Editas Medicine at Leerink’s Global Healthcare Conference: In Vivo Focus

On Monday, 10 March 2025, Editas Medicine (NASDAQ: EDIT) presented its strategic shift towards in vivo gene editing at Leerink’s Global Healthcare Conference 2025. The company highlighted its decision to focus on in vivo methods due to their potential for durable effects and reduced complexity compared to ex vivo approaches. While the transition promises broader patient reach, it also involves significant financial and operational changes.

Key Takeaways

• Editas is transitioning to in vivo gene editing, emphasizing its LNP platform.
• The company plans to select two drug candidates by mid-year, with human proof-of-concept data by 2026.
• Financial stability is maintained with a cash runway extending into Q2 2027.
• The Renesel ex vivo program is winding down, incurring costs of $60-75 million.
• Editas is actively seeking partnerships to monetize its intellectual property.

Financial Results

• Cash Position: Editas ended the year with approximately $270 million in cash.
• Cash Runway: The current runway extends into Q2 2027, supporting key milestones.
• Renesel Wind-Down Costs: Estimated at $60-75 million, to be completed by Q2 2025.
• OpEx Guidance: Specific quarterly guidance is pending, with normalization expected post-Q2.
• Revenue Streams: Royalty revenue anticipated from outlicensing agreements.

Operational Updates

• Transition to In Vivo Editing: Focus on in vivo editing due to promising data.
• LNP Platform Development: Progress in proprietary LNPs to reduce liver exposure.
• Drug Candidate Selection: Two selections expected by mid-year, targeting liver and HSC.
• Partnership Strategy: Actively seeking collaborations to advance the pipeline.

Future Outlook

• Key Milestones: Achieve two drug candidate selections by mid-year and proof-of-concept by 2026.
• Strategic Focus: Leverage LNP platform for targeted delivery and pursue differentiated targets.
• Market Opportunity: Expand therapies for sickle cell disease and beta thalassemia.
• Regulatory Strategy: Expedite approvals using existing genome editing experience.

Q&A Highlights

• In Vivo vs. Ex Vivo: In vivo editing simplifies therapy and reduces risks.
• Sickle Cell Disease: Potential to reach millions of patients beyond severe cases.
• LNP Performance: LNP3 achieved 30% editing in mice, surpassing target thresholds.
• Redosing Potential: Exploring possibilities for redosing in vivo therapies.
• Label and Follow-Up: Aiming for a "one and done" label with validated biomarkers.

Readers are encouraged to refer to the full transcript for a detailed account of the conference discussions.

Full transcript - Leerink’s Global Healthcare Conference 2025:

Unidentified speaker, Host: Alright. So, I guess we’re gonna get started. So welcome to Leerink Global Healthcare Conference twenty twenty five. So this morning, we are discussing with the Editas management team, and we have Eric Lucera, and we have Gilmore O’Neil with us. So thank you again for joining us for this conversation today.

So a lot of exciting things in the making for Editas. So obviously, maybe we can start with the transition, right? The company has been transitioning in kind of focusing on the gene editing, but in the in vivo setting. So I guess the first question would be, what are the type of indication for which you think editing can be a potential advantage over, you know, other genetic medicine, per se, more traditional gene therapy or even RNA approaches?

Gilmore O’Neil, Editas Management, Editas: So that’s a that’s a really super question because it really is at the core of our strategy to make sure that Editas chooses targets that are clearly differentiated. So if you look at editing versus traditional sort of AV delivered type, transgene delivery, really interested in going after diseases where durable effects are required. And that actually is really critical in tissues where there’s any kind of tissue turnover where you’re going to get dilution because an edit makes a permanent change in the genome, which will be copied with every cell division and expressed in every daughter cell, unlike an AAV, for example, where you get a dilution of the effect. And then with regard to other types of therapies like siRNA, ASO, RNA editing, our key focus is on ensuring that we allow CRISPR or use CRISPR to do things that others cannot, that those cannot do. And so one approach that we’re really focusing on right now is going after or targeting non coding DNA, which actually controls the expression of a gene and essentially allows us to dial up the volume of a protein that actually is mitigating or is disease mitigating.

