Cowen's 46th Annual Healthcare Conference. I'm Philip Nadeau, one of the Biotech Analysts here at Cowen. I t's my pleasure to do a fireside chat with Editas. We have with us today, Gilmore O'Neill, the President and CEO, Linda Burkly, the CSO. Maybe I'll kick it to you guys to start. Could you give us a brief state of the company overview, what are Editas' biggest strengths, biggest challenges, what does it need to do to create shareholder value over the next year?
Sure, Phil, thanks very much for having us here. It's great to be here with Linda and yourself. Editas is a preclinical- stage company which is on track to have human POC by the end of this year, 2026, for our lead asset EDIT-401, which is a very exciting in vivo delivered editing strategy that in predictive clinical or preclinical species has a probability of dropping cholesterol, LDL cholesterol by 90%, which will be transformative in the management of hyperlipidemia. From a point of view of our strengths really sit around a very focused differentiated mechanistic approach to the use of CRISPR therapeutics, where we actually use it to increase the levels of disease-mitigating or rescue proteins by editing non-coding DNA.
Another strength sits in our ability to deliver it in vivo, which massively simplifies the value proposition for patients, the ease of use and the value proposition for healthcare systems and payers. Where I would say the key challenges are, I think the key challenges are really for the space, I would say, the CRISPR space, although we have good news this morning in that, you know, one overhang has been the lift, the raising of the clinical hold for Intellia's TTR program with some very specific agreements and guidance coming for with the FDA. I think that's a what I would say the challenging area.
The way we're managing through it is really by absolute focus on being mechanistically differentiated, driving medicines with our lead asset as EDIT-401, that actually can transform, are going to make a meaningful difference and meaningfully change the standard of care. We do it with a discipline around the use of our resources and finances. We are funded into Q3 of 2027 and very excited about the next year as we basically bring EDIT-401 through. You know, it's great to have Linda here. We continue to enforce and optimize follow-up programs that can leverage our in vivo LNP delivery systems.
Before diving into 401 in some detail, we thought we'd ask maybe a couple questions about the platform. Last year you decided to pivot towards in vivo versus ex vivo gene editing. Can you talk about why you made that pivot? What's the value of an in vivo program?
We actually decided that we were going to make that pivot, you know, some three years ago. That was driven by the observation that a single intravenous outpatient infusion is a much easier prospect for a patient as compared, and a healthcare system, as compared to an autologous ex vivo system, which is highly complex, requires multiple cell collections, a tailored patient-specific manufacturing process, and then a transplant, which can actually require inpatient intensive care for four, six-plus weeks in isolation. I think that's the first advantage. The second advantage is that using in vivo system, where in this case we're leveraging nanoparticles and lipid particles off-the-shelf system with a substantially lower cost of goods compared to an ex vivo system.
When you pull that all together, substantial ease of access and use for patients and actually create a value proposition for reimbursement agencies here and around the world to actually make sure that this medicine and these transformative medicines can be used in as many people as should use them.
How is your in vivo program differentiated from some of the others out there, like a Beam or an Intellia?
The key differentiator really comes down to our editing strategy, which is that we are using CRISPR to do things that other things cannot do, other technologies cannot do. We, for example, have a skewed knockdown on the basis that antisense, sRNAs or even monoclonal antibodies further downstream can actually block or knock down the biology. In this case, we're augmenting biology, and we're augmenting biology by making edits in non-coding DNA or regulatory elements that control and regulate, and by making those regulating protein expression. In this case, we are targeting the upregulation of disease-mitigating or rescue proteins. Examples of that would be an LDL receptor.
By directly increasing its levels, we can actually create a very robust effect, using a mechanistically differentiated method, which means that we can differentiate mechanistically, in this case, by efficacy from other strategies.
Maybe to dive into EDIT-401, in a bit more detail. Just broadly, can you discuss the science and the medicine behind EDIT-401? What makes it such a compelling candidate?
