Good morning, and welcome to the Editas Medicine First Quarter 2022 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 Ron Moldaver, Investor Relations at Editas Medicine.
Thank you, Paul. Good morning, everyone, and welcome to our First Quarter 2022 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 on the investors section of our website approximately 2- hours after its completion. After our prepared remarks, we will open the call for Q&A. As a reminder, various remarks that we make during this call about the company's future expectations, plans, and prospects constitute forward-looking statements for purposes of the Safe Harbor P rovisions 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 and 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 Chief Executive Officer, Jim Mullen.
Thanks, Ron, and good morning, everyone. I'm joined today by several members of the Editas executive team, including Mark Shearman, our Chief Scientific Officer, Michelle Robertson, our Chief Financial Officer, and Charlene Stern, our General Counsel. We made excellent progress this quarter and look forward to more meaningful milestones this year. In the BRILLIANCE Trial for LCA10, we dosed the first pediatric patient with EDIT-101. This marks the first time ever a child was dosed using in vivo CRISPR Gene Editing, an incredible accomplishment. Given that LCA10 is one of the leading causes of inherited childhood blindness, pursuing the dosing of younger patients is potentially a critical step forward to treating this disease. Yesterday at the ARVO Conference, we presented data further supporting the favorable safety and immunogenicity profile of EDIT-101.
We expect to complete dosing of our pediatric mid-dose cohort in the first half of 2022 and initiate our pediatric high-dose cohort later this year. We're also planning on providing clinical update for EDIT-101 in the second half of the year. Later today at the ARVO Conference, we'll present non-human primate data with EDIT-103 for Retinitis Pigmentosa, demonstrating the unique design of our in vivo knockout and replace candidate to preserve retinal function. That program is advancing toward IND-Enabling Studies, which we expect to start by the end of the year. Our EDIT-301 program for Sickle Cell Disease and Beta-T halassemia continues to screen and enroll trial patients. For sickle cell, we've successfully edited several patients' cells ex vivo and are on track to begin dosing before the end of next month, and for Beta-T halassemia later this year.
Our cellular therapy programs are advancing. We showed impressive iNK Preclinical Data. We'll have new data on EDIT-202 later this month at ASGCT, and we're pleased to have our long-standing partner, BMS, opt in to a seventh Alpha/Beta T-cell Program. The U.S. Patent and Trademark Office recently issued a favorable patent interference decision to the Broad Institute, affirming our foundational CRISPR-Cas9 Intellectual Property Position. Charlene's joining us today, and she'll discuss the implications of that decision in more detail in a few minutes. Finally, we're excited to announce a new leader for our organization, Gilmore O'Neill, and I'll comment on that in a few moments. First, I'd like to briefly review our clinical programs. As mentioned, we dosed our first pediatric patients in BRILLIANCE Study for EDIT-101 for LCA10.
It's the first time that in vivo CRISPR Gene Editing medicine has been administered to a child. This is a significant milestone for many young individuals living with disease, their families, as well as for the medical and scientific field. The interest and support we've received from the entire patient community has been overwhelming, and it gives us enormous sense of enthusiasm as we continue to apply our gene editing capabilities to other genetic diseases. This is the first of four planned pediatric patients in the mid-dose cohort, which we expect to complete before the second half of the year. Following independent data monitoring committee assessment of the safety data, we will begin dosing the pediatric high-dose cohort, which we expect to initiate later this year. To date, EDIT-101 has been safe and well-tolerated in treated patients.
The Viral Shedding Data presented yesterday at the ongoing ARVO conference supported the program's favorable safety profile. The clinical data demonstrated that EDIT-101 viral shedding was transient, indicating no systemic viral persistence following the administration. There's also no correlation between EDIT-101 dose levels and the levels of Viral Shedding, as we expected based on other ocular gene therapies, including those using AAV5. A more comprehensive clinical update on the BRILLIANCE Trial will be provided in the second half of the year. This update will include safety and efficacy assessments on all patients who have had at least six months of follow-up evaluations, including at least 12 months of data on the adult mid-dose cohort and at least six months of data on the adult high-dose cohort. We anticipate these data will lay the foundation for the registrational trial of EDIT-101.
As we've said in the past, we're exploring the most relevant and sensitive endpoints to support the registrational trial development, continuing to evaluate how we can most effectively interpret trial information while always considering what is most meaningful to the patients. In addition to the trial data, we're also looking at our natural history study data to identify the most reproducible measures. We'll present some data on that study at the upcoming TIDES Conference, with additional findings later in the year. Moving to EDIT-301 and our ex vivo platform. The phase I/II RUBY Trial for sickle cell disease is enrolling study patients, and we are on track to begin dosing in the first half of 2022, with initial top-line clinical results expected by year-end. We have completed Apheresis Cycles in multiple patients to collect enough cells to edit and restore a healthy level of Fetal Hemoglobin.
