EDIT - Editas Medicine Inc. (EDIT) Presents at Wells Fargo Securities Healthcare Conference Call Transcript
2023-09-07 19:11:10 ET
Editas Medicine, Inc. (EDIT)
Wells Fargo Securities Healthcare Conference Call
September 7, 2023, 15:00 PM ET
Company Participants
Gilmore O'Neill - President and Chief Executive Officer
Baisong Mei - Senior Vice President and Chief Medical Officer
Conference Call Participants
Yanan Zhu - Wells Fargo
Presentation
Yanan Zhu
Great. Thanks everyone for being here. My name is Yanan Zhu and I'm one of the biotech analysts here at Wells Fargo. It's our privilege to have Editas Medicine management team with us for our fireside chat here today.
With me here are Gilmore O'Neill, Chief Executive Officer, and Baisong Mei, Chief Medical Officer. Thank you Baisong. Thank you Gilmore for being here.
Gilmore O'Neill
Thank you very much for having us.
Baisong Mei
Thank you.
Question-an d -Answer Session
Q - Yanan Zhu
Great. So, I think, if we could -- let's dive right into EDIT-301 for sickle cell disease and the ongoing RUBY trial, if that's okay. Wondering how many sites have been opened? How many patients have been enrolled, and how many have been dosed?
Gilmore O'Neill
Baisong?
Baisong Mei
Sure. Yeah. Yeah. Thanks for a question, Yanan. We shared in June, we already opened 22 sites for RUBY study and have that 20 patient enrolled. And since then, we continue to activate more sites and enroll in dosing more patients. So, we're very excited about momentum for the RUBY trial, as well as for EDIT trial too for thalassemia.
Gilmore O'Neill
And we're looking forward to sharing data at the end of the year with our -- from our sickle cell and our thalassemia studies.
Yanan Zhu
Right. That's -- yeah. Yeah. So, you reported data previously for I think four patients of data that we saw.
Gilmore O'Neill
That is correct. So we presented in June. We presented four patients data from the RUBY sickle cell Study. And in a webinar a couple days later, we shared those data and data from one of our thalassemia patients in the EDITHAL program, and we're really very happy with the data we presented, seeing very robust expression of fetal hemoglobin in excess of 40% for our first two patients in the RUBY study with the third and fourth patients following a very similar trajectory. And in addition, the first two patients at month four to five demonstrated a correction of their anemia to normal physiological ranges. And the -- as I say the third and fourth patients, the RUBY study followed very similar trajectory.
We also presented one and a half months data from our thalassemia patient, first patient in the EDITHAL thalassemia study. And that patient, again, showed a trajectory of fetal hemoglobin progression or increase that was very comparable to that we were seeing in our sickle cell patients. So we're overseeing kind of consistent trajectory of fetal hemoglobin production.
Yanan Zhu
Got it. I was wondering since the presentation of those data, has there been increased interest for participation for these two studies?
Gilmore O'Neill
I'm very happy to say yes. And Baisong has had that sort of personal interaction with patients and physicians.
Baisong Mei
Absolutely. We have a lot of interaction. I mean, we'll focus on the patient community side. We have significant several fold increase of the phone calls and emails from patient and patient community inquiries about the RUBY study after the data release. And actually the trends continues over the last several months since June.
Yanan Zhu
Great. That's great to hear. Thank you. I think as we think about going forward, lovo-cel, exa-cel might get approval in the near term. How do you think those treatment centers might allocate patients to commercial versus clinical trial patients?
Gilmore O'Neill
Well, we're actually very confident that we will continue to enroll patients for a number of reasons. Baisong has himself traveled to many sites, interact with many investigators, and has a much more personal insight into how they're feeling about that.
Baisong Mei
Yeah. I have been traveled many sites over the last several months. I continue to do that actually just at the end of last month. I had within the site also. And they're very enthusiastic to participate in the trial. And with the momentum we have and we are very confident about our enrollment and we do not feel any impact for this commercial or potential commercial for both study.
Yanan Zhu
Okay. Great. Great. Thanks for the color. At the year-end 2023 data update, how many patients do you think we could see? And in terms of fetal hemoglobin, could we see -- expect -- could we expect that fetal hemoglobin levels in the additional patients to be in line with the levels reported previous -- in previous patients?
