Good morning, everyone. My name is Gena Wang. I'm a Sector Biotech Analyst at Barclays. Welcome to Barclays' 27th Global Healthcare Conference. It's my great pleasure to introduce our next presenters. Sitting right next to me is Erick Lucera, Chief Financial Officer and the EVP from Editas Medicine. There is Gilmore O'Neill, Chief Executive Officer and the President of Editas Medicine.
Good morning.
Good morning. Thank you very much for giving us this opportunity. Maybe before I dive into the questions, do you want to give a...
Sure.
Brief overview?
Yeah, happy to, Gena. Thanks very much for the opportunity to be here. Editas is a CRISPR gene editing company. We are at a position now where we are a pure in vivo gene editing company, driving towards exploiting the true differentiated potential of CRISPR editing. I'm looking forward to talking more about this. Most particularly, we are using CRISPR really to do things therapeutically that other modalities cannot do. We believe that creates a significant opportunity for us to differentiate from other companies and certainly create significant markets for ourselves. We are tracking well on progress. We are a preclinical company, effectively, and are tracking well towards achieving our objectives of drug candidate selections in the middle of the year, sharing significant amounts of data at that time, and tracking to at least one IND in 2026 and human POC by the end of 2026.
We do that with a cash position that gets us into Q2 2027.
Great. Maybe I wanted to ask about your in vivo... Okay. Your in vivo program, the preclinical data you shared early January. You did share regarding the mouse HSPC versus non-human primates data. You shared multiple different layers of data, lipid nanoparticle one, two. Maybe give us a little bit of update, the plan for the next steps.
I'm happy to distill that for you. We had set out an objective for last year, which we really exceeded, that we were going to have data by the end of the year for one in vivo POC in one species. We managed to get two targets with POCs in two species each, which is really, I think, a testament to our discovery group and, more importantly, I think signifies the urgency and the drive with which we're moving our pipeline forward. Apropos the data and what is coming, what we presented earlier this year was essentially a series of evolving lipid nanoparticles, which we call one, two, and three. As you can imagine, as you move from one to three, things get better. The potency was better.
We actually were very excited to see in the context of editing HSPCs and HSCs that with our so-called LNP2, which is an LNP with a ligand that's specifically a novel ligand that specifically targets hematopoietic stem cells, we were seeing already there 10% editing just after a few days in mice which had been engrafted with human stem cells. We were so excited by that data that we actually moved it immediately to non-human primates and actually at seven days achieved 17% editing of hematopoietic stem cells. Very importantly, as that was happening, we continued to evolve our LNP to LNP3, so-called, where we saw a threefold improvement just at seven days, where we saw 30% editing in the human CD34 or stem cells engrafted in mice at seven days. After a few more weeks, we had saw it at 40%.
That is now also moving into non-human primates. What we actually see is an evolution of our targeting LNP or in-house delivery technology that will give us potencies that certainly exceed a threshold, our anticipated thresholds required for meaningful clinical benefit to patients with sickle cell disease, for example, and obviously beyond to thalassemia.
Regarding the lipid nanoparticle one, two, three, what are the main differences there, which are the key components? I know you may not be able to disclose in detail, but the key components.
I'm happy to go as far as I can.
Okay, good.
The key difference with the LNP2 versus LNP1 was that we actually added on or conjugated a novel targeting ligand that would actually deliver the LNP to hematopoietic stem cells. What I should pause for a moment and say is that our approach is to use lipid nanoparticles with a conjugated where we actually adjoin or link in a plug-and-play manner a targeting ligand or molecule that can actually allow you to plug and play depending on the cell type you want to select. In this case, we are talking about hematopoietic stem cells. The difference between LNP2 and LNP3, which was associated with threefold increase just at seven days of exposures after a single dose, was really tied to reformulating and tweaking the lipo, the lipids, and the ratios within the lipid nanoparticle.
That actually had a significant improvement, largely because we're using that to detarget the liver. We're actually very happy where we are with regards to that biodistribution and detargeting of the liver. Overall, by detargeting the liver with that ligand, we're actually really seeing what we believe are very exciting and, frankly, likely meaningful, clinically meaningful potencies.
The components did not change between lipid nanoparticle two and three. The key change is the ratio of each component of the.
