Geulah Livshits, a biotech analyst at Chardan, and it's my pleasure to introduce Erick Lucera, our CFO, and Cristi Barnett, our VP Corporate Communications and IR at Editas. Thank you both for joining us today. Most in the room are likely familiar with Editas, but maybe you guys can start with a high-level overview of Editas's platform and programs, and then highlight some catalysts for the remainder of the year. Yeah, well, thanks for having us. It's an honor to be here, and thank you for all the great work that you guys have done across the biotech community and things that I know and love. You know, Editas, as you may know, is a gene editing company. We were born out of the Harvard-MIT Broad with the license to the foundational Cas9, Cas12 enzyme patents that we have, that give us broad applicability across the gene editing spectrum. Our company was founded about 10 years ago, IPO'd about six years ago, and currently, as we sit now, I think we're at the most exciting point in the company's history, as we not only have human data for our reni-cel product for sickle cell disease, but we're also expanding into the in vivo gene editing reni- cel is autologous. It is very much an individual personalized medicine, whereas in vivo will be something that we can do much more efficiently and access a much broader population of patients. It'll truly be a one of the most innovative things in all of medical history. So we're really excited with kind of where we sit in terms of where are we now, in terms of where we're going to be. We have three main pillars, the way we like to describe the company. The first is reni-cel, where we're progressing really quickly in terms of enrolling patients, getting data, presenting data, and moving towards a BLA at some point in the near future, and all the data looks really good, and we can get into kind of where we see points of differentiation in a moment. The second pillar is the in vivo, where our CEO, Gilmore O'Neill, brought in a new CSL last year, Linda Burkly, who is a well-known drug hunter, and she and her team of geneticists have identified a number of targets that we think can be first-in-class and best-in-class, in the in vivo world. And then finally, the IP/BD business, where our Cas9, Cas12 patents are truly foundational, necessary for freedom to operate, much like Cabilly, if you're old enough like me, to remember the Cabilly patent, where anyone that's in gene editing is going to need a license to these patents. And for us, and for me as a CFO, that's a great source of non-dilutive capital. We did a couple of deals before I got here with Bristol Myers and Immatics and Beam. Last year, we did a deal with Vertex for Casgevy and with Vor Bio. We think there's about 100 programs in development, most of which are at about 10 companies, and we're looking forward to having license discussions with all of those folks. And again, it's just a great source of non-dilutive capital, and as we get more deals, we'll announce them. Mm-hmm. Great. So maybe let's jump to reni-cel for sickle cell disease. Yeah. This is an indication where you've shown some exciting data, but there's also, obviously, another therapy that's also in gene editing on the market, Casgevy. So could you first walk us through the data that you've reported, and then we'll get into the differentiation and the commercial outlook? Cristi, why don't you start with the data- Yeah. And I'll talk about the commercial. Mm-hmm, yeah. Happy to share about the data. So we most recently shared data at EHA, the European Hematology Association, this past June. And we showed for reni-cel, for Ruby, which is the sickle cell, we showed 18 patients worth of data. We also showed seven patients for EdiTHAL, which is the beta thalassemia. But I'll focus on the Ruby sickle cell data. So we showed, as you mentioned, some differentiated data. So very excitingly, in those 18 patients, they were all still VOE-free, so that's kind of the standard. These are patients that have severe sickle cell disease. They had two to four pain crises a year, roughly, before enrolling in the trial. Since treatment, no VOEs, completely VOE-free. So that is amazing. They're staying out of the hospital, they're able to work and do things that they previously couldn't. From a differentiation standpoint, we're also seeing total hemoglobin levels into the normal range for both genders. So our mean total hemoglobin is about 14 grams per deciliter, which puts normal range for both genders, and we think that that's a differentiator for a couple of reasons. But one of the main ones is, we all used to know this disease as sickle cell anemia. Anemia was a big part of that, and so it's still something that these patients have. Mm-hmm. And so to be able to actually correct that and get people normal, we think is a huge