Q1 2024 Intellia Therapeutics Inc Earnings Call

Participants

Ian Karp; Head-IR & Corporate Communications; Intellia Therapeutics Inc.

John Leonard; President, Chief Executive Officer, Director; Intellia Therapeutics Inc

David Lebwohl; Executive Vice President, Chief Medical Officer; Intellia Therapeutics Inc

Laura Sepp-Lorenzino; Executive Vice President, Chief Scientific Officer; Intellia Therapeutics Inc

Glenn Goddard; Chief Financial Officer, Executive Vice President, Treasurer; Intellia Therapeutics Inc

Yanan Zhu; Analyst; Wells Fargo Securities, LLC

Maury Raycroft; Analyst; Jefferies LLC

Troy Langford; Analyst; TD Cowen

Luca Issi; Analyst; RBC Capital Markets

Costas Belarus; Analyst; BMO

Brian Cheng; Analyst; JPMorgan Chase & Co

Mary Kate Davis; Analyst; Bank of America

Ben Carsky; Analyst; Cancer

Silvan Tuerkan; Analyst; JMP Securities

William Pickering; Analyst; AllianceBernstein Holding L.P.

Presentation

Operator

Good morning, and welcome to Intellia Therapeutics First Quarter 2024 financial results 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. (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

Thank you, operator, and good morning, everyone. Welcome to Intellia Therapeutics First Quarter 2024 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 and 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'd 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 John Leonard, Chief Executive Officer, David Lebwohl, Chief Medical Officer, 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 pipeline progress. Laura will review our R&D updates, and Glenn will review our financials before we open up the call for your questions.
With that, I'll now turn the call over to John, our Chief Executive Officer.

John Leonard

Thank you, Ian and good morning, everyone, and thank you all for joining us today. We've made outstanding progress in the first quarter of 2024, with one ongoing in two soon to be initiated pivotal Phase 3 trials, Intellia is undoubtedly leading the gene-editing revolution and with well over 100 patients already dosed across our two lead programs. We have already amassed the largest set of safety and clinical activity data for any in vivo crisper based therapies. Notably, we believe our onetime treatments for ATTRNHIE. offering potentially unmatched clinical profiles, could overcome key hurdles faced by patients in two large and rapidly growing commercial markets for over our first two investigational gene editing therapies are designed to be especially patient friendly and convenient for physicians and caregivers. There's no extensive preconditioning regimen, no long-term steroid requirement and no hospital stay, all of which can be very challenging for patients and limit commercial uptake associated with other gene therapies.
And of course, with a onetime treatment, there's no annual insurance reverification needed, which is typically required for chronic specialty therapies and can be a tremendous burden. But this is just the beginning for industry leading crisper based technology. We're now entering the next stage of growth, pushing the boundaries of what we can do and expanding where we can go with crisper from gene knockdown to gene insertion from liver targets to a broader set of tissues. Our first wholly owned crisper based gene insertion program until 831 is expected to enter human clinical development this year until 831 holds the potential to provide normal Alpha-1 levels after a single-dose treatment for people with alpha-1 antitrypsin deficiency. We will also have a second clinical program utilizing our modular gene insertion platform run by Regeneron for hemophilia B expected to start patient dosing later this year.
Building on our clinical success, we are now pursuing gene editing in five new tissue types outside the liver. As part of this expansion strategy, we have and will continue to establish collaborations with external innovators. These R&D efforts have already yielded at least a dozen potential drug candidates utilizing our technology. Further, we are advancing our modular platform by developing a diverse set of editing and delivery tools for in vivo and ex vivo applications, whether it's our proprietary LNP formulations, novel gene editing tools or differentiated allogeneic cell therapy approach. We emphasize safety and therapeutic activity at each step of development through our commitment to these principles, we are well on the path towards transforming cutting-edge scientific tools into real-world medical treatments. With this as a backdrop, we expect to end this year with five enrolling clinical studies, three of which are in Phase 3. This includes a newly planned Phase 3 for until late 21 in patients with ATTR polyneuropathy. Additionally, we plan to submit a BLA submission in 2026 for until late 2002, which we anticipate will lead to the first ever approval for an in vivo crisper based therapy. By that time our expectation is we'll have accumulated safety, efficacy and durability data for over seven years and have treated as many as 1,000 patients in our clinical studies.
In summary, we will continue transforming medicine with gene editing therapies with at least three important clinical data readouts expected this year.
I'll now hand the call over to our Chief Medical Officer, David Lebwohl, who will provide an update on our clinical programs.
David?

