Editas Medicine, Inc. (EDIT) Earnings Call Transcript & Summary

Good evening, and welcome to the Editas Medicine's Conference Call. [Operator Instructions] Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Cristi Barnett, Senior Vice President of Corporate Communications and Investor Relations at Editas Medicine.

Thank you, Shamali. Good evening, everyone, and welcome to our strategic update conference call. Earlier today, we issued a press release providing several new corporate updates. A replay of today's call will be available in the Investors section of our website approximately 2 hours after its completion. After our prepared remarks, we will open the call for Q&A. As a reminder, various remarks that we make during this call about the company's future expectations, plans and prospects constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent annual report on Form 10-K, which is on file with the SEC as updated by our subsequent filings. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Except as required by law, we specifically disclaim any obligation to update or revise any forward-looking statements even if our views change. Now I will turn the call over to our CEO, Gilmore O'Neill.

Thank you, Cristi, and good evening, everyone. Thank you for joining us today for this Editas Strategic Update Conference Call. With me today are 2 other members of the Editas executive team, our Chief Financial Officer, Erick Lucera; and our Chief Scientific Officer, Linda Burkly. This afternoon, we announced our strategic transition to be a purely in vivo gene editing company. Why are we making this pivot and why now? As we have said over the past 2 years, we believe that the ability to provide in vivo gene editing that functions via gene upregulation across different tissues holds the potential to dramatically expand the addressable therapeutic possibilities for CRISPR-based gene editing and to position Editas to be a leader in the field. Over the past 2 years, we reset our leadership and brought in a world-class Chief Scientific Officer in Linda Burkly. We built the right team for in vivo medicine development and refocus our discovery and technology groups. Execution is all about having the right people, and we are confident that we have the team to support our in vivo goals, and we developed the right delivery technology. As a reminder, we have been working on in vivo delivery for quite some time as well as having significant in-house expertise around guide RNA and Cas12a enzyme. This year, we developed the internal and in-licensed external LNP delivery technologies. We began 2024 by laying out our corporate goal to have in vivo editing in at least 1 species by year-end. As you know, we focused discovery of in vivo editing on hematopoietic stem cells and in other tissues and have some exciting updates today. Importantly, recent scientific breakthroughs by the Editas team have convinced us that the time lines around the near-term viability of in vivo CRISPR-edited medicines have accelerated meaningfully. Less than 2 years after announcing our strategic reset, we have achieved in vivo proof of concept with a high level of HBG1/2 promoter editing with associated fetal hemoglobin induction in a humanized mouse model for the treatment of sickle cell disease in beta thalassemia using a single dose of an HSC or hematopoietic stem cell-targeted lipid nanoparticle or tLNP formulation. Today, we shared that it has had achieved approximately 40% editing of the HBG1/2 promoter site with longer-term follow-up after using a novel, Editas-proprietary tLNP for extrahepatic tissue delivery to deliver a single dose of our clinically validated Cas12a editing machinery directly to hematopoietic stem cells in mice engrafted with human hematopoietic stem cells, which is a meaningful advancement for the 29% editing data that we previously shared in October. Importantly, editing in HSCs with our tLNP formulation results in a meaningful functional outcome of HbF or fetal hemoglobin induction indicated by the presence of fetal hemoglobin expressing human red cells on average 20% that populate in the host by 1 month. And remember, the HBG1/2 biology has already been validated and derisked in patients with reni-cel in our RUBY trial, making a true plug-and-play element of our in vivo strategy. As we turn this week from the American Society of Hematology's Annual Meeting and Exposition or ASH, and see data from others in the field, we continue to review our preclinical data as highly competitive and meaningful and believe that our strategic pivot will allow us to achieve human proof-of-concept in approximately 2 years. These advances create the opportunity for us to deliver an in vivo HSC therapeutic to treat many more patients with sickle cell disease and beta-thalassemia more simply and without the risk and morbidity of chemotherapeutic conditioning required for cell therapies. On top of our significant progress in extrahepatic tissue delivery and editing, we also share today that we have now achieved in vivo proof of concept of high-efficiency editing in the liver in nonhuman primates and our collaboration with Genevant. We believe our in vivo HSC editing success will enable targeting of other extrahepatic tissue or cell types, targeting beyond HSCs and demonstrate the potential of so-called plug-and-play targeting in an in vivo extrahepatic LNP formulaic platform. Our upregulation capability additionally enables a differentiated strategy for liver targets for diseases with high unmet need and first-in-class opportunities. We will share additional preclinical data and time lines for our in vivo programs in the first quarter of 2025. So based on these in vivo advances and breakthroughs, now is the time for Editas to transition to a fully in vivo company. As part of this critical pivot to a purely in vivo company, we are ending the development of reni-cel after an extensive search process did not yield a commercial partner, and we are initiating an approximately 65% reduction in our headcount. These actions together, while undoubtedly difficult and not made likely, will optimize our cost structure and extend our cash runway into Q2 2027, funding our efforts to achieve in vivo human POC in approximately 2 years. Before turning to Q&A, I want to address several important groups of people, including our employees, patients, caregivers, investigators and clinical trial sites. We have achieved significant progress in advancing our strategy and prioritization over the last 2 years, which would not be possible without the tremendous dedication and commitment of all of our employees. To our colleagues who will transition from Editas over the next 6 months, I'm so proud of the work of each and every one of you. More than 35 patients to date have been functionally cured through the RUBY and EdiTHAL clinical trials. Reni-cel has helped validate and derisk our pivot to in vivo and laid the groundwork for us to develop an in vivo HSC medicine for the treatment of sickle cell disease and beta thalassemia. And to the patients, caregivers, investigators and clinical sites involved in the RUBY and EdiTHAL trials, we owe you a debt of gratitude. Your dedication to developing a potentially transformative medicine for sickle cell disease and beta-thalassemia and your work in these clinical trials has both strengthened, reinforced our commitment to sickle cell disease and beta thalassemia and significantly contributed to scientific advances that will enable in vivo edited therapies that can treat many more patients with less risk conditioning. Finally, Editas is in discussions and consultations with clinical trial sites, regulators and other parties to determine the best path for patients currently enrolled in the RUBY and EdiTHAL trials. With that, I thank you very much for your interest in Editas. And I'm happy to answer questions.

