EDIT - Editas Medicine Inc. (EDIT) Morgan Stanley 21st Annual Global Healthcare Conference (Transcript)
2023-09-11 13:26:03 ET
Editas Medicine, Inc. (EDIT)
Morgan Stanley 21st Annual Global Healthcare Conference Call
September 11, 2023 10:00 AM ET
Company Participants
Gilmore O’Neill - President and Chief Executive Officer
Baisong Mei - Senior Vice President and Chief Medical Officer
Conference Call Participants
Terence Flynn - Morgan Stanley
Presentation
Terence Flynn
Great. Well, thanks for joining us, everybody. I'm Terence Flynn, the U.S. biopharma analyst at Morgan Stanley. Before we get started, for important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative.
With that out of the way, we are very pleased to have Editas joining us this morning. Today from the company, we have Gilmore O'Neill, who is President and CEO; and Baisong Mei, who is Senior Vice President and Chief Medical Officer. Thank you both so much for being here today.
Question-and-Answer Session
Q - Terence Flynn
Maybe to start us off, just kind of a high-level question here. Back earlier this year, you announced plans to reprioritize the company's pipeline. Maybe just give us an update on kind of where that stands and the latest strategy for the company.
Gilmore O’Neill
Yes. Thank you very much. It has been a very exciting year to date. Having enrolled out the strategy, we have really focused significantly on execution. As part of our focusing, we terminated or divested some assets, and we were very delighted to have Shoreline take our NK oncology asset, and that has been a very exciting collaboration and our divestiture and they are very happy with how things are going, I'm pleased to say.
On the internal point of view, we redeployed a substantial amount of our resources and capital to our CMC support for our EDIT-301 autologous ex vivo hemoglobinopathies therapy, [both CMC] and two clinical execution. And Baisong's leadership has actually been very important here, in that he really has transformed the development organization. And by the end of May, we were able to share that we had already doubled enrollment, indeed had enrolled 20 patients into the RUBY study. Why does that matter? Because as part of our strategic refocusing on execution of 301, narrowing and sharpening our focus on in vivo and then changing our business development posture. We also said that we would shoot for 20 patients dosed in the RUBY study by the end of this year. And that matters because we felt that would likely be a meaningful efficacy cohort. And indeed, that hypothesis was validated when the FDA accepted the BLA filing for exa-cel, which includes about 17 patients in their efficacy set with 15 to 18 months of follow-up data.
So overall, we've done very well there. I'm actually delighted to say that from the second part of the pillar, it was wonderful to announce just a few weeks ago that Linda Burkly had joined as our new Chief Scientific Officer. She will be an important catalyst in driving the building of our in vivo pipeline, which we believe ultimately is going to be the way to truly unlock the full potential for editing as a technology for therapeutics and actually also for Editas.
I think the other piece that's important, and it's always hard to do, but when we described or reset our strategy and sharpened our focus, we did reduce our headcount by 20% in a very targeted manner where we took out capabilities that we no longer required. And then we read out data as we had promised in June of this year at the European Hematologic Association and shared exciting data for our sickle cell program, where we demonstrated not just robust expression of fetal hemoglobin in our first two patients who had at least six months data where they crossed the threshold and maintained a threshold above 40% at fetal hemoglobin, but actually also both corrected their anemias and returned total hemoglobin to physiologic ranges by the fourth or fifth month, which is a very good time line because that's when you tend to see plateauing, but also full washout for any donor blood that had been given to the patients during their transplant.
So all in all, a very satisfactory outcome, even more so when we looked at the third and fourth patients with shorter follow-up, but where the trajectories of fetal hemoglobin expression followed, and we are very consistent with what we saw in the first two patients. And indeed, in a webinar a few days after EHA, we shared not just those data, but the data from our first thalassemia patient EdiTHAL, who again had a very similar trajectory with their fetal hemoglobin.
And then on the head of that, we were able to raise a net $117 million. And what that basically means is between the reorganization, the redeployment of capital, our cash runway extends out into Q3 2025. And that matters because with that 20-patient cohort that we will have – we are on track to dose by the end of the year, if you consider that the efficacy data set 15, 18 months with 17 patients is kind of the range of efficacy data set. And obviously, this is contingent on our discussions with FDA and their agreements, then you could actually see that it's plausible that we would have a similar data set 15 to 18 months with 20 patients by the middle of 2025.
