Intellia Therapeutics, Inc. (NTLA) May 20, 2026 Conference Transcript

All right, great. Hello, everybody. Luke AC, Senior Biotech Analyst here at RBC Capital Market. Today's our great privilege to have Intelia as part of our 2026 Global Healthcare Conference. Representing the company, we have John Leonard, Chief Executive Officer. John, thanks so much for joining us. How are you doing today? I'm doing well. It's a pleasure to be here. Good to see you. Good to see you too. Yeah, good to see you too. John, we have a long list of questions here, but maybe before we go into the specifics and we ask you about all the individual programs, it would be great if you can maybe step back and give us kind of a big picture or overview of what progress has the organization made over the last few months and maybe what's ahead here for Italia. Yeah, super.

Well, we're very, very proud to say that we have completed the very first phase three program for an InVivo CRISPR product. I mean, we've been pioneers since the very early days of the CRISPR era by being the first people to go and do InVivo genome editing. And as I'm sure you've seen, others are going into that space as well. But it's pioneering the use of lipid nanoparticles, reporting the first cases of any human genes being edited in people. And we did that first and second company to do that. And so what we're seeing is the fruition of that work. Data we released was phase three results for hereditary angioedema. I suspect we'll probably be talking a little bit about the data. but we were excited that we were able to get results that confirm what we'd seen in some of the earlier studies where patients who get this outpatient IV therapy in the vast majority of cases are essentially devoid of their disease afterwards. I think that shows the promise of CRISPR. The second program, which is a larger program, is for the treatment of transdiretin the TTR amyloidosis, two primary indications of that, polyneuropathy and cardiomyopathy, where we've rebooted our phase three programs and are excited about completing that work. So, and then we still have, as you might imagine, a lot of work going on on the research side, things that we'll talk about down the road, but we try to be pioneering yet again and doing some things that are a little outside the standard approach. Gotcha.

That's super helpful. Well, let's maybe double click here on Hereditary Angioedema. I know you have started the rolling BLA submissions and you're obviously hoping to complete that by second half of the year. Maybe just remind us what are the benefits of doing a rolling BLA submissions versus kind of standard BLA submissions. And then how confident are you in, well, I shouldn't say maybe how confident, but like how should we think about priority review versus standard review in the context of obviously now there's a bunch of other therapies available there for HAE?

Yeah. I mean, we benefit not only in HAE, but also the TTR program by having RMAT designation. And what that affords us is the opportunity to have frequent engagement with the FDA. And we've used that to our advantage to get a really good notion of what they're looking for. And we've shared the progress that we've made. Part of that also enables the rolling BLA. We had started that before we released our phase three data. And so you can imagine the preclinical work, some of the CMC things, which has been largely put to bed, if you will. So, you know, the overall advantages have to do with an early start, the likelihood of having a priority review, and some opportunities for having this whole thing being foreshortened. I mean, we'll know more when the filing is complete, which we've said will be in the second half of the year. Again, I would say we try to under-promise and over-deliver, have things moving along at a quite prodigious rate. And at that point, we'll know a little bit more about the trajectory of that review and other things that lie ahead. Gotcha.

Maybe kind of higher level, you know, one of the common conversations we have with investors is, you know, data is great, but there's also a lot of other therapeutical alternatives available out there where you're looking at Donzera or TechZyro or some of the CSL drugs or some of the others. So, you know, again, the comparative landscape continues to intensify here. Just maybe remind us why you think you're different and why you think that a relatively large proportion of patients will actually pick a one-and-done therapy that comes, you know, with the permanent editing of your liver and other kind of considerations there.

