Intellia Therapeutics Inc

NASDAQ:NTLA

Earnings Call Transcript 2023-Q2

[Operator]

Good morning and welcome to the Intellia Therapeutics' Second Quarter 2023 Earnings Conference Call. My name is Drew and I will be your conference operator today. Following formal remarks, we will open the call up for a question-and-answer session. This conference is being recorded at the Company's request and will be available on the Company's website following the end of the call. As a reminder, all participants are currently in a listen-only mode. [Operator Instructions]. I will now turn the conference over to Ian Karp, Senior Vice President of Investor Relations and Corporate Communications at Intellia. Please proceed.

[Ian Karp, SVP, IR and Corporate Communications]

Thank you, operator and good morning, everyone. Welcome to Intellia Therapeutics second quarter 2023 earnings call. Earlier this morning, Intellia issued a press release outlining the Company's progress this quarter, as well as topics for discussion on today's call. This release can be found on the Investors & Media section of Intellia's website at intelliatx.com. This call is being broadcast live and a replay will be archived on the Company's website.

At this time, I would like to take a minute to remind listeners that during this call, Intellia management 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 from Intellia are Dr. John Leonard, Chief Executive Officer; Dr. David Lebwohl, Chief Medical Officer; and Dr. Laura Sepp-Lorenzino, Chief Scientific Officer; and Glenn Goddard, Chief Financial Officer. John will begin with an overview of recent business highlights. David will provide an update on our clinical programs, Laura will review our R&D progress, and Glenn will review Intellia’s financial results for the second quarter 2023 before we open up the call for your Q&A. With that, I'll now turn the call over to John.

[John Leonard, President and CEO]

Thank you, Ian and thank you all for joining us this morning. At Intellia we are leading the genome-editing revolution with the broadest and deepest toolbox of novel editing and delivery solutions. 2023 continues to be another year of important progress across our clinical pipeline and differentiate genome-editing platform. We're particularly pleased with a significant advancement of our two lead clinical programs. Not only are these two programs potentially paradigm shifting treatments for patients with ATTR amyloidosis matrix E [ph] for a success from learning from these investigational therapies will help set the foundation for our broader long term goals and strategic priorities.

Starting with NTLA-2002 in development for the treatment of hereditary angioedema today we announced that in just a handful of months, we were able to identify all patients required to fully enroll the ongoing Phase 2 portion of the study. Notably, we now expect to initiate the Phase 3 program as early as the third quarter of next year, subject to regulatory feedback. In addition to the exceptional clinical development, execution, and recent positive data update for NTLA-2002 we're getting very close to submitting our second in vivo IND application. This next IND submission expected in September, will support the planned pivotal trials of NTLA-2001 for people with a cardiomyopathy manifestation of ATTR amyloidosis. Some estimates indicates there may be as many as 500,000 people around the world who suffer from this disease. Subject to regulatory feedback, we expect to initiate the global Phase 3 by year end.

We believe all this progress positions us well to deliver on initiating pivotal studies for both programs, a core strategic priority over this year and next. Lastly, I'd like to take this opportunity to thank Jean-François Formela one of our founding Board Members who retired from our Board in June. Jean’s vision and leadership over the past decade have been integral to our growth and recent achievements. I'll now hand the call over to our Chief Medical Officer, David Lebwohl, who will review the lead clinical programs in greater detail. David

[David Lebwohl, EVP and CMO]

Thanks, John. And welcome everyone. I'll begin with 2001, our in vivo CRISPR base candidate with the potential to halt and reverse disease in people living with ATTR amyloidosis after a single dose. For ATTR-CM, consistent with our prior guidance for a mid-year submission, we are on track to submit an IND application in September for a global pivotal study of 2001. We are in the final stages of preparing the comprehensive IND package and expect to initiate the study by year end, subject to regulatory feedback. For hereditary ATTR-PN, we are continuing to make steady progress with the preparations for a Phase 3 study. Looking ahead, we plan to present additional data from both arms of the ongoing study later this year.

Moving to 2002 in development for HAE. We have been really pleased with the interest and enthusiasm for the 2002 program from investigators and patients alike, both in the U.S. and internationally. The updated Phase 1 data presented in June has fueled this enthusiasm even further. Across all temptations, a 95% mean reduction in monthly attack rate was observed after a single dose of 2002 through the latest follow-up. The medium duration of follow up was nine months and at all three dose levels, 2002 has been well tolerated and any adverse events were grade one or two in severity.

