Editas Medicine, Inc.'s (EDIT) Management Presents At 4th Annual Evercore ISI HealthCONx Conference (Transcript)

Editas Medicine, Inc. (NASDAQ:EDIT) 4th Annual Evercore ISI HealthCONx Conference December 2, 2021 9:40 AM ET

Company Participants

Mark Shearman - Chief Scientific Officer

Lisa Michaels - Chief Medical Officer

Conference Call Participants

Liisa Bayko - Evercore ISI

Disclaimer*: This transcript is designed to be used alongside the freely available audio recording on this page. Timestamps within the transcript are designed to help you navigate the audio should the corresponding text be unclear. The machine-assisted output provided is partly edited and is designed as a guide.

Liisa Bayko

00:01 Hi, there. Good morning. This is Liisa Bayko, Biotech Analyst at Evercore ISI. Very pleased to be joined by one of the leading CRISPR companies Editas Medicine’s. We have two of the Medical Scientific kind of tied from the call with us Lisa Michaels and Mark Shearman, who are going to go through some of the pipeline questions. But I just wanted to start off by sort of a broad question and I'm kind of asked this all the CRISPR companies that I'm talking to over the course of our conference, but as I reflect on CRISPR kind of where it started, right? It's just taken so many different forms. So, know you guys are initially focused on Eye (ph) and you've got some other, ex-vivo output, some people started with ex-vivo are going down.

00:49 The route of CAR-T and then others are regenerative medicine and other people are focused on in vivo as an initiation, sort of what was your like, how did you come to the notion that you kind of start with the Eye and sort of go from there, the idea there?

Mark Shearman

01:09 Well, I will take a stab at that explaining, I think the logic of our -- mine and Lisa’s predecessor of the company, but I think part of that is around delivery of the editing machinery, right? So, it's well known that AAV can be used as an effective way of delivering payload to the back of the retina. And you can fit the appropriate guy in nucleo (ph) agent to an AAV. So, I think that's the logic from the technology and delivery side of things and then also having worked [indiscernible] therapy previously there are known indications and targets in the eye that are very straightforward relatively speaking to go after. And so, I think for a company that had a new technology, it made a lot of sense that this would be one of the first approaches because there was a clear path to getting proof concept in humans?

Lisa Michaels

02:13 I think from you're asking a question at [indiscernible] both of us history of the company. But if you just take the broader perspective about it, I think what it really reflects the power of the platform and the fact that every -- there's no gene in the body that potentially can't be edited to some benefit or disadvantage. I think that's the nature of the power of the platform. Back to the eye is an interesting one from the perspective that I think at least our target which is Lebers can generally [indiscernible] nine mutations, actually shows the sweet spot of some of the power editing because this is not a disease like, which could treat through gene therapy because the gene is too big to deliver through an AAV. And it has to have some other mechanism in which you can correct it. So, if you can do gene therapy in that setting, then you could do a very specific knock out of the gene let’s call as a part of the gene that’s causing a problem. So, it's really shows the benefit in that particular setting and differentiates that from such as [indiscernible]. Equally, awful a lot of the companies have gone into the space of cyclical disease. Real interest and now, of course, it is the most common in heritage genetic sort of with a very well described mutation in place.

03:31 I think what’s really interesting, however, is that for all the players in the space were all approaching it in the difference in unique fashion different enzymes to different approaches within those cells. All of which fit differentiate if not an efficacy in terms of long term safety durability and benefit to the participation. So that's the other really interesting part about this is the invariability and approaches. And then at the end of the day, we're also looking at ex-vivo cellular (ph) therapies. And it's one thing to Editas sell in body, it's another thing actually to exploit its behavior into use cells as medicine. So, the fact that we're playing in all three of the space is in many ways is a representative of the power of that platform as well as wide breath of diseases that can retrieve it. So, it's kind of exciting and also very interesting to see how the different companies are approaching it.

Liisa Bayko

04:22 There's a recent clinical hold related to chromosomal abnormalities using CRISPR. What are you doing to address some of these safety concerns?

Mark Shearman

04:35 Sure. I'll take that question. I think it's not so much what we're doing now, but what was put in place in the past to evaluate and minimize this risk. So Editas has a large suite of sequencing tools together with a bioinformatics platform that allows us to very specifically monitor the edits that we make, whether it's on target or off target. We're also able in many cases to design guides, in conjunction with our AsCas12a very highly specific nuclease to the point where we do have no off targets.