David Lebwohl

Thanks, John, and welcome, everyone. I'll begin with 21. Our in vivo crisper candidate for the treatment of ATTR amyloidosis is a multisystem disease, primarily manifest as either cardiomyopathy due to amyloid deposits in the heart or polyneuropathy through the progressive accumulation of protein deposits in the nervous system, as demonstrated in our Phase 1 study, a onetime treatment of 21 led to greater than 90% TTR reduction. Importantly, we demonstrated best-in-class reduction of absolute TTR levels among TTR silencing agents, which we believe will be a key differentiator for treating patients with HCM and or PN in ATTR-CM.
Despite the introduction of TTR stabilizers, patients continue to experience worsening heart failure, hospitalizations, strokes and heart attacks. Ultimately, it remains a fatal disease day. I'm pleased to report that patient enrollment in the Phase 3 magnitude trial for patients with cardiomyopathy is off to a great start in March, we announced the first patients in both the U.S. and globally had been dosed with over 30 patients already dosed another 40 plus in screening. We are tracking well ahead of our initial projection. Further, we expect many additional sites to open in the weeks and months ahead, which will further accelerate enrollment in the trial. While we will not be providing patient by patient enrollment updates.
Moving forward, we will look for opportunities to keep you abreast of our progress. The rapid rate of enrollment reflects the enthusiasm we hear from physicians and patients who believe 21 holds the potential to revolutionize the ATTR. treatment landscape.
In parallel, we are also excited to announce today that we now expect to initiate a new Phase 3 trial for patients with ATTR polyneuropathy by year end. Importantly, ATTRPM. patients are typically diagnosed earlier in adulthood and their disease often progresses more rapidly than a TTRCM. published data from chronically dosed TTR silencing therapies demonstrate that deeper reductions of TTR are highly correlated with improvements on standard measures of neuropathy to date, no other agent approved or in clinical development has demonstrated the depth and consistency of TTR reduction regardless of baseline levels like 2001, which gives us tremendous confidence in our ability to positively impact patients based on productive discussions with the FDA, we have aligned on a trial design to support a BLA filing for 2001, subject to review of the IND application, we plan to initiate the Phase 3 by year end. The study is expected to be a small placebo-controlled trial of approximately 50 patients conducted in ex U.S. regions with limited or no access to silencers. We are making significant strides in advancing 2001 and look forward to presenting data from the ongoing Phase 1 trial in the second half of the year, we expect to be presenting safety and TTR reduction data on all 72 patients from both the CM and PM. arm. Additionally, we plan to include for the first time data beyond TTR levels such as NT. pro-BNP, six-minute walk test and n plus seven.
In summary, we continue to believe 2001 may halt and potentially reverse the disease as well as dramatically reset the ATTR. treatment landscape.
I'll now turn to 2002. Our in vivo crystal program for the treatment of hereditary angioedema for HAE. in January, Landmark findings from the Phase 1 were published in the New England Journal of Medicine, highlighting a single dose of 2002 led to a 95% attack rate reduction on June 2, we will be presenting updated data from this study at the European Academy of Allergy and Clinical Immunology Annual Congress these long-term data will speak to the safety and durability of effect on both kallikrein and attack rate reduction. Importantly, we will also present on the number of patients who remain completely attack-free. We've extended follow-up now reaching beyond 18 months for all patients and longer than two years. From
Additionally, we plan to report top line results from the randomized placebo-controlled Phase 2 study shortly thereafter, full results evaluating the 25 milligram and 50 milligram doses are expected to be presented at an upcoming medical meeting. These data updates will provide clarity on which dose to move forward into the Phase 3 trial. Assuming 2002 continues to show a strong safety and efficacy profile, we believe that 2002 will become the preferred prophylaxis treatment in a growing commercial market in the U.S. market. For example, currently about 70% of HAE patients use chronic prophylaxis treatments, and that number is increasing. Many patients continue to seek better efficacy and more convenience, expressing a strong willingness to switch to new treatments that can deliver on both fronts.
As previously discussed, we plan to initiate the pivotal Phase3 trial in the second half of 2024. At this point, we are mainly waiting for the Phase 2 data before submitting regulatory amendments to begin our global Phase 3 Notably, we have now also completed the additional preclinical mouse study requested by the FDA to support inclusion of women of childbearing age in the U.S. As expected, these data did not show an impact to female reproductive health in the animals treated with 2002. This is consistent with the extensive preclinical work completed and reviewed by regulators prior to our initial IND clearance, and we plan on submitting these data to the FDA prior to Phase 3.
Let me now turn to exciting developments with our modular gene insertion platform. Here we are leveraging the same LNP platform used in our gene knockout programs to deliver the Crystal machinery, along with an AAV to deliver a functional gene. Unlike traditional gene therapy, we expect our approach will permanently restore a missing or defective protein without a waning of effect over time. We expect to begin this year a first-in-human study of 3001. Our wholly owned gene insertion program for alpha-1 antitrypsin deficiency. As a reminder, the main hurdle with treating this disease is getting patients to consistently normal levels of Alpha-1 current standard of care, which involve weekly infusion of augmentation therapy does not achieve this. Other approaches in development have also been unable to yield normal levels of alpha one and in some cases have only been able to produce a modified version of the protein with unknown consequences. 3001 is the only drug candidate to show AAT levels restored to normal levels after a single dose in nonhuman primates. It is designed to precisely insert the wild-type surface, a one gene and permanently restore production and secretion of fully functional Alpha-1 protein. Assuming success, 3001 could be life-changing for alpha-1 patients and unlock a whole new category of diseases we can pursue with in vivo gene insertion. Separately, our collaborator, Regeneron has achieved clearance from both US and EU authorities for the Factor 9 program using our modular gene insertion platform and plan to enroll the first patient later this year. Our clinical development of the in vivo pipeline is rapidly accelerating and Intellia is well positioned as the leader in this new era of medicine.
I'll now hand over the call to Laura <unk>, our Chief Scientific Officer, who will provide updates on our R&D efforts and what coming next?

