Morning, everyone, and thank you for joining Editas Medicine Strategic Update Webinar. This webinar is being recorded and can be accessed in the future through this same link or through the investor section of the company's website. After the webinar, the call will be open to Q&A. To ask a question, please click the Raise Hand feature in the webinar portal. As a reminder, various remarks we make during the presentation 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. I'd now like to turn the call over to Gilmore.
Thanks, Christi. Good morning, and thank you for joining us for this strategic update webinar, where we shall share progress toward our 2024 strategic objectives. We are excited to be here today to share our in vivo proof-of-concept data and development financial update. Our four other members of the Editas Chief Financial Officer, Eric Ek, our Chief Medical Officer, Baisong Mei, and our Chief Commercial and Strategy Officer, Caren Deardorf. In January 2023, we shared our long-term objective to become a leader in in vivo gene-edited medicines by combining Editas's deep CRISPR editing know-how with in vivo delivery. We launched a new three-pillar strategy for Editas to achieve this long-term objective and reorganize Editas to deliver on this strategy. We launched Editas' three-pillar strategy.
To drive reni-cel to BLA approval, in vivo medicines, and not create any new standard of cell therapies, and to pursue non-dilutive financing using RFP, we had three key assumptions. One, that our new leadership team with an in vivo pipeline differentiate from the other CRISPR and nucleotide competition by focusing on functional gene upregulation and targeted delivery to hematopoietic stem cells and other tissues, and preclinical proof of concept by the end of 2024. In for sickle cell disease and beta thalassemia, reni-cel provides human POC validation of functional upregulation as a therapeutic strategy and of AsCas12a as a highly efficient CRISPR editing enzyme. I am pleased to share that less than two years after our reorganization, we have achieved preclinical in vivo proof of concept for a key area of interest, sickle cell disease and beta thalassemia.
Specifically, we have achieved highly competitive editing relative to data in the public domain, using a novel Editas proprietary targeted lipid nanoparticle, or tLNP, for in vivo extrahepatic tissue delivery in the humanized mouse model, which has been engrafted with human hematopoietic stem cells. Additionally, we have shared several reni-cel clinical data updates, which suggest that reni-cel is a highly effective differentiation late stage asset that has been significantly de-risked for clinical and manufacturing data and has a robust manufacturing process. We have now dosed 28 adult patients in the Ruby trial for sickle cell disease and are scheduling dosing for multiple adolescent sickle cell patients. We remain on track to share additional clinical data with more patients and longer follow-up at this year's ASH annual meeting in December.
Finally, we have delivered approximately $80 million in non-dilutive financing to Editas in the last nine months, enabling us to fund the current business into 2026. Nevertheless, we are mindful of the capital requirements necessary for a small company to commercialize an ex vivo autologous cell therapy, and simultaneously, we're excited by the potential of an in vivo pipeline that focuses on functional upregulation, particularly in light of the updates we're sharing with you today. We have previously said that we'll be open to partnering reni-cel, but now, with the progress we're making on in vivo editing, we are actively undertaking a process to partner or outlicense reni-cel to most effectively drive it to commercialization while allowing us to deploy our full attention and capital to in vivo medicines. The in vivo data we are sharing today makes us even more confident in this decision.
Now, where is Editas going as a gene editing company with our clinically validated technology? As we shared in January 2023, Editas's long-term vision is to be a leader in in vivo programmed gene editing that leverages cutting-edge technology to deliver therapies that simplify the usability and impact of Editas' medicine by minimizing the burden to patients and healthcare systems, and can meaningfully differentiate from the current standard of care by Editas' focus on discovering and developing first and or best-in-class medicines. With that, I'd like to turn the call over to Linda for an overview of our in vivo upregulation strategy and an update on our progress towards developing an in vivo medicine for the treatment of sickle cell disease and beta thalassemia.
... Thanks, Gilmore. I want to take a moment to reiterate our in vivo strategy to develop a pipeline of gene editing medicines for patients with serious genetic diseases. As a reminder, our internal development approach is differentiated from established modalities, and we are not pursuing the same gene editing approach as others. First, our in vivo strategy is using our indel technology for functional upregulation of gene expression to address loss of function or deleterious mutations. Let me be clear, our strategy is not the knockdown strategy that others in gene editing are pursuing, and it is worth highlighting that we have already demonstrated that our indel technology can drive functional gene upregulation, thus creating a differentiated experimental medicine in our ex vivo development of reni-cel.
