Intellia Therapeutics, Inc.

Hello, and welcome to Intellia Therapeutics' third quarter 2025 financial results conference call. My name is Rocco, and I will be your conference operator today. Please be advised that today's conference is being recorded. I will now turn the conference over to Jason Fredette, Vice President of Investment Relations and Corporate Communications at Intellia. Please proceed, sir.

Thank you, Rocco, and hello, everyone. Earlier this afternoon, we issued a press release and filed our 10-Q, outlining our recent business updates and our third quarter financial results. These documents can be found on the Investors and Media section of Intellia's website at intelliatx.com. At this time, I would like to take a moment to remind listeners that during this call, Intellia management may make certain forward-looking statements. We ask that you refer to our SEC filings, available at scc.gov for a discussion of potential risks and uncertainties. All information presented on this call is current as of today, and Intelia undertakes no duty to update this information unless required by law. Joining me on the call are John Leonard, our Chief Executive Officer, and Ed Dulac, our Chief Financial Officer. With that, I'll turn the call over to John. Thanks, Jason.

And thanks to all of you who have tuned in for today's call. In terms of the agenda for today, we'll begin with the status of our NEXE program in ATTR amyloidosis, since that is obviously top of mind for all of you. We then will provide an update on the significant progress we have made with LanvoZ, which is being developed as a potential one-time treatment for patients with hereditary angioedema, or HAE. And we will close with Ed's financial review. First, for NEXE. Since the start of 2024, we've been enrolling patients in magnitude or phase three clinical trial for ATTR amyloidosis with cardiomyopathy. And we've been enrolling magnitude two for patients with hereditary ATTR amyloidosis with polyneuropathy since the start of 2025. Both trials have advanced rapidly, which we believe demonstrates patients' interest in a potential one-time treatment option. On October 24th, a patient was admitted to the hospital after reporting abdominal pain to his principal investigator. This is a patient with ATTR cardiomyopathy in his early 80s who enrolled in magnitude and received a dose of Nexi on September 30th. The patient's labs showed that his AST and ALT levels exceeded three times the upper limit of normal, and that his bilirubin exceeded two times the upper limit of normal. These levels triggered a protocol-specified pause on patient dosing and screening for magnitude in the interest of patient safety. We decided to also pause patient dosing and screening in magnitude 2 as a precaution. On October 29th, the FDA notified us verbally that it had placed a clinical hold on magnitude and magnitude 2. We are now awaiting the FDA's formal clinical hold letter. We were very saddened to learn that the patient passed away last night. We have been advised by the treating physician that this is a case with complicating comorbidities and the case is being further evaluated. Since learning of this case, we've taken a number of actions in the interest of patient safety. For instance, we've mandated that clinical sites collect additional labs from patients in the initial weeks following dosing to detect potential liver elevation sooner. An internal team has been closely reviewing the blinded safety data, baseline characteristics, among other factors to identify potential contributors to the liver-related events seen in magnitude. We've been working with the trial's independent data safety monitoring committees as we consider other potential monitoring and risk mitigation strategies. And of course, we are engaging with global regulatory authorities and other stakeholders to understand their perspectives, concerns, and requirements so we can develop a plan that would allow us to resume enrollment as soon as appropriate. Not surprisingly, given the clinical hold, we are unable to maintain our milestone guidance for NEXE, and we expect to provide an update once we finalize a plan with regulators. Simply put, a lot has transpired over the past couple weeks and in recent hours, and there is still much work ahead. There's a lot of focus on the safety profile of Nexi at this stage, as there should be. That said, we continue to believe in this product candidate's potential to address important omit needs for patients with ATTR amyloidosis. This is based on a few key factors. First, ATTR amyloidosis is a disease with high mortality. While undeniable progress has been made in its treatment, Current therapies only slow its advance, and most patients continue to face progressive morbidity and mortality. Second, we've enrolled more than 650 patients in magnitude and 47 patients in magnitude 2. To date, grade 4 liver transaminase elevations have been reported in less than 1% of all patients enrolled in magnitude. Each of these cases has been observed approximately three to five weeks following randomization and dosing. There have been no grade four liver transaminase elevations in magnitude two. And third, we are highly encouraged by the data from our ongoing phase one clinical trial of Nexi. On Monday, in a late breaker oral session at the 2025 AHA scientific sessions in New Orleans, we will have the opportunity to share longer term data for Nexi that we believe demonstrates its potential to improve various disease measures and mortality Let's move on to WAMBO-Z, which is being investigated in our ongoing Halo Phase III clinical trial for HAE. Over the course of 2025, we've made considerable progress in this trial. Enrollment was completed in September, less than nine months after we dosed our first patient. This puts us on track to share top-line data by mid-2026 submit a BLA to the FDA in the second half of 2026, and prepare for an anticipated commercial launch in the U.S. in first half of 2027. We believe La Vozzi could completely redefine the HAE treatment landscape. We aim to reset expectations and the standard of care for patients living with a stabilitating disease by completely eliminating attacks and the need for other HAE medications for a majority of patients all with one dose. This Saturday, at the American College of Allergy, Asthma, and Immunology Annual Scientific Meeting in Orlando, we will be presenting longer-term safety and efficacy data from all of the patients who received a 50-milligram dose of LomboZ in our Phase 1-2 clinical trial. I'll now hand over the call to Ed, our Chief Financial Officer, who will provide an update on our financial results for the third quarter 2025.