Laura Sepp-Lorenzino

Thank you, Dave, and good morning, everyone. At Intellia, we're advancing novel gene-editing and delivery technologies for in vivo and ex vivo therapeutic applications. As John mentioned core to our strategy is the emphasis on safety and performance at each step of development. Our success to date is not by chance, and it's a common misconception that gene editing and delivery tools have become commoditized. By leveraging the experience of a world-class team and making dramatic improvements and adaptations to our platform and technology. We have been able to lead the entire industry forward, but don't just take my word for it. Let me give you some real world examples. Intellia is now planned for filing INDs approved by the FDA for our investigational therapy. Groundbreaking clinical data set for both India late 21 and NDLA. 22 have been published in the New England Journal of Medicine. We have already gained regulatory clearance for multiple clinical trials in eight different countries. Together, we Regeneron work on that being the largest global Phase 3 study of genetic medicine.
Intellia has become the reference gene editing company, which has to help us foster important relationships with the world's leading scientific and medical experts as well as advocacy organizations and now building on the success of our work pieces that originate in the liver for expanding the tissue types that can be targeted with our crisper based technologies. We now have active research programs in five different tissues outside the liver, either independently or in collaboration with partners. This includes the bone marrow brain eye, lung and muscle. We're particularly excited about pursuing diseases such as sickle cell disease, muscular dystrophy, cystic fibrosis, MS and many other daily liquidity correlation. We're also advancing a pipeline of ex vivo programs, both wholly own and in collaboration with partners for the treatment of immune oncology and autoimmune diseases.
In fact, two of our partners are leveraging our allogeneic platform, one of which is already in the clinic. Our differentiated allogeneic solution, including HLA matching, is uniquely positioned to avoid both T cell and NK cell mediated rejection and result in cell persistence and disease control. Further therapies here with our allogeneic platform, combined with added to enhance and function offer a new approach to target solid tumors. We look forward to updating you on our progress across our R&D platforms more broadly this year, and I now hand over the call to Glenn, our Chief Financial Officer, who will provide an update on our financial results for the first quarter 2024.

Glenn Goddard

Thank you, Laura, and good morning, everyone, and tell you. It 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 approximately $953.4 million as of March 31, 2024, compared to $1 billion as of December 31, 2023. The decrease was driven by cash used to fund operations of approximately $137.2 million. The decrease was offset in part by $58 million of net equity proceeds from the company's at-the-market program $12.6 million of interest income, $5.9 million of collaborator reimbursements and $2 million in proceeds from employee-based stock plan.
Our collaboration revenue was $28.9 million during the first quarter of 2024 compared to $12.6 million during the first quarter of 2023. $16.3 million increase was mainly driven by a $21 million non-cash revenue recognition adjustment related to the admin cell collaboration for R&D expenses were $111.8 million during the first quarter of 2024 compared to $97.1 million during the first quarter of 2023. The $14.7 million increase was mainly driven by the advancement of our lead programs.
Stock-based compensation included in R&D expenses was $20.2 million for the first quarter of 2024. G&A expenses were $31.1 million during the first quarter of 2024 compared to $27.4 million during the first quarter of 2023. $3.7 million increase was primarily related to stock-based compensation. Stock-based compensation included in G&A expenses was $14 million for the first quarter of 2024. Finally, we expect our cash balance to fund our operating plans until late 2026. Notably, our strong balance sheet gives us the financial power to execute on the three-year strategic priorities laid out at the beginning of this year first to execute pivotal trials for our first two in vivo crisper based therapies, second, to launch the next wave of the in vivo and ex vivo clinical programs. And third to deploy new editing delivery modalities. We are well on our way to realizing the promise of gene editing. This will be a catalyst-rich year for Intellia, and we look forward to updating you on our continuing progress, but that we will now open the call for your questions. Operator, you may now open the call for Q&A.

Question and Answer Session

Operator

We will now begin the question and answer session period to ask a question, you may press star than one on your touchtone phone. If you're using a speakerphone, please pick up your handset before pressing the keys to withdraw your question, please press star then two. Please limit yourself to one question. At this time, we will pause momentarily to assemble our roster. The first question comes from Maury Raycroft with Jefferies. Please go ahead.
We'll go to the next questioner, Yanan Zhu with Wells Fargo Securities. Please go ahead.

Yanan Zhu

Break.
Thanks for taking our questions and a lot of progress this quarter. So congrats on those progress. So I have a question about your comment about the be that the enrollment in ATTR Phase 3 trial are tracking ahead and expect the internal expectation. One, wondering how many sites have you opened, what what's the number of U.S. versus ex U.SU.S. sites and what is the per site per month patient number that you are currently tracking and any updated thinking on CT enrollment completion time line on the families use at in terms of the currently enrolled patients?
And I think, yes, yes. Thank you a lot of questions.

