Good morning. My name is Jessica, and I will be your conference operator today. Welcome to the Intellia Therapeutics First Quarter 2019 Financial Results Conference Call. At this time, all participants are in a listen-only mode. Following the formal remarks, we will open up the call for your questions. Please be advised that this call is being recorded at the company's request. At this time, I would like to turn it over to Lina Li, Senior Manager of Investor Relations at Intellia. Please proceed.
Thank you, operator. Good morning, and thank you all for joining us today to discuss Intellia's first quarter 2019 operational highlights and financial results. Earlier this morning, we issued a press release outlining our progress this quarter and the topics we plan to discuss on today's call. This release can be found in the investor section of our website at www.intelliatx.com, and there is also a presentation available for download under the Events and Presentation section so that you can follow along. This call is being broadcast live, and a replay will also be archived on our website. We also plan to hold quarterly earnings calls similar to this one going forward. More details will be made available closer to the date of the specific earnings call. Before we get started, on slide two, you'll find our forward-looking statements disclaimer.
I would like to remind you during this call, we may make certain forward-looking statements and ask that you refer to our SEC filings available at sec.gov for a discussion of potential risks and uncertainties. All information in this presentation is current as of today, and Intellia undertakes no duty to update this information unless required by law. Joining me on today's call from Intellia are Dr. John Leonard, our President and Chief Executive Officer, Andrew Schiermeier, our Executive Vice President of Development and Corporate Strategy, and Glenn Goddard, our Executive Vice President and Chief Financial Officer. As outlined on slide three, for today's call, Dr. John Leonard will provide an update on the company's research and development progress, and Glenn Goddard will review our financial results from the first quarter of 2019. Following our prepared remarks, we will be available for your questions.
With that, let me turn the call over to John.
Thanks, Lina, and thank you all for joining us today. Here at Intellia, we're pursuing a full spectrum strategy. We have an in vivo approach in which CRISPR complements the therapy and an ex vivo approach in which CRISPR provides an essential tool used to create engineered cell-based therapies. We believe our CRISPR-Cas9-based platform has the potential to cure genetic diseases with a single administration, and it can also be used to create novel engineered cell therapies that can effectively target various cancers and autoimmune diseases, as illustrated on slide four. Today, I will highlight recent advances in our programs that are progressing to the clinic and that demonstrate the power of Intellia's full-spectrum approach to genome editing. Already this year, we've made significant progress across both our in vivo and engineered cell therapy pipeline.
Specifically, we can use systemic delivery to knock out a disease-causing DNA sequence common in autosomal dominant genetic disorders. We can introduce a targeted insertion of DNA to make therapeutic proteins at normalized levels, permitting the treatment of autosomal recessive genetic disorders, and we can design engineered lymphocytes recapitulating normal cell physiology with the potential to address hematological and solid tumors. We are advancing our lead programs toward the clinic for transthyretin amyloidosis and acute myeloid leukemia. Our recent gene knockout and targeted insertion results in the liver of non-human primates are enabled by our leading position in systemic delivery. Coupled with our expanded engineered cell therapy efforts, Intellia is now uniquely positioned to move forward a robust and diverse pipeline.
In addition, we and our partners delivered two presentations at the 22nd Annual Meeting of the American Society of Gene & Cell Therapy, or ASGCT, and we will be giving a third presentation later today. These presentations feature Intellia's innovative science and demonstrate key points of validation for our approach. We're excited to walk you through some of this data today. Let's turn first to our lead in vivo development program on slide five, which is for transthyretin amyloidosis, or ATTR. This disease results from deposits of insoluble amyloid fibrils within multiple organs and tissues caused by accumulation of TTR protein. The data shown on slide six captures our progress toward identifying our lead candidate for our ATTR program. The very first studies in non-human primates, as captured in the yellow bar, produced low but promising levels of editing in the liver.
These results were highly encouraging, and they were the first demonstration of a dose-dependent CRISPR-Cas9 mediated edit in the liver of non-human primates. In a matter of months, our team made substantial progressive improvements to the CRISPR-Cas9 LNP, enabling us to achieve significantly higher levels of editing and limited variability, as shown here in blue. We're very proud of this work and its rapid pace and believe it establishes a unique capability in the CRISPR gene editing space for Intellia. Moving forward to slide seven, for both hereditary and wild-type ATTR, the therapeutic objective is to reduce the levels of protein available to form amyloid. On the chart on the left, you will see the TTR editing results from our lead candidate. On the chart on the right, following a single dose, we achieved an average reduction of greater than 95% of circulating TTR protein in non-human primates.