There are some components, but also ratios as well. Essentially, it's essentially more a tweaking of the formulation of the LNP itself rather than the targeting ligand.
Right.
Targeting ligand is the same.
My question for lipid nanoparticle itself, you have key components, ionizable lipid, right? You have a cluster, you have a few others. Did you change some of, say, the key one is ionizable lipids? Did you change that part?
I'm not going to go into the details, but we changed some of those components, yes.
Okay. Okay, good.
That is exactly, you are on the right track, which is what these are, what we are trying to do with this, say, manipulating or altering the ionizable, the cholesterol, the pegylated, et cetera.
Okay. Is that because the affinity change or you think?
We feel it's a great question. By detargeting the liver, you achieve a number of things. One of the things you do is you essentially significantly reduce the potential for toxicity. Obviously, the key toxicity that has been observed with lipid nanoparticles has been liver toxicity. Detargeting the liver is actually a very effective way of dealing with that. The other thing, of course, is that you change also the kinetics and the circulating kinetics. That in itself can enhance the availability of the LNP with its target for the hematopoietic stem cell that you want to deliver the editing mechanism to.
What is the half-life of lipid nanoparticle two and three?
We have not disclosed that yet. Obviously, that's the.
Are there any differences? Like I know maybe you may not be able to.
I won't be able to share that right now.
Is there any improvement, like a shorter half-life for lipid nanoparticle three?
I think we will be sharing more of those data later in the year. I think the best thing to say, yes.
Okay. It's fair. Okay. Now the next data update, maybe give us a sense of the timing.
Yeah.
The level of detail, like the data points you may be able to share.
Yeah. We're, as I say, looking forward to announcing two drug candidates in the middle of the year. We'll be sharing data around that time. The data will consist of, we're certainly going to be talking about the editing efficiency. We'll look at, talk probably about biodistribution. We'll actually outline our plans as we move forward to the INDs or CTAs in the middle of 2026.
What is your goal for the editing efficiency?
Yeah. From an editing, so specifically talking about hematopoietic stem cells, because we have another program as well, which is not stem cell targeting, but liver targeting. I will come back to that. With regard to stem cells, the allogeneic experience, the allogeneic transplant experience, when it looks at chimerism or the mixture of donor cell or the mixture or ratio of donor cells to recipient cells post-transplant in sickle cell disease suggests that a target somewhere between 20%-30% chimerism, or where it is 20%-30% minimum of donor cells, or in this case, we would say we would translate that to edited cells, is a very good threshold.
The reason we believe that is because that allogeneic transplant experience has demonstrated that even in the context of that kind of mixed chimerism and a ratio of 30%-70% or 20%-80%, 20%-30% donor cells, you will actually have effective control, total control of your vaso-occlusive events. I think that is actually why we have set that threshold and believe that's a meaningful threshold.
That's referring to the HSC, right?
That's for HSCs, yes.
Yeah. Okay. Okay. Which means like your, I think, LNP2 is almost there, 70%.
It is almost there, certainly in the monkeys. That is at seven days. Obviously, those monkeys, the nice thing about monkeys is you continue to follow them. We have further time points to evaluate those animals. Our LNP3 was threefold more potent in the mice. These are human stem cell engrafted mice, threefold more potent than the LNP2. Overall, we feel very good about where we are tracking to meet that threshold.
When you're quoting the editing efficiency and those not biallelic editing, right? It's a monoallelic editing.
Actually, we found that if we're talking about allelic editing, what we've actually found is that interestingly, and this was based on our, we can use our data from reni-cel when we were actually editing those cells, that you tend to get, if you have monoallelic, you're more likely to get biallelic. In other words, it's not an equally distributed editing. You tend to get higher allelic editing or a skew to the right. If you know, if you go from one to four, you're skewed to the right for bi or higher.
I see. Good. All these data will be around, like the timing-wise?
We're saying the middle of the year.
Middle of the year.
Yeah, middle of this year, middle of 2025.
Okay. How will the venue look like? Will you just have a press release?
Oh, we haven't determined that yet. Obviously, there are a number of scientific meetings coming up as well. We haven't actually defined exactly how or what medium we would use for sharing those data. We'll share that and give notifications that's closer to the event.
