Good morning, and welcome to Editas Medicine's Second Quarter 2021 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. Open.
I would now like to turn the call over to Ron Waldaver, Investor Relations at Editas Medicine.
Thank you, Daryl. Good morning, everyone, and welcome to our in the Q2 2021 conference call. Earlier this morning, we issued a press release providing our financial results and corporate updates for the Q2 of 2021. Prepared remarks. We will open the call for Q and A.
As a reminder, various remarks that we make during this call about the company's future in the 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, participating in the Risk Factors section of our most recent Annual Report on Form 10 ks, which is on file with the SEC. 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 in a 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. Joined today by several members of the Editas executive team, including Mark Sherman, our new Chief Scientific Officer Lisa Michaels, our Chief Medical Officer in the line with our Chief Financial Officer. I want to start off by providing some highlights from the Q2 and reviewing our upcoming milestones. Editas has had a strong first half of the year with excellent momentum across our platforms and lead programs. The EDIT-one hundred and one BRILIENCE trial for LCA10 is proceeding very well with the independent data monitoring committee recently endorsing enrollment of the first of 2 planned pediatric cohorts We've also started enrolling patients in the adult high dose cohort.
We are also expected to share initial in the Q1 of 2019. This will mark the company's first ever clinical data readout. Reviewing the RUBY study of EDIT-three zero one for sickle cell disease in screening patients and we remain on track to begin dosing by the end of the year. In the pre IND work for EDIT-three zero one in beta thalassemia is progressing and we remain on track to file the IND before year end. Additional data supporting the unique properties of our proprietary Cas12a enzyme was recently published in Nature Communications, And we plan to present new data on our multi transgene noccan proficiency at upcoming Cold Spring Harbor Meeting.
These accomplishments further support the incredible potential of our gene editing platform. Our manufacturing capabilities for lead programs have advanced nicely and ready to manufacture all clinical supplies for the RUBY trial. We continue to progress our oncology programs, including our iPSC derived NK cell program advancing in preclinical studies. And finally, we continue to make headway on our remaining preclinical programs, including ocular diseases. Additional updates on those programs will be provided later this year.
On the leadership side, we had several important announcements last quarter. Doctor. Mark Sherman joined the company as our new Chief Scientific Officer. Mark is an experienced executive who has brought multiple programs from ideation into and through the in the clinic and has led numerous successful partnerships. He brings an extensive track record of achievements in drug discovery and clinical development across multiple therapeutic modalities.
Mark is 2 months into his new position, and I'm pleased to have him on the call with us today. We're also delighted that Doctor. Chi Li joined us as Chief Regulatory Officer. Chi brings an extensive resume guiding over 30 development programs through regulatory in the process, including multiple U. S.
And global submissions, and he will be a critical part of our leadership team as we advance our pipeline. Open. And finally, we're pleased to announce the promotion of Bruce Eaton to our executive team as Chief Business Officer. Bruce has been involved with Editas in various capacities since 20 15, starting as a consultant, then a research collaborator and as a full time leader of our Boulder site. He brings a successful track record, including more than 30 years of scientific operations, business development and corporate strategy experience in both public and private companies.
At the table will have a critical impact on how Editas continues to evolve. So overall, I'm extremely happy with the progress through the first half of the year and with our expanded executive team, I have the utmost confidence that we have the right people in place to lead Editas to the next phases of the company's growth in towards long term success. With that, let me turn the call over to Mark for his first earnings call as Editas' Chief Scientific Officer. Mark?
Open. Thank you, Jim, and thank you to everyone dialing in. So I'm thrilled to have joined Editas and to have the opportunity to lead an extremely experienced and dedicated group of researchers and scientists. My short time at the company has only reinforced my excitement working with Wim, the rest of the leadership team and the exceptional people throughout the organization. To To give you a brief background about myself, I have almost 30 years of drug discovery and development experience and I've been fortunate enough to be a part of advancing around 15 drugs into clinical development.
