Q4 2023 Intellia Therapeutics Inc Earnings Call
Participants
Ian Karp; SVP, IR and Corporate Communications; Intellia Therapeutics Inc
John Leonard; President & CEO; Intellia Therapeutics Inc
David Lebwohl; 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
Mauri Raycroft; Analyst; Jefferies LLC
Luca Issi; Analyst; RBC Capital Markets
Greg Harrison; Analyst; BofA Securities
Gena Wang; Analyst; Barclays
Troy Langford; Analyst; TD Cowen
Konstantinos Biliouris; Analyst; BMO Capital Markets
Dae Ha; Analyst; Stifel, Nicolaus & Company, Incorporated
Brian Cheng; Analyst; J.P. Morgan Securities LLC
Debjit Chattopadhyay; Analyst; Guggenheim Securities, LLC
William Pickering; Analyst; Sanford C. Bernstein & Co., LLC.
Rick Bienkowski; Analyst; Cantor Fitzgerald & Co.
Yanan Zhu; Analyst; Wells Fargo Securities, LLC
Timur Ivannikov; Analyst; Raymond James & Associates, Inc.
Jay Olson; Analyst; Oppenheimer & Co. Inc.
Silvan Tuerkcan; Analyst; JMP Securities LLC
David Lebowitz; Analyst; Citigroup Inc.
Jack Allen; Analyst; Baird
Presentation
Operator
Good morning, and welcome to the Intellia Therapeutics Fourth Quarter and Full Year 202320 financial results conference call. My name is Drew, and I will be your conference operator today. (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, and welcome to Intellia Therapeutics Fourth Quarter and Full Year 2023 earnings. 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 would like to take a minute to remind listeners that during the call, Intellia management may make certain forward-looking statements and ask that you refer to our SEC filings available at SEC.gov for 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 questions.
With that, I'll now turn the call over to John, our Chief Executive.
John Leonard
Thank you, Lee. And good morning, everyone, and thank you all for joining us today. 2023 was an outstanding year for Intellia, and that strong momentum has carried into 2024 with our two lead programs, either in or approaching Phase three clinical development for now closer than ever to the first in vivo crisper based therapies reaching the market, we've made critical advances for the field of genome editing and for patients suffering from ATTR amyloidosis or HAE. Notably, our onetime treatments offering potentially unmatched clinical profiles would address significant patient unmet need in two large and rapidly growing commercial market, having clinically validated our in vivo gene editing technology by inactivating genetic targets in the liver, we're now bringing forth the next wave of innovation. This new Frontier will come in two dimensions, broadening what we can do and expanding where we can go, all of which will allow us to increase the number of diseases we can pursue the genome editing revolution is only made possible by the unique properties of per caps. Intelli-check's expertise with crisper cast side is unsurpassed and serves as the foundation for the diverse set of editing tools we've developed and continue to advance whether using base editing or G&A writing tools. Each of these technologies rely on the specificity and versatility of the crisper system with our wide range of editing and delivering capabilities, we can apply the best tool for each therapeutic application. This allows us to address diseases where there is a meaningful opportunity to improve the standard of care. In some cases, we may even be able to pursue diseases that would otherwise be considered untreatable if not for the power of Christmas, it is this expansive and modular platform, coupled with our strong balance sheet that will allow us to achieve the three year strategic priorities announced earlier this year. Our focus remains on both near-term clinical execution as well as value creating platform innovation. With this as a backdrop, we expect the following by the end of this year, two in vivo knockout programs and active Phase three studies, two in vivo gene insertion programs, the first in human studies, and five different tissues outside the liver with active research programs. And additionally, we expect to have six or more collaborations with at least a dozen potential drug products utilizing our technology and research and development. We're confident in our ability to deliver on these ambitious goals. We have a proven track record of success with regulators and advancing crisper based therapies and clinical trials. We've consistently delivered on our commitments to the scientific patient and investment communities. And finally, we have a world-class team of drug developers who have pioneered some of the most innovative and commercially successful medicines in history.
