Intellia Therapeutics Inc

NASDAQ:NTLA

Earnings Call Transcript 2020-Q1

[Operator]

Good morning. My name is Andrew, and I will be your conference operator today. Welcome to the Intellia Therapeutics First Quarter 2020 Financial Results Conference Call. All participants will be in listen-only mode. [Operator Instructions] After today’s formal remark’s there will be an opportunity to ask questions. [Operator Instructions]

Please note this event is being recorded.

I would now like to turn the conference over to Lina Li, Associate Director of Investor Relations at Intellia. Please go ahead.

[Lina Li, Associate Director of Investor Relations]

Thank you, operator. Good morning everyone, and welcome to Intellia's first quarter 2020 earnings call. Today we are coming to you from different locations and we ask that you please bear with us in the event we have any audio interruptions on the call.

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 Investors and Media section of our website at www.intelliatx.com. This call is being broadcast 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 presented on this call 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 Chief Executive Officer; Dr. Laura Sepp-Lorenzino, our Chief Scientific Officer; and Glenn Goddard, our Chief Financial Officer. Following our prepared remarks, we will be open for Q&A, for which Andrew Schiermeier, our Chief Operating Officer; and José Rivera, our 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 from the first quarter of 2020.

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

[John Leonard, Chief Executive Officer]

Thank you, Lina. Good morning, everyone. We certainly appreciate your joining our call today during these challenging times. First and foremost, I hope you and your families are all staying healthy and safe.

At Intellia, we continue to advance our full spectrum strategy applying genome editing in vivo and ex vivo to develop a diverse pipeline of novel medicines that address critical areas of unmet need.

As a reminder, our in vivo approach delivers CRISPR/Cas9 components as a therapy. With our systemic lipid nanoparticle or LNP based delivery system, we believe we have unlocked treatment of genetic diseases that originate in the liver. We've demonstrated we can selectively knock out disease-causing genes and also precisely insert genes to produce normal human proteins for therapeutic purposes. Further, our robust set of preclinical data supports our potential to cure genetic diseases with a single administration.

Ex-vivo we use CRISPR/Cas9 as a tool to create engineered cell based therapies. Here we are redefining lymphocyte engineering to overcome many of the limitations are currently available cell-based immunotherapies. Our approach focuses on the identification of a high affinity T cell receptor sourced directly from a healthy donor and then engineering T cells to only express the therapeutic TCR, which results in a homogeneous and robust cell product. This is based on our view that engineering lymphocytes to retain normal cell physiology is key to the success in targeting a variety of cancers.

So far in 2020, we've taken key steps in advancing our pipeline. In a matter of months we've gone from one development candidate to three. NTLA-2001 our lead candidate applies an in vivo liver knockout approach for the treatment of transthyretin amyloidosis or ATTR. This program continues to rapidly progress towards the clinic.

Further today, we are excited to announce the nomination of NTLA-2002 as a development candidate for the treatment of hereditary angioedema or HAE. We are particularly proud of the nomination of NTLA-2002 as it also employs an in vivo liver knockout approach, demonstrating how the modularity of our platform supports a rapid progression to a clinical candidate. And with respect to our ex vivo pipeline we're now in IND-enabling activities for NTLA-5001 our lead TCR T cell therapy for the treatment of acute myeloid leukemia or AML.

Before handing the call over to Laura, I'd like to take a moment to comment on the COVID-19 pandemic as it relates to our business operations and upcoming milestones. I want to start off by thanking the Intellia team for their focus and commitment to our mission and for their adaptability, which have enabled much of our work to continue during these unprecedented circumstances.

Like many of our colleagues across the industry, we mobilized quickly to adapt to public health recommendations to ensure the safety of our team. The majority of our team continues to work remotely with a limited number of essential personnel coming into our facilities to perform critical activities that can only be completed on site. Fortunately at this time, we remain on track to achieve our milestones as previously guided. We recognize the risk posed by COVID-19 and are closely monitoring the situation as it continues to evolve.