And this is something that really, in the main, those other modalities cannot do or rarely could do.

Unidentified speaker, Host: Great. And so how should we think about specificity, specifically in the context of trying to dial up those genes by targeting non coding elements?

Gilmore O’Neil, Editas Management, Editas: I think we actually should be, obviously, with the the appropriate humility before nature, we should actually feel very confident about it because we actually have generated significant experience and indeed we have actually been in humans with precisely this strategy. Yes, we were using an ex vivo strategy with our Renesel asset, but we learned a lot about it was that we can be very confident about the specificity of the targeting of that editing. And as I say, we had a super experience with Renesel from that point of view.

Unidentified speaker, Host: So actually, talking about Renesel, so before we dive a little more into what’s coming in the in vivo pipeline, so looking back a little bit with brand new sales. So obviously, at first, you know, you had some exciting data in the in vivo pipeline, kind of leading to the company trying to focus more on in vivo in the third, fourth quarter last year. And then you set out to find a partner for this particular program. And then toward the end of the year, the program was terminated. Can you tell us a little bit more about the journey that it was to kind of try and look for a partner for the program?

Yes. And maybe what were the challenges there?

Gilmore O’Neil, Editas Management, Editas: Well, I might preface it, but a little bit of the journey of the company in that, when two years ago, we announced that we were actually going to really focus our attentions and really drive towards being a leader in in vivo editing. Notwithstanding that we had a very potent asset we believed in ReniCell. The end of last year, we had a convergence of two points. As you said quite correctly, we had some very exciting data for in vivo editing, both for a undisclosed target, liver target, as well as for a in vivo editing of hematopoietic stem cells. And at the same time, we had run this process.

And I think what we learned was in that process as we were looking for partner that a lot of the target companies were very intrigued by the data. They actually were very excited about the potency of the data with Renesal and really wanted to see it in vivo. And I think that’s where the key takeaway was that, they see and they saw, as we do, a significant opportunity to treat sickle cell and beta thalassemia. They actually think there is a not surprising, there’s highly prevalent diseases and they believe there’s a very robust market. However, they think that in vivo is the right approach and that’s what we are pursuing.

Unidentified speaker, Host: Great. So obviously, the work you’ve done there, there’s been a lot of both investment in terms of R and D, in terms of capital in that program. So have you seen now that you’re switching into in vivo? You’re not starting from scratch, right? You’ve been working on that in vivo pipeline for a while now.

But what are some of the learnings from that brand new cell program that you’re taking with you into this transition to in vivo?

Gilmore O’Neil, Editas Management, Editas: So there are a number of learnings. The first is that, our editing strategy that is focusing on functionally dialing up, the expression of a disease mitigated protein is a very potent therapeutic strategy. Second, we really are very confident about the particular target in the HBG12 promoters that we are targeting. Indeed, we’re using that guide as we go forward in our in vivo program. So, that’s a very nice piece of de risking.

We’ve actually used ASCAS12A, which is developed at Editas, and that has been robustly validated now in humans. And that actually also is another significant de risking event. And then finally, we know a lot about the disease space, both in sickle cell disease and beta thalassemia. And those are all elements which combined together will help us drive the in vivo programs.

Unidentified speaker, Host: So I guess thinking more now on the capital investment side of things. So how should we think about, the winding down of the ex vivo program? And how should we think about, kind of capital investment in the infrastructure to continue to support the in vivo programs?

Eric Lucera, Editas Management, Editas: Yeah. I’d say with respect to the wind down, I think when we filed our Q and our K, we estimated $60,000,000 70 5 million dollars that would go into the second quarter, and we expect that that should be basically done by then. With respect to, in vivo, you know, unlike us having clean rooms with the autologous program, we’re just going to do pure outsource model for that.