In summary, Intellia is the company with the most advanced and expansive in vivo and ex vivo pipeline in the industry. With the potential BLA submission in 2026, we are well positioned to bring forward the first-ever in vivo crisper pace there.
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. In December, we initiated the Phase three magnitude trial for patients with cardiomyopathy. Since then, we're hitting the aggressive timelines. We have set for ourselves, including multiple sites, opening and regulatory approvals in geographies with large patient numbers. Notably, we have our first U.S. site actively enrolling patients and on track to dose the first patient in the first quarter. We are making great progress and expect many additional sites to ramp up throughout.
At the same time, we are actively preparing for a global pivotal Phase three study of 21 for the treatment of patients with polyneuropathy. We expect to provide additional information on our Phase three plans later this year.
Finally, we plan to present new data from the ongoing Phase one study this year.
I'll now turn to 2002, our in vivo crisper candidate for the treatment of hereditary angioedema or HAE, a few weeks ago, the New England Journal of Medicine published our landmark Phase one data. This marks the second consecutive InteLite in vivo program to have initial clinical data published in this prestigious medical journal. We are continuing to follow the Phase one patients and plan to present additional data this year. As previously announced, high interest in 2002 allowed us to identify all patients for the Phase two study in only six months we have since completed enrollment and dosing. We look forward to presenting the initial results for the first time later this year. Importantly, these data will determine the dose selected for the pivotal Phase three studies. We expect to initiate the Phase three study in the second half of this year of course, this is subject to regulatory feedback, but we think we're in an excellent position with five special regulatory designations granted to 2002. We've taken advantage of the opportunities for additional interactions with the FDA and other agencies to gain early alignment on our Phase three plans.
In summary, we believe both programs could reset the standard of care for people living with ATTR amyloidosis or HAE.
I'll now hand over the call to Laura, our Chief Scientific Officer, who will provide updates on our R&D efforts.
Laura Sepp-Lorenzino
Thank you, and good morning, everyone. For continuing to advance novel gene editing and delivery technologies for both in vivo and ex vivo therapeutic applications.
Building on the success of our in vivo gene regulation programs were leading the development of Kris pervasive targeted gene insertion share. We're leveraging the same and then B platform using our gene knockout programs to deliver decrease per machinery along with an AAV to deliver a functional gene. Unlike traditional gene therapy, we expect our approach will permanently restore in leasing or defective protein without a waning of effect over time earlier this month, our collaborator, Regeneron announced that the Factor nine gene mutation program for hemophilia B has achieved IND clearance. This milestone puts Entavio at 234 in-vivo Vpns as within 30 days of submission is testament to our high standard for drug development.
In parallel, we also expect to be in this year the Phase one study of our wholly owned program MDNA 31 for alpha-1 antitrypsin deficiency based on our preclinical data and BLA, 31 could potentially achieve normal human levels of the Alpha-1 protein after a single dose. Further, the potentially human proof of concept of our modular gene fusion platform would open a whole new category of diseases that require restoring missing or defective protein. This may include diseases that are not addressable by either base editing or DNA viruses beyond our liver-directed program, our goal is to harness the full potential of gene editing by extending the reach of our industry-leading platform to other diseases. Recently, we announced a collaboration with Brickell therapeutics to accelerate the development of crisper based treatments targeting genes in the lung for cystic fibrosis. This collaboration provides yet another example of our partnering strategy to enable pipeline optionality outside our core areas of focus while retaining attractive commercialization rights. With this new collaboration alongside our own and our partner programs, we are actively pursuing gene editing programs across five different features.
Finally, in the ex vivo setting, we're continuing to advance multiple programs, both wholly owned and with collaborators, for example, at Intel is now dosing patients in their first-in-human study of an allogeneic candidate. Cyberknife is utilizing our allogeneic platform to advance in next-gen CAR-T program for autoimmune disease. Both collaborators are using Intellia's proprietary, the allo solution, which is designed for both both T cells and NK cell mediated rejection in previously unsold challenge for the field of cell therapy.
I'll now hand over the call to Glenn, our Chief Financial Officer, who will provide an update on our financial results as of Q4 2023.