John Leonard

Sorry about that, Yonah, and thank you for the many questions you just asked and that one question, and we're not going to be giving updates on patients per site, numbers of sites, et cetera. As we said before, this is a balanced study around the world. We're still actively initiating study sites. We've said that we expect about a third of all of the ultimate sites will be in United States and the remainder will be spread around the world. I think the takeaway that I would encourage you to see here is that we're early in this process and things are going very well. I mean, we're very excited about that enthusiasm that we see with investigators. We've been clearing the regulatory submissions expeditiously. We've been able to initiate sites and patients have been waiting to come into the study. We think it's a testimony to what patients and physicians see with the current state of therapy, which, as you know, with current approved drugs, patients continue to suffer from the morbidity and mortality of disease with ongoing progression. So we will not be giving updates patient by patient as we go. But I would encourage you to see that we're off to a very, very strong start or enthusiastic about the progress we're making.

Yanan Zhu

Thanks for those cover.
If I may, I make a quick follow up on that on that from what you your from your interaction with you. But in particular in the US sites, what you hear from PI.s and patients in terms of how do you think about the potential upcoming approval of silencers?
And how does that it impacts their thinking of going on the gene therapy treatment

John Leonard

in our interactions thus far, it hasn't influenced how they're thinking about the trial or putting patients on it.
Again, I think people are have been very impressed with the data that we presented and are encouraged to put their patients on the study. I'll remind you that we created a study that's very favorable to patients we've put into study, the ability for patients with stage three heart failure, higher pro-BNP level, et cetera, a two-to-one randomization that favors drug over placebo. There's lots of reasons to patients for patients and physicians to want to participate in the trial, and we're seeing that nice early results.
Thanks.
I look forward to the next question.

Operator

Next question comes from Maury Raycroft with Jefferies. Please go ahead.

Maury Raycroft

Hi.
Sorry about the technical issue and thanks for taking my question and congrats on the progress for the ag team, our PN study. I'm just looking at our precedent studies in the space of IONA's. Their study was 168 patients. Apollo was 225, and then Helio's A. was 164. And so just wondering if you can talk about how the conversation with FDA to align on your Phase 3 with 50 patients, maybe talk about what expectations are for clinical endpoints and results on those endpoints? And then what does this imply about the size of what your HAE. Phase 3 study could be?

John Leonard

Well, let me take the last point first and then I'm going to hand it over to David to address the specifics upon neuropathy. He endpoints and polyneuropathy inputs are two totally different animals, and I wouldn't read how one study is designed into how we think about the other. And as we get more specificity with respect to both of these trials will certainly speak to that. So you can see, but I would just emphasize before David speaks to some of the specifics. We've developed a very close working relationship with the Food and Drug Administration and other regulatory agencies around the world. I think they have a very good understanding of the expected effects of these drugs and have a very good understanding of how to show them in a meaningful way for their own purposes as well. So for physicians and ultimately for other regulatory agencies around the world, David, maybe you can say a few things about how we're approaching that study and why we think it will be successful.

David Lebwohl

First comes the big picture is that we and the FDA recognize that patients are still progressing despite the existing drugs, and we talk to them about this design, what they say they have seen our clinical data. An important part of that is that we're getting very deep and consistent reductions in TTR. And we do think that's been a positive effect on our discussions with them in terms of the number of patients. The FDA also has seen a number of studies that show TTR reduction leads to a benefit in patients. So that's becoming a well-established fact. Of course, the FDA is more interested in how biomarkers may be a way to to not only reflect what happens with disease but actually go forward to approvals in the future.
Some.
So I do think that the size of the trial has to do with their confidence in how we're working and on of course, we also have not only the 50 patients this trial, but a much larger database from the Phase 1 as well as the ongoing cardiomyopathy Phase 3.

Maury Raycroft

Got it. Thanks.
For taking my question. I'll hop back in the queue.

Operator

Next question comes from Troy Langford with TD Cowen. Please go ahead.

Troy Langford

Congrats on the progress this quarter and thanks for taking our question. So for until 301, how quickly do you think you can move through development with this asset?
So you tried to take this asset into a pivotal study shortly after the Phase 1 does work like with InterOil to 2001, where you think we'll have more traditional placebo-controlled Phase 2 to further refine the dose for pivotal study like with InterOil 2002.

John Leonard

Thanks for the question, Troy. I just start by saying, as was emphasized in our comments earlier today, we emphasize understanding these drugs, especially from a safety as well as from an efficacy point of view. And so that those will be our guiding principles as we carry out the study of 3001. We're excited with what we think the drug can do. I'll remind you that in the preclinical data we've established that we're able in nonhuman primates to reach normal levels as seen in human beings. We think that's fundamental to the regulatory strategy. Our hope is that we'll show that in Phase 1 studies and assuming that we see that we will progress as quickly as we can working with the Food and Drug Administration and other relief related agencies to establish what is the shortest most efficient way we have regulatory approval. So that lies ahead and we'll give you updates as we proceed it.