Thank you, John, and good evening, everyone. Intellia continues to maintain a solid balance sheet that allows us to execute on our clinical pipeline and build important capabilities required for future success. Our cash, cash equivalents, and marketable securities were $669.9 million as of September 30, 2025 compared to $861.7 million as of December 31, 2024. During the third quarter, we raised approximately $115 million from our ATM facility. When combined with the benefits of the restructuring initiatives we implemented in early 2025, this enables us to extend our cash runway into mid-2027. and through Lambo Z's anticipated commercial launch in the U.S. for HAE. Collaboration revenue was $13.8 million during the third quarter of 2025, compared to $9.1 million during the prior year quarter. The $4.7 million increase was mainly driven by cost reimbursements related to our collaboration with Regeneron Pharmaceuticals. R&D expenses were $94.7 million during the third quarter of 2025, compared to $123.4 million during the prior year quarter. The $28.7 million decrease was primarily driven by employee-related expenses, stock-based compensation, research materials, and contracted services, offset by an increase in the advancement of our lead programs. Stock-based compensation expense included within R&D was $12.2 million for the third quarter of 2025. G&A expenses were $30.5 million during the third quarter of 2025 compared to $30.5 million during the prior year quarter. Stock-based compensation expense included within G&A was $7.4 million for the third quarter of 2025. Finally, net loss for the third quarter of 2025 was $101.3 million, down from $135.7 million for the prior year quarter. We continue to expect a year-over-year decline in GAAP operating expenses of at least 10%. And as stated before, our cash runway is expected to fund operations into the middle of 2027. With that, we are ready to begin our question and answer session. Before we do, we would like to let you know in advance that we will be unable to answer some of your questions given a variety of factors, including the fact that we are still awaiting the FDA's clinical hold letter and a more thorough evaluation of the patient's case. We appreciate your patience and understanding. Operator, would you please open the line for questions?

Absolutely. To ask a question, you may press star then one on your telephone keypad. If you're using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star then two. We ask that you please limit yourself to one question. Today's first question comes from Gina Wong with Barclays. Please go ahead.

Thank you for taking my questions. I'm really sorry to hear the unfortunate event. I know you are still collecting tons of data, but just wondering if any initial hypothesis of the reason for liver enzyme elevation since, you know, this is a one month after dosing, is that because of lipid nanoparticle, Cas9, or age-related or disease? You know, any initial thoughts, that would be fantastic. And the related question is, You know, you share the color on grade four, less than 1% in ATTR cardiomyopsy. How's that rate for ATTR polyneuropsy and the HAE patient population?

So, Gina, thank you for the question. At this point in time, we can only speculate, which we're not going to do, in terms of What's the source of the liver function test abnormalities? As you pointed out in your question, we've seen across the entire study with over 650 patients enrolled, an incidence of less than 1%. This particular case is distinct from what we've seen. It was a very complicated clinical course with other comorbidities that may have had some influence in the outcome of the patient. Of the other cases that have occurred, all of those cases have either resolved or are resolving, and no one is in the hospital.

Thank you. And our next question today comes from Mari Raycroft with Jefferies. Please go ahead.

Hi. Thank you for taking my question. Maybe one more on the patient. I know you can't say much, but you mentioned the other comorbidities. Can you say what those were and also potentially whether the patient was managed in the United States or ex-US? And then, yeah, I guess if you can't answer those, if you talk about just potential risk mitigation strategies that you could implement going forward.