Unidentified speaker, Host: Okay. Thank you. So I guess, as I mentioned, the transition was kind of prompted well, I mean, you’ve set to be the leader in in vivo editing for a couple of years now, but the transition was prompted by some, in vivo data. Before we dive into that, can you tell us a little more about your LNP platform and how do you see it being differentiated versus competitors?

Gilmore O’Neil, Editas Management, Editas: Yes. So as we look at first of all, one of the important things for NVivo is to have that LNP delivery technology under your roof. And so when it comes to a targeting LNP, we’ve actually made significant progress in developing our own targeting LNP, which comprises a unique combination of lipids that detarget the liver because we actually want to significantly reduce where we want to target tissues other than the liver, like the hematopoietic stem cell, we want to significantly reduce or eliminate the exposure to the liver, which is a source of toxicity with LMPs. And the second thing we want to do is significantly enrich the targeting of a specific cell type. And we’ve done that by essentially developing a method for conjugating a targeting ligand.

So basically a molecule, it can be a peptide or something else that can be tied to or linked to the LNP or lipid nanoparticle that would then actually deliver it to a specific cell, and in this case, the hematopoietic stem cell. And from a point of generalizability, we’ve talked in the past about plug and play for the genetic targeting, you change a few nucleotides on a guide RNA and you can change the gene that the editing mechanism targets. We in the same way can change the targeting ligand that we bind to the LNP in a plug and play method and then target a different tissue or different cell type beyond the hematopoietic stem cell.

Unidentified speaker, Host: And so specifically to that, so you had presented late last year some preclinical data relating to your optimized tLNP. Can you maybe give us an overview of the data and its significance?

Gilmore O’Neil, Editas Management, Editas: Yes. So I think the first thing that the key takeaway is that we are actually in those data we presented, we were actually already approaching a threshold that is going to be clinically meaningful for editing in HBG or HBG 1.2 in hematopoietic stem cells. What we essentially have shown is the transition as we’ve moved from and evolve our LNP, so called LNP one, two and three. When we had our second key iteration LNP where we had actually done some tweaking of the lipid nanoparticle chemistry and put on a targeting a novel targeting ligand to go to HSCs, we saw already in mice a 10% editing in HPG one, two. And we were so excited about that, that we actually took that into monkey and I’ll return that in a second.

But with our LMP3, where we had further optimized and significantly detargeted the liver, so called LMP3, we actually were achieving 30% editing of HbG1.2, which is nicely above a threshold. We think the threshold is about 25% editing required. Now that is moving into monkeys. But indeed, when we took LNB2 into monkeys, the data we shared in January on that was that that 10% already translated in monkeys or non human primates into 17% editing. And that was just at seven days follow-up.

The nice thing about non human primates is that you can continue to follow them after each assay on length of the device. And so we’re really looking forward to sharing more of those data in the future, because we’re very excited about the data that continue to generate both for LNP2, but actually also for LNP3, which is we believe is threefold more potent than LNP2.

Unidentified speaker, Host: So to that effect, when should we expect additional data for LMP2, so second generation in monkey, so longer follow-up? And then when should we expect initial of monkey data for LMP3?

Gilmore O’Neil, Editas Management, Editas: Yes. So what we’ve guided to is that we are actually looking to we’re targeting getting to two DCs or drug candidate selections, one for in vivo HSC and the other for a liver target. And we’re planning to do that in the middle of the year. And so in the middle of the year, we plan to share more data. And obviously, we’ll be disclosing more data at scientific meetings going through the year.

Unidentified speaker, Host: So you mentioned obviously that we will see more data throughout the year. Are there any tissues that you’ve seen the platform being applied to that are easier to target than other? Like, so we’ve talked about the targeting of the liver, but in terms of the other tissue that you’re going after, are there some that are easier to target than other?

Gilmore O’Neil, Editas Management, Editas: Well, I can step back for a second and say that in addition to our own proprietary target LNP, we actually have a wonderful collaboration with Genovant, who have a liver targeting LNP. And obviously, the liver is very easy, well, very easy, that’s standing on the shoulders of thirty years of research. But today is it’s relatively easy tissue to target. And indeed, we continue to see really exciting data on in vivo editing coming out, not just from us pre clinically, but others clinically in the field. So this is all wonderful for us all and for the patients that we look forward to treating.