These patients have already had their cells extracted, their extracted cells edited, and we're in the process of scheduling their actual dosing where we reinfuse their edited cells. This requires an extended hospital stay so that each patient can undergo the required preconditioning regimen necessary to have their edited CD34 Cells successfully administered back to them. We're also preparing to initiate the phase I/II trial of EDIT-301 for the treatment of Transfusion-Dependent Beta Thalassemia, or TDT. EDIT-301 recently received a rare pediatric disease designation for Beta Thalassemia, which it has for Sickle Cell Disease as well, and we remain on track to dose the first TDT patient this year. We're very excited as we approach the first patient dosing of EDIT-301. We believe this program can be a one-time treatment for both Sickle Cell Disease and TDT.
Our unique approach recreates the same protective mutations that result in hereditary persistence of Fetal Hemoglobin. Patients with these protective mutations are essentially asymptomatic. We're also utilizing our Editas engineered AsCas12a Enzyme, one of the most specific enzymes in the gene editing field, to make these precise complex edits. Because of the natural validation underlying the approach grounded in human genetics, we believe EDIT-301 will be a safe and durable approach to treating both of these indications. Finally, I wanna mention the upcoming management change we announced a few weeks ago. Starting June 1, Gilmore O'Neill will take over as CEO, and I will assume the role of executive chairman. Gilmore brings an incredible breadth of experience to Editas, including 20 years in genetic medicine clinical development, both as a physician and a scientist.
He has overseen the development of numerous successful products, many addressing rare disease indications as they made their way from early discovery to launch and now accessible to patients worldwide. As executive chairman, I'll be working closely with Gilmore and the rest of the executive team to drive long-term value. When the announcement was made, one frequently asked question we received was, "Why now?" The simple answer is that Gilmore is the right person for the job, and this is the right time. His creative experience of drug development, including preclinical and medical, is exactly what Editas needs today. Not in a year or two, but now. We're in an excellent position with two early-stage clinical programs making good progress, with several preclinical programs, and we're continuing to enhance our technology and capabilities to address other clinically significant indications.
This is exactly the right moment in time to bring in Gilmore, where we can leverage his expertise to address later-stage clinical trial design, prepare the next several clinical programs, and select the next clinically relevant targets to pursue. His experience and passion for creating genetic medicine will add depth and vision to our team for years to come. Now I'd like to turn the call over to Charlene to update everyone on the recent patent decision regarding the foundational IP surrounding Cas9. For some background, Charlene was one of the first people to join Editas to launch the company in 2013, and she was, and continues to be, instrumental in developing the company's IP strategy. I'm thrilled to have her join us this morning. Charlene.
Thank you, Jim, and good morning, everyone. Since the founding of Editas, we have placed substantial importance in securing robust intellectual property protections covering our scientific discoveries. We were pleased with the recently issued favorable patent interference decision from the U.S. Patent and Trademark Office, reinforcing Editas' Foundational Intellectual Property Position. This was the second favorable ruling determining that Broad Institute was the first to invent the use of CRISPR-Cas9 editing in Eukaryotic Cells. Those patents are owned by Broad and exclusively licensed to Editas Medicine for the development of medicines for people living with serious diseases. This decision means that Editas is uniquely positioned to make licenses available to those companies interested in using Cas9 for developing human therapeutics.
Given the size of the U.S. patient market and the number of companies vying to develop CRISPR-Cas9 medicines, the decision supports Editas to engage in broader licensing discussions regarding future CRISPR-based medicines. As anticipated, the University of California group, known as CVC, filed its appeal of the USPTO's decision to the Federal Circuit. That appeal will focus on whether the USPTO decision was factually supported and whether it correctly applied the law to those facts. Those facts were thoroughly reviewed by the USPTO, and we believe it correctly applied the law. Thus, we believe that the Federal Circuit will affirm the Patent Office's decision. We remain confident that the validity of Broad's patents will continue to be maintained, further strengthening Editas' IP position.
Regardless of the appeal outcome or potential settlement between Broad and CVC, our exclusivity agreement means that we are the party responsible for any licensing discussions as CRISPR-Cas9 products enter the market. Looking at the next several years, Editas will continue to play this important role as the CRISPR Gene Editing market matures. Although the interference focused on Broad's Cas9 portfolio, importantly, Editas is the exclusive licensee of both the Cas9 and the Cas12a patent estates for making human medicines. As such, we are able to issue exclusive and non-exclusive sublicenses for Cas9, Cas12a, as well as Editas' owned patents in the field of human therapeutics. This includes in vivo and ex vivo therapeutic uses. Again, our intellectual property is one of the most important facets of the company. We've always believed that our cutting-edge science is one of the ways we attract world-class scientists.
Their research subsequently builds on top of our existing platforms and capabilities for which we seek new patent protection. That is why at every step of the way, we try to protect the intellectual property surrounding our Gene Editing advancements while bringing novel medicines to patients in need of them. With that, let me turn the call over to Mark to review our preclinical programs.
