Intellia Therapeutics Inc

NASDAQ:NTLA

Earnings Call Transcript 2019-Q3

[Operator]

Good morning. My name is Derrick, and I will be your conference operator today and welcome to the Intellia Therapeutics’ Third Quarter 2019 Financial Results Conference Call. At this time, all participants are in a listen-only mode. Following the formal remarks, we will open the call for your questions. Please be advised that this call is being recorded at the company's request.

At this time, I will turn it over to Lina Li, Associate Director of Investor Relations at Intellia. Please proceed.

[Lina Li, Senior Manager, Investor Relations]

Thank you, operator. Good morning and thank you all for joining us today to discuss Intellia’s third 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 on the Investor section of our website at www.intelliatx.com. This call is being broadcasted live and a replay will also be archived on our website.

Before we get started, I would like to remind you that 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; Dr. Laura Sepp-Lorenzino, our Executive Vice President and Chief Scientific Officer; and Glenn Goddard, our Executive Vice President and Chief Financial Officer. Following their prepared remarks we will be open for Q&A for which Andrew Schiermeier, our Executive Vice President and Chief Operating Officer and José Rivera, our Executive Vice President and General Counsel will also be joining.

For today's call, John will begin by discussing the company's highlights, Laura will provide an update on our R&D progress, and Glenn will review our financial results for the third quarter of 2019.

With that, let me turn the call over to our CEO. John?

[John Leonard, President and Chief Executive Officer]

Thanks, Lina, and welcome everyone to our third quarter earnings call. At Intellia, we are pursuing a full spectrum strategy to rapidly develop a diverse pipeline [ph], including programs led by genome editing in vivo where we deliver CRISPR/Cas9 components as a therapy and ex vivo where we use CRISPR/Cas9 as a tool to create engineered cell based therapies.

We continue to believe our modular approach and innovative science position us well to translate genome editing into new medicines that address critical areas of unmet medical need. Today, we've generated a robust set of preclinical data supporting our potential to cure genetic diseases with a single administration and we're especially excited about the progress of our ex vivo approach, which we believe can capture the full promise of novel engineered cell therapies for the treatment of cancer and autoimmune disease.

On the in vivo side, with our systemic lipid nanoparticle or LNP based delivery system, we believe we have unlocked treatment of genetic diseases that have their origin in the liver. We have demonstrated we can selectively knock out disease-causing genes and we can also precisely insert genes to produce normal human proteins for therapeutic purposes.

On the ex vivo side, we focus on engineering lymphocytes that retain normal cell physiology while targeting various hematopoietic and solid tissue cancers. Our approach to engineering lymphocytes is designed to overcome the limitations of most currently available cell based therapies.

In the third quarter and more recently, we've continued to progress our lead programs for transthyretin amyloidosis in acute myeloid leukemia and successfully executed on our objectives as we prepare to enter the clinic, and just last week we presented data at the 2019 European Society for Gene and Cell Therapy Annual Meeting or ESGCT.

These results included the first demonstration of our consecutive in vivo gene editing approach to address alpha-1 antitrypsin deficiency. This novel editing strategy provides further validation of our modular approach and importantly offers yet another proof point for the advantages of our proprietary non-viral delivery system for systemic administration of CRISPR/Cas9.

I'll now hand it over to Laura to review our R&D progress in detail. Laura?

[Laura Sepp-Lorenzino]

Thank you, John, and good morning. Indeed this is an exciting time for us as we continue to validate our novel therapeutic modality and progress our initial programs to the clinic. I would like to first talk about our in vivo pipeline starting with NTLA-2001, our development candidate for the treatment of transthyretin amyloidosis or ATTR.

As you know, ATTR is a progressive and fatal disease that results from the production of [indiscernible] TTR protein in the liver and the deposition of insoluble TTR protein fibroids in multiple organs, leading to diverse disease manifestations, including peripheral neuropathy and cardiomyopathy.

Over 120 genetic mutations are known to manifest at hereditary ATTR which affects approximately 50,000 patients worldwide. Furthermore, in the absence of a genetic mutation, ATTR can also develop spontaneously known as wild-type ATTR, which affects an estimated 200,000 to 500,000 patients across the globe. With NTLA-2001 our goal is to treat patients with ATTR regardless of whether they have either the hereditary or wild-type form of the disease, because we will be knocking out the underlying disease causing TTR gene.

