Let's get started. Thanks everyone for being here. My name is Yanan Zhu, and I'm one of the biotech analysts here at Wells Fargo. It is my great pleasure to introduce our next company for the fireside chat session, Editas Medicine. Here with me are the management team, Gilmore O'Neill, Chief Executive Officer, and Erick Lucera, Chief Financial Officer. Thank you for being with us.
Good to be here.
Thank you.
Great to be here.
Great, great.
Great meeting.
I was wondering if you can give a brief overview of the company's platform and program?
Yeah, happy to do that, and, thanks again, Yanan, to you and to Wells Fargo for this opportunity. Editas is a CRISPR-based genome editing company that is focused on three strategic pillars. Driving our what we call the best-in-class autologous edited ex vivo cell therapy for sickle cell disease and thalassemia. The second pillar is a refocusing of our discovery efforts to build an evolving in vivo editing therapeutic pipeline. And the third is to leverage the foundational IP that we've exclusively licensed from Broad, Harvard, and MIT as an alternative or non-dilutive source of financing. So with regard to the progress that we're making on those three pillars, reni-cel has actually been doing really well.
We have just recently presented a dataset at EHA, the European Hematology Association, for our RUBY sickle cell study, as well as our EdiTHAL, and we presented a total of 25 patients. Eighteen of those were in the RUBY sickle cell study. We also announced at the time that we have dosed more than 20 patients and indeed have continued to dose since then. It's worth pointing out this is a registration study that we're in now with RUBY, and we have completed enrollment for both adults and adolescent cohorts, so we're really actually making a very good progress there. I think the most important takeaways from EHA are that the differentiated and, frankly, excellent profile for reni-cel continues and is maintained.
We have seen no VOEs to date in patients who have been transplanted with reni-cel. From five months onwards, all patients treated have a sustained correction of their anemia to well within the normal range. Indeed, the mean or the population mean for anemia is, again, well within the normal range for that population, and it's actually very favorable. So that's a very exciting where we are with reni-cel. We actually also provided excellent, and what I would say, generally very supportive data for thalassemia.
With regard to our in vivo pipeline, we are on track as we set as a goal at the beginning of this year to have in vivo proof of concept for in vivo editing by the end of this year. Just to recapitulate, we have articulated an interest in a number of things. We want to develop in vivo therapeutics that are first or best in class. To do that, we want to use a differentiated editing approach in that we are targeting the functional upregulation of proteins to compensate for or treat loss of function or disrupted function, genetically determined diseases. I think it's a very important distinction from others, because people who use siRNA or ASO are knocking things down, and then many other editing companies are knocking down.
We want to make sure we're clearly distinguished by functionally upregulating, and why does that matter? Among other things, it means we go into a different space, and also, very importantly, it expands the number of diseases that we can potentially treat and address with this editing approach. So we're very excited about that and very happy with the progress we're making. With regard to our IP pillar, it's worth repeating that we did a very good deal with Vertex just December of last year, which I think was very favorable for both companies, enabled the launch of CASGEVY, but very importantly, validated or confirmed the validity of our IP estate around the sort of foundational IP for Cas9.
It actually also validated our view of its value, and has enabled us to extend our cash runway at that point. I thought I might pass it to Erick, though, to talk a little more about that element of the business, if that's okay.
Yeah. Thanks, Gilmore. The IP business is a crucial, and as Gilmore mentioned, the third pillar of our strategy. And just a reminder, we are the exclusive licensor from BHM for the Cas9, Cas12 IP estates. We believe they are foundational patents that everybody who's pursuing a gene-edited product that use that enzyme will require a freedom-to-operate license from us. There's about 100 products that we've tracked in development. Half of them are about 10 companies, so we'll have conversations to execute licenses with those. And those licenses can take a variety of forms. One is the Vertex license, as Gilmore mentioned, where we kind of constructed it as an upfront and sort of an annual payment.