Terence Flynn
Okay. That's a great overview, great place to start. The other one, there are kind of two subsequent ones I want to follow-up on. But the first is just differentiation. Obviously, the pace of genetic medicine is accelerating here. There's a number of new technologies, new platforms that are being rolled out across the landscape. And so maybe just help us think through where you think you can differentiate most in terms of the CRISPR platform that you guys are working towards and again, this pivot towards in vivo?
Gilmore O’Neill
Yes. So I'd be delighted to do that. I think a key thing and one of the things that actually drew me to Editas was Editas' proprietary AsCas12a enzyme, CRISPR enzyme, which actually we believe is meaningfully differentiated. And indeed, in our hands and the hands of others, it is both more efficient in editing than Cas9 and actually more specific or higher fidelity. And indeed, again, across a number of labs, including our own, where we submit the two to a sort of global genome screen for off-target, we cannot detect with AsCas12a as we can with Cas9. This is obviously within the constraints with limitations of the detection systems, but that's still a meaningful difference from off-target.
And then from an efficiency point of view, we actually see real benefits. And indeed, we were very happy with the efficiency of editing that we actually were able to share in June for the drug product from 12 patients enrolled in both – in the Ruby and the EdiTHAL study, so nine plus three, respectively. So that's the one, I think, critical differentiation because that has an impact on dosing risk, et cetera.
From the point of view of how we would then apply that as we move into our in vivo pipeline, I think that differentiated our separation for the technology itself is meaningful. I think the other thing is actually also our approach. And we've talked about that before. And one of the reasons I was so happy to welcome Linda is that she and I and frankly, Baisong and the senior leadership in the organization, share a very similar mindset about the criticality of differentiation at the commercial side.
But obviously, you want to focus on areas where there's high [probity] of technical translational, and this is important and probably one of the reasons I'm so happy with Linda, who is not just a successful drug finder and biologist, but somebody who has actually had the experience of and the understanding of the criticality of understanding the patient and the translation experiment before you even select the target. And so that translatability and obviously, the regulatory path. So as I say, our philosophy will very much focus on going to areas where we believe our technology or our focus is going to create a meaningful difference for patients.
We are not necessarily interested in going to an area where there are lots of technologies that can leverage and lots of players already there. So I think that's a critical part of how we are thinking about that future in vivo. And we look forward to sharing more about that in an appropriate time as Linda just has her feet under the desk.
Terence Flynn
And Mei, can you give us any early insights in terms of like where – what types of diseases you might be interested in?
Baisong Mei
I think it's too early to say. What we did say when we rolled out at JPMorgan was that we did articulate our indication interest already in targeting hematopoietic stem cells in general and specifically the gamma globin promoter, which we believe is a meaningfully different choice for editing. And indeed, we believe that's one of the reasons that we're seeing that correction of anemia with our 301 product. So we believe that actually bringing that in vivo space is really very valuable and meaningful. And then from the point of view of looking beyond that, we're going to talk about that more in the future.
Terence Flynn
Okay. Understood. One of the other challenges broadly for genetic medicines is delivery. And maybe just, again, high level, where are you now? And as you think about this pivot to in vivo, is this going to be an internal effort? Or are there external opportunities to bring technologies in? Again, I know a lot of different technologies out there, but maybe where are you most focused as you think about that?
Baisong Mei
Well, when we rolled out the strategy in January, we said there are three pillars, and I just [indiscernible] the 301 focus, the in vivo focus, and then the business developed, that third business development posture had two elements. One was sublicensing, but the other was a shift in posture that we don't actually have to invent everything that we are actually, in fact, actively looking for those capabilities or technologies that would complement ours to drive and realize our in vivo vision. And so that is an exercise we are going through.
With regard to something more specific, what we did do was take out AAV. So when we actually refined and narrowed, sharpened the pipeline, we stopped any further ex vivo cell therapy discovery. We actually also stopped the use of AAV and have looked beyond to non-viral delivery for in vivo. And I think the nanoparticle space general and the lipid nanoparticle space, specifically is an area of significant interest. We do have in-house expertise, but we are actually looking to make sure we get the right balance and come from charity and leverage where the terms and the lineup of the match-up and synergies would actually be most effective.
Terence Flynn
And why – maybe just on why remove AAV from the equation? What was kind of the key piece of it?
Gilmore O’Neill
Well, I think there are a number of elements. I think the key piece was that you want to really focus on areas where you have true and deep expertise. I think there are other – some other additional challenges, but that was the key one, which is we are an editing company. But that's where our expertise is, that's where we should actually focus.