Baisong Mei
Sure. Yeah. So, we really feel confident that the -- with the four patients we see [technical difficulty] with the data we see released in the last June, the past June that we are confident that the future patients will have a similar trajectory for the total hemoglobin and the fetal hemoglobin wise. That is based on not only the clinical data, but almost also the consistency between the clinical observation and our preclinical data.
As we probably discussed -- as we discussed before, we have a rational design to choose approach of in targeting the HBG12 promoter region rather than BCL11A, and then also using the AsCas12a as an enzyme to do that with the preclinical data had comparison. So now the clinical data actually validated our clinical findings.
Gilmore O'Neill
In indeed, Baisong and I come from R&D background and we're hardcore empiricists. What has made us feel very good about our data, as Baisong says, is not just the consistency that we saw in the trajectories followed by those first four patients that we presented, but indeed in the webinar and it's on our website, we actually also shared drug product editing data for the first four RUBY patients, plus an additional five RUBY patients who yet to be dosed at that time. And for the first EDITHAL patient and additional two. So, in all 12 patients drug product, obviously the drug product is individualized for each patient. And what was really striking in addition to the consistency of the data we saw on the clinical side, we saw a consistent level of editing, high level editing, roughly between 80% to 90% consistent levels across the edited drug product. All of those things come together and give us a conference notwithstanding that statement about being in empiricists, that we are actually going to continue to see that consistent replication of data by the end of the year into the future.
Yanan Zhu
Got it. So the replication also apply to the height or normalize the total hemoglobin?
Gilmore O'Neill
Well, we actually believe so. As Baisong said, when you actually line up that consistency in trajectories in the clinic, you line up that consistency of editing in the drug product. And then you look at the deliberate design and selections or choices we made using AsCas12a in a high efficiency enzyme to target the gamma globin promoter, that we actually expect or anticipate seeing that consistency continue.
Yanan Zhu
Great. Great. Great to hear. Thank you. Do you plan to report additional efficacy measures beyond fetal hemoglobin, such as hemolytic markers at the year-end data readout?
Gilmore O'Neill
Well, what we're actually planning to do is we -- we'll actually talk more about what we will be sharing the number of patients of data we'll have later, but at a time sooner and closer to the actual disclosure of those data.
Yanan Zhu
Got it. Got it. Do you still continue -- do you continue to think that total hemoglobin normalization is a differentiation from CRISPR's exa-cel I guess, through your continuous dialogue with investigators in the field? Yeah. I think, that's…
Gilmore O'Neill
Well, let me start, and then Baisong who has been speaking a lot to investigators, but we do actually see the normalization or correction of anemia as a potential differentiator. It was a deliberate part of the design. We selected the gamma globin promoter as our target rather than the BC -- the erythroid B78 for the very simple reason that we believed. And then our nonclinical data showed that you got better red cell output, red cell health and red cell longevity, all pointing towards a correction of anemia. And obviously anemia itself is an independent risk factor for end organ damage. Those two things tied together, really would suggest that this will have a meaningful effect on the physiological parameters for end organs, including cardio, respiratory, et cetera.
And then Baisong can tell you about how investors are thinking about it, and also more -- maybe a little better how we're thinking about our clinical trial and collecting additional data.
Baisong Mei
Yeah. Certainly, Gilmore. I think -- maybe I can back up a little bit for treatment in rare disease and devastating disease perspective. And Gilmore and I work on many -- several different rare disease in -- before life. When you get into the new disease area, which have less treatment options and no cure options in there, you focus on most important symptom in this case, for example, sickle cell, you're talking about vaso-occlusive events, but sickle cell clinical manifestation is much more beyond vaso-occlusive events, right? They have an organ damage, the anemia, fatigue and pain and all those in there too. So I think exa-cel have demonstrated excellent data to be able to actually manage the VOE patient symptom wise.
Then we're thinking about to say, can EDIT-301 do more than that, right? In addition to VOE, can we correct the anemia, and as Gilmore mentioned, anemia is actually important that factor for an organ damage among other symptoms in there too. So that's kind of direction we're looking to. We hope that in the community together keep improving the standard-of-care for those patient population. So I think that's a direction we're trying to go.