But then we're also open to kind of doing deals with earlier-stage companies, where it may be more of a back-end loaded biobucks deal. So-
... We think this is a very nice potential source of non-dilutive capital for us, and was one of the reasons that, one of many reasons that I came to the company, was to be able to finance the company, in part, with that as an arrow in our quiver. And just finally, just before handing it back to you, Yanan, just looking forward over the next few months from a sort of a catalyst point of view, we are on track to present data at the end of the year, additional data for reni-cel in both the RUBY and EdiTHAL studies. And I think it's important to point out that, as I said earlier, we had announced we've already dosed more than 20 patients in the RUBY study. We have continued to dose.
When you talk about that end of the year, it's worth remembering that as a benchmark, the BLA approval for CASGEVY was granted with actually, it was really in the range of 20-30. The original planning was 20, an additional 10 in the efficacy cohort, and with 16-18 months of follow-up. So we're very excited now to be actually sitting within that range already and looking forward to presenting a data set at the end of the year with longer follow-up and more patients, and obviously, the same will be true for EdiTHAL. We are, as I said, on track for in vivo proof of concept by the end of the year.
Overall, very pleased with the progress against the goals that we outlined at the beginning of this year.
Great. Thank you for that very comprehensive overview. So maybe let's focus on reni-cel in sickle cell disease. Wanted to touch on the data, the differentiation, but, you know, there is one approved CRISPR editing product on the market. So let's start there. You know, looking at the initial launch, launch updates provided by Vertex CRISPR, as well as by gene therapy, company Bluebird, what's your takeaway, and what is your outlook for the sickle cell market's adoption of genetic medicine?
Yeah. I think there are a couple of comments I want to make. First of all, you know, we are very bullish about the prospects of a market for sickle cell disease, and this is not just based on you know, hope. This is based on experience, and we have a significant experience in our leadership team. It's myself, Baisong Mei, our Chief Medical Officer, our Chief Commercial Officer, Caren Deardorf, in launching medicines, developing and launching medicines in the rare disease space, particularly where there was no previous market. And, again, we've often seen this kind of bearish view that things just aren't going to pan out. But we've always found a way to do that, largely because some of those elements, there's always this... Many of the elements are the same.
You know, are patients aware? How are the physicians trained to understand? And also very importantly, you know, how are the administrating or administering institutions ready for the point of contracting, et cetera? So that's a sort of a general remark. Then I would say our perception of the Vertex launch, and I'm just gonna focus on the Vertex launch just for simplicity, has been that it is exactly what we predict, and we were actually very pleased to see at the end of the second quarter earnings that they'd had an effective exponential increase in the number of patients who had started or completed cell collections. It was a threefold increase or fourfold increase, which is actually very good, and what we, again, we would expect, and we expect to continue to see that over time.
I think a key thing, which is important to call out, is that because of the nature of the treatment, that there is a sort of vein to vein time. You know, the cells have to be collected and then edited, and before they're reinfused in the transplant unit, the time to booking revenues is going to be substantially delayed. It's not like your standard therapy. So it's very important, I think, for people to look at a surrogate marker, such as cell collection, where you can actually see that increase, understanding that revenues will be booked later. So I think overall, we feel very good about that. I think the other things we have learned from our observations are that the contracting process is getting faster and faster. Why does this matter?
Because we are very pleased that we're a fast follower of what we believe is a differentiated and potentially best-in-class product. And so what do I mean by a shortening of contracting? So when Bluebird launched LYFGENIA, you know, we could infer from the timeline to the announcements of their qualified treatment centers and contracting, that it's probably taking 18-24 months for contracting with the treatment centers. It appears, based on the very rapid activations that we're seeing for CASGEVY and Vertex, that their contracting time is probably taking 9-12 months. And we would anticipate, based on prior experiences, that that will even be shorter in the coming years. And so things will be very well set for when we would launch reni-cel.
It's also important to point out that the Medicaid budgets, and they're important because the budgeting process is important there because about 60% of patients are on Medicaid, but those budgets are now being updated. We will see that updating again next year, and we anticipate that that will actually also mature and be ready for our launch. It's also worth pointing out that the federal government is now also involved in the Medicaid negotiation through the CMMI, the Center for Medicare and Medicaid Innovation, which has started a pilot program around sickle cell disease specifically, is anticipating launching that in 2025. Again, but the idea is that they can actually coordinate with multiple states to speed up the negotiation process and contracting processes with manufacturers.