I began my career in academia and then moved to the corporate on the R and D side where I conducted research into Alzheimer's disease, other neurodegenerative disorders as well as autoimmune diseases. For the last 6 years, I was the CSO at Applied Genetic Technology Corporation, developing AAV gene therapies mostly for ocular diseases. The impressive technology platform and the potential breakthrough capability of gene editing technology in the regenerative medicine space is what brought me to Editas. Most of my scientific work revolves around ophthalmology, immunology and neurology, pleased with truly a remarkable opportunity. I've always been intrigued by new aspects of sites of technology that can improve the likelihood being successful in drug development, for which open new treatment avenues for patients who otherwise might not have other options.
Editas' gene editing platform has the potential for both of those. It allows us to address certain diseases not easily addressed with other treatments, And I'm excited to be part of its mission to transform medicine. So two examples illustrate this point. Firstly, The recent publication in Nature Communications that Jim mentioned earlier detailing an engineered AS Calc 12a Nuclease, at the end of the year, which we believe to be a significantly advanced enzyme with editing efficiency approaching 100% across sites in multiple cell lines on target specificity. This engineered nuclease alleviates many off targeted editing concerns often observed with Cas9 enzymes, consequently leading to an improved safety profile and making it ideal for complex in the range of therapeutic gene editing applications.
It also greatly reduces the process chemistry challenges associated with the manufacturing of high quality This proprietary tool could be an important step forward in the development of novel therapies Secondly, the development of SLEAK technology, which stands for Selection by Essential Gene Exon, knock in. We're excited to announce that this new gene editing strategy enables us to achieve nearly 100% knock in of functional transgene cargoes using CAR T and CAR NK cell therapies, but beyond those applications, it could have immense potential in protein replacement strategies, for example. Details of this exciting technology will be shared later this month in an oral presentation at the Cold Spring Harbor Laboratory's Conference. So having been with Editas for about 2 months now, I've outlined my high level priorities as CSO, which are firstly, to continue to advance our current in vivo, in the next phase of the Phase III study, to progress our in vivo gene editing ophthalmology programs and further strengthen our existing preclinical pipeline, expand our world class gene editing capabilities and the delivery technologies they rely upon and finally, continuing to grow and develop the scientific base and build upon a research and development team that is second to none.
With this impressive technology and world class talent at Editas, I'm excited to discover and develop revolutionary new medicines to help people living with serious diseases. Open. With that, I'd like to turn it over to Lisa.
Thank you, Mark. And I wanted to simply say I'm excited to have you join us as part of our team. Okay. As part I'd like to start with an update on the BRILIENCE trial for EDIT-one hundred and one for the treatment of LCA10. Last quarter, we completed dosing of the adult mid dose cohort.
And as Jim mentioned, we met with the study's independent data monitoring committee to review the safety data from the adult low dose and mid dose cohorts. Enrolled since LCA10 is an early onset retinal degenerative disease, which results in vision loss and blindness at an early age. From around the world, so new therapeutic options are urgently needed. And we continue to believe that a single administration would be preferred over a chronic dosing regimen by clinicians, parents and the patient community. In addition to enrolling patients in the pediatric mid dose cohort.
We're also enrolling patients in the adult high dose cohort. Both cohorts are planned to have 4 patients each, and we expect to complete dosing of the 2 dose groups in the first half of next year. We intend to present initial clinical data from EDIT-one hundred and one at at the International Symposium at Retinal Degeneration in September. Now this is an exciting milestone as it will be the first time that Editas will present clinical data at a meeting. The data will include safety and evaluation of the measures of biological activity from the 6 adult patients that have been treated in the first two dose cohorts.
Now the primary objective of the study is safety. Our goal is to develop a safe treatment that's not limited by dose limiting inflammatory reactions, conducting a question and answer session. This concludes our prepared remarks. This concludes our prepared remarks. This concludes our prepared remarks.