Gilmore O'Neill
As sort a very high level, patients visually complain about fatigue. It's a dominant symptom when you ask patients about what they suffer from day to day with a sickle cell disease. And drivers of fatigue include pain, but actually also anemia. In fact, anemia is a classical etiology for fatigue. And actually also can limit exercise tolerance and the activities of daily living. And the good news is that within our clinical program, we are collecting patient reported outcomes, which include domains that focus on these things.
Baisong Mei
Yeah. Just kind of add on that as also we have interaction with investigators and KOLs. They're also very pleased to see the correction of anemia with our patients. And so they have experience with other therapy people before, and they feel that it's really good that we see the correction of anemia for those patients.
Gilmore O'Neill
And I think that's an important piece of what I think you asked myself and Baisong about how investigators are thinking now when they actually see, this potentially differentiated hematologic parameter and what the downstream effect will be and impact will be on patients.
Yanan Zhu
Got it. Very helpful. For the year-end data, what might be the forum? Would do you be targeting ASH or?
Gilmore O'Neill
So we've kept our options open, and we'll share -- that more detail closer to the time. For EHA -- we presented both at EHA and a webinar. In last December we did a webinar. We'll make sure that people are notified in adequate time so that everyone actually can see the data. But we're really excited looking forward to showing those data.
Yanan Zhu
Great. Great. Maybe a curious question here about a definition of severe VOC. There is a little bit of a controversy when Azzur put out its report comparing lovo-cel, exa-cel and said the criteria is a little different. When is more lenient, the other is more stringent, or at least the company's claim as such. So I was wondering, what's your take on that and what's your -- the stringency of your severe VOC definition?
Gilmore O'Neill
So this is something that Baisong and I have lived through our earlier careers in defining outcome measures and so on. And we've talked a lot about this, but Baisong you have some insights to share.
Baisong Mei
Yeah. Yeah. I mean, when I look into our definition of VOE as well as lovo-cel and exa-cel, I think they're very consistent in general that one is clinical symptom and one is required medical attention. So that's kind of the generally consistent there. There's still -- you can see between lovo-cel, exa-cel, there's slightly difference in there. And so I think that's just generally consistent.
And with we -- what we have is that also require clinical, severe clinical symptom and medical attention. And we have -- when we develop our protocol, we have a lot of engagement with our investigators who have been in multiple different trials before as well as KOLs. So we're very comfortable with our definition on that too. So, I mean, that's very important for this definition, because you're going to use that definition as your exclusion criteria, right? Then you'll use the definition for your primary endpoint in this case. So I think that's -- certainly, I can see that attention to these, but I think it's generally consistent.
Gilmore O'Neill
Yeah. So we see a general consistency across, and then as long as there's a consistency within a protocol about what the definitions before and the definition is after, that really minimizes or say takes away any risk to the integrity of the study or the interpretability of the data. And we believe with the broadly shared commonalities of or overlaps with those definitions, it will still enable physicians, patients, not really payers to actually understand the impact of therapies.
I think another important point which is really important to take is that the patients that we're enrolling our studies are very severely affected by their disease. Indeed, we require a minimum of two events per year in the two years prior. Our patients more than they see that. So these are patients who are manifestly visibly profoundly impacted by their disease, and you match that against the large impact. I mean, the super impact of these potent therapies, there really is not going to be any difficulty in actually seeing the benefit that we can give to these patients with these therapies.
Yanan Zhu
Got it. I was wondering also, are you still on track to engage the FDA on the sickle cell program in second half of, or in the remainder of this year? What would be your focus for the meeting and when might we hear about the outcome of the meeting?
Gilmore O'Neill
We are definitely on track as, you know, a sort of, I should say, a fundamental rule that we have is that we say we're going to do something, we're going to make sure we do it. And that's been true for a number of things. And this is one of them.
And Baisong, you have obviously some.
Baisong Mei
Yeah. We absolutely on track on that. And so we -- from clinical perspective there, we are thinking about get alignment with the FDA with the registrational package and study design and everything too. So we are very much on -- this will be our topic in the two. And we are also very interesting to see the ADCOM information coming from exa-cel and we will -- which will also give us more information on that end too.
Gilmore O'Neill
So overall, we -- this is an important half of the year for us with our own individualized interactions with the agency, but actually also I think it's going to be a very valuable experience for all of us to actually see the ADCOM on October 31st for exa-cel.