Earlier this morning, we announced that we have identified all patients needed to complete enrollment in the Phase 2 portion of the study. Based on the high level of interest for 2002, all slots have been allocated to current ex-U.S. sites. Other sites plan for Phase 2, including U.S. sites will now be part of the planned Phase 3 study. Following the clearance of our IND, received requests from the FDA to provide supplemental preclinical data related to the inclusion of female patients of childbearing potential. While we could have proceeded with enrolling U.S. patients outside of this subgroup through the protocol amendment, the study was already rapidly enrolling at ex-U.S. sites and soon to finish. After discussion with the FDA, we have come to an agreement on the design of a reproductive study in mice to supplement the data that we have already supplied in our initial IND submission. Such data are often required as part of a registration or program and will now be submitted along with additional data being generated in advance initiation of the Phase 3 study.

The main objective of the Phase 2 is to confirm the optimal dose for Phase 3. By enrolling a diverse patient population ex-U.S., including women of childbearing potential, we are in a great position to move forward to do just that. Further, we announced today that we now expect to begin the Phase 3 study as early as the third quarter of 2024, subject to regulatory feedback. We are full steam ahead and look forward to updating you on our progress for initiating the 2002 global pivotal study. I'll now hand the call over to Laura, our Chief Scientific Officer who will provide updates on our R&D efforts.

[Laura Sepp-Lorenzino, EVP and CSO]

Thank you, David. Beyond our lead programs we are advancing a pipeline of in vivo and ex vivo programs towards the clinic. For NTLA 3001, our first wholly owned in vivo insertion program, we continue to conduct IND enabling activities and plan to submit a CTA by year end. We're excited to be moving this program into the clinic for a number of reasons. First, there are few effective therapeutic options for patients suffering from alpha-1 antitrypsin deficiency, a frequently debilitating and fatal disease. Based on our preclinical work, we believe in NTLA-3001 can normalize alpha-1 levels for patients following a single dose. Additionally, NTLA-3001 will be Intellia’s first gene insertion program to enter the clinic. If successful, we believe we can apply this modular approach to a host of diseases caused by a missing functional protein where there is high unmet need. We look forward to updating you on our progress across our R&D platform more broadly as we move through the second half of the year. And I'll hand over the call to Glenn, our Chief Financial Officer who will provide an overview of our second quarter 2023 financial results.

[Glenn Goddard, EVP and CFO]

Thank you, Laura. Good morning everyone. Intellia continues to maintain a strong balance sheet that allows us to execute on our pipeline and platform. Our cash, cash equivalents, and marketable securities were $1.1 billion as of June 30, 2023 compared to $1.3 billion as of December 31, 2022. The decrease was driven by cash use to fund operations of approximately $227.3 million. The decrease was offset in part by $24.6 million of interest income, $8 million of collaborator reimbursements, $3.3 million in proceeds from employee based stock plans, and $1.5 million of net equity proceeds from the company's at the market program. Our collaboration revenue decreased by $0.4 million to $13.6 million during the second quarter of 2023 compared to $14 million during the second quarter of 2022.

R&D expenses increased by $25.1 million to $115.3 million during the second quarter of 2023 compared to $90.2 million during the second quarter of 2022. The increase was mainly driven by the advancement of our lead programs and personnel growth to support these programs. Stock based compensation included in R&D expenses was $22.4 million for the second quarter of 2023. G&A expenses increased by $8.5 million to $30.7 million during the second quarter of 2023 compared to $22.1 million during the second quarter of 2022. This increase was primarily related to an increase in stock based compensation of $5.1 million. Stock based compensation included in G&A expenses was $14 million for the second quarter of 2023.

Finally, we expect our cash balance to fund our operating plans beyond the next 24 months. It's certainly been a very productive first half of the year. We have a number of additional milestones still to come in the months ahead. With that we will now open the call for your questions. Operator, you may now open the call for Q&A.

[Operator]

[Operator Instructions]. The first question comes from Maury Raycroft with Jefferies. Please go ahead.