Our analysis of this early data set will consider all the observations across the multiple measurements that have been collected and are currently being collected, participating in the symposium. Representative endpoints could and would provide evidence of productive editing may include measurement of retinal responses to light participating in the Q1 of 2019 as well as clinically relevant outcomes such as reproducible improvement in patient reported visual acuity or in the ability to maneuver around objects at different levels of illumination. Following the main study protocol, we will monitor patients for both safety and for secondary clinical endpoints every 3 months for And we aim to maintain the same pace for enrolling and dosing patients in the next two cohorts. Now moving to our ex vivo programs, participating in EDIT-three zero one. As we've said before, we believe that EDIT-three zero one has the potential to be a differentiated in an important medicine for sickle cell disease and beta thalassemia patients.
Our Phase onetwo RUBY study of EDIT-three zero one is active in screening patients and we continue to add trial Our CMC group is ready to support us with all clinical manufacturing required for this phase of the study. We also have received an approved clinical trial application from Health Canada, on track, which will expand the number of potential study sites, and we remain on track to begin patient dosing by the end of 2021. Additionally, we also remain on track to file our investigational new drug application for EDIT-three zero one in beta thalassemia by the year end. Providing further preclinical support of the potential benefits of EDIT-three zero one, we presented additional data at the European Hematology Association Congress in June. This data showed that editing at the beta globin locus using our proprietary Cas12a enzyme results in a highly robust fetal hemoglobin induction erythroid progenity cells.
Importantly, this occurred at a high level of specificity and no detection of off target editing. EDIT-three zero one mimics a naturally occurring mutation associated with hereditary persistence of fetal hemoglobin as opposed to other approaches that target BCL11A. This approach and the presented data support our view that EDIT-three zero one differentiates itself from other programs through its highly efficient editing and specificity, in the range of 2,000,000,000,000, which we anticipate will result in optimal safety and efficacy. And by demonstrating robust and sustained fetal hemoglobin expression with both short and long term safety, ready to take questions. We aim to have a best in class medicine to treat sickle cell disease and beta thalassemia that will hopefully lead to longer lifesponse for these patients.
Our clinical operations teams for EDIT-one hundred and one and 301 have already been working very tirelessly to move these programs forward. And I truly believe that the sooner we can get our medicines patient, the sooner we can deliver on our promise to transform people's lives. And with that, I'd like to turn things over to Michelle to briefly run through the financial results. Michelle?
Thanks, Lisa, and good morning, everyone. Ready. I'd like to refer you to our press release issued earlier today for a summary of our financial results for the Q2, and I'll take this opportunity to briefly review a few highlights.
Comparing the first half of
this year to last year, total operating expenses increased by approximately $25,000,000 This was primarily related to an increase in stock based compensation in a $14,000,000 as well as a $9,000,000 success payment due under one of our institutional licenses that was expensed in full during the Q1 of this year. The remaining increase is driven by our expanding clinical regulatory and manufacturing efforts to support both our BRILIENANCE and RWBY trials and the pre IND work for EDIT-three zero one to beta thalassemia. Quarter over quarter, total operating expenses were $56,000,000 in the 2nd quarter compared to $63,000,000 for Q1. Excluding stock based compensation of $12,000,000 in Q1 and $14,000,000 in Q2 in the $9,000,000 success payment in Q1, operating expenses were essentially flat in the 1st 2 quarters of this year. Editas' balance sheet and cash position very strong.
Our cash balance as of June 30 was $698,000,000 compared to $723,000,000 at the end of Q1. This capital will allow us to execute on our strategy to progress our clinical programs, further develop our pipeline and continue to build our internal manufacturing capabilities. We anticipate that this cash position will fund our operations well into 2023. With that, I'll hand it back to Jim.
Thank you, Michelle. The first half of this year has been very productive for Editas and the gene editing community. We continue to see important accomplishments in in the field, including the successful demonstration of in vivo gene editing. This milestone reflects ongoing maturation of this novel therapeutic modality and immense looking at the potential for the technology. It supports the fundamental notion that a gene editing medicine administered directly to people can have a clinical benefit.
And more importantly, this marks a monumental milestone for patients living with genetic diseases. Validating the potential power of CRISPR gene editing is a major strike forward for the GeoMx feel and people who we are trying to help. As I've said on our previous call, it's truly a remarkable time to be involved in gene editing. I I believe we have an obligation to utilize this once in a generation technology to develop the best possible treatments for patients and promote progress within the scientific and medical communities. We thank all of you for your support and interest in the company.