But I’d say the liver is a relatively easy one and that is why we have a program or a lead program that we hope to DC in the middle of the year. Now we haven’t shared the target, but we look forward to sharing that very soon. But the key thing again is it’s differentiated. Going back to your original question about how is how are we using CRISPR to differentiate from other technologies. And again, this is about potent, high efficiency dialing up of the dose of the disease mitigating protein.

And we did actually present some sort of anonymized data earlier this year for that liver target, where we again showed very high levels of editing. We basically had nearly maxed out editing in the liver at around 70%, where hepatocytes represent about 70% of a liver cells. And we actually saw, again, a fourfold increase in the target of interest with substantial like a 60% reduction in a critical biomarker, which is actually meaningful in human disease. So overall, we’re very excited about that. And again, it’s a nice example of how we are going after an additional tissue to hematopoietic stem cells.

Apropos targeting and the plug and play, in many ways, changing the ligand is going to be the key thing. So identifying the ligand for the cell that you want is going to be a critical element for those targeting LPs as we move beyond HSCs.

Unidentified speaker, Host: And so you mentioned partnerships. So if you see those partnerships kind of based on the value that you bring with your LNP platform, can you tell us a little more about the IP portfolio that surrounds the platform?

Gilmore O’Neil, Editas Management, Editas: Sure. So we actually have built a robust IP portfolio around both our targeting LNP, we’re building that and obviously around our editing technology. Indeed, we have foundational IP that is relevant not just to us, but to others in the space as they move their programs forward. And obviously, that latter part was emphasized, validated and indeed valued by the agreement we made with Vertex just a year ago to enable the launch of KAS JV. And since that time, we actually further monetized that deal with monetized the downstream payments with DRI.

Unidentified speaker, Host: So can you tell us so you mentioned the different portion of that DIP portfolio. Can you tell us a little more in terms of your licensing monetization strategy, the existing collaboration and where you see potential for growth?

Eric Lucera, Editas Management, Editas: We are very fortunate to have the foundational Cas9, Cas12 license from Harvard MIT Broad. It’s a traditional university royalty rate that we think that we can outlicense to everyone that’s pursuing a target in that area. As you know, those are sort of low single digit type royalties. So, we have the deal with Vertex on one hand, but we also did deals with Vore and Bristol Myers and several others. And, we’re really looking to just create a bespoke agreement with any company that, looks to use the technology to advance the field.

Unidentified speaker, Host: And so how should we think about, existing collaborations? So the cadence of potential development milestones, in the short to midterm?

Eric Lucera, Editas Management, Editas: So I would say with respect to some of the IP licenses, each one is different. Obviously, I think the most advanced one beyond the cash GB license is the deal we have with Bristol Myers. If you go back on their R and D day from a couple of years ago, there’s several programs that they are progressing and we would expect, incremental payments along the way. For some of the earlier deals, those are more back end loaded, based on the fact that they’re just smaller companies. So it really is a case by case basis with each one of them.

Unidentified speaker, Host: And so I guess kind of walking back to my original question, where do you see, greatest potential for growth? What would be, ideal partner for where the pipeline or where the platform is at this stage?

Eric Lucera, Editas Management, Editas: I think, you know, when you think about partnering the the pipe the pipeline of IP, it’s really on a case by case basis. I think the Intellia assets are the ones closest to market. You know, so those are the ones that are most interesting to us.

Unidentified speaker, Host: Great. And so I guess, so maybe just kind of zooming back on the corporate side of things. So we’ve talked about the transition from ex vivo to in vivo. We talked about the winding down. So how should we think about the cash runway as of now, what it covers and kind of the next key catalyst for the company?