So all of those things will be in place. And indeed, those are things that others are doing, so we can leverage that. We're actually observing and learning and actually intervening and doing some additional activities ourselves, that we believe will substantially accelerate and help the growth of what we believe is a very real market. Because what we're talking about here are patients with extraordinary serious disease, and we're actually probably talking about some of the most exciting medicines to be developed in the history of therapeutics.
I don't know of any. I certainly, in my career, have never seen a medicine like reni-cel or indeed like CASGEVY, where you're talking about 100% of patients treated, having an enormous effect size and almost complete elimination, CASGEVY, or complete elimination of vaso-occlusive events, both severe and mild, and in our case, a correction of their anemia. I think the last time we got that close was something like penicillin. So, it's an extraordinary time, and so it's really interesting to sort of see some of the challenges that we're facing when we're dealing with probably one of the most exciting therapeutics for one of the most severe and neglected diseases that we have seen.
Got it. Great. Yes, thanks for those insights. Let's talk about differentiation from CASGEVY. You alluded to that point already. Can you go over the data you reported so far and highlight for us which part of the data differentiates your product from-
Yeah.
CASGEVY?
I'd be happy to do that. I kind of got a little carried away with the excitement of the data. Sometimes because I have to remind myself to pinch myself, saying, "You've never seen anything like this." What we've reported is, again, that 100% of the patients treated at six months or earlier have fetal hemoglobin levels which are greater than 40%. In fact, the mean is around 45%. Why does that matter? Because that's well above the threshold required, as determined by nature's natural experiment in hereditary persistent fetal hemoglobin, to actually control VOEs. And indeed, we are seeing that coincident control of VOEs with that high level of fetal hemoglobin.
The second thing that we're seeing is, as I said earlier, a correction of anemia, and this is universal for the patients. By five months and on, we see sustained correction of anemia. We've actually also seen engraftment occurring, neutrophil engraftment, which is a critical milestone for reducing the risk of opportunistic infection and allowing discharge of a patient from an isolation ward or isolation unit home. And, we're seeing that at 23 days, which seems to be shorter than what we have seen for some other products, including CASGEVY. And that is actually meaningful both to patients from a risk point of view, meaningful to patients from getting home, back to work point of view, and it's also meaningful for hospital institutions, that it means that they can actually, you know, free up capacity.
Frankly, it creates value for them, too, based on the way the DRG model works, and if you want more on that, Erick can tell you more about that. We've actually also been very happy with the success, you know, the rate of successful editing that we've seen. We talked about that in our Q2, second quarter earnings call, where we've actually been, you know, very happy with where we are with the CMC success rates for release back to patient, and this is important because, you know, what we hear from centers is, they want to be sure that when a patient commits to a treatment, that there is a very high probability that the editing and the manufacturing will go well, and the cells will come back to that patient.
So we've been very happy with that, too. So, I think finally, you know, the safety, I think it's always important to mention safety. Sorry. You know, the safety profile that we're seeing is absolutely compatible as we've seen before, with the effects of busulfan, and the safety profile of autologous cell therapies. And we haven't seen anything that we believe is related or has been assigned to the actual editing itself. So all of that is actually very positive from a benefit and a risk point of view.
Got it. Got it. So, on the correction of anemia point, could an argument be made that CASGEVY's hemoglobin level, even if it's not normal, is close enough to normal, and therefore it shouldn't make much of a difference?
I think there are a couple of points. I think that argument certainly could be made. I think the feedback that we're getting from investigators, treating physicians, hematologists, not all, but the majority, are saying, "It's a no-brainer. If I can correct somebody's anemia as well, why wouldn't I do that?" I think it's also worth pointing out that if that mean difference of, you know, 1.8 g-2 g/dL at six months and beyond is, you know, is sustained, which it appears to be, that's meaningful. It's meaningful from the view of hematologists, and indeed, it's worth recalling that, the FDA used an improvement or increase of 1 g/dL as a meaningful predictor of clinical benefit to give the accelerated approval to OXBRYTA.
So I think there are a number of elements that I actually would say that there is an advantage to this, you know, being normal rather than close to normal. Having a two-gram, you know, difference, and obviously the view of the hematologist, that this is important for overall health.
