on in the call. We are energized by our progress and execution this quarter. With our sharpened strategic focus, our world-class scientists and employees, our keen drive and execution, and strong balance sheet, 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 (CMO)
Thank you, Gilmore. Good morning, everyone. Let's talk about reni-cel, which is under clinical development for severe sickle cell disease and transfusion-dependent beta thalassemia. As Gilmore shared, we are pleased that we have completed enrollment in the adult cohort of the phase one to three RUBY trial, and the dosing continues. In the adolescent cohort of the RUBY study, we have enrolled multiple patients and several more patients in screening. The interest and demand are high. I'm very pleased about how quickly we have moved in screening and enrollment of adolescent cohort. I'd like to thank colleagues and Editas and our clinical trial partners for the collaboration and hard work. And more importantly, I would like to thank patients, their families, investigators, and the study site staff for their trust and support. In the EdiTHAL trial for transfusion-dependent beta thalassemia, we continue to move forward with enrollment and dosing.
We look forward to sharing clinical data in the middle of this year and also at the year-end. As I have shared, I visited and continue to visit our RUBY and EdiTHAL clinical trial sites and speak with the investigators. I appreciate the enthusiasm and support from the investigators and study sites. I'm pleased with the momentum of reni-cel in patient recruitment, apheresis, and dosing in both studies. I'm excited to hear from the investigators that patients, those doing reni-cel, have already seen positive changes in their lives. As we shared in our February earnings call, we aligned with the FDA that RUBY clinical trial is now considered a phase I, II,III trial for BLA filing. We also have alignment with the FDA on the study design, endpoint, and sample size. We look forward to future discussions with the FDA and continue the collaboration.
Turning to clinical data, as Gilmore mentioned, we are 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, and a further update by year-end 2024. What we will show? The RUBY dataset will include clinical data from at least 18 sickle cell patients with a two- to 21-month follow-up, and the EdiTHAL dataset will include the clinical data from seven patients with a four- to 12-month follow-up. We will present efficacy data, including total hemoglobin, fetal hemoglobin, and the vaso-occlusive event, or VOE, for sickle cell patients in RUBY study, and red blood cell transfusion for transfusion-dependent beta thalassemia patients in EdiTHAL study, and safety data, including neutrophil and platelet engraftment for both studies.
As a reminder, in December 2023, we shared safety and efficacy data from 11 RUBY patients and 6 EdiTHAL patients. Once again, the data confirmed the observation from our prior clinical readouts, including reni-cel drove early, 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 level 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 patients and transfusion-dependent beta thalassemia patients have shown successful engraftment, have stopped red blood cell transfusion. The safety profile of reni-cel observed to date is consistent with busulfan and melphalan myeloablative conditioning and autologous hematopoietic stem cell transplant.
This data reinforce our belief that we have a competitive product and a product potentially differentiated from other treatments with rapid correction of anemia, thanks to the deliberate choice of our discovery group have made early in the program. The choice of CRISPR enzyme and the target to edit for increased fetal hemoglobin expression matters. reni-cel uses our proprietary AsCas12a enzyme to upregulate the HBG1/2 promoter. Based on the clinical data thus far, we believe that sustained normal levels of total hemoglobin could be a potential point of differentiation for reni-cel. Now I turn the call over to Linda, our Chief Scientific Officer.
Linda Burkly (Chief Scientific Officer)
Thanks, Baisong, and good morning, everyone. I'm happy to be talking to you this morning to share more details about our in vivo strategy and our progress towards building an in vivo pipeline. I would like to take a moment to remind you why we believe in vivo medicines will be a disruptive, transformative development in medical history, with the potential to address genetically determined diseases with durable and curative outcomes for patients. First, in vivo medicines may reduce the administration burden of delivering editing medicines to patients in need, which will provide for broader access to patients all around the world. Second, off-the-shelf administration may allow for scalable manufacturing and lower costs to produce. Based on these two principles, we believe that in vivo gene editing will provide accessible cures for genetic diseases, and therefore, may be the most disruptive development in medical history.
So how will Editas position itself? There are many monogenic diseases that can potentially be cured with a gene editing approach. We have said that we will, at first, target the development of treatments that are clearly differentiated from current standard of care, and that will leverage the aspects of CRISPR editing that give it a unique advantage over other therapeutic modalities. Our internal development efforts are differentiated by leveraging the indel CRISPR technology we use to upregulate gamma globin expression through direct editing of the HBG1/2 promoter site in our ex vivo reni-cel program. Our in vivo approach is aimed at functional upregulation of gene expression in genetic diseases in rare and orphan patient populations, from which we intend to expand to more common diseases.