Eric Lucera, Editas Management, Editas: As we stated on the last time we reported earnings, we ended the year with cash of about $270,000,000 which gets our runway into the second quarter of twenty twenty seven. Included in that runway are not only the two DCs that we expect in the middle of the year, as Gilmore mentioned, but also human proof of concept by the end of twenty twenty six. So in sum, our cash runway allows us to get that that first set of human data.

Unidentified speaker, Host: And can you talk a little more about, how to think about OpEx moving forward? So again, you know, there’s been, investment made in the ex vivo side of things, transitioning into in vivo. How should we think about OpEx?

Eric Lucera, Editas Management, Editas: Yeah. I would say it’s a little bit muddied by the fact that we’re going through the transition of the wind down of Renacell. But as I mentioned, we expect that to be concluded by the second quarter of this year, at which point, you know, you’ll see a more normal level of OpEx. So if you know, we haven’t given specific quarterly guidance, but if you sort of look at where we’re beginning with two seventy million dollars and getting into second quarter of twenty twenty seven, you can look at the runway of OpEx for this quarter and say we do that for another quarter as we wind Renacell down, and then just take the remaining cash and then divide it over the couple of quarters. That should get you close to what the run rate OpEx will be.

Unidentified speaker, Host: All right. So I just want to check if we have any questions for the from the audience? Great. So now, I guess this will be a good day to dive a little bit more into maybe the sickle cell disease space and where do you see an advantage of editing over, other modality? And then within editing itself, how can in vivo be differentiated from all of the ex vivo approaches that we’ve seen?

Gilmore O’Neil, Editas Management, Editas: So that’s a great place to go and, the truth is that by going to in vivo, you massively simplify the therapy. You significantly reduce the risks. And frankly, you reduce the burden on patients, their families, and health care systems. And those altogether come forward and actually create the ability for a therapy used across a much larger proportion of patients with sickle cell disease and with beta thalassemia. And the reasons for that are that you don’t have to first of all, you eliminate Biosulfa, and the conditioning is a substantial risk for patients.

The second and basically because of that, really forces patients with the most severe forms, refractory forms of the disease, in the case of sickle cell, or indeed thalassemia, to really consider a transplant. And most others don’t, even though the diseases are still dreadful. I think it’s worth reminding everybody that, you know, where you don’t have supportive care or the access to supportive care is much more limited, in Sub Saharan Africa, the mortality for sickle cell disease is of the order of sixty percent to eighty percent by the age of five. So eighty percent of, babies born are most likely not to see their fifth birthday. So it’s it’s absolutely diabolical disease.

With significant supportive therapy, where it’s accessible in The US and other, much richer countries, you can actually get that the median survive is around fifty. So it really is a terrible disease. So expanding beyond that most narrow sector to actually, you know, the vast majority of patients creates a huge opportunity within all the health systems. So I think this is really where we see a huge opportunity. And you’re not talking about 10,000 or 20,000 patients in a handful of countries, but you’re talking about potentially reaching hundreds of thousands and millions of patients.

Unidentified speaker, Host: And so there are a few companies that are working on non genotoxic conditioning for sickle cell disease specifically. How do you think, you know, if successful, those approaches would change the market opportunity for in vivo editing?

Gilmore O’Neil, Editas Management, Editas: I think at the end, what I left out, as I was talking about differentiation beyond just the toxicity of conditioning, is the journey. You know, we look at an in vivo therapy as a single infusion. So again, simplicity and the burden of therapy is it’s massively simplified. I think obviously pursuing a non toxic or less toxic conditioning is a wonderful approach. It still, however, requires patients to have their cells mobilized, collected, edited and then go through obviously one hopes is a much simpler transplant process, but they still have to go through that.

So there’s a complexity and a burden for the patients, which in vivo could essentially bypass completely.