I think the first thing that makes it really compelling is the effect size we're seeing. When we look across the spectrum of hyperlipidemia treatment development, the non-human primate has been highly predictive across multiple mechanisms for the effect size that you can achieve in humans. That I think is a very compelling element because when we look at our program, we're seeing a 90% reduction of LDL cholesterol in non-human primates. I will add that we have yet to find the minimally efficacious dose in that dose-response curve that generated those data. That 90% matters for a couple of reasons.
One, it is substantially different from that what we see with sort of the next or the closest approach, which is PCSK9 antagonism, where we can see in humans a 50%-60% mean reduction in LDL cholesterol. What does that mean out there in the clinic? What it means is that with a single therapy potential reduce the vast majority of patients treated with a single therapy levels well below the 50 milligrams per deciliter, which is a threshold for really maximally reducing cardiovascular risk, and indeed has been associated with reductions in the size of atheromatous plaques when they're followed in outcome studies.
Could you discuss the genetics that led to this specific edit you're making?
Absolutely. I might turn to Linda.
Yeah.
Excellent.
That would be great. We used human genetic databases to inform our editing strategies. This particular example, we defined our strategy, we informed our strategy through an Icelandic kindred. This particular family exhibits a variant in the three prime untranslated region of the LDLR gene. That variant basically informed a way to edit in the non-coding region of the LDLR gene to increase the expression of the LDLR protein. In that kindred, they have an increase in LDLR protein and thereby an increased clearance of LDL-C. They have a very marked reduction effect size, if you will, in their LDL-C levels, as low as 13 mg per deciliter in some family members. What's happening in the three prime UTR region is that there are various regulatory elements that affect the expression of the LDLR gene and protein.
By deleting those, one can increase the expression of the protein. We essentially identify that through human genetics and then optimize that approach in our EDIT-401 program.
I think it's very important to highlight a number of things, from Linda's description. One is that by editing non-coding DNA, we're essentially increasing the levels of a protein that is normal and is known to the patient. Their immune system is not going to see this as potentially foreign or anything like that. They're actually seeing-
Mm-hmm.
normal, wild-type protein to which they've been exposed their entire lives. I think the second thing that's important is that Linda has described our approach to de-risking and validating targets, that we want to try to treat as uniquely or select uniquely. In other words, when you start going after unique targets, you're going to go after targets that others haven't necessarily gone after, and you don't have the comfort of pharmacologic validation. We now live in 2026 with the power of genetics completely changed from 20 years ago, where we have well-curated human databases or biobanks of hundreds of thousands of genotypes with carefully created clinical data associated with that.
That enables us to select targets like the LDLR that actually have been effectively de-risked by nature's own experimentation when it creates variants that what we're looking for create gain- of- function.
Gilmore, you referenced the broad drops in cholesterol that you've seen in the preclinical models. Could you go into maybe a bit more detail on exactly what you did in the mice, the data that were presented or that were released, and also in non-human primates?
Yeah, absolutely. We first started obviously in primary human hepatocytes to show that our EDIT-401 strategy works in human cells, but we progressed, as Phil has mentioned, into a very robust pharmacology package that we created both in mouse models and non-human primates. Going to the non-human primates first, since they are so translatable to human, as Gilmore has mentioned, we showed dose ranges from 1.5 to 4 mg per kg lowering LDL-C on average over 90% across all of those dose ranges. This was very, very impressive obviously to us. Also in those studies, we saw a very well-tolerated response to our EDIT-401 drug product. There were no clinical observations in those animals. It was very safe and well-tolerated in those studies.
We also saw those drops in LDL-C occurring very quickly within two days in the studies that we've reported in last year's ESGCT and AHA disclosures. We're very excited to see that the edit occurs quickly and the LDL-C clearance occurs quickly. It was durable, so out to one month in the NHPs as we described, and we described a three-month duration in our mouse models, which I'll come to. We leveraged the mouse models to make the point that we could lower LDL-C even regardless of the baseline levels of LDL-C. The monkeys are healthy monkeys, and we wanted to have models in which the LDL-C baseline levels were higher.