And with that, we'll open it up to questions and answers. Operator?
Our first questions from the line of Gena Wang with Barclays. Please proceed with your questions.
Thank you for taking my
questions. Open. I have two questions. The first one is regarding the ALC-eight ten program. I think you mentioned the primary The clinical measurement you will share.
Just wondering, like you mentioned visual acuity, wondering first, will you also share Mobility Core score and then how should we look at this in the context of a natural history And the second question is regarding the 301 for sickle cell disease. Just wondering, Has the FDA partial clinical hold already resolved? When you see an on track dose in the first patient, do you
Lisa, are you there?
I pardon. Gina, I apologize. I was on mute. I was trying not to cough into my microphone.
So to
your first question, Gina, So regarding what's going to be reported in RD-three zero one for the EDIT-one hundred and one program moving into the RD-twenty 21 meeting. So I've already summarized the meeting is, that the primary outcome of the study really remains safety and dose limiting toxicity. So the data and the cumulative safety data of the patients dosed in the first two cohorts will definitely be presented at that meeting. What I want to remind people is that this is still an ongoing study moving forward over time being able to demonstrate that editing has actually occurred in the eyes and that would be a very interesting proof of concept for us to share regarding any potential changes that have I want to remind everybody it's still quite early in the trial. The longest patient in the mid dose cohort was only dosed in January.
So we're still collecting data prospectively. It's certainly our intent to look across the entire range of measurements in each individual patient moving forward and that we will be sharing at least Data that will be comprehensively looking at both the possibility of being able to show both efficacy as well as clinical outcomes at the study. Beyond that, I'm not yet prepared to give you more detail. To the second question with 301, I just kind of remind everybody, it's not a complete clinical hold. It is The partial hold, basically in order to be able to validate the clinical assays that we're using to correlate dosing to clinical efficacy.
It does not interfere at all with our ability to move forward. We are able to dose the patients in the trial, in an ongoing fashion as already outlined in the protocol. And so it's actually having no impact on our ability to move forward. We will need to have some patient data to correlate in order
ready. Thank you. Our next questions come from the line of Matthew Harrison with Morgan Stanley. Please proceed with your questions.
Good morning, everyone. This is Costas on for Matthew. One question from us on EDIT-one hundred and one. Can you please remind us what the stopping criteria are in the high dose cohort? Thank you.
So the stopping criteria is very clear across all different dose courts and that is basically the dose limiting toxicity. This would include inflammatory
Thank you. Thank you. Our next questions come from the line Phil Nadeau with Cowen and Company. Please proceed with your questions.
Good morning. Congrats on the progress. A follow-up question for me on 101. In your corporate presentation, you mentioned secondary efficacy endpoints in 101's trial, including macular thickness, electroretinogram and Pupilometry. It sounds like you're going to use those to figure out if there's sufficient editing going on in the retina.
I guess I'm not all that familiar with answering those measures. Can you give us some idea of what changes you'd need to see to have confidence that there is a sufficient amount of editing in vivo That there could be ultimately improvements in visual acuity in a young enough patient population?
Okay. So basically the way I've been dividing it up is and I think you summarized it actually quite well. The first one is a lot of electrophysiologic measurements as well as memorizing physiologic responses to either different colors of light, Pupillary responses to light being shine in the eyes because these patients do tend to have either reduced or very sluggish responses. If we were to see consistent changes moving forward in any of those measures. That at least would be a signal to us that editing is taking place in the back of the eye.
This is sort of my indirect way of measuring it without the ability actually measure the protein that's being created in the eye moving forward. As to the clinically relevant endpoints, I would Agree with those that say that basically, definitely those things that impact a patient's ability to function, such as visual acuity Or also the ability to maneuver around the maze would be the approval endpoints and the ones that would bring those value to the patient.
Perfect. Then another follow-up question on 301. And the answer to the last question, it sounds like you'll need some clinical data to validate the assays necessary to remove the clinical hold. Do Do you have a definitive agreement with the FDA on the amount of clinical data that's necessary, the number of patients or duration?
