EDIT - Editas Medicine Inc. (EDIT) Presents at Stifel 2023 Healthcare Conference (Transcript)
2023-11-14 17:15:26 ET
Editas Medicine, Inc. (EDIT)
Stifel 2023 Healthcare Conference
November 14, 2023 01:50 PM ET
Company Participants
Erick Lucera - EVP, CFO
Cristi Barnett - VP, Corporate Communications and IR
Conference Call Participants
Dae Gon Ha - Stifel
Presentation
Dae Gon Ha
Okay, let's go ahead and get started with the next session. Thanks everyone for joining us. For the next half hour or so, we're going to be talking Editas Medicine. My name is Dae Gon Ha, biotech analyst at Stifel. Joining me here on stage, we have Erick Lucera, Editas Chief Financial Officer; and then Cristi Barnett from Investor Relations. So thanks very much for spending the time. Before we dive into the questions, maybe I'll just turn it over to you guys. Brief recap of Editas Medicine, the programs you guys are working on and then we will get into Q&A.
Erick Lucera
Yes, thanks. So Editas is a company where we edit cures for genes. The company will be 10 years old tomorrow, and was founded with technology that came out of the broad Harvard and MIT for Cas9, Cas12 editing. The company's been around, like I said, for 10 years. We brought in a new CEO about a little over a year ago and he refocused the company on autologous stem cell therapies for sickle cell disease, so he announced that last year at a competitor conference. So our lead asset is EDIT-301 for sickle cell disease where we initially had some data at EHA last year or this year. We'll have more data upcoming at ASH and we can look forward to talking about that. The second pillar that we have for our growth is out-licensing of those Cas9 and Cas12 licenses for sources of non-dilutive capital. So we look forward to discussing that when we get to it. And then finally, the third pillar of our growth story, which Gilmore announced last year, was the pursuit of in-vivo technology. So we think autologous is a great way to prove the gene editing works, but the future will be in-vivo due to ease of delivery and lower cost of goods, which should allow it to get to a broader set of patients.
Dae Gon Ha
You mentioned this as your first pillar. But EDIT-301, I guess, you also guided towards update at ASH following up on your earlier EHA update. What exactly are you planning on disclosing to the extent of how many patients, duration of follow up and the kind of metrics you'll be disclosing?
Erick Lucera
Yes. So I'll get started with that. So if you think back to the trial that we're having for EDIT-301 in sickle cell disease, we originally put up a document on clinicaltrials.gov that talked about 40 patients in total that would be enrolled in that. Gilmore and Baisong, our CEO and CMO, have each developed 10 medicines over their careers, and they postulated that we would probably need an initial data set of 20 patients. That all was verified based on the data set that came out of the Vertex filing in the summer. So what you're going to see out of us over the coming nine months is we originally had four data -- patient data on four patients at EHA in June, we'll have 11 patients at ASH, we expect to have the 20th patient dosed by January. We'll continue to be adding patients and enrolling them. There will be a very wholesome data set that we have at in the middle of next year. When you look at our data, you'll see somewhere around months three to five is when you have the bulk of the editing where you're getting to those total hemoglobin levels being restored. So when you get to the middle of next year, you're going to have a very nice data set that shows how well the drug work with three to five months of follow up for each of those 20 patients. So it's really been an evolution of patient data. The more enriched it gets we'll be showing that at the medical meetings. So Cristi, I don't know if you want to comment anymore on…
Cristi Barnett
Yes, I can just add. For ASH, as Erick mentioned, 11 patients in RUBY, which is for sickle cell and another six from the EdiTHAL which is for the beta thalassemia trial. For those 11 sickle cell patients we’ll have two patients with greater than a year of follow up. So some nice duration to look at, another four with greater than five months. So as Erick mentioned, that's where you kind of see the hemoglobin normalizing and then the rest at about, anywhere from one to five months.