In particular with respect to the planned launch of our first clinical trial, we are in active discussions with global regulatory agencies about our ATTR program. We're also in close contact with investigational sites and leading physicians around the globe to ensure patient safety and smooth initiation of a planned clinical trial this year.

I'd like to now pass the call over to Laura who will provide additional details on our lead programs.

[Laura Sepp-Lorenzino, Chief Scientific Officer]

Thank you, John, and good morning everyone. I will start with our lead in vivo program NTLA-2001 new development for the treatment of ATTR, a progressive and fatal disease caused by the deposition and buildup of misfolded TTR protein in multiple organs. It can be either hereditary or nonhereditary known as wild-type ATTR and can result in diversity's manifestations most commonly polyneuropathy and cardiomyopathy.

NTLA-2001 applies our in vivo approach to knockout the TTR gene in the liver, which is a source of circulating TTR protein. Approved treatments for ATTR have both clinically validated the rationale for knocking down TTR and also increase disease awareness. Still we believe it is a highly under-diagnosed condition for which unmet needs remain. Moreover as our preclinical data has shown, we believe NTLA-2001 has the potential to hold disease progression with a single course of treatment offering a differentiated profile as compared to chronic therapies currently available.

We're pursuing a global development strategy for NTLA-2001 to support regulatory submissions in multiple geographic regions for the patient population and qualified investigators reside. Further, it has provided us flexibility to address the challenges created by the pandemic. As John noted earlier, we have been speaking with regulatory bodies around the world and are committed to pursuing the most efficient path to be in the clinical program this year. This quarter, we manufactured Phase 1 materials are finalizing regulatory documents and remain on track to submit our IND or IND-equivalent need this year.

As previously shared, the Phase 1 trial will be a single ascending dose study in TTR patients intended to assess safety of NTLA-2001. Given the readily observable serum biomarker, we will also be able to evaluate activity by monitoring the decrease in circulating TTR levels. We aim to release the finalized Phase I study design prior to study start expected in the second half of this year. While this remains subject to the impact of COVID-19 on regulators and clinical trial sites, we will continue to carefully monitor these conditions to ensure patient safety.

We are very excited about this program and our key opinion leader feedback indicates that there is a great deal of enthusiasm about a potentially curative treatment for ATTR. Of note, NTLA-2001 is anticipated to be the first systemically delivered CRISPR/Cas9 therapy to enter the clinic and is being developed as part of our collaboration with Regeneron with Intellia as the lead party.

Now moving on to our next in vivo program in development for the treatment of HAE. HAE is a rare genetic disease characterized by recurring, painful and unpredictable edema in various parts of the body. Most patients with HAE have a C1-esterase inhibitor deficiency resulting in unregulated release and buildup of bradykinin, which in turn mediates vascular permeability and painful swelling. The disease affects about one in 50,000 people and can be fatal in certain cases.

When there are acute and prophylactic therapies for HAE, the treatment burden of patients is still significant. With this program, we aim to knockout the KLKB1 gene to reduce plasma kallikrein activity to prevent excess bradykinin production resulting in HAE attacks. We believe KLKB1 knockouts these cells as humans with prekallikrein deficiency appear to have no non-health effects. In addition, innovation of kallikrein activity is a clinically validated approach towards treating HAE.

Today, we're pleased to share additional durability data showing plasma kallikrein protein and activity reduction sustained through six months following a single dose in an ongoing non-human primate study. We're encouraged by these results as they show that we can achieve levels of plasma kallikrein activity reductions expected to be clinically efficacious. Based on these results and other data, we're excited to nominate our third development candidate today NTLA-2002 for the treatment of HAE.

Our rapid and efficient path to selecting our HAE development candidate builds on the foundation developed for our ATTR program demonstrating the strength of our molder approach. We have recently begun IND enabling activities for NTLA-2002 and plan to submit an IND or IND-equivalent in the second half of 2021. We look forward to sharing additional data on HAE at the American Society of Gene and Cell Therapy Annual Meeting taking place virtually next week.