Okay. Maybe you wanted to go back to the 20%-30% editing efficiency. How that actually others, right? The fetal hemoglobin level, some, I think, CRISPR, sorry, beam data even shows 60%, right? Fetal hemoglobin level. In order to, I mean, those are the ex vivo and the in vivo, of course, the bar would be different. What will be, like if we're talking about 20%-30%, how much do you think that would translate to, say, the fetal hemoglobin level or in terms of.
Yeah. We're now moving to the realm of speculation here. Obviously, we're generating those data and we will have that. I think the reason that we sort of look at that 20%-30% editing threshold is because we actually have that data from the human experience with allogeneic transplant. Obviously, those patients are being transplanted with normal, normal, or their donors have normal genotypes. They're not upregulating fetal hemoglobin. Those are data that we will have later as we get ready to move to the clinic.
I think maybe regarding the clinical development, you have done a lot previously for the reni-cel and accumulate lots of clinical experience. How would that help you for this next-gen in vivo approach?
I think it's going to be tremendously helpful for many reasons. Obviously, at the very minimum, we have strong relations with sites. We have relationships with patient groups, patient advocacy groups. We know the experts in the field. All of that is incredibly helpful to advancing the program. We also have strong relationships with regulatory authorities. I believe that puts us in a very good place as we think forward. I think importantly, you know yourself, running a clinical trial tells you so much because you always learn so much more about what you can do differently.
Obviously, as we think about in vivo, the beauty of in vivo is it addresses or has the potential to address many of the challenges and issues we saw both in the clinical trial experience and now what is being observed in the commercial experience with autologous ex vivo, whereby going to in vivo and ideally with a single dose or a handful or two doses, which is a simple infusion, a couple of things arise. You do not have to immunosuppress or condition the patient with that toxicity. You do not have to worry about fertility preservation. The safety profile with the elimination of busulfan is already significantly improved and allowing you potentially in the future to access more patients or have more patients to access the treatment.
Of course, you eliminate the long delay and the need for mobilization and collection of cells, which turns the whole journey for a patient into 12 months with a long period in an isolation unit when you're immunosuppressed post-conditioning and transplant to sort of cap that journey. We eliminate all of that with the in vivo. Overall, you can see how all of that feeds into that experience, feeds into how we will think about our clinical trial. That gives a benefit.
Maybe mid-year you will share initial data. Moving forward, what are the steps you need to prepare in order to, say, file IND?
I think the key.
The key steps will obviously be around, and obviously we're starting that work or start that work is around obviously manufacturing, creating the scale, doing and agreeing on what the non-clinical tox packages will look like for that first-in-human experience. I think those are the key things that we'll be working through. Obviously, we're doing likewise for our other program that we hope to DC in the middle of the year, which is this yet to be disclosed, but we hope to disclose it. We'll certainly be disclosing about the time of the DC, which is a target in the liver where, again, we differentiate from other approaches because we are functionally upregulating or essentially dialing up the amount of a disease mitigating protein that essentially can significantly reduce or control the complications of another disorder that is caused by mutations.
Maybe ask, since you brought up liver indication already, I think I have a sentence quoting that not addressable, the candidate would be not addressable by other knockdown approaches such as the siRNA, ASO, or certain other CRISPR edited approaches. So what make.
What's the difference?
Yeah.
Yeah. The difference is that largely, generally, the rule is siRNAs, ASOs largely can knock things down. They can switch off genes. Now, in occasions with a particularly novel area, you may sometimes be able to amend or alter expression. Spinraza has a good experience of using an ASO to alter that or indeed Vyondys or other things. In the main, siRNAs, ASOs can only knock things down. What we're actually doing is we're essentially targeting non-coding regulatory elements of genes to switch them on or essentially increase the dose of that gene product being made. We are selecting very carefully and have selected carefully those targets where there is evidence, usually human, natural human variant genetic evidence to suggest that there will be a benefit from upregulating that protein.
We did the same with sickle cell where we used natural variant data in human biobanks that showed that hereditary persistence of fetal hemoglobin would mitigate or control the effects of sickle cell as in thalassemia when co-inherited. We are using a similar strategy using human genetics to de-risk targets that have not previously been targeted. We are switching them on so that as that protein increases, the theory is that we would actually reduce the effects of the disease. Indeed, we actually feel very good about where we are right now because the preclinical data that we showed earlier this year showed that we were actually getting in one iteration a 4x increase in the expression or increased expression of this protein that we want to increase.