I am also pleased to share several progress updates as we advance our in vivo capabilities toward our long-term vision of being a leader in in vivo programmable gene editing. First, and most importantly, as Gilmore mentioned, we remain on track to establish in vivo preclinical proof of concept for an undisclosed indication by the end of the year. Editas is well positioned with established capabilities in the four main components of in vivo gene editing medicine. One, guide RNA. Two, editing enzyme. Three, messenger RNA, and four, delivery technology. And we are currently evaluating lipid nanoparticles for delivery of gene editing cargo into multiple tissue types with multiple companies. Additionally, we're evaluating next generation delivery technology.
Second, our in vivo capabilities with the potential to be used in developing transformative in vivo gene editing medicines are demonstrated by the preclinical data we are presenting at the American Society of Gene and Cell Therapy, or ASGCT, annual meeting in three presentations taking place on Thursday and Friday of this week. On Friday, in an oral presentation, we will share in vivo preclinical data from mouse studies using lipid nanoparticle-mediated delivery of an optimized guide RNA and engineered AsCas12a messenger RNA. In poster presentations on Thursday and Friday, we will share preclinical data demonstrating AsCas12a guide RNA modifications that enable high-potency gene editing in multiple cell types, including in the liver, and improve gene editing outcomes in vivo, enabling the development of in vivo gene editing medicines.
Research on identifying potent large serine recombinases, LSRs, as a foundation to develop novel in vivo gene editing technologies for whole gene knock-in, expanding potential in vivo gene editing targets for developing medicines. Third, Editas' CRISPR-based in vivo gene editing capability has been clinically validated. Notably, in 2020, Editas was the first company ever to treat a human with an in vivo-delivered CRISPR-based gene-editing medicine, EDIT-101. In fact, earlier this week, the New England Journal of Medicine published a manuscript entitled "Gene Editing for CEP290-Associated Retinal Degeneration," detailing our former lead development candidate, EDIT-101, for the treatment of Leber Congenital Amaurosis type 10, or LCA10. Editas established clear in vivo human proof of concept in 2022, and we are pleased that the results from this groundbreaking clinical trial were published by the New England Journal of Medicine.
These progress updates demonstrate Editas' execution on our in vivo strategy and our proven in vivo gene editing capabilities, and I look forward to sharing more details about our in vivo development strategy and our progress towards building an in vivo pipeline later this year. Now, I will turn the call over to Erick, our Chief Financial Officer.
Erick Lucera (CFO)
Thank you, Linda, and good morning, everyone. I'm happy to be speaking to you, and I'm excited to provide updates on our business development achievements, intellectual property, and financial results for the first quarter of 2024. First, in regard to business development, as Gilmore mentioned, in March, we announced a two-year extension to the collaboration with Bristol Myers Squibb to research, develop, and commercialize autologous and allogeneic alpha/beta T cell medicines for the treatment of cancer and autoimmune diseases. We also have options to extend the collaboration for an additional two years. To date, Bristol Myers Squibb has opted into 13 different programs across 11 gene targets to date. Two programs are currently in IND-enabling studies, and four programs are in late-stage discovery.
As a reminder, for each new experimental medicine that Bristol Myers Squibb develops and commercializes using opted-into genome editing tools, Bristol, Bristol Myers Squibb will pay Editas Medicine potential future milestone payments. Following the approval of any products resulting from the collaboration, Editas Medicine is also eligible to receive tiered royalties on net sales. We are pleased that our Bristol Myers collaboration has proved to be a productive partnership, and we are committed to future collaborations and partnerships that will allow for the continued access and advancement of gene editing. In IP, as Gilmore mentioned, yesterday, the oral arguments were held before the U.S. Court of Appeals for the Federal Circuit regarding the CVC's appeal of the PTAB's decision involving patents for CRISPR-Cas9 editing in human cells.
As you know, the Broad Institute has previously prevailed three times against the CVC, twice with the PTAB and once at the Federal Circuit. The Federal Circuit's review will determine whether the PTAB correctly applied the law. It is important to remember, the court will not hear new evidence. An appellate court decision in the Broad's favor would reaffirm Editas' position as the exclusive licenser of the patents covering Cas9 used in human medicines in the U.S. It is also important to remember that only a small fraction of the IP we licensed from the Broad are involved in the ongoing USPTO interference proceedings. We expect a decision on the case in the second half of 2024. We remain confident that the Broad will once again prevail.