Got it. Got it. And the other differentiation that you talked about, faster engraftment-
Mm-hmm.
Neutrophil engraftment, maybe high manufacturing success rate. Do you feel those can be differentiation advantages or?
Yeah, we, we believe so. You know, from the point of view of the success, I think, you know, success selecting that's very important for the treating physicians, the transplanters. They want to be able to be as confident as possible that when they collect cells from patients, those cells will come back as desired, and the support that we can give is very important there, and we've actually learned a lot about that through our experience with the clinical trial. With regard to the shorter engraftment time, I hinted at, you know, how it benefits patients from a risk management point of view. You know, that the faster you engraft your neutrophils, the shorter period of time is your risk of an opportunistic infection, and the faster you can get home.
I think there are additional advantages from the transplant centers, and maybe, Erick, you could explain a bit about how that impacts their bottom line.
Yeah. When you think about sort of the average length of stay calculation that goes into DRGs and CPT codes, whatever they're using for the facilities, you know, the large bulk of the expenses are in those first few days or weeks. As you start getting to the tail end of that length of stay, the expenses are coming down as the patient is, you know, becoming healed or whatever, so in general, those last few days are extraordinarily profitable to hospitals because there's just not that much cost matched up against it, and most of it's in the beginning. So when you think about a hospital, and I was. I followed hospital stocks for many years, like, they operate on relatively low margins, particularly the not-for-profits and things like that.
So the ability to have three better days or three fewer days in engraftment time is extraordinarily meaningful, and benefits patients to get them out of there quicker, improves the profitability of the hospital, and then allows them to reuse that bed for something else. So it's actually quite meaningful.
Got it. Interesting. So, moving towards... Maybe I'll ask this question before talking about data expecting-
Yeah
For your end, and that is the topic of infertility risk from, you know, the marketed products, the both of them, and also, reni-cel.
Can you talk about whether that is a barrier to adoption? And of course, there's fertility preservation as a mitigation.
But then, you know, in that regard, recently, some government agency decided not to allow coverage for-
Yeah
Genetic medicine, right? So how do we think about those things?
Yeah, I think that's a very important question to address. You know, first of all, let me just correct one. I just want to be sure that everyone's clear about the perception. The threat to fertility for patients really comes from the Busulfan conditioning. It's not from the actual gene modification. I just want to be sure that people are very clear about that. There is no doubt that patients already have compromised fertility from their disease. Sickle cell disease actually compromises the circulatory health of all end organs, including the organs of reproduction, so that has an impact on fertility. Fertility actually also sometimes becomes very important to patients when they suddenly believe or see that their life is about to be transformed.
You know, if they're actually looking at a therapy which moves them from having four severe vaso-occlusive events per year, which is the average each year for the two years before our patients have entered our study, they suddenly say, "If I'm cured or my disease is arrested, now I can actually think about having a family, something I haven't thought about before." So I think those are important. In many ways, the first thing is that the treatment itself creates the opportunity and reactivates the dream of having a family. Then from the point of view of fertility preservation, it is an additional procedure. It's not a trivial procedure, certainly for women who want to actually preserve fertility, but it is one that we have learned a lot about in our clinical trial experience.
We have actually used what sort of best practices that have been adopted in some centers and actually shared them across centers to really maximize the success and the timeline for fertility preservation. The final piece about the government is worth pointing out a couple of things. It was an interesting judgment made by the inspector general who was concerned that preserving fertility might be seen as an incentive to patients to go through a transplant. I think many people would sort of say that's a quite an interesting view. It is interesting that Medicaid does cover fertility preservation for allogeneic transplantation. So I think this is some...
There is, and indeed, I think Vertex has actually addressed this now and has actually instituted a suit to address that. I actually think that this is something that will be resolved, and I think that, you know, ultimately, the desire to help patients with a very poorly disease will prevail.
Got it. Great. So let's talk about year-end readout expectations. You know, what incremental data could we get, and what will make you, you know, incrementally even more positive about this program?