Troy Langford

Thanks for the color.

Operator

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

Luca Issi

Well, great. Thanks so much for taking my question.
And congrats on all the progress maybe gave you the TTR cardiomyopathy.
And given the recent changes from your competitor, are you rethinking any aspects of your trial design, mission area where Helios be hit on the monotherapy and show no benefit as add-ons to Santos.
Do you have any optionality to split the primary endpoint between the overall population and the monotherapy are similar to what they did.
And then moving quickly on TTR polyneuropathy, can you just expand on why not enrolling patients in the U.S. for the pivotal?

John Leonard

So I will have David speak to some of the specifics of the trial. But I'd just start by pointing out that there's some fundamental differences in how we've approached the pivotal trial in the case of PR. We've certainly been mindful of understanding the rates of progression. We've been able to learn from other drugs as they presented data as we've gone about this that have gone before us and we've been really thoughtful about an endpoint driven study, which is driven by the rate at which things happen, not by some prespecified moment in time when we surmise that all the events may be. And I think the standard approach these trials is, in fact, endpoints driven approach and and that's what we've embraced from the beginning. And I think, David, maybe you can just say a few words about how Healios does or does not affect our thinking at this current time.

David Lebwohl

The first point is that we are confident as John is saying in the design of the magnitude study because in all those point to maybe being conservative in the assumptions we've made as we designed it, Chris, it is a larger study than Healios. I think that's very important. And we also took on some more advanced disease in these patients. The pro-BNP is higher and we don't have enough eliminate that. We don't limit the amount of time that we follow these patients in this event-driven trial. Of course, we as we've stated before, because we get consistently deep and durable TTR reductions, we do think we can be the best in class and can be better than the drugs in other studies. So we will became very, obviously very close attention to the data that comes out from Healios state, and we do expect it to be a positive trial as you point out the how much it will add to families. We don't know at this point both whatever comes out from those results, we have the potential to modify our trial in order to address whatever and sound of the other drug.

John Leonard

Thank you, Lucas.
Also looking for some insight into the polyneuropathy study for Phase 3, and we are conducting it.

David Lebwohl

And why I'm sorry, discussions with the FDA was clear that was important to have a control arm the placebo control arm. So these are patients in the world who do not have access to silencers in the U.S., there is very good access to silencers. So the main reason we would not be again having patients in the U.S. is because of other satisfied need for that phone for those patients.

John Leonard

And it's important to note that we're aligned with that approach to understand how we would be doing a study and where we'll do it. And because the treatment practices are so similar, we think that these This information should be readily applicable to the United States kind of excellence.

Luca Issi

Thanks so much.

Operator

Next question comes from Gena Wang with Barclays. Please go ahead.

Hi, good morning. This is Josh on for Gena.
Thanks for taking our question on just a quick one on U.S. from us on until at 2022. Now that you completed the preclinical and biological development study, are you able to provide more granular color on when you plan to submit this data is the submission imminent and any color you can provide on how long it will take the agency to review this data. And I understand that you can't speak for the agency and each situation is unique.
But if you're able to provide at least a range on time lines, that would be helpful. Thank you.

John Leonard

Thanks for the question. Harshita up. We don't go through report by report and submission processes and procedures for each of those things. And I'd remind you that this is not even gating for the Phase 3vprogram.
The first point I think to make is that we've seen the data as it's as expected. There's no issues and we're in a really good position to proceed.
What's really going to drive the Phase 3 start is getting the data in with respect to our Phase 2 program and as was referred to by David during the comments earlier, when we have those, we'll be sharing those up later this year. And that's something we're very enthusiastic about. And because we have some regulatory designations that allow us to interact more readily with the FDA. We think we're going to be in a really strong position, actually poised to take that data and very, very quickly submitted to the FDA to begin Phase 3, which as a reminder, we said, will we expect to start this year and hopefully we'll be in a position to enroll patients before the end of the year.

Operator

Next question comes from Costas Belarus with BMO. Please go ahead.

Costas Belarus

Good morning, everyone.
Thanks for taking our questions and congrats on the great progress.
One question or 2001 from us.
You have previously showed data from other types of amyloidosis that suggests that the lower the residual TTR levels post treatment, the higher the survival may be given that you are presenting more data from LPLA. two zero zero one this year. I'm wondering whether the data you have collected so far across different doses can be sufficient to ultimately show trends that allow you to test the relationship between TTR levels and survival time.

John Leonard

David, do you want to speak to what we can extract so far from TTR decreases and points. I know it's early, but any additional comments you might want to put there?

David Lebwohl

So the you're right, when you say that the of what's been found with other diseases is lowering the protein and is extremely important back when you achieve a complete response. For example, with light chain disease for patients essentially have a normal survival. But we do see this as an important goal and why we're very excited about the deep levels of reductions we're getting to do that because our actually our results are so consistent in our own data, we won't be able to see a relationship between TTR reduction survival because while the patients are getting very good production. But you can look back for example, to the data from poly neuropathy with silencers that as you do go to deeper reduction, you see, for example, a greater improvement in the neuropathy. So the really one really important findings already. It goes along with the findings in other types of cardiomyopathy and just gives us the confidence that this trial will be successful and what it's trying to do.

