Call Start: 08:00 January 1, 0000 8:47 AM ET
Intellia Therapeutics, Inc. (NASDAQ:NTLA)
Q1 2019 Earnings Conference Call
May 2, 2019 08:00 AM ET
Lina Li - Senior Manager, Investor Relations
John Leonard - Chief Executive Officer
Glenn Goddard - Executive Vice President and Chief Financial Officer
Andrew Schiermeier - Executive Vice President, Corporate Strategy
Conference Call Participants
Maury Raycroft - Jefferies, LLC
Gena Wang - Barclays
Steven Seedhouse - Raymond James
Silvan Turkcan - Oppenheimer
David Nierengarten - Wedbush Securities
Geulah Livshits - Chardan Capital Markets
Good morning. My name is Jessica and I will be your conference operator today. Welcome everyone 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 conference this quarter and a topic 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 & 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 those specific earnings call.
Before we get started, on Slide 2, 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 as you refer to our SEC filing 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 3, 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 for the first quarter of 2019. Then, 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. Intellia we are pursuing a full spectrum strategy. We have an in vivo approach in which CRISPR components of 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 4.
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 not have 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. A recent gene knockout and targeted insertion results in the liver of nonhuman 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 and 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 are excited to walk you through some of those data today.
Let's turn first to our lead in vivo development program on Slide 5, which is for transthyretin amyloidosis or ATTR. This disease results from deposits of insoluble amyloid fibers within multiple organs and tissues caused by accumulation of TTR protein. The data shown on Slide 6, captures our progress toward identifying our lead candidate for our ATTR program. The very first study is in nonhuman primates as captured in the yellow bar, produced low, but promising levels of editing in liver.
These results were highly encouraging and they were the first demonstration of a dose-dependent CRISPR/Cas9 mediate edited in the liver 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 7, for both hereditary and wild type ATTR, the therapeutic objective is to reduce the levels of protein available for amyloid. On the chart on the left, you will see the TTR editing results from our lead candidate. And on the turn on the right, along a single dose, we achieved an average reduction of greater than 95% or circulating TTR protein in nonhuman primates. A reduction of 60% has been associated with human clinical benefit, a benchmark we readily surpassed.
Since announcing these results in February of this year, we’ve a 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 a 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 nonhuman 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 the CRISPR mediated edit highlighting the curative potential of our technology, which of course is our ultimate objective for patients.
Moving now to Slide 8. Based on these encouraging results, we're pleased to announce that we’ve 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's 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 9, we look forward to presenting new data later today at ASGCT, providing further evidence of our ability to knockout additional target genes in the liver, using a primary hyperoxaluria type 1 or PH1 here in disease portal. 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 knockout the targeted gene in one case lactate dehydrogenase A, or LDHA. And in the other case hydroxyacid oxidase 1, or Hao1.
Based on the therapeutically relevant urinary oxalate reduction sustain for 15 week observation period. A 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 of knockout target genes of interest in 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 nonhuman primates, achieving normal circulating human levels of 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 bidirectional insertion template that enqoutes 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 our targeted insertion approach, the goal is to restore function, where the effect is durable without the need for re-dosing and intervening earlier in disease progression. In contrast, as shown on slight 12, conventional gene therapy typically uses a viral system to deliver therapeutic gene. AAV despite several shortcomings, its most often a system choice. Because AAV generally does not integrate into the genome is lost in organs where cell division levels are significant, which is undesirable in applications requiring long-term durability.
And a low retroviral vectors to integrate into the chromosome. They do so randomly and thereby introduce the risk of insertional mutagenesis. Now with our LNP AAV delivery approach for targeted stable gene insertion, we’ve the potential to overcome limitations of viral-based gene therapy.
Now on Slide 13, here we use our hybrid LNP AAV system for target insertion of Factor 9 gene which -- it's Factor IX protein missing or defective in hemophilia B patients into the hepatic albumin locus in nonhuman primates. We selected the albumin locus as an attractive insertion site because it is the most highly expressed gene in liver, which helps ensure substantial expression for the inserted Factor 9 gene.
Slide 14 displays the protein expression levels after a single administration of our hybrid delivery of the Factor 9 gene in nonhuman primates. On the left side of the graph you'll 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 hyper function of human Factor 9 DNA template achieves human Factor 9 protein production.