With reni-cel, we leverage our indel CRISPR technology to upregulate the expression of the gamma globin gene, a functional homolog of the beta globin gene, through direct editing of the HBG one-two promoter site. We are now applying the same approach to in vivo therapeutics by utilizing our indel technology to functionally upregulate the wild type allele or functional homolog of target disease genes as we build our differentiated pipeline. Why does the difference between our functional upregulation strategy and the knockdown strategy used by other companies matter? Because with our in vivo strategy, we are not knocking down causal pathways that are addressable by other modalities or technologies. Secondly, our indication strategy is targeting rare and orphan diseases that we believe will allow us to be first or best in class for a given indication. We expect to move into diseases with larger patient populations in the future.
Our lead discovery work is in in vivo therapeutic targets in hematopoietic stem cells and other tissues. Third, Editas is well positioned to achieve success with our in vivo strategy and pipeline, with our established capabilities in the four main components of in vivo gene editing medicines. One, our guide modifications that enable high-potency gene editing in multiple cell components, including in the liver, and improve gene editing outcomes in vivo, enabling development of in vivo gene editing medicines. Two, a superior gene editing enzyme in AsCas12a. Three, our messenger RNA, and four, delivery technology, where we are utilizing lipid nanoparticles, or LNPs, for delivery of gene editing cargo into multiple tissue types, while also evaluating additional next-generation delivery technology.
I am excited to share with you our in vivo preclinical proof of concept of hematopoietic stem and progenitor cell, HSPC editing, and fetal hemoglobin HbF induction in a humanized mouse model and the SGW mice engrafted with human hematopoietic stem cells. With a novel LNP and targeting strategy, we achieved HSPC editing at a level of 29% and HbF induction in red blood cells after a single dose, outperforming data we've seen in the public domain. With these data, not only have we achieved the preclinical POC we had set out to achieve by the end of the year, earlier than expected, but we also achieved preclinical POC using our upregulation strategy, which continues to move us towards developing an in vivo medicine for the treatment of sickle cell disease and beta thalassemia. Now, I will take you through the data.
On this slide, we are showing the high levels of editing achieved with a novel LNP and HSC targeting strategy in a mouse model, where mice which lack their own hematopoietic cells have been engrafted with human hematopoietic stem cells. The graph on the far left shows only very low levels of HBG one-two editing, approximately 0.25%, with an LNP using a given HSC targeting moiety strategy. Pivoting to a different HSC targeting moiety conjugated to an Editas LNP formulation enabled substantial editing efficiency at approximately 10% after a single dose of tLNP. LNP formulation optimization enabled an even higher editing level to be achieved, third to right graph, at 29% editing in HSPCs after a single dose.
This level of in vivo editing in the humanized model after a single dose constitutes a highly competitive data set relative to that in the public domain for the development of an in vivo medicine for sickle cell disease and beta thalassemia. Even more significantly, on the right-most graph, we show editing with our tLNP formulation results in a functional outcome of HbF induction. This is shown by the presence of HbF+ expressing human red blood cells, on average, approximately 20% that have populated the host by approximately one month. This POC is significant for multiple reasons. First, we achieved this with a clinically validated target and enzyme that, from our reni-cel experience, is emerging as a differentiated medicine for sickle cell disease.... Second, we devised a novel HSC targeting strategy and a proprietary LNP to deliver our editing cargo.
Third, our editing data set is competitive, and additionally, we show functional outcome as measured by HbF expression. Fourth, our combination of a competitive data set and differentiated therapeutic strategy, validated by reni-cel, creates the opportunity for a first and best-in-class in vivo medicine for the treatment of sickle cell disease and beta thalassemia. Fifth, and finally, we are well positioned to develop an in vivo medicine for the treatment of sickle cell disease, given our preclinical in vivo POC and our domain expertise in the sickle cell disease space. From the delivery standpoint, this POC has additional importance. Overall, our work with our proprietary LNP formulation provides the foundation for a potential LNP platform for delivery to extrahepatic tissues. We have demonstrated the ability to deliver gene editing cargo and effectively edit HSPCs with an HSC targeting moiety conjugated to our proprietary LNP formulation.
From here, we can potentially deliver our cargo to other tissues and cell types of interest with the respective targeting moieties. With that, I'd like to turn the call over to Eric for a business development and financial update. Eric?