[Operator Instructions]. Our first question comes from the line of Samantha Semenkow with Citibank.

I have a few questions on the updated in vivo sickle cell disease data. You mentioned the study achieved 40%. It has a longer follow-up versus the data we've seen previously. Can you just share a bit more details on what was different in this study? Was it just a longer follow-up? Or had you optimize some of the other components in the study? And I have a follow-up.

Thanks very much, Sam. I'm going to ask Linda to take that question.

Yes. Thank you for the question, Sam. There were a couple of differences. So there are 2 independent studies first to clarify. Importantly, the 29% that we previously reported is 29% allelic editing of HBG1/2 in hematopoietic stem progenitor cells. And the 40% update that we're reporting is very importantly, the editing level that we've achieved in hematopoietic stem cells, the long-term hematopoietic stem cells. So there's a longer-term follow-up in this experiment, but also we're measuring the editing in the most relevant cell type because the long-term hematopoietic stem cells are the self-renewing stem cells responsible for repopulation of all the hematopoietic lineages. And so this is really the meaningful cell type. And this is corresponding with the approximately 20% HbF induction of the RBCs in the bone marrow.

Okay. Got it. That's very helpful. Yes. So the follow-up, I guess, just on that 20% HbF expressing cells, it seems a bit low versus what we've seen for ex vivo approaches. I guess, are there experimental conditions we should be considering when we think about that data point? And do you have some strategies to increase the percentage of HbF [ induction ] going forward?

Yes. So we are continuing to optimize both the cargo and the LNP formulation. So both of those strategies are ongoing, and we will report on those experiments as we -- the data become available. But we have those actively going on and are seeing encouraging results in those avenues.

Our next question comes from the line of Gena Wang with Barclays.

So I have 2 sets of questions. One is regarding the guidance regarding the cash. Do you have a $265 million cash as of 3Q and you will have additional $70 million cost. Can you walk us through like how could that support cash runway into mid-'27? If my math is correct, every quarter would be less than $25 million per total. And then my second question is regarding the in vivo approach. Maybe I wanted to ask you, we also saw other competitive data for the in vivo approach. Like what will make you confident yours will be differentiated from competitors? And also since this first indication is still sickle cell, why let the CMO go since his focus is sickle cell?

Thanks very much, Gena. So for the first question, I'll have Erick address the guidance for cash. And then I think Linda and I can address your in vivo approach questions, particularly about competitor data. Erick?

Yes, Gena, thanks for the question. So if you recall, we ended the third quarter of this year sort of pro forma for the DRI deal of about $320 million. So if you think about sort of what our burn had been on a quarterly basis and then think about having substantially less activity as you transition towards an in vivo only company, that's sort of how we get there. So we're -- actually, the starting point is $320 million from the third quarter, essentially.

Thanks very much, Erick. And then Linda, I propose the competitive differentiation.