Thank you, Charlene. We're making strong progress with our preclinical pipeline, and we've just announced compelling data for several of our programs. First, EDIT-103 for Rhodopsin-Associated Autosomal Dominant Retinitis Pigmentosa. RHO-ADRP is a disease of the retina leading to blindness, typically later in life, although a significant number of patients experience onset of symptoms in their early years. There are currently no approved treatments. EDIT-103 uses two Adeno-Associated Virus Vectors or AAVs to knock out the disease-causing Mutant Rhodopsin Gene while simultaneously replacing that Aberrant Gene with a functional one. The knockout of the gene in the Retinal Photoreceptor Cell can only occur if the components for the replacement gene are also delivered to that same cell. This approach can potentially address more than 150 gene mutations that cause RHO-ADRP.
As Jim mentioned, we'll be presenting preclinical data on EDIT-103 at ARVO later today. That data reports that EDIT-103 achieved nearly 100% productive editing in non-human primates, generating over 30% functional Rhodopsin Gene Replacement, resulting in corrected protein levels, which in this study proved to be a therapeutically effective level. The program is moving rapidly toward the clinic, and we expect to initiate IND-Enabling Studies before the end of 2022. We're especially excited for this program because it serves as a proof of concept for the treatment of other Autosomal Dominant Disease Indications where a gain of negative function needs to be corrected. We're also very pleased with the progress we're making with our iPSC-Derived NK Cell Medicine Program for solid tumors.
Using our proprietary engineered AsCas12a Nuclease and SLEEK Technology, we've developed engineered NK Cells that we believe have potent antitumor activity and substantially increased persistence, an important limitation with many existing NK Cell approaches. At the American Association for Cancer Research conference in April, we reported in vitro and in vivo preclinical data on the enhanced tumor-killing capacity of a double knock-in iNK Cell. A Cleavable CD16 and Membrane-Bound IL-15 were knocked into cells, increasing Antibody-Dependent C ellular Cytotoxicity, or ADCC, while prolonging iNK Cell persistence in vivo. These two knock-in edits have thus far produced tremendous preclinical results, and as many of you are aware, our EDIT-202 construct incorporates these edits, plus a knockout of Cytokine-Inducible SH2-Containing Protein, or CISH, and TGF Beta Receptor 2.
These two knockouts are designed to enhance the function of the iNK Cells with the two knock-ins, supporting our belief that EDIT-202 will be a Differentiated Allogeneic Cell Therapy. To our knowledge, this is the only program that incorporates these four edits in a single engineered NK Cell. New preclinical data on EDIT-202 will be presented at the upcoming American Society of Gene & Cell Therapy, or ASGCT, conference. It will show in vitro and in vivo data demonstrating significantly augmented ADCC against multiple solid tumor cell lines and prolonged in vitro persistence in the absence of Exogenous Cytokines. EDIT-202 combined with Trastuzumab resulted in greater reduction in tumor burden and prolonged survival in an ovarian cancer mouse model when compared against the antibody plus wild-type iNK Cells.
An important element of our iNK products is the actual cell editing and clone selection process, which allows Editas scientists to identify single clones having the precise combination of edits desired, while eliminating those having unwanted editing results. It's an exquisite approach to limit the risk associated with a complex Gene Editing process, because we can characterize a single clone extensively and know that we have exactly what we want, with no off-target edits or chromosomal abnormalities, for example. We believe our Cell Therapy Platform has the potential to create highly active, off-the-shelf NK Cell Therapy Medicines that could be used for the treatment of multiple types of solid tumors. In addition to our in-house oncology programs, our productive partnership with Bristol Myers Squibb around Alpha Beta T-Cells continues to advance, with BMS opting into a seventh program.
We believe that these programs could result in novel, Potent T-Cell Therapy approaches for cancer. The BMS programs leverage several of our unique platform technologies, including the proprietary Cas9 and AsCas12a Nucleases and our guide RNA design to create autologous and allogeneic approaches in immuno-oncology. The most advanced program from this collaboration is in our IND-Enabling Studies, and we look forward to continuing our collaboration with BMS to develop important new medicines for cancer. Finally, I'd like to say a few words on the recently issued FDA guidance for industry on Human Gene Therapy Products incorporating Human Genome Editing. The safe development of Gene Editing therapies is, as you would expect, of foremost importance to Editas. We were very pleased to see that the FDA guidance is highly consistent with the steps that we've already taken to ensure the safety of our products.
We rigorously characterize on and off-target editing as part of our preclinical development activities, and we see ourselves as being at the vanguard of Gene Editing, computational biology, and bioinformatic software development. We also pay particular attention to the stringency and quality required to design, manufacture, and test Genome Editing Components being considered for our product development. We've always placed the highest priority on ensuring patient safety and closely review and follow the FDA's recommendations and guidance in our development plans. With that, I'll turn the call over to Michelle to review our financial updates.
