Editas Medicine, Inc. (EDIT) Earnings Call Transcript & Summary

Good afternoon, everyone, and welcome to Barclays Global Healthcare Conference. My name is Gena Wang. I cover U.S.'s Mid-Cap Biotech. It is my great pleasure to introduce our next presenting company, Editas Medicine. With us today, we have Gilmore O’Neill, Chief Executive Officer. We also have Erick Lucera, Chief Financial Officer. Before I dive into specific questions, Gilmore, maybe you wanted to give them a bit high-level overview of Editas.

Yes. Thank you. Thanks very much, Gena. Very nice to be here. So Editas is a genome CRISPR-based editing company. We have, say, three core pillars to our strategy. We are driving our lead clinical asset, reni-cel, a CRISPR-edited AsCas12a edited cell-based therapy for sickle cell disease thalassemia, which were driven through the clinic, and I can tell you more about that in a moment. The second pillar is a sharpened focus on the discovery side for in vivo CRISPR editing, which we believe is the real path to unlocking the true and incredibly exciting potential of CRISPR editing technology to really transform and disrupt health care with single-use very durable therapies. And the third is a more aggressive posture in business development with two elements. One, bringing in -- evaluating and bringing in technologies that enable our in vivo platform and pipeline to accelerate. And the second is to share and out-license the IP -- exclusive IP technology foundation to use Cas9 and Cas12 in human therapeutics.

Great. So maybe tell us your lead indication reni-cel in sickle cell. And so can you walk us through the potential regulatory time line for BLA?

Yes. So just quickly, reni-cel, we see as a fast follower with the potential to be best-in-class and certainly significantly differentiated from other cell therapies in that it both up-regulates the fetal hemoglobin Humalog for the disease or mutated beta-globin in sickle cell disease. And it also normalizes and corrects anemia, and that's what we have seen to date in our clinical experience. With that, our regulatory path is actually developing very nicely. Back in November, we achieved or were given our mass designation by the FDA, which I think was a recognition of their anticipated continuing unmet need as well as we felt a validation of the nonclinical or preclinical and clinical data that we shared when we submit our application for RMAT. Since then, we have seen the approval of Casgevy, which I thik is a very nice benchmark of what the regulatory path is. And we've had interactions with the FDA where we achieved or reached agreement on the conversion of the RUBY sickle cell study for reni-cel from Phase I/II to a Phase I/II/III effectively a registration study had a single registration study at that to BLA. It enables us to use all the clinical data for all the patients that we have dosed to date, and we'll be dosing in the future as part of that package. We also agreed on the primary outcome measure around our definition for severe vaso-occlusive events and vaso-occlusive events. What we have left open is that against that background of a benchmark set by exa-cel, where they filed with 20 patients in the efficacy cohort at the end of the first quarter of last year, and then achieve their PDUFA and approval in December. What became clear was that during that review, they submitted additional data and additional 10 or so patients. That's in the correspondence that was published at the end of January. So we use that benchmark and understand also that in that benchmark, they used a 16- to 18-month follow-up post the treatment of those patients in their submission for efficacy. Against that background, then you consider that with RMAT, we continue our dialogue with the FDA and because our RUBY study is open label and enables us to essentially cut data at intervals. As we see that data strengthening and evolving, we can contain that or include that in our discussions with the FDA as we drive to refine what will be the final patient number in the clinical data set that we were to submit for our BLA.

So is it fair to say the initial submission package that likely will be also similar like 20 patients and 16 to 18 months follow-up?

I think that's a very reasonable benchmark against which to measure. And obviously, our dialogue will then confirm what exactly that will be.

Okay. Okay. That's good. And maybe also a little bit about time line for the data foresee.

Yes. So the -- I should say, by the way, the other thing we're very happy with how reni-cel is going to RUBY study, we -- as we announced it a couple of weeks ago, we've now enrolled 40 patients, 40 adult patients. We have dosed 18 patients. That's a substantial uptick over just the quarter between Q3 and Q4 earnings. And in addition, we have enrolled 9 and dosed 7 patients in our thalassemia EdiTHAL. So on both counts, things are actually moving very well, even against the background and approval, and I think that's worth highlighting. And obviously, there remains a lot of enthusiasm from the investigators and propose the regulatory path for thalassemia. We haven't actually shares that yet. But what we are doing is obviously continuing our clinical investigation and drive, and we'll update you at a later time when we have come to those agreements.