In our most recent study, initial results indicate that a single dose achieved approximately 3 to 4 micrograms/milliliter circulating human Factor 9 protein at day 14. This level lies within the reported range of normal circulating human Factor 9 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 are encouraged by this latest Factor 9 data and view this as a significant breakthrough in our genome editing capabilities. Now contextualizing what this all means for our platform based approach on Slide 15. These achievements across our in vivo efforts are testaments to the tremendous advances we’re making. Effectively, we believe we’ve solved several key aspects of delivery to deliver on nonhuman primates as we've demonstrated our ability to selectively knockout target genes of interest with a minor change of the guide RNA.
We’ve now achieved target insertion of the DNA template to restore normal functionality of the missing protein. These capability 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.
Now 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 solid tumors.
On Slide 16, we outline our independent work streams towards achieving these goals. For today, we will focus on our TCR replacement approach for a wholly-owned lead autologous program in development for acute myeloid leukemia or AML. As we review on Slide 17, AMLs are 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% 5-year overall survival rate. In 2018, there were approximately 20,000 new cases in the U.S alone. Over the past 2 to 3 decades, there have been limited advances in treatment options for AML patients.
As shown on Slide 18, we've chosen the 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 cancer.
As illustrated, the approach here max out both the alpha and beta chance, the T cells endogenous TCR is depicted by the red dot at 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 mis-paired TCRs between the endogenous and insert TCRs. And 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're 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 tumor.
On Slide 19, at ASGCT, our collaborators Ospedale San Raffaele presented in vitro data which show that CRISPR/Cas9 editing resulted in greater than 98% knockout with the endogenous TCR, but 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 interest, which was restricted to the HLA-A 02:01 allele.
We are pleased to announce today that we will advance the lead TCRs into functional testing and patient derived Xenograft Models late 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 the genome editing company for long-term sustainability and success. With our innovative science, strong platform capabilities and world class team, we believe, we're poised to deliver transformative therapies for patients.
And with that, I will turn it over to Glenn Goddard, Executive Vice President and CFO, who will walk you through our first quarter financials.
A - Glenn Goddard
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, cash equivalent and marketable securities as of March 31, 2019 were $297 million compared to $214 million as of December 31, 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 aftermarket agreement, and $1.5 million of reimbursable NLTA-2001 cost received from Regeneron.
Our collaboration revenue was at $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 agreement. Also, Regeneron's co-funding of NLTA-2001 related activities is included within collaboration revenue. Our R&D expenses were at $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 NLTA-2001 into development and related activities. Our G&A expenses were at $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 operations. Finally today we’re reconfirming our previous guidance that we expect our current cash position to fund our current operating plans into the first half of 2021.
And with that, I will turn the call back over to John to summarize our key achievements and the upcoming milestones.
Thanks, Glenn. On Slide 22, in summary, based on the significant progress we've made on our platform capabilities, we cannot have 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 ATTR program, we plan to initiate IND enabling toxicology studies midyear and we plan to commence manufacturing of Phase 1 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 drive Xenograft Models. So multiple lead TCRs and mid-2019 and planned a nominator. First, engineered cell therapy development candidate for AML by year-end. With that, I would like to thank you all for tuning in the today and a special thanks to our team at Intellia for their dedication and commitment in bringing forth this ground breaking work.
We will now open up the line to any questions. Operator?
Thank you. [Operator Instructions] We will now take our first question from Maury Raycroft of Jefferies. Please go ahead, sir.
Hi. Good morning everyone and 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 looks solid, so far especially with the new LNP formulation in nonhuman primates. I was just wondering if you can comment on what next steps would be with this approach?
Thanks, Maury. There -- as we commented in the call, it's an ongoing study. We are certainly very excited about the results we presented here. As I point out is, as I’ve tried to my comments that I think the really exciting aspect of this thing is that we are talking about actual levels of protein that are circulating in terms of micrograms per million. So when you look at it from that point of view, we think this is a very, very exciting data and has implications. Not just for a hemophilia B, but also for any other genes that you want might want to insert. We're not only trying to reconstitute enzymatic activity but even other source of protein. So I think it's important to look at the data with that in mind. So 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. So we will continue to observe these sounds for some time and we will decide what’s appropriate. Safety is obviously of interest to us. The animals are doing very, very well. So that's extremely encouraging us. Its frankly been the case across all the work that we've done so far. So that’s been a very good news. And this is a program that we're doing in collaboration with Regeneron. So 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. And 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 derisk the technologies. And you've got Regeneron involved, but 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 relationships 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 uprights to do some things outside of that, should they choose to do so. But it's still -- it's a collaboration that’s focused primarily on in vivo use of the technology targeting liver. So when you talk about T cells, it's important to recognize that T cells and cell engineering in general and ex vivo uses, when I think about in those terms are with the exception of the relationship that we have with Novartis on Car Ts and some limited number of HSC [indiscernible] entirely in the hands of Intellia. And 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. So the first TCR program that we discussed about, I think a promise to show the utility of that approach. And then 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. And last question is just on ATTR. So given that the dose ranging studies are nearly -- completely that you’ve done on the preclinical setting, can you provide more details on how you anticipate a dose escalation in humans good luck. And, I guess, did those preclinical studies inform how that dose escalation in humans to look and what variables you're considering coming into humans?