Unidentified speaker, Host: And so now looking into circling back to what you’ve seen with LMP1, LMP2, LMP3 in terms of hematopoietic stem cell editing. Where do you see so are you confident with the level you’ve reached with LMP3, that it would translate to human? Would you want to continue the optimization before you go in human with this program? Where do you see, the vivo data translating? We actually feel very confident

Gilmore O’Neil, Editas Management, Editas: about the threshold, we believe so. We’re setting a threshold, a targeting threshold for editing about 25%, you know, 20% to 30%. And that’s based on the allogeneic transplant experience, which is shown that once you’ve actually achieved that kind of level, you know, and we’re basically doing an equivalence, you know, of chimerism. So, basically, you know, post transplant patients may have 30% of the cells are from the donor and 70% are their own cells still. So, once you get to the about that 30% or 25% to 30%, you basically damp down or control the complications, the vaso occlusive events and the other complications of sickle cell disease based on that published experience.

So that’s very good. And as I say, we are feeling very good about the potency that we’ve seen to date and where it is. We’re actually already in mice, have exceeded that with LNP3. And it’s important to emphasize that those mice are not just it’s not myosinomatopoic stem cells, I should have said that, forgive me. Those mice are engrafted with human stem cells.

And so that is very compelling. And so as I say, we’ve already exceeded that threshold in the mice and we’re looking forward to sharing more data in non human primate in the future and expect and hope to see that.

Unidentified speaker, Host: And so, I guess maybe one last question. So when we think about so we’ve talked about the limitation in terms of non toxic conditioning. We’ve talked about, kind of the potential for in vivo to simplify the journey. So now that we’re talking about in vivo, can you maybe contrast and compare the editing specifically approach versus a gene therapy approach?

Gilmore O’Neil, Editas Management, Editas: Well, I think this goes back to your question of what we’ve learned from Renaissance. We’re actually simply using the same targeting strategy. We’re using the same enzyme. We’re using the same guide. The only difference is that we are putting that editing machinery into a lipid nanoparticle, so we can do a single or possibly two infusions, but we’re targeting a single infusion injection.

And so overall, we have substantially derisked the targeting in the human with the use of that editing mechanism that we’ve already validated.

Unidentified speaker, Host: And so you mentioned one infusion, two infusions. So if you see using LNP, how should we think about the need for potential redosing?

Gilmore O’Neil, Editas Management, Editas: Well, it’s something that we obviously are making sure that we can do. We are obviously actively looking at that. In an ideal world, we would go to a we would try and get to a single infusion that would actually much simpler and easier for patients to deal with. But, you know, prudent says that you can actually look and we should look to assure that we could actually possibly do a repeat infusion. And even then, that would still be a much, much simpler journey for a patient in the health care system than autologous ex vivo.

Unidentified speaker, Host: And so far, far, I guess, in the future from now, looking at what a label could look like, how long of a follow-up do you think you would need in a pivotal study to demonstrate durability and potentially have a label that’s kind of a one and done?

Gilmore O’Neil, Editas Management, Editas: So that’s a great question. I think, obviously, I have a view. Regulators might have a different view and obviously be a matter of degree. But what I can tell you is that one of the things that’s really good about where we are today is that we have substantial experience now across a number of different platforms when it actually comes to making permanent editors or genome changes, using both CRISPR as well as other mechanisms. And there’s a lot of regulatory and frankly, clinically experience.

So what would be required for the duration of follow-up for an approval or what endpoints you would use? I think actually there’s a lot more opportunity to actually use the more aggressive strategy and potentially focusing on fetal hemoglobin alone rather than actually having to follow patients for a planned period of time. We will do that anyway. But I obviously think that there’s been obviously substantial cross platform experience with using fetal hemoglobin, for example, as I would say now robustly validated biomarker to predict efficacy. And again, obviously, because we can actually, we can monitor, calculate or quantify the edits, once an edit is in the genome, it’s in the genome.

It’s not going anywhere.

Unidentified speaker, Host: All right. I guess we might have one more minute for maybe one question from the audience. If anybody has a question. All right. Well, I think we are set here.

Thank you again for your time. I very appreciate the time and the conversation.

Gilmore O’Neil, Editas Management, Editas: It’s very lovely talking to you.

Unidentified speaker, Host: Likewise. Thank you, everyone.

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