Switching now to our ex vivo efforts in immuno-oncology. At Intellia, we employ a TCR-based approach for adoptive T cell therapy. TCRs, unlike CAR-T, can target a much broader set of targets including both surface and intracellular tumor antigens.

As John mentioned, our focus is to engineer the lymphocytes that retain normal cell physiology. By identifying a high affinity natural DCR and applying our proprietary T cell engineering process more designed in a cell product that closely mimics the natural biology of T cells to attack tumor cells.

As shown at the Keystone Symposium in February, we applied this approach to identify NTLA-5001, our engineered T cell therapy development candidate for the treatment of AML. It targets the Wilms' Tumor 1 or WT1 antigen which is over-expressed in over 90% of AML patients regardless of driver mutations and disease subtypes.

At Keystone, we highlighted these attributes of NTLA-5001. First, it contains a naturally occurring TCR. This TCR is a modified, high affinity and a resourcefully healthy donor to minimize risk of immune toxicity. Second, the TCR binds to a novel WT1 epitope, efficiently processed by the tumor protostome and presented by AML blast.

Third, our proprietary engineering process achieved greater than 98% removal of endogenous TCRs from nearly all T cells to create a brand slate for the efficient insertion of the therapeutic TCR. This results in at T cell product with high TCR expression potency and specificity.

This represents a significant improvement over alternative TCR approaches where the native TCR is either partially removed or not removed at all creating a heterogeneous T cell product with not only reduced activity but also unpredictable specificity resulting from its paring alpha and beta chains of endogenous and therapeutic TCRs.

We look forward to presenting additional data next week at ASGCT's annual meetings on an important process advancement in our cell engineering platform. We will show highly efficient editing of multiple genes with levels of translocations indistinguishable from background level and favorable sold product attributes including high viability and expansion potential. Notably, we have incorporated this improved T cell engineering process into NTLA-5001.

In preparation for the clinic, we continued to advance IND-enabling activities including process development in support of clinical T cell manufacturing. We remain on track to submit an IND or IND-equivalent in the first half of next year.

Looking more broadly at the AML landscape while treatments developed over the past several years have led to improved response rates, long-term outcomes continue to be core.

Overall, five-year survival remains below 30%. Our hope is that NTLA-5001 will deliver a well-tolerated treatment that improves low term outcomes for AML patients, regardless of the limitation and background of their underlying leukemia.

Additionally, as we've noted in the past, WT1 is over-expressed across many tumor types as such we're actively evaluating the potential to use the same WT1 TCR in multiple solid tumors.

Outside of our wholly owned ex vivo efforts, the FDA has accepted Novartis' IND application for OTQ923 a CRISPR/Cas9 based engineered cell therapy brought out of our research collaboration in development for sickle cell disease.

We are pleased to share this important milestone as this will be the first ex vivo application of our technology to be evaluated in patients and we believe this program will provide important validation for our platform.

Finally, we continue to maintain a strong research engine, leveraging our modular platform to deliver the next wave of clinical candidates. These research programs apply our various genome editing and delivery capabilities across a variety of diseases, including hemophilia B, alpha-1 antitrypsin deficiency and others.

With that, I would like to now hand over the call to Glenn, who will provide an overview of our first quarter 2020 financial results.

[Glenn Goddard, Chief Financial Officer]

Thank you, Laura, and good morning. Intellia remains in a strong financial position as we advance our pipeline. Our cash, cash equivalents and marketable securities, as of March 31 2020, were $250.3 million compared to $284.5 million as of December 31 2019. The decrease was mainly due to cash used to fund operations of approximately $40 million which was offset in part by $4.5 million of net proceeds raised from the company's at the market offerings, $1 million of funding received under the Novartis collaboration and $0.3 million in proceeds from employee-based stock plans.

Our collaboration revenue was $12.9 million for the first quarter of 2020 compared to $10.4 million for the same period in 2019. The increase in collaboration revenue in 2020 was mainly driven by the $5 million milestone payment earned from Novartis for the IND submission of OTQ923.