Thanks, Linda. I'd like to provide financial commentary around each of the three pillars of our strategy for building a capital-efficient in vivo gene-editing company. We have made great scientific and clinical progress and believe reni-cel is a highly effective, differentiated, late-stage asset. However, the cost to complete development and commercialize is too much for a company the size of Editas to do alone, and as we have seen from other larger companies, in a complex place in which to launch. Therefore, we believe the best option is to find an alternative that continues the development and hopefully commercialization without all of the costs being borne by Editas. We are constantly building different scenarios to challenge our assumptions regarding cost of capital and return on capital. Dilution, an outcome we seek to avoid.
To a fully owned commercial launch, we believe that it's in the best interest of patients and shareholders to partner or out-license reni-cel globally, which better positions reni-cel for broad patient access, long-term financial viability of Editas to pursue our in vivo strategy. As the company makes progress towards developing in vivo medicines, we believe there are several beneficial financial differences versus making ex vivo autologous cell therapies. Among them is our belief that in vivo medicines will provide larger market opportunities and do so with lower cost of goods and lower Phase 3 clinical trial costs. Just yesterday, we announced a collaboration and non-exclusive license agreement to combine Editas Medicine's AsCas12a genome editing systems with Genevant's proprietary LNP technology in the development of in vivo gene editing medicines, directed to two undisclosed targets in Editas' upregulation strategy.
With respect to our BD strategy, I'm sure that you saw our recent deal with DRI, which was just announced on October third, in which we received $57 million in exchange for most of our future Cas9 license payments from Vertex Pharmaceuticals. We're extremely excited to be partnering with DRI on this deal and look forward to possibly partnering with them again in the future. As a reminder, our BD strategy with respect to IP is to sub-license foundational Cas9 and Cas12 licenses to third parties. Within the last year, we brought in more than $80 million net to the company of non-dilutive financing from our license with Vertex and our subsequent monetization deal with DRI. We ended the third quarter with approximately $265 million in cash and approximately $320 million after accounting for the receipt of the upfront payment from DRI.
Now, I'll turn the call back to our CEO, Gilmore.
Thank you very much, Eric. In closing, the path to building our in vivo pipeline, starting with an in vivo sickle cell medicine, is a top priority for us. We have met our goal of in vivo proof of concept for disease of interest by end of 2024. We believe we are well positioned to develop an in vivo medicine for the treatment of sickle cell disease, given our preclinical in vivo HSPC with our proprietary clinically validated editor, our proprietary TLNP or targeted lipid nanoparticle, and our domain expertise in the sickle cell space. Indeed, we have a proprietary TLNP platform that could expand beyond HSCs to other extrahepatic tissues. We believe reni-cel remains on track to be a promising medicine for sickle cell disease and beta thalassemia, with differentiated hematologic effects that include robust correction of anemia in treated sickle cell patients.
And we look forward to sharing additional clinical data in December at the ASH meeting. Now, while we believe that reni-cel will be a superior medicine for patients living with sickle cell disease and beta thalassemia, we also believe that it will be best commercialized with the resources of a partner. And we have therefore started a global process to partner or out-license reni-cel to ensure the best interests of patients and shareholders, and we have engaged Moelis & Company LLC, a leading global independent investment bank, to lead the process. Before we turn to Q&A, as always, it must be said that we could not achieve our objectives without the support of our patients, caregivers, investigators, employees, corporate partners, and you.
We are energized by and proud of our progress and execution this year, meeting our objectives of preclinical in vivo POC in an animal model using our functional upregulation strategy to hematopoietic stem cells with a new proprietary targeted LNP. Achieving POC ahead of schedule puts us on a path to develop a best-in-class in vivo gene-edited medicine for the treatment of sickle cell disease. With our sharp and strategic focus, our world-class scientists and employees, our keen drive and execution, and a strong balance sheet, we continue to progress our strategy to deliver differentiated editing medicines to patients with serious genetic diseases. Thank you very much for your interest in Editas, and we're happy to take questions now.
We will now take questions. Please use the Raise Hand feature to join the queue. Please limit your questions to one question per follow-up. Our first question comes from Samantha Semenkow from Citi. Please unmute yourself and ask your question.
Hi, good morning, and thanks for taking the question, and congratulations on all the work on the in vivo pipeline. I'm wondering, what are the next steps for the in vivo HSPC-targeted program? Will you continue to iterate to improve editing efficiency and HbF induction? And when could we see this program ready for IND filing and clinic entry? Thank you.
Thanks very much, Sam, for your question. I'm going to pass that to Linda.