We used wild-type mice that were fed a high-fat diet, but we also used a mouse model in which the LDLR gene is heterozygous for loss of function, so mimicking a genotype in familial hypercholesterolemia. Those animals have a haploinsufficiency for one of their alleles, so they have elevated LDL-C, but also in a high-fat diet, even higher elevated. On average between 200 and 250 mg per deciliter. Regardless of the baseline, we were, with our EDIT-401 surrogate that we use in the mice, able to lower on average greater than 90% mean reduction in LDL-C. This was durable out to, as I've just mentioned, three months post-treatment.
Very excited to be able to show this regardless of baseline, and durable, in our mouse and in NHP studies.
You've guided to proof of concept data by the end of the year, human proof of concept data by the end of the year. Can you take us through the timelines of how you're going to get there? Is the ID on track? When could that happen?
Yeah.
When could patients be on it?
We have not decided or we're not sure whether we are doing an IND or CTA. We are basically developing and creating an opportunity for us to do either or both. We are guiding towards the middle of the year for those filings, and we will have the human POC or early POC by the end of the year.
What can you share about the trial's design?
Well, to date, what we can tell you are obviously the ambitions. The objective is to demonstrate tolerability with a particular focus on liver, obviously. We want to demonstrate robust re-reductions of LDL cholesterol. We are currently targeting a HEFH population, that is a heterozygous familial hypercholesterolemia patient population to start with.
In terms of the robust reductions in LDL, can you give us some sense of what you need to see to continue to progress the program? I'm sure there's a minimum in your mind. I guess you might not want to share it, but give us some sense.
Sure. Well, you know, to progress the program, we will have that early POC by the end of the year. We will continue. We probably do anticipate some dose escalation beyond that, into early 2027. What we're actually targeting is, again, at reasonable doses, and well-tolerated doses that we would actually see something that points towards a very competitive package. We want to develop a medicine that is better than a PCSK9 medicine.
What would be the next steps in the program? What trial would you do after the first one here?
We have sort of focused a lot in our discussions to date on the first part of our phase I. How we actually expand that population, expand our safety experience is something that we will actually share at an appropriate time. We believe that based on the precedent we're seeing around us, that we could actually progress from the sort of a phase I/II into pivotal.
Can you help us frame the opportunity for gene editing in high cholesterol? I think the most prominent question we get from investors is who would need a gene editing solution to this problem? Which patients are most appropriate? What proportion of patients are not getting to goal? Where could this really be used?
Well, where we see the early opportunities for this medicine, will be in patients who are refractory to therapy. I think two very important early patient populations spring to mind. Those are the heterozygous familial hypercholesterolemia, and the other would be those with established cardiovascular disease, those patients who already actually had an MI or other cardiovascular event. Those in the United States alone represent about 10 million patients, and that 10 million represents the sort of 75% of that patient population described that are not getting to goal. Those goals right now aren't even that ambitious. You know, right now the goal that's being set by the current guidance is to get to about 70 milligram per deciliter or lower. It is worth highlighting that that actually is moving.
I just want to say that goal is moving lower, and that's important because, I mean, that's a goal that we believe, if we translate to the humans what we've seen in these predictive animal models, is achievable. That goal has already moved in Europe. The joint guidance from Europe just published and updated in the last, in the last quarter of last year really is shooting for targets of 40 milligrams per deciliter or lower for patients with established cardiovascular disease or sitting in that very high-risk group.
What target product profile is necessary to be able to get into these populations? What proportion of patients get to goal? How long does that last? Which goal would you have to take patients down to? What do you think would be not necessarily ideal but something that is competitive and successful commercially?