I mean, there's no doubt that it's better to be a patient with HHE today than it was 10 years ago. I mean, the pharmacopoeia has moved forward. That's good for patients. And that really falls into, you know, two broad categories. Patients take long-term prophylaxis. Some patients take on-demand therapy, and there's a lot of overlap between those two. So drugs are, as I say, you know, are reasonably effective in this patient population. The challenge that patients have, however, lies in, you know, what they experienced as they do that. So most patients continue to have attacks when you go out and, you know, and we've done this work, as you might imagine, just asking, you know, free range patients, well over 80% of them will report having had attacks in the last year. So from the standpoint of control of the disease, it's better, it's not perfect. All of these patients take drugs that are typically very expensive, which require ongoing prior authorizations, at least annually, sometimes twice a year, depending on the drug and the carrier. And that represents, in addition to the disease itself, a burden for these patients. And it's, you know, the living with the disease and the uncertainty of when you're going to have an attack, but also living with the uncertainty of knowing that you're going to continue to be able to have access to the drug. So when they have jobs, and most of these patients do have commercial insurance, they don't change jobs. I mean, they adhere to that because they're afraid that as they move into other places, there'll be real limitations. And so whether it's the experience they have with respect to the disease itself, accessing the therapy, taking a therapy, there's a burden that patients have to contend with. And the promise of a one-and-done approach, the potential of it, is that much, if not most, or all of that can be addressed. What we've shown in the data that we've presented thus far is that following a single application, this is an outpatient therapy, there's no conditioning, there's no virus, these are all synthetic molecules, patients get a simple regimen the day before and on the day of therapy, they're done and they go home. And with that, in most cases, over time, these patients get to a state of no attacks and no therapy. And so if you look across the program from the time that we started phase one through phase two and now through phase three, essentially all, nearly all of these patients, once they get the drug, are off long-term prophylaxis. And for any patient that has an attack, which is the small minority of these patients, the utilization rate is a fraction of what it was previously. So the patient experience improves, the certainty of access goes up, the anxiety that comes with whether or not I'm going to have access to my drug or any interruptions goes away. And when you look at this, we've said, you know, from a financial point of view, we will not be setting any new records in terms of sky high prices, even though, you know, some of the traditional measures would suggest that we should, we will not. This will be resource sparing across the board, to payers, to patients, and to the physicians to take care of them. So I think it's a win-win across the board.

You're not. obviously you're not commenting directly on price. I know it's premature and, you know, there's still a lot of things that has to go through it, but would it still be fair for us to assume that the price is going to be higher than, you know, whatever is the annual price of Donzera or Texira or some of the drugs that are available out there? And if so, will the payer get it? Meaning, will the payer understand the pharmacoeconomic value of your drug and we'll think two, three, four years down the line and not, I'm going to just reimburse whatever is cheaper today because the price tag is probably going to be lower from an annual standpoint.

It's like, I guess, how do you think about all that? No, it's an important question. I mean, when you have a one and done therapy, it is a different model than if you have chronic therapy, which is what applies to a large part of the pharmacopeia. Yes, I think it's a reasonably safe assumption it would be more than the annual use of or cost of those typical agents. The way payers usually look at this and we look at similarities, there's some multiple of a reference product and that might range from two to five times typically. What goes into the thinking of that is the outcomes themselves, the quality of that response. I mean, we have essentially all of our patients responding. The durability, we are now on our fourth year. We have not a single patient who's lost the effect thus far. We don't expect that to change as far as we can tell. When we look across programs to TTR, I include them who are now the earliest treated patients out in their sixth year. We don't have a single example of patients losing effect. So from the standpoint of, you know, when they look for analogs, they're not good ones. I mean, some of the hemophilia products were valiant attempts, but fell short in terms of either the outcomes and or the durability of the response that doesn't apply to us. And, you know, it's interesting when these patients typically, they're a little different from standard sort of commercial and commercially insured patients where our data says that they stay with a carrier for over four years. And so, you know, as we think about kind of the standard models, these insurers should see a payback. And certainly across, you know, as patients move amongst carriers, clearly they will see a payback. Gotcha. Gotcha.

That's helpful. I'm just kind of reflecting back on the commentary you just made around we don't have patients losing effect, right, which I think is an important distinction of your therapy versus others. In that context, are you potentially considering value-based agreement with payers where, you know, if a patient does lose that efficacy and it will require to go back to a prophylactic regimen to any capacity to get some sort of discount or price cut or reimbursements or, I guess, how should you think about value-based agreement in that context?