I can start off by commenting on that. So our approach, of course, is using a targeting strategy and an enzyme that we've learned through the Reni-cel/ex-vivo approach, and therefore, it's a clinically validated approach to upregulating gamma globin for anti-sickling. And so we're taking the learnings from reni-cel that are clinically validated to then design our in vivo approach and combine that approach to targeting the site of interest with a delivery strategy that we've now created in a targeted LNP. The competitor approach, for example, base editing the HBB locus for converting back to the wild-type beta globin. This is a different approach. This is not a clinically validated approach. So we don't really know that by comparison to our clinically validated approach, how well that can work. And we also know that over increased expression of gamma globin is the more potent anti-sickling approach than increased expression of wild-type beta globin chain than increased expression of gamma globin. So we feel confident that the increased gamma globin expression is a competitive approach. Gilmore, did you want to add anything?

No. I think, as you said, the key thing also is that beyond the targeted LNP, we have validated both the editing machinery and the gamma globin promoter targeting or HBG1/2 promoter targeting strategy. Thanks, Linda.

Our next question comes from the line of Joon Lee with Truist Securities.

This is Mahdi on for Joon. I want to continue on the differentiation with competitors. And basically back to Linda's point, I just want to understand how HBB reverting back to normal is not anti-sickling compared to HbF induction. So basically, the question would be how this strategy of induction of HbF can compare to HBB reverting back to normal?

Yes, of course. I think if -- obviously, if you change every beta S back to wild type, you would have completely created the wild-type situation. But if you haven't edited in a very high efficiency way, then it's a question of relative potency of gamma globin versus wild-type beta chain in terms of anti-sickling activity. And so there is biochemical evidence that gamma globin is a very effective anti-sickler as compared to the wild-type beta chain in terms of disrupting polymerization of beta S with the alpha-globin chain.

And a follow-up question would be if there was a way to reverse enough of HBB, which we see evidence of that at ASH being presented like [ testers' ] data. So then in face of that eventuality, how competitive would be the HbF strategy -- HbF upregulation strategy?

Yes, I think, we know from the hereditary persistence of fetal hemoglobin that is a very protective strategy to upregulate gamma globin. So -- and again, it's very clinically validated. Both by reni-cel and as well as by the HbF patients -- individuals to be genetically validated. So we have confidence in this strategy.

Thanks, Linda. I mean the key thing there is that we have both genetic and pharmacologic validation of this strategic approach with obviously very powerful data from our experience with reni-cel. Thanks, Linda.

Our next question comes from the line of Jack Allen with Baird.

I have one to start and then one follow-up. I guess to start, I just wanted to clarify. On the 2 years to human proof of concept, is that in hematopoietic stem cells? Or is that just generally for in vivo gene editing?

Thanks very much, Jack. We've actually made, in general, we have a number of approaches in our pipeline. And obviously, why we call out hematopoietic stem cells because the secret about that work we've been doing over the last few years. We do have some other shots for that in vivo POC.

I guess to that regard, would you view the stem cell work as the most advanced in your pipeline? Or is it being a nonhuman primate with the liver-targeted asset via the partnership with Genevant viewed as more advanced in your eyes?

I think they're actually -- what I would say is that we are developing them together. Obviously extrahepatic delivery to -- or rather HSC delivery of a validated both genetically and in our hands, pharmacologically validated target is very exciting. But we say, with a couple of approaches and targeting programs, we are confident that we can get to human POC in the -- within 2 years is good.

Okay. Got it. Great. And then this is very much off topic, but I wanted to ask about IP. I think there was a U.S. appeal ongoing surrounding the CRISPR/Cas9 IP that was expected to read out this year. How are you thinking about the intellectual property aspect of the business these days?

Yes. No, I appreciate that, Jack. We believe that it still remains a part of our business. It has generated significant upside from a nondilutive point of view. The appeals court has not actually read out its decision yet. And it remains to be seen, whether it will be the end of this year or early next year. But our IP business still really remains an important part of our business, largely because we have seen it well validated, both -- and most particularly by deals that we have recently done. And so we've had both validation and valuation of that IP business. Erick, is there anything you want to add to that?

No, I think you answered it well.

Our next question comes from the line of Dae Gon Ha with Stifel.

Two-part question for us would be, number one, when you say 2 years to human proof of concept, I mean, is there a point where you would need to decide between HSC targeting versus other extrahepatic. And if so, what would be sort of the deciding factor? And if you can maybe even provide a little bit more granularity, like when would you make that decision point? Would it be some late-stage preclinical data that starts deviating towards one program versus the other? I mean just wanted to get some sense on that. Second question is when we look at the reni-cel discontinuation or the ending development after extensive search did not yield I think it was late October, you talked about starting to look for a partnership for that reni-cel alongside your in vivo preclinical data. It seems pretty quick. So if you could provide any more context around that or if there is any possibility of salvaging that deal?