Well, we believe overall. If you actually look at the way labels, et cetera, are published, we actually believe that achieving a 70%-90% reduction would actually be a very meaningful opportunity for patients. We actually think that combined with the liver tolerability would actually also be very good from profile point of view. I think it's important to say that beyond just the label, and the indications, that ensuring that this medicine is accessible and easy to use would be very important.
We are actually going for an easy-to-use outpatient infusion, and as I've already alluded to, leveraging the opportunity created by using lipid nanoparticles where it's highly scalable, therefore the cost of goods is a fraction of that what we're seeing with cell therapies and therefore enables us to create an offering that not only significantly changes risk for patients and is easy to use for patients' healthcare systems, but actually creates a significant and meaningful value proposition for payers and reimbursers, even while it creates value for our shareholders.
Beyond EDIT-401, what programs does Editas prioritize next? In the past, you've talked about going after other cells or tissues.
Mm-hmm.
-or organs. Where is Editas' pipeline in that respect?
We haven't shared a lot about the pipeline. Our focus, sort of publicly has been very much on 401, what we have said is that we continue to optimize our work for hematopoietic stem cells and looking particularly at for an in vivo editing strategy for the treatment of sickle cell disease and thalassemia. We actually had made substantial progress last year, in the interest of discipline and, you know, fiscal discipline and choosing the fastest path to proof of concept, we prioritized our LDLR program over our HSC program, which enabled our discovery group. I can never resist saying this, I've never met a scientist who didn't say, "I could make that better." They continue to optimize on that side.
We have obviously with our targeted LNP platform, which we use to deliver hematopoietic stem cells, additional programs for other cell types, as well as additional programs for the liver, which can leverage the significant platform validation we'll have done by then. Obviously, at an appropriate time, we'll be sharing more on that.
What work is being done internally on the LNP platform? Where are you innovating and, how quickly?
Well, our innovation's actually, I'm going to pass that to Linda because I have to say, you know, just by introduction, I've been really impressed by the internal work and the speed at which they've actually moved that innovation. Linda.
Yeah. I mean, our liver LNP, we're very pleased with the EDIT-401 platform, where we've leveraged our partnership with Genevant to identify our liver LNP. Now we're moving that to, you know, obviously manufacturing for enabling our first- in- human. We do internally, as Gilmore's alluded, have a proprietary LNP that we're have been working on optimizing for getting to cell types and tissues outside of the liver. HSC has been one of our lead cell types, and we're optimizing our targeted LNP for that, as well as getting to other cell types and tissues of interest.
Great. A couple of questions on intellectual property. In the patent dispute with the Broad, University of California and University of Virginia, the Court of Appeals issued a ruling last year that I quite frankly don't understand. Is there any update on the case? Where does it stand today and what could happen next?
quickly, I hate to do this, but University of Vienna.
Sorry, University of Vienna.
No worries. No worries. The point is that I think the key elements are a couple of elements. One, the interference is only restricted to some subset of the foundational IP that we've exclusively licensed from Broad, Harvard, MIT. I think that's important. The second part is that others who actually need access to foundational IP need the foundational IP even outside that IP that's subject to the interference. From point of view of the PTAB, our understanding is the PTAB was on track. They should actually give their own judgment late Q2 or in Q3 is what they're tracking for. That's the standard guidance.
Our belief is that, you know, based on what the appeals court returned to them, that they're really looking for just some more robust writing around their conclusions. We remain very optimistic that the conclusion will return in favor of Broad and therefore ourselves.
In the past, Editas has licensed its IP to other players in the CRISPR space. Should we expect more of those in the future?
We do anticipate that, yes. As I said, people will need that foundational IP, both at outside the inference as well as within the interference. We would continue to expect to see licenses for those who will be launching products.
A few more corporate questions. In terms of manufacturing, that's obviously a big topic of discussion in gene therapy and gene editing. How do you plan to manufacture?