So at the moment, we have at least proposed a matrix, in order to be able to show how the across multiple different measures to show
Thank you. Our next questions come from the line of Yanan Zhu with Wells Fargo. Please proceed with your question.
Thanks for taking my questions. So on the biomarkers, for lack of better words, the several measures that you will investigating to see to understand whether there is editing. Do we know that those measures, Do they change simply by subretinal injection, for example?
Thanks. So and I invite Mark to jump in if he feels like he wants to add color to it. But I think one of the most important things 1st of all, the biologic markers are basically physiologic responses. So these are purely objective measures that we can actually measure physiologic changes that can take place. The concern about placebo is that it is unblinded, both the treater and the patient both know of which eye has been treated.
And this is the primary reason why we're actually focusing on reproducibility. A one time measurement that shows a Significant change in vision is not going to be enough for us. It really needs to be able to be sustained across multiple different measures over time.
Yes. And if I could add a thanks for the question, Yaron. As you know from covering the companies that are administering subretinal AAV, There is a possibility of slight changes in and around the surgical procedure as the retina reattaches. Those are usually tracked by companion, the untreated and as Lisa pointed out, over time, they generally settle down within a couple of weeks. And All of that data gets collected and tracked and the intention is to show over time a real treatment effect that's separate from any surgical or any other intervention related change.
Got it. That's very helpful. And for you mentioned the longest follow-up in mid dose cohort since January. What about the shortest follow-up? Does has that
I can tell you we're coming down to the wire on that one. So I'm not I need to be able to see what the timing of that visit is going to be.
Ready. Thank you.
Yes.
Thank you. Our next question comes from the line of Cory Kasimov with JP working. Please proceed with your question. Hey, good morning guys. Thanks for taking the question.
My question is on 101 and 301 recovered. So I wanted to ask about the iPSC
Mark, do you want to handle that one?
Yes. We've indicated in the corporate presentation some of the changes that are being made and We continue to develop the necessary editing for the final construct And also the differentiation profile and process for that. And so right now, that's really what we're focused on. On mute, and we'll be providing updates again later in the year on the progress.
Open. Thank you. Our next questions come from the line of Joon Lee with Truist Securities. Please proceed with your questions.
Hi. Thanks for taking our questions. For the Cohort 2, are the patients enrolled also like perception only like cohort 1 or are they able to perceive hand motion or better in the cohort 2? And have a follow-up on 301.
Okay. So for 101, the way the protocol is basically written is we were able to Based upon the safety that was seen in the first cohort, we were able to modify the protocol so that we could proceed beyond just like perception patients. However, at each dose level, we do have 1 sentinel patient who is involved primarily for the purposes of evaluating safety and making showing no inflammatory reactions that would limit treatment of further patients. So the first patient is light perception, but each additional patient involved And
so,
I guess, following up on that, if you look at the There are visual improvements, including BCVA and mobility evident as early as month 12. Is there any reason to believe that the effects of EDIT-one hundred and one would be any slower than the antisense mediated exon skipping? Curious if you have any thoughts on the kinetics of the onset of clinical side between Genome editing versus antisense oligo?
So I guess the way if you're thinking in terms of the absolute timing, we do know that from our non clinical data that the optimal editing has occurred by about 6 weeks after in the injection. As Mark has alluded to, there are also because of the procedure needs to be some healing that needs to take place in the back of the eye. So the first measurement that we would expect to see some change would be at 3 months. However, because we're really looking for consistent responses as well as potential improvement, Following it out to at least 6 months or longer is going to be what we're going to be looking at. But is there any it's hard to compare the 2 different modalities since they're very different approaches.
At it. And just for clarification, the Cohort 2 will be 4 patients worth of data?
So Each cohort is planned to be 4 patients and then we'll evaluate.
Okay. Thank you.
Yes. Ready.
Thank you. Our next questions come from the line of Thiago Fouth with Credit Suisse. Please proceed with your questions.