Over the past few years, our peers have made tremendous strides in certain patients with ATTR. They have validated a target and shown that reducing expression of TTR protein is an effective way to achieve clinical benefit. We hope to build on those results as both fundamental to the premise of gene editing with CRISPR/Cas9 and true to our mission, we believe that the potential to provide a one-time potentially curative treatment and address need for patients and represents a key differentiating factor of our approach.

Today, we have demonstrated this potential in studies with our lead LNT formulation targeting the TTR gene in nonhuman primates. Following a single administration, we achieved an average reduction of greater than 95% of circulating TTR in nonhuman primates which is expected to be clinically efficacious. As part of the ongoing durability study, we have demonstrated 10 months of durable liver editing with sustained reduction of circulating TTR proteins. We are very pleased with these results and continue to advance our IND enabling studies.

We also announced today that we have commenced clinical scale manufacturing for our Phase 1 materials and importantly we remain on track to submit an IND application for NTLA-2001 in mid 2020, which we expect to be the first systemically delivered CRISPR/Cas9 therapy in the clinic. As a reminder, for this program, we have a 50-50 co-development and co-commercialization agreement with Regeneron with Intellia as the lead party.

Let's now turn to our target and insertion efforts in the liver. As discussed on prior calls, we've demonstrated this first CRISPR/Cas9 mediated targeted transgene insertion in the liver of nonhuman primates using Factor IX inserted into the albumin locus. As a reminder, Factor IX echos [ph] the blood clotting protein that is missing or defective in hemophilia B patients. This study used our proprietary hybrid delivery vehicle which combines our CRISPR LNP delivery system with an AAV vector encoding the Factor IX gene.

In a nice demonstration of the modularity of our platform, the CRISPR LNP delivery system is the same as the one used in our ATTR program with the sole change being the guide RNA. We believe our targeted insertion approach provides key advantages over traditional gene therapy in both safety and efficacy. Targeted insertion should reduce the risk of mutagenesis due to random integration of retroviral vectors. In addition, targeted insertion should provide durable efficacy with a single course of treatment and potentially cure the disease.

So we are working with Regeneron to identify next steps for the hemophilia B program and have been simultaneously exploring the insertion of other transgenes to support the expansion of our in vivo pipeline. As part of this effort, and again highlighting the modularity of our approach, we have exchanged only the DNA template or the gene of interest in the hybrid LNP AAV delivery system.

Building on our insertion work with factor IX and alpha-1 antitrypsin, we have now generated in vivo protein expression for two additional genes of interest and are evaluating several more. These results are highly encouraging and we look forward to presenting this innovative science at upcoming scientific meetings.

At the June period we've reported on this 2019 ESGCT Annual Meeting the first demonstration of a consecutive in vivo gene knockout and insertion in a mouse model of alpha-1 antitrypsin deficiency or AATD. This disease requires dose [ph] and reduction in the level of the disease-causing protein and restoration of the wild-type protein to ameliorate the disease. The consecutive edits led to a greater than 98% reduction of the disease-causing protein and sustained restoration of the missing protein through therapeutically relevant circulating protein levels throughout the study.

We believe this presents compelling and differentiated therapeutic approach for AATD as it addresses both the liver and lung manifestations of the disease. Moreover, this is another example of our leadership in sustaining genome editing to treating genetic diseases. We will be moving forward with our consecutive editing strategy for AATD in higher animal species.

Moving on to our engineered cell therapy pipeline, we are designing engineered cells to treat a range of hematological and solid tumors. As we've discussed on prior calls, we have four work streams towards this end, so our focus today will be on our wholly-owned T cell receptor or TCR replacement approach.

Initially we are utilizing this approach to target Wilms Tumor 1 for acute myeloid leukemia and then potentially a variety of additional liquid and solid tumors. As a reminder, our proprietary and highly efficient TCR based approach knocks out the endogenous TCRs by eliminating the alpha-beta chain and simultaneously inserts the therapeutic TCR in-locus. Relatively the therapeutic TCR we precisely insert is a naturally occurring TCR that can be found in healthy donors.

This approach should enable us to preserve normal T cell physiology, enhance and stabilize expression of the inserted therapeutic TCRs, and reduce the risk of graft versus host disease that could result from the sparring between endogenous and inserted TCRs. In contrast to CAR-Ts TCRs expand the range of addressable tumor types because they can recognize a broad set of tumor antigens or CAR-Ts typically recognized on these surface proteins. In addition, we will lead [ph] our TCR directed engineered cell therapy approach offers meaningful efficacy and safety advantages over currently available engineered cell therapy treatment.