[Maury Raycroft, Jefferies]

Hi, good morning. Congrats on the progress and thanks for taking my question. When you get the 2001 pivotal IND cleared after filing the IND in September, can you clarify if you will disclose details of the trial design and is base case that the trial size and duration will be similar to Alnylam’s HELIOS-B or based on the trial results recently do you have more confidence you can run a smaller study compared to HELIOS-B?

[John Leonard, President and CEO]

Thanks Maury for the question, good morning to you and all the listeners. As we've done in the past, when we get to a state of some finality with the protocols, we share the details and we would expect to do the same here. With respect to the particulars of the study, maybe David you could tell us whether or not the Bridge Bio or Jonas [ph] approach is more or less in focus for us.

[David Lebwohl, EVP and CMO]

Yeah, thanks. So there's a Bridge Bio resolve which is obviously very encouraging to us that after their first result, people were concerned that this area was hard to improve. The patient's status, they were too healthy, it's clearly not true from what we see in their overall results. We do need to see the details of what they have and that will be coming up. Those details are going to be very helpful to us in the design of our trial. We'll know more about event rates, we'll know a bit more about the status of patients. And the drug itself, the Bridge Bio compound is obviously very similar to [indiscernible], it works by a different mechanism and we do think that these are likely not as good as reducing TTR, imagine that we have been able to get to very low levels of TTR. So chemists, so we use all the information coming from this as well as later studies to size the trial. But we do think it'll be about the size that are pretty similar to Alnylam trial to HELIOS.

[Operator]

The next question comes from Luca Issi with RBC Capital. Please go ahead.

[Unidentified Analyst, RBC Capital]

Hi, this is Reena on for Luca, thanks for taking my question. Just wanted to ask, could you remind us what the latest thinking is on gene-editing outside the liver, if I recall, I think you showed us some tantalizing data last year for in vivo editing of CD34 hematopoietic stem cells, so wondering if you had any update there?

[John Leonard, President and CEO]

Generally speaking, I can tell you that we continue to work very, very hard on moving in vivo editing outside the liver. You're right, we've presented some really encouraging data, particularly with respect to hematopoietic stem cells thinking down the road, in terms of things like sickle cell disease, etc. where the preferred approach would be not to do a transplant, but to actually use an LMP in vivo editing approach to avoid the morbidity that typically accompanies a bone marrow transplant. We continue to do that work. I will say that we are pursuing a variety of different modalities that target even beyond HSCs and has been typical for us in the past as we think that we have a body of work that is ready to be presented scientifically, we will share that. But rest assured there's more to come.

[Operator]

The next question comes from Joseph Thome with TD Cowen. Please go ahead.

[Joseph Thome, TD Cowen]

Hi there. Good morning. And thank you for taking my question. Maybe just one on the additional data for the women and childbearing age. I guess, was there anything that spurred this asked by the FDA, and then as you think about applicability to your other programs, obviously TTR-CM is more predominantly a male disorder and in older patients, I guess, is there any implications for this for the upcoming IND submission? Thank you.

[John Leonard, President and CEO]

There's no safety data that's provoked this particular request of extensive work that we supplied in the IND which includes very large breeding studies and careful analysis of that data. We've looked at germline cells specifically. We know that they're unaffected. Our view is that this is the FDA taking very considered view of the space and looking for us to fill out what is a typical set of data that usually is supplied a little later in the program. But from the standpoint of the study itself, this is something that is commonly done. No clinical data, etc., has appeared that speaks to this at all. And we're well on our way to completing the work and supplying it to the FDA so we can get on with the study, as we have said.

I guess I'm sorry, before I forget you asked about implications with respect to 2001. At this point, we don't see that and certainly your point of you look at the demography of that disease, it's typically a set of patients that are older, bias to men in general. And so we just don't see it playing out in any really fundamental way with respect to the program.

[Joseph Thome, TD Cowen]

Okay, thank you.

[Operator]

And the next question comes from Greg Harrison with Bank of America. Please go ahead.

[Mary Kate, Bank of America]

Hey, good morning, this is Mary Kate on for Greg. Thank you so much for taking our questions. It's great to hear the interest from HAE program. I guess, looking at your other programs, what feedback have you received from physicians and patients in the ATTR programs ongoing?