05:17 And so in terms of your question, we've done several things based on sequencing, we know that these events occur at a very low frequency. We are able to determine exactly any recessions or translocations that do occur and determine if they are going to interrupt or impact on any known feeds of interest that maybe available in sort of oncogenic databases. We know, for example that in-vitro, we see no transformation of CD34 positive cells following treatment and then with an extensive in-vivo work, especially in the sort of safety studies to show that there's no potential for tumor [indiscernible].

06:02 So I think right now, a combination of very specific technology in making the edits and then ability to carefully evaluate those edits, gives us confidence that that risk is as minimal as it can be.

Liisa Bayko

06:16 So, I want turn to EDIT-101 and I know you've been humbled with in terms of questions on these patients. We're not going to get into details on every single little patient, but I do want to ask some like sort of more broad high level questions. And there is reflect on the data, it seems to me like, some of its encouraging, but some of it is confusing. There's a lot of noise and this is actually kind of typical when you're in the stage of development that you're in. So, I guess, as I reflect, I'm really kind of understand, like, did you -- do we really have proof of concept yet that, EDIT-101 has did the work and LCA10 or where are we kind of on that path to getting the proof of concept? Do we have the aha moment yet? Or is it more just like we know we could give the safely and now we're going to see if it really can deliver to patients what the needs to do?

Lisa Michaels

07:06 It depends how you define that aha moment. You can't do phase clinical trials in any therapeutic area unless you are comfortable with ambiguity. And at the end of day, it's the way of the evidence across multiple different patients that really sells on whether or not this is a clinical product but not. What I can tell you is the academic organizations and the patient community, we're incredibly excited by the data that we shared. And I think if you look at it from just a segment point of proof, this is the first clinical trial that was ever did done in human beings. We were editing within the body. And so, the trial design being very first is both the [indiscernible] because no one had done it, nobody really knew it was going to be safe or not.

07:49 And so the trial was designed even before lot of the AAV based genetic and gene therapy programs are even out there. Based upon very limited information and knowledge, so no one knew this would be safe, particularly there would be unknown immune responses against the protein, which continues to be result in patients losing with little much of ahead. So, for me the first, and I recall it in aha moment is the fact that we're able to progress from the lowest dose and now treating patients at the highest plant dose, without any adverse events that are atypical for treatments in this particular space using AAV subretinal therapies. There was nothing that raised any additional to safety concerns. That to me is a very important outcome because that's the first special we had to overcome and it was the first thing on unknown.

08:36 The second one is, could we find evidence in a disease where you can't retentional a blood test. There's no easy biopsy. How can you show that editing okay, it’s safe, if that editing actually occurred, did we actually change something about the function, how that eye proceeds light? And what we saw in early -- very early data is that yeah, we actually achieved that. We had some patients who demonstrates -- who had evidence of editing occurred and even more importantly that that editing could translate into an improbable endpoint such as being able to [indiscernible] or improvements in BCVA and even FST which would be predicted to result in clinical improvements in ability to visual fields as well as seeing like dark. So that's a very exciting very promising, it shows the platform works in this scenario.

09:27 So the next moment of course is how does that translate into a clinical or pivotal clinical trial that can be used as a clinical therapeutic, and that's really the next stage that we're looking at is how we can actually define the endpoints of the patients who benefit those treatment. So, all of this is actually very good news for the company and for the platform in a very challenging disease to measure those imports.

Liisa Bayko

9:51 Speaking off people who would -- patients who would benefit most from the platform. When you looked across, these handful of patients you have tried at 101 and the best patient with the most persistent data was the almost Eye patient. And we kind of bounce that off you guys, you thought maybe [indiscernible] there's no rationale to believe that they would, have a better response, and then [indiscernible] always spoke to said, yes, they would because [indiscernible] disease. I just wanted to come back to you and as you've been thinking on the data now is there any reasonable that [indiscernible] would do better that a specific population that should be prioritized in some way or is that really just a like, a one off finding at this point?