Our R&D expenses were $34.7 million for the first quarter of 2020 compared to $23.7 million for the same period in 2019. This increase was mainly due to the advancements of our lead programs, research personnel growth to support these programs as well as our expansion of the development organization.

Our G&A expenses were $11.3 million for the first quarter compared to $10.5 million for the same period in 2019. This increase was mainly driven by an increase in intellectual property-related expenses due to increased patent activity. Finally, today we are reaffirming that we expect our current cash balance to fund our operating plan through at least the end of 2021.

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

[John Leonard, Chief Executive Officer]

Thanks Glenn and Laura for the updates. Before concluding the call, I'm excited to introduce Dr. David Lebwohl, as Intellia's new Chief Medical Officer. David recently joined us from Semma Therapeutics, where he was Chief Medical Officer. He served in roles of increasing drug development responsibility over a 16-year tenure at Novartis most recently as Senior Vice President and Global Head of the CAR-T team, where he developed and launched Kymriah and the multi indication cancer blockbuster Affinitor. He's one and a handful of R&D leaders who has successfully brought a novel entered cell therapy product through FDA approval and to patients. David's deep development expertise in rare diseases, oncology and engineered cell therapy are a huge asset and complement the scientific capability and talent we have amassed at Intellia. We're incredibly fortunate to welcome David to our team and to gain his medical and clinical development expertise particularly in interim cell therapies.

And of course, this comes at a critical juncture in the company's growth. We continue to make rapid progress across our emerging pipeline for severe genetic diseases and cancer as we prepare NTLA-2001 to enter the clinic with other programs poised to follow.

Looking ahead to the balance of 2020 and beyond, we have several important milestones upcoming. In summary, for NTLA-2001 we plan to submit our IND or IND-equivalent to the middle of this year and current conditions permitting plan to dose our first ATTR patient in the second half of the year. For NTLA-5001, we continue to advance IND-enabling activities and anticipate submitting an IND or IND-equivalent in the first half of next year. And for our newest development candidate NTLA-2002 we expect to submit an IND or IND-equivalent application in the second half of next year.

Additionally, we look forward to presenting preclinical data supporting certain programs and platform improvements at the ASGCT annual meeting next week. Again, I'd like to thank you all for tuning into the call today.

We will now open the line to any questions. Operator?

[Operator]

We will now begin the question-and-answer session. [Operator Instructions] The first question comes from Steve Seedhouse of Raymond James. Please go ahead.

[Timur Ivannikov, Raymond James]

This is Timur Ivannikov on for Steve Seedhouse. And our first question is maybe for José. In terms of the oral argument for the IPR that's scheduled on May 18, could you remind us about the potential set of outcomes for the hearing and then maybe the general timeline for this case in terms of the potential resolution?

[John Leonard, Chief Executive Officer]

José you want to take that?

[José Rivera, General Counsel]

Yes. Sure. Good morning. So the potential outcomes at this point obviously there's a motion by de broad seeking to essentially terminate the interference. If that were to happen and that the UC side would have it's current set of patents that cover single guide in any setting and then the board would have for now subject to appeals the eukaryotic patents. We believe obviously that likely our commission will move forward to the second phase. A decision on the motions is likely to occur within three months. That's usually the time line although, we can't guarantee how long. And then the second phase would happen after that. And that's where inventor ship would be decided.

[Timur Ivannikov, Raymond James]

Okay. Thank you. And then our second question about the ATTR program. I think, you mentioned potential delays due to COVID-19. Could you just provide any color in terms of the impact on the ATTR study? Is it more of an impact just on hospital and patient arrangement? It sounds like you have the supply ready to go. So any color would be appreciated. Thank you.