[John Leonard, President and CEO]

Maybe David, you can speak to your interactions that are becoming pretty extensive at this point, what are you learning.

[David Lebwohl, EVP and CMO]

Yeah, thanks. The biggest group that we hear from of course, is investigators who were in touch with around the world. I would say we've talked with every investigator who treats patients at the leading centers with this disease. And there is a lot of excitement. We do know most of those sites or maybe all of those sites will end up joining the study. And as you've seen in some of the other studies, these studies do enroll quite briskly. And there really is an increasing population of patients with ATTR amyloidosis and cardiomyopathy. We also hear about patients through some of these physician’s excitement that is there, we actually are starting to hear directly from patients, people trying to get into studies. And of course, we want to satisfy that need if possible. So, as you know, we're working to get to the Phase 3 study opened as quickly as possible and estimated to be at the end of this year.

[Operator]

The next question comes from Joon Lee with Truist Securities. Please go ahead.

[Unidentified Analyst, RBC Capital]

Hi, good morning. And thanks for taking our question. This is Mavey [ph] on for Joon. So earlier this year, [indiscernible] of Phase 2 study achieved very high 90% reduction in ZAAT. But the impact on liver fibrosis improvements still unclear. And Takeda is doing Phase 3 study with 160 patients. So could you please elaborate on your plans and expectations for NTLA 2003? Thanks.

[John Leonard, President and CEO]

David, any thoughts on terms of how other data is affecting our thinking for 2003?

[David Lebwohl, EVP and CMO]

We've been encouraged by the data that we're seeing coming from the Takeda studies. And we do think it's -- obviously it's not a Phase 3, a definitive study, but it's very supportive of the benefit of reducing the mutant protein and the benefit for the liver. So we are for that program completing our IND enabling studies this year. And we'll be talking soon about when that will be getting into the clinic.

[Unidentified Analyst, RBC Capital]

Thanks.

[Operator]

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

[Unidentified Analyst, RBC Capital]

Hi, good morning. This is Harshita on for Gena, thank you for taking our questions. Just a quick clarification. I think you've covered this in the prepared remarks but just wanted to confirm, is that right for 2002 you've identified all the patients in Phase 2 and all of the patients in this study will be enrolled ex-U.S. and you will be waiting till the Phase 3 to enroll U.S. patients, can you clarify again, what's the reason for this and why you're waiting to enroll U.S. patients in Phase 3 and not in Phase 2 right now? Thank you.

[John Leonard, President and CEO]

Thank you, you're correct, that the study is fully enrolled. We've identified all the patients as we've said. The study has been moving extremely quickly as you can see. I mean, we began enrolling patients just in March of this year and here we are at the very beginning of August, and we've identified all of the patients and then some to come into the trial. So this is one of those things that's moved very, very aggressively and we're excited about that and what that means, by the way, that same enthusiasm is reflected with U.S. investigators and patients who contact us. The reason for that particular choice was with the feedback from the FDA after the successful clearance of the IND to complete the work that we would have needed to do to allow women of childbearing potential in the U.S. Remember, we're enrolling women of childbearing potential in every site, every country outside the U.S., we would have delayed the study substantially. And given that the objective of the program is to capture the demographics, which we're doing, range of different disease states, range of ages, women of childbearing potential and not, and men, etc., we were accomplishing that, especially with the primary goal of identifying the dose to take into Phase 3.

So rather than delay, the idea was to complete the work, submit that to the FDA, and bring U.S. patients into the study in Phase 3. By the way, there are many U.S. sites who have wanted to participate and given again, the repeatidity of the enrollment, they weren't able to come online fast enough anyway. So we think we're going to be very well situated in the U.S. We will have an abundance of U.S. patients and I think we'll be well prepared to begin the Phase 3 program, potentially as early as the third quarter of next year. And that's what we're working towards.

[Operator]

The next question comes from Debjit Chattopadhyay with Guggenheim Partners. Please go ahead.

[Debjit Chattopadhyay, Guggenheim Partners]

Hey, good morning and thanks for taking the question. Let's do 2001. Do you think a mid-90% TTR knockdown under very tight control that you have over the TTR, will that translate into survival advantage and could you remind us where you stand with respect to manufacturing, as you prep for two Phase 3 studies over the next 12 months? Thanks.