differentiator. We all feel better when we're not anemic. Mm-hmm, mm-hmm ... and so that's kind of as even if we don't have sickle cell disease, so that's a big differentiator. A couple other things we shared, we are showing really robust, fast engraftment times. Mm-hmm. So our neutrophil engraftment time is a mean of 23 days, which we also think is meaningful because that's actually three days or 23 days is, could be an earlier, a shorter hospital stay. That's great for a patient and a caregiver, but it's also great for the hospitals. That could be meaningful for them on the back end from a, you know, profitability standpoint. So kind of good for the entire system. And then lastly, apheresis cycles- Mm-hmm We shared as well. So we have a mean of two apheresis cycles with a range of one to four. So that, too, if that's, you know, kind of something that's a tight range- Mm-hmm That is good for our patients. Mm-hmm. Got it. And just staying on the differentiation point, what about things like clinical outcomes? You know, how fast do we expect, or what should we expect in terms of when we might see differentiation on, you know, organ damage and things of that nature? So some of those things will play out over time. We will be sharing more data by the end of this year. So one of our things for this year was to show data twice. Mm-hmm. Midyear, end of year, so that is forthcoming. We are looking at different parameters and trying to decide, you know, when can we show some of those things, like patient-reported outcomes and any impact on end organ damage, and kind of where is the right time? What we will definitely share, though, is more patients and longer duration of follow-up, too, at the end of the year, which will be great to kind of see and hopefully kind of see the trajectory continuing. You may have kind of answered this already, but what's beyond the vaso-occlusive events, what's known regarding the relationship between hemoglobin levels and some of these other manifestations? Is that something that you also expect, just based on the data in the field, to see improvements on? So I don't know the exact kind of correlation there, but I think we would hope to see some improvements. So, for example, as I mentioned, total hemoglobin rising, one would hope that, you know, any of us, if we're anemic, we feel fatigued and short of breath when we're going upstairs, that sort of thing. So one would hope to kind of see that actually correlating in a meaningful, you know, kind of plottable way, where you can kind of see that change. But again, we haven't shared that data yet, but that. Got it. That would be where we're hoping to see. Mm-hmm. And so in terms of the readout later this year, again, you kind of touched on this, but to expand on it, what should we expect from the readout, and how are you envisioning the path to BLA filing? Certainly. So, definitely by the end of the year, more patients, 'cause, you know, we showed 18 at EHA. We've obviously been continuing to dose, so more patients, longer follow-up. At EHA, we showed patients with roughly two and a half years to about 22.8 months of follow-up. So if you kind of add, you know, five or six months to that, puts you out that you'll have some patients that are over two years as well, which is great, to start seeing the maturing of the data as well. So those are definitive, and we'll keep showing the same endpoints we've been showing, VOEs. Mm-hmm Total hemoglobin, Hemoglobin F, et cetera, and then, potential to add some other data points as well. Mm-hmm. I don't know if you want to address that. Yeah, and I would just say one of the other things to keep an eye on is we've always said that the Vertex- Mm-hmm Data package is a good surrogate for us. Mm-hmm. We're tracking that closely, and I think that's a good surrogate for kind of our filing. Mm-hmm Timelines- Got it As well. Moving to commercial outlook- Yep Obviously, there's been considerable debate and discussion regarding the demand and trajectories for commercial products for Casgevy- Yep And other ex vivo engineered cell therapies in this space. So obviously, we're early still in the launch trajectory, but how are you thinking about the outlook for genetic medicines and, in particular, reni-cel here? Yeah, I think that the early data is still too early to tell. I can say, you know, I was on the buy side for a long time, so for me, the fact that this is a slow launch is not to be, you know, not unexpected. I think when you look at the actual blocking and tackling that has to go on in all of these centers, you have to retrain them. They have to build some CapEx out. They have to do contracts. I mean, where does the risk go? Who takes the risk? When Bluebird was launching some of their products before Lyfgenia, that we've heard the contracting process