Hi. This is Jonathan on for Thiago. Thanks for taking our question. For EDIT-one hundred and one, In light of the upcoming readout for the low and mid dose cohorts, for the adults, how should we be thinking about how these results may translate
to the respective doses in the PDASIA cohorts.
What are the key differences we
should be thinking about there? Thanks.
I think we still have yet to kind of learn that in terms of the observations. In general, the maturity of the human eye after you get about 3 years of age, at least the anatomy and the size of the eye are relatively similar. Most of the changes that occur in the eye are more or less completed by about 6 to 8 years of age. So I'm not I don't know that we're going to see a difference in terms of clinical response or safety. Will have a chance to evaluate that as we move forward.
Got you. Thank you very much.
Open. Thank you. Our next questions come from the line of Steve Seedhouse with Raymond James. Please proceed with your questions.
Open. Good morning. Thank you. 1st on EDIT-three zero one, I'm just curious beyond editing efficiency, what advantages you might anticipate from using the AS Cas12 A, in sickle cells, specifically like cell viability, doubling time, manufacturing success rate, things like this compared to legacy using Nucleases that may obviously correspond to improved clinical outcome. And then also on that ultra nuclease, It looks like it's small enough to package into AAV5.
Any thought on advancing that nuclease into LCA10 Or in future ocular disorders, is this the nucleus you're planning on using? Thanks.
So maybe I can take those questions. So As you saw in the Nature Communications paper, the Cas12 Engineered Cas12a or Cas12a Ultra on target, editing, efficiency, potency, all of that. One other factor which is Important for us also is the guide RNA size tends to be quite a bit smaller than the Cas9 and that's important when you're manufacturing these guide RNAs because the fidelity decreases the longer the length of the Guidance, so we feel that, that is definitely advantage for intrinsic on target editing. And so the second part of your question, of course, yes, we can fit a Cas12a into an AAV. And so we're looking to deploy that in some of the in vivo gene editing programs that we have ongoing and potential future ones and actively working on optimizing the
Thank you. Our next question comes from the line of Joel Beatty with at Citi. Please proceed with your questions.
Hi. This is Joel from Baird. Thanks for taking the questions. For the LCA10 program and the pediatric mid dose cohort, what ages and what status of disease course in the children do you anticipate enrolling in? Enrolled in.
What could that mean for the ability to interpret clinical results compared to the first cohorts that we'll be reading out in September?
So we've got a little bit of a balancing act in all of this because the protocol does allow us to go as young as 3 years of age in the treatment of the patients. But I think one of the Key outcomes that we want out of this is just not it's not just safety, but it's also the ability of the patient to be able to cooperate with the various different ready to participate in the observations. And I think there's no solid drawn line in here, but if you think about your 5 or 6 year old, whether they can sit through a long day Of observations and walking through vases, I think, is part of our consideration.
I appreciate that. Thanks.
Yes. Open. Thank you. Our next questions come from the line of Jay Olson with Oppenheimer. Please proceed with your question.
Hey, congrats on the progress and thank you for taking our questions. On the EDIT-one hundred and one data coming in September, Can you talk about, whether or not we should expect to see the clinical measurements fluctuate over the follow-up period or remain relatively consistent? And then, for any safety signals, Are there ways to tell whether potential side effects are coming from the administration procedure,
Okay. So I guess the first One is the consistency of measures. I just want to remind everybody, it's still relatively young days for that middle dose cohort, Because like I said, the first patient was started in June and the next three patients were enrolled over the following 5 months. So for some of these patients, we won't have that much reproducible data just yet. As for the safety observations, it is one of the more important observations of So that data is being collected prospectively.
Great. Thank you. And then for 301, in the SCD study, Can you just talk about your timeline for completing the target enrollment in that study? And then maybe comment on what the FDA might want to see in terms of a follow-up period in SCD, given some potential safety concerns from other companies using gene therapy?
So the second half of the question is we are expecting and in fact it's sort of standard across the entire gene therapy and gene editing space that long term follow-up for safety will be a requirement. So pharmacovigilance is going to be something that all of us have to be addressing moving forward. As to our timeline, it's still again early days. We actually are actively opening up sites. We have a number of patients who are undergoing screening.