Right. So dose range finding work sets up the formal GOP tox studies. That's all part of ongoing work and discussions with the FDA, but lays the groundwork for exactly what you're talking about which is that first clinical study in many respects. I anticipate that that study will look a lot like what you would expect a first single sending dose study to look like. We recently talked to investigators who are eager to participate in that. We anticipate that we will have a good supply of patients who want to be part of that work. And once we have all the material ready to go, we are very excited to move into the clinic. So, we will keep you informed as the IND date tightens, as some of these pieces come together, but that's obviously our target, being in the clinic as quickly as possible.
Got it. Thank you very much for taking my questions.
Our next question will come from Gena Wang of Barclays. Please go ahead.
Thank you for taking my questions. And first one, John, that would be for the PH1 program. Just wondering would that be also leading a same LNP systems that you would -- that is used for the ATTR program?
Right. So PH1 -- and again this is a presentation that will 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 the TTR data that we show here, this presentation I’ve shown elsewhere. So this goes back to the modularity of the approach we’ve tried to develop. So once you saw the 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 you want to actually go after. So this is an example of that modularity, and with minimal change we see that in fact it's quite effective. Anyway, so I would say Gena, with respect to PH1 where this plays out ultimately from a development point of view, is the decision yet to be made. This is work that’s been done in our research last, just demonstrated the overall approach of modularity.
Okay. And then my next question will be regarding the insertion programs. The Factor 9 model actually looks very impressive, the editing efficiency when we look at you presented positive sales actually around 50%. Just wondering in a philosophical way, because you’re inserting at the first into in an albumin, would that be necessary given the high editing efficiency and would there be any safety concern since albumin is a very strong promoter in our body?
Yes, I commented in the talk, we are obviously paying attention to albumin. We've been following that very, very carefully. And thus far albumin levels appear to be unaffected even in animals that have, yes, 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 this protein levels? There are different elements that we have to toggle, if you will, to determine where we want to go. One is where you place the guide and the actual cut site, which is something that we look very, very carefully at. What is the dose of the LNP and what is the dose of the AAV? And as we've shown here and elsewhere, the combination of those three elements is what’s going to ultimately determine the levels of protein production. So safety and mind and ultimate therapeutic objectives, I think it's going to be very much a balance of those. Just thinking about albumin a little bit, recognize that we frequently forget that hepatocytes [ph] have multiple alleles. There's a significant ploity [ph] here and we should not assume that every single allele, it's been edited in these hepatocytes. We can detect the presence of the transgene in cells, up to 50% capacity in every single new husband edited in. And there's a reason to believe that there's feedback loops where the body looks to maintain levels of that, even given that’s essential use and plasma.
Okay. Thank you. And then my last question, just wondering is there any change in senior management recently?
Could you repeat the question? I didn’t -- changing, I didn’t hear the -- what …?
We has been building our team for some time. As I’m sure you not, as you’ve met him. Glenn Goddard joined here as CFO in November of this past year. We have -- 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 expose potential. We have no plans to have any senior management leave. But it's our expectation that we will have -- we will continue to grow our senior team as appropriate as we move forward.
Okay. I think in the region, I’m asking, is there any other departure in the past senior management?
Well, not at the most senior level, I mean, 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, like I’m just curious about if Tom Barnes is still with the Company?
Tom has left. Tom joined the company at the very, very beginning. He was 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.
Our next question will come from Steven Seedhouse of Raymond James. Please go ahead.
Thank you. Good morning. In the planned Phase 1 ATTR study, do you want to explore re-dosing of LNPs in some patients either in the protocol itself for an extension study or will you just have single dose administration of NTLA-2001.
I think it's a really important question. And it's one that we want to work through with the Food and Drug Administration. I would say there's two elements of 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 a change that’s been made. And one of the things that we again need to work through the Food and Drug Administration is whether or not we offer to those patients assuming the data merits said, an opportunity to be re-dosed at higher doses if we do see an effect. And secondly, there is just an economy to doing this work. If we can come back and re-dose patients subsequently, but very much a work-in-progress and a point of discussion as we work through this and finalize the approach, obviously, we will share it with all of you.