As you know, acute myeloid leukemia or AML is cancer of the blood and bone marrow with significant unmet medical need. Generally outcomes for the majority of AML patients remained poor and the five-year overall survival rate is less than 30%. By directing TCRs towards the Wilms’ Tumor 1 antigen which is overexpressed in the majority of AML patients, we believe it provides tremendous opportunity to develop a broadly applicable treatment for AML regardless of mutation and background of the patient's leukemia.

As discussed on our last quarter's call, we are currently conducting functional testing in patient derived [ph] xenograft models of multiple lead [ph] WT1 TCR candidates that recognize the primary WTI epitope of interest in AML with high affinity. Data from these ongoing studies will inform the nomination of our development candidate which we remain on track to achieve by year end.

In parallel to ongoing studies, we are advancing GMP manufacturing and related development activities in support of a Phase 1 clinical trial. We believe our AML program will lay the foundation to pursue a broad array of cancers including solid tumors. As WT1 is highly expressed across many liquid and solid tumor types, there is significant opportunity to target a number of subsequent tumor types with the same TCR. And we've begun to generate promising in vitro activity in solid tumor cell lines. We expect this work will unlock new immuno-oncology opportunities to further expand our pipeline.

With that, I would like to turn the call over to Glenn who will go through the third quarter's financial statement.

[Glenn Goddard]

Thank you, Laura, and hello everyone. Intellia remains in a strong financial position as we advance multiple programs forward into development. Our cash, cash equivalents and marketable securities as of September 30, 2019 were approximately $295.8 million compared to $314.1 million as of December 31, 2018. The decrease was mainly due to cash used on operations of approximately $91 million which was offset in part by $54.1 million of net equity proceeds raised in the company's after market agreement, $8 million of funding received under the Novartis collaboration, $7.3 million of ATTR development cost reimbursements made by Regeneron, and $2.8 million in proceeds from employee based stock plans.

Our collaboration revenue was 10.6 million for the third quarter of 2019, compared to $7.4 million for the same period in 2018. As a reminder, our collaboration revenue is related to our partnership agreements with Novartis and Regeneron, also Regeneron funds approximately 50% of the development costs for our ATTR program.

Our R&D expenses were $27.5 million for the third quarter of 2019, compared to $23.2 million for the same period in 2018.This increase mainly relates to the progress of our lead programs and our in-vivo and engineered cell therapy platform efforts.

Our G&A expenses were $8.4 million for the third quarter, compared to $8.3 million for the same period in 2018. This increase was mainly due to employee-related expenses. So finally today, we are reconfirming that we expect our cash balances to fund our current operating plans through at least the next 24 months.

And now I'll turn the call back over to John to briefly summarize our upcoming milestones and corporate update.

[John Leonard, President and Chief Executive Officer]

Thanks, Glenn and Laura. In summary, we are extremely pleased with the achievements we've made so far in 2019. We continue to demonstrate our leadership in systemic genome editing with the potential first LNP CRISPR program in IND enabling tox [ph] studies, and several breakthroughs and editing approaches.

In addition, we've seen our TCR directed engineered cell therapy efforts move forward at a rapid pace. Looking ahead to the balance of the year, our team remains focused on advancing our lead programs for the treatment of ATTR and AML. We remain on track to nominate our development candidate for AML by year-end and for ATTR program.

We're on track to submit an IND application for NTLA-2001 by mid-2020. We believe there is incredible opportunity ahead as we leverage our CRISPR based platform and prioritize next programs to build a robust pipeline of in vivo and engineered cell therapy programs. We look forward to sharing plans for pipeline expansion in 2020 and I'm confident that we have the team and expertise in place to accomplish our mission.

With that I'd like to thank you all for tuning in today. We'll now open up the line to any questions. Operator?

[Operator]

Thank you. [Operator instructions] And your first question comes from the line of Gena Wang with Barclays. Please go ahead.

[Gena Wang, Barclays]

Thank you for taking my questions, and congrats on all the progress, and really glad to hear the IND moving forward. So regarding the WT1 TCR program, just wondering what additional data we will see before you file for IND?

[John Leonard, President and Chief Executive Officer]

Thanks, Gena, this is John. Good morning. As we've said, we're working towards our development candidate and there is few finishing touches between now and the end of the year and we think we'll be in a position to share that data in upcoming scientific conference in 2020 some time and we'll tell you when and where that will be when we're ready to go.