Reduction of 60% has been associated with human clinical benefit, a benchmark we readily expect. Since announcing these results in February of this year, we have substantially completed dose-ranging finding studies that show a favorable tolerability profile. In addition, we've observed sustained protein knockdown of our lead candidate through 100 days as part of an ongoing durability study. Importantly, the data shows once reaching maximum TTR protein reduction around day 30, the reduction remains essentially unchanged at day 90, with no significant loss of effect from the liver editing. We've also accumulated data from earlier studies in non-human primates demonstrating durability of both liver editing and TTR reduction through 10 months of observation following a single dose. These studies reflect precisely the durable effect one would expect to see with a CRISPR-mediated edit, highlighting the curative potential of our technology, which of course, is our ultimate objective for patients.
Moving now to slide eight. Based on these encouraging results, we're pleased to announce that we have nominated our first in vivo development candidate, NTLA-2001, for the treatment of ATTR. We expect to advance into IND-enabling toxicology studies in mid-2019. NTLA-2001 will be Intellia's first systemically delivered CRISPR-Cas9-based therapy. We're co-developing and co-commercializing NTLA-2001 with our partner, Regeneron, and Intellia as the lead party. We remain on track to submit an IND application for NTLA-2001 next year, and we expect to refine IND guidance later this year. On slide nine, we look forward to presenting new data later today at ASGCT, providing further evidence of our ability to knock out additional target genes of interest in the liver. Using a primary hyperoxaluria type 1, or PH1, mirroring disease model, we knocked out two individual targets that play a role in urinary oxalate production.
As shown on slide 10, a single administration of our CRISPR-Cas9 LNP knocked out the targeted gene. In one case, lactate dehydrogenase A, or LDHA, and in the other case, hydroxyacid oxidase one, or HAO1. Based on a therapeutically relevant urinary oxalate reduction sustained for the 15-week observation period, the knockout of LDHA or HAO1 each represent potential standalone approach to treat PH1. This is an important step in the validation of our modular platform by again demonstrating our ability to knock out target genes of interest in the liver to achieve sustained and therapeutically relevant effects. Moving to slide 11. Earlier this week at ASGCT, we presented data that moves beyond gene knockout to targeted gene insertion. Our researchers demonstrate the first successful CRISPR-mediated gene insertion in non-human primates, achieving normal circulating human levels for the protein.
This is a major step forward for our in vivo efforts as it adds a key functionality to treat genetic diseases, specifically those which require a gain of function. As illustrated here, and as part of our collaboration with Regeneron, our researchers combined our standard format CRISPR LNP delivery system with an AAV containing a proprietary bi-directional insertion template that encodes a functional gene. This hybrid approach allows for transient Cas9 expression and precise targeting of a chosen insertion site to achieve gene insertion, resulting in high levels of protein production from the introduced gene. With a targeted insertion approach, the goal is to restore function where the effect is durable without the need for redosing and intervene earlier in disease progression. In contrast to shown on slide 12, conventional gene therapy typically uses a viral system to deliver therapeutic gene.
AAV, despite several shortcomings, is most often the system of choice. Because AAV generally does not integrate into the genome, it is lost in organs where cell division levels are significant, which is undesirable in applications requiring long-term durability. Although retroviral vectors do integrate into the chromosome, they do so randomly and thereby introduce the risk of insertional mutagenesis. With our LNP-AAV delivery approach for targeted stable gene insertion, we have the potential to overcome limitations of viral-based gene therapy. On slide 13, here we use our hybrid LNP-AAV system for target insertion of a Factor IX gene, which encodes Factor IX protein missing or defective in hemophilia B patients into the hepatic albumin locus in non-human primates.
We selected the albumin locus as an attractive insertion site because it is the most highly expressed gene in the liver, which helps ensure substantial expression of the inserted Factor IX gene. Slide 14 displays the protein expression levels after a single administration of our hybrid delivery of the Factor IX gene in non-human primates. On the left side of the graph, you will see that protein production does not occur in our experimental controls. On the right side of the graph, we show that LNP-based genomic editing combined with an AAV to deliver a hyperfunctional human Factor IX DNA template achieves human Factor IX protein production. In our most recent study, initial results indicate that a single dose achieved approximately three to four micrograms per milliliter of circulating human Factor IX protein at day 14.