Thank you, Mark, and good morning, everyone. I'd like to refer you to our press release issued earlier today for a summary of our financial results for the first quarter of 2022. I'll take this opportunity to briefly review a few items. Our cash equivalents, and marketable securities as of March 31 were $566 million, compared to $620 million as of December 31, 2021. We continue to be disciplined with our expense management, and our cash runway extends into early 2024. Revenue and Operating Expenses were relatively flat year-over-year. Revenue for the first quarter was $6.8 million compared to $6.5 million for the same period last year, and that slight increase was mostly driven by our collaboration with BMS.
G&A expenses for the quarter were $20 million, compared with $21 million for the first quarter of 2021. R&D expenses were $38 million this quarter, compared with $42 million for the same period last year. This decrease was driven by success payments triggered during the first quarter of 2021, but which there was no similar activity in the first quarter this year, slightly offset by increased manufacturing and clinical investments. Overall, Editas remains in a strong financial position as we advance our programs. With that, I will hand it back to Jim.
Thank you, Michelle. We're looking forward to an exciting set of milestones for our programs and company in 2022. We expect to complete dosing the pediatric mid-dose cohort for EDIT-101 in the first half of the year. In the second half of the year, we'll initiate dosing for the pediatric high-dose cohort and provide a clinical update on the program. With EDIT-301 for Sickle Cell Disease, we anticipate dosing the first patient in the first half of 2022 and provide top-line data by year-end. We also expect to have the first TDT patient dose as well. We're advancing our EDIT-202 INK Cell Therapy Program towards IND-Enabling Studies, and we expect to release additional preclinical data as we move towards that goal. We'll continue supporting BMS as they advance their Alpha Beta T-Cell Programs toward the clinic.
We'll further advance our innovative platform technologies such as our innovative SLEEK Platform that enables our cell therapy programs. On the top of our internal objectives, we anticipate business development efforts for future development and commercialization opportunities. We have a robust pipeline and technology platform secured by a broad foundation of intellectual property that was recently affirmed by the U.S. PTO ruling. We're excited by the advances across our pipeline, and we aim to bring these programs to patients so they can benefit from the tremendous potential of Gene Editing. Finally, I'll once again welcome Gilmore to the company. I still plan on engaging with many of our stakeholders, including our investors, and look forward to maintaining a productive dialogue. We thank all of you for your interest and support. With that, we'll open it up to questions and answers.
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'd 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 key. One moment please while we poll for questions. Thank you. Our first question comes from Joon Lee with Truist. Please proceed with your question.
Hi. Thanks for taking our questions and for the updates. We're getting a lot of questions from investors on Sickle Cell Disease recently. As you discuss your trial with the FDA and what sort of trial, the study size and the duration of follow-up the FDA is asking for, to get a 301 approved, can you share any information around that? I have a follow-up.
Well, I mean, we haven't probably our next engagement with the FDA will be after we have completed dosing of the first few patients in the trial. At this point, we don't have any reason to believe that our pathway to through clinical trials is any different than what we've seen from the competitors. I still anticipate that we're probably looking for, you know, 40-60 patients ± and the same efficacy outcomes that they're looking and durability outcomes that they're looking for, whether it's bluebird bio or CRISPR Therapeutics or anybody else.
Great. The second most inbound question is around your BD and licensing strategy, given your favorable IP position in the U.S. You know, what types of BD and licensing deal do you have in mind in the foreseeable future? Thank you.
Yeah.
We envision doing a wide range of licensing deals. We're going to continue to do both exclusive and non-exclusive licensing. You know, this would be true for both Cas9 as well as Cas12a. You know, I would expect that some of these arrangements may be strategic licenses, partnerships, and collaborations, where others, you know, I would expect will be straight licenses.
Okay. A quick one, if I can. You know, since you dosed the first pediatric patient in April for EDIT-101 and requirement of six-month follow-up prior to data disclosure, can we expect something around October? Or is your data disclosure strategy such that you're gonna wait until all four pediatric patients have been dosed by the end of the first half, which would put data disclosure towards the end of the year? Thank you.
Yeah. The data disclosure we've talked about. We've talked about the adult mid dose, the adult high dose, and then previously we said we would expect that we would update on sort of the safety outcomes from the first pediatric patients at that readout, which you know October you know that's probably October November probably is a reasonable timeframe to be thinking about. Unlikely that we'll have. We will try to actually have complete cohorts of data going forward before we try to report out on the efficacy part, but the safety obviously is a little bit more of a rolling information.
Thank you. Our next question comes from Joel Beatty with Baird. Please proceed with your question.
Hi. Thanks for taking the questions. For potential BD, do you see that happening for some of your lead agents that are in the clinic or entering the clinic within the next year? If so, are there certain, you know, time points or catalysts that you'd like to hit before, you know, that could make more sense?
Yeah, Joel, good question. You know, I've in the past tried to address this a bit. You know, so let's start with EDIT-301, the Sickle Cell Disease, Beta Thalassemia. You know, it's always been my view that, over the longer term, we would want a commercial partner, for that product, particularly for outside the U.S., but potentially to share, some of that inside the U.S. Inevitably that comes with probably they become a bit of a development partner in the late stage.