[Gena Wang, Barclays]

Okay, that's fair. And also just wondering given current, like newly emerged technology, I wanted to hear your thoughts on, I think that maybe last week the Nature publication on the prime editing and how do you see the few evolve over time?

[John Leonard, President and Chief Executive Officer]

Well, all of these technologies are based of CRISPR Cas9 which is the core of the work that we do here. We haven't seen any format come out that makes us feel that we're using the wrong work or doing the wrong work or using wrong technology. I think there's interesting data, but there's a long, long way to go before any of that will be ready for patient work. So we'll follow the fuel closely as it evolves and continue on with our own programs.

[Gena Wang, Barclays]

And the last question is regarding ATTR program. So the IND is mid-2020. Just wondering, would there be, or what could be the initial dose? Are you looking for reaching minimum within the therapeutic window and will you be thinking about single dose or double dose?

[John Leonard, President and Chief Executive Officer]

Well, we haven't designed the program finally, yet. With respect to Phase 1 work, obviously that's discussions that we will have with the regulators. As we've said previously, this is likely to be a single ascending dose and it will be a balance between the appropriate place to begin from a safety point of view, and then we'll see the rate at which we can escalate into areas that would be expected to be therapeutic.

[Gena Wang, Barclays]

Would that be a 3 plus 3 trial design?

[John Leonard, President and Chief Executive Officer]

We're not ready to talk about the trial design. There's lots of choices and we're trying to do one that will enable us to move appropriately in patients as prudently and as quickly as possible.

[Gena Wang, Barclays]

Thank you.

[Operator]

Thank you. Your next question comes from the line of Maury Raycroft with Jefferies. Please go ahead.

[MauryRaycroft]

Hi, good morning, everyone, and congrats on the progress. First question is just with the starting of your manufacturing of materials for both ATTR and WT1. Can you provide more specifics including anything on the supply chain contingency plans and then and capacity and how this might factor into expenses going forward?

[John Leonard, President and Chief Executive Officer]

Hi, Maury. Good to hear from you. We're not giving any substantial details in terms of all of the pieces and how they come together. Obviously, this is an important part of moving the program forward and we pay a lot of attention to it. We think we've put in place a plan certainly for ATTR that will get us well into the clinics. So we can establish key data and go forward from that. And as WT1 evolves, we're assembling that supply chain as well. I think we have the benefit of learning from others who have gone before us and we're applying those lessons. So more to come.

[Maury Raycroft, Jefferies]

Got it, okay. And then for your WT1 TCR program, I know it's autologous. You alluded to the design in your comments. I guess with gene editing capabilities, you've got a lot of options. Just wondering if there's anything else in the works as far as novel modifications to enhance safety and efficacy with the TCR engineered cells that you're thinking about?

[John Leonard, President and Chief Executive Officer]

Yes, the first development candidate is, as you pointed out autologous. We think that nicely isolates the key variable here which is the T cell receptor. We presented data on the efficiency, the very, very high efficiency with which we knockout the alpha and beta chain and the very high efficiency with which we can introduce the TCR of choice and we're very, very excited about that.

We think that represents a real step forward in terms of this type of work. As we presented elsewhere, there is a series of other things underway to enhance how we can think about allergenicity, that's separate from this particular development candidate, but we're making very good progress there and when it's appropriate to bring that into this program we will do so and share that data.

[Maury Raycroft, Jefferies]

Got it. And then last question just on AATD. The data at ESGCT was interesting. Just wondering if you can provide any more specifics on timelines for that program and for the NHP studies? And then separately, if you can talk more about the efficacy you're seeing with AATD and also with F9 [ph] and if those data are consistent based on the dose with what you are using in ATTR to affirm that you can switch our guidance and hit new liver targets?

[John Leonard, President and Chief Executive Officer]

So thanks for asking about that exciting data. We think it's another demonstration of the importance of modularity. And yes, the LNP format and the dose are essentially the same going from model to model system. So we're excited about that. So, first and foremost, it's demonstration of that. That work was done in a metering [ph] system. There's work to extend that into nonhuman primates. And as that data evolves, we'll be talking about it at future presentations, but it's moving along very, very briskly and we're excited about it.

[Maury Raycroft, Jefferies]

Great. Okay, thank you very much. Thanks for taking my questions.