Sure. Thanks very much, Dae Gon, for your questions. So with regard to the timing and selection criteria, that is something that we're going to give more updates in the future. As we said, we will have -- give more updates on data and more precision around time lines in the first quarter of next year. But obviously, it's an important thing, and I appreciate why you're posing the question. With regard to the reni-cel process, this was a very extensive and formal process run with our partners, Moelis. We actually spoke with multiple strategic partners, large and medium-sized and believe that this, from an [ outbuy ] point of view was exhaustive. Erick, I don't know if you want to add anything to that?

Yes. I would just add that to your October date, that's when we announced that we had begun the process during the quarter. So that would push the introduction of the process back a little bit further than a late October date. We've actually been at it since the end of the summer.

Got it. So Gilmore, 2 years to human proof of concept, just to be clear, is that for both extrahepatic and HSC or just one?

So right now, we are giving some guidance probably for one, but we will actually, obviously, as time evolved, we have clarity of our time lines and our data, we will give more clarity.

Our next question comes from the line of Phil Nadeau with TD Cowen.

Two from us. One, a follow-up on the prior question and maybe it's also too early to answer this one. But in terms of the milepost from here, the human proof-of-concept data, can you give us a sense of what you'd be willing to disclose between here and there? Maybe not specifically when it could be disclosed, but what types of information can we look forward to from here until you establish a proof of concept? That's first question. And then second question, on the resignation of the Board members, was that due to this decision? Was this a controversial decision within the Board? Or did those Board members resigned for other reasons independent of the strategic direction?

Yes. Thanks very much, Phil. Let me answer the second question first because I think it's very important to be clear about that. This was a difficult but not controversial decision. We had unanimity and support of the Board and the Board members who are resigning have done it for other reasons. It is probably also worth saying that with the change in the company and the size of the change -- the change in the size of the company and the staging of the company, I think there was a feeling also that this is an appropriate sizing. But I think I just want to emphasize, absolutely there was unanimity in support of this decision and the Board members who are -- [ had off the resignations argues ] for other reasons. And then with regard to your first question -- sorry, with regard to data updates and so on, we will actually outline with more clarity in the first quarter about time lines, et cetera, and do have -- anticipate being able to have lay out what we will be doing and when.

Our next question comes from the line of Luca Issi with RBC Capital.

Great. Maybe 2 quick ones. Gilmore, going back on Dae Gon question, the decision to terminate reni-cel. Can you just maybe expand a little bit more on that? I guess the question is, what was the main pushback that you were getting from strategic? I think many of us think that problem with pushback was around the commercial opportunity given busulfan, but would love to kind of hear a thought on what was ultimately made strategic kind of passing on this asset. And then second, can you maybe just talk a little more about, this is Gena's question, earlier on the departure of Baisong, given you still focus on sickle-cell disease just maybe tell us a little more about the decision.

Thank you very much. And let me address that question first from Gena. And my apology, Gena. I completely missed that question. So my apologies. So based on his departure, is really, again, part of the appropriately resizing and or staging of the company. Based on has been a significant contributor and a really important part of the leadership that I described earlier, which really has driven Editas ability to execute with the change -- and I should say, are moving our program to focus on in vivo. And with that, human POC being intended for 2 years, we felt that it would be appropriate to -- with our restructuring and reorganization of the company to focus our resources on the discovery. And then obviously, we will build as we advance our data and rebuild a development team. But baseline has been a critical and incredibly valued member of our leadership team. And by the way, is fully supportive and was part of management's thinking to recommend this course of action. So that was the first thing. I just want to make sure because I apologize for answering that question. And then with regard to the feedback from potential strategic partners, as I said -- as Erick said, we started this process at the end of the summer. We spoke with many strategics. And the feedback was largely the same, which was that really around the commercial benefits, they actually saw that the evolution and uptake has been slow for existing and currently approved cell therapies for sickle cell and beta thalassemia. And I think very importantly, they shared our view that the potential and reality and time lines for in vivo really look much more crystallized and their near-term viability time lines have really accelerated meaningfully. So those are really the key elements. Erick, I don't know if there's anything else that you want to add.

No. I think it's a good answer. I'd say it's the time line to in vivo relative to the capital investment required to get the autologous to market. And what is the best use of capital? And I think everybody shares the same view on that.