This level lies within the reported range of normal circulating human Factor IX protein levels in humans. Importantly, these protein levels were sustained at day 28, with albumin levels maintained at day 28 as well. This experiment is ongoing, and observation of protein levels will continue. Additionally, the latest study utilizes the improved CRISPR-Cas9 LNP discussed earlier in the ATTR program, highlighting the modularity of our platform. We're encouraged by this latest Factor IX data and view this as a significant breakthrough in our genome editing capabilities. This all leads for our platform-based approach on slide 15. These achievements across our in vivo efforts are a testament to the tremendous advances we are making.
Effectively, we believe we have solved several key aspects of delivering to the liver in non-human primates, as we have demonstrated our ability to selectively knock out target genes of interest with a minor change of a guide RNA. We've now achieved target insertion of a DNA template to restore normal functionality of the missing protein. These capabilities should expand the scope of addressable genetic diseases in the liver well beyond our initial indications. Our achievements in the liver also serve as a foundation for targeting genetic diseases in other tissues. Transitioning to our engineered cell therapy strategy. Here, we are similarly leveraging our modular platform-based approach to design engineered cells that we plan to administer as therapies for immuno-oncology. We believe our CRISPR-mediated engineered cell therapy efforts open the potential to pursue a range of hematological and solid tumors.
On slide 16, we outline our four independent work streams towards achieving these goals. For today, we will focus on our TCR replacement approach for our wholly-owned lead autologous program in development for acute myeloid leukemia, or AML. As we review on slide 17, AML is a cancer of the blood and bone marrow with significant unmet medical needs. The disease is rapidly fatal without immediate treatment, with a less than 30% five-year overall survival rate. In 2018, there were approximately 20,000 new cases in the U.S. alone. Over the past two to three decades, there have been limited advances in treatment options for AML patients. As shown on slide 18, we've chosen a TCR replacement approach to modify lymphocytes, in contrast to taking a CAR T-cell approach.
This is because CAR T-cells can only recognize surface antigens, whereas TCRs can recognize a wider range of antigens, in particular intracellular antigens such as Wilms' tumor 1, or WT1. TCRs can even recognize specific mutations that occur uniquely in tumor cell genes, also known as neoantigens, which is a growing area of interest in the immuno-oncology field. By choosing TCRs, we believe our work can be applied to a broader array of cancers. As illustrated, the approach here knocks out both the alpha and beta chains of the T cells' endogenous TCR, as depicted by the red dotted icon, and inserts a new TCR targeting an important epitope of the WT1 antigen in locus. By knocking out the endogenous TCR, we expect three main benefits. First, to enhance and stabilize the expression of the inserted TCR.
Second, to reduce the risk of loose paired TCRs between the endogenous and inserted TCRs. Third, to allow for targeted insertion of the new TCR in locus rather than random integration to preserve cell physiology. Notably, the WT1 epitope we are targeting is overexpressed in greater than 90% of AML blasts. Our work in WT1 for the treatment of AML serves as the foundation to pursue additional indications, as WT1 is overexpressed across a broad range of tumors. On slide 19, at ASGCT, our collaborators at Ospedale San Raffaele presented in vitro data which show that CRISPR-Cas9 editing resulted in greater than 98% knockout of the endogenous TCR, while also achieving insertion of a WT1 specific TCR in a greater than 95% isolated T cells. These engineered T cells were fully functional and capable of specifically killing high levels of patient-derived AML blasts.
Based on this approach, we've identified multiple lead TCRs that recognize the primary WT1 epitope of interest, which is restricted to the HLA-A*02:01 allele. We're pleased to announce today that we will advance the lead TCRs into functional testing in patient-derived xenograft models mid this year. These studies will inform nomination of our first engineered cell therapy development candidate targeting WT1 for the treatment of AML, which we expect to name by the end of this year. As shown on slide 20, we believe that our focus and dedication in developing a modular platform across our in vivo and engineered cell therapy efforts is leading to a robust pipeline, enabling us to fulfill our goal to build a genome editing company for long-term sustainability and success. With our innovative science, strong platform capabilities, and world-class team, we believe we are poised to deliver transformative therapies for patients.
I'll turn it over to Glenn Goddard, Executive Vice President and CFO, who will walk you through our first quarter financials.