Dae Gon Ha
I know people haven't really been focusing too much on EdiTHAL, and even in the case of CRISPR the AdCom was really on the sickle cell, not so much on the beta thal side. How are you looking to differentiate, and I guess this is all encompassing, sickle cell versus exa-cel, maybe even lovo-cel. But even on the beta thal side, where do you think 301 kind of differentiates itself and when we might see that?
Erick Lucera
So if you look back to the last few years, we made a conscious decision, the scientists at our team decided to focus on Cas12 as opposed to Cas9 and to go after the gamma globin promoter, and that all took about a year or two to differentiate between what we were seeing in Cas9. And the reason they chose that enzyme and that target was because we felt that that was the best way to increase total hemoglobin. When you look at the data that we have disclosed at EHA and at ASH, you see the restoration of that hemoglobin levels pretty nicely. And with respect to differentiation, that's where we think we are going to get the differentiation is the by design effect of raising hemoglobin. If you remember, at least when I was a kid, sickle cell disease was called sickle cell anemia and they broadened the definition to sickle cell disease to encompass all these vaso-occlusive events. But the original risk was always the anemia and that's why by design we target what we target and that's what we are seeing in the initial results.
Dae Gon Ha
So we will look forward to the ASH update. Another thing that is of great interest to us is the fact that your milestone of 20 patients dosed is now in January. Just out of curiosity, are we talking like Jan 1st or 2nd that your prior guidance was year end '23, now it is in January. So are we just taking things over or is it sort of like late part of Jan? The bigger question I have is, what's the backlog that you are seeing given that exa-cel has kind of chartered this new path, but the data looked really good. So I would imagine there to be some reflection of that patient demand?
Erick Lucera
Yes. So to answer your question, we have no issues with patient backlogs. There is no issues with manufacturing. There is no issues with centers. It is purely a scheduling and timing thing. Whereas, I think when you lay out a goal and you say by year end and then the reality of maybe before patients get dosed, they have a vaso event and it pushes it out, because they have to recover from that. So you push out the timing of the collection and the dosing, or perhaps there is something happening over the holidays. These patients spend a lot of time in the hospital after dosing. I don't think anyone wants to get dosed on December 15th and then spend the next two weeks or whatever in the hospital. So there is no issues, again, with patient demand, no issues with centers, no issues with manufacturing. In fact, Baisong, our CMO, has visited all the centers that we have. He has great relationships with all the physicians in the trial. And we saw an uptick in requests after the EHA data. So there is no shortage of interest in the trial. And whether it’s early January or late January, I don't think I have that answer. But the most important point is getting to that data in the middle of the year and then getting to a mid '25 having a final data package, and that's all unchanged.
Dae Gon Ha
So I guess, the precedent right now is about end of '24 for that initial submission. But obviously, continuing to dose and follow and then use that as an amendment, if you will, as a supplement. Key question being a differentiation, though. You have that playbook from exa-cel, but do you envision yourself maybe one upping them with like a 30 patient submission first or maybe even a 40 patient submission to make it more thorough, more, I guess, comprehensive versus just a 20 patient followed by a supplement down the line?
Cristi Barnett
I don't think we have shared our exact kind of what that package would look like. But what our hypothesis was, was that we would need at least '20 patients, which we have seen that play out with a kind of a 15 to 18 month follow up. So that's kind of what we're going with. And of course, after conversations with the FDA, we'll be able to update that a bit more granular.
Dae Gon Ha
And so on that point, are you guys meeting with the FDA at some point in 2024 given that you'll be dosing your 20th patient, or any guidance in terms of when that meeting might happen?
Erick Lucera
We haven't disclosed any specific guidance, but I'll just discuss a few things and Christie can elaborate. One is we have the RMAT designation, which allows for a more fluid dialog with the agency. And the second is, I think, anyone in this area would want to see how exa-cel panel went before approaching the FDA. So with those two things out there, again, we haven't commented specifically on when we'll be having those meetings but we are in dialog with them and planning to do so soon.
Dae Gon Ha
Coming back to Erick, what you mentioned earlier about the site enthusiasm being ticked up after the EHA update. I guess quick clarification, what's that sentiment been like after the exa-cel AdCom, has that further ticked up or no real change since the EHA update? How would you characterize that?