[John Leonard, Chief Executive Officer]

Yes. This is John. Just to be clear, we're not saying that we know there's a delay. In fact everything that we can control on our end is on time which is our guidance that we will have the regulatory applications in and we fully expect to be dosing patients before the end of the year where things get beyond our control and would be later this year, if we have other waves of COVID that interfere with individual clinical sites or the transit of patients to them. But we're very, very carefully engaging with the clinics to make sure that to the best of our ability we're able to avoid that kind of an eventuality.

[Timur Ivannikov, Raymond James]

Okay. Thank you very much.

[Operator]

The next question comes from Gena Wang of Barclays. Please go ahead.

[Unidentified Analyst]

Hi. This is Jin Tao for Gena Wang. I have two questions to start. My first question is for your ATTR program. It seems like that's going to be the first in vivo IND application for CRISPR/Cas9 technology. Do you expect actually extra scrutiny from the FDA? Would you share with us when the IND cleared -- when the IND would be cleared? And when you will file? And so since the pipeline is that there's several hold before. So that's my first question. Second question about your HAE program. What additional steps you need to take actually before your IND submission in the second quarter of 2021?

[John Leonard, Chief Executive Officer]

Yes. So thank you for the question. First for TTR. Extra scrutiny. I guess, I think, of it as applying the appropriate scrutiny which is the basis of how we approach the FDA in the various regulatory engagements that we have with them. As we start the regulatory process in particular with our pre-IND meetings part of this is to make sure that we have a shared understanding of the nature of the data that we need to present so we can go and generate that for them so that there will be an adequate package for them to determine that we're able to proceed. That's true for all regulatory agencies whether it's the FDA or agencies outside the U.S. So we think we're addressing their questions.

I would say that in most cases what one needs to generate largely overlaps what is true for other products as well. There's not a unique set of circumstances or data that one needs to generate for these sorts of products. So we think we're going to be in a position to address what they need to make a determination.

I think you asked when we would announce where we are with the program, our plan is to announce once we're up and running and we've cleared the regulatory process. And that's our plan for now. And certainly, we'll give good insight as to what the protocol is and how we're going to approach these patients.

With respect to HAE what are the additional steps? I mean, we just announced development candidates. We're moving very expeditiously and appropriately to the clinic. Again, this is generating the standard, sort of, regulatory information completing the necessary manufacturing and tox work. I think we've learned how to do that pretty effectively now with our first go at a TTR and we're hoping to leverage all the insights that we've gained not only from manufacturing, but from a toxicological work. And ultimately perhaps even from the clinical work that we're doing with TTR. So we're very excited about this application of our modular approach as we move forward.

[Unidentified Analyst]

That's great. So I have one quick follow-up. For the Novartis collaboration program in SCD could you remind us the modification you made?

[John Leonard, Chief Executive Officer]

Yes. So just to be clear this is Novartis' program. We'd like to think of it as Intellia inside. We've done the basic work on the discovery side on a collaborative basis with them. We've determined key elements for the data package that went to the FDA. But the particulars of how the gene is edited in the development program itself applies to Novartis so they're in the better position to describe that work and how they're progressing it.

[Unidentified Analyst]

Okay. Great. Thank you very much.

[Operator]

The next question comes from Maury Raycroft of Jefferies. Please go ahead.

[Maury Raycroft, Jefferies]

Hi. Good morning, and thanks for taking my questions. I'm not seeing a TTR title at ASGCT. So just wondering if you can provide the latest status update on NHPs treated with 2001. I think your last update was with follow-up up to 52 weeks. And so how long is follow-up today and our TTR reduction is still flat?

[John Leonard, Chief Executive Officer]

Yes. There's no additional data that we're presenting and essentially that's where we cut the experiment at this point. So that was the duration of the work.

[Maury Raycroft, Jefferies]

Got it. Okay. And then congrats on the 2002 update. I'm just wondering if you're seeing any phenotype in the NHPs that have been treated so far? And is there anything unique you're seeing relative to your treated TTR NHPs?

[John Leonard, Chief Executive Officer]

Maury we look very closely at these animals. Of course, these are exaggerated pharmacology studies, where one can try to determine any sort of readily observable effect. And to date we've seen nothing.