Terence Flynn
Okay. And as you think about the BD licensing side, do you feel like there's enough opportunity out there? And is this mainly among private companies? Is it among academic institutions? Like where is the opportunity set lie in terms of the delivery technology?
Gilmore O’Neill
We actually see a sort of a broad set of opportunities across that spectrum of that line from academic to private to public. And obviously, what we will finalize in those kind of set of situations would be the ideal and the optimal balancing of our capabilities and those capabilities and also how we think about the degree of investment.
Terence Flynn
Okay. Great. Maybe Baisong, I'll pull you into this. Gilmore touched on some of this, but just the data that was presented at EHA, what else stood out to you is, again, I think investors are trying to differentiate as we think about two other products potentially coming to market early next year. What is most encouraging about the data that you saw as you think about that differentiation piece?
Baisong Mei
Yes. I think Gilmore touched upon a little bit, but I think happy to follow-up on a little bit more on that. Maybe back up a little bit, when we designed EDIT-301, these are rational design, we actually did head-to-head comparison between the Cas9 enzyme versus the Cas12a enzyme between the BCL11A target versus also the HBG1/2 target in that two.
And Gilmore touched upon the enzyme and add on that is actually for the target. When we do the head-to-head comparison between the BCL11A and the HBG1/2 promoter, we find that the HBG1 promoter targeting give us more red blood cell production, red blood cell health and more [indiscernible] process. And then when we – last December, we see our very initial data, we find, wow, this first patient actually go to – did go to normalized total hemoglobin, and which is very exciting to us. Then in the June, we see additional patients due to normal range, and also the other two patients go to the same trajectory. This is very important to us because, I think that the two molecules ahead of us, and they also have very good results, for example, preventing the BOEs, which is great.
But when we look in the rare disease eyes, when we have very limited choice, we will first get into to target the most severe symptom, which is in this case for sickle cell. But the sickle cell symptoms way beyond BOE, so we are looking to that. One of the important thing is actually to be able to have normalized total hemoglobin to the corrected anemia, sickle cell is actually called sickle cell anemia also in it before. So when we see this data, we feel there's a good chance for us to actually to be able to differentiate to beyond correcting the BOE, then we'll be able to normalize the total hemoglobin. That is related to the end organ function and the quality of life, right?
So that's kind of the three category direction, we're looking to that. When, of course, we're looking to lab value the hematological parameter. But we're also looking to the end organ function, for example, cardiopulmonary we cardio echo pulmonary function and liver function and kidney.
Then the patient report outcome is very, very important in this case. For example, one of the important complaint from sickle cell patients is fatigue. And that fatigue is very much related to the anemia. And we all actually experience that, too. We will go to high attitude, we feel fatigue with short of breath. So that's kind of the direction we're looking to.
When I look at that is, generally, I've been working in rare disease for 20 years, more than 20 years now. And when you go to the rare disease, you start with the severe symptom you're trying to address. Now we're trying to together elevate the standard-of-care for this patient. Hopefully, that's kind of the direction we're getting to. I'm sure there'll be more things behind us in the future to be able to even further elevate. I think that's the direction we're going to treat the disease.
Terence Flynn
Okay. Great. And I know we had the presentation at EHA and Gilmore, you kind of walk through the highlights there. But as we think about the next update, I think you guys have said sometime by the end of this year, I'm assuming ASH is probably one of the key venues just given that's where we typically see data. Is that a fair assumption then anything more you can share in terms of, obviously, beyond longer follow-up on the existing patients? I'm assuming more patients. But again, anything else you can tell us about kind of how you're thinking about that updated data disclosure?
Gilmore O’Neill
Yes. So two things. First, we're maintaining our optionality for the end of the year. It could be ASH, it could be webinar, it could be a combination. We have that optionality. We obviously share that sooner and closer to the time presentation.
You're absolutely right. The minimum data we'll be showing will be those five patients, one thalassemia, four sickle cell patients that we've already presented with longer follow-up. And indeed, all those patients would have had more than six months of follow-up, which will be very interesting indeed we have patients with more in a year of data, and we would have additional patients. And what we would share without going to specifics, again, we will talk more about that closer to the event, will be, again, our hematologic parameters, safety, VOC, VOE data.
Terence Flynn
And do you think – again, you talked about this a little bit, but in terms of the other two products, let's say they do secure approvals later this year, early next year, does that change the bar in terms of what FDA – how FDA approaches unmet need, I guess, in this space, meaning maybe they hold you guys to a somewhat higher bar than they did before because you already have these two other products? And have you talked to FDA at all about that in the event that, that does happen?
