Editas Medicine, Inc. (NASDAQ:EDIT) 2022 Wells Fargo Healthcare Conference September 7, 2022 1:55 PM ET
Company Participants
Gilmore O’Neill – Chief Executive Officer
Mark Shearman – Chief Scientific Officer
Conference Call Participants
Yanan Zhu – Wells Fargo Securities
Yanan Zhu
Hi, everyone. Thanks for joining us. We are very fortunate to have the team from Editas Medicine with us here for a fireside chat. My name is Yanan Zhu. And with me here are the CEO of Editas Medicine, Gilmore O’Neill, as well as the Chief Scientific Officer, Mark Shearman. So, Gilmore and Mark, thank you for being with us today.
Gilmore O’Neill
Thank you. Thank you for having us.
Question-and-Answer Session
Q – Yanan Zhu
So, Gilmore, you joined the company in June. And what is your initial observation — and looking forward, where do you — where would you like to take the company from a strategic level?
Gilmore O’Neill
Well, my initial observations really started during my diligence before joining the organization and I was really drawn towards the incredible potential of the technology in general. And then specifically, was drawn to Editas, because of the advancements made in the technology, characterized by amongst other things, it’s AsCas12a CRISPR enzyme, which has done a lot of work in optimizing and developing.
But in addition, the capabilities that exist including a super core expertise around guide RNA chemistry and design. It’s computational bioinformatics CMC, where the investment of time and people has been substantial with a huge effort on quality and analytics, which I think has actually been reflected in our ability to bring both in-vivo program into the clinic as well as in ex-vivo. We can talk more about that later, if you wish.
My observation since I’ve arrived, really confirmed those preliminary diligence questions or observations as well as also confirming sort of the challenges and opportunities. And one major challenge and huge opportunity is around clinical execution and I think that’s something that we have actually lent in hard.
One of the first things I did was recruit a new Chief Medical Officer, Baisong Mei, who has actually hit the ground running since joining in July, just six weeks after I joined. And he brings a depth of experience in rare disease drug development. But very importantly, not just in development, but actually bringing across the finishing line, global approvals and all the other elements that are required on the R&D side to support commercialization.
And that’s important because looking forward for the company, the company, thanks to the efforts of Mark, other members of the executive team, and my predecessor, Jim Mullen really positions the company to make that next step in transformation from being a platform technology company to a fully integrated commercial therapeutics organization.
And beyond that, the vision, obviously, for something as powerful as CRISPR gene editing or genomic editing more generally is to use that technology really transform the phase of medicine.
That will require certain steps. It will require additional investments in our — continuing to improve our technology as well as looking beyond our current programs. So, I can tell you more about that, but I’ll pause and give you a chance to take a breath or ask me a different question.
Yanan Zhu
Right. Yeah, yeah. Thanks for that. That give us insight look into the — how the company is progressing and give us an outlook for where you envision the company to be in the future.
So, the company does in-vivo editing as well as ex-vivo editing. I was wondering, if we could start with maybe talking about the ex-vivo program, EDIT-301 for sickle cell disease. An obvious question is compared with some of the other gene editing programs that might be more advanced in the clinic, what is the differentiation of EDIT-301, and how will these advantages manifest in a clinical setting?
Gilmore O’Neill
Well, ultimately, that differentiation is going to be very important for patients and their clinical outcomes. And obviously, what we’re targeting is not just the simple control of — in the context of sickle cell anemia, the control of vascular cuisine [ph] events, but all the other complications as well as the adverse elements of quality of life and long-term organ health.
So where we see ourselves as differentiated is in essentially driving towards a more robust hemoglobin expression and more durable fetal hemoglobin expression. And that will actually in the long-term transmute within the patient into clinical-related outcome such as improved quality of life and organ health.
So why should that be? And why do we think that we will differentiate that way as opposed to other programs? Two reasons. One is that we’re using AsCas12a, as our editing enzyme, which is in contrast to every other approach, which uses the Cas9 technology. And that AsCas12a enzyme, as I think I already said, is a high fidelity, highly efficient CRISPR nuclease.