Erick Lucera
The exa-cel panel a week ago, so I don't think I have that real time. We did have some statistics on the amount of -- number of inbounds that we got, and it was a pretty significant increase after EHA. I don't think the time has been long enough. But I mean, that'd be a fair question maybe for the next quarterly earnings call.
Dae Gon Ha
When it comes to trials, the execution is front and center, timing is important but you also want to make sure the quality of the data are intact. I think one of the key things you and Gilmore and the rest of the team have emphasized is we want to broaden the exposure and the experience of our medicine before we launch, so that creates a nice foundation for the commercial uptake. I guess the question there is how do you balance exposure increase by enrolling more sites but at the same time, not spreading too thin, such that you end up losing that quality aspect from the emerging data?
Erick Lucera
Yes, I mean, I think that's the central risk of quality clinical trials is working with people that are experienced in the trial and understand the protocols and understand the patients. There is benefit to reaching out to more centers. But I think this is probably a type of disease where maybe 50 centers are doing a large number of the transplants. It's a very small world in that regard. It's not like a oncology or some other area where there's maybe hundreds of centers, this is a very small area of target.
Dae Gon Ha
I'm assuming you're -- the 50 number you're throwing out, that's a ballpark, right, that's not necessarily…
Erick Lucera
Yes, it's a ballpark estimate. I'm just trying to differentiate that between oncology, which was my prior company.
Dae Gon Ha
When you think about the procedure itself, the mobilization and then the editing, infusion back and as well as the conditioning part, how much of a difference is there between a 301 versus an exa-cel versus lovo-cel? I mean, we just broadly categorize them all as ex-vivo cell therapy for sickle cell, but there are nuances and there might be some technical differences. Anything you can comment on how different it would be for a doc using exa or lovo-cel moving on to a 301?
Cristi Barnett
I think there's actually, well at least between exa-cel and us, there's not much of a difference in kind of that process and in the patient journey timing too. So it is similar in that regard. Obviously, what we do on the manufacturing side is what becomes different.
Dae Gon Ha
So more nuances on your side, but not necessarily on administration side, okay. And so we have touched on exa-cel a couple of times, so let me just hit on that a little bit more. That being sort of the pioneering gene edited product, I am sure there were a lot of takeaways that you guys internally discuss about pre as well as after. So maybe I'd love to get your thoughts on sort of what the discussion points were, what your expectation was, what played out, what didn't play out? And broadly speaking, how are you thinking about 301 strategy, does it change a lot or does it kind of stay on course?
Erick Lucera
So with respect to expectations going in, we did not expect that there would be any issues with the panel or -- I was on the buy side for 15 years and you are always anxious about those briefing docs, there was no surprises of any substance in any of that. I would say, as a company from Gilmore on down, we are just ecstatic that the panel went well, first, for the patients, to be able to bring a great therapy to them. And second, for the field of gene editing that we finally are on the verge of having an approved drug and building a pathway for more drugs in the future. I would say to your question about what did we learn? Specifically, for us, again, Gilmore and Baisong have developed 10 drugs and they are very happy with the way the panel went in terms of validating our approach. So we felt like there was nothing that came out of that, that says, oh shucks, we should have done this. I think, it was, yes, we expected this, we expected this, and we are on track with everything in our program.
Dae Gon Ha
Can you talk about, sorry Christi [Multiple Speakers] with regards to the key point on the AdCom, which was an off target editing. What sort of -- what are you guys doing with regards to 301? And understanding that exa-cel has set a precedent for what is satisfactory? Do you think there would be a higher bar, if you will, or do you think FDA will start asking you additional things like a lot of the discussion was on whole genome sequencing, for example, and doing an actual patient data collection during the trial. Do you see that happening for you guys or have you already implemented that as part of your trial protocol?