[Maurice Raycroft]

Great. Okay. And then last question. It sounds like at ASGCT we'll see some data on improved T cell engineering and Laura talked a little bit about the proprietary engineering process for 5001.

I guess how much of that will be disclosed at ASGCT? What should we focus on and then for the program, can you provide a few specifics around manufacturing such as the number of days it will take to process cells from start to finish?

[John Leonard, Chief Executive Officer]

Yes. So with respect to the editing this is work that we're very, very excited about. And what we'll show or the performance of those cells in terms of how well we edit them, how well the cells behave. And importantly, the ability of those cells to robustly divide. And in fact far exceed the division and multiplication expansion that typically takes place with cells that are edited in the standard fashion.

We think that that is hugely important for the ultimate performance of these cells but equally important and something I can't stress too much is the ability to serially edit and have a level of translocations that's essentially indistinguishable from background levels. And we think that that by itself is going to really enable our ability to have multiple edits in these cells.

But when you think about where one might want to go not just for the first product, which for the treatment of AML. But as we think about other indications and other modifications that we want to make, the ability to make a multiplicity of changes and not induce translocations is something that we think essentially puts very few limits on where we can go.

So very excited in terms of how we do it. Well that's work we've done and something that is proprietary. But I would say this there are multiple steps along the way that one can look at very carefully. And improve and we've tried to do that each step of the way. So you'll see the data and the performance of the cells and I think that will speak for itself.

[Maurice Raycroft]

Got it. Will we learn some of the process at ASGCT then? I guess will some of the proprietary information come out at that point?

[John Leonard, Chief Executive Officer]

No.

[Maurice Raycroft]

Okay. Thanks for taking my question.

[Operator]

The next question comes from Mani Foroohar of SVB Leerink. Please go ahead.

[Rick Bienkowski, SVB Leerink]

Good morning, everyone. This is Rick on the call for Mani. Congrats on all the progress. So first I also wanted to touch on the timing for the upcoming dosing of the first ATTR patient in the 2001 study. So we know that clinical trials have been slowed down across the board due to COVID-19 and it's mostly due to hospitals not being able to perform elective procedures. Could you comment, specifically for their clinical trial sites that are planned for the 2001? Study if these sites are currently performing elective procedures? Or if there are any time lines in place for restarting these?

[John Leonard, Chief Executive Officer]

Yes I can't speak to what sites are doing for their other programs. We focus on the work that we're going to do. With respect to the timing we've given guidance and continuing to provide that guidance that we expect to be dosing patients before the end of this year. I think, one point to take away is that programs have been most effective ones that are currently in the clinic today.

And in some respects where we are I think is somewhat advantageous being on the cusp of beginning clinical work. Where we can think very carefully about how to navigate this process, look at the logistical challenges that have been presented by the virus, look at how sites are dealing with it and not do it on the fly. But come prepared with whatever the circumstances are. So again, expect to be dosing patients before the end of the year and the particular clinics et cetera, is information that we'll provide down the road.

[Rick Bienkowski, SVB Leerink]

Great. That's very helpful. I do have a follow-up question for the HAE program. So we saw the ASGCT abstracts and the earlier Keystone presentations that you're able to achieve a 90% knockdown in plasma kallikrein in mice and nonhuman primates. So are there any internal models that would make a prediction for what kind of effect this would have on the HAE attack rate? I'm just trying to get a sense of what the target profile for the gene editing product would be compared to the current standard of care.

[John Leonard, Chief Executive Officer]

Yes. Thanks for the question. What we try to do is benchmark off of what's been done in human studies using other modalities. And so when you think about kallikrein and its inhibition, antibodies all the places that we look to. And attack zero I think it's a useful benchmark where one looks at degrees of inhibition and then the concomitant attack rate that results. So we expect to be competitive with those kinds of attack rates and perhaps more so. It's certainly our objective to provide a one-and-done approach that has zero order pharmacokinetics speeding invariant and that has attack rates that are -- we hope below those already achieved.