Our IP portfolio of foundational U.S. and international patents covering Cas9 and Cas12a use in human medicines are a source of meaningful value, as we believe that globally, there are more than 100 Cas9/Cas12a programs in development worldwide, with the majority of the programs being developed by 10 companies. We believe these potential deals represent a potential material source of non-dilutive capital, as evidenced by our deal in the fourth quarter of 2023 that extended our cash runway by two quarters. We look forward to future discussions. And now 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 2024. I'll take this opportunity to briefly review a few items for the quarter.
Our cash, cash equivalents, and marketable securities as of March 31st, $377 million, compared to $427 million as of December 31st, 2023. We expect our existing cash, cash equivalents, and marketable securities, together with the near-term annual license fees and contingent upfront payment payable under our license agreement with Vertex, to fund our operating expenses and capital expenditures into 2026. Revenue for the first quarter of 2024 was $1.1 million, compared to $9.9 million for the same period in 2023. The decrease relates to the January 2023 one-time sale of the company's wholly owned oncology assets and related licenses. R&D expenses this quarter increased by $11 million to $49 million from the first quarter of 2023.
This increase relates to additional clinical and manufacturing costs that support the continued progression of the company's reni-cel program. The increase is also attributable to one-time payments related to sublicense and license obligations. Editas will continue to incur these types of payments as we and our collaboration partners advance certain license programs in the gene editing space. G&A expenses for the first quarter of 2024 were $19 million, which decreased from $23 million in the first quarter of 2023. The decrease in expense is primarily attributable to one-time professional service expenses related to the 2023 strategic initiatives and business development activities, as well as reduced legal and patent costs. With our BD and IT activity and a cash runway into 2026, Editas remains in a strong financial position.
We have ample resources to continue the advancement of our reni-cel program, support the progression of our in vivo capabilities to develop our pipeline, and leverage our strong IP position for additional business development and licensing opportunities. With that, I will hand the call back to Gilmore.
Gilmore O’Neill (CEO)
Thank you, Eric. We are proud of our progress in the first quarter of 2024, and we look forward to continuing to accelerate the momentum in 2024 as we continue to evolve from a development stage technology platform company into a commercial stage gene-editing company. We look forward to continuing our transformation and sharing our progress with you. As a reminder of our 2024 strategic objectives, 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 have now completed the adult cohort enrollment and have started enrolling patients in the adolescent cohort in RUBY.
We will also continue enrollment in EdiTHAL and dosing in both trials. For our in vivo pipeline, we will establish in vivo preclinical proof of concept for an undisclosed indication, and for BD, we will leverage our robust IP portfolio and business development capabilities to drive value and complement core gene editing technology capabilities. As we shared today, we are making significant progress in all three pillars of our strategy this quarter, including reni-cel, in vivo, and business development, including intellectual property. We entered 2024 with great momentum, and I am proud of the Editas team's significant progress towards becoming a commercial stage company and on developing clinically differentiated transformational medicines for people living with serious, previously untreatable diseases. As always, 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 (participant)
Thank you. We will now be conducting a question-and-answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Please limit your questions to one question. One moment, please, while we poll for questions. Our first question comes from Samantha Semenkow from Citi. Please proceed.
Samantha Semenkow (VP of SMid Biotech Equity Research Analyst)
Hi, good morning, and thanks very much for taking my questions. I'm wondering about your in vivo pipeline and the proof of concept that you're expecting by the end of this year. What would be the bar for success that you're looking for in this program? Thank you.
Gilmore O’Neill (CEO)
Thanks very much, Samantha. I'm going to ask Linda to address that.
Linda Burkly (Chief Scientific Officer)
Thank you, Sam. Thank you for the question. We are looking for proof of concept for high efficiency delivery and editing for our target of interest in vivo in this preclinical POC. That will give us confidence in our ability to target the target of interest. We are going to be sharing more information on this at a future date. Thank you for the question.
Operator (participant)
Our next question comes from Joon Lee, from Truist Securities. Please proceed.
Joon Lee (Managing Director and Senior Biotech Analyst)
Hey, congrats on the progress, and thanks for taking our question. An interesting update on your disclosure is the plan to identify large serine recombinases, which implies sort of a newer approach to that many of your peers are also developing. You know, some call it gene writing, some call it pasting. Does the size of the recombinase-mediated insertion allow for, you know, inserting a coding sequence for dystrophin, for example, and are you able to comment on whether DMD is out of the question regarding your in vivo aspirations? Thank you.