Yeah. I think the thing about this program is that it has really done very well in continuously reaffirming what we first saw. You know, surprisingly, we were quite confident when we saw our first patient's data in November of 2022. We said, "We're seeing a differentiation declaring itself already." Now, we had confidence for a couple of reasons, and that, you know, in that we saw this correction of anemia, which we had not seen in other therapies. And we were confident first, because it really affirmed what we had seen in the non-clinical data, the preclinical data. We had seen a similar, very high and normal output of hemoglobin, high erythrocytosis, not high erythrocytosis, but high erythrocyte output, and that is high normal. And what's the word I'm looking for?
Normal erythrocyte health compared to an alternative approach, such as a BCL11A knockdown, where we saw reduced erythroid output, reduced erythroid life. So we actually said the human data reaffirm what we've seen preclinically. I think the other point, of course, was the effect size was so robust, it gave us a lot of confidence. And what has happened every six months since then, when we have actually presented additional patients and longer follow-up, it's a really confirmation of what we've seen. And that's actually unusual. Honestly, you know, in the world of small molecule antibodies, where I worked before, your data set doesn't tend to get better.
But what we've actually seen is a continuous, consistent reaffirmation of that initial observation, where we're seeing robust correction of anemia, robust expression of fetal hemoglobin, sustained expression of both over time and control of vaso-occlusive events. So that actually really excites us, and that's what we anticipate seeing at the end of the year again. And what we will see that is, we will see that with a large number of patients. Remember, in June, we had announced that we dosed more than 20 patients. We have continued to dose since then. What that puts us in is well within the guardrails of the 20-30 patients in the benchmark, as I would call it, efficacy package submitted to the FDA for CASGEVY's approval. And remembering, of course, that they had 16-18 months of follow-up.
So I think that we are already within that range, and so we are looking forward to showing just how much that progress in dosing patients into that meaningful range or number for an efficacy data set, and reaffirming what we've seen to date particularly around the correction of anemia, control of vaso-occlusive events, et cetera, and, of course, we will have longer follow-up, so we will continue to expect to see a reaffirmation of the sustained effects we're having on fetal hemoglobin levels as well as total hemoglobin levels.
Got it. Some observation from the approved product could be that a patient could have more than a year event-free.
Mm-hmm.
But, you know, may have occasional VOC. But what's your thought there? Is that, you know, an okay outcome, you know, no problem outcome, or is there something room for improvement, for example?
You know, I don't think you'd ever find a physician or a therapist who feels there isn't room for improvement. So, you know, we actually always see room for improvement. And, you know, if I can use, you know, based on Mei's words, he's our Chief Medical Officer, "You know, being first is great, but it actually creates an opportunity to improve." And, you know, we hope that this medicine of ours is actually a further improvement in what already, let's acknowledge, is an incredibly exciting medicine. I don't want to. I mean, CASGEVY is a remarkable medicine, as are LYFGENIA. They are transformative medicines, but we believe that this, this medicine can actually do even more, to help patients, and I think that's an important point to make.
and that's where you may see advantages for in vivo, where when you have a less burdensome treatment, there could be the opportunity to redose if-
Yes
... if there is a need to. So it, the field is gonna continue to advance forward, and, you know, it's just a tremendous potential.
Indeed, you know, I'm sure you're going to come back to it, but one of the reasons we want to continue the in vivo is because, again, that's the next step. We believe that's the important next step to improve both outcomes, reduce the burden on patients, and frankly, expand the number of patients with benefit. Because, you know, we're using the cell therapy for severe or, dare I say, refractory sickle cell disease. Sickle cell disease is an extraordinarily serious disease. You know, the patients who are classified as moderate or mild are getting substantial amounts of supportive therapy within the U.S. healthcare system.
You know, outside the United States, where such care is not available, you know, just to put it in perspective, the mortality in Sub-Saharan Africa for sickle cell disease, where no supportive therapy or very little is available, runs around 70%-80% by 5 years of age. You know, that was published there in The New England Journal about 10 years ago. This is a very serious disease. Basically, in vivo therapy, where you eliminate or remove the burden and the risks of transplant, allows that benefit-risk argument to enable you to improve in a way that you can move into the moderate and mild as well. I think the in vivo is going to be very important for an evolution. This is an example of evolving and continuously improving.
Right. So, you know, you touched on in vivo earlier-
Mm-hmm
... but that's specifically for the upregulation platform.
Mm-hmm.