Lisa Michaels

10:35 Well I think Liisa we know about the diseases, [indiscernible] are very rare. Most patients actually have compound heterozygosity. What does it really need? I mean, this is a disease where you have to have both the [indiscernible] in a cell with a mutation [indiscernible] loss division. So, every one of the patients in this trial had a parent who already had one dysfunctional or reveal (ph) and they all mostly or should have had normal vision. And what that tells you is, you only need to correct one of the two genes in the cell in order to restore function. So that's the first important takeaway.

11:11 So, in a patient where there is homozygous, I guess theoretically you have twice the amount of time that hits twice the opportunity to correct one of the two alleles, but you only need to correct one of them in order to be able to make improvement. And I think the important thing for me in this scenario is the non-clinical data suggest that we actually achieve a very high efficiency of editing at least one alleles themselves. And so, when we projected that I only need one corrected to have improvement in-vision. So having only one patient with homozygosity in the trial so far, it's going to be a little hard to say, yes, homozygosity gets to the patient population. We're continuing to evaluate the effect in both heterozygous and homozygous.

Liisa Bayko

11:55 So where are you now with enrollment and then where, -- what I know you've said you'll provide an update kind of next year data readout will be I believe 2Q next year.

Lisa Michaels

12:06 I've actually clearly, identified when I'm coming forward with the additional data. But I think the important thing is, as you said, there was a fair -- the date that we shared in September, it's fairly early data in a very small number of patients. So now that we've been able to demonstrate that we have some level of efficacy at least in early readouts in some of these patients.

12:31 At the moment, as we move into the high dose in the pediatric cohorts, there hasn't been any new signs or signals of safety concerns, which allows us to continue to enroll trial. I think we're actually now starting to talk about what is the body of evidence supporting either particular doses or particularly patient populations or supported data to our endpoint are going to be. So, at this point, this is where it gets exciting because that's where the real detailed data analysis starts to occur.

Liisa Bayko

12:58 You've got your next program is USH2A, EDIT-102 and then I think you might even have an RFP program behind that. The editing efficiency and or EDIT-102 it seems to be materially lower than what you've seen with LCA10. So how do you think about them, like, how important is the data from LCA10 in terms of read through to the rest of the portfolio for the eye, at least, considering that maybe it's got the best adrenal insufficiency?

Mark Shearman

13:33 So I think I can answer that in two ways. One is that we're going to be using the same capsid and at least for the USH2A program the same promoter, so you could argue that that those two components have been somewhat derisked by EDIT-101 in terms of their use in a subsequent human trial. Yes, with 102 when I joined Editas, one of the goals I had was to continue to kind of improve the configuration of that construct to give us an opportunity to edit higher levels and that's what we've been doing for a period of time.

14:11 And then I'm also excited about the RFP4 program because that's our [indiscernible] and replace based strategy where we have two different AAVs one that provides the guide and the replacement reduction and the other one provides nucleus. And so again, that's interesting technology and we have spent a lot of time optimizing the gene to sets for that dual vector system. So right now, both programs are in lead optimization and we hope to progress those into IND-enabling studies in the near future.

Liisa Bayko

14:46 Let's move on to your ex-vivo program. I promise we would spend all of our time on LCA10. So, EBIT-301 is coming forward in sickle cell disease and beta - thalassemia. Can you just describe how you see that as; this being positioned differently from other ex-vivo therapies for these two diseases? There's a lot going on in the field, CRISPR/Vertex have looked like they're kind of leading the charge there. But how do you plan to be different from others in that field?

Lisa Michaels

15:22 I guess the way that I would look at it is that we're all targeting the same disease. We're all looking at various similar or overlapping outcomes, but the way in which we're doing it is uniquely different across every one of the companies. So, none of us, they all be gene editing over editing taking very different editing approaches. And I think at this point in time, it’s going to be very interesting to see how those different methods -- different that sort over time. I think one of the things that we have to remember is that and you started the questioning with it, at the end of the day is how safe the therapy is, okay. This is all great cutting edge science at the moment. The unknowns that we're facing at the moment are still quite severe. And at least in sickle cell disease and thalassemia, we are looking at disease for patients having extremely limited lifespan. And really would benefit from a therapy that effectively gives the mature with an understanding that you don't know what's going to happen in the long term.

16:19 One of these is durability and we saw recently that saying the most TDT program actually had problems with durability because they weren't editing both long term short cell populations. Again, it reflects the differences in the processes and procedures that we are doing. With Bluebird with their gene therapy approach, we began to see that there were some unknowns we made to help patients bone nerve to sustain a function over time. So, you're beginning to see there that there are potentially long term concerns with what has it actually been of ground breaking therapy. As we move into the CRISPR brings some of the other editing techniques, the target that we're going after is quite different as well as the enzymes are different across different programs.