Erick Lucera
So maybe I will start out by saying, as a reminder, we have the RMAT designation, which allows for a wholesome dialog with the agency. Christi, I don't know if you have any comments on…
Cristi Barnett
In terms of that, I mean, we are confident after what we heard and saw in the AdCom. We are confident in what we're doing to assess off targets…
Dae Gon Ha
And can you remind us what the methodologies are that you guys are using?
Cristi Barnett
Yes. We have multiple orthogonal approach where we do various process, but we use all the different -- we have our own assays, then we have also use digenome, et cetera.
Dae Gon Ha
Okay. And then you're doing the whole genome sequencing on patients or no?
Cristi Barnett
I would have to check the specific. There is a nuance in that in the process in terms of -- it's to a portion of the sets…
Dae Gon Ha
Okay. How would off target editing in any way be different for a beta thalassemia patient versus a sickle cell, are you guys using the same methodologies?
Cristi Barnett
Yes, the same approach.
Dae Gon Ha
Okay. And then remind me, do you have the RMAT designation for beta thal as well?
Cristi Barnett
No, it's for sickle cell.
Dae Gon Ha
Okay. By the way, if anyone in the audience has any questions, please feel free to jump in. Otherwise, I will continue. All right. So going back to the sites, the reason, Erick, I wanted to ask you about the 50 sites that you were throwing out. And just to be clear, that was a ballpark. There have been skeptics who talk about how lovo-cel and exa-cel being approved by December, knock on wood, could eat up all the patients that are out there, because of the conditioning and the burdensome treatment, you're likely going after that sliver of the market that's the severe, right, which I think depending on who, which management you talk to, it's roughly between 10,000 and 20,000 patients. And so those two products coming couple years earlier than you by the time you come to the market will not have any patients left for your opportunity. How do you rebut that, how do you challenge that notion?
Erick Lucera
So, I think, any new medicine in general has to go through a number of different hurdles, right, to be adopted. The first is getting approval from Managed Care, when the formularies update midyear next year, who knows, I'm sure that's a negotiating process and some of them are updating throughout the years. So you have to go through that. My guess is there's probably, and I don't know this for certain, we'll see what happens there’s usually going to be for this level of cost, there's probably going to be have to think be things that you have to fail first, right? So there's going to be another hoop to jump through. And then you have to talk about training the centers and getting everybody up to speed for that. There's obviously some centers that are involved in their clinical trial and they'll be ready and then others as they expand will need some training. So I think there's going to be a lot of things out there that are going to make this a launch that is going to have some steps in front of it before you really get going. And we think there's a lot of patients out there, they're not all going to go. We have not commented at this point on sort of how many patients we think are going to be out there the first year, that's why we hired Karen, our new Chief Commercial Officer, to really help us nail down the market size and timing of all of that. So we think there's going to be a lot of patients that are still left for us. We believe we have a differentiated product and we'll see what happens. But we'll have more clarity on that as we learn more.
Dae Gon Ha
Out of curiosity, of your trial centers, how much of an overlap is there between 301 and those experienced with either exa or lovo-cel, rough estimate?
Cristi Barnett
I don't know that we've shared that estimate, but there is an overlap and we do have roughly, I think, for RUBY, more than 20 centers online currently in the US and Canada. And there is some sort of some overlap but we haven't heard any -- there's no problem with that. I mean, that's actually people -- the physicians are very excited about EDIT-301, and as Erick mentioned, Baisong has been visiting all the centers.
Dae Gon Ha
I guess, the question that I was trying to get at is, if you talk to these docs who obviously have multiple agents that they've gotten their hands wet. What's sort of the feedback you guys are hearing on sort of the interswitch ability? Like do they feel comfortable treating one patient with this one lovo-cel and then moving away to exa-cel or they feel fairly preferential to one agent versus the other? Any kind of dynamics that you can comment or anything that Baisong has shared?
Cristi Barnett
I think they are more concerned with helping their patients above anything. These are physicians with very sick patients and who -- many of whom, since this is the severe population that's being treated right now through these trials, these are people that have it -- for our trial, for example, they had to have at least two and most had about four vaso-occlusive crises per year, hospitalized for a hundred days a year that sort of thing. So these are very sick patients that the physicians are just trying to help and they finally have these game changing medicines that can actually do that.