Our next question comes from the line of Alec Stranahan with Bank of America.

This is Matthew on for Alec. Maybe 2 quick ones from us. First of all, how do you think about the potential manufacturing ramp that you'll have to do for in vivo, especially as you get closer to clinic? And is this currently baked into the guidance for the cash runway? And then maybe second, any color on the correlation between editing percentage and HbF induction and whether you expect any of those to trend differently over time, potentially with longer follow-up?

Yes. Thanks very much, Matthew, for your questions. I'm going to ask Linda to take the second question. And in regard with the ramp, we have very carefully structured the company to ensure that we are in an aggressive -- you're right, aggressive is the wrong word, but anticipatory posture to ensure that we are looking to the manufacturing ramping to line up with the timing for human -- our intent -- to meet our intent for human POC within 2 years. And indeed, our current cash runway anticipates or builds in that posturing right now. Erick?

No, that's exactly correct that we did take into account the incremental manufacturing costs to scale to human POC testing.

Okay. I can take the second question. It broke up a little bit for me, but I think what the question was, was -- what was the correlation? Or what do you think the correlation is between the editing and the HbF induction? And we expect it to -- how do we expect it to change over time? And so we do expect there to be a correlation between the editing level and the HbF induction. And over time, I would expect it to increase as the edited cells, the long-term HSCs give rise to progeny in the erythroid lineage and repopulate and expand -- and those cells proliferate and expand. So we are very interested in following looking at the HbF positive cells, the F positive cells over longer intervals of time. So we're looking at the kinetics actively. And that's why we also think we're going to get a higher percent as well when we look at different time intervals.

Our next question comes from the line of Yanan Zhu with Wells Fargo.

Two questions, if we may. As you optimize the LNP, which obviously is a major focus, I was wondering what will happen on the payload side. Will reni-cel be the default one to go into that payload? Or is there any reason to consider further engineer the payload given the recent base editing data showing higher HbF induction? And the second question is, I was wondering for the in vivo liver targeted program, is the plan still -- or is the scope still an upregulation approach? Or has that changed?

Thanks very much, Yanan. So let me answer the second question, and then I'll pass you back to Linda for the first. So with regard to the second question, our focus for liver is up regulation because that's where we believe the key differentiated opportunity is it allows us to go after diseases which are not addressable by other knockdown approaches such as sRNA, ASO or certain other CRISPR-edited approaches. So that's really our focus for liver. Obviously, when you go [ extra hepatically ], those restrictions or constraints are reduced. And then with regard to your comment about the reengineering of the payload, and the default -- is there a default for the reni-cel payload? I'm just going to pass that to Linda.

Yes. Thank you, Gilmore. So we are working on -- we do believe in upregulation of gamma globin, as I was explaining earlier for the reasons I explained earlier. And we are looking at various ways to do that amongst them with the targeting sites that we have already validated clinically, we are looking at different ways to increase the potency of our guides. We have a lot of capability on guide mod optimizations. We reported last May at ASGCT approaches where we can increase the potency of our guide five to tenfold with certain modifications. So we're working on increasing the potency of our HBG1/2 guides now at that locus, but we also are open to considering all other approaches again at -- for upregulating gamma globin.

Our next question comes from the line of Mani Foroohar with Leerink Partners.

You have Ryan on for Mani. Maybe just thinking broader in terms of the BD strategy, how are you guys thinking about BD in terms of the in vivo pipeline? Do you think at this point, this is something that you would also look externally to find a partner for or whether you would kind of keep this one more in-house for the time being? And then, I guess, just going off of that, in your conversations with those strategic partners, did you get any sense that there was more of an interest in the in vivo that those partners kind of expressed an interest to keep the dialogue open there?

Thanks very much, Mani. With regard to the BD strategy, first of all, we have designed our restructuring to enable us to move to human POC on our own with a set of conservative estimates around upside. But obviously, we are a fiscally responsible company and where a partner -- potential partner approaches and the terms are right, we will entertain that. It is worth highlighting that those strategic discussions we had with potential partners showed again with their belief, our shared belief in the potential for in vivo that, that would be an area of interest and obviously, that is something that we would continue to be open to discussing. And then I'm afraid that I have managed to miss your second question. I apologize. Could you restate that for me, and I apologize.

No. No, you covered it. It was more just in the conversations with the strategic partners, whether there was a level of interest at this point. So...

My apologies. My apology. I had combined the questions and then loss count. Thank you, Ryan.

Thank you. And ladies and gentlemen, we have reached the end of the question-and-answer session, and this concludes today's call. Thank you once again for your participation. You may now disconnect.