Why does that matter? That increased efficiency, we believe, will in itself transmit or transmute into a more robust expression and higher efficiency EDITs and in addition, the high fidelity will actually reduce and certainly in our hands and Mark will expand on that is really associated with no detectable off-target EDITs.
The second element that supports our differentiation is the deliberate targeting of the BCL11A pressor binding site in the promoter of the gamma globin genes, which are HPG 1 and 2. And why does that matter? Because that element is, it drives expression of fetal hemoglobin independently of stress erythropoiesis. And in addition, is associated with more robust erythroid health. We know this based on empiric experiments that we’ve actually carried out internally, and I think we presented at previous meetings in 2018,as well as supported by independent literature from other laboratories. Mark, I don’t know if you want to add or expand on that?
Mark Shearman
I was going to add a little to the customer base. So the corollary nucleated the guide RNA. And in this particular case, it’s a 41 month and I think it has two advantages: one in terms of the synthetic RNA chemistry and our ability to synthesize our high-yield, high-fidelity guide, which will be important in directing to the sequence of going to EDIT. And secondly, when we make these choices, we can screen a lot of different guides. And so augmenting silico prediction about the on-target and off-target editing, we can also test hundreds of guides to pick the one that’s most suitable for the purpose. So I think that, combined with the intrinsic benefits of the AsCas12a gives you a nuclease that is eventually most efficient plus the EDIT that you want.
Yanan Zhu
Got it. That’s very helpful. Thank you. So what is the current status of the RUBY program? I think you announced that the first patient had finished not only dosing, but actually engrafted. So have you dosed the second patient yet? And what is the cadence for the subsequent dosing?
Gilmore O’Neill
Yes. Thanks for actually calling out the RUBY study, which is for sickle cell anemia. I did like to talk about thalassemia, but it’s worth pointing out that many of the elements that I’ve described for differentiation apply to thalassemia as well.
We are using the EDIT-301 program or product to investigate as potential therapies for both sickle cell as well as thalassemia. The thalassemia study is Editas and we are planning to dose the patient in the Editas study before the engineer returning to RUBY.
Yes, we’ve had one patient dosed and engrafted. We have multiple patients who have actually had hypothesis perform and whose cells have been edited and are actually frozen and ready for infusion.
The second patient, we have been released by the Independent Data Monitoring Committee, which has carried out a safety evaluation following engrafted with the first patient to allow us to schedule the second patient, and we anticipate dosing that patient soon. And what we would hope to have by the end of your plan — have by the end of the year are data from our first patient potentially from our second patient, if the follow-up is long enough to be meaningful, as well as hopefully a patient dosed or Editas.
Just with regard to the RUBY study and the cadence, excuse me. Thank you. Forgive me. The Independent Data Monitoring Committee essentially meets on two occasions with regard to Central. So we essentially have two sentinel patients in the RUBY protocol.
We’ve had one dose engrafted and the IDMC has met. The second patient when engrafted will trigger another IDMC meeting. Once that IDMC has met and given us the all clear then we have essentially no limit or time limit or time restrictions between dosing of subsequent patients. And so we may be able to and should be able to put protocol to enroll in parallel.
But as I say, in the meantime, we have already freezed multiple patients, edited their cells, having stored, ready for initiation of infusions. We have multiple sites activated around United States versus North America and are continuing to engage with those sites, activate other sites and identify patients for subsequent enrollment in our protocol.
Mark Shearman
Yeah. And I think just to add an important aspect of this cadence was that the FDA also removed the partial clinical hold that was in place as a consequence of us submitting a very detailed package delineating the potency assay matrix that we would use. What that means practically is that the patient data that we now accumulate can be used in a future filing, and so all of that efficacy data will now be included in that.
Yanan Zhu
Right. Got it. Yeah, yeah. Thanks and congrats on that progress. So it sounds like the enrollment in the RUBY study could really accelerate once the second patient engraft and — at the — reviewing the data?
Mark Shearman
So that’s what we’re targeting. This is why we have doubled down on clinical execution. This is why we have our new Chief Medical Officer, with his expertise and experience in the rare hematology space, all of that to help drive that momentum.
