Good morning and welcome to Intellia Therapeutics' Fourth Quarter and Full Year 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. As a reminder, all participants are currently in listen-only mode. If anyone requires operator assistance during the conference, please press star zero on your telephone keypad. I will now turn the conference over to Brittany Chaves, Manager of Investor Relations at Intellia. Please proceed. Thank you, Operator, and good morning, everyone. Welcome to Intellia Therapeutics' Fourth Quarter and Full Year 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 would like to take a minute to remind listeners that during this call, Intellia Management may make certain forward-looking statements and ask that you refer to our SEC filings available at sec.gov for 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, Ed Dulac, Chief Financial Officer, and Birgit Schultes, our Chief Scientific Officer, who will join for Q&A. John will begin with recent business highlights. David will then provide updates on our clinical pipeline progress, and Ed will review our financials before we open the call for questions. With that, I will now turn the call over to John, our Chief Executive Officer. Thank you, Brittany. Good morning, everyone, and thank you all for joining us today. We're off to a strong start in 2025 with renewed focus on our operational execution. With growing support and interest from investigators and patients, we're making remarkable headway with enrollment across our late-stage studies. We see significant promise with NTLA-2002 for the treatment of Hereditary Angioedema, where we expect a complete enrollment in our phase III study, HAELO, in the second half of 2025. We are similarly encouraged by the pace of enrollment with our phase III studies for transthyretin amyloidosis and expect enrollment in MAGNITUDE, our cardiomyopathy study, to exceed 550 total patients by year-end. Both HAE and TTR represent substantial market opportunities, and we have doubled down on our efforts to ready the company for the rapidly approaching commercial phase. In November, we presented positive extended follow-up data from patients in the ongoing phase I trial of nex-z, previously known as NTLA-2001, in patients with transthyretin or ATTR amyloidosis. The phase I data offered compelling evidence that deep and persistently low levels of TTR reduction achieved with nex-z may favorably impact disease progression for people living with ATTR amyloidosis. David will review these results in greater detail. We are actively screening patients with ATTR amyloidosis with polyneuropathy in our phase III MAGNITUDE-2 study and are on track to dose the first patient in the coming weeks. As you may recall, this pivotal trial is an efficient study with expected enrollment of 50 patients. We plan to measure mNIS+7 at 18 months and serum TTR levels as key endpoints in the study. We expect enrollment to be completed in 2026, enabling our second BLA filing by 2028. Last month, we announced the first patient had been dosed with NTLA-2002 in HAELO, our phase III study in HAE. Enthusiasm for NTLA-2002 from patients and our investigators is high, and we believe this phase III study will enroll rapidly, enabling us to submit a BLA filing in 2026. At the beginning of this year, we conducted a pipeline prioritization to focus our resources and efforts on these late-stage and high-value programs, NTLA-2002 and nex-z. We discontinued our work on NTLA-3001 in favor of a second-generation approach and will now look to see human proof of concept for our insertion technology by Regeneron in their hemophilia A program. As we look ahead to the rest of the year, we are well positioned for near-term value creation. We have three phase III programs actively recruiting and one singular focus, getting the work done to enable three launches between 2027 and 2030. We're excited by our progress and by our prospects, so we look forward to sharing data from both of our programs later this year. Lastly, I would like to take this time to welcome Birgit Schultes, our newly appointed Chief Scientific Officer. She's an outstanding scientist with over 20 years of experience in drug development and biotechnology, including the clinical development of cell therapies and complex biologic products. She has experience with our entire suite of gene editing technologies and is leading our more concentrated in vivo and ex vivo research efforts. I'll now hand the call over to our Chief Medical Officer, David Lebwohl, who will provide an update on our clinical programs. David? Thanks, John. I'll begin with NTLA-2002 in development for HAE. As John noted, we dosed the first patient with NTLA-2002 in our HAELO phase III study last month. As a reminder, the HAELO study is a 60-patient global randomized double-blind placebo-controlled study. This is an exciting milestone for Intellia and the HAE community. We see high interest for NTLA-2002, which we believe will drive rapid enrollment of our phase III study and commercial uptake once approved. Based on the promising data we've presented thus far, we believe patients could achieve a functional cure. In other words, freedom from HAE attacks and independence from chronically administered prophylactic medications that are commonly used to treat this disease. We plan to present longer-term data from the phase I-II study later this year, including patients in the phase II portion who initially received a 25 mg dose or placebo and were subsequently given the 50 mg dose of 2002 selected for the phase III study. With HAELO well underway, we believe 2002 is well positioned to be the first-ever one-time treatment for people living with HAE. The therapy is administered with a simple infusion and no need for extended steroids or other preparative drugs. This transformative therapy would also be the first