Gilmore O’Neill (CEO)
Thanks very much, Joon. I'm going to have Linda take that.
Linda Burkly (Chief Scientific Officer)
Yes, thank you for commenting. We're excited about the LSR technology that we're disclosing here. We are identifying many different novel LSRs. We're not disclosing at the moment the size of the integrations that can be accommodated by these large serine recombinases, but we have quite a few novel LSRs that we've identified, and we're further characterizing them. Thank you for the question.
Operator (participant)
Our next question comes from Mary Kate Davis, from Bank of America. Please proceed.
Mary Kate Davis (Head of Biotechnology and Pharmaceuticals)
Good morning. Thanks for taking my question. Looking at the reni-cel program here, how are you guys looking at the midyear reni-cel update compared to the year-end update here? As follow-up time progresses, what should we look for from treated patients in terms of safety and efficacy moving forward? Thank you.
Gilmore O’Neill (CEO)
Thanks, Mary Kate. Baisong Mei is going to take that one.
Baisong Mei (CMO)
Yeah. Thanks, Mary. So we, in this midyear release, we expect to have at least 18 patient data for RUBY study. And within the 18 patients, and four of them will have 12 or longer, 12-21 months of exposure, and seven will have 5-12 months exposure, and another seven with two-five months exposure. With that, we feel this data is very meaningful to see the direction, not only the increase of total hemoglobin, normalization of total hemoglobin, and increase of fetal hemoglobin, but also the durability of the study and the impact from efficacy perspective, for example, the free of vaso-occlusive events. For the EdiTHAL study, we will have patients from at least seven dose patients with four-12 months of exposure, which also will be very meaningful.
That is compared to the December release. We have 11 RUBY patients and six EdiTHAL patients, so that's substantial more data will help us to understand the program much better. Thank you.
Operator (participant)
Our next question comes from Jack Allen, from Baird. Please proceed.
Jack Allen (Biotech Senior Research Analyst)
Hi, congratulations to the team on the progress, and thanks for taking the question. I'm gonna stick with the reni-cel program. I was hoping you could provide some color on, dosing of the pivotal cohort. I know you've commented on the adult cohort being fully enrolled, but have all those patients received therapy? And any other comments you can provide as it relates to the size of the cohort that you've agreed to with regulators would be very helpful. Thanks so much.
Gilmore O’Neill (CEO)
... Thanks very much, Jack. I'll answer the first part and then pass it to Baisong to back you up, you know, maybe give it more color to regulatory interactions. We have obviously completed the adult enrollment, which we're actually very excited about, not least because that is in the context of two approved therapies. So it really is a very concrete reflection of the enthusiasm that Baisong has found and described, indeed, increasing enthusiasm about our program with his visits to sites and conversations with investigators, healthcare providers, and indeed with patient advocacy groups. We have scheduled many of those patients already for dosing, and we'll give you further updates on the progress of dosing at a later date.
With regard to the regulatory color, I think, Baisong, you might want to maybe just share a little more there.
Baisong Mei (CMO)
Yes, for regulatory, as we shared, that we have alignment with FDA, that the RUBY study is a phase I, II, III study for the VOE. And we also have alignment on the sample size, duration, and study design of that. So we continue to have a collaboration with FDA, on the further discussion about this program.
Jack Allen (Biotech Senior Research Analyst)
Great, thank you.
Operator (participant)
Our next question comes from Gena Wang from Barclays. Please proceed.
Gena Wang (Managing Director and Biotech Equity Research Analyst)
Thank you. If I may, very quick, two questions. First, should we read into your ASGCT presentation for in vivo indication, such as, glaucoma? And the second, I know you mentioned also a little bit, but when we look at the current approved genomic therapy for sickle cell, we still have a 10% patient relapse with VOE events. What do you think is the key factors that we should look into for the potential to differentiate durability with hopefully 100% control rate?
Gilmore O’Neill (CEO)
Thanks very much, Gena. I'm gonna ask Linda to handle the first part of your question, around the ASGCT, and then, Baisong can talk about, durability, what we're seeing to date.