17:00 So, CRISPR’s big data which is very impressive and right now is sort of barred match has targeted the BCL11 gene, which is a very important concern gene in the body where they tend to be a lot of mutation and the reason why it's called BCL is, it was originally described as a gene that was important to quite some differentiation. So BCL leukemia or lymphoma is, how that was first identified. So far that's not been a concern in terms of safety, but we don't know what that's going to mean over five, ten or fifteen years after treatment. Instead, we're using one of different enzyme than many of the other competitors. We're the only company that's actually using the Cas12a enzyme.

17:41 That enables us to actually hit a more complex work as on the hemoglobin B promoter and in the site where BCL buying, so we're sort of hitting the other ends of the gene function there. What's nice about that spot is, there's a lot of unique and normally occurring mutations that occurred there that aren't associated with long term concern to disease people actually impaired probably more efficient and mutations in that space and have a long happy healthy life got complications. And so that target we think will result in better hemoglobin F production, but we also think has the potential would be a better long term safe target.

18:17 So, I think it's too early to say anyone program different than another. It's clearly in disease, one better is better than another. It’s clearly a disease where there's a lot of patients with a lot of unmet need. The safety and the benefit would certainly aren't been in favor for treating these patients by these more approaches and how that actually sorts over time. I think it's too early though.

Liisa Bayko

18:40 The time it remains, I just want to talk about your fleet technology is pretty cool. So maybe you can talk a little bit about that and when this is going to start producing product, they take into clinic.

Mark Shearman

18:52 Yeah. So SLEEK stands for SeLection by Essential-gene Exon Knock-in. It's a mechanism of methodology that allows you to vary selectively knock-in one or more transgene into a specific locus we published a lot on the GAPDH locus. And in doing so, it also allows you to enrich the cell populations that have had the positive outcome. So far, we've used it to edit IPSC for our iNK program. You can edit NK cells directly. We are using it to edit the alpha beta T-cells in our BMS collaboration and we can also edit other cell types.

19:33 So it's a pretty versatile methodology that we're using to added along with the AsCas12a program. So actually, you're seeing the results of that. Already, we've published some of the work at [indiscernible], there'll be more coming at ASH in a week or so. And so, yeah, we really like the technology. It has a lot of utility and we already have some pretty interesting ideas on how we can continue to expand the point.

Liisa Bayko

20:00 When it's going to be ready for prime time, meaning, human?

Mark Shearman

20:06 It is going to be ready for primetime very soon. I mean, as I mentioned, we have the alpha-beta T-cell program, obviously we don’t control the development of that program, but BMS has continued to opt into additional targets and are progressing some of the original products that we used our technology. And then as I mentioned, we have the IPSC edited program for iNK that's moving forward. And so pretty soon, it's going to be in the clinical setting we hope.

Liisa Bayko

20:36 Okay. So, we're at the top of the hour. I just want to end with the question on what's the store for edit in twenty twenty two. What can investors look forward to in terms of key value training events?

Lisa Michaels

20:47 I think it's going to be a very exciting and interesting year for us because continued data readout from the 101 programs. The approval, the IND for our beta thalassemia program, the first dosing and potentially from the first dosing of patients from that study of the dosing of the first patients who are all now like scheduled in cell program. And then additionally, something that Mark is doing, if you wanted to highlight some of that.

Mark Shearman

21:14 So, yeah, the two ophthalmology programs we talked about will publish more information and data on those, people will get to see the specifics on the iNK configuration one that will be progressing. And then we're publishing, we'll be publishing the SLEEK technology in a full paper next year. And yeah, some of the other target’s choices that we're currently working on, we like to communicate next year.

Liisa Bayko

21:40 Okay. Great. Well, listen, Lisa and Mark, thank you so much for your time today. So funny, that's my name, my husband's name like.

Lisa Michaels

21:49 It was nice to talk to you today. Didn't catch up. And I'll look forward to updates in twenty twenty two and actually in the near term honestly.

Liisa Bayko

21:57 Thanks.

Mark Shearman

21:58 Thanks. Bye.

Question-and-Answer Session

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