Yeah. Thank you, Sam. Thanks for the question. We... Yes, as you indicate, like, we continue to iterate various parameters. We're very pleased with the robust level of editing that we're seeing with the tLNP. We're very pleased with the design of our LNP, carrying the cargo for our clinically validated targeting approach and our clinically validated enzyme. We continue to optimize all of the various parameters associated with the tLNP, both in the humanized mouse model, and because of the robustness and reproducibility of the data in the mouse model, to advance this to NHP studies. And, you know, we're on track with progressing this forward.
Our next question comes from Gena Wang of Barclays. Please unmute yourself and ask your question.
Thank you. I will also follow the similar line of questions. So regarding the data LMP three, at 29%, in the efficiency, did you test with other targets? Is that also falling to the similar range of editing efficiency using LMP three? And the related questions, I know you are- you will seeking the licensing or partnership for reni-cel. Are you planning to do also in vivo sickle cell approach, or will be completely different target for the in vivo target?
Thanks very much, Gena. What I'm going to do is have Linda address your first question about other targets edited using the tLNP in hematopoietic stem cells. And then I will take the question on how we're thinking about the approach to out-licensing or partnering reni-cel.
Yeah. Thank you, Gena. Yeah, we are showing the 29% here with our HBG1/2 targeting guide RNA, which is obviously our approach to targeting sickle cell disease. While we're not disclosing here, our work using other guide RNAs, we will potentially be sharing data of that kind in a future venue and time. Obviously, we're very excited about this platform, because with an HSC targeting tLNP platform, we could potentially reach other hematologic disorders. We're very excited about the potential for an HSC targeting platform.
And then, you know, in answer to the second part of your question, Gena, you know, our primary focus is on out-licensing and partnering reni-cel. Nevertheless, you know, as we are all about commitment to partnering, you know, discussions can go in a number of directions, and there is no doubt that having this in vivo data is very exciting and certainly builds the opportunity for franchise. And, you know, with our expertise, with our know-how, with the proprietary validated clinically validated enzyme and guide RNA from our reni-cel experience, and obviously our targeted LNP, I think this puts us in a very good position for building franchise with our know-how.
Thank you.
Our next question comes from Jack Allen of Baird. Please unmute yourself and ask your question.
Great. Thank you so much for taking the questions, and congratulations on the progress. I wanted to ask again also about the editing efficiency you're seeing with the in vivo approach. I guess, how does the 29% editing efficiency compare to some of the ex vivo programs and the number of cells that are engrafting with those ex vivo programs? And then also, I did notice that there was a very tight variance on the editing efficiency, but a little bit more variance as it relates to the fetal hemoglobin fraction. How should we think about that difference there as well?
Thanks very much, Jack. I'm going to ask Linda to address the question about the meaningfulness of the editing that we're seeing, and then obviously to address your question about the variance and why we see that between editing and fetal hemoglobin expression.
Yeah. Thank you. Thank you, Jack. Yeah, in regards to meaningfulness, like, let me first clarify that the editing efficiency, the 29% is we're speaking about there, is measured by next gen sequencing. So this is allelic editing of 29%. And I think I would speak better to the HbF induction and the meaningfulness of the HbF induction. So we know HbF expression is a, is really a meaningful functional readout, because we know that increased expression of gamma globin in the erythroid lineage in red blood cells is known to reduce sickling of the red blood cells in sickle cell disease patients. Like, we know that from the clinical validation and from the patients with hereditary persistence of fetal globin.
So if one reaches gamma globin expression in red cells at a high enough level, it will be anti-sickling. So if we focus on the HBF induction, I think that's a very meaningful functional readout. And then in terms of, you know, the percentage of cells that one would want to increase the HBF in, the information from hematopoietic, allogeneic, hematopoietic stem cell transplantation studies kind of guides us to what percent of cells might be relevant, and that is around 30% allogeneic chimerism. So I think here our editing data in the preclinical model in this range, on average of 20%, is getting us in a very promising level of being therapeutically relevant. So I hope that answers your question.
In terms of sort of the meaningfulness of the data, I think the range of 15%-35% is probably reflecting, at this level, our experimental variation, which we'll be certainly improving upon. Does that answer your question?
Yeah, definitely. Thanks so much for the call.
Our next question comes from Yanan Zhu of Wells Fargo. Please unmute yourself and ask your question.
Great, yes-
Yanan, we're not hearing you.
Oh, hi. Thank you. Congrats on the progress. I was wondering, is the targeting moiety on this LNP an antibody, or is it a lipid? And, what's the manufacturability of this targeted LNP? And secondarily, was wondering about the cell type specificity of the in vivo editing. How important is that? Is there any downside of transducing other cells at this hemoglobin fetal hemoglobin locus? Thank you.