Thank you, John, and hello, everyone. Moving to slide 21, as we move programs forward into development, Intellia is in a strong financial position. Our cash equivalents, and marketable securities as of March 31st, 2019, were $297 million, compared to $314 million as of December 31st, 2018. The decrease was driven by cash used to fund operations of approximately $29 million, which was partially offset by $6 million of funding received under our Novartis collaboration, $3.6 million of net equity proceeds raised from our at-the-market agreement, and $1.5 million of reimbursable NTLA-2001 costs received from Regeneron. Our collaboration revenue was $10.4 million for the first quarter of 2019, compared to $7.5 million for the same period in 2018. Collaboration revenues relates to our Novartis and Regeneron agreements. Also, Regeneron's co-funding of NTLA-2001 related activities is included within collaboration revenue.
Our R&D expenses were $23.7 million for the first quarter of 2019, compared to $22.5 million for the same period in 2018, as we continue to expand our in vivo and engineered cell therapy platforms and move NTLA-2001 into development-related activities. Our GA expenses were $10.5 million for the quarter, compared to $7.4 million for the same period in 2018, largely due to increased expenses to support our growing research and development operation. Finally, today, we are reconfirming our previous guidance that we expect our current cash position to fund our current operating plans into the first half of 2021. I'll turn the call back over to John to summarize our key achievements and upcoming milestones.
Thanks, Glenn. On slide 22, in summary, based on the significant progress we have made on our platform capabilities, we can knockout a disease-causing DNA sequence with high levels of protein reduction. We can introduce a targeted insertion of DNA and normalize protein levels, and we can design engineered lymphocytes to preserve cell physiology. These platform capabilities will enable us to deliver on our mission and move forward a robust and diverse pipeline, with ATTR and AML being our lead in vivo and engineered cell therapy indications. Looking ahead on slide 23, we remain focused on carrying out our 2019 milestones across our full-spectrum CRISPR-mediated approach. For our ATTR program, we plan to initiate IND-enabling toxicology studies mid-year, and we plan to commence manufacturing of Phase I study materials this year, all in support of filing an IND in 2020.
For engineered cell therapy program, we expect to initiate functional studies in patient-derived xenograft models of multiple lead TCRs in mid-2019 and plan to nominate our first engineered cell therapy development candidate for AML by year-end. With that, I'd like to thank you all for tuning in today, and a special thanks to our team at Intellia for their dedication and commitment in bringing forth this groundbreaking work. We'll now open up the line to any questions. Operator?
Thank you. Ladies and gentlemen, if you would like to ask a question, please signal by pressing star one on your telephone keypad. Please make sure your mute function is turned off to allow your signal to reach our equipment. Again, press star one to ask a question. We will now take our first question from Maury Raycroft of Jefferies. Please go ahead, sir.
Hi. Good morning, everyone, congrats on the progress. First question is just starting with the hybrid system for hemophilia B data that you've reported. The approach and data look solid so far, especially with the new LNP formulation in non-human primates. I'm just wondering if you can comment on what next steps would be with this approach.
Thanks, Maury. As we commented in the call, it's an ongoing study. We're certainly very excited about the results that we presented here. I point out, as I tried to in my comments, that I think the really exciting aspect of this thing is that we're talking about actual levels of protein that are circulating in terms of micrograms per mil. When you look at it from that point of view, we think this is a very exciting data and has implications not just for hemophilia B, but also for any other genes that you might want to insert, where you're not only trying to reconstitute enzymatic activity, but even other sorts of proteins. I think it's important to look at the data with that in mind. First things first, it's follow the animals, follow the duration of the effect.
As we said elsewhere with other work we've done, we're out past 10 months now in terms of durable effects. We'll continue to observe these animals for some time, and we'll decide what's appropriate. Safety's obviously of interest to us. The animals are doing very well, so that's extremely encouraging. It has frankly been the case across all of the work that we've done so far. That's been very good news. This is a program that we're doing in collaboration with Regeneron. This is a shared responsibility, and I know that they're quite excited about this as well, and together we'll figure out how we want to prosecute the rest of the program.
Got it. That's very helpful. For both the hybrid approach and the proof of concept with T-cell therapies as well, so you've done a lot of work there to build value, de-risk the technologies, and you've got Regeneron involved. I'm just wondering how you think about the platform potential and potential for strategic development with partnering some of these technologies out. What are your thoughts there?