That was associated with a 60% decrease in a soluble biomarker that is actually measurable in humans and is actually predictive of human disease complications and relevant to it. That is sort of in a nutshell what we're trying to do and why we feel so good about where we are right now.
I wanted to recap what I understood. You are targeting the non-coding sequence, and my guess could be suppressor, whatever the regulation of a downstream likely five prime UTR or whatever before the coding sequence. You are targeting that sequence by cutting it. Of course, the body tries to repair and introduce basically non-functional sequence. Then you turn that whatever suppressor sequence off for the downstream transgene can actually upregulate.
Yes. Correct.
I see. Okay. Okay. Good. This also target you will share with us later this year, right?
Pardon me?
The target.
We'll share the next edition of this. Yes, we're sharing at the middle of the year as well. Yes.
Okay. Okay. Good. Regarding that, you did say the what about the disease indication is that you didn't mention there is a human genetic supporting this.
Yeah. We have shared.
How big the patient population?
Yeah. One of the things we're actually trying to do, we're very conscious of is getting the balance. There are advantages to doing rare diseases and there are advantages to high prevalent diseases. We're trying to find a balance because clearly it has become increasingly challenging for us to basically focus from a business point of view, frankly, on purely rare diseases. In the same way that you can look at sickle cell disease and see there are highly refractory populations in which you could get the benefits of a more rapid regulatory path, you can look at subsets of a patient population. Likewise, we're looking here where there might be subsets or a subsegment of patients with a very severe refractory disease in which you could actually move relatively quickly.
Obviously, life cycle expand into larger segments of that prevalent population with the same molecule without having to create a new molecule. That is really our approach. Obviously, we look forward to sharing a lot more detail about that population and those segments when we are disclosing our target.
Sorry, should I push it a little bit more?
Of course. I would expect you to.
Initial patient population, are we talking about tens of thousands patient population?
We could potentially be talking about tens of thousands, yes.
Okay. Okay. Good. I know we only have a few minutes left. I do want to ask Erick regarding the financial and also the BD part. Financially, we have a cash $270 million runway into second quarter 2027. What are the assumptions building for this cash runway?
Yeah. Thanks for the question. In terms of the assumptions for the cash runway, obviously we have the exit from reni-cel, which will occur over the next two quarters, Q1 and Q2 of 2025. That is about $60 million-$70 million as we disclosed in our filings. I think once we get to that level, you'll see a more normal level of burn that you would expect out of a preclinical publicly traded company. In terms of any other revenue expectations or deal expectations, the only things that we have in our plan are deals in which we've already inked and have the cash flows coming in, whether it's a Bristol Myers or a deal we did with Vertex and DRI. Really no heroic assumptions whatsoever.
Okay. You did mention the partner, the deal you've done quite successfully in the past. Any additional thoughts, especially given you are like the discovery engine is very strong and then certain indications or certain capability platform thinking about potential partnership?
Yeah. Yeah. We really have three ways that we could bring in capital aside from the traditional raises. One is by outlicensing the Cas9, Cas12a IP portfolio as we've done in the past with Vertex and then subsequently monetize that with DRI. The second way that we can do that is you've seen the deal that we did with Bristol Myers where we created products for them and licensed them. We create the package and license that whole thing to them. That obviously brings you a higher amount of economics than a pure freedom to operate license.
The third way that we could bring in products is if we have a complete molecule that we're not interested in doing on our own, but because the platform is so flexible, we can certainly go to folks that have existing antibody or franchises and things like that and license them an editing product as well. We have lots of ways to bring in non-dilutive capital.
Since you talk about potential monetization, any new update regarding reni-cel, is that possibility you can monetize that?
No. We partnered with Moelis, as you may have seen from our filings. They did a fantastic job reaching out to as many folks as possible. Where we saw the interest really was on the in vivo platform. There will not be any updates on reni-cel from here.
Okay. For the in vivo product, are you thinking to partner or you wanted to carry this on your own?
I think we're open and agnostic to anything that can create products that get to patients and value for shareholders. I mean, there's so many different monogenetic diseases in which we can use the platform and we're just going to listen to whatever ideas people have.
Great. We're on time. Thank you very much. We look forward to the mid-year update.
Thank you.
Thank you.
Thank you very much, Gina.