Yanan Zhu
Yeah. Right, right. So I think you have committed to sharing data from RUBY by year-end. Is that — are you targeting a scientific meeting or is that a company release? And I think you mentioned the scope, maybe one patient definitely maybe the second patient as well, if the follow-up is long enough. But can we talk about endpoints like what are the focus for HBF? What’s like your target?
Gilmore O’Neill
Yes. So, we stand committed to the original guidance. We will be sharing data at the end of the year. As I said, it will be at least one patient, possibly two. We will be sharing safety engraftment data. We’ll be sharing hematologic parameters, including GT, total hemoglobin, fractionated hemoglobin, specifically fetal hemoglobin F-cells and all of those parameters, probably five months of data, so follow-up for that first patient. So, we would not plan to share clinical data, because calculating those events with less than year follow-up would be inappropriate. And then specifically what the success look like?
Well, we are looking for success to seeing fetal hemoglobin, total hemoglobin levels that would result in clinically meaningful outcomes for patients. And obviously, the history of driven by that natural experiment of inherited or familial persistence of fetal hemoglobin gives us a good range as well as the hydroxyurea therapeutic. So the range is anything from 20% and higher for fetal hemoglobin, and that’s what we’re looking for, so if you.
Yanan Zhu
Yes. Got it. And in relationship to competition because there is a more advanced program, is it fair to say that the bar, instead of 20% should be closer to what the competition has done or is there a different way to think about this?
Gilmore O’Neill
Well, I think one can always think in terms of simple comparisons, I think in the end, the use of therapeutics, particularly complex novel therapeutics in serious diseases requires a very balanced approach, looking at the totality of the data, where you actually understand the full benefit risk. Notwithstanding that or maybe because of that, I believe that we are competitively differentiated for all the reasons I outlined, both from a safety point of view with our fidelity and from an efficacy point of view with the efficiency of our editing as well as the targeting of the gamma-globin promoters. And the totality of that, I think push us in a very good position to be not just competitive, but competitively and really significantly differentiated from a clinical point of view.
I think the other point I’d just like to make, because you sort of said we’re behind is that in addition to that differentiation, I think we strongly believe and not just based on some kind of internal dogma or zealotry [ph], but based on an observation on the field in the last five to 10 years of launches of complex therapies, particularly in that sort of curative — under that curative rubric is that the ramp time for launch is actually quite low from a slope.
I think we all hoped 10 years ago that it would be asymptotic. I think the reality has been much less deep. And so, we believe that the vast majority of the prevalent population in the United States will still be awaiting therapy by the time we bring EDIT-301 to market. And when we bring what we believe will be a competitively and clinically meaningfully differentiated product.
Yanan Zhu
Got it. Got it. And in terms of the functional data, VOC data that you mentioned like without a 12-month follow-up, it wouldn’t be very informative to look at the data. When can we expect that kind of data next year then?
Gilmore O’Neill
Well, we are planning — the way that the study is designed; it is an open-label single-arm study. So that gives us the ability to look at and reveal data over the future time. And obviously, next year, we haven’t actually determined the optimal timing for that, but we will be working to that and talk about that in the coming months.
Yanan Zhu
Got it. And I think in the past, the company has mentioned, you’re looking for partnership for the EDIT-301 program that maybe before you took over. Any update on that kind of a strategy and any activities that’s ongoing?
Gilmore O’Neill
Yes. So, I certainly stand by that. I agree with that, as I say, that guidance. We see distinct upside in finding a partner for 301. I have to say that our plan is to bring 301 all the way to approval. The upside for 301 certainly exists where we find a partner.
Our preliminary desire is to look for a partner with commercial rights ex-US. That may include some development rights and responsibilities, but we’re certainly open to looking at even a shared commercialization within the United States, so that we are — have the flexibility to deploy capital in a way that allows us to fully unlock the potential of our technology and our platform.
So, I think, the key elements there or the key message there is that, we see this as an upside. Yes, from the point of view of ongoing activities, we’re not going to really discuss or share things until we’ve actually really come to and closed an agreement with that partner.