Well, let's step back, and I just want to make sure that we're talking about the same thing. The relationship that we have with Regeneron, which we're well into, and you see the results of some of the work that we're doing collaboratively, is primarily focused on hepatic targets. They do have rights to do some things outside of that should they choose to do so. But it's a collaboration that's focused primarily on, in vivo use of the technology targeting liver. When you talk about T cells, it's important to recognize that T cells and cell engineering in general and ex vivo uses, if you want to think about it in those terms are, with the exception of the relationship that we have with Novartis on CAR Ts and some limited number of HSC HPCs, entirely in the hands of Intellia.
Back to your observation about building out a platform and the extensive utility of it, the approach that we're taking with cell engineering is exactly that. We want to build out functionality, capabilities that permit the broadest range of uses. The first TCR program that we discussed about, I think, promises to show the utility of that approach. Once we have that in hand, I think, the potential is essentially unlimited in terms of what you can do with T-cell engineering, and we will pursue that.
Got it. Very helpful. Last question is just on ATTR. Given that the dose ranging studies are nearly complete and that you've done in the preclinical setting, can you provide more details on how you anticipate a dose escalation in humans could look? I guess do those preclinical studies inform how that dose escalation in humans could look and what variables you're considering going into humans?
Right. Dose range finding work sets up the formal GLP tox studies. That's all part of ongoing work and discussions with the FDA that lays the groundwork for exactly what you're talking about, which is that first clinical study. In many respects, I anticipate that study will look a lot like what you would expect a first single ascending dose study to look like. We've certainly talked to investigators who are eager to participate in that. We anticipate that we'll have a good supply of patients who want to be part of that work. Once we have all the material ready to go, we're very excited to move into the clinic. We will keep you informed as the IND day tightens, as some of these pieces come together. That's obviously our target, being in the clinic as quickly as possible.
Got it. Thank you very much for taking my questions.
Thank you.
Our next question will come from Gena Wang of Barclays. Please go ahead.
Thank you for taking my questions. The first one, John, that would be for the PH1 program. Just wondering, would that be also using the same LNP system that is used for the ATTR program?
Right. PH1, and again, this is a presentation that'll be taking place at ASGCT today, where one of our scientists will be going through a more extensive review of the work here. This program uses the same enhanced LNP and cargo approach that we've been talking about. This is the LNP that corresponds to that TTR data that we show here in this presentation and have shown elsewhere. This goes back to the modularity of the approach that we've tried to develop. Once you solve LNP delivery to the liver, work out the cargo aspects of that, we think that you can turn the crank essentially by keeping much of that constant, but only swapping out those elements of the guide that determine what gene you want to actually go after.
This is an example of that modularity, and with minimal change, you see that in fact it's quite effective. Anyway. I would say, Gena, with respect to PH1, where this plays out ultimately from a development point of view is a decision yet to be made. This is work that's been done in our research labs, just demonstrating the overall approach of modularity.
Okay. My next question is regarding the insertion programs. The Factor IX level actually looks very impressive. The editing efficiency, when we look at, represented positive cells actually is around 50%. Just wondering, philosophically, because you're inserting at the first intron, in albumin, would that be necessary given the high editing efficiency? Would that be any safety concern, since albumin is a very strong promoter in our bodies?
Yes, I commented in the talk. We're obviously paying attention to albumin. We've been following that very carefully. Thus far, albumin levels appear to be unaffected, even in animals that have these very high levels of protein production. Back to, I think the premise of your question in terms of what you have to do to achieve these protein levels. There are different elements that we have to toggle, if you will, to determine where we wanna go. One is where you place the guide in the actual cut site, which is something that we look very carefully at. What is the dose of the LNP and what is the dose of the AAV? As we've shown here and elsewhere, the combination of those three elements is what's going to ultimately determine levels of protein production.
With the safety in mind and ultimate therapeutic objectives, I think it's going to be very much a balance of this. Just thinking about albumin a little bit, recognize that we frequently forget that hepatocytes have multiple alleles. There is a significant ploidy here, and we should not assume that every single allele has been edited in these hepatocytes. We can detect the presence of the transgene in cells up to 50%. That doesn't mean that every single allele has been edited in them, and there is reason to believe that there's feedback loops, where the body looks to maintain levels of albumin, given its essential use in plasma.
Okay. Thank you. My last question is just wondering, is there any change in senior management recently?
Could you repeat the question? I didn't hear the what part.
Senior management.