approved using in vivo CRISPR gene editing. Let's move on to nex-z in development for the treatment of ATTR amyloidosis. Starting with ATTR amyloidosis with cardiomyopathy, enrollment in the pivotal phase III MAGNITUDE study is progressing ahead of our target enrollment projections, and we expect cumulative enrollment to exceed 550 total patients by year-end. In November, we presented data from the phase I study at the 2024 American Heart Association Scientific Sessions and published the findings in the New England Journal of Medicine. Across all 36 patients, a single dose of nex-z led to rapid, deep, and sustained serum TTR reduction, regardless of baseline levels, through the latest follow-up. At month 12, the mean serum TTR reduction was 90% from baseline, and the mean absolute residual serum TTR concentration was 17 mcg per mL. All patients achieved deep and durable TTR reduction after a one-time infusion. Notably, the TTR reduction occurred rapidly, with the nadir reached at 28 days, when every day matters. Achieving TTR reduction as quickly as possible is crucial in this life-threatening illness. With TTR silencers, the reported mean reduction was approximately 80%, which is not reached until six months after starting chronic treatment. Now, we have observed that the very low levels of circulating TTR seen with nex-z are associated with disease stabilization or improvement across several markers of cardiac progression at month 12 compared to baseline. These favorable results were observed even though half of the patients met criteria for Class III heart failure, and about 30% had a mutated TTR gene, both characteristics of patients with more rapidly worsening disease. This is a significant insight because when patients are untreated, disease progression as measured by these markers is typically evident within 12 months. In addition to the favorable results across markers of cardiac disease progression, we have also observed a low rate of cardiac hospitalizations in our phase I study despite the advanced patient population treated with nex-z. This event rate, if reproduced in our pivotal trial, will be associated with a compelling clinical benefit for patients suffering from ATTR cardiomyopathy. Now on to ATTR amyloidosis with polyneuropathy. Patients are actively screening in the phase III MAGNITUDE-2 study, and we're on track to dose the first patient in the coming weeks. At last November's Investor event, we presented data from the phase I study. Across all 33 patients who received the dose of 0.3 mg per kilogram or higher, the mean serum TTR reduction was 91%, and the mean absolute residual serum TTR concentration was 20 mcg per mL at month 12. Consistent with the observations of ATTR-CM, the rapid, deep, and durable reduction in serum TTR observed in all patients was accompanied by evidence of disease stabilization or improvement across multiple clinical measures of neuropathy. Across NIS, mNIS+7, and mBMI, there were favorable trends of clinical benefit at month 12 compared to baseline levels, with further improvements noted in NIS and mBMI in the part one patients for whom 24 months of follow-up was available. Nex-z has continued to demonstrate a favorable safety and tolerability profile. In recognition of the potential clinical importance of nex-z for the treatment of ATTRv-PN, the FDA granted nex-z Regenerative Medicine Advanced Therapy designation, or RMAT. This will enable closer collaboration with the FDA as we approach a BLA filing in 2028. We look forward to presenting longer-term data from both ATTR-CM and ATTRv-PN patients in the phase I study later this year. The data will include updated measures of clinical efficacy and safety. Regarding our research platform, we're dedicated to using our toolbox to bring forward breakthrough products, both in vivo and ex vivo. You'll hear more about that in the time to come. I'll now hand over the call to Ed, our Chief Financial Officer, who will provide an update on our financial results as of fourth quarter 2024. Thank you, David. Good morning, everyone. Intellia continues to maintain a solid balance sheet that allows us to execute on our pipeline and platform. Our cash, cash equivalents, and marketable securities were approximately $861.7 million as of December 31st, 2024, compared to $1 billion as of December 31st, 2023. Our collaboration revenue was $12.9 million during the fourth quarter of 2024, compared to negative $1.9 million during the fourth quarter of 2023. The $14.8 million increase was mainly driven by the Regeneron license and collaboration agreement. R&D expenses were $116.9 million during the fourth quarter of 2024, compared to $109 million during the fourth quarter of 2023. The $7.9 million increase was primarily driven by the advancement of our lead programs. Stock-based compensation included in R&D expense was $24.4 million for the fourth quarter of 2024. G&A expenses were $32.4 million during the fourth quarter of 2024, compared to $29 million during the prior year quarter. The $3.4 million increase was primarily related to stock-based compensation. Stock-based compensation included in G&A expenses was $15.2 million for the fourth quarter. As we turn our focus to the future, I want to share a few thoughts regarding the restructuring we announced on January 9th and how this changes the complexion of our GAAP operating expenses. In the first quarter of 2025, we expect to incur wind-down costs associated with certain programs like NTLA-3001 that have been discontinued or deprioritized. We expect the difficult decisions made to reduce our workforce and focus our pipeline will result in year-over-year declines in GAAP operating expenses of approximately 5%-10%. The operating leverage and savings created in 2025 are expected to benefit the company over the next couple of years and allow us to make important investments in