Glenn Goddard
Thank you, Laura. Good morning, everyone, and tell you 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 $1 billion as of December 31st, 2023, compared to $1.3 billion as of December 31st, 2022. The decrease was driven by cash used to fund operations of approximately $448.8 million The decrease was offset in part by $119.8 million of net equity proceeds from the company's at-the-market program, $49.8 million of interest income, $18.7 million of collaborator reimbursements and $10.5 million in proceeds from employee stock plan.
Our collaboration revenue decreased by $15.5 million to negative $1.9 million during the fourth quarter of 2023 compared to $13.6 million during the fourth quarter of 2022. This decrease was mainly driven by a $10.3 million one-time revenue recognition adjustment related to Regeneron, extending the technology collaboration to April 2026. Intellia will receive a $30 million payment due in April as part of that Regeneron extension.
R&D expenses increased by $9 million to $109 million during the fourth quarter of 2023 compared to$ 100 million during the fourth 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 $21.7 million for the fourth quarter of 2023.
G&a expenses increased by $5.4 million to $29 million during the fourth quarter of 2023 compared to $23.6 million during the fourth quarter of 2022. This increase was primarily related to an increase in stock-based compensation of $4.3 million. Stock-based compensation included in G&A expenses was approximately $13.3 million for the fourth quarter of 2022.
And finally, we expect our cash balance to fund our operating plans until mid 2026. 2024 will be another productive and catalyst-rich year for Intellia, and we look forward to updating you on our continued progress.
With 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
(Operator Instructions) Mauri Raycroft, Jefferies.
Mauri Raycroft
Hi, good morning. Congrats on the progress, and thanks for taking my question on. As you accumulate data from the Phase one 21 cardiomyopathy study, are you getting a sense of how TTR levels are tied to CV events in individual patients and how this compares to silencers potentially as it relates to APOLLO-B in newly Healios be and how much data and follow-up do you aim to collect before providing your update and maybe talk more about what you'll report in the update later this year.
John Leonard
Thanks, Maury. It's John. Appreciate your question. Remember that the Phase one study is limited in size so that the amount of information we'll provide from a clinical point of view and the ability to tie TTR levels to clinical progression is going to be inherently limited. We look to what we see other competitors doing in the space and use that as a complement to what we see on our with our own work. I don't think that anything that we've seen thus far that's been put out there is really changing fundamentally how we're thinking about prosecuting the Phase three program, but I'm sure we'll be talking a little bit more about that as the call progresses. I don't know, David, if you wanted to add anything to what might be presented later this year.
David Lebwohl
Yes, I think you've given the most important points on people, it's just recall that the dose expansion just completed it towards the end of 22. So the patients have had just a little bit over a year. And we've seen in other studies that I'm even it's just the difference between placebo and treated patients in the Phase threes of other compounds start to diverge with about one year. So we do need significant follow up on to see trends. And of course, we don't this is a single arm trial, so we don't have the quite the right controls to compare any of our results too, on that we do have the results, of course, from the other studies to look at.
Operator
Luca Issi, RBC.
Luca Issi
Great. Thanks for taking our question. This is Lisa on for Luca. And just a quick question again on TTR cardiomyopathy. And our INCREASE study is going to readout this summer. So just wondering, should this readout positively as a result and an early termination of your TTR cardiomyopathy study with NTLA. two oh one. Any color there would be helpful.
John Leonard
I don't see how the Healios results are going to affect the early termination of our own work. I mean, just to remind you what David went through in the earlier comments, we're actively enrolling the 21. Our Phase three trial, which we called magnitude, were aggressively opening up sites. We've got multiple sites open and enrolling now, and we'll communicate more about the progress later this year. Obviously, we look to information as it's presented, whether the Healios study or other studies to think about how we conduct our own program. But based on everything we've seen thus far based on our own data of the data that's accumulated by others, we're very confident and satisfied with the trial design that we have. I'll remind you, it's an endpoint study. So whatever happens from a time point of view of Healios really doesn't relate to the work that we're doing. This is an events-driven study. We size the study appropriately, and we're going to have patients that we expect to present clinical endpoints just based on the stage of their disease, which is somewhat more advanced in our study. So all things considered, we think we're in a really good position. Of course, we'll watch Healios as it comes out but doesn't really fundamentally change anything that we're doing.