[Rick Bienkowski, SVB Leerink]

Great. Thank you. And we’re looking forward to SVB [ph] presentation.

[John Leonard, Chief Executive Officer]

Thank you.

[Operator]

The next question comes from Madhu Kumar from R.W. Baird. Please go ahead.

[Madhu Kumar, R.W. Baird]

Hey, guys. Thanks for taking our question. So kind of following on the kind of considerations of the clinical execution plan for 2001 in ATTR to what extent can the kind of management of patients in the clinical trial be done remotely can you do kind of blood collection from home? Do kind of safety and tolerability systems from home versus having them come on site?

[John Leonard, Chief Executive Officer]

Yes. Those are important questions Madhu and all parts of things that we're working through. Again back to the earlier question, we got in terms of being in a position to engineer some of these ways of following patients. We're taking that into consideration as we go. There's a lot that we think we can do. Obviously, in a Phase 1 study there is a point where patients are confined in the clinic. And so it's hard to do that virtually. But after that I think, there's lots of opportunities to go and follow those patients remotely. So we hope to engineer that in. And again, we're trying to learn from those that have gone before us.

[Madhu Kumar, R.W. Baird]

And kind of following from that thinking about the assessment strategy in the Phase 1 does COVID impact kind of your ability to look at endpoints beyond serum TTR level? So things like polyneuropathy endpoints or cardiomyopathy endpoints that are -- that would require like pretty extensive clinical visits or at least some kind of in-person clinical assessment.

[John Leonard, Chief Executive Officer]

It's not apparent to me how that would influence this. I mean, obviously, we don't want patients to become ill during the course of the study. So that was part of the discussion in terms of transit of patients to and from the clinic and making sure that patients when they come in are otherwise well.

But the biggest part of what we're looking for in our very first study is safety and the extent of TTR knockdown, which is an objective readout that we get with a simple blood draw after a few weeks of observation. So I think what we're looking for in Phase 1 should be readily observable despite what's going on out there.

[Madhu Kumar, R.W. Baird]

And then finally interesting about the Phase 1 trial is there any possibility of kind of subsequent dosing of patients at kind of earlier subtherapeutic doses to kind of get PCR down to the kind of target profile for TTR suppression you're looking for?

[John Leonard, Chief Executive Officer]

Yes. That's an important question. And it comes from the notion that this is a single ascending dose study where one starts lower in the therapeutic index and dose fines as we ascend. Obviously, the objective is to do that with the fewest number of patients the fewest number of dose escalations. About possible, but it is entirely possible that that first set of patients which we would expect to be small would have a subtherapeutic dose.

In the Phase 1 study itself they as at least it's currently planned they would not be subject to redosing, but in the course of a larger program once we find those therapeutic doses we would definitely try to make provisions for patients to come back. That's all work underway.

[Madhu Kumar, R.W. Baird]

Okay. Thanks very much. By the way that was really great. Intellia's side that's classic.

[John Leonard, Chief Executive Officer]

Thank you.

[Operator]

The next question comes from Tony Butler of ROTH Capital. Please go ahead.

[Tony Butler, ROTH Capital]

Yes good morning. John, I just want to follow-on on that series of questions with respect to the clinical outcome of TTR administration. And the question really is you had alluded to subtherapeutic doses obviously in the ascending dose study. Understand that. But as TTR as a surrogate diminishes in the serum how do you believe that that correlates with an improvement or potential improvement in peripheral neuropathy or hydrocephalus or whatever the case may be clinically?

And I'm making an assumption here and I'm asking you to -- I'm sure you've given this tremendous thought. But in the end from an FDA perspective would you not have to demonstrate some level of improvement in those particular clinical markers which I think will be very important beyond that surrogate?

And I guess follow-on to that is when you get to a certain level that has -- and at least in the Phase 1 which has an appropriate knockdown that you like. How are you actually able to gauge whether or not that that might be the appropriate dose to move forward because clinically you're not really sure that those particular neuropathies if you will be totally aggregated. Thank you.