commercial infrastructure and capabilities while keeping total company expenses below the level of reported results in 2024. While we anticipate greater sales and marketing investments in 2027 to support a successful commercial launch of NTLA-2002 in HAE, the company's capital needs to support multiple phase III studies will begin to diminish during that year as some of these programs complete enrollment and supporting costs naturally wind down. We expect to incur approximately $8 million in severance and other employee termination-related costs. Finally, we expect our cash balance to fund our operating plans into the first half of 2027. Thanks, Ed. In conclusion, Intellia continues to deliver on the promise of gene editing, and we look forward to sharing more clinical progress with you mid-year. With that, we will now open the call for your questions. To do our best to address as many questions as possible, we will only be able to take one question per caller. Operator, you may now open the call for Q&A. We will now begin the question-and-answer session. To ask a question, you may press star then one on your touch-tone 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. Again, please limit yourself to one question. At this time, we will pause momentarily to assemble our roster. The first question comes from Mani Foroohar with SBP Securities. Please go ahead. I don't know about SBP Securities, but thanks for taking the call, guys. Can you help give us a little bit of an update on the tempo of OpEx decline over the course of this year as you execute on the restructuring and looking out over the course of the next several years? There's been a lot of concern from investors around OpEx ramps as you have large pivotal studies growing. Can you clarify that a little bit to the extent to which that OpEx ramp is going to happen or the extent to which we should think more in terms of stabilization from clinical trial costs around the pivotal stage? I know this is a little bit of a compound question, but broadly, if you could help people help us, I suppose, trace out the trajectory of that OpEx over the course of those pivotal trials, that would be really helpful. So, Mani from Leerink, thank you for the question. Obviously, I'd made some comments about the rate of spend and how the restructuring addresses that, but maybe Ed, you can give some additional details of what you think the trajectory of spend is going to be over the coming years here. Yeah, so I'll say a few things thanks to the question, Mani. As we reported operating results this morning, operating expenses on a GAAP basis were up, I think, 7% year-over-year. That's pretty consistent with how the company has had momentum in terms of supporting this evolution from a research-based company into a clinical-stage organization. That evolution, as you know, is expected to continue. So we are committed to fully investing in the clinical programs that we have. That's reflected in the financial guidance that we have provided for 2025. And we are very committed to building the U.S. infrastructure, at least initially, to support the launch of NTLA 2002 in the U.S. In my prepared remarks, I gave commentary to help with 2025 guidance. If I can put a little bit more color on this year in particular, the first quarter will be a little bit noisy. Having announced this on January 9th, we have some wind-down costs associated with some of the programs, but you'll begin to see the effect already in the first quarter, and that benefit will continue to accrue throughout the course of 2025. What makes this dynamic and complicated to be overly prescriptive at this point is the reality of what you described as the three phase III studies that we have ongoing. So those costs are well underway for MAGNITUDE in cardiomyopathy. There are costs now associated with the HAELO study for which we dosed the first patient, and we still expect to dose the first patient in our third phase III study, MAGNITUDE-2. So you'll see some increase in costs that are offsetting the benefits that will come with the restructuring. So too, the cost of the restructuring will be the investment that we make in the U.S. for the commercial infrastructure that's required. As you get beyond 2025, though, we kind of hit steady state. We're fully enrolled in HAELO at that point by 2026. We'll be well on our way within the MAGNITUDE-2 study, and we'll be substantially on our way with MAGNITUDE. So we kind of hit steady state in 2026, and for which we'll get into 2027, costs will begin to naturally sunset and wind down for the HAELO program, then MAGNITUDE-2, and then ultimately MAGNITUDE. So I think it's important just to take a step back. We have made significant restructuring efforts that allow us to make the investments we need in the new priorities for the company, particularly clinically and commercially oriented. It's hard for me to see a scenario in 2025, 2026, or at least through the first part of 2027 where our OpEx is at the level of what we've seen this past year in 2024, so I do think peak operating expenses are behind us. The only thing we'll have to assess closer to the launch will be what incremental investments we need to support NTLA-2002 in HAE. That's really helpful. Thanks for the question. I know you guys have a lot of those online as well. The next question comes from Maury Raycroft with Jefferies. Please go ahead. Hi, good morning. Thanks for taking my question. For nex-z, NTLA-2001, what's the latest regarding your assumptions on phase III events or accrual rate based on longer-term data that you have? Can you say more on what would enable the interim analysis for the MAGNITUDE 3 study at this point? Maybe David, you can address how we're thinking about the event rates for the MAGNITUDE study and lay out some of our initial thinking for the interim analysis. For