Yeah. At this point, Maury, we can't go into the comorbidities. I can only say that the patient had a very complicated medical course. and these other comorbidities may have influenced the ultimate outcome along with the hepatic abnormalities. We're not commenting on geography. I can only assure you that the patient received what we believe to be excellent medical care, and we have no reason to believe that there was any shortfall in taking care of the patient. With respect to risk mitigation strategies, that's ongoing work. As you might imagine, we're doing as comprehensive analysis as we're able to do, looking at all of the data we've collected, coming up with any potential hypothesis. The ultimate goal would be to find a way to exclude patients who may be at risk, should we identify it or impose interventions that could deal with the liver function test abnormalities if they do occur.

Thank you. And our next question today comes from Alex Shanahan with Bank of America. Please go ahead.

Hey, guys. Thanks for taking our question. I guess how many ATTR patients are currently within that, you know, three to five-week post-dose window on the study right now? Thank you.

I can't give you precise numbers, but it's the vast majority of patients have passed through it. And with each passing day, there's a smaller and smaller set of patients who have yet to go through it. All right. Thank you.

Thank you. And our next question today comes from Manny Ferubar with Lyric Partners. Please go ahead.

Hey, guys. My condolences. A tough outcome for the patient for sure. Can we dive in a little bit on a hypothetical that I've received from a number of clients, which is, if this gold were to remain for an extended period of time, what does that mean for the ongoing op-ed spend of the company? I.e., I know it extends the duration to whenever we get a potential pivotal outcome for the study, but does it change the total amount of spend over the course of the study? Is your spend at a normal level during this hold? Are at least some activities interrupted? How should we think about that from a financial modeling perspective, recognizing that that, of course, is a secondary concern to the moral obligations of the patient?

Thanks for the questions. It was a little garbled, Manny, but I think you were asking how does the hold play into the financial model? runway of the company and how do we manage through it? I think there's going to be a two-part answer. Ed can speak to the runway and how we currently view it. As you can imagine, our priority is going through the data and coming up with the best possible path forward. And that is job one at this point. And it's something that we're working very, very hard to do. The goal is to be up and running as soon as appropriate and so that we can regain what was very substantial momentum. As we said, we had enrolled over 650 patients, and that's, I think, just a really stellar record. But maybe, Ed, you can say a few words about the runway and how we're thinking about this may impact that.

Of course. Thanks, John. Yeah, I would say it's premature to be too precise with any guidance, but as we sit here today, based on the information we know, As we indicated, the timelines and the plans for Lambo Z are unabated, so we continue to operationalize that study as we have been. While we are in clinical hold and therefore unable to enroll new patients or screen for patients, As we reported, we do have now more than 650 patients in magnitude, and we have 47 patients on magnitude 2 that still remain on study, are still being managed according to the protocol. So the appropriate follow-up for that will continue as we work our way through our clinical hold. Maybe to your point, the only thing that changes is the incremental cost of dosing per patient. So in many ways, near term, as we work our way through the clinical hold, you could argue we're going to spend a little bit less money. We'll still have program management fees related to CRO costs and our own internal work, but the incremental cost per patient will not occur during this time. And we really reassess what the timelines look like once we have a clearer path on getting off the clinical hold. And then we don't talk much about it, but we do have research priorities within the organization, and that continues. So, again, sitting here today, we don't see a substantial shift in the operating needs or the cash needs of the company, and we'll look to reevaluate that in a collaborative effort, including with the regulatory authorities in the weeks and months to come.

Thank you. And our next question comes from Yanen Zhu with Wells Fargo Securities. Please go ahead.

Oh, great. Thanks for taking our questions, and sorry to hear the update about the patient. I was wondering, when you talk about comorbidities, is there any liver-related comorbidities? And then additionally, you know, when you talk about less than 1% of the enrolled patients have grade four enzyme elevation, could you, are you able to disclose how many cases of grade four liver enzyme situation has happened and how many are still resolving? Thank you.

Thanks, Yann. The 1% applies to The more than 650 patients, I remind you this is an ongoing placebo-controlled double-blinded study. And what's attributed to what in precise numbers by case, et cetera, is not possible for us to get into. But you should think of this as less than 1% across that number. With respect to the comorbidities, it's not something we can get into at this point. I can assure you that there's an ongoing evaluation where we'll get more information that I think will be very helpful to understand the clinical course that this patient experienced. And we'll present that information at the appropriate time once we have it. But until that information is in our hands, I think it's premature to discuss.

Thank you, and our next question today comes from Troy Lankford with TD Calum. Please go ahead.