Gilmore O’Neill
So I’m going to begin perhaps with some remarks and then Baisong can talk a little bit more about that. We don't necessarily see that. I mean the interesting is Baisong and I have worked in the rare disease space on the development side and have been on point negotiating with regulators. And that's actually not the path that we see. I know people talk about it a lot. But in fact, sometimes it's actually the opposite.
As comfort is developed, [indiscernible] with the technology, or a rare disease or indeed some of the outcome measures, indeed, you can sometimes see things going in the other direction. And so that's obviously – I'm not saying that's going to happen, but I think that's one of the things, things that we're certainly worth used to and accustomed to discussing with the agency and other agencies as well. So we don't see that as – indeed, we actually see it as an opportunity. Baisong, I don't know if you want to add to that?
Baisong Mei
Yes, absolutely. I was just continue on the last topic – last point is actually as an opportunity. We really feel that these two molecules recent [indiscernible] opportunity for us that help the agency and help the community to understand better the technology, right? Both technology actually chromosome gene editing, right? So gene chromosome editing on that too. So then we will see that how do we know this technology, how safe it is and how well this can actually change patient life? So that's going to be very positive for us.
And in terms of the fast follower, whether you have a higher standard as Gilmore said let me give examples. As long as your drug is safe and efficacious, and all the players of stakeholders here from agency to the patient community, the HSCT into the payer, they're all welcome choices, right? So we feel EDIT-301 will be a competitive product and potentially differentiated as Gilmore just mentioned earlier. So we feel this will be very well welcomed by the community and by agency, by payers. And we already – our investigator has been very experienced in many different trials before, without specifics. They very much welcome that we have this EDIT-301 molecule, we have different approach. I appreciate that and they're actually very excited, especially now we see actually be able to correct the anemia and they are very excited to see before, hey, my patient was much lower before in a different trial. So that's kind of what we've seen.
Gilmore O’Neill
So Baisong used the term fast follower and differentiation, I'd say that fast follower with potential differences – strong potential differentiated, we believe actually put us in a very good position because, because frankly, this is a new space that's been developed. And we appreciate that the trailblazing work done by our friends at Bluebird and ultimately Vertex and CRISPR. And I think that will actually enable the sites who have to make an adjustment, both from a capacity point of view.
The development of autologous ex vivo basically means that whereas currently, a patient sickle cell or thalassemia has to find a highly matched donor 10% to 20% probability at best, they will find them. So we're going to increase that eligible patient population five to 10 fold. So those sites are going to have to expand and lean in to support that patient growth.
And then obviously, they're going to move from what is essentially a reimbursement model around which is largely procedural to one that is a combination or hybrid of both procedure and transplant, harvesting of cells in transplant, but actually also the pharmaceutical reimbursement component as well. And then obviously, the patient community is going to have to adopt. So what we're actually looking to and expect to see is really a very compelling set of work done by excess sort of Bluebird and Vertex.
But that will enable us really, I think, to both exploit that work, but actually also take all the lessons learned as we move through. And as we said before, we anticipate the vast majority of patients. We estimate there are between – I think the analyst consensus is somewhere between 20,000 to 35,000 patients who'll be eligible in this country from the present patient population. That's not counting incident, present private patient population that will be waiting for this therapy. And the vast, vast majority of those patients will be waiting by the time of our approval. As I say, we can't make promises. We have to agree with the agency. But as I say, if we have 20 patients dosed by the end of the year, and we are on track for that, then we're in a very good place by mid-2025.
Terence Flynn
Okay. Great. Two follow-ups on that. So any perspective on the AdCom coming up. So one of those two companies has an AdCom, one of the products doesn't – any idea on why that would be the case? And how you think about some of the key questions FDA might be considering for that outcome?
Gilmore O’Neill
Yes. So I think there are two big areas to consider over the AdCom and it will very interesting for all of us to actually see that on the 31st of October. One is around CRISPR. This is the first time that our CRISPR technology is being approved. And I would think a big focus of the questions will be on AMC and other pieces on just essentially the risk. I will say that from risk point of view, I think much of the discussion around risk on the clinical side will effectively be discharged by the lentiviral discussion last year when there was an AdCom Bluebird's thalassemia program.