MAGNITUDE. Yeah. Yeah. Yeah. So this study is, as you know, enrolling at a very good rate. We're ahead of what our projections were. And the evolution of events, we expect to be similar to the other recent studies, acoramidis and vutrisiran. So now there is a lot of data available on events rates in this disease. The management of disease has not changed significantly from the time of those trials. So that's what we're expecting. We haven't said exactly what that is publicly, but you could see it from the historical data. In terms of the interim analysis, what we have said is what we've seen in our trial is from the phase I, our results that look quite favorable. They look very good. There is a low event rate in this population suggesting that the patients are benefiting from therapy both in terms of stabilization and even improvement. This does look different from all the other treatments for ATTR that are out there in which the patients as a population continue to get worse. Based on that, we are obviously going to follow up this data carefully this year. We'll be seeing the evolution of the events in our MAGNITUDE trial. Based on that, we will be able to, in the future, give better estimates about the interim. There is, based on what we're seeing, a good possibility that we could see favorable findings at the interim analysis that would allow us to stop the program earlier. There'll be more details about this from us as time goes on. Got it. That's helpful. Thanks for taking my question. The next question comes from Luca Issi with RBC. Please go ahead. Oh, great. Thanks so much for taking our question. This is Liisa on to Luca. You know, we saw earlier this week that Alnylam is moving forward with a next-generation TTR silencer, and they're proceeding with a pivotal trial design, which is about two times the size of their HELIOS-B trial. So we're just curious if this larger trial size has made you reflect on the MAGNITUDE study and if you are considering making any trial changes, such as increasing your patient population size. Any color here would be helpful. Thanks. Thanks, Lisa. Maybe I can make a couple of comments. And David, if you see fit to add, be my guest. We always look at data, and we always look at what the competition is doing and think about that very carefully in terms of what it means for the program that we're carrying out. Any information that we can gather that helps us think more clearly and accurately about where we're going is always helpful. We do see important differences, however. And David has touched on how we're using some of the clinical data that we've accumulated already in observations that come from patients who have been treated with our own drug. I think for details in terms of how Alnylam is approaching their work, I would encourage you to ask them. However, I imagine that one of the considerations will be they're looking to achieve an effect on top of TAF, which was not seen in the earlier study, and I'm sure they're doubling down to try to capture that. We think we'll be in a really strong position with respect to that category of patients. And also, my guess would be that the proportion of patients who are taking Tafamidis will only increase over time, and so there'll be a far greater proportion of patients taking that drug in their study as that plays out. Those are some top-line comments. I'm sure they have their reasons for some additional details. But with respect to our own work, we're quite pleased with the design we have. As David said, as we continue to look at event rates as they occur in our own phase I patient population, that influences how we think about adjusting, if at all, the trial that we're doing. Just mention one observation about the Alnylam announcement, is that you see that they are talking more and more about how important it is to get to lower levels of TTR. And that was actually used slides very close to our slides showing that as in AL amyloidosis, you see that patients who get very low levels have a better result, as well as in polyneuropathy, the greater the TTR reduction, the better result. So this is good to see in a sense that they are now agreeing with the hypothesis that we have about lowering of TTR. The next question comes from Kostas Biliouris with BMO Capital Markets. Please go ahead. Hi, this is Yuri on for Kostas. Congrats on the progress, and thanks for taking a question. So we have another question on vutrisiran. Can you provide your thoughts on the potential competition from vutrisiran and ATTR-CM that has Q6M dosing, strong TTR knockdown, and can launch around the same time as nex-z? Thank you. Were you asking about Amvuttra? The next gen. Yeah, I'm sorry. It was a little unclear. Well, I don't know if it'll launch around the same time. We'll see how that all plays out. Clearly, people are trying to move very, very quickly to get improved therapies to the market. Our basic perspective, I think, was captured by David, which is this is all about ridding TTR levels from the body to the greatest extent possible. And what we've seen thus far, certainly in the patient population, is that we've gotten to extremely low levels. We've presented not just percentage reduction, but the absolute levels of TTR, which I think is the more meaningful measure just with respect to Amvuttra, which is what we expect to be in the market sooner. We're talking about levels that are about a third with nex-z compared to what's been reported for Amvuttra. We'll see how it plays out with the follow-on compound for Alnylam. But we think that certainly a one-and-done therapy that allows physicians and patients being treated by them to have access to the drug that will have benefits essentially that are in place, we suspect, for the rest of their lives will be critically important. I would point out that when it comes to pricing of these drugs, access