Dae Gon Ha
You mentioned Karen's doing like a lot of work on that commercial market sizing and the launch prep and whatnot. So maybe we'll get more data there. But I guess at this juncture, what's sort of your expectation for when those two agents do come to market? Is this something that's going to be sort of inflecting parabolic kind of a move where you have a bunch of people lined up because the demand is high and they're taking whatever agent is available? Or do you consider this to be a very slow and gradual launch with the early adopters with the four, five, six VOCs, and then after watching how they do then you see the twos and three VOCs come to market? What's the kind of scenario that you guys think is probably appropriate for modeling purposes or expectation purposes?
Erick Lucera
Yes, I don't think we've given any guidance on what we think a competitor launch would look like. But obviously, if there is a patient who's at a center where physicians in the trial, they're obviously going to try and get them on an approved medicine and again, they're just going to have to work through the reimbursement process, and how long that takes we have no visibility into…
Dae Gon Ha
Okay. Any early thoughts on pricing?
Erick Lucera
I think, there was an organization that suggested about $2.5 million is kind of the number that's been floated around, and I think some of the other therapies are closer to three. So I think anything in that zip code is going to [Multiple Speakers] yes, probably where it shakes out.
Dae Gon Ha
Okay. Any questions before…
Unidentified Analyst
So you outlined three pillars, but you've really been talking about the programs. What about the out-licensing and [Technical Difficulty]…
Dae Gon Ha
Yes, so that was going to be my next transition but [BD] out licensing…
Erick Lucera
So as I had mentioned to you, one of the reasons I came to Editas was the very rich IP portfolio estate of Cas9, Cas12 licenses, which we think can be a source of non-dilutive capital. We've done a lot of work. I think there's a lot of companies that probably are going to have to have a conversation with us about using our license from a freedom to operate standpoint, and we are open to those discussions. We're not talking about any particular licenses until they're signed. We have signed a few to date, they've been earlier stage and hence smaller size deals. But I think, you all know the companies that are out there. And as we have conversations and get anything done, we will discuss it when it's signed.
Dae Gon Ha
I guess, one of the key areas that is -- I guess, a weakness for gene therapy, gene editing is the delivery tech, which I think over this past weekend we started seeing some of CRISPR Therapeutics show some in-vivo data and that's obviously an area you guys are focused on as well. Some latest thoughts on where you're going, where your head's at?
Erick Lucera
Yes. So the in-vivo is the third of the three pillars that we've generally been discussing. We believe in-vivo is going to be the future. We think there has been some pretty good proof of concept with respect to delivery to deliver using LMPs. One of the reasons we hired Linda Berkeley is to develop that early stage pipeline with in-vivo assets. As you may recall, when Gilmore announced the strategy shift last year at a competitor conference, he eliminated a lot of the pipeline in AAV type delivery and other targets with the intention that in-vivo was the future and we would focus on that. And he brought in Linda, who's a fellow Biogen person who he refers to as a very good drug hunter. And we expect that as we start looking at different delivery technologies, she's hired a team of geneticists and we will have -- we'll announce things when we're ready to announce them.
Dae Gon Ha
The in-vivo, at least my perspective and please correct me if I am off track, is that in-vivo provides a lot more opportunities…
Erick Lucera
Yes.
Dae Gon Ha
Just because it's easier and a lot less cumbersome for patients.
Erick Lucera
Yes, that's right.