[John Leonard, President and CEO]

Well, I'll have David address why we're excited about, as you pointed out the very, very deep reductions and critically for the study. The very low variance that we see across all the patients treated so far, we're quite convinced that that's going to be a meaningful advantage for patients. But with respect to Phase 3 readiness, we put a lot of work into preparing for that IND that will enable that Phase 3 program. And your point about having commercial material readiness as one carries out these Phase 3 trials is a really important observation. So the idea is to complete this trial, get the results that we're looking for, have the final material in the study, and be in a position that when we achieve approval for the product to move forward as quickly as possible to the marketplace. And we've always been shooting ahead of the duck so to speak and this is very much a part of how we've been thinking about it. David, if you have something to add with respect to TTR levels and how that translates into clinical benefit.

[David Lebwohl, EVP and CMO]

We do believe that these deep reductions we're getting not only being at the 90% and greater range, but also having the great consistency means that we can -- we have the potential benefit of all patients. There aren't patients who are having lesser amounts, when you have an average of 80% with other agents, half the patients have less than 80% reduction. So that's very important. The other thing we're learning in terms of survival advantage, I think, is what we've seen in the Bridge Bio study. We've talked a lot about how we don't think the six-minute walk is a great test. And in fact, their study failed on that test. What we're seeing is that you do need a longer period to see the benefit of these agents. And we do think by having a large study with long follow up, we will come out positive on the most important endpoints that will include cardiovascular events and mortality. That's what we're looking forward to in our Phase 3 study.

[Operator]

The next question comes from Yanan Zhu with Wells Fargo Securities. Please go ahead.

[Yanan Zhu, Wells Fargo Securities]

Thanks for the questions. What would be the timeline for completing the supplemental free clinical data that the U.S. FDA has agreed upon about the design [ph] and do you think -- do you plan to collect certain data from the female patients of childbearing age in the upcoming Phase 2 study, and if so, what might those data points be? Thanks.

[John Leonard, President and CEO]

Well, the particular studies that we're doing are in abbreviated form of what are typical studies that look at embryological development that will be done well in advance of what would be the earliest Phase 3 study start for us, which I said earlier, it could be as early as three quarter. With respect to precise month and all that, it's just not going to have an effect in terms of how the program proceeds. So I think we're well on our way. David, anything different that we're doing for collecting patient data in women.

[David Lebwohl, EVP and CMO]

They get the same complete data collection that other patients get. Of course we'll look at all patients, we look at studies by gender and other things to see if there's any difference in the effects. We don't expect to see any difference between males and females or older or younger women. Of course, another part of follow up in these studies is looking at pregnancies that may occur after the study. We know we have a number of those patients who are specifically getting on the trial so that they can move on to have successful pregnancies. Of course, we look forward to bringing that great result forward in the future, if we can.

[John Leonard, President and CEO]

And just a reminder to the audience here that in the preclinical work, there's been zero evidence that there's any germline involvement in any way.

[David Lebwohl, EVP and CMO]

One other point there that is important to talk about before, the [indiscernible] gene is not needed at all for normal life span. So that -- or development or fetal development. So we know very well from humans that this gene is not essential for embryo development.

[Yanan Zhu, Wells Fargo Securities]

Got it, very helpful. Thank you.

[Operator]

The next question comes from Dae Gon Ha with Stifel. Please go ahead.

[Dae Gon Ha, Stifel]

Hey, good morning, guys. Thanks for taking the question. Just staying with this preclinical idea, I guess one of your peers in the Boston area also provided a pretty substantial data from animals, I believe it was NHPs as well as mice. Looking at pretty robust set of data demonstrating the germ line, but still got a clinical hold. So any additional color you can provide in terms of the size and breadth of this experiment that you think will be sufficient, has the FDA clearly outlined exactly how many sample size that they want to see before they kind of confirm that it is substantial or kind of related to that, have they expressed any N from the Phase 2 that might substantially get their questions answered? Thanks so much.