to insurance, the authorization procedures that are necessary to have year-on-year dosing, we think we'll be in an advantageous position. We like where we are. As you heard from David, the study is progressing well. We expect that we will meet our objectives and look forward to bringing the product to the market. The next question comes from Gena Wang with Barclays. Please go ahead. Thank you. What makes you feel confident to pick 550 patient numbers by year-end for the enrollment regarding the ATTR cardiomyopathy trial? Does that mean you will complete your trial enrollment in first half 2026 for the total 765 patients? Gena, thanks for the question. You know us well. We underpromise and overdeliver. And that's been the guidelines for how we've run the company and how we talk about who we are, where we're going, and how we do our work. When I say 550 patients by the end of the year, you can count on that being a very highly likely outcome. Yes, we've said that we expect enrollment of the study to be done by 2027. In almost any scenario that we can imagine, even if we were to adjust the trial once we see the Amvuttra data or as we get additional exposure to our own event rates, we are confident that we will fall within that timeframe. But meanwhile, you can count on those 550 patients being enrolled because I see the enrollment rates, and we're not going to give patient-by-patient updates, but it's rolling robustly and doing very well. The next question comes from Joseph Thome with TD Cowen. Please go ahead. Hi there. Good morning, and thank you for taking my question. Maybe just one on sort of the commercial approach here. We've seen some gene therapies enter the market for chronic conditions where there's an established standard of care, and some of them have had some issues with reimbursement and leading the companies to even discontinue it. Pfizer did with their new 3AB gene therapy last week. I guess, what can you do now to kind of make sure that the reimbursement environment is favorable and you can drum up patient interest so that specifically in HAE, where there is that established standard of care, you'll be commercially viable? Thank you. It's an important question. When we think about, I would start by pointing out that we don't think gene therapy, certainly the application of AAV to supply missing genetic function is the relevant comparator. Gene editing, which is a really readily straightforward application procedure, is something quite different from the compounds that you mentioned. I just remind you and the other listeners that when we think about dosing patients with our drug, there is a very straightforward treatment regimen that consists of a single dose of dexamethasone the day before therapy. Then on an outpatient basis, and I repeat, outpatient basis, patients come in, get another dose of dexamethasone, some antihistamines, a two-to-four-hour infusion, and go home. That is the regimen. Extended steroids, biological product handling, etc., just doesn't apply in this case. So with respect to, as you said, drumming up interest, it starts with the performance of the drug. And in the case of HAE, remember what we've presented thus far, an entirely new category of response for these patients. We're talking about following a single application, patients having what we have been calling a functional cure, which is the absence of attacks and the absence of the need to take any ongoing therapy. If you ask patients what they want, that is exactly what they're looking for. So I think a good proxy for how the drug will be received in the marketplace will be the enrollment of the study. And I can report at this time that, well, we've certainly talked about dosing our first patient. We have patients waiting at multiple clinical trial sites. So we expect this to go very, very well. And I think that's an indication of patient response. With respect to payers, that work is already underway, and we think we will have a very favorable profile that we'll be able to present to not just the patients themselves, but to the physicians and the payers. And so we look forward to talking more about that as the year goes on. Great. Thank you very much. The next question comes from Alec Stranahan with Bank of America. Please go ahead. Hey, guys. This is Matthew on for Alex. Thanks for taking our question. Maybe a quick one from us on the HAE phase I to follow-ups. Looking at sort of the incomplete responders, any color on how these patients are doing currently with a longer follow-up period and what you're expecting or hoping to see in the next update in 2025? Thanks for the question. I'll start with a topic sentence or two, and then David can fill in some of the details. But I would just point out that the nomenclature used is probably inappropriate. Every single patient has responded, and every single patient is better off than the patient was before they came into the trial. Most of the patients that we reported in that short 16-week observation period for phase II had a response that we have been terming a functional cure. That is, they've been able to abandon their therapy, and they have no ongoing attacks. We've treated patients or offered to patients who are in the placebo arm in the phase II study or in the 25 mg dose the opportunity to be redosed at the phase III dose of 50 mg, and we'll be in a position to report on those patients and the extended follow-up of the other patients from the phase II group, both for the duration of those patients who have already achieved a functional cure and those patients who had not yet achieved that during the 16-week observation period. I would point out in our phase I work, we've seen that patients mature in terms of the response over time, and we expect that to be occurring as well for the patients in the phase II study. I don't know, David, if you want to