Yanan Zhu
Yeah. I was going to ask you what might be focusing on at the ADCOM and how that inform your development strategy.
Gilmore O'Neill
So I think there'll be two focuses. If you like broad categories, obviously this is the first time a therapeutic using CRISPR technology is being approved, which by the way, it's worth pointing out. That's 10 years, within 10 years the publication of the original idea, which is a phenomenal timeline from a new technological idea to approval, almost unprecedented. And so we learn a lot about the FDA's views around, and indeed the expert's view around the benefits and the risks of CRISPR based editing.
And then in the context of the disease sickle cell itself, will I get a very good sense of how people are thinking about risk benefit, both from the FDA briefing and from the experts on the committee. And then we'd be very interested in the specifics, particularly around outlier analyses, the impact on total hemoglobin and any -- what are the adverse event experience and risk benefit calculus that the sponsor FDA and ADCOM are thinking about.
Baisong Mei
Yeah. Just to add on that, this is like -- the impact from our view is actually beyond sickle cell itself, right? It's actually first time that we use the CRISPR editing technology that we are in the new era to actually change the chromosome of human, human cells to be able to cure the disease. So we're looking forward to that. And also very much to see that, in general, the regulatory environment is encouraging innovation too. So we're excited about that.
Yanan Zhu
Got it. Very helpful. And could you comment on whether you are planning on requesting RMAT [ph] or BTD designation for 301?
Baisong Mei
Yeah. So we are certainly considered multiple options on the different designation, regulatory designation. For example, we have often direct destination for both. We have a pediatric rare disease vaccination for both RUBY and EDIT-302. We're certainly looking for other destinations, and we will share the information when we have that update.
Gilmore O'Neill
We embrace the potential use of all the mechanisms that the FDA has made available to enable us to advance this product.
Yanan Zhu
Got it.
Gilmore O'Neill
As effectively as possible. Sorry.
Yanan Zhu
Got it. Got it. Any thinking or update on the X-US regulatory front?
Gilmore O'Neill
So the way we're thinking about it is that, what I would say is if you were to describe the strategy we presented rolled out last January is one of simplicity and focus. And we're a small company and we want to be sure that we focus our attention resources mindshare as effectively as possible. So we are focusing on sort of North America. We are applying and running our clinical trials in North America.
We have said before that a partner certainly is a significant potential upside for us in that they would enable us as long as the partner has and partner would kind of look for, would want, would have a large footprint, would enable us to expand the availability through development commercialization of 301 beyond the coastline of North America.
Yanan Zhu
Right. Right. Right. That leads into perfectly the next question. Any partner interest on the program? And from your perspective, what is the right time and what is the right structure?
Gilmore O'Neill
Yeah. So the way we look at partnerships are that -- we see that certainly as a potential upside for us as a company and also for patients around the world who are waiting for something as exciting as EDIT-301 to treat their hemoglobinopathies. The type of partner and the timing really, as I said, really we want a large partner with a big footprint that can actually develop and commercialize beyond North America.
With regard to timing, the timing is actually -- there is a rather large window. Obviously, it really is going to come down to the perfect convergence of comfort with our data. One of the things that's really evolved over the last year, beyond just our generating clinical data, showing potential differentiation, but actually also more clarity around where we can see BLA on the horizon. As Baisong has said we are on target to have dosed 20 patients by the end of the year. That is a meaningful clinical that could lead to a meaningful clinical efficacy data set. If you look at the efficacy cohort that has been accepted by regulators on both sides of the Atlantic, we're looking at efficacy data set of about 17 patients with approximately 15 to 18 months of follow-up data. So you can actually see that that horizon is there. So we have all those elements, and then obviously the perfect balancing of the commercialization plans, et cetera. So we see a window. I think it's a broad window, and I think ultimately the terms we'd be interested in and the kind of structure would really come down to one that's going to optimize the availability, the access, the commercial journey for patients around the world.
Yanan Zhu
Got it. Has there -- have been any initial interest or interactions?
Gilmore O'Neill
Well, we have had -- obviously, there was always some interest in our programs. Our programs have generated interest, really are quite broadly over the last year or so, particularly as we're moving it forward. But we would only talk about any specifics if and when we would actually have a deal partner.