Operator
Greg Harrison, Bank of America.
Greg Harrison
Hey, good morning and thanks for taking the question. Could you give some color on your latest thinking on 20 two's potential, please, in the treatment landscape given recent competitor data update?
John Leonard
It's an important question because we acknowledge there's other drugs out there that have some activity nature either. Certainly over the last few years, progress has been made in the Pharmacopeia for the HAE patients, which is great news. The fundamental problem. The challenge for patients that we hear from doctors and from patients themselves is to make a tactical way, make them be in a position where they never have to worry about an attack and don't have to carry on-demand therapy. So as new forms of on-demand therapy come out that fundamentally, we don't think addresses what patients are looking for from a prophylactic point of view, as long as those drugs need to be re administered, that is going to be a continuing burden for those patients. So as we look at where we are with the data that we've seen thus far and look forward to continuing to expand. We believe that we're going right to the heart of the matter, which is preventing attacks once and for all of which we anticipate, assuming the success we've seen thus far continues that patients will be able to dispense with their therapy once and for all. And I think that's the lead solution patients are looking for.
Operator
Gena Wang, Barclays.
Gena Wang
Hi, good morning. This is Harshita on for Gena. Thank you for taking our questions. I just had one on the magnitude ATTR-CM trial on clintrials.gov. Your secondary outcomes included a change in baseline to month 18 in serum TTR and also KCCQ. So first, I wanted to confirm that these were the only secondary endpoints being measured. And if so, I wanted to get your thoughts on why these were selected as the sole secondary endpoints versus some other common ones such as Six Minute Walk and major class NT Pro-BNP echo parameters. So any color you could provide there would be really helpful. Thank you.
John Leonard
david, do you want to speak to how we think about secondary endpoints where we included the ones we chose.
David Lebwohl
Those were chosen as being the most important secondary endpoints, of course, and consultation as well with regulatory agencies.
The important things for patients we think are, first of all, what we see in the primary endpoints, reduction in cardiovascular events and mortality. Of course, that's the most important thing this will be associated, we think with the improvement in quality of life and of course, quality of life is, therefore an important endpoint for these patients.
The other measures like six-minute walk have been have had inconsistent results and recent studies as you've seen, and we don't think is a really important part of what's happening for patients, especially because they may have other things other than their heart disease that's really affecting their six minute walk as these are older patients, same for pro-BNP. It's a biomarker that indicate something about heart function, but not really getting to the heart of what's important to patients.
Operator
Troy Langford, TD Cowen.
Troy Langford
Congrats on the progress this quarter and thanks for taking our question for 22, you are expecting to file regulatory regulatory application in Europe that are on the same time as in the US and European regulators.
Do you think that European regulators seem mostly aligned with what the FDA wants at this point or do you see any divergences there?
John Leonard
David, do you want to address to the conjugate filing of the 2002?
David Lebwohl
So this is for 2002. The design of Phase threes is fairly well set for this indication. You've seen a number of drugs on going forward, both with approvals or with new Phase three studies and they all have really similar design that includes a future that they're they tend to be very small studies that could be well under 100 patients. And um, and really looking to in our case, the idea that we may be able to prevent any events in these patients. And this is in coordination with the FDA filing, which would be sort of an end of Phase two meeting in Europe. They don't have that kind of meeting, but we have other types of discussions that indicate the designs that we have moving forward. We'll be acceptable in Europe as well.
Operator
Konstantinos Biliouris, BMO Capital.
Konstantinos Biliouris
Good morning, guys, and congrats on the progress and thanks for taking our question. Maybe one question on your recent collaboration with Ricoh. Can you provide any additional color on approximately when we can see the first early data at that? And how are you thinking about the competitive landscape, especially other gene-editing approaches that are being developed for this disease?
Thank you.