[John Leonard, President and CEO]

Yeah, I would draw a distinction between what I've seen reported in terms of breeding studies and litters, etc. That is not what this is. That question has been addressed with information that was supplied with the already cleared IND. So as far as we can tell, in our dealings with the FDA and every other regulatory agency, that particular germline question has been put to rest with the data that we have supplied. This particular study asks a different question, which is, does the embryological development of a fetus in mice be affected potentially in any way by having been exposed to call it the chemicals even that are part of an LNP. This is something that is typically done with many agents. The distinction in this case is that this has been done a little earlier than would typically be the case, which as we said at the outset, I think, is just FDA taking very considered view. We do have agreement with the study. It's, as I said, a modified or I'm sorry, an abbreviated study, which is quite readily addressed, and something that we're well on our way to completing. So, standard stuff and we look forward to sharing that information with the FDA.

[Dae Gon Ha, Stifel]

Great, thanks so much.

[Operator]

The next question comes from Myles Minter with William Blair. Please go ahead.

[Myles Minter, William Blair]

Hi, thanks for taking our question. Just another one on the preclinical studies. Since the platform approach is similar between several of your programs, just using a different guide, does this particular reproductive study need to be generated per product or do you believe just once for the platform and that should sort of cover several programs?

[John Leonard, President and CEO]

Well, well, I can't speak for what the FDA will ultimately require. It is generally applicable as you point out, it's the LNP itself that determines where the material goes. We've characterized that extensively, as we said, we've done the breeding studies, and we would expect the results to be no different with any other guide. So I do think in many respects, this should be a platform answer, whether or not the FDA will immediately see it that way remains to be seen. But our senses, that's how we think about it and they may ultimately as well.

[Operator]

The next question comes from Brian Cheng with J.P. Morgan. Please go ahead.

[Sung Yoon, J.P. Morgan]

Hi, this Sung Yoon, I'm working with Brian Cheng. Thank you for taking our questions. What's the latest for ATTR polyneuropathy and when do you think you will be able to give a bit more granularity on the timeline for pivotal study in polyneuropathy? And what are some of the gating factors if any, thank you?

[John Leonard, President and CEO]

David, you want to address that.

[David Lebwohl, EVP and CMO]

Yeah, what we've been saying and have said is that we are preparing the design of the pivotal studies. This is obviously we now have a lot of information from patients followed more than two years. We'll be talking more about that data later this year. And so that's where it is at this point, we're not guiding exactly to when that trial will start yet. In terms of gating factors, so this is -- what will be great going into this next study of course, is all the CMC issues will all be resolved. We know a lot about safety in both patients who polyneuropathy and cardiomyopathy. So there are very few gating factors other than getting regulatory agreement on the trial design.

[John Leonard, President and CEO]

And that's the primary thing we're looking for the regulatory feedback at this point.

[David Lebwohl, EVP and CMO]

Yes.

[Sung Yoon, J.P. Morgan]

Thank you.

[Operator]

The next question comes from William Pickering with Bernstein. Please go ahead.

[William Pickering, Bernstein]

Hi, good morning. Thank you for the question. As you think about the CM trial design, and the time that it will take to show an outcomes benefit, are there other endpoints that you might be able to update investors on as the trial progresses and use these to point towards the differentiated clinical profile even before we see the outcomes data? And very quickly, could you share what sorts of clinical endpoints you were thinking of sharing towards the end of this year? Thank you.

[John Leonard, President and CEO]

David.

[David Lebwohl, EVP and CMO]

What could we share during a blinded pivotal trial, unfortunately, I think as you probably recognize, you can't share anything from a blinded trial because we don't say anything about the data by arm. So we'll have patients who are on the drug and patients who are off the drug. However, we should say we expect to have other studies that will go at the value of the deep reductions in TTR, generally call these mechanistic studies or that type of study, and we will bring that data forward as soon as we can. We do recognize from the Phase 3s that are going on, these results do take a while to mature. This is the changes don't happen very quickly. But as you've seen in everything we've done, we bring forward data when we have meaningful, interpretable, and consistent results that we can show you what the story is. So we will wait for that as we -- whenever we bring up the data.

[Operator]

The next question comes from Rick Bienkowski with Cantor Fitzgerald. Please go ahead.

[Rick Bienkowski, Cantor Fitzgerald]

Hi, good morning. Congrats on the progress. And just a quick question for me. Last quarter, it was noted that the re-dosing of patients from the low dose polyneuropathy arm of 2001 has started. I'm curious if we could expect to see any of these data from the re-dosing cohort in the end of your update and what type of data could potentially be shared from these patients?