Yanan Zhu
Got it. Yes. Thanks for all the color there. I think in the remainder of the time, maybe we should switch gears to EDIT-101 for LCA10, which is your obviously in vivo editing program. So you have the BRILLIANCE study ongoing. Can you talk about the status of the various adult and pediatric cohorts that are ongoing in the study?
Gilmore O’Neill
Yes. So, first, couple of things, just by preamble, if you don’t mind. First, EDIT-101 is our first in vivo human clinical trial. It was the retinal disorders or retinal dystrophies, I should say, inherited retinal dystrophies were chosen as a first tissue compartment for in vivo human proof of concept, because of the nature of the eye.
The fact that it’s immunologically privileged, which allows re-dosing in the second eye down the line. And also, the fact that with that restricted tissue space, it allowed us to really understand and control risk in the context of a very new technology being given to humans in vivo. And I think BRILLIANCE has delivered on that from the point of view of defining the safety.
In addition, BRILLIANCE is also designed to do a few other things, which are maybe not standard in the ocular space, when you think as many people do in ocular space about diabetes or AMD, where the pathway is well defined, the disease is well characterized clinically and interventional studies have been performed multiple times with multiple approvals.
BRILLIANCE does not have that luxury. LCA10 is an ultra-rare disease with no therapeutic experience or regulatory path with clear precedent or approvals. And so, BRILLIANCE is designed, amongst other things, to define or identify a segment of the patient population most likely to have a clinically meaningful response to the therapy, and I’ll return to that in a minute. It is also designed to identify clinical endpoints or other outcome measures that are likely to predict a clinically meaningful response for these patients, who it is worth reminding everyone essentially have profound visual impairment by the time they’re two or three years old, rendering sort of the standard ETDRS eye chart that actually, as I look around most of us in this room would have used it some time to get a prescription for our glasses. They’re not able to see those. They have to use much cruder high-contrast visual acuity measures.
But in addition, we are looking at endpoint measures that include other measures of function, which include the Visual Function Navigation course akin to the multi-luminance maze-test used by LUXTURNA in its pivotal program and approval as well as other psychophysical including FST, full-field sensitivity or retinal sensitivity, structural measures like OCT and patient-reported outcomes.
And so we identify a patient segment, we identify clinical endpoints most likely to determine the efficacy and then ultimately, we look at the totality of the data and the safety. What we will have for patients to analyze, we will have four mid-dose cohort adult patients with 12-month data, four high-dose adult patients with six-month ,data and we will have the totality of the exposure, including two pediatric patients for safety.
The — you asked me about the status of enrollment. So, the adult cohorts are fully enrolled. We do have the capacity to expand as required in those adult cohort. The mid-dose pediatric patient cohort has recruited two out of four patients, a little slower they wanted. But we are actually evaluating — actually, we’ve actually looked at that and actually found ways to improve our approach to identifying patients and we’ll actually give further guidance on that in the future.
But more importantly, two out of those patients have been dosed, we have scheduled an Independent Data Monitoring Committee, which will occur later this month. And once they actually give the all clear or they permit us, and then we’ve been able to start enrollment in the high-dose cohort.
Yanan Zhu
Got it. And you touched upon the scope of the data a little bit in terms of patients and their follow-up, would that — in terms of the timing because its guided at the second half, any additional granularity?
Gilmore O’Neill
Yes, sorry, I left that out. So, we will be — we are targeting October-November timeframe. And with regard to the venue, I didn’t answer that question, I think, for — was that we are looking to — it will probably be a webinar or a sponsored presentation, we don’t see a scientific meeting in which we will present in that timeframe.
Yanan Zhu
Got it. Got it. That’s very helpful. And then let’s talk about the efficacy endpoints that will be read out because we have some sense from your prior data. So, could you — would it be the same endpoints, anything that could be additional and how do we interpret the data?
Gilmore O’Neill
Yes. So, let me reemphasize the importance of looking across the totality. There’s a complex interaction because — within the elements of the study, not just with the segmentation of the patient population where we will be looking at baseline characteristics structural, such as OCT, functional or psychos — physicals such as FFT, other parameters like OCI or ocular stability, pupillometry, et cetera. We will — from a baseline point of view. Then, from an efficacy point of view, we will be looking at similar end points, the visual function navigation course, BCVA, FFT, ocular coherence tomography structure. We will also be looking at patient-reported outcomes, which we have not actually shared before. And — sorry.