And then on the sickle cell disease side, I think the benefit risk, once they have talked about the CMC will actually be quite clear, we'd have a good sense of that. But I think it would be very interesting for us all to see – to get a breakdown of what additional clinical data has been collected and actually also to maybe get a more granular view of what the fetal hemoglobin and hemoglobin responses were. But I anticipate this would be a – I think we expect this to be a positive one. We actually feel that the AdCom was very clear last year when they recommended unanimously the approval of Bluebird's product for thalassemia with the benefit risk, and that was actually with some myelodysplastic syndrome outcomes in some of the patients. So I think overall, I think this is a – I think we will learn a lot, and that's how I think we see it lining up.
Terence Flynn
Okay. Great. And the other question you mentioned, site capacity, that's something else I know from just following the CAR-T space has been pretty important. There are some centers that have been investing to build out their capacity because they don't have a number of beds, so et cetera. So what have you learned so far about thinking about that aspect, this like capacity because you're talking about 20,000 to 30,000 patients, but do the sites – are there enough sites to work through that?
Gilmore O’Neill
So the broad question, and I'll pass – Baisong will have some granularity about the next part. There are two pieces. I'd say the one is, I think, overall, we actually anticipate that, that investment will be made.
The other piece, which is of more immediate interest to us, okay, so what happens with the balancing capacity with our ongoing study and with commercial drug. And we actually anticipate – in fact, our experience today has been that this is not going to be a challenge for us. And Baisong, maybe you could build on your conversations with the sites and the investigators?
Baisong Mei
Yes, yes, certainly, I think it's great you actually mentioned the CAR-T experience. That's kind of what we see in this space, too and every stakeholder in this space when you have learning and building up space. So that's where we feel the early uptick will be relatively slow and taking time and eventually will beat all the system there.
And many of our sites actually have both CAR-T and these hematopoietic stem cell transplant experience. And the several of them, as you mentioned, they are actually already experienced the space of hematopoietic cell transplant because they see a lot of demand in there, too. So I think the general thinking is to see – you will see this entire space grow, it's like the CAR-T cell space and going there, too, because then people appreciate the value of that, I appreciate how this strategy can do, that's also valued by [ICE] report to see how this space goes. So we're optimistic, but I think it will be taking time and to get all those set up on that. So I think that will give us good opportunities to really catch up to actually be able to help the patient?
Gilmore O’Neill
I think the other point, of course, is for the near term is that we do not see a challenge with commercial launch for our recruitment and you can – based on conversations. In fact, the ongoing uptick in interest. We saw an 8- to tenfold increase in inbound from patients. And indeed, the investigators continue to recruit into both studies, and really have articulated desire to continue that. I think both based – both on the data they have seen, but frankly, actually also that where a patient is eligible in the clinical trial setting, it's actually easier than certainly working out sort of going through the teething of that sort of early launch of this new type of therapeutic.
Terence Flynn
Okay. Great. Maybe just in the last couple of minutes, the IP portfolio is, again, another part of the company strategy here. Maybe just walk us through on kind of plans to monetize that? And how should we think about next steps milestones to be on the lookout for?
Gilmore O’Neill
Yes. So very quickly, Cas12, we can license both Cas12 and Cas9. Cas12, we don't have any Cas9 products ourselves. So we're focused on our Cas9 sublicensing. We have ongoing sublicensing to developers indeed four, was one company that announced just three weeks ago that they have – sorry about that.
And then with regard to programs that are late – later, they all need our IP. We have a robust set of foundational IP sublicense from Broad Harvard MIT. Some, not all of the IP that's required by others is subject to interference. I know there has been some confusion about that. But we have other IP, not subject to any interference, which also people will require. And so we are – expect that we will be doing licenses for that IP for these programs as they come close to approval and launch.
Terence Flynn
Okay. Okay. Would any specific products you can point to?
Gilmore O’Neill
Well, obviously, the first one that will be coming up for approval is Vertex CRISPRs, exa-cel.
Terence Flynn
And have you had any conversations with them yet that you can tell us about?
Gilmore O’Neill
So we will share if and when we have an agreement. But obviously, we're looking to what we philosophically embraces the idea that we want to make this technology available to patients and therapeutic developers and obviously do it at terms that are meaningful and valuable for both parties.
Terence Flynn
Okay. Well, thank you very much, Gilmore, Baisong. I really appreciate the time today.
Baisong Mei
Thank you.
Gilmore O’Neill
Thank you.
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Editas Medicine, Inc. (EDIT) Morgan Stanley 21st Annual Global Healthcare Conference (Transcript)