Thanks very much, Yanan. What I have is, if Linda, you want to just address the questions, you know, insofar as we can, about the targeting moiety, which we have not disclosed, obviously.
Yeah. So Yanan, yeah, thanks for the question. You know, we haven't... We're not providing details at the moment regarding the targeting moiety, and such, so this is certainly something that we would be willing to disclose at an appropriate time. We do believe that the approach can be scalable for clinical manufacturability. And we also believe that there should not. So that is a very positive. We're already scaling for NHP studies. And we also do not believe there should be concern about upregulation of, as far as HBG1, 2, upregulation of fetal globin if it were to occur in other cells and tissues.
We know that from our reni-cel experience, and from HP, hereditary persistence fetal hemoglobin patients, because there are variants in those patients that express upregulated fetal hemoglobin in other tissues, and there's no safety issue in those patients.
Super helpful. Thank you.
Our next question comes from Soumit Roy of Jones Research. Please unmute yourself and ask your question.
Good morning, everyone, and thank you for taking the question. The first one is, your peers have shown maybe three years ago, they had to do multi-dosing of for in vivo editing in the sickle cell model to achieve up to 50% editing efficiency. Should we think it would kind of track similar for an Editas case also, where you have to do multiple dosing, and if you have tried it? And the second question is, RNA-based approaches are seeing better high interest due to comparatively lower price, and now with the in vivo approach, you don't have to do stem cell transplantations and all, should we think it would come down from the $2-plus million dollar range?
... So, thanks very much, Soumit, for your question. I think I'll have Linda ask the first part of your question around, you know, the consideration of multiple dosing, and then I will address your follow-up question.
Yeah. So, yeah, thank you for the question about multiple dosing or redosing. This is certainly a consideration in order to potentially get a high enough editing efficiency. You know, we are, as I mentioned earlier, working on the various optimization parameters to increase the level of editing, you know, including aspects of the LNP, aspects of cargo optimization that may allow us as a single dose to get high enough editing, but redosing is also certainly a consideration, and you know, we're encouraged by the possibility of redosing from the demonstration of Intellia recently being able to redose patients with an LNP, so I think both possibilities are out there, and we are exploring redosing in our preclinical experiments, so with that, I think Gilmore could take the second.
Yeah, thanks very much, Linda. Soumit, obviously, our aspiration to lead as an in vivo company is driven by our desire to create medicines that have increased usability for both patients and for multiple global healthcare systems. While it'd be very premature to discuss pricing, I think there are a couple of other things to consider, which I think have driven this success for RNA-based medicines and vaccines, which is you're moving from a customized, autologous, patient individual starting material to an off-the-shelf product. You're also moving to a manufacturing process where you get economics of scale because it's off the shelf. Obviously, there are many advantages to in vivo.
And of course, additional advantages are for patients is that you don't ultimately have to go through the rigors of a transplant and immunosuppressive conditioning. And of course, as a result of that, it also means that you can expand into a larger patient population. Because it is important to remember that in the context of sickle cell disease and beta thalassemia, the diseases are severe diseases. We talk about severe, moderate, and mild, but what we're really talking about is refractoriness. And so severe sickle cell patients are actually refractory to therapy, but the disease overall is still a very serious disease which actually truncates the quality of life, and very importantly, causes significant complications and shortens lifespan with a median survival of around 50 years of age.
Overall, I think this is a very important step forward.
Thank you again, and congrats on the progress.
Our next question comes from Brian Cheng of J.P. Morgan. Brian, please unmute yourself and ask your question.
Hey, guys. Thanks for taking our questions this morning. First, how do you view the market opportunity with an in vivo option compared to reni-cel in sickle cell and beta thal? And I guess more broadly, do you see sickle cell and beta thal as more of a beachhead indication to test drive your in vivo platform to springboard yourself into other extrahepatic indications? And, how does the set of indications look there? Thank you.
Thanks very much, Brian. I suspect there are about three or four parts to your question. So what I'm going to do is ask Caren to address your first question about how you- how we perceive the markets. And I think from a point of view of your later question about what this means as an extrahepatic delivery platform, I'll pass that to Linda. So, Caren, with regard-
Great.
To the market.
