Thanks for joining us today for our Fireside Chat with Editas. My name is Liisa Bayko. I'm a biotech analyst at Evercore ISI, and I'm joined by, the team here at Editas. So I'll just turn it over to you. We can do some brief introductions and then just dive right in. Hi, my name is Erick Lucera. I'm the CFO. Happy to be here, and thank you for your support, both on the research and banking side. Pleasure. I'm Cristi Barnett, Head of Corporate Communications and Investor Relations, and also happy to be here. Thank you. Okay, wonderful. Let's start off with just a one-minute overview of Editas. Yeah, so I'll take that. Editas is a gene-editing company. We're actually 10 years old this week, this month, and our focus is on editing for cures. We have one lead product in the clinic for sickle cell disease, and we've been releasing data at major medical meetings this year, and looking forward to providing another update on that data in a few weeks. Great. So tell us a little bit more about, kind of... We'll start off with sickle cell. I know you've got a pipeline behind that, but, what is your approach to sickle cell, that might be different from what might be, I think, the first, genome-edited medicine to be approved, which is, Vertex's, Vertex and CRISPR's exa-cel. How, how are the two different? Well, obviously, you know, from a 30,000-foot view, we're really excited about the progress that Vertex is making, not only for the patients, but also for the field of gene editing. But as you mentioned, there are a few differences between our approach and their approach. The first is they're using Cas9, and we're using Cas12a, so it's a different enzyme, and we're targeting the gamma-globin promoter, which we believe, based on our research, leads to a little bit better hemoglobin data. So we think that'll be a point of differentiation that we'll see play out over time, and we're seeing it already, so. Great. You have intellectual property rights to Cas9. Is that correct? Yes. And then how are you thinking about, you know, I guess your kind of approach when exa-cel does get approved, curiously to think about it? Yeah, well, I'd say, you know, we can't comment on any specific program or product or company in terms of discussions, but we can talk broadly. You know, we think that we have the foundational patents for both Cas9 and Cas12. We've got great intellectual property estate licensed from Harvard, MIT, and Broad, and we are open and to anyone that wants to talk to us about getting a license. We'll leave it at that. Okay. So EDIT-301, which you just alluded to, your lead program, we've got the ASH meeting coming up. What can we expect to hear from Editas at the ASH meeting? Maybe I'll put it in a little bit of context, and then I'll turn it over to Cristi. But as you know, in the beginning of the year, we had data on one patient, and that's what I looked at when I was interviewing—was that one data—and we revealed four more, or total data on four patients at EHA of last year. And as you know, we had—we designed this to have, and we announced in the beginning of the year, that we would dose 20 patients this year, that will slip a little bit into January. But the intent was based on the experience of Gilmore and Baisong, who have each brought—who have total—brought a total of 10 products to market in this area. We thought that would be a good package of data to have that was validated by what we saw from Vertex this summer. So we are going from the 4 patients at EHA to a nice data set at ASH, and we're also gonna have an analyst meeting that day as well. We'll have a little bit more data. I'll turn it over to Cristi to go over some of the specifics. Sure. Yeah, so at ASH and in our analyst meeting, we'll have 11 patients worth of data from Ruby, so that's the sickle cell trial. Two of those patients will be out past a year, which is great long-term follow-up. Another four will be past five months, which is important because that's where we really think we're starting to see the differentiation- Okay ... play out. And then we're also gonna be showing 6 patients from EdiTHAL, which is the beta thalassemia trial as well, 2 of those past 5 months. So, should be a nice, you know, kind of 17 patients worth of data that we're, that we're sharing and hoping to see similar to what we showed this summer and kind of following that same trajectory. A lot of people have been following this space, especially from the Vertex perspective, sort of wonder about the market size. I mean, clearly, you know, the approach is medically a huge, you know- Yeah ... a huge transformative event for the patients. But it is a big process to undergo, and it's also probably gonna be pretty expensive, I would imagine. So, you know, people kind of wonder about the market opportunity. Can you kind of walk us through, like, what are your thoughts on what the size of the market opportunity is, and sort of how do you get there? What are some of your key assumptions? Well, obviously, there's a prevalence pool of about 20,000 patients, and we don't yet know what ones will be amenable to this kind of procedure or have ability to get, you know, to endure it or to get even reimbursement for that. So that aside, you know, we do see value in this procedure. There's. I think the entry criteria for our trial is 2+ vaso-occlusive events a year. We have some patients that have had 100 days a year in the hospital, and when you think