Mark Shearman
Maybe — yes, thanks. But first stage of release in September of last year, we’ve also completed a natural history study, and that’s allowed us to get insights into performance of the LCA10 patients against the outcome measures and in some cases, their ability to improve upon that baseline status apart that helps also to form the choice and the reporting back of the endpoints, and we have better visibility into the test-retest reliability of the different measures and whether we can exceed that with the treatment treated to us.
Yanan Zhu
The natural history study’s data will be shared at the time of your next update for BRILLIANCE?
Gilmore O’Neill
We will be looking at the interventional data in the context of the natural history data. I think it’s worth pointing out that, that natural history data actually increases the number of patients that we can look at, and I think will increase the robustness of the analysis that being carried out in determining if we have not just proof-of-concept, we believe we achieved already, but proof-of-product and a path — what the path forward would be to a regulatory approval, where we would actually use the data to select the patient segment as well as the outcome measures that we would bring to regulatory authorities, including the FDA to negotiate the design of a final pivotal study.
Mark Shearman
And there were some patients in natural history study that made into the interventional study. So essentially, we have a one-year baseline for those patients already, which helps with the interpretation of the treatment, right?
Yanan Zhu
Got it. Very interesting, very much looking forward to see the — it sounds like a very rich data set. Any read-through from this readout to your other ocular programs?
Gilmore O’Neill
So, I think the key read-through will be that we are using AV Cas9, and that is actually probably the first time that has been used in humans. The read-through would be run safety. And I think that we’re very satisfied with safety as it stands today. I think we should be very careful about reading beyond that.
Certainly, on the efficacy side, our next program, which is the 103 program, which is targeting rhodopsin or RP4, which is an autosomal dominant retinitis pigmentosa. Amongst other things, it’s using a much higher efficiency editing with using a single guide, and with approaching pre-clinically 100% editing. So that’s where I think we should look at read through, and then be very cautious or careful about read-through on the efficacy side, because we’re talking about a more potent editing therapeutic.
Yanan Zhu
Very interesting. So when will that RHO-adRP program in terms of time line development?
Gilmore O’Neill
Yeah. So, the key thing is we have recently, and I think we talked about that at our quarterly Q2 call. We’ve received feedback from the FDA from a pre-IND point of view. That was extraordinarily helpful, and we are targeting initiation of our IND enabling, or CTA IND enabling clinical talk at the end of the year.
Yanan Zhu
I see. I see. In the remainder of the time, could we talk a little bit about the CRISPR IP dispute? What — I guess, what is the next milestone? What would the Appeal Court’s decision mean for you? And how will this play out as the competition product will be nearing the commercial stage at that point?
Gilmore O’Neill
I think — very quickly, the key thing is the dispute is limited to Cas9. It does not involve AsCas12a. Broad from whom we have exclusive license for Cas9 has prevailed twice with PTAB once already with the Federal Appeals Court. The Federal Appeals case that is running now is essentially not a reevaluation of the facts. Those are established. It’s reevaluating or confirming that PTAB applied the law, it went through a very thorough process in its second review. And it is our belief that we will prevail. The decision will come out mid to late 2023, and it is our belief that any sponsor plan to launch a Cas9 therapeutic will have to come to us for a license. And I think most importantly, just remind everyone that from a 301 point of view, that is AsCas12a.
Yanan Zhu
Right, right. And maybe a quick follow-up here. When other people — companies come to you for the license, let’s say, you eventually prevail. What does it mean for you economically?
Gilmore O’Neill
So we see substantial upside for us from this IP from those licenses. But — and we would expect to see that in the negotiated agreements that we make with the sponsors. But we will not share those details until we actually have finalized an agreement.
End of Q&A
Yanan Zhu
Understood. Understood. It seems like we’re right on time. Thanks, everyone, for joining us, and thank you, Gilmore and Mark, for being with us today.
Gilmore O’Neill
Thank you very much
Mark Shearman
Thank you.
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