Brian-
Okay
... thanks, thanks for the question. So I'll reiterate a little bit of what Gilmore said earlier. When we think about how transformational all of these gene editing approaches are, we start with the ex vivo, and we look at the potential here for really curative therapies. We also recognize that there are some limitations in terms of not being able to reach all patients due to comorbidities, those that may not be able to sustain the busulfan and the conditioning regimen that's required, and the hospitalization. And there is also, for ex vivo, it is more complicated to try to reach many parts of the world.
And so we see in vivo in the future being the opportunity to still bring these transformational therapies to patients in need, but to be able to, as Gilmore said, have a cost of goods that is lower, that allows us to reach many more patients globally. What I'll say, though, is today, it's so critical that these ex vivo therapies are accessible to patients, because patients can't wait. As we know, the risk of disease progression happens with every VOE, but also every year of untreated or undertreated disease. And so we see it as a both. We really believe in the potential of these ex vivo therapies like reni-cel, but we also know there will be patients still remaining in the United States needing to be treated, but also globally.
So we're really excited about that future. Thank you.
Thanks very much, Caren. And then, Linda, just about the potential with our targeted LNP to move beyond HSCs.
Yeah. Thank you. Because of the fact that, you know, we are able to use this LNP, this LNP formulation now with a targeting moiety to get to the effectively deliver and edit an extrahepatic cell type, namely the HSPC, we're
... envisioning and have the potential to deploy it to get to another, hepatic, extrahepatic tissue or cell type of interest using other, targeting moieties. So we're very excited about that, potential of the platform to do this, and this is something we are, you know, actively, moving forward to pursue. I think it's, a platform capability now that, is a very exciting direction for us.
Thanks, Linda.
Our next question comes from Joon Lee of Truist. Joon, please unmute yourself and ask your question.
So for minimum, my guess is that you'll have to continue to at least follow up with the patients who got reni-cel. So how much will that cost per year? Thank you.
Thanks very much. Our year-on-year development of reni-cel. Obviously, we remain entirely focused and fully focused on driving and continuing to execute on the Ruby and EdiTHAL trials. We have patients, we have fully enrolled our adult and adolescent cohorts. We have manufactured the drug or product for these patients, and we are actually scheduling dosing for these patients. I think it's, you know, the key focus for us right now with regard to the out-licensing or partnering is on that actual process. We're very enthusiastic and excited about the data. We think that we have potentially best-in-class medicine here for patients, particularly differentiated by its impact on total hemoglobin, and specifically robustly returning patients to a normal hemoglobin range after treatment.
Obviously, discussions take time, when it comes to negotiating and seeking partners, and we would only share details, if and when we have a deal executed.
Our next question comes from Dae Gon Ha of Stifel. Please unmute yourself and ask your question.
Hey, good morning, guys. Stifel, just to kind of correct that. Two questions. One question for Linda, one bigger picture for Gilmore, I guess. Linda, if we go back to the preclinical data on slide seven, I guess one of the key details or several key details I wanted to dig a little deeper on, specifically LNP one, two, and three, wondering if all those doses were equal, because the timing of the observations are slightly different between the three HSPC data, and as it pertains to the RBC, the F-cell data, wondering if you have any details that you can share on the time course, in terms of whether that 20% emerges further higher as you follow up longer, or if it's kind of plateauing at that 20% range. Question for Gilmore.
As we think more broadly on this HSPC in vivo data you're disclosing today, are you looking to expand on this to go further into non-malignant heme, or are you also contemplating some malignant side of the story as you look to maximize on this particular moiety?
Thanks very much, Dae Gon. So, Linda, I might just pass to you to let you share what you can at this point.
Yeah, thanks, Dae Gon. So these data are representative of data that we've gotten at. We're not divulging the dose, obviously, we're not disclosing the details of the dose, but the doses that we've tried, we have tried different doses, but these are representative of data that we've gotten at the same dose level. And as far as timing is concerned, we are also doing more kinetics to fully understand the cell induction over time.
Thanks very much, Linda. And, Daegon, with regard to looking beyond, hematopoietic stem cell target for sickle cell and beta thalassemia into non-malignant heme or indeed malignant heme, you know, the wonderful thing about having a clinically validated proprietary editor and a proprietary targeting LNP with these data in hematopoietic stem cells, it gives us optionality. And I think, you know, we can consider these things. But obviously, I think the key thing is that as we do that, and as Linda articulated, we can do that, we are also a company that is very much focused on the efficient use of capital and resources as we drive forward.
And so we actually are balancing a sense of urgency to create value for patients and shareholders, but actually also maximize the benefits and potential value of the assets and discoveries that we're making in the company.