Costas Belarus

Thank you very helpful.

Operator

The next question comes from John Baugh with Stifel. Please go ahead.

Hi, this is Ben.
As you're on for data, we noticed that recently there was a Stanford group that published ANA containerized insertion on web cast and a the immediate or repair templates are introduced. Can you comment on what methods you're employing to detect such incidents with NTLA-2001 and in your interaction with the.
Yes, have they kind of discussed this phenomenon?

John Leonard

Maybe, Laura, if you take the question was an academic group has found customers for insertion and or their techniques that one can employ to understand the extent to which that might occur.

Laura Sepp-Lorenzino

And so I don't want, of course, you know, that's part of the ongoing clinical development, right. And you could use different types of next-generation sequencing, including long range in a sequencing to understand whether you have a simulators are competitors.

Okay, excellent. Thank you.
Has the FDA brought anything about wanting that kind of information now.

John Leonard

The FDA hasn't asked about that until November.

Thank you.
Very.

Operator

Next question comes from Brian Cheng with JPMorgan. Please go ahead.

Brian Cheng

Yes, thanks for taking my question this morning.
I recall from a prior conversation, the goal is to always have about two years cash on the balance sheet. Can you give us a sense of how you're thinking about your cash burn and runway overall as Aricept to try to pivotal study later this year. How are you prioritizing and allocating resources when you're moving forward with Focus sets like TTRHAENHD.
Thank you.

Glenn Goddard

Yes, Brian, it's Glenn.
Thanks for the question.
So um, basically with what we talked about this morning is we're having runway now to late 2026. That's about 2.5 years for the cash that contemplates the three year strategic priorities all being funded that we've been laying out for investors.
So we feel like we're in pretty good shape there.
The other thing I would say is just the operating expenses are going to stay pretty consistent as we go forward here from what you've seen last.

Operator

What are next question comes from Debjit Chattopadhyay with Guggenheim Securities. Please go ahead.

Good morning, Tim, this is Robert from budget.
Answer particular questions to from us this morning what I can tell you his view on potential synergistic effects of 2001 knockdown and timing of stabilization and on gene insertion, how does Intellia and Regeneron plan to maintain expression within a therapeutic window, particularly in a disease like TMB?
Thank you.

John Leonard

David, do you want to say a word or two about how we're thinking about the interaction between 21 and the families. And then maybe, Lars, you can follow up is how we and for the therapeutic levels that we're pursuing here with a reminder that hemophilia B is being pursued primarily by Regeneron at this point.
David here soon.

David Lebwohl

But as discussed already, the way we think about it is that the lower the amount of this precursor protein of the abnormal protein, the better the effect on the disease. And in fact, if the protein gets low enough, then what we expect not only that you don't start accumulating still keep accumulating or amyloid, but you actually might see the reduction of amyloid antibody will remove the animal Lloyd from organs. So our goal is to get the lowest absolute TTR levels, which we've talked about. And some of our recent work, in fact, is some people at some point people may asking what is what is your TTR number that's to me the important thing of moving forward. So what happens with the families and if you do get the levels low enough then to families could be valuable still because the bit of remaining abnormal protein could be stabilized. So you go from a very low amount already with our drug to make it even somewhat better perhaps with its families. So it may be a valuable interaction. It might be a synergistic interaction as you get to these very low levels.

Laura Sepp-Lorenzino

With regards to the question on the gene insertion and how do you maintain therapeutic levels in as part of the preclinical development package involves doing a matrix of a dose of how much MB&O much insertion Tenplay right and you, it's clearly and deeply characterize what's the range of insertion that we sold to therapeutic protein production. And that data is then taken taken into account. And, you know, I know, Magic scaling for shipments, right. As part of your clinical development plan in the clinic, there is going to be a very purposeful and safe way of dose escalating to understand what's the level of expression and how does that translate across multiple patients in the cohort?
So United, reminding that immunocompromised is being driven by Regeneron. So we know they're already approved arm to move into the clinic. And we're expecting we're going to be seen and data clinical data in due time, which not only is important for that program, but it's a validation of the insertion platform that will translate to 31 and the number of other diseases for which insertion is the most appropriate gene editing modality, be part of the question was how to maintain levels.

Maybe you could say a word about potency stability that we expect by end for maintenance.
Right.

Laura Sepp-Lorenzino

We have shown now for factor nine for alpha one and other insureds that when such savings are day into the genome, you see very, very stable insertion. And this is a key difference from the traditional gene therapy where you have an episode or overtime that episode could be silent or can be lost just by the proliferation of the of the liver cells over time. So we expect that once you achieve those stable levels, those are going to be persistent and welcome all.

Operator

Next question comes from Mary Kate Davis with Bank of America. Please go ahead.