Okay, thanks. And just relatedly, I guess, generally what are your thoughts on sort of some of the work that’s been done on Cas9 immunity and can you talk about any work you've done re-dosing 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, and as you know, there's multiple aspects of that. With respect to human immunity and the formation of antibodies, a couple of considerations first remember we are using a lipid nanoparticle that contains RNA. It doesn't contain the Cas9 protein. We’ve seen the formation of antibodies after dosing with the LNP. However, when looking for re-dosing activity we’ve not found any effect of those antibodies.
Okay, great. And just on the Factor 9 and HP studies where are you on the curve of the LNP dose relative to the ATTR studies and the factor expression that you see in primates. Do you know what level of editing that correlates to in the liver of the primates? And have you looked at editing and either I guess primates or mice by DNA sequencing? What’s the percent 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 what are the determinants or something that, obviously, we will take into consideration because there are multiple toggles to determining that. But it's some of the early days here in terms of what we can get with insertion, but we are very, very excited about where we are already.
Okay. Just last question on -- again on Factor 9, and this is regarding the rodent or the mouse study presented at ASGCT. Any thoughts -- I mean, you are obviously getting pretty good Factor 9 expression. Any thoughts on why the expression increases still between weeks 20 to 40? Is Cas9 continued to be expressed, I guess, on tissue past 20 weeks after a single dose?
Cas9 and our work is transiently expressed as a result of using the lipid nanoparticle approach. So 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 protein is produced. The protein goes away. So there is no ongoing source of it to go into editing. The slide you're referring to I think is Slide 11, where there's some drift between 20 and 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 would be illuminating and that’s what we will look for.
Okay. Appreciate all the data and thanks so much for taking my questions.
Sure. Thank you.
Our next question comes from Silvan Turkcan 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 in 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 1 material?
It's really the standard set of work that needs to be done. As I referred to my comments earlier, the dose range finding work has been done. This is where animals are exposed to ascending doses of the material to get to a point that essentially brackets that range of doses to be tested. That lays the foundation for the formal GOP 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, 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.
Thanks for taking the question. I actually had one on the WT1 program [indiscernible]. Just a couple quick ones. If you could remind us on the HLA restriction for the program and what percentage of patients would have the appropriate HLA allele. And then also were you planning at some point to develop an allele approach for AML, or is there an allele approaches for other tumors or other targets? Thanks.
Yes, right. So on Slide 19, we identified the HLA type which is HLA-A 02:01. That -- depending on the population you are in, but in a standard western population, we are talking 50-ish percent or so patients would expected to have that. And 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 a -- we think an ideal way to begin and explored the overall TCR approach in the thesis that we’ve used. WT1 as I’m sure you remember, David, is an ideal target for AML. But if you look beyond that into solid tumors, it's one of those very attractive over expressed proteins that’s broadly applicable. So it's -- we view this as a staged approach where looking blood with a TCR that we think is appropriate and naturally occurring, but selected in a -- the appropriate -- most appropriate way with our colleagues at OSR and [indiscernible] show that works in blood and then move broadly as quickly as we can. With respect to the first development candidate, you asked will the allele or auto? Our base case at this point is that we -- this would be an autologous approach. As I said, we’ve a parallel work stream which is rapidly moving along. If there's opportunities to move to that, we will, but I think at this point you should assume that 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. So build the TCR platform, build out what we view as true allergenicity and by that I mean cells that are measured to persist in the presence of cells, designed to kill them as opposed to merely knocking out MHC1 or MHC2. And at the appropriate time merge those work streams to get the benefit of all of them.
Okay. Thank you.
And thank you for asking about our engineered cell therapy program. That’s something that just for the other listeners, I would point out is 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 are advancing both aspects in parallel and as you can see, the engineered cell therapy Act is actually catching up with the in vivo works. So we're very, very excited.
Our next question comes from Geulah Livshits of Chardan. Please go ahead.
Thanks. 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. So I believe the [indiscernible] presentation at ASGCT showed delivery of the TCR with a vent of [indiscernible]. Could you talk about whether this is something that will be the case for until your first product candidate, or if you plan to do the targeted insertion into the track locus? And also [indiscernible] as part of that development and would you -- 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 this type of approach? Thanks.
Geulah, 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. Lengthy to demonstrate that the TCRs if they've identified have high activity and can -- and are broadly active against an array of different AML blast. So we are very, very excited about what they fished out. In terms of our approach, we are not yet ready to disclose the ultimate approach that we are 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 will talk about when we are 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.