John Leonard
Thanks for the question. We're really excited about the work that we're embarking on with recode. I think it's a little early at this time to project exactly what we're going to have and when we're going to have it. But we're convinced that the work that they've done with LNP delivery to the lung, puts us into a really interesting position where we can take the gene writing approach that we've developed and go and address a variety of different genetic lesions that yes, I would currently and satisfied for patients with CF. Obviously, that's a landing pad from which one can expand it and think more broadly about what might be possible in that space.
In terms of other competitive approaches, I think there's obviously a race to get to of solving once and for all the problem that these patients suffer from and we think we've chosen the best partner to be in a position to be highly competitive and ultimately prevail.
Thank you very helpful.
Operator
Dae Gon Ha, with Stifel.
Dae Ha
It has been here. I'm on for data or maybe a couple of questions on NTLA. 3,001. And given the rapidly crowding of the gene therapy gene editing approaches and MATD., what is the ideal product profile for NTLA-2001?
And then can you remind us again that the therapy one gene insertion on, is it directional and what are some supportive of pieces of evidence or tools that are available to detect the correct insertion of the gene?
John Leonard
Thank you. So we'll turn to Laura to speak to what the insert is. And if there's any sort of direct and directionality to it, we think we've addressed it nicely.
Just with respect to the product profile. And our objective is to get to essentially normal human levels of wild-type protein. Once one does that which we've accomplished preclinically in nonhuman primates, those patients should be essentially the same as patients without the mutation of the first place, at least with respect to their lung disease. So whether or not I will get to that in humans is the basis of the Phase one trial that we're embarking on now as we speak. And of course, we're really excited about getting that information, which we think will address not only what we're doing with 31, but a whole plethora of other sorts of insertion programs that will be associated with that or you want to say a word about the insert and how that --
Laura Sepp-Lorenzino
Sure And this is where using our insertion platform where we're inserting into the interim one of the albumin locus. So the expression is driven by albumin, which is a really strong promoter. And of course, the gene right is wild-type, so DC. in a fully functional wild-type. And so there is no issues with any errors and sequencing or bystander edits, for example, they do introduce with other editing modalities.
Operator
Joon Lee , Truist Securities.
Hi, good morning. This is [Maddie] on for Joon and thanks for taking our question.
This one also maybe for Laura on NTL. eight period one. So could you please talk about that a potential risk of exacerbation in the liver manifestation of patients treated with 1001 based on the Hetero polymerization capacity of the normal form with the mutant form. Thank you.
John Leonard
You want to address that?
Laura Sepp-Lorenzino
Well, yes, we haven't seen any in our preclinical models used in renal cell lines were these expression of the mutant form that would lead us to and a concern with regards to exacerbation of some aggregation after 31st treatments.
Operator
Brian Cheng with JPMorgan.
Brian Cheng
Yes, good morning. Thanks for taking my questions on what's the latest thought around the three 31 Phase one trial design specifically, how do you sequentially space out the AB. and RM. team initiations and I'm can you touch on also the Bar FCMAT. that you're aiming to unpack here?
John Leonard
David, can you summarize the essence of the Phase one design I think it was a little hard to hear, but I think part of the question was how much time elapses between a V and LMPI. administration within a particular patient.
David Lebwohl
We haven't told the exact our signed a clinical study, but they are both going to be not giving exactly at the same time because we do want to separate them a bit, but the and they are given sequentially and the both crisper mechanism and the AV will be present in the cells at the same time once they are administered and that's the key feature to be successful to get there for gene insertion. Otherwise, it really is a standard Phase one study with a dose escalation arm based on the preclinical findings that we have. And again, we'll be giving more details of that once the trial is fully approved.
Operator
Salveen Richter, Goldman Sachs.
Hi, sorry. This is Lydia on for Salveen. Thanks so much for taking your question on just another on 21, could you just speak to your comfortability around the powering for the magnitude trial? And when do you expect to complete enrollment in so much?
John Leonard
David, can my address?