[John Leonard, Chief Executive Officer]

So, Tony, thanks for the question. A couple of things wrapped up in that. So, first we look to those who have gone before us, who have demonstrated a tight link between TTR knockdown levels and therapeutic outcomes, particularly with respect to Polyneuropathy.

And here we certainly look to Alnylam and the outstanding work that they've done and Ionis where with two different modalities, that both lead to the same biochemical outcome which is a reduction in TTR, they both see clinical improvement. So, when you think about it from that standpoint, and just thinking about the pathophysiology of the disease which is in most cases, an aberrant protein that is deposited in tissue, I think the treatment logic is clear.

The idea is to reduce that protein. So, there's not a lot of discussion about that. Utility however, of TTR levels as a surrogate marker for a drug approval, as opposed to an indicator of what is a likely outcome is a different thing. The regulatory agencies have not yet moved to make those reductions, surrogate indicators that service the basis approval. So you have to do the clinical work. Excuse me.

So again the idea is to, find a dose. And as was asked earlier maybe even a second dose a second treatment or application if necessary. To get to those TTR levels that we already know are associated with good therapeutic outcomes, and to do that in a way that is highly competitive with what is already out there.

So that in a nutshell is, the logic that we apply to the program that would apply to polyneuropathy and also cardiomyopathy and it. I think here in this space, there's less complete information on the correlation of the extent of the improvement between TTR knockdown and the effect of cardiomyopathy but that's accumulating.

And again, we feel that we're well positioned, because we're being taught by people who are a little bit ahead of us, so that we can apply those learnings directly to our program. And design a clinical study that we think would be highly likely to succeed. And be very, very efficient.

[Tony Butler, ROTH Capital]

Thank you, John. I appreciate it.

[Operator]

And the last question today will come from Jay Olson of Oppenheimer. Please go ahead.

[Jay Olson, Oppenheimer]

All right, congrats on the progress. And thanks for taking my questions. Maybe just to follow-on, a little bit to Tony's question, as you look ahead to moving 2001 into the clinic can you comment on the potential value of NT-proBNP, as a biomarker for ATTR? And whether or not you could plan to measure NT-proBNP, as an endpoint?

[John Leonard, Chief Executive Officer]

I'm not in a position today to talk about that yet. Certainly, it does relate to the questions that Tony was asking me, in terms of the biochemical markers that we can measure. And projecting from them likely clinical benefit to cardiomyopathy where there's an emerging story, in terms of the relationship of actual knockdowns to outcomes.

I would start with the premise that we're going to measure everything we can, in the Phase I studies, to make sure that we have the most information possible. And then of course we would relate that to what the experts can guide us, in terms of its meaning in utility. And related to whatever others have found as they proceed with their various knockdown programs.

So, I wouldn't base it solely on that. Again, the basic logic here is about reducing a protein and I think that is going to be the first and foremost in our minds and that is directly measurable and that will be our primary guide.

[Jay Olson, Oppenheimer]

Great thank you. And then, maybe just on 2002, I think you said you had six months of data in HP. Is that sufficient for your IND? Or do you plan to submit 12 months of data?

[John Leonard, Chief Executive Officer]

So, this is a model that shows the extent of the effect. If you're asking, the toxicological work, that would be part of that program. That's distinct from the data that we presented so far. And your question relates to, how much we're going to be able to build off of prior work that we've done from a toxicological basis. And that is a point of some discussion as we proceed. So, stay tuned.

[Jay Olson, Oppenheimer]

Great thanks so much for taking my question, looking ahead to ASGCT. And stay healthy.

[John Leonard, Chief Executive Officer]

Thank you and you too.

[Operator]

This concludes our question-and-answer session. I would like to turn the conference back over to, Lina Li, for any closing remarks.

[Lina Li, Associate Director of Investor Relations]

Great, thanks Andrew. Thank you all for joining today's call and for your continued interest and support. We look forward to updating you on our progress. Hope everyone has a nice day.

[Operator]

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.