was upwards of two years. Mm-hmm. And we've also heard that some of the contracting for the sickle cell products has been around a year. So it's not unexpected that you haven't seen a lot of patients going in, because each center has to, rightfully so, figure out, okay, what's the CapEx investment we're going to make? Mm-hmm. How do we train the people? Who has the risk? We expect, and one of the benefits of being a fast follower, hopefully with a better product, is that by the time we get to market, the contracting should go from two years to one year to three months. By the time we get to market, these contracts will be standard. That, that's the first thing. The second is the patient awareness and education. If you listen to our conference calls earlier in the year, we experienced a really big uptick in enrollment in our trial after the approval of Casgevy and Lyfgenia. They definitely created a bolus of patient awareness and education. So we think that, again, having two years or whatever of them on the market before we get there is gonna just help build that market and incrementally will be less capital for us. Mm-hmm Again, as a fast follower, that we have to spend and let them build the awareness. So that's all great. And then finally, the state Medicaid budgets. If you look at both of these products getting approval in December, the annual budgets for Medicaid were probably locked at that point, so we have to go through a whole year, and I'm sure there's a lot of lobbying and discussion going on in all the state capitals, and they should start having more funds available in the Medicaid budgets for the coming years. So you know, yeah, the numbers look a little slow, but there has been a pretty good acceleration. I think they said there was, you know, single digits after the first quarter, and now they're up to 20, so still small numbers, but we think they're moving in the right direction, but not unexpected, based on the heavy lift that has to go. And again, for us as a fast follower, we're happy to kind of watch that- Mm-hmm and hopefully come to market with something a little better. Mm-hmm, and how are you thinking about the opportunity ex US? Our intention, OUS, and I can say as a former investor, I've seen a lot of small companies run into trouble trying to launch OUS. It's really expensive. It's very risky. You know, our intention has always been to partner the product- Mm-hmm ... ex-U.S., and we're open to those discussions, and you never know how those are gonna go, but we are open to- Mm-hmm Our U.S. partnerships for sure. Okay, great. So I did want to touch on in vivo editing, whether in hematopoietic stem cells or other tissues. Yep. It sounds like that's going to be the direction for Editas' future programs. Yes ... going forward, and so you've talked about a focus on upregulation. Can you tell us a little bit about that, your approach there? Yeah, as I mentioned earlier, we want to be first in class and best in class, and I'd say we haven't really disclosed what we're gonna do other than, obviously, the sickle cell and beta thal. But what we have spoken about more is what we're not gonna do. We're not gonna be doing liver knockdown, PCSK9, and any of these crowded targets. In vivo gene editing is the ultimate first mover advantage in biotech, and it doesn't make sense for us as a small company to be doing a, you know, twelve thousand patient cardiovascular outcome trial. You know, we don't have the capital for that. We'd much rather focus on rare genetic diseases, first-in-class, best-in-class. And, you know, if Gilmore were here, he would tell you very eloquently that he believes that the FDA is gonna need a long, long trajectory and history of safety data before they let gene editing get into categories that have large numbers of people in the population. So we're content on the rare disease. You know, we wanna use our capital efficiently, focus on rare disease, and things like that, where there's a much greater need for therapy, as opposed to something that may be adequately treated with an RNAi technology or an antibody. We wanna go to something new, where there's not an alternative treatment. Mm-hmm. One of the challenges that we have is, with in vivo, it's very easy to kind of plug and play. So if we told people what we were gonna go into, you just swap out 20 of the nucleotides on the guide RNA, and someone has just leapfrogged us. So we're gonna be, you know, careful about disclosing what we get into until we're ready. Mm-hmm. Got it, but it sounds like, you've made quite a bit of progress on that behind the scenes? Oh, yeah. Yes, we have. Yeah. Mm-hmm. And the approach to sharing it... Like, I guess, how far along do you plan to be when you decide to share? So we did say as part of our corporate goals that we would have in vivo