Mary Kate Davis

Good morning. Thank you for taking my question. I guess looking at your earlier stage pipeline with your recent collaboration with recode, could you talk about the opportunity and potential market, the gene-editing medicine in cystic fibrosis and maybe also the opportunity of utilizing your D. and A. rating technology to address this indication.
Thank you.

John Leonard

Of all start, why we're excited about cystic fibrosis. And maybe Laura can talk about some of the technical things that we believe we can address successfully with our approach. As I think it's well known, there's many people who suffer from cystic fibrosis in the United States and around the world in therapies that currently addressed or chronically administered. There's no doubt that that's represented in advance for patients relative to where they were some years ago. But the fact remains a business chronic therapy and many patients continued progress. There's a set of patients for whom no therapies available. And as exciting as some of the advances are that they're just irrelevant to a large subset of these patients. This is a very large market as we've seen with other companies, and it's something that we think we can make some very, very significant contributions to it.
Maybe, Laura, you can say a word about how we can address that and our work with Rico also in

Laura Sepp-Lorenzino

as John was saying, why do we believe that cystic fibrosis is, you know, if they still have significant unmet medical need, not only the people who don't respond to Kuvan therapy by the patients who don't tolerate them important among those patients is what's called a Class one that based on makes CFTR protein. So we believe that that's a perfect place for us to start by combining our DNA writing efforts with Ricoh MP., we were encouraged to see in OCMT. development by recode and particularly there in the clinic, right? We didn't fall in MP for two indications, one being CFTR, they have we have robust preclinical data demonstrating that they can get to the cells that we need to either have to have in a persistent long-term CFTR correction. So we're very enthusiastic about the collaboration and lean on and really pushing experiments to move as fast as we can and great team on both sides,

John Leonard

working together to recode work is a good example of our approach to partnerships.
In general, we look for leaders in the space, people that share our values and approaches to patients and you build sort of the partnerships that we think are going to yield important new drugs and we look forward to?
Yes, that's the five areas that we've talked about in our comments as we progress outside the liver.

Operator

Next question comes from Ben Carsky with Cancer. Please go ahead.

Ben Carsky

Hey, good morning, everyone. Congrats on all the progress and thanks for taking the questions. So for 2001 and TTR., I had a follow-up from Lucas earlier question on magnitude. I was hoping to hear your thoughts on how important it is for 2001 to show a strong treatment benefit on top of just diabetes and what the potential commercial implications would be for showing different treatment effects in the patients on baseline, tafamidis versus those not on treatment.

John Leonard

David, do you want to address the benefit and the importance thereof?

David Lebwohl

And so the on that, we believe that the drug can be 2001 could be better than two families as a single agent. And we also believe that there will be a benefit on top of the family. Of course, that's still to be proven the what we what we are hearing from investigators and physicians is that they are looking for better drugs for this disease. Patients continue to progress on to pharma. This arm virtually all the patients as best we can understand from investigators and from from the literature. So we do think there is a role for a single agent that is better than what the family is doing. This could be seen in the patients who are others who are not receiving to families in the study. So this will be an important analysis as part of our work.

John Leonard

I think it's important to state that nobody is satisfied with the, but it's I mean, patients or progress on that drug. The disease remains a mortal illness and investigators and patients know that and what we think will prevail in the marketplace is drugs that offer the very best outcomes to patients. And that's the approach we've taken from the beginning of the development program. We're excited with the data we've seen thus far, which we've been sharing, and we expect to show that at the end of our Phase 3 trial that we represent a significant advance over what is currently the state of treatment, whether used in combination or allowed, and that's going to be a real advance for the field.

Ben Carsky

Great.
Thank you.
And a quick follow-up. I just had a quick follow-up on Alpha-1 since there's two moving parts here. The LMP. and AV., I was hoping you could just comment on how you're thinking about the dose escalation. Would you be able to escalate those components in tandem? Or would you have to maybe do an extended dose escalation to control for those two different delivery vehicles.

John Leonard

I'll turn to David, but just to set the table, we do a lot of preclinical work to tried to address as many of the variables as possible before ever entering into the clinic. So I don't want anybody to think that we go in with a complete unknown just as our work with 2001 and 2002, where we shared earlier, our modeling was essentially dead on in terms of what we saw in the clinic. We expect that many of the insights we've learned from the preclinical work will apply very, very directly to 301 as well.
So David, maybe you could just say a word or two
about some of the contraction of what would be a standard sort of checkerboard study now 301, right?

David Lebwohl

So with these two parts, the LNTMAV., we've learned a lot already about LNP. The ability to go to a particular site and target that site. And what we've learned from both 2002 and 2001 program is that we can achieve essentially every every meal being targeted with this so that we can open that up for the contribution that the NAV. will make. So we think it's more as we have a good idea of the LNP dose and the variation will be more in terms of how much energy is needed to optimally get expression of alpha one antitrypsin. Again, our goal is to get normal levels that's what we've achieved preclinically, and that's our goal clinically as well.

Operator

Are you ready for your next question?
The next question comes from Joon Lee with Truist Securities. Please go ahead.