We've actually used a very carefully constructed, outsourced model. We have a lot of very senior talent inside the organization, the reason we can outsource on the LNP manufacturing is 'cause in many ways, it has become, I hate to use the word commoditized, but actually as close as you can get to commoditization for this. That enables us to be flexible, it enables us to manage our costs very well, and enables to leverage substantial experience. Let's face it, I don't think any good thing came out of the pandemic except the validation of the methodologies for manufacturing LNPs, or conjugated with messenger RNA, or combined with messenger RNA.
I think that that has created a phenomenal amount of talent and expertise and know-how that we can leverage in the best possible way, but also, you know, really controlling the costs and et cetera.
In terms of your pipeline and your toolbox, do you feel that you have all the technologies that you need today, or are there any that you would want to bring in from outside?
I'll start, and then I'll hand it to Linda. I think we have actually a very robust set of technologies. I think the critical thing, and sometimes people underestimate, is just how much know-how we have. A lot of people talk about CRISPR, but the know-how that sits with inside our organization or just a handful, a very small handful of CRISPR companies, is really important because the know-how to actually turn CRISPR from a tool into a profoundly potent therapeutic is really large, and we have that internally, and we're very happy with that. I think we're very happy with our LNP and delivery technologies, but that's not to say we wouldn't ever actually look beyond.
Yeah. I mean, I would just add thinking of it in terms of two buckets, the payload piece and the delivery piece, where, you know, we have a lot of Assets in terms of how we edit and how we think about designing our cargo, and so we're very pleased with that piece of our technology. In delivery, we have delivery technology platforms for getting to the liver, but also for getting to extrahepatic tissues. We feel like we're in a very good place.
Would you ever consider in-licensing or acquiring another candidate? Use your internal expertise to evaluate a candidate that's external and bring that in-house. Do you feel like you have enough going on with EDIT-401 that's not a consideration?
Well, what I would say is that it'd be foolish never to actually have an open mind. I think we're very happy with the tools. We're very happy with the capabilities, we're very happy with the assets we have. I will tell you that Linda and I can speak for the two of us, have a history of, you know, ensuring that we will invest our resources, our know-how, and our dollars in the best possible product. I think that's the best way of putting that. Obviously, if an opportunity, and it's appropriate, arises, you know that's something we would consider. We would never exclude an appropriate or meaningful asset. I say we're very... what's the word? Unemotional about our assets. We're emotional about the mission, but we're not emotional about the assets.
Can you remind us of your cash balance and your guidance for cash runway?
Yeah. Our runway extends into Q3 2027. Our cash balance, we will actually be sharing that just the next, our quarter. I think that'll probably be more appropriate update at that point. I think we ended 2025 with $65 million.
Perfect. Anything else I should have asked you that you'd want to communicate today about Editas and the upcoming milestones?
I think the key thing is that we are very happy and excited about where we are with our lead asset for a couple of reasons. First of all, we believe that it's potentially transformative. Two, in many ways, it moves CRISPR editing into a couple of spaces where it can truly mechanistically differentiate. By using augmentation, we actually believe that it actually is going to differentiate from efficacy with creating a meaningful clinical impact with a 90% reduction potentially for LDL cholesterol, which could really transform outcomes. It also moves CRISPR into space where the prevalent population and the value proposition for public health is much greater, where traditionally it was sort of sitting in sort of rarer diseases. I think that's very exciting.
I think the other part that's exciting about it is that it is a robust validation of a strategy we laid out three years ago, which is to use CRISPR editing to do something that only CRISPR can do by doing non-coding edits that functionally upregulate disease mitigating or rescue proteins. I think we're also very happy with the culture of the company and how it really is executing very effectively, efficiently in a disciplined and fiscally disciplined manner, that really it has an eye laser focus on getting to proof of concept and getting value to patients as quickly as possible.
Great. With that, we're nearly out of time. I'd like to thank you guys for coming by the conference.
Thanks very much.
Thank you.