proof of concept in an animal species by the end of the year, and we're on track to have that released by the end of the year. And while we won't disclose what the indication is, what we will do, and again, I spent fifteen years on the buy side, so I wanna help people build their models, we'll give you incidence, prevalence, TAM, what the cost might be, what some of the competing therapies may or may not be that are out there. I wanna do everything that I can to help people build models and understand the market, but we won't say exactly the target is AB. You know, we won't say that. Mm-hmm For competitive reasons. Obviously, once we file, the IND to get into humans, then that's obviously gonna show up on ClinicalTrials.gov, so at that point, it'll- Mm-hmm It'll be public, but we'll at least have the trial going at that point. Mm-hmm. Got it. And what's your approach to the delivery part of the equation, in or out of the liver? We have a number of LNPs that we've been evaluating, both internally developed and potentially partnered from external sources, and you know, we think we're in a good spot with regard to that, and I think once we're ready to say whose it is, we'll make that announcement. Mm-hmm. So earlier on, you talked about your IP. Yeah. Can you expand a little bit about your strategy there? Again, I know you've made some deals with Vertex- Yeah And others, yeah. Yeah, we wanna. You know, we think the IP is a great asset that we have. It's actually one of the reasons that I came to the company so quickly after the close of the AVEO sale. It's a great source of non-dilutive capital, and we wanna make it available to as many people as we can. We wanna create sort of individual bespoke agreements. So if you think about the deals that we did last year, on the one end of the big company, we had Vertex that had a lot of cash but is probably more sensitive to earnings. So we did a structure that I think enabled them to potentially protect their earnings and give us an annual license payment that was known and quantifiable when we signed it, which could potentially be an in-process R&D charge. Whereas we did another deal with Vor Bio a few months earlier, which was kind of your traditional biobuck, back-end loaded kind of deal. And we wanna do, like I said, anything that we can to get the fair value of the license and structure that in a way that works for both parties. And if your question is, "Well, how do you think about the fair value?" Again, we believe this is a Cabilly-like patent estate. If you remember Cabilly back in the Genentech days, it was kind of a 1%-2% royalty. If you think about consensus revenues for any given product, you put the 1%, 2% royalty on that, discount that back at a cost to capital of about 10%. Mm-hmm. That kind of gives you a good sense of what the NPV or the value of this arrangement would be, and then we just try and fit it into the bucket that works best for whatever company in terms of where they are in development, obviously factoring in probability of success and kind of time to market. But it's a fairly mechanical process that I think most people agree on kind of the inputs, and it's just a question of, do they want the license now, or do they want it upon approval? Mm-hmm. I see. And so maybe another strategy question: Can you talk about how you're balancing platform advancement with progressing the programs in what has continued to be a pretty challenging environment for biotech? I think that when you talk about platform, I'm assuming- Mm You're viewing in vivo. Mm-hmm. And the one thing that we can say at this point, when you're in mice and monkeys and things like those are not big dollars. And I think the beauty of kind of what we're doing is that plug-and-play nature, where once we get the delivery done and get successful to certain tissues, we know that we can basically swap out those 20 nucleotides and kind of target different either tissues or disease states. So right now, it's the in vivo is not a large dollar expense for us. And I think if we're going to continue to do rare diseases, those will not be big trials either. So I think from our standpoint, it's a very capital-efficient way. Mm-hmm To get some differentiated molecules. Mm-hmm. Got it. And back to reni-cel, what is your strategy regarding manufacturing? Yeah, that's a good question. I think if you look at what a lot of companies do, is they go out, and they raise $100 million and build a nice, shiny plant. We didn't really feel like that was in our best interest, so what we did is we have an arrangement with a company called Azzur, where we lease clean room space... and then we fill it with our staff and our stuff, right? So we have the equipment, and we have the people. We're just renting incremental clean room space. So this allows us to kind