[Operator]

Thank you. Your next question comes from the line of Mani Foroohar of SVB Leerink. Please go ahead.

[Unidentified Analyst]

Hey, good morning, this is Rick dialling in for Mani. Congrats on all the progress and all the great presentations at ESGCT. My first question is about the cell therapy program. Could you maybe discuss some of the next steps, once the WT1 candidate is nominated and the anticipated timelines for how long you anticipate the IND enabling studies will take to complete?

[John Leonard, President and Chief Executive Officer]

I was waiting for the second question there, but this is the first one. As I said earlier in the WT1 program we are in the final stages of selecting our development candidate. I would expect early next year we will share more details about what the timeline is for progress in that program. So today is not the right time to be talking about IND timelines.

[Unidentified Analyst]

Okay, got it. I'll shift over to the alpha 1 antitrypsin program then. So just thinking about the competitive landscape for this disease, there are competitive oligonucleotide programs that are specifically going after the Alpha-1 liver disease and they are designing n clinical trials with just the logical endpoints. So I was wondering are there ongoing animal studies or you're specifically looking at reduction of TTR protein in the liver or maybe histological improvement.

And since these programs are specifically just looking to knock down the [indiscernible] just maybe share some of your thoughts on the importance of knocking out diseased [indiscernible] versus restoring expression of a wild-type protein in this disease and what it could mean for competitive positioning for your program?

[John Leonard, President and Chief Executive Officer]

Yes, thanks for the question. As you know, Alpha-1 Antitrypsin deficiency has two aspects to it. One is the liver disease which is best addressed by knocking that protein down. Most of the pathology and morbidity and mortality frankly comes from the lung disease and to deal with that you need to reconstitute normal levels of protein. The work that we did shows that we can address both and that would be the format that we think is most clinically relevant and one that we would intend to bring forward.

So to the extent that we achieve those normal levels as we continue our work of circling protein, we believe that that would constitute the best solution for patients and that's the bar we’re setting for ourselves.

[Unidentified Analyst]

Okay and as far as the histological endpoints for liver disease, is that something you'll be looking at in your ongoing animal studies?

[John Leonard, President and Chief Executive Officer]

We've already shown in mice, that you can have an effect and that's certainly something that we'll continue to study as we progress the program.

[Unidentified Analyst]

Great, thanks for taking my questions.

[John Leonard, President and Chief Executive Officer]

Sure.

[Operator]

Thank you. Your next question comes from David Nierengarten with Wedbush Securities. Please go ahead.

[David Nierengarten, Wedbush Securities]

Thanks for taking my question. I just had one curiosity. You're a little bit different with AML and having an autologous approach. Are there other safety or your other preclinical data we should be looking for when we take a look at your efforts versus some of the highlights, approaches for AML? Thanks. [Indiscernible]

[John Leonard, President and Chief Executive Officer]

Yes well, thanks for the question. Our approach with an autologous cell source, we think is one of the very key aspects of addressing safety and then the precision with which one can introduce the chosen TCR in locus and eliminate the endogenous TCR change that could potentially miss care we think constitutes a real step forward for patients with this particular approach.

So obviously we study that in a variety of systems, some of them in vivo and as we bring our development candidate forward at a future scientific meeting we’ll position to share the results of some of those studies with you. But at this point, we're very excited about the activity that we're seeing certainly in AML blasts as well as other solid tumors as we study them in in vitro systems. And we expect that we will have some exciting clinical candidates to – investigate here on next year and shortly thereafter.

[David Nierengarten, Wedbush Securities]

Right and maybe just a quick check, there is no difference or any reason to think there'd be any difference besides tumor biology or having -- besides we said solid versus liquid tumor between the candidates for solid and liquid tumors?

[John Leonard, President and Chief Executive Officer]

No.

[David Nierengarten, Wedbush Securities]

Okay. Just checking, thanks.

[John Leonard, President and Chief Executive Officer]

You bet.

[Operator]

Thank you. We’ll next go to the line of Amanda Murphy with BTIG Capital. Please go ahead.

[Amanda Murphy, BTIG Capital]

Hi, good morning. I just had a question on TTR, so obviously the [indiscernible] seems to be going pretty well there. I just was curious, in terms of what the lessons learned there with the lessons learned are in terms of physician education and diagnosis, and it seems like there is a little bit of, I mean obviously - wide range in terms of the market opportunity and a little bit of discussion there. So just curious, your thoughts as that market evolves just how big it actually ultimately is, first on the wild-type perspective?