I have, you know, we thought about that probably a couple of years ago and concluded that the better time to engage on those conversations was once we start to get some clinical data, because in my view, you know, that's what the bigger partners are always going to look to, and that's where we can create sort of the maximum value for ourselves. That's one. I would say a second area that we look to is, with the iNK Platform, the IO space is particularly, as you know, it's complex, it's expensive, and there we would look to, for partnerships to enhance both our depth of expertise as well as, you know, just the ability to finance and run clinical trials over a longer period of time, and ultimately commercialize.
That's not an area where I think we're likely to play any time that I can see. In the ocular space, we like those programs. There's a suite of those programs, and some programs that we have not yet disclosed. We'll start to talk about those later in the year. But those are small enough clinical trials and targeted enough in what I'll call high unmet need, but not hyper-competitive space. Our current thinking is we continue to just own those. Then maybe lastly, and to expand a little bit on what Charlene said, there's certainly some areas that we have thought about and done some work in, but it's a question of could we accelerate and create more value for everybody by partnering those up sooner rather than later.
I'm in particular thinking about, you know, potentially in vivo targets.
Great. Thank you.
Thank you. Our next question comes from Dae Gon Ha with Stifel. Please proceed with your question.
Yeah, good morning. Thanks for taking our questions, and congrats on all the progress. Two questions from me, one on EDIT-101 and one on EDIT-301. Looking at EDIT-101, your recent competitor, not in the Gene Editing space, but using ASO, read out sort of their comprehensive analysis, following their phase II-III disappointment and couldn't really find anything in terms of trial misconduct. Just wanted to get your take on what your thought process is when it comes to de-risking of your trial. When you commented on, Jim, in your prepared remarks on looking at additional endpoints through the natural history study, I think so far, we've only seen the BCVA, FST, and navigation. Any additional endpoints that you've collected that hasn't been presented that your kind of leaning towards based on the natural history analysis? That's question one.
On EDIT-301, just curious, since you seem to be following the rubric of a competitor that's about to file by the end of the year, recognizing there are some points of differentiation here, but can you set some expectations for the year-end data? Specifically, is it HbF content that's going to be the point of differentiation or VOC, since we've already seen some pretty compelling data from your competitor? Thanks.
Okay. Let's see, ProQR. The first question was really EDIT-101 and endpoints and what, if anything, do we make from the ProQR. We have as you know, we've talked about visual acuity, we've talked about retinal sensitivity with FST, and we've talked about mobility. There are other measurements that we have used in that trial, such as Pupillometry and OCT and other things. What we haven't spent time talking about is also patient-reported outcomes. That would probably be the other element that we're interested in making sure we match up what the patients and physicians are reporting to connect to the more objective data, which would be maze, visual acuity, retinal performance sensitivity, et cetera.
Those would be the kinds of things that we're thinking of looking at, and probably the ones that we've not spoken about much are the patient-reported outcomes. What are we doing is we're trying to learn as we go, plus to use the information from the natural history study to ensure that after we get past the sentinel patients. Remember, the sentinel patient for each one of our dose groups is always light perception only, so very, very poor incoming vision. And to make sure that we select patients after that are most likely to be able to show a response with those endpoints that we're using, in particular it's the visual acuity, retinal sensitivity, mobility measurements. That's actually the logic for extending the cohorts that we've talked about before.
We'll add at least another four patients, probably in the High-D ose Adult Cohort. Did I answer, Mark, did I get all the questions on that one? I'm looking over at Mark to make sure I answered the question.
I think so, yeah. I think the other thing, you know, the ProQR data is a valuable data set for us to track, right? It was very unfortunate for the patients and them that they got the surprise they did with the phase II/III. We know that we have to focus on, you know, response rate and true performance against the endpoints before we make the decision on the registrational trial. I think that's gonna be helpful.
Yeah. I'd say, you know, unfortunately, I think ProQR got pushed into this. I'm guessing, I'm speculating, probably got pushed into this, you know, sham procedure as the control. I don't think that's something that we could do anything in any event. I also don't think it's, you know, based on everything we've seen from the natural history study, that it's actually warranted, or you'd even get it past an IRB. That's just an editorial comment. EDIT-301, if I remember, Dae, your question is, well, what's our expectations for data by year-end, and what will we have that will start the point of differentiation? Expectations for data by year-end is really going to be, for the patients that we will have dosed by then, in engraftment, and we'll start to see the Fetal Hemoglobin levels.
There will not be sufficient data set to make any conclusions on VOCs or anything until, you know, sometime next year. From that perspective, then you'll have to look at how people want to extrapolate, if you will, preclinical data and actual data in the clinic to decide whether, you know, to think about differentiation on either efficacy or durability. Mark, do you have anything else that we should add to that?
Only that we're making, you know, very good progress on generating the dataset to respond to the FDA on the questions that they had on the study. That's going really well.
Yeah.