David Lebwohl
Sure. So the we're very confident in the design. I recall that we've used an event-based study rather than happening the follow up on patients. So the advantage of this, of course, is that we would not need to extend the time of the study based on them and perhaps lower event rates than they do predict. But given that we did make a very conservative estimate, both on our powering and predicts predicted event rate. So again, we're confident in what we have with the design with a larger study than see it Healios be at 750 patients see on the completion of enrollment. We've said it's going to be in the yes, it would be looking at some of the other studies to get a sense. And you've seen that these studies enrolled very quickly. And so that would that would give you a good idea when we do expect to complete enrollment enrollment.
Operator
Debjit Chattopadhyay with Guggenheim.
Debjit Chattopadhyay
Good morning. This is Ryan on for Debjit, do you see opportunity for 21 differentiation by potentially enriching the magnitude trial with NYHA Class three subjects or other patient demographics that capture a sicker population relative to contemporary ATTRCM. trials.
John Leonard
David, do you want to speak to the mix of patients we have allowed in patients who are if we have more advanced disease what does that do for us?
David Lebwohl
We do allow, of course, Class three patients. An important feature of what we looked for is patients who are on somewhat sicker than the other study from the way we did this is to have the baseline pro-BNP be greater than 1,000 and to not have an upper limit on the pro-BNP. This could differentiate us in a few ways. First, we did this because the some of the events occurring more rapidly, the trial will be completed more rapidly. In addition, we do think these sicker patients are the one most likely to benefit from TTR reduction. If you're if you have a very healthy patient, they won't have events in either arm of the trial and they really won't contribute up to what we learn about the trial. So we do, but I do think that by choosing these patients, we will be able to differentiate our treatment of getting to lower TTR.s and the other treatments arm in this study.
Operator
William Pickering, Bernstein.
William Pickering
Hi. Thanks for taking my question in ATD., what dose level of AV. was used in your NHP. studies?
And how is the human dose equivalent compared to what we see from traditional AAV gene therapies that are integrating into the genome and how much margin for error do you have on not lowering albumin in terms of the insertion efficiency that you're expecting versus the levels that would be required to make a meaningful dent in albumin levels? Thank you.
John Leonard
But we're not speaking to the precise dose of AAV, but it's lower than what's used for standard gene therapy.
Laura, maybe you could say a word about the strength of the albumin promoter and life us just a few integrins are necessary to get to the levels we need.
Laura Sepp-Lorenzino
yeah, so IBM and promoter is the strongest promote they're going to try and sell. You just mean in a few percentage of sales. Two have been a productive insertion to achieve normal levels in retail, we're looking at 22 micromolar B&O as an average rates. So the preclinical data, of course, we the major sources of LMP. and AV. at keeping the goal, as John just said, to ensure that the AB. does ease is slow. We do not need to hit all the all the cells in the liver cancer field. And that gives us safety. We feel very good about the margin.
And with regards to albumin, we do not see significant decreases in albumin right, because you're only anything in a few cells. So albumin expression remains constant and that we've seen in preclinical models, and that was further evaluated in our GLP tox studies.
Operator
Rick Bienkowski with Cantor Fitzgerald.
Rick Bienkowski
Great. Good morning, everyone. Thanks for taking the questions for the pivotal study in HAE. Given the timelines for the potential 2026 BLA filing. I wanted to ask about the degree of confidence in being able to use a six month primary endpoint in the pivotal study just given gene editing mechanism is so different from the competitors here. And also in the Phase one data, there was the initial 16 week period after dosing where some patients experience breakthrough attacks. I was wondering if this phenomenon could be accounted for in the pivotal trial design in any way.
John Leonard
David, do you want to speak to six month endpoints. I mean, obviously, you've been on the front line and talking to regulators around the world, do you think that will be the need to extend beyond these standard sorts of approaches?
David Lebwohl
What we believe is that the six month endpoint, which has been standard in these studies will be the same standard that we apply to this study.
In terms of longer follow-up, of course, we will have Phase one and Phase two patients with longer follow-up when we file the BLA and as well as a very extensive safety database from our other gene knockout program with TTR. So we do feel very confident that the safety database with bringing will be satisfy what the regulators want course for all gene therapies. We will continue to follow the patients for the standard 15 year period.