Linda Burkly (Chief Scientific Officer)
Yeah, thank you very much, Gena. Primary open-angle glaucoma is obviously an area of very high unmet need, and while we conducted those studies because of that, we are not currently pursuing that indication. But we were able, through those studies, to really demonstrate impressive preclinical POC and showcase our in vivo capabilities with respect to three components: our ability to deliver lipid nanoparticles in vivo with our gene editing cargo, our proven capability of our proprietary enzyme, AsCas12a, to edit in vivo, and our guide modifications to enhance a gene-editing potency. So these capabilities really position us well for delivering in vivo gene-editing medicines, and we're real pleased with the ASGCT disclosures. Thank you.
Baisong Mei (CMO)
Yeah, Gena, I will take up on the question about the VOE relapse for sickle cell patients. First, I would like to say, I wanna congratulate the entire field for the effort of treating sickle cell disease, including the recent approval of the two molecules. So I think what we see is that with the continued effort of all of us, we will continue to improve and transform the treatment for sickle cell disease patients. With the reni-cel, and we are still continuing to collect the clinical data, as I mentioned, we expect that this is a different, not only competitive, but differentiated molecule, and with the normalization of the total hemoglobin, correction of anemia. So we're looking forward to see our own data on the VOE.
As we reported so far, we have seen all those patients, those with reni-cel, is free of the VOE event.
Gena Wang (Managing Director and Biotech Equity Research Analyst)
Thank you.
Operator (participant)
Our next question comes from Mani Foroohar from Leerink Partners. Please proceed.
Mani Foroohar (Senior Managing Director)
Hi, good morning. This is CJ on for Manny. Thanks for taking our question. Ours is following the agreement with Vertex last year, just how are you thinking about future IP monetization opportunities?
Gilmore O’Neill (CEO)
Thanks very much. I'm going to ask Eric to address that question.
Erick Lucera (CFO)
Yeah, thanks for the question. Obviously, as we said in the transcript, we view the future potential, royalty, monetization, and licensing activities as an integral and very important source of non-dilutive capital. As you know, these are foundational IP patents, which are applied to just about everybody's projects in Cas9, Cas12. And we expect to have conversations with those folks, you know, as soon as we can.
Mani Foroohar (Senior Managing Director)
Thank you.
Operator (participant)
Our next question comes from Brian Cheng from JP Morgan. Please proceed.
Brian Cheng (Executive Director and Senior Biotech Analyst)
Hey, guys. Thanks for taking our question this morning. Can you just remind us what's your latest thinking around the timing of holding a discussion with regulators on sickle cell? You know, just given the data that you are going to present midyear, any updates and color on, you know, the timing of holding a productive conversation with regulators will be appreciated. Thank you.
Gilmore O’Neill (CEO)
Thanks very much, Brian. I'm going to ask Baisong to talk about that. I think your two questions really, which is about what the data are in the middle of the year and how they integrate with our discussions with regulators.
Baisong Mei (CMO)
Yes, so Brian, as I mentioned, we are very pleased with the data we're going to release in the middle of the year, and which is substantive and also give us good direction, how much work we will get and, to have, for example, a data set to have equivalent to the, Casgevy, BLA filing, for example, right? So that's kind of one part of that. We're very happy to see the amount of data and the patient outcome from the data. And then the other thing is about the regulatory engagement. As I mentioned, we already have aligned this as a phase three study to support the BLA, and we have then we have, continued engagement with the, with the, with FDA.
We have not disclosed all those details of the interaction yet, but as a reminder, we have RMAT designation, and which allow us to have frequent interaction with agency, but also with a high level interaction with agency. And this, of course, help give us opportunity for potential priority review and rolling submission. So we're very excited to the direction. We continue to have engagement and collaboration with FDA.
Brian Cheng (Executive Director and Senior Biotech Analyst)
All right, thank you, Baisong.
Operator (participant)
Our next question comes from Eric Schmidt from Cantor Fitzgerald. Please proceed.
Eric Schmidt (Biotechnology Analyst)
Thanks for the question and congrats on the progress. Are you able to give the approximate number of patients who are enrolled in the RUBY trial with sickle cell disease? And then, it sounds like you've been able to make pretty good progress in enrollment in that study, despite the availability of commercial cell therapies. I was just wondering at centers that have both experimental and commercial cell therapy available, maybe Baisong could talk a little bit about what's driving the decision to use the Editas product over others. Thanks.
Gilmore O’Neill (CEO)
Thanks very much, Eric. Baisong will kind of update you on where, you know, our clinical trials. ClinicalTrials.gov sets as a target for the cohort in our trial, and then obviously build on his perceptions of why we're doing so well with enrollment, even in the context of commercial therapies being available.