provide any other color or have any other. Yeah, that's the most important thing. Obviously, we're going to wait until we give our report about how those patients are doing. But to just reiterate what John has mentioned, what we've seen over time is that patients improve. It may be related to the fact that they now know they're on the drug, but it certainly is what we've been seeing, and we will talk to you more about that and the patients from the phase II later this year. Thanks. The next question comes from Brian Cheng with JP Morgan. Please go ahead. Thanks for taking our questions this morning. Maybe going back to HAE, how should we think through the gating factor as you get ready for the BLA filing? Outside of the clinical package that we're waiting for from HAELO, what are some of the other important items that you need to align between now and then? Thank you. Maybe I'll say a few words, and then David, you could add just in terms of being in a position to file the BLAs. I mean, we've said that our objective is to file a BLA in 2026. I can say next year now. It's becoming quite close. And obviously, based on some of the earlier questions, we're thinking about the market and being prepared for that. But in terms of the product itself and the filing that we're putting in place, obviously, that'll consist of the pre-clinical package, which is done. It has the continued observation of our phase I and phase tII patient population, and then the phase III data that will come from the HAELO study, which we'll be reporting out in the first part of next year as that study completes. It's important to note that the product itself is in really good shape. We're using the commercial form of the product in our phase III trial. So some of those things that can take place where some companies try to bridge to the commercial product, that work is done. And we think we're going to be in a really good position to move very quickly. I would add that we have RMAT designation for the product, and that already puts us in a strong position to deal in an accelerated fashion with the FDA. We've been using that designation to our advantage, and we expect that that will be very meaningful as the review ensues. Anything to add? Just to add that we've had multiple interactions with the FDA, very favorable interactions, and all the things that John is saying, we think we will be ready for the BLA. The next question comes from Rick Bienkowski with Cantor Fitzgerald. Please go ahead. Hey, good morning, and thanks for taking the question. I wanted to follow up on Ed's comments around the marketing build-out for 2002 and the associated costs. Could you comment on how big of a sales force you anticipate needing to launch 2002 and what other preparations need to be built out prior to a commercial launch? And if I heard correctly, it sounded like most of the spend would take place in 2027. So I just wanted to confirm you don't anticipate significant spend here in 2026. Yeah, thanks, Rick. So we're not going to describe the size of the sales force. I think we look at the opportunity as a well-defined market. The patients know each other. There's good patient advocacy groups. It's a well-established market opportunity. We think the footprint to operationalize that is relatively tidy and neat for a company our size. And so we're very confident in our ability to create that infrastructure and have a very successful launch. The investment in this broader commercial consideration started already in 2024. We've brought in senior leadership that has very relevant experience, particularly in HAE. And we have very clear plans in 2025 and 2026 to further extend that leadership team. We've had a number of questions today already on market access and pricing considerations. We've made that important hire. So we have more senior leadership coming on board in 2025. As we get into 2026 with the BLA filing, we're sort of at T minus 24 or T minus 12 months and in. And so we'll think about hiring additional marketing and sales force at that time. So we don't think it's a significant investment relative to the other aspects of our business, particularly the clinical expenses, but we've got a very clear two-year plan on the expertise we need, the hiring plan to achieve that, such that we're ready for launch in 2027. The next question comes from William Pickering with Bernstein. Please go ahead. Hi, thank you for taking the question. Also on HAE, you've talked about how some patients may be experiencing pseudo attacks that will potentially go away with the longer follow-up, especially if they know they've been treated. So it sounds like the data you collect in the long-term observation portion of the phase III could be pretty important to demonstrating functional cure, and I think that would be collected after you submit the original BLA. So I was wondering if you thought about how long you'd want to follow those patients in the long-term observation before submitting a supplemental filing. Would it need to be the full 104 weeks, or could you do it sooner if it's clearly apparent that all the attacks have stopped? Thank you. David, can you outline how we think of long-term follow-up and what's shared with the FDA and when? Yeah, so it is true we won't have the 104 weeks at the time of the initial filing. However, by the time we do have the approval, we will be close to having all that data on the patients, including, recall, many patients crossing over in the phase I and two experience or receiving the drug in phase I and two. So we would think about a supplemental BLA fairly soon after the initial approval as we think about it right now. Of course, we'll be following those patients. We've been here for 15 years. There'll be lots of data to come over. Beyond the 104, yeah, we'll have the 15-year follow-up. The next question comes from Jay Olson