And I'm focusing mostly on getting my first patient dosed by the end of this year.
Great. Thanks for taking the questions.
Thank you. Our next questions come from the line of Madhu Kumar with Goldman Sachs. Please proceed with your questions. Open.
Great. Thanks for taking our questions. So when we think about N101, the high dose versus the mid and low dose, frame those doses relative to the preclinical dose range you described in your previous studies? And then kind of following from that, what's driving you confidence that
Mark, do you want to try that one or you want me to bite?
No. So the doses as I'm sure you've already asked a similar question before, the doses chosen for the clinical study were obviously guided by the preclinical pharmacology and toxicology work that was done in mouse and nonhuman primate. To address the question about whether we think a higher dose will lead to better editing, we have evidence, particularly in the humanized mice model that would be the case. I think in non human primates, there is some indicating that that could also occur. The data was, I would say, less clear in terms of the fact that the NHP guides were not performing as effectively as the human ones, but in principle, yes, the expression of the nuclease components And the editing productive editing increased with dose.
And so going from the mid to high dose, which is a factor of 3, going into it, we would have an expectation that that could yield better results, but obviously the clinical data will have to bear that out.
Hi, thanks for taking the question. I'm wondering, as you think about the kind of available visual field for these patients for EDIT-one hundred and one. Can you maybe describe Kind of with the way you're administering, how much kind of, I don't know, in a way surface area would be available for editing? And is there anything you can do to kind of expand that further?
Go ahead, Mark. We can fight each other for this one if you want.
No. All I would like to say is that across in different fields where companies have introduced a bleb up to, for example, 300 microglia, covering about a 20 degree So I hope that answers your question, but that's the intent with the current dosing paradigm.
Okay. So what you're saying is you can cover the entire macula with that with a bleb and so that Should be sufficient in terms of like kind of covering the visual field in a way.
Well, that's covering The majority, if not all of the cones expression, which are obviously concentrated in the macularin fovea region, plus The rods which are also expressed more sparsely, but expressed in that area. So again, this is a, I would say, pretty
Okay. And I would say that LCA10 is somewhat of a central retina. Basically what's happened in many of these patients There is a preserved area of normal cells where there hasn't been degeneration, and actually that's in the central retina itself. So these are the cells that Most likely the ones that we're going to have the best effect from.
Yes. And maybe just to reiterate, I mean, companies have attempted to put the bleb either outside the mid periphery or in some cases multiple blebs for the former approach. The disease quite often is heterogeneous in the periphery. So it's not that straightforward to actually carefully cover the degenerative On the one hand, yes, you can cover a greater area, but then you're introducing multiple retinotomies. And One of the things you absolutely want to avoid is reflux of the product because as you may be aware, intravitreal dosing, Which essentially what's been happening leads to a greater likelihood of ocular inflammation.
And so those are the trade offs that you're considering.
Okay. Okay, that's helpful. Thank you. And then for EDIT-three zero one, As you kind of look at the data, the clinical data coming out from companies like Vertex CRISPR And where do you see the opportunity? I know theoretically the kind of advantages you're describing And those make sense.
But sort of in a practical form, as you kind of look at the data that's evolving, where do you see the opportunity to make a difference with EDIT-three zero open.
Do you want me to take that one, Lisa?
Well, you always answer it really well. I'm actually what you say, but usually answer it really well. Well,
yes, so I'll take that one. This is Jim. I You have to take a little bit longer view of what trials in sickle cell and beta thalassemia extension of life, which is a big issue for these patients. So I think as you see things unfold, yes, the Initial data coming out of the other companies is actually impressive and that's great for the patients. But I think we have to see how this unfolds over a longer period of time.
And so I would expect that this field there'll be long term efficacy and safety studies used in this field, and that's how things will differentiate. And then ultimately, as Efficacy is demonstrated and the safety is demonstrated. The companies are going to go to work and some already are on what are the conditioning strategies or basically how to make the treatment burden as light as possible for patients. Collect, etcetera, etcetera. So I think there's a number of other variables that will come into play as things unfold.