Right? I don't know, do you bucket sickle cell-
Yeah
... which, of course, is the upregulation?
Yeah.
So-
We do, actually.
This is actually part of it.
Yeah. In answer to your question, yes, we do, and in fact, we bucket it. In fact, I often refer, or we often refer to sickle cell disease as the archetype or the example of a functional upregulation strategy. Here in the context of sickle cell disease or reni-cel, we're using functional upregulation of gamma globin, a functional homolog of beta globin, to either replace the dysfunctional beta globin of sickle or to elevate and replace the missing or massively reduced beta globin of thalassemia. So that's a very classic example of how using functional upregulation to replace. And essentially, that's the philosophy that we're using for our in vivo, our selection or expansion of other upregulation targets, but in the context of in vivo.
The in vivo upregulation for sickle cell has, I'm not sure.
I think it's maybe a little more difficult than a liver target, for example, because delivery to the hematopoietic stem cell.
Yeah.
Hasn't been shown.
Yeah.
By others, right? So when you now, you know what. You know, you haven't disclosed, you know, you're going to show some proof of concept data.
Mm-hmm.
Animal data.
Mm-hmm.
I guess, by year-end, right? Are we talking about sickle cell there, or is sickle cell more of an aspiration, you know, aspiration of both?
We haven't shared which tissue or which diseases that we're actually going to talk about, or that we are actually going to have proof of concept by the end of the year. I would say is that we are moving in parallel on a number of targets.
Our hematopoietic stem cell delivery target is one, and we have other tissues, particularly liver, again, with upregulation as our goal. You're absolutely right. You know, delivery to hematopoietic stem cell will be important. That's part of the triad, you know. The first part of the triad is the target, where we have human validation of the target, genetic sequence or genomic sequence in the regulator or promoter of the HBG1/2, check. The enzyme Cas12a, we have human validation and proof of concept of that, check. The third is the delivery. We actually have been working on that internally and in some collaborations, and obviously more on that later.
Then in parallel, we've been working on delivery to the liver, but also, and other tissues, wedded to functional upregulation and choosing targets in which we functionally upregulate, to compensate or replace loss of function, genetic defect.
Got it. Great. That, that's, you're looking, totally looking forward to that.
Yeah
... proof of concept,
And we're very excited.
Right.
Because we actually do believe this is. This is where I think the real value for editing is, because then suddenly, not suddenly, it's been hard work, but this is when you can actually move into a very new type of therapeutic philosophy. You know, healthcare today is largely dominated by chronic treatments, which are rarely curative. They're truly palliative. They sustain, maintain, or palliate.
Here, we're actually talking about arresting a disease with a single or a couple of administrations, but also, in contrast to cell therapies, in a way that's very low burden to patients. And actually, from a healthcare system, requires very little infrastructure, an infusion or an injection.
Got it.
So this is, again, this is where we actually see the vision for it, and obviously, these are the steps we're taking to actually begin to realize that vision.
Great. Great. Looking forward to hearing more about that. Lastly, I wonder if you could talk about cash runway and what assumptions are built into it, and maybe talk about the recent expansion of T cell agreement with BMS.
Yeah, real quick, as we're running out of time, cash runway is into 2026. You know, we're basically don't have a lot of assumptions in there outside of the regular burn. We're not building in partnerships or things like that. With respect to the Bristol Myers agreement, if you look on their website, there are approximately six products in the oncology section of their R&D day, which happened about a year ago to the day. It's been a great partnership, and I think the extension just demonstrates both sides' commitment to continuing to try and find more products to push into the clinic.
Got it.
Could I make one closing remark? Because I think it's one thing we have said, I think it's very important to people, that notwithstanding our aspirations and how we're executing, the senior management at Editas are not a bunch of starry-eyed idealists. We are pragmatists, and we know what we have to do to basically make sure that we get therapeutics to patients, but we actually also get value to shareholders. You know, we're very conscious of that, and we think about it all the time. So I think it's very important for you to understand that this is a very hard-nosed, pragmatic team here that's driving and leading Editas.
Great. That's a great parting thought for investors to chew on. Thank you so much for-
Thank you. Thanks for having us.
A great session. Thanks very much. Thanks, everyone, for being here. Thank you very much.