If I may add just one quick follow-up to the EDIT-101 question. On the press release, and you said this previously, your goal here as of next steps would be to expand one or more dose levels in the adult cohort. Would it make sense to expedite that process by at least starting on the mid dose since you've already dosed low and mid, and we might be seeing some kind of a dose response in the mid-level, and then depending on the high, decide on whether to pursue that second dose expansion, whether low or high? I hope that makes sense. Thanks again.
Yeah. Now that you gave me a really difficult question, Dae, I'm looking over to Mark.
It's a good question. You know, we're gonna look at the data as it rolls out. As you heard, we've dosed the first pediatric patient in the mid-dose cohort too. I think we really want to make sure that we have, taking a close look at the data, both the safety data as well as any emerging information that comes from the efficacy assessments, and use that to drive final decision on whether we expand in one or both of the available cohorts for the adults.
Yeah. The preclinical data would say the high dose is most likely to have the best effect. As Mark said, we just have to react to the data as we see it roll in.
I mean, we will have six-month data on the mid dose and 12-month data on the low dose that we'll report next. As you recall, we finished dosing of the initial four adult patients in December of last year. That data will come through in the third quarter as well.
Yep.
Thank you. Our next question comes from Debjit Chattopadhyay with Guggenheim. Please proceed with your question.
Hi, this is Ry Forseth. I'm for Debjit. For EDIT-301, could you walk us through the timing between subject dosing and how you account for the necessary engraftment time and safety evaluations?
Sure. Once the patient has their cells reinfused, we expect approximately 40-day period over which we are going to monitor Neutrophil Engraftment. That's the first step, followed by patient engraftment with general safety evaluations and clinical chemistry. At that point, when we have proof of engraftment, that will be the trigger for the second patient to be dosed, and then they will go through a similar evaluation.
Got it. Thank you.
Thank you. Our next question comes from Steven Seedhouse with Raymond James. Please proceed with your question.
Hi. Good morning. Thanks for taking the question. I had one on sickle cell and one first on LCA10. Just looking at the Viral Shedding Data from ARVO, you know, as you look across the patients, there's like six or seven orders of magnitude difference in virus copies, and it doesn't look like it's related to dose. On the x-axis, you know, most patients have, you know, below the limit of detection Viral Shedding. There's one that is detected out to week week. I just wanted to ask, what are the drivers, I guess, of just the heterogeneity here, and what are the implications? Does it tell you anything about Pharmacodynamic expectations or safety expectations?
Then the question on Sickle Cell is just, you know, appreciating that your hypothesis sort of lends to an expected difference in safety long term, but I'm curious if around the time of transplant, whether it's engraftment time or, you know, early safety events if your preclinical data suggests you'd expect to see differentiation versus the BCL11A approach. Thanks for taking the questions.
I'll take the first one on Viral Shedding. You're correct. You know, the data is somewhat variable. I would say based on my prior experience; this is exactly what you expect with subretinal administration of AAV Viral Vectors. There are variability in the way that the virus is administered, meaning sometimes the volume of the bleb may be slightly different. Occasionally, you will get reflex from the retinectomy. Just generally, this is a kind of a messy procedure to get tight data on Viral Shedding. I think the overall message is it's in line with what we would expect from an AAV-based therapy. There's no clear dose response or relationship to the administration, and it's just a general pretty benign response.
The expectation is, you know, given subretinal administration that the Vector really doesn't get much beyond the eye in any appreciable amounts, and I think that's essentially what we're finding. Albeit on occasion, you'll get some outliers, but in general, that's what we would expect.
Your question on EDIT-301 was about engraftment and anything about our product that is likely to point to early differentiation. That's, you know, a question of, you know, watching the data, which is what we're going to do and, you know, seeing how it in fact mimics what we've seen in the preclinical. If it indeed mimics what we've seen in the preclinical, we'd expect to have, you know, quite high. We'd expect the engraftment to be what we've seen with other programs similar to this. That we have very high editing levels, et cetera. I don't, you know. Hopefully that will also correspond to, clinically relevant, production of HbF, and we'll see how high that is. I don't know that once you get beyond a certain threshold, anybody actually knows how much higher is better.
Mark, I don't know if you have anything to add to that.
No, I think you're correct. It's, you know, we think the high editing efficiency of the AsCas12a Nuclease is really important here. We know from the preclinical data that we are getting very good editing of the progenitor cells, which could be a determinant of the durability of HbF or general response, and that we know with the mechanism that we are pursuing, we don't get any lineage skewing following editing. I think that could be an important factor that plays out over the longer term too.
All right. Thank you.
Thank you. Our next question comes from Jay Olson with Oppenheimer and Company. Please proceed with your question.
Hi, this is Chung, on the line for Jay. Thanks for taking the question. I guess for EDIT-101, you mentioned, you're looking for more sensitive endpoints and also maybe patients that are more responsive to the treatment. Just wondering if the same applies to the pediatric patients and also if you are collecting patient-reported outcome, from those pediatric patients. Thank you.