In terms of the breakthrough attacks, we are looking at how do we account for this in the pivotal study. We're not talking about the exact design. You have to recall those patients are only the patients who had very unusual number of attacks now as up to 15 attacks a month, as you recall, so that there's some. We don't expect that that's an unusual patient kind of patient who is waiting for the Phase one study. Most of the patients in the study will be more like the other patients where the attacks are were pretty much gone after the infusion.
John Leonard
Rick, I appreciate you're noting the BLA in 2026. That is one of our key strategic objectives for the company in the next two to three years. And we're very excited about being in a position to take what we think will be the very first in vivo crisper based approach to approval and go into what we think is a marketplace that we can be extremely successful in.
Operator
Yanan Zhu with Wells Fargo Securities.
Yanan Zhu
Great.
Thanks for taking our questions. So just wondering a very quick one on a magnitude. What is the percentage of onto pharma this patient you target in the trial? And also wondering if you could talk a little bit little bit about your DNA writing technology.
I think this is the first time we hear about a program since you acquired the technology in 2022. So wondering if, for example, is there a correction template and whether it is RNA or DNA format?
Thank you.
John Leonard
And maybe I can say a word about the rating DNA writing approach, and David will address how we think about the parameters in the magnitude study. It is the way we think about it, gene editing in general is capabilities by that. I mean, introducing that particular type of change that one is interested in in introducing into the genome for whatever therapeutic purpose. There's different ways to introduce those changes. When we think about gene writing tests, that's a category that brings with it a variety of approaches to introduce a string of nucleotides. And as you commented, we acquired a work that was complementary to the work that we're doing a couple of years ago, and we're excited with what that brings to us to add to the work that we're already doing. And at the right time and the right place, we'll talk about exactly what we're doing and how it fits into our pipeline but I think it's just important to note at this point that we're making excellent progress and doing everything that we want the technology to do.
Maybe you want to say a word about the family medicine for Fabry.
David Lebwohl
We expect about half the patients to be treated with a family of and this is similar to what's been seen in the pivotal studies that have been reported so far as well.
Operator
Steve Seedhouse with Raymond James.
Timur Ivannikov
Good morning. This is Timur Ivannikov on for Steve Seedhouse.
So we have a question and ATDI. historically, it's been difficult to show improvement in lung function with augmentation therapies and other therapies on endpoints such as SD-WAN or pulmonary exacerbations and even more advanced augmentation therapies haven't attempted to show this improvement.
And so how do you think about improvement in lung function? Do you expect regulators you require you to show an improvement?
John Leonard
David, you want to --
David Lebwohl
Yeah, the regulatory standard hasn't been set here. There have been some reports publicly that the FDA may accept having normal levels of alpha-1 antitrypsin could be a way to move forward for us with some associated clinical findings, but not that flare. So really a definitive improvement and we do think because our program can get to normal levels, really the only gene editing program that's shown there so far that this may be something that the regulators will work with us on and it gives us a way forward to an approval mostly based on that on the high levels that we'll be achieving.
Operator
Next question comes from Jay Olson with Oppenheimer.
Jay Olson
Please go ahead, but a thanks for providing the update and congrats on the recent collaboration with recode in cystic fibrosis. Can you just talk about some of the features of the LNP platform that you found attractive?
And what is the route of administration? And is the collaboration only focused on cystic fibrosis or could you potentially leverage the collaboration to study additional targets and diseases.
Thank you.
John Leonard
Laura, you want to take them?
Laura Sepp-Lorenzino
Yes, sure.
And so recode has been pioneering a new class of lipid nanoparticles that are targeted to different audiences have disordered lipids and they have we were quite interested in what we're doing in the lung. And as you may know, they're already in the clinic with to inhale LNP mRNA for PCV in cystic fibrosis. Actually, I think they dosed the first patient with an mRNA yesterday. So with these MMP. that goes to lung for which they already have preclinical and clinical data and the manufacturing and the route of administration of inhalation, they have demonstrated that they can get to not only the mature cells, but also the target cells that you would need to edit have long lasting and yet even benefit if you're looking after a CFTR correction. So when we're looking at partnerships, we're looking to marry technologies. You know, we have a strong gene-editing technology that allows us to add target specific mutations and they bring in a validated delivery modality. So I think it is a great partnership, and we're looking forward to make quick progress.