Great. Thanks so much, guys. Look forward to ASH.
Next question comes from Alec Stranahan of Bank of America. Please unmute yourself and ask your question.
If you were to partner reni-cel, how much of current expenses are related to supporting this program, given, you know, how far along Ruby is at this point, maybe on a percent basis, if you can provide that? Or is it more of a function of reduction of future predicted cash outlay, in order to extend the runway? And, as a follow-up, curious as to the gating around these partnership discussions, do you think the substantive update at ASH will be for these conversations, or do you think, maybe a bit more data will be needed beyond this? Thanks.
You know, as he just kicks on, let me address the second part of the question about the data. We have you know, the data that we have presented are very robust. You know, we really believe that we have a potentially best-in-class medicine here. Obviously, ASH, we're very excited to present additional data at ASH, and obviously, we'll have more patients followed up for longer periods of time. With that, Eric, I might just ask you to address the first part of the question about the cost benefit, et cetera.
Yes, Gilmore. With respect to the two pieces of your question, kind of the current spending and then future projected spending, can't really say. You know, we haven't given too much guidance on how much the trial costs, but if you were to look at sort of the R&D component of what we've disclosed in our Qs and press releases, you know, obviously, the vast majority of that is on reni-cel, so you can get a sense for that. At this point in the development of the in vivo work, you know, when you're in mice and things like that, it's just not that expensive.
However, as you get down into the future, to the second point of your question, you know, while I don't really wanna speculate on what a pure in vivo company would look like, 'cause we're not there yet, the cost of running in vivo are significantly less, all other things equal, than running an autologous trial. I think when you think about that nine months, six to nine-month vein to vein time, and then having to do the redosing with the infusion, those are not inexpensive things. So I'd say it, you know, all other things equal, on an apples-to-apples basis, an in vivo trial would be significantly less expensive than an autologous trial. And indeed, it would also have significantly less cost of goods.
One of the aspects of autologous cell therapy is-
Mm-hmm
... it's very labor intensive, so. Whereas in vivo gene editing would be more akin to a standard, you know, antibody or something like that.
Thanks very much, Eric.
Thank you.
Our next question comes from Rick Bienkowski of Cantor Fitzgerald. Please unmute yourself and ask your question.
Hi, good morning, everyone. Thanks for taking the question. So I'm just trying to tie together the data generated with your proprietary LNP using internal experiments, along with the announcement yesterday with Genevant for the LNP technology. Could you just maybe go into a little more detail about why you chose Genevant as a partner here, what you hope to gain from their LNP technology, and how you could incorporate the innovations you developed internally into future LNP candidates under this collaboration?
Thanks very much. So before I talk to Linda about you know, the view, I think let me just be very clear about one thing. I just make sure there's no confusion. The targeted LNPs that we have used and developed internally, our proprietary targeted LNPs, are used for direction to cells with the potential to move beyond with a different targeting ligands. The Genevant collaboration, or deal is tied to a separate set of LNPs that can enable us to target. You know, we've actually always said that we would be targeting HSCs, but other tissues as well, including the liver. So Genevant is not related to our HSC targeting. It's an LNP that we are using for other tissue.
With that, Linda, I don't know if you want to just talk about the advantages that you have seen in Genevant, or have I said enough?
I think that Gilmore covered it.
Yeah.
-with that.
Great. Well, thanks very much.
Thanks.
Our next question comes from Phil Nadeau from TD Cowen. Please unmute yourself and ask your question.
Hi, good morning. Thanks for taking our question. One follow-up and then one question. Follow-up to a prior question, I don't believe that I heard you answer is, can you give us some sense of the timelines moving forward? When could you formally nominate a development candidate, and when could you be in a position to file an IND? And then second, in terms of just the theoretical benefits of in vivo versus ex vivo HSPC editing, what data is out there to speak to the longevity of the effect in the patient? Ex vivo so far looks like a functional cure. Any reason to think that that could be different for an in vivo approach? Thanks.
Thanks very much, Phil. So you know, let me just address the first part with the timeline. You asked about INDs and so on. We are very excited to be sharing this data. We will actually share, you know, timelines to IND and human clinical studies at an appropriate time in the future. We haven't gone into that detail or shared that with you yet. With regard to the theoretical, you know, longevity of in vivo, I'll just make a comment and ask if Linda wants to build on that any further, but we would anticipate that because of the methodology we're using, where you're using actually editing, permanent editing of the genome, that means that the effect should be durable and sustained.