of scale up or scale down how much we're making at any given point without having to worry about asset impairment, or is there some fixed asset that we're not using anymore? So it's a very, again, a very capital-efficient way to think about manufacturing that gives us a lot of flexibility. Mm-hmm. And as you think about the future in vivo programs, what's gonna be the strategy there? Yeah, we haven't really commented too much on where that would be, but that is gonna be more of a traditional kind of antibody-type manufacturing process. So I think that gives us a lot more opportunities to think about outsourcing. Mm-hmm. You know, again, I don't think building plants is what we want to do with our capital, but we'll- Mm-hmm W hen we get to that point, we'll figure that out. Great. And then at the beginning, you also mentioned some collaborations you have, including with Bristol Myers. Can you tell us a little bit about that and what kind of value that provides and what the role currently looks like? Yeah, it, you know, if you were to look at Bristol Myers and go to their website and, and you look on their R&D analyst meeting from last year, you'll see there's about a half dozen of our programs on their oncology pipeline. So essentially, what we did was we partnered with them on alpha-beta T cells. We come up with the package, we give them the license, not only for the Cas9, but also for a new composition of matter for this molecule. And then we've licensed it to them, and then they run the clinical trials. And I think this is something, again, from a business development standpoint, as we get into in vivo, and we've said, "Hey, we don't want to do liver knockdown," there are antibody companies, there are RNAi companies out there that have franchises that may want protection. That's not where we want to put our capital, but for small dollars, we can do the same thing, license that. So the Bristol deal is not only a great deal for us in terms of what we got out of it, but also a blueprint of deals that we could do with in vivo. Mm-hmm. Got it. And in the last few minutes, I did want to ask what you think the market might be missing about the Editas story. I think what, you know, the market is missing on the Editas story is a couple of things. Obviously, there's concern about the reni-cel market- Mm-hmm But I think as we talk to investors, where we see the greatest interest is in vivo. I think all of the investors that we're meeting with recognize the potential for in vivo, a one-shot potential cure, maybe two shots, we'll see what it is, that would transform a lot of business, a lot of treatments. I think what they want to see is the data. Mm-hmm. So, you know, non-human, you know, animal data and then eventually human data, and we're out to get that as fast as we can. So I think, you know, we have a pretty good. You know, we do a lot of investor relations feedback. I was on the buy side for fifteen years. We're constantly asking people, "What do you think? What do you recommend? Do you have any criticisms for us?" And that's kind of what we're hearing back from investors is, you know, "We're concerned about the Casgevy launch," which, again, you know, we've discussed, and, "What's the potential for in vivo? And we want to see some data," and we're barreling ahead as fast as we can to get that data. Mm-hmm. Maybe to come back to the commercial outlook and the competitive landscape. We talked about Casgevy, but there are also some other editing programs that are also in the clinic. Yeah. How are you thinking about the competitive dynamics there? Yeah, well, obviously, you know, we have Beam behind us. Do you want to address Beam, and I can take a breath there? Yeah, sure. Yeah, no, I mean, you know, and we've seen, and you see this in a lot of rare disease spaces, there is room for more than one, more than two, more than three products, and they all can be successful. These are, you know, intense procedures to go through, you know, roughly a six to 12-month patient journey for these products. You have a lot of patients that are there, and as we're seeing, you know, kind of it's not gonna be this kind of huge, huge ramp-up, so there is going to be room for other products, and it'll really, it'll really be good for patients to have that, and physicians, and hospitals, and also I think all of them can be successful, and serve the patient community. Yeah, we've done some ad boards and things like that. Mm-hmm And our best guess is a tiny fraction of patients are gonna be served in the next couple of years before we get approval. So we think there's gonna be ample opportunity for multiple products to serve the needs of the patients. Mm-hmm. Fantastic. I think we've reached the end of our questions, so- Great I'd like to thank you both. Let's all thank Eric and Cristi.