about that over a lifespan, a shortened lifespan, that adds up pretty quickly. So I think you see, from a pharmacoeconomic standpoint, a pretty good justification for whatever prices get put out in the marketplace, and it's obviously a. We all know it's a terrible disease, and I think what you'll see is, as patients see different therapies out there approved and start hearing stories about how people's lives are transformed by this, I think once it's able to be marketed and these stories get out there, you'll start seeing people raising their hand and saying, "Yeah, I will do this. ... What have you heard on how, like, different pricing arrangements, and I'm not talking about the total value, but, the way we've been thinking about it in our model is, like, payments over time, you know, kind of equal installments- Yeah over five years. We just kind of use a very simple approach. Yeah. Is that, like, the right way to think about it, or are there other models that make sense to you? I think it's the type of thing... I mean, look, one, one of the beauties of living in, you know, a country like this is that you can have creative approaches to financing, and that approach you mentioned would certainly be something that I think, you know, people are gonna be looking for flexibility. Okay. What are you doing on the, kind of the whole, concept of moving towards, you know, gentler, conditioning regimens? 'Cause that's, like, one of the things that I think probably is a little bit of a limiting part of- Yes of the equation for how big this market could be. Yeah. So, what are you doing on that front? You know, obviously, yes, getting to a milder conditioning is one thing that we're looking into, whether that's something that we, you know, bring in-house or whatnot. Another thing that we're also working on that we've talked about is also, can you bring this medicine into an in vivo approach as well? Which would also be a much less burdensome process for the patient as well. So that is one thing that we're working on as well, and we've already, you know, solved for two of the problems. We have the target, we have the enzyme, so working on the last piece of the puzzle, which is the delivery part. So once a depletion, like we hear about the gentler conditioning regimen, we hear a lot of talk about this, but I haven't seen a lot of tangible progress. Like, where are we really at? What's the, like, latest kind of developments in that field? I know there's companies beyond just, like, the players in the actual, like, gene-editing space that are working on that, and then I think you guys are probably working on it yourselves as well. I know, you know, CRISPR Vertex has their own efforts there, too. Like, what is the sort of, like, latest and greatest there, and is, like, when do you expect—do you think in vivo will come before that, or like, what makes it over the hump first? That I don't know for, you know, to speculate on, but what I do know is that right now, since we're working on the development of 301, you kind of don't wanna couple two new things together- Mm-hmm, right ... in a way. So we're developing the 301 kind of as is, as the model as is, while simultaneously working- Right on in vivo, and then again, just looking at the field in terms of what is there in terms of milder conditioning that could be out there for the future. And what's next for the program? So you've got the upcoming data, ASH, and what should we expect after that? You know, how quickly do you think you'll have enough patients to maybe file for approval? Kinda what are your use—what are your sight lines for that? I'm curious. Yeah, we think that, you know, 2024 is gonna be a great year for the company, and we're gonna have more data from the 301 trial. If you think about last year at EHA, having 4 patients and now having data on 11, we're gonna continue to report out more data to the investment community and the physicians and the patients, you know, at a regular cadence. And I think as you think about getting towards a mid-year data set, you know, as we mentioned on the last call, we'll have 20 patients dosed by January. As you can see from the data in our corporate deck, we get most of the editing done by 3-5 months, which is when you see the correction of the anemia and the fetal hemoglobin levels. So we think that by the time you get to the middle of next year, you're gonna have a very robust data set of those 20 patients, with enough follow-up to, you know, see how well the drug's working. You know, in terms of going from there, we've continued to guide people to the data set that Vertex produced. So they had 17 patients at 18 months follow-up, so if you roll- Mm-hmm ... from mid-year next year, another 12 months, we'll have a, you know, a BLA-ready data set, and, and we'll see how things go. As you know, we have RMAT designation, so that's gonna give us a lot of flexibility with respect to having discussions with the FDA, and, and we'll learn more about what our final package needs to be. So I think next year is gonna be a great year from, from a EDIT-301 standpoint, and also from a in vivo standpoint. You know, we are looking for some sort of delivery technology, and we expect to have more on that in the coming year. And then finally, the third pillar of our story, the Cas9, Cas12 licenses, we think there's a lot of companies out there that are probably needing to have discussions with us, and we look forward