Okay. Good. So then since you mentioned like enrolled 40 patients dosed the 18 patients. If I recall correctly, Casgevy, it totaled maybe 45 patients, 50 in the -- like when they submit to data package.

Yes. So I think one has to distinguish between the total number of patients and the initial -- or sort of the efficacy cohort. So I would look at -- people should look at these packages and particularly, how should I say, clear when you're talking about rare diseases and small populations. So the total package filed includes all patients dosed and will include safety and graft and data. And then a subgroup of that, a smaller number, and this is where they have the 20 to 30 is your efficacy cohort with that minimum follow-up agreed with the agency to declare efficacy and sufficient durability for approval. So we have, in our clinicaltrials.gov at site, you will see that for the RUBY study, we have called out for the enrollment of 45 patients. We have enrolled 40 adult patients. We have said that we will complete enrollment for adults this year. And more importantly, we have actually also initiated our adolescent cohort and screening is actually going really well, actually better than we had expected. So overall, a lot of strong movement there.

Okay. Good. And maybe based on your clinical experience so far, usually how many cycles you need to do in order to collect sufficient cells?

Yes. So our experience has actually been good, and we've had the opportunity during the [ excusical ] trial to optimize and share best practices across sites. And what we've actually seen is that we are collecting with our sites between 1 and 3 cycles are sufficient. We haven't gone into more detail about that because obviously, we want more data to get a clear understanding of what exactly that's going to mean for the commercial population and what that commercial experience would look like.

Good. And regarding the data update later this year, maybe can you lay out what kind of data metrics will you be looking?

Yes. So later this year, midyear and at the end of this year, but let's talk about midyear. We intend to share hematologic parameters, safety and engraftment data. What we had anticipated is that we will have safety engraftment data, considering that we have more patients scheduled for dose in the next few months, that will exceed about 20 patients. We will have 18 patients with at least 3 to 4 months of follow-up. And there, we will share clinical vaso-occlusive event experience and hematological parameters, including fetal hemoglobin, total hemoglobin. We have made a decision about other outcome measures. Obviously, we're interested and are collecting clinical [ ad ] measures for organ systems as well as patient reported outcomes. But we are getting an understanding. Some of those instruments we're using have not been used by others in more recent studies. And as I think I've said to you and I shared with others, one of the good problems to have when you're working with a high potency medicine against a background of previously developed lower potency medicines is that it is difficult sometimes to understand exactly how those outcome measures at a clinical level are going to respond with a very high biological outcome effect size. And so that is something that we're actually getting our understanding around what are the impacts on variability, the performance characteristics and outcomes because there's been little or no experience with those outcomes in the context of sickle cell disease with high potency therapies. And so we actually will be evolving our thinking as we see those data mature and determining what and when we should share. How and when we should share these data.

Okay. Good. And then maybe like once you share that data, how would that -- regarding -- if we think about fast forward, regulatory feedback and also the future commercials, how would you incorporate this into, say, the approval data package or the commercial?

Yes. Well, I think what you'll actually get is a very good view, a snapshot view of the size of the data package where we are and you think about a time line against that benchmark of 20 initial efficacy cohort patients with 6 to 18 months follow-up. So we will have -- you will have the spread of our experience of follow-up in that midyear review with 18 patients with at least 4 months, 3 to 4 months of follow-up. And then you can actually draw the line from their to what that benchmark sets for us. And then obviously, we haven't decided yet when and how we would be talking about the refinement of our engagement with the FDA when it comes to locking down the numbers of patients that we would include in that first filing. Does that make sense?

Yes. So now given the competitive landscape and you just say those are the things you wanted to focus in order to provide a differentiated profile and now with the two drugs already approved, do you see any impact on your enrollment or any -- the speed of enrollment.