It's, as we've had conversations with payers, and we've been doing this for over a year now, I mean, so we've been sharing the information we have, which will now be augmented by the phase three data. Generally speaking, the payers are not all that enthusiastic about, you know, pay for performance or value-based agreements, because there's an administrative aspect that comes with that. and you know assuming what i just shared uh it doesn't change all of a sudden i don't know why it would uh you know we would expect that in most cases kind of standard models will apply at least that's what we're taking away from some of these conversations um you know i mean it's it's one can imagine that in some cases they'll require step edits and that sort of thing and as you might imagine as the price goes up, the obstacles become progressively more onerous. So our approach is to make sure the value is clear and not put this in a zone where we're going to encounter all kinds of resistance. We want it to be a clear win for the patients, the doctors, and the payers.

And I would point out that when you think of what step edits are, our experience is that the vast majority of these patients will have already been through the necessary steps even to get to the therapies that they would you know uh be starting on sure that's awful um appreciate that the uh you know on their relative basis number of patients on the prophylactic therapy for hereditary angioidema in the u.s is a much larger proportion versus number of patients that are on prophylactic therapy x us but how are you thinking about the ex-U.S. opportunity, like pursued by yourself, partner, have a distributor? How are you thinking about the ex-U.S.?

There is an opportunity outside the U.S. It's different from what we see in the United States. will be launching this product ourselves. This is, in some respects, a good one for a company like us. We have people who have been in the space who know it well, who have been involved with the leading products. The aspect of finding new patients is really not challenged, you know, such a challenge as it might be with other examples. These patients are known. It's a prevalence, you know, patient population as opposed to an incident one. So with a modest size effort, we think we can reach them. It's very much an access game. And that's where we've been putting a lot of our emphasis. As we look outside the United States, yes, we think there's value to be captured. And we're working through what those options are. And it ranges from potential partnership to distributors and that kind of thing. So we'll do what we think is right for the company that captures the right balance without about extending us beyond where we want to go.

Gotcha, super helpful. Maybe if you have a TTR in the interest of time here, I mean, congrats obviously on the recent clinical hole being lifted. Maybe can you just recap what happened there and maybe why you're confident the new mitigation strategy that you have put in place will allow you to spare that tox and then maybe related to it, can you just maybe comment, there's a question we get from investors all the time, If you just comment about expectations for enrollment pace before and after is, you know, obviously this is now in the news and people have talked about it. We anticipate that the enrollment pace will be a little slower going forward.

So what happened? I mean, TTR is two indications, polyneuropathy, cardiomyopathy. The manifestations overlap somewhat in patients, but from a regulatory point of view, those are the two manifestations that are primarily measured. And we had an incidence of liver injury at the end of October last year in a patient who had a very, very complicated clinical course who died of a perforated duodenal ulcer and sepsis related to that. People get confused. You know, the patient did not die of liver failure, but he did have some degree of liver injury. We paused the study, worked with the FDA, and looked for anything that could help identify patients who might be at risk or find ways that we could reduce the risk. But we didn't come up with a smoking gun, at least not yet, and we continue to do this work. We did agree with the FDA that the appearance of the injury followed a pattern that was very representative of what we thought was an immune-mediated sort of event. And so the way we've addressed that is because these instances, when they occur, are all highly reminiscent of each other. It was essentially a stereotypical pattern where there's a time period where when the events happen, it's essentially always there between weeks three and five, and they resolve by themselves. But what you don't want to do is have high excursions like this particular patient who had the unfortunate outcome did. So what's in place is kind of the standard approach for immune-mediated events. will surveil carefully for any indication that patients are starting to have any kind of evidence of liver injury, even modest. And then we would begin a course of steroids. When we apply those rules retrospectively to the first 650 patients, there's a handful of patients that will have received any steroids. No one will have received it for over a week, including the one case that We just talked about typically if anyone receives steroids, it'd be like days three to five or so. And so it's kind of a standard sort of thing. With respect to enrollment, we were very close to completing the study for the polyneuropathy program that will finish its enrollment here on the second half. And it's a time-bound observation period, so 18 months after the last patient. comes into the study, we'll do that determination of how he or she is doing. With respect to cardiomyopathy, which is a larger undertaking, I mean, we're looking for 1,200 patients. We had over 650 when we paused. There's more sites spread out in more countries, so it's just a bigger thing to get going, but that's happening. I mean, informed consents, the protocol amendments, which are modest changes from what we had before, and dealing with IRBs, et cetera. So we're actively screening. And I think, you know, we'll know later this year where this all plays out in terms of, you know, that hitting that final enrollment number. Gotcha.