to having those in coming months and quarters. What do you think that that could be worth, that piece of the equation? It's hard to put a dollar value on it. I think as you look at all the companies that are pursuing CRISPR gene-editing programs, you know, whether it's a Cas9 or Cas12, they're all in various stages of development. Some are early on, and I think, you know, not talking about our product in particular, but earlier-stage biobuck deals generally have a different structure than what you see for later-stage companies, where certainty is higher and, you know, perhaps earlier milestones may have been missed, for lack of a better term. So I think there's a range of opportunities that exist out there. What kind of a royalty arrangement makes sense? I think- Like, what are some benchmarks, I guess, you could point to? Like, not what you're thinking, but just others that have happened. Yeah, I mean, obviously, we have the deal with Bristol Myers Squibb, which is out there, where you know, we announced the deal with Vor, and I think each one of those is a combination of the prototypical upfronts, development milestones, and royalties. So I would imagine that this would take a similar format. Okay. As for your in vivo program, what's the timing on kind of, I guess, getting, you know, into clinic on that one, and when should we expect to hear more about that? ... Yeah, we haven't really commented yet on that. Obviously, we need to get make a decision on which way we want to go with respect to the delivery technology. The team's working away at trying to identify the targets, and I think as those activities are going in parallel, we'll have more visibility in the year and be able, you know, within 2024, and we'll be able to lay out a development timeline from there. 'Cause that just seems really transformative- Yeah And very exciting, I think. Yeah, I think for the autologous cell therapies, which we all know are sort of one and done, the ability to transform to a in vivo medicine, which not only is less burdensome on the patients, the caregivers, and their families, but allows you then to expand to a broader patient pool. I think it's totally transformative. When you look at the kind of competitive landscape, there seems to be a lot of players going after sort of ex vivo sickle cell and beta thalassemia treatments, and seems to have been some have gone by the wayside. Yeah. Who do you think about as your sort of key competitors out there? And I know what you're differentiating on hemoglobin. Do you see anyone else with any interesting, I don't know, points of differentiation? I mean, ultimately, it's good for patients to have… Yeah ... to have lots of choices- Things in development, lots of choices, lots of companies working to solve these diseases that have no treatment. So I think if we can all, you know, get there, that's a win for everybody. And then back to the point on the IP, if you know, if that is something, you know, if we have the foundational IP, then that also is, you know- Awesome ... a win for us. So. Okay. On the foundational IP front, as you think about how you might approach that, what are some, like, benchmarks out there, for kind of like what... You know, if people want to, like, kind of model that for you guys as part of your value stream, what would you point to other companies that have had foundational IP and have been able to extract some value from that? Yeah, I think when you think about foundational IP and licensing to multiple companies, you're generally talking about non-exclusive licenses. And when you think about business development and licenses of IP only for an FTO, freedom to operate standpoint, versus licensing a product with data and, you know, kilograms of material and a manufacturing process, they're completely different. And, you know, I think you can see over the history of biotech, you know, there have been several examples of situations where there's been those companies that have licensed to dozens of companies their IP, whether it's Dyax or the, you know, Cabilly patents and things like that, versus sort of a, you know, the Vertex CRISPR deal, which was really a product license and an exclusive license. So I would say, you know, we're generally, if you're going to license any product to more than one person, it's obviously non-exclusive, so it's a different spectrum. Okay. Just in the last kind of minute or so we have, maybe you can talk about your cash runway and then kind of catalysts that we could expect, in as we turn the clock into the new year. Yeah. We ended the last quarter with $444 million of cash, and we stated at the time that that gets us into the third quarter of 2025. As I mentioned, you know, we view the license as a potential source of non-dilutive capital, which may help with our fundraising efforts. In terms of catalysts for next year, we think next year is going to be a great year for the company. Obviously, we're going to continue to show more progress on EDIT-301, with getting a wholesome really nice data set by the middle of the year. We're going to have progress on in vivo with some sort of delivery technology put in place, and then, you know, sort of go from there towards proof of concept. Then with respect to the Cas9, Cas12 licenses, we're going to be open for business and look forward to talking to as many people as want to come by. Okay, great. Well, thank you. Thank you. Thank you. Thanks again.