Hi, thanks for taking our question, and my condolences on the unfortunate update today. I guess just to kind of like follow on to some of the previous questions, is there anything that you all can do preclinically to try and disprove any sort of causation between next-d treatment and the safety event? And then I know you all can't say that much, but is there – If you all can provide any sort of color on potential timelines or next steps with the FDA around reinitiation of the study, I think that would help a lot.

Yeah. I can't speak for the FDA, and we're certainly waiting for the letter that we expect to receive from them, the clinical hold letter. And that will be obviously very influential in how we think about going about getting back the protocol up and running. With respect to preclinically evaluating, it's hard to know at this point. But as I said before, we're looking at every source of information that we have to see if there is some way that we can identify patients who may be at increased risk and When we find that information, I'm sure we'll be talking about it in a way that'll be meaningful, but only when we're convinced that we have that information well in hand.

Thank you. And our next question today comes from Brian Chang of JPMorgan. Please go ahead.

Hey, guys. Thanks for taking our question this afternoon or this evening. Ed, earlier this year in January, I remember that you said that the ATM would be used at an opportunistic time. And looking at your 10Q, 128 million this quarter was executed through the ATM. What changed your mind here in executing the ATM? And is the ATM your path going forward in raising additional cash? Thank you.

Brian, thanks for the question. And Ed, do you want to talk about how we think about the various tools for raising funds?

Yeah. So we've often talked about ATM as not a primary strategy, but a tool within the toolkit to raise capital for the company. We're not going to comment on specifics going forward, but we do believe in having options. And so whether it's traditional equity, that's often done in biotech, including the use of the ATM. You should expect us to continue to have that available to us and potentially circumstances dependent to utilize that strategy. But there are others for a company like ours that is approaching phase three data and has a BLA filing. And so whether it's collaborations that we could consider, debt structures or more creative financing opportunities, I do believe we have the balance sheet to get to those milestones and multiple options to consider to improve the balance sheet in the future.

Thank you. And our next question today comes from Jay Olson at Oppenheimer. Please go ahead.

Oh, hey, we're sorry to hear this news. Since you mentioned there are no grade four liver transaminase elevations in magnitude two, can you just talk about any notable differences in the baseline characteristics for magnitude versus magnitude two and any particular changes you may be considering to the enrollment criteria? Thank you.

The primary difference is the indication itself. Patients in magnitude 2, as I'm sure you know, have polyneuropathy, which is a manifestation of TTR amyloidosis. And in magnitude, it's cardiomyopathy as the primary manifestation. Other than that, the differences tend to be really minimal, and I would think of it as on a continuum with respect to the drug as a whole.

Thank you. And our next question today comes from Salveen Richter with Goldman Sachs. Please go ahead.

Good afternoon. Thanks for taking my question. I was just wondering if we step back, whether you could just help us understand you know, the steps from here, you know, apart from the FDA letter? Thank you.

Well, central to the way forward is the FDA letter and coming to terms with what they'll require. But you can imagine that we're already working very hard with all of the information that we've accumulated. We're looking clinical information, preclinical information, manufacturing, et cetera. All of this is part of a very, very comprehensive analysis to see if there is any indication of a particular thing or a characteristic that puts patients at risk. While we do that, we wait for the FDA and the information that it requests. And as that information, as that letter becomes available to us, we'll think through what we need to do. And we believe we'll have the tools to address what we imagine may be things that are of interest to them. And we will work very, very closely with them to come up with the best possible plan that we think is an appropriate way to mitigate risk.

Thank you. And our next question comes from Jake Allen at Baird. Please go ahead.

Hi. Thanks for taking the questions, and I also wanted to pass along my condolences. A tough update here. Stepping back, I was hoping you could help remind us of the differences in the construct as it relates to the ATTR candidate as compared to HAE. I believe they're using different LNPs, but could you help me understand that? And then also, obviously, targeting different genetic diseases as well. Thank you so much.

Thanks for the question. As we've shared elsewhere, the LMP is the same. That is the lipid constituents. The mRNA is the same. It's the guide RNA that differs between the two. But that leads to a totally different sort of outcome in patients. So ultimately, the patients themselves are different. The disease that they have is different, and the gene that is targeted is different. So we view Lombozi and Nexi as absolutely distinct from each other, and the patient experience thus far aligns with that.

Thank you. And our next question comes from Sylvan Turkin with Citizens. Please go ahead.

Thanks for taking my questions this evening, and my condolences as well. to the clinical team. My question is, do you add any additional liver monitoring in the Longvo Z trial in HAE? And I'm asking because, you know, if the percentage is less than 1% on 650 patients, if you do the math, less than a patient in an HAE trial, right? So, Any chances you can pick up slight liver increases there before there's a potential launch?