Dae Gon Ha
When you think about where Editas sits today, hematology, obviously, with the 301 is a good pillar to start with. How are you thinking about, as your programs expand and the freedom to operate is going to benefit that, what you keep and what you outlicense but also maybe a step beyond that or before that is, what's your target indication? Do you want to go after indications that are derisked, approvable endpoint already well-established, regulatory path also well-defined, or an uncharted territory where you can be the first-to-market and be almost a one and only…
Erick Lucera
Yes, I think it's a bunch of different criteria. First and foremost, we are very focused on not destroying capital. I can tell you from my history on the buy side, I hate the words broad and deep pipeline and lots of shots on goal. I have said that many times. I believe and one of the reasons I came to this is the shared vision with Gilmore that we are going to focus on high conviction targets. We are not going to spread our bets around for the sake of derisking. We believe the investors should do the diversification. We want to focus on high conviction targets. Given the fact that we are looking to do some in-vivo work after the autologous, it probably leans toward areas, which have been uncharted. But that really remains to be seen and we will see what Linda comes up with and the rest of the team.
Dae Gon Ha
Okay. And what about 301 specifically given your lean and mean organization, how are you thinking about ex-US commercial opportunity?
Erick Lucera
Yes, I think we have said many times we are open to finding a partner for ex-US. It’s not an area where we want to or even should be building sales forces. I think every CEO I have worked for since I left the buy side prefers to outlicense OUS. I think it has been, for a lot of reasons, it’s not the easiest thing for US companies to manage OUS from a small company standpoint. There is just so many resources to go around. So better left in the hands of the local.
Dae Gon Ha
Okay. Another advantage you guys have is the IP. But it has been a long and arduous process of Berkeley versus Broad, Broad versus Berkeley back and forth. So I think we are still at that stage. But as it stands now, what do you -- how are you thinking about maximizing that freedom to operate, monetizing some of that? What's the sort of lowest hanging fruit versus something that you can look broader into sort of…
Erick Lucera
You know, I think to answer the question, it is really just focusing on this. We have dedicated one of our three pillars to getting licenses for the Cas9, Cas12 portfolio. We have couple of people that are working on this almost full time and reaching out to people and/or fielding calls from people, and the deals will happen when they happen. There is the potential that the CVC resolution could be a catalyst. As you know, we have won two or three times and there is one last appeal, and that could be a catalyst that gets people to the table as well. But I don't want to speculate on any of that stuff, it’s really just -- it’s a relationship game. All business development is relationships and just getting down and getting something done.
Dae Gon Ha
Okay. AsCas12a is unique to you guys and it’s not part of this whole IP challenge battle for…
Erick Lucera
That’s right.
Dae Gon Ha
Going forward, how do you decide SpCas9 versus AsCas12a, is it more leaning towards AsCas12a given the IP freedom or given the superior position you have, you're going to continue to look at both?
Erick Lucera
I mean, Cristi can probably answer this better than I can. But I suspect that we think that Cas12a is generally just a better cutting enzyme. And so I think that's our intention is to try that first and see where we go from there.
Dae Gon Ha
Okay. Anything to add, Cristi?
Cristi Barnett
No, that's -- we could use both, but we've been focused on Cas12a..
Erick Lucera
And there maybe things that come out of research where it -- they may suggest something different. But I mean, we're agnostic, I think, we'll -- whatever the science tells us to do, we'll pursue.
Dae Gon Ha
Okay. We'll always have to touch with the cash question. So remind us of your position, anything milestone payment wise that we should be keeping an eye out on the next say 12 months?
Erick Lucera
Yes, so we ended the last quarter with $446 million of cash, that gets us into the third quarter of 2025, so about two years runway. As I mentioned, the Cas9, Cas12 licenses would be a nice source of non-dilutive capital, which could extend our runway. Outside of that, there's really nothing to speak of at this point…
Dae Gon Ha
Unless something happens…
Erick Lucera
Unless something happens, yes.
Dae Gon Ha
Any last questions before we wrap up? If not, Erick, Cristi, thank you very much for your time.
Erick Lucera
Thank you very much. And I'll just mention as a former buy side person, we are always open to investor, analyst feedback, so we take it very seriously and I always have since I left the buy side. So please do not hesitate to reach out with any suggestions or criticisms. So thank you.
Cristi Barnett
Thank you.
Dae Gon Ha
Great. Thank you very much.
Question-and-Answer Session
End of Q&A
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Editas Medicine, Inc. (EDIT) Presents at Stifel 2023 Healthcare Conference (Transcript)