Yanan Zhu
Got it. Got it. Let's talk about the CRISPR patent interference case. Can you review the next steps for this interference case? Have oral presentation been scheduled yet? What is the next milestone that we should be watching for and when is the CAFC decision expected?
Gilmore O'Neill
So there's a lot to unpack there. So let me start at a high level and first of, I'll say that we are exclusive licensers for the Cas9 and Cas12 IP from Broad Harvard MIT. The Cas12 is the enzyme that we are using and focusing on internally for our pipeline. Cas9, we don't have programs in Cas9 in our development or our pipeline. But that IP would be required for others using Cas9 technology for human therapeutics.
With regard to interference, some of that IP, not all of that IP is subject to interference. There is other IP that is also needed that is not subject to interference. I proposed the interference. We have already had three reviews, two by PTAB, one by the appeals court. The last appeal is now going through or working its way through the appeals court, the federal circuit. And oral hearings have not yet been, or oral presentations have not yet been scheduled. But notwithstanding that we would anticipate that the resolution will occur in early to mid to 2024. And finally, we have prevailed in the last three. And we're optimistic and confident -- indeed confident that we will prevail again.
Yanan Zhu
Got it. If the CAFC decision is indeed favorable, what are your plans in terms of licensing and economics? Would the potential economics be different for a sickle cell related license versus a non-sickle cell license given that you are competing directly in a sickle cell space?
Gilmore O'Neill
Well, let me just clarify one thing about the impact on interference on doing deals. The key thing, first of all, is we are the patent holders. We have prevailed in every interference decision to date and therefore are in a position to license. And indeed, we are licensing. In fact, you would see one of those deals was announced just a couple of weeks ago. WAR had taken a license for their portfolio. So we are continuing to do licenses.
With regard to the actual details of licenses, we would only disclose those once, if and when we have actually finalized those and would be obviously we'll talk about them then.
Yanan Zhu
Great. Perhaps just to talk -- to cover the base for TDT and EDITHAL study. So I was wondering, I think you said you plan to provide a clinical update to that program by year-end 2023. I'm wondering, does that mean clinical data and if so, roughly how many patients can we expect? And what would be the benchmark for total hemoglobin for your program? Do you also expect a higher total hemoglobin compared with competitor programs?
Gilmore O'Neill
Well, let me address that second part and then I'll ask Baisong to talk about what we're going to update. But with regard to our expectations, we presented the first patient from our -- our first thalassemia patient for EDITHAL study in June. Now we just showed a month and a half of follow-up data and that patient's hematologic data really followed a very favorable trajectory and was very -- absolutely consistent what we were seeing with our sickle cell patients. That gives us a lot of confidence, that we will see a very meaningful impact from our therapeutic. And we look forward to sharing that at the end of the year.
With regard to what we are going to share at the end of the year Baisong might want to give a…
Baisong Mei
Yeah. Yeah. So, we share one patient data in June for EDITHAL. Certainly we have more patient dosed so that -- and year-end, we're going to have a longer follow up for this first patient and additional data for the additional patients in there too. We should be similar for the RUBY study too. We'll have like longer follow up for patients we have done before -- release before them additional patient dose in there too. So we're going to have the package in there. And certainly that when we have even 45 days of data in -- one and a half months data in for EDITHAL that we already see significant increase of the fetal globin level, right? So in the beta cell, they all actually -- they don't have sickle globin. They are all in the fetal globin level. So we're very pleased to see the data about the first patient.
Yanan Zhu
Got it. Got it. And is -- do you expect the gamma globin targeted approach, could it produce higher fetal hemoglobin in TDT patients compared with the BCL11A?
Gilmore O'Neill
That in fact was -- indeed was the attempt or the intent of the original design, which was to generate a robust, very durable fetal expression, but actually also increase red cell production because in the end, hemoglobin rather red cell is -- the hemoglobin has to be packaged in red cell. So the overall intent of design, which was universal across sickle cell and thalassemia, was to have a robust red blood cell output with the associated robust fetal hemoglobin output. So what that means is that our intent is to have a very robust total hemoglobin response, which will be driven by fetal hemoglobin as Baisong quite correctly says. And as I say, with the consistency of the data that we saw with that first patient, our nonclinical data and then the consistency of the editing of the drug product, again, we feel that we are going to see a very robust hemoglobin response.