[John Leonard, President and Chief Executive Officer]

I'm not sure I heard all of the elements of your question Amanda, but I think you are asking me about the market opportunity and how it's evolving for TTR. We clearly are watching it as it happens. We have some new entrants into that marketplace and as you know, this is a market that didn't exist previously. So there is a lot of learning that will take place. Typically in cases like this we see the early estimates tend to underestimate what's actually out there as doctors learn to recognize the disease and one might conclude - some of the early Pfizer data that in fact that's happening already.

So as we put our program in place, we want to position ourselves so that we will be able to address both aspects of this, both neuropathy and cardiomyopathy or doing it in a way that we can address TTR whether it's mutated or wild-type. And lot of work to do lies ahead, but we're very, very excited about the opportunities as we understand it better.

[Amanda Murphy, BTIG Capital]

Yes that was the sales I was asking just around the – what we learned so far on the Pfizer launch, but that makes sense. And then just another one on the TCR program and I realize it's just early, but we said that this may be too early to ask the question, but obviously you're kind of focused on having a modular approach in general. So going forward longer term is the right way to think about expansion of indications really focused on WT1 or would we also think about maybe target expansion or use of different targets going forward and is that a 5-year kind of timeline or is that potentially nearer term?

[John Leonard, President and Chief Executive Officer]

Right, so modularity is key to all that we're doing here and that's certainly poised on the cell-based side as well. The way I would think about the first step that we're doing with WT1 is to validate the T cell receptor and a particular approach that we're taking, but that's immediately extendable into solid tumors and we would hope to be in a position that we could pursue that very, very quickly or even shortly thereafter the AML program begins.

Ways to expand on that include building out the TCR set and doing that across HLA types and then moving into other particular TCR target. So, we think once you have that basic module in place, there is many, many opportunities to move forward very broadly and very aggressively.

[Amanda Murphy, BTIG Capital]

Again, just last one on the bidirectional template insertion concept, just curious how, I don't know if the right word protected, is that I mean it's been pretty interesting and you make some sense. Is that something that you're pursuing, in terms of patent protection, just obviously again, going back to the modularity concept of insertion approaches?

[John Leonard, President and Chief Executive Officer]

Yes, I'd rather not comment on the particular IP approach that we take. Certainly, as we bring our products forward we would expect to have many layers of protection. It's not just one thing or another, it's the various components as they come together for a particular therapeutic approach and that's the way that we approach holds the potential products that we have here and then tell you [ph].

[Amanda Murphy, BTIG Capital]

Yes, okay. Thanks very much.

[Operator]

Thank you. Your next question comes from the line of Steven Seedhouse with Raymond James. Please go ahead.

[Steven Seedhouse, Raymond James]

Good morning. I had a question about the strategy and AATD strategy and data at ESGCT, were you knocking out the diseased allele and then sequencing the second editing step to insert wild-type gene at the albumin locus I think 3 weeks later. I was just curious, what are the pros and cons of sequencing those edits versus just multiplexing them at the same time, because two editing steps are targeting different low size or – I guess theoretically you could multiplex them?

[John Leonard, President and Chief Executive Officer]

Well, the first step was to carry out the experiment in a way that would be very, very clear. So we wanted to show that we had achieved a knockout and that we could then sequentially dose the LNPs which is an important element of the study by itself, and get an effect, we demonstrated that. So it comes back to the very notion of the basic notion of re-doseability with LNPs and I think we've demonstrated that in this particular program.

The optimal timing of when to do this is something yet to be worked out. I think that will be dependent on additional studies and data as we accumulate going forward. But you should take this first experiment as already very, very exciting, because it has not been subjected to much optimization, but we're able to get very high levels of protein. But as we think about the ways to control that further, there is many ways to enhance the system and make it efficient. So work that lies ahead, nonhuman primate data, et cetera, stay tuned.

[Steven Seedhouse, Raymond James]

Okay, I appreciate that and one short one on the optimization that you alluded to, what is the percent efficiency for wild-type gene insertion at the albumin locus that is getting you already to therapeutic levels of AATD [ph]?

[John Leonard, President and Chief Executive Officer]

No we haven't presented that data yet. So that will be upcoming work that we do as we pursue various targets, it's early days yet.

[Steven Seedhouse, Raymond James]

Okay, thank you.