Baisong Mei (CMO)
Yeah. Yeah, thanks, Eric. We are very pleased with the momentum about the enrollment in both the adult cohort and the adolescent cohort. And for the adult cohort, we shared that in February with those, we enrolled 40 patients. Now we enrolled slightly more than 40 patients, and therefore, we closed the adult cohort enrollment. And for adolescent cohort, we started, like, beginning of this year, we already enrolled multiple patients and have multiple patients screened. We're very pleased with that. Then, as I mentioned, I'm on the road all the time to visit our investigators and the study sites. And then they really feel that one is actually their belief on the reni-cel, based on the MOA, based on the data we have continued to sharing on that.
I also give credit the entire field in working on that with the two, gene therapy approved for sickle cell. It's also increased the interest in the direction of the gene therapy for sickle cell disease. So that's how we see, you know, over the last year or so, we see really great momentum, that for reni-cel, enrollment, especially after we release our data.
Operator (participant)
Our next question comes from Jay Olson from Oppenheimer & Company. Please proceed.
Jay Olson (Research Analyst)
Oh, hey, congrats on all the progress, and thank you for taking the question. Can you talk about the timing of the collaboration extension with Bristol? Was there some new data that triggered the new collaboration? And is there any color on what new data Bristol may have seen? And then, separately, can you talk about any work that you've done on developing a milder conditioning agent? Thank you.
Gilmore O’Neill (CEO)
Well, what I'm going to do is ask Eric to address the question about the BMS. What I do want to say, I can address the conditioning, which is that just at our last earnings, we talked that we are going to continue monitoring the space. We have significant context in the academic and non-academic worlds around the field, but we have actually really deployed our efforts and our resources internally to focusing on our in vivo pipeline, including developing hematopoietic stem cells. The rationale for that being that we see that where a milder conditioning therapy is actually approved, it would be used universally and adopted universally in transplant centers across multiple indications, including stem cell transplantation for hemoglobinopathies.
With that, I'm just going to pass to Eric just to talk about the BMS deal.
Erick Lucera (CFO)
Yeah, thanks for the question. With respect to the timing of the renegotiation or the extension, obviously, we put out a press release in the very recent past, a week or two ago, something like that, and that would give you an update on the timing. I'd say with respect to the data-
... Bristol Myers, as you know, recently completed a portfolio review, and we were pleased to see that all of the projects that we're working on them are continuing to move forward. I think if, you know, we would leave discussion of specific programs to them to talk about anything that they're seeing in those programs. I would highlight the fact that at their most recent R&D day last September, which I think was the first one they've done in several years, they did mention six products on their pipeline chart, which were using our technology. So I would refer you to their R&D disclosures from that meeting to get an update on the work that they're doing with us. But we are very excited about working with them.
This has been a partnership that has survived several mergers, and several portfolio reviews. So, you know, we're very excited about what we're seeing.
Jay Olson (Research Analyst)
Thank you.
Operator (participant)
Our next question comes from Phil Nadeau, from TD Cowen. Please proceed.
Alex Kelly (Research Analyst)
Hi, this is Alex on for Phil. Thanks for taking my question. So given the association between total hemoglobin, hemoglobin levels and end organ function, do you plan to utilize any quantitative endpoints, basically assessing end organ function in the RUBY trial? And if so, what might those look like, and when could we maybe expect initial data? Thanks.
Erick Lucera (CFO)
Thanks very much, Alex. I'm going to ask Baisong to address that question.
Baisong Mei (CMO)
Yeah. Thanks, Alex. We certainly have measurements for the end organ function. We look into the several major organ system to monitor the function improvement. For example, we monitor the liver function, not only with these different lab values. We look into pulmonary function to check the respiratory system, and we also have cardio echo and other measures to measure the cardiovascular system in that too. So we are looking forward to see more data on that and give us more understanding of the end organ function may behave after the treatment.
Just a reminder that we also, of course, look into the not only sickle cell, but also other area in these in terms of the anemia, how that impact function and how that correction of anemia may be able to improve that function after the, after the treatment. And in sickle cell, specifically, over the last couple of years, you already see more publications about end organ function, given after the allogeneic transplant to treating sickle cell patients. We are very excited on that. But just to be very honest to ourselves, right, this field is still fairly new, and we see some really good publication and direction in this, and we're looking forward to our own study as well as the literature on this field.
Alex Kelly (Research Analyst)
Great. Thank you.
Operator (participant)
Our next question comes from Yanan Zhu, from Wells Fargo. Please proceed.