Yes. No, it's a great question. And I think the way I've answered that question are in two ways. The first way is the sort of intangible sentiment. When we last presented our data at ASH, there was tremendous excitement maintained and growing with increasing belief in the competitive nature of our product, its usability and meaningfulness for patients as well as the correction of anemia that we see consistently across all patients. So just to recapitulate, in all patients who have been dosed, who have been followed for at least 4 months, we have seen correction of their total hemoglobin to a normal physiologic range. And we believe that this is an important differentiator. From a point of clinical meaningfulness, many, not all, but many KOLs and investigators said, this is a no-brainer. This actually is meaningful. And the fact that when they actually look at our population means versus the population means of others, they actually see that to highlight that, that is something they see as meaningful in their clinical practices. And indeed, a 1 gram per deciliter change was used for the accelerated approval by the FDA for Oxbryta. So the FDA sees that as a meaningful difference. So neurophysiologic range and a mean -- population mean differences that are in a meaningful range. So that's kind of the intangibles and then a sort of more concrete in Q3 of this year, we announced that we had dosed 11 patients and enrolled 27. In our Q4 earnings just 2 weeks ago, which spans the AdCom, the approval and the holiday -- the winter holiday, we actually increased from 11 to 18 dosed and enrolled from 27 to 40. So intangibles, concrete, we would say that we have seen no impact.

Okay. Very good. Another question is more like a process time. The -- from the start to complete the dosing, usually how long that will take and then also additionally, you dosed 18 patients but you have 22 patients waiting to be dosed, like what will be the timeline reshape?

Yes. So the time lines are impacted by a number of things. One critical element obviously is the vein-to-vein time as we call it, which is the first vein or the first vein time starts when you structure first collection of cells. And the last is when you actually infuse the edited cells back into the patient. We're seeing a range of about 5 to 12 months. The 5 months really is determined by the collection, the editing, the manufacturing editing and then a large part of that actually sits around the quality release assays, which are comprehensive, take some time. The rest of that variance is created beyond 5 months is created by issues that may arise with the patient. Obviously, they have life to lead, professional and personal lives to lead, which may impact scheduling. Other elements, of course, are that these are patients with severe sickle cell disease. Our protocol requires that they have at least two severe vaso-occlusive events per year in the 2 year, each of the 2 years before enrollment. In fact, our experience has been that they have a mean of 4 -- 3.9. 4 vaso-occlusive events per year. If you spread those equally, which is unusual. But if you do, you'd anticipate that within each quarter, they would have at least 1 VOE, that in itself can set a patient back because you want them to be optimally -- you want their health to be in its optimal place when you actually do that infusion. So those events. And then the other issue, of course, is that busulfan does have an impact on fertility. So many patients as they anticipate a new future, where their vaso-occlusive events are controlled and their disease is improved, start to think about families. And naturally turn to with the concept of busulfan, preserving fertility, we can actually add to that cycle. We are learning from all of these things to make sure that we can create and optimize that experience. Right now, we're doing it in the clinical trial and sharing best practices across these variables. And obviously, that's something that's going to evolve over the next couple of years as we get ready for a launch, and we'll flow that into our commercial planning. And obviously, we'll also inform that further as we observe what is happening with the commercial launches for Casgevy and [indiscernible].

Okay. That's very helpful. So maybe -- how many patients actually will need the pretransfusion before you start the cell collection? And what type of -- yes.

So we don't necessarily transfuse before collection of the cells. The one place where patients -- well, first of all, in some patients with severe anemia or the manager of very severe vaso-occlusive events, you may do exchange transfusions. You may transfuse to elevate anemia or in the context of a severe vaso-occlusive event, the practice may be to do exchange transfusions. The other place where that happens is around the time of the transplant. Because you want to actually get these patients as fit and healthy as possible before they go through the transplant. So that's where you would actually say carry that out. I will tell you that the sort of the protocols for optimization of patients is not in our protocol. It is in the protocols at the transplant centers. But that's where you will see the use of exchange transfusions. And it's really largely prespecified in the context of preparation for the transplant itself.