That's helpful. I do want to go back to something you just mentioned a couple of minutes ago because I think it's important for the broader field of genetic and you guys are pioneers so it's important to broader field Lawrence from the pioneers as well so no smoking gun but immune mediated so who's the person of interest who's you know the primary suspects here like I guess how should I think about is that because of the bacterial enzyme is that because something happens Like, this happened late in the game, right? Like, relatively later in the game. So what's the primary hypothesis at this point?

It's not the OMP. I mean, that's one question we got a lot. And we've looked, as you might imagine, very, very carefully into that. You know, you can measure the presence of the components, which are gone within just a few days after a patient's administered the drug. um what appears to be happening is that there's a response to something something has changed and what that is uh we can't rule in or rule out just yet uh but what we're doing is a very very extensive effort of looking at uh essentially all of the patients uh we haven't completed every single patient yet. But as many of them as we can across the program, and certainly in the magnitude study, to see if we can find a molecular signal of what correlates with the finding in the study. And is there some mechanistic link between those two things? So that work is ongoing. And it's something that we've prioritized. And I believe that, you know, if we can find a, quote, smoking gun, you know, the thing that we can point to, we'd be in a better position than we are now. Yeah, we're confident that the site can be done safely for patients as it is. But I think if we can take out the patients, at least for the meanwhile, who may be at increased risk, then patients will enjoy the benefit of the therapy, which is substantial based on everything we've seen thus far, and presumably, you know, we'll be able to ward off some of the other issues that applies to just a tiny percentage of these patients.

Sounds good. And, you know, all is super important to keep risk-benefit profile in mind here. Maybe on TTR cartomyopathy, you just mentioned you enrolled half of the patients, roughly, that you were supposed to enroll, and now you have a little pause, and now obviously you're enrolling them again. Does that complicate the stats in any capacity like obviously going to have events this is event driven you're going to have kind of wave one of the events and wave two if you will it's probably an oversimplification but there's gonna be a wave before the pause and after pause i appreciate the pause is relatively short here but like does that complicate complicated kaplmeyer curves and you know anything considerations in the stat or it's yeah i'm not sure it complicates it so much uh it does change where the majority of events will come from I mean exactly as you pointed out you know if you have a three and a half or so a month you know time gap between the you know that first

group of patients and then this enrollment you know momentum pickup in the second half you know a disproportionate share of the endpoints will come from the earlier set of patients i don't think that's really going to affect uh how things turn out it it delays it somewhat because you know the average patient would have been you know to the left on the gantt chart if you will then uh will be the case what you worry more about is does the patient population change somehow is the therapy different or you know have you altered the protocol in such a way that who comes in part two doesn't look quite the same as part one that's not the case so i think that our approach that you know we put in place last year applies um and you know as you might imagine even during the hold we were having events and monitoring those patients that had come in so So, you know, if that affects the very last patients, we'll take that into consideration. But right now, we're sticking with the plan that we had.

Gotcha. Gotcha. I know we're already out of time. Maybe last question, John, before I let you go. On TTR polyneuropathy, and correct me for a moment, I believe that that trial is being run exclusively ex-US. I don't think there's any sites in the U.S. So how confident are you that a trial that is exclusively ex-US will help them lead to an approval?

We've worked on the FDA with this. I mean, this is a placebo-controlled trial. The only way that you can carry out a placebo-controlled trial is essentially outside the United States at this point, where a drug may not be available. And this is a source of care for these patients. uh and with that you can run a very compact uh study because the effect size is so big uh with the drugs uh so the study is done under the ind uh it is a protocol we worked on with the fda they are fully aware and agree that this is done outside the united states with no american patients uh and uh we would only do that if if we had good alignment with fda there was never or considerations at some point to run kind of synthetic placebo type of trials.

I see some of your competitors have done that.

And I appreciate those are different molecules at this point, but or if you have access to that data from your prior programs, as is the case with Alnyla, it's harder for us to be able to do that. John, I have 3,000 more questions, but no more time.

So I appreciate you joining us here at RBC. Thanks everyone for joining. We'll talk soon. Appreciate it.