Oh. We have been building our team for some time, as I'm sure you know, because you've met him. Glenn Goddard joined us as CFO in November of this past year. I intend to stay around for a long time, Gena. Andrew is with us, obviously, and has been the architect of a lot of our strategic thinking in the ex vivo program, and I know he wants to execute that to its fullest potential. We have no plans to have any senior management leave, but it's our expectation that we will continue to grow our senior team as appropriate as we move forward.
Okay. I think the reason I'm asking, are there any also departure in the past, senior management?
Well, not at the most senior level. We have had some of the scientists who were here at the very beginning as part of the startup mode who have left, but no one in senior management. If you're asking about particular individual, happy to talk about that, but I don't know what you're referring to.
Oh, sorry. Just curious about if Tom Barnes is still with the company.
Oh, Tom has left. Tom joined the company at the very, very beginning as one of our very first employees. Was instrumental in some of the early work that we did. Had a position as Senior Vice President of Innovative Sciences as time went on, but did not have a management role for the last year or so with the company.
Okay, great. Thank you very much.
Sure.
Our next question will come from Steve Seedhouse of Raymond James. Please go ahead.
Thank you. Good morning. In the planned phase I ATTR study, do you want to explore redosing of LNPs in some patients, either in the protocol itself or in an extension study, or will you just have single-dose administration of NTLA-2001?
I think it's a really important question, it's one that we want to work through with the Food and Drug Administration. I'd say there's two elements of that that I think are pertinent. In a standard single ascending dose study, typically one begins at very low doses, and it's not obvious that one would expect to have a therapeutic effect for patients who are exposed to an editing approach that is permanent, as far as we can tell, change that's been made. One of the things that we again need to work through with the Food and Drug Administration is whether or not we offer to those patients, assuming the data merits it, an opportunity to be redosed at higher doses if we do see an effect.
Then secondly, there's just an economy to doing this work if we can come back and redose patients subsequently, very much a work in progress and point of discussion as we work through this and finalize the approach, obviously, we'll share it with all of you.
Okay, thanks. Just relatedly, I guess, generally, what are your thoughts on sort of some of the work that's been done on Cas9 immunity? Can you talk about any work you've done redosing primates, and if you see any adaptive immunity to Cas9 and impact on the editing potential of subsequent doses?
Yes. We do follow immune response, as you know, there's multiple aspects of that. With respect to humoral immunity, the formation of antibodies, a couple of considerations. First, remember we're using a lipid nanoparticle that contains RNA. It doesn't contain the Cas9 protein. We have seen the formation of antibodies after dosing with the LNP. However, when looking for redosing activity, we have not found any effect of those antibodies.
Okay, great. Just on the Factor IX NHP studies, where are you on the curve of the LNP dose relative to the ATTR studies? The factor expression that you see in primates, do you know what level of editing that correlates to in the liver of the primates? Have you looked at editing in either, I guess, primates or mice, like DNA sequencing? What's the % editing there?
That work is underway. We have not tried to achieve a maximum effect, if that's what you're asking me, in terms of where we are in the dose response curve. We did do dosing based on our preclinical in vitro work that would suggest that we would have a big effect, if we were going to find one, and we certainly have seen that. Whether or not there's more to get is something that we have yet to determine. I think it's very exciting the extent of the effect that we can get. The earlier question about controlling dose and whether that's determinants or something that obviously we will take into consideration because there are multiple toggles to determining that. It's some of the early days here in terms of what we can get with insertion, but we're very excited about where we are already.
Okay. Just last question, again, on Factor IX, this is regarding the rodent or the mouse study presented at ASGCT. I mean, you're obviously getting pretty good Factor IX expression. Any thoughts on why the expression increases still between weeks 20-40? Is Cas9 continued to be expressed, I guess, on tissue past 20 weeks after a single dose?
Cas9 in our work is transiently expressed as a result of using the lipid nanoparticle approach. Remember that unlike AAV approaches, where that's the vehicle used to deliver Cas9, which results in a persisting expression system. With LNPs, what we have is a transient expression system. You provide RNA, the RNA degrades after a protein's produced, the protein goes away, so there's no ongoing source of it to go and do editing. The slide you're referring to, I think is slide 11, where there's some drift between 20-40. I think that you have to bear in mind error bars and things like that. It's not obvious to me that those are radically different levels. Subsequent time points, I think, will be illuminating, and that's what we'll look for.