Hi, good morning and thanks for the update and taking our question. This is mainly on for June, sustained on ATTR. So assuming a positive update from Helios be possibly at May June and July. So how does a third generation R&I candidate with potential of once a year dosing could change the treatment landscape in Europe? Thank you.

John Leonard

Well, I would point out that things that follow us will be by definition after us. And we expect to be in a position where we will demonstrate the effect of our drug, which we think is going to be defining for the space. And our belief is that people will be comparing themselves to us as opposed to the agents that are out there. And regardless it's I've not seen data that surpasses anything that we presented thus far, patients will still be receiving the drug chronically, which brings with it all of the issues that apply to that and we think that a one-and-done approach, it's ideal for this patient set, and we are unique in that space. So it's important for patients to have different options. But nonetheless, we think that we will be setting the standard.

Thank you.

Operator

The next question comes from Silvan Tuerkan, with JMP Securities. Please go ahead and

Silvan Tuerkan

thank you for taking my questions.
My mind is more strategically, maybe you can give us like a 10,000 foot view on your strategy in the new tissues. I know you touched before on bone marrow and today a little bit on on cystic fibrosis, but within all of these tissues that you've mentioned, which ones are closer to IND-enabling studies, which ones are further along, and how should we think about those programs coming to fruition over the next couple of years towards, you know, moving towards 90.

John Leonard

Thank you.
Thanks for the question. It's an important one, but I don't want you to think it's a horse race and we give updates from the individual laps, the relay races run. All of these tissues are very, very important and really goes back to the philosophy and the strategic intent that has been the basis of the company since we first set out, it's a very deliberate approach that thinks about delivery and editing technologies. So as is apparent. We started out with knockouts in the liver, which you see with the 301 program as a gene insertion into the liver. We have technology to add to that in the form of gene writing in the liver.
And the goal has been to take these various editing technologies and apply them to diseases that reside outside the liver. And as Laura has mentioned earlier. We do that with collaborators where people have the technologies that can supplement our own and take us to places that we may not be you'll get there by ourselves. We're excited about the work with recode through and we're doing work with sparing vision. We have collaboration, as you know, with Regeneron, each of these tissues, five of them that were delineated earlier, have very important diseases with large populations with unmet medical need. Some of those opportunities surpass what we see in the liver at the current time. And so all of them benefit from the common approach from an editing point of view and all of them are being resourced very, very aggressively to get to those preclinical development candidates.

Operator

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

Hi, good morning. This is actually more Evonik of on for Steve Seedhouse. So congrats on the rapid enrollment in Phase 2 magnitude study.
One thing we would like to clarify is what type of patients are expressing more interest in the study is that patients who have no access to any treatment patients who couldn't enroll under the trials are patients on the time it has or some other category. And one other thing we'd like to clarify is what is the screen failure rate. So out of the 40 patients that are screened, what proportion do you think will be dosed? Thank you.

John Leonard

Thanks for the question. We're not going to go into the details of screening failures. And as I said earlier, a number of sites and patients for sites and all that, that's that's our work to do and we'll share as appropriate as we go forward. But David, is there any general insight you can provide in terms of the type of patient that's coming or not coming into the study at this point?

David Lebwohl

Yes, we were actually just meeting with investigators earlier this week, and there's excitement from these investigators for all of their patients, but this can affect the disease at all stages. So you can imagine patients with early disease, they want to prevent progression of disease. If they're doing well for the sicker patients, they want it at least stabilize or even reverse their disease so that they are really coming forward from what we are hearing from the investigators with all their patients. What we expect is about half of them have access to family this about half don't around the world of exit the proportions we expect and the trial screen failure rate at McNeilus is low, but we will continue. You know, that's obviously piece of any trial with some patients might be too sick or or or too healthy in some cases, but it's going very well, as you've heard with more than 30 patients already randomized and more than 40 right behind them.

Thank you very much.

Operator

And our last question comes from William Pickering with Bernstein. Please go ahead.
Brian.

William Pickering

Good morning.
Congrats on all the progress this quarter. And thank you for taking my question. I believe you said that you filed the ATDCTA application in December. Could you share if you have received any response or feedback to that application and once the trial is underway, what duration of follow-up would you want to include in any initial data presentation?
Thank you.

John Leonard

David, do you want to speak to CTA. status of the alpha one program with the TCCTA.?

David Lebwohl

We've gotten some straightforward questions that we've addressed where we're expecting to hear and gave back about the status of that.
On terms of follow-up, we will follow the principle. We always have that when we have a significant body of data to report on, I think that we will be bringing the data forward. As a reminder that Regeneron has gained approvals of both Europe and the IND. cleared so that, you know, in terms of the application itself to platform, we have high confidence in its ability to do go forward around the world.

William Pickering

Thank you very much.

Operator

At this time, I would like to turn the conference back over to Ian Karp As this concludes our question and answer session for any closing remarks.

Ian Karp

Well, thanks so much, Drew, and thanks everyone for joining us today for your great questions and for your continued interest in Intellia.
And we look forward to updating you as we continue to progress.
Have a great day.
Everyone.

Operator

The conference has now concluded. Thank you for your participation. You may now.
Yes.