Yes, the same logic would apply to the pediatric patients going forward. I just wanna be careful about how we describe, you know, how we're selecting patients. It's less about do we think the product works or doesn't work, and it's probably more about over what range are these endpoints sensitive enough to actually pick up a difference, right? That's really more what we're trying to target here is to ensure that the incoming, the baseline site for the patients is in a range where these endpoints will work. As you can appreciate, you know, BCVA and even the Berkeley, you know, if they have very, very low vision coming in, it's not a very useful, you know, there's not too much information you're going to get from that.
By the same token, if they have very good eyesight coming in, their ability to maneuver through the maze is already at sort of the top of the scale, right? I just use those as kind of examples of how we think about adjusting the incoming, the inclusion criteria, if you will. Do we have more questions? Yep.
Thank you. Our next question comes from Rick Bienkowski with SVB Securities. Please proceed with your question.
Hey, good morning. Congrats on all the progress, and thanks for taking our questions. First, I was hoping you could clarify exactly where in development the EDIT-202 Program is. I know a lot of your recent scientific presentations have highlighted this program, but I don't believe we have any guidance for an IND filing. Could you maybe discuss some of the work that's ongoing for EDIT-202 and what steps need to be completed before an IND filing? I have a second question. The press release guided for cash runway into early 2024. Could you also just dive into some of the major assumptions around this number, including maybe how many clinical programs you expect to advance in parallel and whether or not this is dependent on any incoming milestones?
This is Mark. I'll take the EDIT-202 questions. You're correct. We haven't yet given specific guidance on the date of the IND filing. As you can imagine, all of our efforts are directed towards completing the data package that will be necessary to file an IND, which includes all of the pharmacology and toxicology work, preparations for an IND-Enabling GLP Toxicology Study, which includes both the pharmacology side but also the preparation of the cells. You know, clinical clone selection and then expansion and differentiation of that to produce sufficient cells to conduct all of these studies. That's where we're going right now, and as the plans solidify, we'll give, you know, maybe later in the year, give more guidance on, you know, narrowing a date as to when we think the IND could be available.
I'll take the second question, Rick. Our cash runway is based on and includes our current plan, so our current clinical programs as well as our preclinical programs that we've spoken about. It does not assume any incoming cash from milestones or BD.
It essentially assumes everything that we've tested and talked about in our clinical or preclinical pipeline moves forward at pace.
Great. I just wanted to follow up on the EDIT-202 Program. The press release mentioned advancing internal and external manufacturing capabilities in tandem. Is that perceived to be a bottleneck for the IND filing as well, or is that just, you know, work that's ongoing in parallel with the other preclinical work?
It's the latter. It's just the approach we're taking to develop a methodology for the expansion and differentiation and then the transfer of that methodology to an external CDMO.
We don't view that as.
Useful business, yeah.
Yeah, normal business, and we don't view that as rate-limiting to moving this program to the clinic.
Thank you. Our next question comes from Madhu Kumar with Goldman Sachs. Please proceed with your question.
Hey guys, this is Rob on for Madhu Kumar. Thanks for taking our question. I was just wondering, does the High-Dose Cohort of BRILLIANCE include any Homozygous IVS 26 patients? Thanks.
I don't believe so at this point in time.
We haven't released the specifics of the patients included in that cohort.
Okay.
as you know, Homozygous patients constitute probably about 10% of the population, and so we're focusing on the entire population, not just those.
Thank you.
Thank you. Our next question comes from Luca Issi with RBC Capital. Please proceed with your question.
Oh, great. Thanks so much for taking my questions. Congrats on all the progress. Just a few, one here. On LCA10, you know, maybe circling back on a few prior questions, maybe ask a little bit more directly, and I understand lots of moving parts as the data is still evolving, but what will be the endpoint that you will pitch the FDA today as the primary endpoint for LCA10? And then the second on the IP, can you just talk about how we should think about the long-term implications given you now have the upper hand in the U.S., but my understanding is the CVC is in a stronger position in the E.U. Would it be fair to assume that this will all come down to cross-licensing agreement between the parties where the economics depends on the geography?
Lastly, can you just give us any update on the Chief Medical Officer search and maybe remind us who is the ideal candidate given the breadth of the pipeline, which obviously spans ophthalmology, hematology, and oncology? Thanks so much.
Luca, you're assuming that we can remember a compound question. Do you wanna start with that, Mark Shearman?
Yeah, with EDIT-101 .
Yeah.
Yeah, we haven't made that decision yet. As we've indicated, there's a lot of data coming in, and the decision will be data-driven based on what that looks like in both the adults and hopefully, you know, in the pediatric patients, and that will guide our final choice. Right now, still under evaluation.
Charlene, you wanna take that?
Sure. We see tremendous value in our IP, and we think that we have a significant longer-term opportunity to think about how we license the technology. The USPTO decision is very favorable to Editas and Broad, and, you know, we believe that that decision will be upheld on appeal. We also believe that there's a majority of drug development and commercial sales will play out here in the U.S., and so that really underscores the importance and value of the IP that we have.