with Oppenheimer. Please go ahead. Oh, hey, thanks for providing this update. I wanted to follow up on the commercialization of 2002. It sounds like you're planning on building out a commercial infrastructure in the U.S. I was wondering what your thoughts are for commercializing 2002 outside the U.S. and whether or not that might be a partnership opportunity. Thank you. Thanks for the question. We are focusing primarily on the U.S., and we want to make sure that that is well conceived and well carried out. We are thinking through our options for how we would extend outside the United States, and there's a variety of different approaches that we might pursue, and a partnership option is one of those possibilities, but we haven't decided exactly how we're going to pursue that just yet. Great. Thanks for taking the question. The next question comes from Silvan Türkcan with Citizens JMP. Please go ahead. Yeah, thanks. Thanks for taking my question. Just a quick question about, I guess, the upcoming Quad AI presentation where you plan to show additional quality of life data in HAE. Can you just characterize a little bit what we may see there and how that could help us understand your opportunity in HAE? Thank you. David, do you want to speak? We haven't really shared details of the results yet. Please stand by and watch that presentation. As you can imagine, a therapy that is very easy to take from the beginning and then patients having no events after that, think about your being a patient is very favorable. So look forward to you seeing those results. Thank you. The next question comes from Yanan Zhu with Wells Fargo Securities. Please go ahead. Great. Thanks for taking our questions. Just wondering, for the long-term ATTR data readout this year, what might be the incremental learnings to further inform product profile? Thank you. If I can address that. We would present essentially the results, the categories of assays, etc., that you've already seen extended over on the order of a year or so. What does that mean? As David referenced in earlier comments, we're looking for a continued low rate of progression of the disease. I think it'll be very interesting to see if any additional patients have improved relative to where they were at baseline. Certainly wouldn't rule that out. And we'll look for continued confirmation of what we think is a very low event rate and think through how that relates to our own phase III trial. But bottom line, what we're seeing is the first clinical manifestations of what we think is a very, very low TTR level and what that means for these patients. Thus far, with the results that were published in the New England Journal of Medicine and presented at AHA in November, those results are very, very exciting, and we think very, very important for these patients with severe cardiomyopathy. Great. Thanks for the color. The next question comes from Liisa Bayko with Evercore ISI. Please go ahead. Hi there. Thanks for taking the question. I'd love to just get a little bit more color on how you're thinking about the attack-free rate in the context of your reduction in kallikrein and how you're thinking about potentially trying to evolve this number so it can be a little bit even greater number of patients who are attack-free in phase III. Any color or additional work you've done there? And what's been the preliminary feedback, I guess, on the data as well at this point from the community physicians, etc.? Thanks. Maybe a general comment on kallikrein and its relationship to attacks. It's not strictly linear. There may be some patients that, for just variability in the patient population reasons, react a little bit differently. But what we do know is that as you go below 60% reduction, attack rates start to fall precipitously. And as you get to the very low levels that we've achieved, it's even beyond that. So part of the challenge for observing these attacks are the consequences of a double-blind study and medical treatment for patients who don't know if they've received drug or not act on any, let's say, twitch or early indication that they may or may not be having an attack, which is what the medical guidance is for them to behave. So smaller, shorter-term studies can be influenced by that behavior, which, again, is appropriate medical therapy. We think that with extended observation, that will likely lessen. I think that an important aspect from what we've seen in work already presented, particularly when we look at the phase I results and add that to the phase II results, is the longer patients go, the more confident they are, and we see attack rates falling to very, very low levels. I think there'll be an opportunity later this year to see how that plays out with additional patients and the additional follow-up that we've accumulated. Just mentioning the phase III, one difference in the phase III is we do follow the patients for a longer period of time. Instead of the 16-week follow-up, the follow-up is between weeks 5 and 28, which we also think will support seeing a better result there. Thank you. The next question comes from Myles Minter with William Blair. Please go ahead. Hey, team. This is John on for Myles. Thanks so much for taking our question. I was just wondering if you could give us any updates on how stabilizer usage in the MAGNITUDE study is tracking compared to your original projections, which I believe were for around 50% usage in the study. Thanks. Yeah, I think we had said there would be at least 50%, but David, you want to give some insights? Yeah. What we are seeing is greater usage of tafamidis around the world. In particular, the UK has now supplied that to the patients there. We actually think this is actually going in a good direction in terms of our ultimate results because what we think is important to show is that we can have a significant benefit