[Operator]

Thank you. Your next question comes from the line of Madhu Kumar with R. W. Baird.

[Madhu Kumar, Robert W. Baird & Co]

Good morning everyone. Thanks for taking our questions. So our first one is, could you just generally walk through the remaining steps for NTLA-2001 between now and the mid-20 IND submission? And then thinking about our clinical program for NTLA-2001 and a kind of broad strokes level, what is the target TTR suppression level you're looking to achieve or you mean for Onpattro [ph] level of TTR suppression or something deeper? Thank you.

[John Leonard, President and Chief Executive Officer]

Thank you, Madhu. We don't give a step-by-step analysis of our work in the IND. There is general steps I think are broadly understood. Some of this is time gated work. It relates to the tox studies and we're well into that. There is manufacturing of material, which we, as we talked about on the earlier part of the call, we've begun and all of that stuff is on its way. We expect to hit the target of 90 [ph] or mid 2020 next year. We're all working very diligently to achieve that.

With respect to the targeted suppression levels of TTR, we've learned from those that have come before us that levels below 60% are associated with therapeutic activity and that's certainly foremost in our mind, but we want to hit the benchmarks that we think will represent a therapeutic advance for patients. So, we are striving to achieve higher levels of suppression and would hope to exceed levels of 80% suppression of TTR and certainly demonstrate that we can do that in non-human primates. So it's all a question of moving into the human clinical situation and collecting data, but that is our benchmark at this point.

[Madhu Kumar, Robert W. Baird & Co]

Excellent, thanks very much guys.

[Operator]

Thank you. [Operator Instructions] We'll next go to Silvan Tuerkcan with Oppenheimer. Please go ahead.

[Silvan Tuerkcan, Oppenheimer]

Thank you for taking my questions and congratulations on the impressive AATD data. At ESGCT you also presented updated data in a mouse model in primary hyperoxaluria, PH. What is your current thinking around the best target gene in between Hao1 and Ldha?

[John Leonard, President and Chief Executive Officer]

So we continue to think about PH1. It's in our discovery group and we've done a fair amount of research. One aspect that we've learned from that is the modularity of our system and you should think of some of the data that we presented that way to take the LNP and across all of these different targets in the liver whether the PH1 targets - alpha-1 antitrypsin or TTR, we've demonstrated that same LNP is useful against all of those targets. So part of the data speaks to that.

With respect to the best way to proceed in PH1 we haven't decided, but we've demonstrated that there is more than one way to be successful there. And how we advance that program and if we advance that program is a function of some of the other choices that we've been working on, so stay tuned.

[Silvan Tuerkcan, Oppenheimer]

Great thank you. And with respect to the Novartis collaboration that's coming to the opt-in decision point in December 2019. Is there any update you can give us or how you think or what the plans are?

[John Leonard, President and Chief Executive Officer]

That's for Novartis to decide and as appropriate we will provide updates, but none today.

[Silvan Tuerkcan, Oppenheimer]

Great, thanks for taking my questions.

[John Leonard, President and Chief Executive Officer]

Yes.

[Operator]

Thank you. We’ll next go to the line of Tashdid Hasa with Roth Capital. Please go ahead.

[Tashdid Hasa, ROTH Capital Partners]

Hi, good morning, thank you for taking my question. Going back to data presented at the Gene and Cell Therapy Conference, in the mouse model of primary hyperoxaluria, it looks like while there is a very good correlation between reduction in oxalate levels and in editing percentage, however, but that that seems to break down between 1 milligram and 2 milligram dose, I would like to hear your thoughts on this if possible? Thank you.

[John Leonard, President and Chief Executive Officer]

Well, and I could go into all of the details of the data other than say generally speaking, there is a relationship between the extent of editing and the effect that you achieve. And the extent to which you knock out the gene of interest that's going to have the attended physiologic correlate, and that's work we've demonstrated across all the targets as I think you should expect, so it's not surprising.

[Tashdid Hasa, ROTH Capital Partners]

Thank you.

[Operator]

Thank you. And it does appear we have no further questions at this time, I'd like to turn the conference back over to Lina Li for any additional or closing remarks.

[Lina Li, Senior Manager, Investor Relations]

Thanks. And thank you all for joining today's call and for your continued interest and support. We look forward to updating you on our progress. Have a great day.

[Operator]

Thank you. And again, that does conclude today's call. We do thank you for your participation, you may now disconnect.