Operator
Next question comes from Silvan Tuerkcan with JMP Securities.
Silvan Tuerkcan
Good morning and congrats on the quarter and congrats on the progress, and thanks for taking my question. Just a quick one on the HAE program and what are some of the considerations that you're thinking about selecting the dose for the Phase three and what can we see in the Phase two data that later this year to and give us confidence in that dose selection?
And then regarding the Phase three design overall, is there any impact or any information it will get from the Phase three OSSHAU. study from a bonus and that will be presented midyear that will help us also like in the design or think about the design of the Phase three trials yet even though you can choose your dose for Phase three?
David Lebwohl
We have new So recall that we've completed the enrollment through a Phase two in which the patients there are 10 patients on 25 milligrams, 10 patients on 50 milligrams and five patients on placebo. So we have a very good setting in which to evaluate those two doses. We chose those two doses because in the dose escalation phase. And as you recall, all patients basically achieved no events after the infusion except a single event and in one patient a year after treatment, which was related to a sports injury. So the on the Phase two we'll have a very extensive database of these two doses. The things we'll be looking at, of course, is the clinical findings, the event rate, but also the consistency of the pharmacodynamic effect we'll be looking at as part of this, there was more variability at the lower dose. So on first principles, we would tend to think that the 50 dose is going to be better, but we want to look at all the data and make a decision about the Phase three and will be a very robust decision based on this Phase two study.
Operator
Next question comes from David Lebowitz with Citi.
David Lebowitz
Thank you for taking my question. A competitor has a switch study for its HAE. trial, and I'm just curious as to whether there is a similar type of study that would be needed or what that would look like and for a gene-editing product, and I'll speak to that we haven't talked about doing a switch study in the arm in the pivotal studies.
David Lebwohl
What usually happens is that you withdraw from any kind of prophylactic therapy we have seen of our study patients withdrawing from added value I-Mab as well as other prophylactic therapies. And we do think that will be of interest of patients when this is an approved therapy to get off the therapies that they have to take repeatedly and go on to a onetime therapy and so on. We haven't yet guided to there being a switch therapy, but this is something obviously, that would be considered a switch study.
Operator
The next question comes from Jack Allen with Baird.
Jack Allen
Thanks for taking my question and congratulations on the progress.
I wanted to ask if you could comment a bit more about your plans to enroll slightly more advanced patients in magnitude as compared to Helios B and how do you expect positive results from Healios B could affect enrollment in magnitude?The magnitude will be a placebo-controlled study.
John Leonard
David.
David Lebwohl
The idea of enrolling more advanced patients is that these are the patients who can can really benefit from the therapy. If you imagine some of the studies we've seen, some patients who are on drug can be quite healthy despite having some early heart failure. And those patients have very few events and therefore contribute very little to the findings in the study. So that's the idea of doing that. And the arm. We do think a positive Healios BE study is a positive for us as well. It would show that TTR reduction is a value to patients with cardiomyopathy. The hypothesis that really all the experts, I really believe. And so we do think as well that it's very likely that Healios will be positive. The physicians are already very excited about our therapy. So that on a first of all, they see that we have a very consistent and deeper reduction in TTR. It could be the best in class agent. So the we expect the enrollment to be brisk. In any case, of course, having a positive study demonstrating that TTR reduction is important.
Maybe for maybe I further value in driving our enrollment as well.
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
Thanks so much, Drew, and thank you, everyone, for joining us this morning. It's certainly been a eventful and a successful start to the year, and we look forward to updating you out updating you throughout the year with additional progress. So thanks again, look forward to talking with everyone soon.
Operator
Thank you. The conference has come to a close. You may disconnect your line.