Okay. Appreciate all the data, and thanks so much for taking my questions.
Sure. Thank you.
Our next question comes from Sylvain Toutain of Oppenheimer. Please go ahead.
Thank you. Congrats on the presentations and thank you for taking my questions. Could you just expand a little bit more on details that you have left for the IND filing in ATTR in terms of what toxicology studies you need to run and what are the boxes you need to check in terms of manufacturing for phase I material?
It's really the standard set of work that needs to be done. As I referred to in my comments earlier, the dose range finding work has been done. This is where animals are exposed to ascending doses of a material to get to a point that essentially brackets that range of doses to be tested. That lays the foundation for the formal GLP tox study that we will be doing later this year. Obviously, the material that's tested in that study is key in producing it under the proper circumstances of material that will be representative of what we use in the clinic is the basis of the work that's ongoing now, and all of that is proceeding as per plan.
Well, thanks for taking my question.
Our next question will come from David Nierengarten of Wedbush Securities. Please go ahead, David.
Hi, thanks for taking the question. I actually had one on the WT1 program for a change. Just a couple of quick ones. If you could remind us on the HLA restriction for the program and what % of patients would have the appropriate HLA alleles. Also, were you planning at some point to develop an allo approach for AML or is there allo approaches for other tumors or other targets? Thanks.
Right. On slide 19, we identified the HLA type, which is 0201. That, depending on the population you're in, but in a standard Western population, we're talking 50-ish% or so patients would be expected to have that. I think it's important to bear in mind that this is our first attempt at this, and one should not view this as limited to that, but it's, we think, an ideal way to begin and explore the overall TCR approach and the thesis that we've used. WT1, as I'm sure you remember, David, is an ideal target for AML. If you look beyond that into solid tumors. It's one of those very attractive overexpressed proteins that's broadly applicable. We view this as a staged approach.
We're looking blood with a TCR that we think is appropriate and naturally occurring, but selected in the most appropriate way with our colleagues at OSR in Milan. Show that it works in blood, move broadly, as quickly as we can. With respect to the first development candidate you asked will be allo or auto. Our base case at this point is that this would be an autologous approach. As I said, we have a parallel work stream, which is rapidly moving along. If there's opportunities to move to that, we will, I think at this point you should assume that the first development candidate, it will be autologous. Back to the general approach that we've used with engineered cell therapy. We've tried to create these parallel work streams to generate maximal optionality. Build a TCR platform, build out what we view as true allogenicity.
I mean, cells that are measured to persist in the presence of cells designed to kill them as opposed to merely knocking out MHC-1 or MHC-2. At the appropriate time, merge those work streams to get the benefits of all of them.
Okay. Thank you.
Thank you for asking about our engineered cell therapy program. That's something that, just for your other listeners, I would point out, of as much progress as we've made on the in vivo side, now about 50% of the effort of the company is on the engineered cell therapy side. We're advancing both aspects in parallel in the, as you can see, the engineered cell therapy aspect is actually catching up with the in vivo work. We're very excited.
Thank you.
Our next question comes from Gbola Amusa of Chardan. Please go ahead.
Congrats on the progress and thanks for taking my question. It's a quick one, and it's actually also on the cell therapy side. I believe the San Raffaele presentation at ASGCT showed delivery of the TCR with a lentiviral vector. Could you talk about whether this is something that will be the case for Intellia's first product candidate, or if you plan to do the targeted insertion into the TRAC locus? Also, are these experiments that you plan to do as part of that development, and for that program, would you do homology-independent insertion like the in vivo program or a more traditional homology-directed repair, like others are doing for this type of approach? Thanks.
Gbola, thank you for paying so close attention, because that's a key point and it's correct that OSR has used for their work, which is related primarily to fishing out the TCRs, lenti to demonstrate that the TCRs that they've identified have high activity and are broadly active against an array of different AML blasts. We're very excited about what they've fished out. In terms of our approach, we're not yet ready to disclose the ultimate approach that we're going to take, but if you consider the advantages of CRISPR engineering in general, and locus is certainly the ultimate objective here, and the best way to do that is something we'll talk about when we're ready to share more details about that.
Okay, great. Thanks.
This concludes today's question and answer session. I would now like to hand the call back to Lina for any closing remarks.
Great. Thank you all for joining today's call and for your continued interest in Intellia. We are excited by what's to come in 2019 and look forward to updating you on our progress.