Yanan Zhu
Got it. Maybe -- let's talk about additional pipeline effort. I think one of the efforts you have touched on is milder conditioning or in vivo therapy for sickle cell. That -- obviously that -- that's a very exciting area and leading to even greater opportunity than what's already been a very big opportunity for the bone marrow transplant mediated therapy. From your vantage point, are there -- you have internal effort, but I believe you also mentioned you're also looking at the development of the field, right? What's your sense of what might be the next breakthrough, or what's the most interesting technology internally or out there and could -- the breakthrough actually come from -- just go right into in vivo editing without needing a milder conditioning in transition?
Gilmore O'Neill
Well, let me start at the end, and say that really what we're all trying to do ultimately is continue to expand the population that can actually use a frankly curative, and I do that with air quotes, but a curative therapeutic, which is going to eliminate with a single treatment symptoms and the complications of two really dreadful diseases. The very first thing we're all doing, essentially already expanding a patient population that can use the drug by moving beyond allogeneic. So if you actually think about the severe, the prevalent patient population, just the United States, just to keep it simple, estimates from various analysts and companies go between 20 to 30 plus thousand patients who are suffering from the disease and waiting therapy who would be eligible for a transplant in that the benefit risk would be positive for them. Of those, about 10%, 15% can find a well adequately matched donor, which basically means that our therapeutic will already -- these therapeutics already with the limitations of use cell fan and the rigors it creates already expands that patient population tenfold to really address the needs of most of that 22,000 to 35,000 patients. So that's already a big step.
If you look at in vivo -- in many ways in vivo is a wonderful way to eliminate the burden on patient from the point of view apheresis and transplantation, it actually also reduces the burden on the healthcare systems where you don't have to worry about capacity build for your transplant centers and the huge use of personnel and resources to bring these patients through sort of that sort of so-called vein to vein time from identification, initiation of apheresis, manufacturing, editing and transplantation and support post transplantation.
So then if you actually go and say, well, how can we further expand? So in vivo kind of really is the ultimate expansion. And I think it's something that we've already started. We have some early work. What I do want to call out, just in passing and I'll return to it, is that we're delighted. We were delighted to announce nearly five weeks ago that our -- Linda Burkly had joined us as our Chief Scientific Officer, and she comes aboard as a critical catalyst to our in vivo work, one part of which we've already highlighted with our work on HSC in vivo editing, with a validated enzyme in humans and a validated target in humans.
With regard to milder conditioning, there have been a number of approaches. What is interesting is that we're really using an approach that was developed decades ago. I think the space is interesting. It has been challenging because you're always dealing with the tension of adequate conditioning, trying to make -- minimize the impacts and the adverse effects while ensuring that you adequately condition and create spaces or niches in the bone marrow for the infused drug product to actually colonize and mature and proliferate in. So there are a number of approaches. We have looked across the landscape, and we actually believe that many of the evolutions in that space CT1 17, for example, is one approach, would have a generalized impact across the field, because when a transplant center embraces a mild reconditioning regime, it's going to generalize its use across indication. So that's really how we think about it right now.
Yanan Zhu
Got it. Very helpful. Thank you. Lastly, I was wondering if you can talk about your cash runway and what major value creation catalyst could have been, or will have been achieved by the end of that cash runway?
Gilmore O'Neill
So, our cash runway extends into Q3 of 2025, and that is a combination of the simplification and focus of our strategy, and a successful raise just last June on the head of 301 data. From a base case point of view, our future catalysts, we look forward to, are sharing the 301 data moving forward. As I said, an efficacy, we will have dosed 20 patients by the end of the year, which really suggests an efficacy cohort that at 18 months follow-up could be a meaningful cohort in mid 2025. And if you actually line up that with our cash runway to 2025, some critical base case catalyst events around our 301 data, that makes us actually feel very good about that. In addition to this potential upside, a partnership around 301 and obviously, a recognition and realization of some of the value in our IP.
End of Q&A
Yanan Zhu
Got it. Thank you so much. I think that concludes the session. Thanks Gilmore. Thanks Baisong.
Gilmore O'Neill
Thank you so much Yanan. Lovely to talk to you.
Yanan Zhu
Thank you very much.
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Editas Medicine, Inc. (EDIT) Presents at Wells Fargo Securities Healthcare Conference Call Transcript