Yanan Zhu (Senior Analyst and Biotechnology Equity Research Analyst)
Thanks, and thanks for taking our questions. So first on the differentiation of total hemoglobin normalization, I was wondering, have you had feedback from sickle cell treaters on that differentiation? And whether there's any hesitancy or pushback that perhaps the current level of hemoglobin achieved by the marketed product is sufficient? You know, you know, how much of that kind of thinking is out there? And on the in vivo side, I was wondering, are you focused on first-in-class targets or perhaps not first-in-class targets, but hoping to have a differentiation on specificity and transduction efficiency, et cetera? Thanks.
Erick Lucera (CFO)
Thanks very much, Yanan. So I'm going to ask Baisong to talk about the differentiation of total hemoglobin, and then I'll ask Linda just to talk about our approach to first in class or clear differentiation and where we would see that with our approach to functional regulation.
Baisong Mei (CMO)
Thanks. Thanks, Yanan. I mean, certainly, we talk about the investigators as well, the KOLs and sickle cell treaters for our differentiation and how we may be able to see and with the position of this molecule. And when we talking to those hematologists and sickle cell treaters that see our data, and one hematologist mentioned that it is no-brainer, it is better if you have a 16 g/dl versus 10 g/dl of total hemoglobin. And then they also, I mentioned, the enthusiasm of our study, and there are quite a few knowledgeable hematologists. They see the difference among several molecules, and one investigator said that he was waiting for our trial and did not participate other. So those are the anecdotal examples on that.
As I mentioned earlier, we certainly want to look forward to see the clinical data.
Erick Lucera (CFO)
It's also worth highlighting, of course, that the FDA has recognized that 1 g/dl difference is meaningful or certainly likely to predict a clinically meaningful benefit, and that they use that threshold to give an accelerated approval to Oxbryta in the past.
Baisong Mei (CMO)
Yeah, talking about that, this is also... When we communicate with FDA, this is also a point we have in discussion with FDA, too.
Gilmore O’Neill (CEO)
... So thanks very much, Baisong Mei. Linda, just regarding in vivo and where our focus is.
Linda Burkly (Chief Scientific Officer)
Yes, in vivo. Our in vivo approach is aimed at functional upregulation of gene expression, genetically determined diseases, and this strategy positions us very well to be differentiated from others in terms of our targets and our target editing strategies. What this means is that we can go after targets that others can't go after. So from an indications perspective, we can go after indications that perhaps others can't go after, and so we could have a first-in-class strategy. Also, within a given indication, we could devise a targeting strategy that would be best-in-class, if you will. So we can have first-in-class strategies as well as best-in-class opportunities. I hope that answers your question.
Yanan Zhu (Senior Analyst and Biotechnology Equity Research Analyst)
Yes. Thank you. Very helpful. Thanks for all, all the answers.
Operator (participant)
Our next question comes from Luca Issi from RBC Capital. Please proceed.
Luca Issi (Senior Biotechnology Analyst)
Oh, great, thanks so much for taking my question, and, congrats on all the progress. Maybe just a quick one on reni-cel and the filing strategy. What's the vision here for the BLA? Are you planning to file adults and adolescents concurrently or sequentially? Any color there, much appreciated. And then maybe quickly on the Middle East, can you just talk about the opportunity for sickle cell disease in the Middle East? Vertex seems really, really excited about that market. So wondering, what's your strategy there to potentially tap that market? Are you still focused on the partnership? Can you potentially access that via distributor? Again, any thoughts there are much appreciated. Thanks so much.
Gilmore O’Neill (CEO)
Happy to do. Thanks very much, Luca. So, I'll ask Baisong Mei just talk about our regulatory strategy as far as we have shared it, and then, Caren can talk about just how we're looking at and thinking about the Middle East, and frankly, in the context of the rest of world.
Baisong Mei (CMO)
Yeah. Yeah. Thanks, Luca. We are very pleased with the interaction with the agency and continued interaction with the agency about the reni-cel and for the RUBY study as a phase III study to support the BLA, and all the front of the phase III study, we have alignment on that, and we have continued conversation with FDA on this route. We have not shared the specifics about the date of the BLA or the indication of adult or alone or adolescent. But as we shared, we are very pleased with the enrollment for both adult cohort as well as adolescent cohort. So that give us, you know, great position for this molecule. Thank you.