[John Leonard, President and CEO]

David, do you want to comment on re-dosing?

[David Lebwohl, EVP and CMO]

Yeah, okay, I mean, what we know all three patients have been dosed at this point. It's gone well. No, we haven't -- I don't think we've decided whether to put that into the next update or future update but we will. We'll talk about it as soon as we can.

[Rick Bienkowski, Cantor Fitzgerald]

Got it. Thank you.

[Operator]

The next question comes from Jay Olson with Oppenheimer. Please go ahead.

[Jay Olson, Oppenheimer]

Hey, congrats on all the progress and thanks for taking the question. Can you talk about the rationale and the strategy behind pursuing a CTA for a 3001 this year, but not an IND and what are the gating factors and timeline to filing an IND? Thank you.

[John Leonard, President and CEO]

David, you want to speak to that?

[David Lebwohl, EVP and CMO]

Yeah. As we've done in the past, I think what you are seeing is we look at several things in the first country that we go to. We look at the sites that are available, the investigative sites, that's very key to us getting high quality sites. We look at the regulatory environment. And all those are pieces of what we put together. And in this case, we did decide as we have in several of the other compounds that that going with the CTA is the best choice. Gating factors for an IND are similar to what we've had for other INDs. Of course, you need the pieces of CMC picture which is a big piece of our applications, and then of course getting agreement on trial designs. So all those things are possible for later submission as an IND.

[Jay Olson, Oppenheimer]

Great, thank you very much.

[Operator]

The next question comes from Silvan Tuerkcan with JMP Securities. Please go ahead.

[Silvan Tuerkcan, JMP Securities]

Hi, good morning and thanks for taking my question. I just have a more general question with the CRISPR SSL [ph] potential approval coming up in the U.S. by the end of the year and then potential subsequent reimbursement, is there anything from those models that we can learn that will be applicable to, for example, your HCR programs or is that too far off at this point? Thank you.

[John Leonard, President and CEO]

Well, obviously, we watch those spaces very, very carefully. I don't think that the world has converged on a final model for drugs like this that are potentially curative. But I see emerging trends, and there's going to be some really interesting, I think, examples that, of course, we will study very, very carefully. Our view right now is to have the best possible drug that moves the efficacy bar substantially forward and captures savings for the healthcare system, etc. And I think that that will be the basis for whatever pricing model we ultimately come up with. But we're confident that the health advantages and the efficacy that we expect to deliver will be of value to payers and whether it's in the U.S. or ex-U.S.

[Silvan Tuerkcan, JMP Securities]

Thank you.

[Operator]

The next question comes from Steve Seedhouse with Raymond James. Please go ahead.

[Unidentified Analyst, RBC Capital]

Hi, good morning. This is Nick on for Steve, couple questions on AATD, so are both knock-in and knockout products intended to target patients with the homozygous V genotype?

[John Leonard, President and CEO]

David, you want to address that.

[David Lebwohl, EVP and CMO]

Yeah, that's really where the need is for the patients who are homozygous V. In terms of the knockout, this is patients where the predominant issue is liver disease. That's the main thing that the knockout addresses, it doesn't address the lung disease, and there are a substantial group maybe well, I guess it's certainly 15% overall of the patients who tend to have liver disease, and that includes patients -- some patients with lung disease. The big majority of patients are the patients who need, the deficiency is affecting the lungs. And that is what the knock in is going to help with by putting in the wild type gene. Many patients will end up getting both because as they start to live longer, the liver disease may become more important. The liver disease can be subtle in some patients, and a lot of the physicians feel that they would want to give their patients both agents over time and both these agents be given should say in either order. One can be given before the other. Either one could be given before the other so that we have a lot of flexibility in how we treat patients.

[John Leonard, President and CEO]

It might be important for listeners to remember that these are independent programs that can be brought together, but we're pursuing them as independent developers.

[David Lebwohl, EVP and CMO]

Yes, these are two separate drugs that are going to be fully developed with all the requirements that you have for each drugs. It's not a combination program per se.