Ready. Thank you. Our next questions come from the line of Luca Izzi with RBC. Please proceed with your questions.
Terrific. Thanks so much for taking my question. Congrats on the progress. Two quick ones, one for Lisa and Mark and the other one for Jim. So for Lisa and Mark, You're obviously using AAV to deliver your construct and I think the FDA is having an advisory committee meeting September 2, 3rd to talk about the safety of AAV.
So wondering, 1, if you're planning to participate in that adcom and 2, what are your expectation getting into that event? And maybe, Jim, for you, bigger picture, What's the latest thinking of business development? When you think about the 3 kind of big dimension of your pipeline, which is obviously the eye, hemoglobinopathies and oncology, Which of them you think are going to be core to Editas story going forward versus which one maybe you're willing to partner? And maybe on the in licensing side, do you have any appetite to actually bolster your pipeline via BD. Thanks so much.
So maybe I can take the first question. Yes, we will be participating in the FDA meeting to discuss some emerging issues with AAV. What I would say to answer kind of the second part of that is People are using AAV for multiple very different approaches and at significantly different And so I think the ocular space, one of the reasons why this was one of the first areas that people using AAV as a delivery vehicle is because you can there's a very defined anatomy, you can deliver the product very carefully to the right place and it's at relatively low amounts, 100 to 1000th of the dose that some of the other systemic So I think that meeting will be important. I think some aspects of it around The meeting will result in some guidelines and some further direction and that's obviously important to be aware of and if it becomes relevant for EDGAS, we'll fully participate and be part of that.
So, Luca, let me take the second part of that, which is sort of BD strategy overall. So in addition to building the leadership group that I talked about early in this call, We have also been building depths below that leadership group. And so for the first time and now Mark's here and certainly have Mark. Lisa is giving a little bit of bandwidth to start thinking about sort of the broader strategy. And we've appointed Bruce Eaton that we've really got the team together now to really rigorously sort of think about Now let me take you to the sort of how we're thinking about BD.
I have been in the industry a long time and so I'm fairly pragmatic about What do we think we can execute and let's and what do we think we will ultimately need help with? So we've got a nice productive relationship with BMS on the T cell side of oncology. We've made, I think, pretty significant advancements on our iPSC derived NK platform. But there's an area where I think going into clinical development and certainly further into clinical development and commercial that We will be best served if we have a partner in that. So that will be something that we will look to.
It's always hard to judge exactly what the right moment in time is to do that, but That will be a high priority. Similarly with the 301 program, I feel very comfortable that we can advance that one clinically, But ultimately, we would want a commercial partner, particularly ex U. S. And certainly, I also know that that means if you get a commercial partner, they're going to want to participate at some meaningful level in the late stage development, right? So Those would be sort of 2 bigger pieces.
With respect to thinking about in licensing things, we are actively talking about that. I think that can in different flavors and forms. We have, as you know, what I consider The sort of the biggest challenge in gene editing is we can edit, we know that. It's Can you get the editing machinery to the right organ or the right cell type, at the right efficiency, with an appropriate safety profile. And so when you think about our 3 programs, Right.
They are in some ways, 3 different ways of delivering editing as a therapeutic, but we'll look at additional ones. So AAV, as good as it is, has its own limitations. We've seen other people with LNPs, for the right indications, LNPs and or, other delivering modalities are certainly something we'd look at. And then lastly, things that potentially complement either our technology or a therapeutic area where we have an interest, for example, ocular where we have a number of programs, we'd certainly look to Think about augmenting the depth of our pipeline there. Hopefully that helps.
Fantastic. Yes, thanks so much. Appreciate it.
Open. Thank you. There are no further questions at this time. I would like to turn the call back over to management for any closing remarks.
Well, thank you very much, everyone. A lot of great questions today. Really appreciate all the interest. We will have, I know, a number of conversations here over the upcoming days. I greatly look forward to talking with all of you in the future.
Thanks again, and I think we will call it a day. Appreciate your time. Take care. Bye.