Caren Deardorf (Chief Commercial and Strategy Officer)
Great, Luca. Thanks for the question about Middle East and certainly just the populations outside the United States, and there's absolutely a number of geographies where there is a significant population of sickle cell patients and really high unmet need, beta thalassemia as well. What I'd say is our continued drive to execute in the U.S. and to move reni-cel forward with differentiation, just continues to support the opportunity for us to partner at the appropriate time, and that's certainly something that we've said we are open to, and we'll certainly provide more color in the future as appropriate.
Luca Issi (Senior Biotechnology Analyst)
Thanks so much.
Operator (participant)
Our next question comes from Steve Seedhouse from Raymond James. Please proceed.
Steve Seedhouse (Biotechnology Equity Research Analyst)
Hi, thank you. This is Nick on for Steve. We actually had a longer-term question. To what extent can you leverage the infrastructure that Vertex is already building out for Casgevy, and will EDIT-301 be able to plug into the existing authorized treatment centers once launched? Thank you.
Gilmore O’Neill (CEO)
Thanks very much. Thanks very much, Nick. I'm going to ask Caren to address that.
Caren Deardorf (Chief Commercial and Strategy Officer)
Yeah. Thank you, Nick, for the question. You know, first, we'd say. I'd say that I'm really pleased to see some of the initial progress for the other therapies and being able to get patients started. We always anticipated that it would be a dip in many centers starting to dip their toe as they build the infrastructure and they gain the confidence. So to answer your question, absolutely. We've always said that in this kind of market of the complexity of the ex vivo, being a fast follower is absolutely an advantage. We also, on our own, have a really strong base of over 20 clinical sites in the U.S. with very strong enrollment and relationships that we're leveraging, and those relationships and the guidance they're giving us will be really pivotal for us as well.
But this is a field that will benefit from the increase in education with patients, which Baisong Mei mentioned, also helps with our enrollment, and just building the infrastructure. But we are engaged on the KOL, the patient advocacy, as well as on the payer front, to ensure that we're prepared. So thanks for the question.
Steve Seedhouse (Biotechnology Equity Research Analyst)
Thank you.
Operator (participant)
Our next question comes from Jack Allen from Baird. Please proceed.
Jack Allen (Biotech Senior Research Analyst)
Great. Thanks so much for taking the quick follow-up here. I just wanted to focus on reni-cel one more time and ask, when we might hear a little bit more about the differentiation as it relates to the treatment process. Have you provided any color on the number of apheresis cycles and how editing efficiency of the AsCas12a enzyme may allow you to be more efficient in manufacturing the process?
Gilmore O’Neill (CEO)
Thanks very much, Jack. So I'm going to ask Baisong to talk about that.
Baisong Mei (CMO)
Yeah, thank you. We have not shared specifics about the number of cycle on the apheresis. What I mentioned before was since I joined, we actually worked together with our internal as well as apheresis external apheresis expert. We actually have protocol amendment to improve the apheresis cycle and also provide assistance at the study site to for the apheresis cycle, which is significant because it's a reduced patient burden, it's a smoother manufacturing process. We're very pleased to see the progress in that front. Just to add on that, we are hoping this clinical experience will be very much helpful for our commercial and endeavor. Yeah. Our next question comes from Mani Foroohar from Leerink Partners. Please proceed.
Jack Allen (Biotech Senior Research Analyst)
Hi. Thank you for taking our follow-up question. Kind of similar to the last question, you've previously talked about optimizing the vein-to-vein process. Would you be able to walk us through how reni-cel could provide advantages from, either both operational or logistics perspective? Thank you.
Baisong Mei (CMO)
Baisong, I'm gonna ask, I'll ask Baisong to address that. Yeah. Happy to. We are over this process, really working together with the study sites to optimize this process, and that coming from multiple factors. One of the factors just mentioned is apheresis. The other factor is the logistics, and we provide support on that. The third factor is actually patient condition. As we know that we are treating severe sickle cell disease, and before the reni-cel treatment, they can have multiple VOE per year, and that also can impact the vein-to-vein time.
Caren Deardorf (Chief Commercial and Strategy Officer)
Mani, this is Caren. I would just add that, again, in the fast follower position, one of the things that it gives us the opportunity to do is to really understand, as the first two therapies are commercialized, what's working, what's not working, what they need to see differently, and really making sure that Editas sets ourselves up as the partner of choice. And so we're working very hard on that, and we'll certainly talk about that at a later time.
Jack Allen (Biotech Senior Research Analyst)
Great. Thanks so much for taking our question.
Operator (participant)
Ladies and gentlemen, this concludes today's call. Thank you once again for your participation. You may now disconnect.