over tafamidis that hasn't been shown yet for any other agent. And that finding we think will be part of superior efficacy that we might see that would drive the usage of our drug. Helpful. Thank you. The next question comes from David Lebowitz with Citi. Please go ahead. Thank you very much for taking my question. This is a follow-up from an earlier question. On HAE, there's a lot of talk about the possibility of a functional cure. I would imagine that that's not the bar ultimately that you see for success. What do you see as the bar for success? We think the functional cure aspect is the key driver for how patients are going to want to use this drug. What we see in our market research, whether it's patients or physicians, is that patients are not looking for marginal improvements in the interval between using prophylaxis or on-demand therapy that takes effect faster than existing therapy. That market is largely satisfied, as what we can tell. What patients are looking for is a completely new category of response. And that is, in fact, the functional cure basis. We think we will have many patients who are achieving functional care. In fact, what we've seen thus far is the large majority of patients already have achieved that in early observation. So that, I think, will be a very, very important driver. I would add that on the more routine measurements of attack rate reductions, we have data that is competitive with any other agent that's been presented. And as observation periods are extended, what we see is that attack rates for any of those patients thus far who have continued to have attacks, the attack rate is very, very low. So we think on any category of potential competition, we're in a really strong position. Thank you so much for the answer. 75 to the chart. The next question comes from Andy Chen with Wolfe Research. Please go ahead. Hey, Brandon on for Andy. Another question from us on competition and enrolling. So by our calculation, HELIOS-B enrolled about 380 patients per year. And you're planning to do 375 per year as a follow-up therapy, which appears to be quite fast. Is it reasonable to use the ratio between that 380 and 275 to determine doctor enthusiasm and patient enthusiasm for your TTR gene therapy? And do you have any other hard quantitative metrics to show the magnitude of patient enthusiasm for your product compared to competition? Thank you. It's not unreasonable to use ratios like that, but at best, that is a very, very blunt instrument in terms of determining how enrollment's going. I would start by just using the numbers we've provided. As I said earlier in the call, there's a very, very high likelihood that we will have in excess of those 550 patients. We expect to be in a position where the study finishes well within the guidance that we've already given. If there's reason to give additional updates as time goes on, we'll consider that. I would not look for routine updates in terms of the numbers of patients that are coming into the study. And just to mention what we're seeing, there is a very high level of enthusiasm from the physicians, and we're hearing it coming through as well from their patients joining the trial. So we're excited about what we're seeing in the field. Thank you. The next question comes from Terence Flynn with Morgan Stanley. Please go ahead. Hi. Thanks for taking the questions. I was just wondering on the Regeneron collaboration, just wondering if you can walk us through kind of the next milestones that we should anticipate here or when we could learn more about the profile? Thank you. Just a couple of high-level comments. The Regeneron collaboration with nex-z is a 25% interest on their part and 75% interest on ours. That's been in place for some time now. There is a point where they'll need to make a determination whether or not they're going to opt in for a co-commercialization partnership. And we look forward to seeing that decision and planning around that. So I don't know, Ed, if you think there's any other milestones that are important to mention at this point. No, I think that's it. And just to double down on John's point, it's a co-promotion in the U.S. that they have the right. The economics don't change. And so what's going to drive that is sort of the timeline to commercialization. As we think about PN indication in particular, I think we've been very prudent in sort of providing guidance on timelines for that. But as we think about alternatives in terms of interim analyses or accelerated approval processes, that timeline could come in. So we're not necessarily terribly far away from that, but that next milestone for them to opt into a U.S. co-promote is an important one, and it's on the horizon. The next question comes from Salveen Richter with Goldman Sachs. Please go ahead. Hey, this is Marc on for Salveen. Thanks so much for taking our question. You guys briefly mentioned earlier that you discontinued NTLA-3001 for a second-generation approach. I was wondering if you could talk more about that. Were there any signals you were seeing with the original 3001 that were unfavorable and any commentary on the second-generation approach? There was nothing on NTLA-3001 from a clinical point of view. We stopped just short of dosing a patient. The preclinical studies we've talked about in the past, as we look at that area, we made a decision on how to pursue NTLA-3001 in the context of the prioritization and restructuring that we announced in January. And we think that the gene writer approach that we've described elsewhere has significant utility in the disease. And at an appropriate time, we'll be in a position to talk about that. This concludes the question-and-answer session and Intellia Therapeutics' Fourth Quarter and Full Year 2024 Financial Results Conference call. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect your.