Thank you. Well, first of all, the LOMVOSI HALO trial is completely enrolled. And as we said in a prior update, that patient population is fully enrolled, and they've all passed through this initial window for the patients randomized in the primary evaluation part of the study. The monitoring that we have is not as intense as what we have in the NEXI trial. But again, our experience to date has been quite distinct. And if there were an issue that we would expect to be able to see it with the monitoring that we do have, I would say that an additional aspect to point out is that on Saturday, as we said in our comments, we'll be presenting at the AACI meeting the combined pooled experience that we have of all patients who have received a 50 milligram dose for Lombosi. And you'll be able to see the same, not only clinical performance, but safety performance that we're seeing ourselves.

Thank you, and our next question today comes from Jonathan Miller at Evercore ISI. Please go ahead.

Hi, guys. Thanks for taking my question, and my condolences as well to the family of the patient and to you guys to update. I guess I would look to dig further into the comprehensive analysis that you said you were doing. Obviously, you're going back over the individual patient, but how deep are you going across both the NEXE and the LONVOZI patient populations thus far, and can you maybe put some guidelines around what sorts of cases you would consider to be possibly fitting the pattern versus the sorts of cases you would be excluding? I'm thinking of patients who have subclinical liver enzyme elevations that might fit a timing pattern. How do you adjudicate whether you think those are part of this signal or not?

Well, the first point I would make is that the Lanvosi experience is distinct from what we see with Nexi. But with respect to Nexi, you're correct in that we'll have more information coming from this particular patient, which I think can be potentially very illuminating in terms of understanding the patient's clinical course. But other than that, when I say comprehensive analysis, I mean comprehensive. And we're looking broadly, we're looking deeply, and the sorts of things that you're raising are all on the list of things for us to consider.

Thank you. And our next question comes from Whitney Ijen with Canaccord. Please go ahead.

Hey, guys. This is Angela Chan on for Whitney. Thank you for taking our question. Also want to express our condolences. So we understand you'll be increasing the monitoring of lab values after dosing, but can you give us a little bit more color on how often the lab values are being monitored previously? In this one patient, the levels were discovered when he had abdominal pain, but in the other patients who did have elevations, how was that discovered?

We've always monitored in the window, and that's how we are aware of what we've seen thus far. We've not only picked this up as a result of more intense monitoring, but what we've done as more information has become available to us is move to at least weekly monitoring for the first few weeks after a patient has been exposed to the drug, to see if we're able to actually characterize the full course of what happens when it happens. Again, it's occurring in less than 1% of all of the patients that have been enrolled in the trial. And the notion there is that if there's information that can be acted on, that that's in the hands of the physicians who are caring for these patients.

Thank you. And our next question today comes from Luca Issi with RBC Capital Market. Please go ahead.

Hi, team. This is Shelby on for Luca, and thanks for taking the question. Maybe a quick one on HAE. We appreciate that you don't see a lot of read-through here, but do you think the patient death in TTR could hurt the potential commercial opportunity for the syndication? Any color there, much appreciated. Thanks.

I can only speculate at this time. I think between where we are today and completing a readout of our Phase III trial for HALO, there's a lot of time and information to be accumulated that will characterize the benefit-risk profile for Lambo Z. Again, I would point you to a presentation that will be given on Saturday, A couple of days from now, where the combined experience of all of the patients, 32, that have received 50 milligrams and the efficacy profile, along with the safety profile, is there for everyone to see. And we think that that is largely going to be representative of what we think we'll see in our phase three or clinical use of the product more broadly. So until we get all of that information, I don't think we're going to be in a position to talk about the commercial opportunity. But thus far, we very much like what we see.

Thank you. And our final question today comes from Miles Minter with William Blair. Please go ahead.

Hi. Thanks for taking the questions, and sorry to hear about the update. Straightforward one. Do you have a cause of death? This is a cardiomyopathy trial. You will have deaths in the trial, unfortunately. Just wondering whether this was a CV-related event or, as it seems, maybe something beyond that. Thanks.

If I heard you right, I'm sorry, I was a little garbled. We'll give the information once we have all of the final material in hand. There are some things that are being done after the death to give us additional insights, and at the appropriate time, we'll share all that.

Thank you. And that concludes our question and answer session. I'd like to turn the conference back over to CEO John Leonard for closing remarks.

So thank you all for joining us. We will look forward to speaking with you again when we have meaningful updates to share.

you. This concludes today's conference call. We thank you all for attending today's presentation. You may now disconnect your lines and have a wonderful day.