I see. Okay. That's very helpful. Okay. So maybe switch gear regarding your in vivo pipeline. So you recently mentioned you would develop an in vivo program for an undisclosed indication. So when should we see the update from this program?

Yes. We're actually getting, I'd say, we are getting quite excited about this now because there has been a lot of work done, bringing in Linda Burkly as our new Chief Scientific Officer 6 months ago. It's now really paying dividends. Now we're seeing substantial progress both in the advancing for the in vivo delivery as well as identifying targets. Obviously, we have disclosed that we are interested in hematopoietic stem cells and other tissues, including the liver. We have not said what -- which tissue we're talking about for the in vivo disclosure or the in vivo POC this year. What we are actually going to say is that in the second half of this year, we're going to share more about the forum, the what and the where and the timing of the disclosure and sharing of the POC data. One thing it is worth saying is that we are obviously being very -- quite cautious about identifying the targets because we're kind of early in our formulation work. And as I say, one of the wonderful strengths of CRISPR, the CRISPR methodology is that once you've actually optimized your formulation for delivery to a given target cell or tissue, you can then plug and play by just simply changing 20 nucleotide on the guide RNA. Now I know that's simplistic, and it's never quite that simple, but it almost is, and it's certainly much simpler than building a new small molecule or screening a new set of monoclonal antibodies. And that's going to be the power, and that's going to be the thing that's going to really allow us to really accelerate through multiple indications once we have that formulation. The downside is that until we have that formulation, while others do have their formulations valid in humans, we're going to be very careful about disclosing or sharing those targets to at least give ourselves a chance to leap ahead. And so what I just want to sort of set some expectations. So we're going to share -- sort of in summary, in the second half of this year, we're going to share more about how we're thinking about the sharing updates. And then also, I just want to set expectations that we're going to be very careful about certainly disclosing the targets that we will personally develop. But at the core, and this would be very important to say, we are absolutely committed to the idea as I said before, that we will choose to develop targets internally that decisions actually are clearly differentiated, commercially and clinically meaningfully from the standard of care, we're really focusing on targets that can only be hit via the differentiated mechanism of genome editing. We don't want to go to areas where other modalities can hit as well. Obviously, if we can clearly differentiated, that's different. But we essentially want to really go where you get a clinically meaningful differentiated benefit from genome editing as opposed to another method of hitting the target and obviously then maximize the probability of technical regulatory clinical success.

Okay. That makes sense. In our last 2 minutes, maybe asking about your business development activity, maybe the licensing.

Yes. So the -- thanks. The business development with respect to licensing will take sort of two paths. One will be the traditional Cas9, Cas12 licenses, such as what you saw with Vertex and Vor last year. We think there's a high double-digit number of companies -- a number of products out there in the Cas9, Cas12 field and about half of them are being worked on by a high single-digit number of companies. So we think there's a lot of discussions to come about getting technology licenses in the coming years. The other side of the business development that we have from an out-licensing standpoint would be to take some of those in vivo targets that we're not going to work on and perhaps someone may have an existing franchise with an antibody or an SRNA and say, "Hey, we have a gene editing package that you might find interesting and have conversations with that." It's kind of similar to what we have with our Bristol agreement, where they contracted with us. We've given them a bunch of molecules, and they're slowly starting to advance through Bristol's pipeline, and we get a much different set of economics on those than we do on the Cas9, Cas12. So 2-pronged strategy for out-licensing.

Any active discussions?

We'll talk about discussions when we have a deal signed.

Okay. That's fair. So lastly, maybe since Erick is here, maybe the cash position and the run rate.

Yes. So we ended the year with $427 million of cash, which we said at the time gets us into 2026. And one of the reasons that I came to Editas was the ability to monetize these royalties as a source of nondilutive capital, as you saw last year with the Vertex agreement, which extended our cash run rate by two quarters.

Okay. Very good. Well, thank you very much for coming.

Thank you very much, Gena. Great to be here.

Thank you, everyone.

Thank you.

Thank you.