Yeah. I mean, I've looked at all of the models that everybody's put together for Cas9 Programs that might get commercialized. You know, it always looks like it always did, which is 2/3 or more of the revenue is gonna come out of the U.S. market. Then there's also an underlying presumption in what some of the companies are saying is that we actually need anything for FTO in Europe, and that's by no means clear at all. Particularly for our Sickle Cell Program. Remember, we're using Cas12a, and so that's you know, the Cas9 question is completely irrelevant for our Sickle Cell Program. It's not clear that we need anything else at this point in time for FTO for any of our other programs outside the U.S.
And the EDIT-202.
Great. Thank you.
Yeah.
No, go ahead.
Mark was just adding that the EDIT-202 program uses the AsCas12a as well. Anyway. You had another. I'm sorry, Luca.
No. No got it. Super helpful. Last one on the Chief Medical Officer search. Thank you.
Chief Medical Officer. See, I told you if you asked me a compound question, I wouldn't get it. We're in the process of interviewing people. What's the perfect candidate? You know, it needs to be somebody that is a clinician scientist. Why that's important here is, you know, obviously, they need to know how to develop a program, and they have to have been part of and overseen successful clinical development from sort of the beginning to the end. Because I've said before, you know, real clinical development starts in phase IV, right? After you get your initial approval. Then the reason they need to be the scientist part is this is a highly technical area that's moving fairly quickly.
They need to be able to partner very closely with Mark's team as they think about what are the next targets, right? So that we make sure we match up, not only targets that are technically doable, but that are clinically relevant, and that we can foresee a pathway develop. Yeah, so that's the second. Lastly, you know, it has to be somebody that sort of knows and has overseen the building and the expansion of a high-functioning medical organization and has had to have that experience. You know, I think those are the profiles we're looking for. For sure, from the people that we're interviewing, we're getting those.
I'm very optimistic we're going to get a very high-quality candidate here, that is, you know, going to be a real addition here to what's now a nicely building team. Remember, you know, Mark has done a great job in not even 12 months, right, Mark? It's not 12 months yet of really getting the research focused and getting all of these programs moving, the preclinical and the technology development. The clinical part of it is moving much better than it was. I think we add a CMO, add that into Gilmore's experience, you know, now we've really got the team necessary to drive this business for years to come.
Thank you. Our next question comes from Gena Wang with Barclays. Please proceed with your question.
Thank you. This is Tom for Gena. We have two questions, one for EDIT-301 for the Sickle Cell Disease and one for EDIT-101. For Sickle Cell Disease, given the dosing interval for the safety and engraftment evaluation, how many patients can we expect for the year-end update? For EDIT-101, I know it's earlier and everything should be data-driven, but just want to get your assumption on would you need additional pediatric cohort expansion to further guide the either dose selection or trial design for the pivotal trial?
The number of patients by year-end was first question on EDIT-301.
Yes, our expectation will be that by year-end, we will have dosed two patients. As I indicated earlier, you know, the start of the trial is very carefully monitored, so the first patient has to get at least out to week six before we will be able to confirm that the edited product has engrafted in that patient. The immune system is being reconstituted, so that takes us. You know, we've indicated that the first patient will get dosed by the first half of the year, so that takes us into sort of the third quarter, and then we hope to get at least one more patient dosed before the end of the year.
We may have more than that, but what Mark's referring to is what we will have for data that we've discussed is really, I think people can expect two patients. Then your question on EDIT-101.
Yes. I think it was the cadence of the additional dosing.
Right.
I think we're sticking with the guidance we've given that we expect the pediatric mid-dose cohort to complete dosing by mid-year and that we will initiate the dosing of the high-dose pediatric patient cohort by year-end. Similarly with the adult expansion cohort, one of those to be initiated and hopefully completed by year-end.
Thank you. Our next question comes from Liisa Bayko with Evercore ISI. Please proceed with your question.
Hi. I think most of my question's been answered. I guess just one outstanding, for EDIT-103, you know, as we're thinking about endpoints and it's, you know, obviously very complex in these ocular diseases, what kind of endpoints make sense to kinda track this disease? I know, you know, vision loss tends to occur later in life. Is this something that's, you know, you think more easily measured in, by some of the endpoints that are commonly used or might require some other kind of metrics? Just curious how you're thinking about the regulatory approach here.
Yeah. It will be our intention to use most of the same exploratory endpoints for the rhodopsin indication as we do for EDIT-101. As you probably know, this is a rod photoreceptor disease, so the initial decline occurs in peripheral vision, so perimetry will be an ideal way of looking at that. right now, we will do all of the things that we've been doing for EDIT-101, which includes monitoring retinal sensitivity, this sort of anatomical evaluation by OCT and so on, patient-reported outcomes. you know, all of those types of typical measures we'll take a look at because this is not an indication for which there is a therapy already. in this patient population, we'll have to see, you know, which of the endpoints is the most responsive to the treatment.
Some of these endpoints will be a little easier to conduct on these patients, because they are coming in with, you know, good eyesight, at least central vision. You don't have the nystagmus, things that make some of the data hard to collect with certain groups of the patients in EDIT-101.