We're not talking about a dilutive effect. By actually editing in the genome, we expect to see a permanent effect that will be carried through to daughter cells with cell division. And so we believe that the durability that we've seen with ex vivo would actually be maintained with an in vivo approach. Linda, I don't know if you want to add to that.
Yeah, I think that, that summarizes with how I would have also said it. And, you know, obviously, we want to achieve the targeted editing that I spoke about earlier for, for the in vivo, to achieve the meaningful level of editing in terms of the % of cells and the, the level of editing in the lineage, but we would then expect it to be permanent edit and durable.
Please unmute yourself.
Hi. I just wanted to ask about sort of ongoing investment in the current program. How will you continue to develop that in light of searching for a partnership? And if you could give us any idea of the kind of partner you're looking for and any interest there. Thank you.
Yeah, thanks very much, Lisa, for your question. Obviously, we remain highly committed to executing towards the BLA. We have made excellent progress in that direction. We're very happy with that, and we essentially are, you know, as I say, we have completed enrollment for our adult and adolescent cohorts. We have already dosed 28 patients. We continue to dose at manufacturing material for the remaining patients to be dosed, and are very happy with the data we're creating clinically, as well as the manufacturing process, and obviously, continue all the activities necessary to build that BLA package. With regard to how we can see a partner working, obviously, that would depend on, you know, the partnering or the partner's needs.
Obviously, a partnership, or an out-licensing, or whatever that looks like, would depend on the both parties. But ultimately, what we're looking for is a global partnership, and we're looking for something that will maximize benefit to patients, by enabling maximum access, and obviously to shareholders, to make sure that we actually deploy capital, and generate value, from reni-cel.
Okay, thanks.
Our next question comes from Mani Foroohar of Leerink Partners. Please unmute yourself and ask your question.
Thanks for taking my question. I guess a little bit of a longer term strategic question. From the perspective of striking a deal for reni-cel, when I think about what a partner would want, would it be reasonable to assume that any partner that takes on the late stages of development and eventual commercialization of reni-cel, would also expect to have rights or an option to in vivo applications in the same therapeutic areas? Given that an in vivo approach, using your more novel platform and next generation technology, would potentially be either a logical disruption of or a logical lifecycle management approach to reni-cel.
Yeah, thanks very much, Mani. And, you know, we're actually in a very interesting position in that we have exciting assets, both in our, you know, late stage, highly de-risked, ex vivo therapeutic reni-cel. And obviously, these new in vivo data for editing, obviously, are profoundly exciting. We are committed to and fully focused on out-licensing or partnering reni-cel as it continues towards, BLA. But decisions can go where they are, and obviously, you outline a logic that some partners may bring to such a discussion. You know, so as I say, we are open, and can explore, you know, what kind of deals will be best, again, to maximize value to patients and shareholders.
Okay, that makes sense. Thanks, guys.
Thank you, Mani.
And we have time for one more question, from Timur Ivannikov. Please unmute yourself and ask your question.
Thank you. This is for Steve Seedhouse, Raymond James. Just to follow up on a few prior questions on in vivo program, just trying to understand your confidence and stage of optimization. Are you still considering using a different LNP or targeting moiety to reduce the variability in HbF induction? Or are you already settled on the contract that you have now, and, you know, have other parameters you can change? And then also, you know, what is your threshold for moving into the clinic? Thank you.
Yes, thanks, Timur. So we, you know, we have a very robust workflow, so we are able to evaluate quite a few optimization parameters in our workflow. We're looking at a variety of these parameters. You know, we're not disclosing all the details of the parameters that we're optimizing at the moment, but I think that because of our strategy and our workflow, we are expecting to be able to progress quickly, and we're going to be evaluating these both in our humanized model and progressing evaluation of optimization parameters into non-human primates. So we can make these evaluations and decisions in a pragmatic fashion based on the evaluation of the results that come out, and we'll be updating and providing information on these in the near future.
Thank you very much, Linda. And, you know, with regard to the confidence, of course, one of the things that we have substantial advantage to our is that reni-cel, in addition to being an exciting, you know, potentially best-in-class medicine, it has actually already substantially de-risked our approach, both with our targeting, of the HBG1-2 promoter and with our enzyme as AsCas12a. So those are important parameters that already we have substantial, clinical validation for, which I think, enables us to, you know, be very enthusiastic about our path going forward in vivo. And obviously, we will share at a more appropriate time what our timelines are to, human studies.
Thank you very much.
Thanks very much, Timur.
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