[Unidentified Analyst, RBC Capital]

Okay, got it. Thank you. And then so from your preclinical work do you suspect the same level of neutrophil elastase inhibition with the AATD protein induced by 3001, compared to wild type MAAT protein?

[John Leonard, President and CEO]

What we've presented in non-human primate work is this approach was able to reproduce levels seen in non-human primates that were essentially in distinguishable from normal human levels of circulating alpha 1. So our target is to accomplish just that in patients and the preclinical model suggests that we may well be able to do that. Laura, is there anything you want to add to how we're thinking about alpha 1?

[Laura Sepp-Lorenzino, EVP and CSO]

Yeah, no. So you need to ensure that not only you have protein levels, but those proteins are at the frame that the TBT is what you need to have. As John just described, that's what we accomplish in the non-human primate. And the expectation is that that's going to translate to humans.

[Unidentified Analyst, RBC Capital]

Got it. Thank you.

[Operator]

The next question comes from Salveen Richter with Goldman Sachs. Please go ahead.

[Unidentified Analyst, RBC Capital]

Hi, this is Shanelle Tron [ph] for Salveen. Thank you for taking our question. So a couple of questions, the first on NTLA-2002. In your data updated EACI, you mentioned that patients were allowed to withdraw from HAE prophylaxis and they've not experienced subsequent attacks. Any further updates on these patients as in have they remained attack free to date? And on your 2001 program could you provide some color on your -- on the regulatory discussions with the FDA, on CM and PN have they spoken about what they would like to see in the pivotal study? Thank you.

[John Leonard, President and CEO]

David, maybe you could remind us more about the data we presented on 2002 and I'm sure we'll be having updates as time goes on.

[David Lebwohl, EVP and CMO]

Yeah, so I think you recall, we did give updated data fairly recently on 2002. Recall all the patients who had received prophylaxis were able to withdraw it. And none of those patients have had a subsequent attack in that report. I should mention that no, we didn't use [indiscernible] as one of the withdrawals because it would affect our biomarker measures. However, what we're seeing in the Phase 2 is we did allow a minute amount of withdrawal and that is we have a number of patients will be treated after that withdrawal. So stay tuned. More data is coming for that as well. When we talk to regulators about the Phase 3, the IND is and we've had preliminary discussions. But of course to get agreement that involves the IND submission that we're doing in September for the FDA, we've also had extensive discussions with regulators outside the U.S. We feel very good that our trial design will address the questions that they will have. For PN, we are a little earlier. We did push first on CM as a much larger medical need, more patients needing this. But also with PN as we will bring you forward more details as we get agreement to the pivotal trial design.

[Operator]

The next question comes from Richard Law with Credit Suisse. Please go ahead.

[Richard Law, Credit Suisse]

Hey guys, good morning. Can you discuss the market opportunity for HAE outside the U.S. based on the reimbursement and usage rates for branded products so far? And what are the learning for 2002 as you think about ex-U.S. market that you will need to include in your studies?

[John Leonard, President and CEO]

The bulk of the HAE market today resides inside the United States. We're well aware of that. We do have an eye to what we can deliver outside the United States. What we've seen through the course of our Phase 1 and Phase 2 work is that there's a great desire to have these products and we will do our very best to show that not only because the product -- does the product work very, very well but that it can be resource sparing to those typically centralized systems. So to the extent that that market opportunity exists, we want to participate in it to the greatest extent possible.

[Richard Law, Credit Suisse]

Can you compare and contrast the reimbursement for U.S. versus ex-U.S., just curious to see how the different markets would affect the product?

[John Leonard, President and CEO]

I think that's something we can address later on as we get further down the road. But generally speaking this is information that's well publicized and available. The market has been disproportionately U.S. market with reimbursement rates that are higher. That's typically the case for most drugs. And again, we see that here. But again, we're trying to think through how this particular approach can be demonstrated to be resource sparing, to what are typically centrally reimbursed approaches and will present that data to those different systems. And we expect it will be of potential value to them.

[Richard Law, Credit Suisse]

Great, thanks.

[Operator]

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

[Ian Karp, SVP, IR and Corporate Communications]

Great, thanks for all the terrific questions and for your continued interest Intellia and our progress. And we look forward to future updates. So have a great day and a great rest of the week.

[Operator]

The conference has ended. You may now disconnect your line. Thank you.