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All right. Well, thanks, everyone, for joining us. I'm Terrence Flynn, Morgan Stanley's U.S. Biopharma Analyst. For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com backslash research disclosers. If you have any questions, please reach out to your Morgan Stanley sales representative. So I'm very pleased to be hosting Intelia today. Joining us from the company, we have John Leonard, the company's CEO, and Ed Dulock, who's the company CFO. Thank you both for being here. Really appreciate it. I'm looking forward to speaking with you. I thought we'd start maybe just high-level, John, to talk about in vivo editing and just, you know, the potential for the platform. I think, again, there have been a lot of, you Know, technology has been in development for a long time now. We're starting to see really impressive use cases here. And so as you think about the potential, maybe just talk to us about high- level, where you think this can go over time, and then some of the outstanding hurdles to really effectively scale it. and then we'll get into your more specific pipeline for sure. Thanks for the question, and I'm happy to be here. We've pioneered the in vivo gene editing space. In the early days, as CRISPR was coming to be, I think a lot of people went off into ex vivo and started off in that space. We bit the bullet and went directly to the in-vivo editing space where they're, you know, that's where most of the actual targets reside in the body. The challenge there is solving for delivery, right? We benefited from people who had gone before us in terms of delivering RNA and set off with a lipid nanoparticle platform that we developed. And so we showed that you can open up the liver, which is, you Know, here we are. End of phase three for the PLA for our first indication, HAE, and then well into a phase three trial for TGR cardiomyopathy and polyneuropathy. I think the opportunities still, there are several that reside in the liver, but developing targeted LMPs to get outside of the liver to certain spaces and then finding other therapeutic delivery modalities that take you into the brain and the lung, that lies ahead. And I think as those insights come, there will be many, many very valuable targets to pursue. But at this point, we're really most interested in getting the first ones across the finish line and showing that we can successfully commercialize the CRISPR-based therapy. Okay, great. Maybe just moving on to your late-stage pipeline here, Lonvo Z, the BLA filing for HAE, Maybe just what are the gating steps here on the filing and then just overall confidence in approval? Well, we heard from the FDA just a week ago that they've accepted the BLA, which is wonderful news. We had benefited along the way from our RMAT designation and other work that we had done with pilot programs and CMC. As you know, many of the RMAT designated programs then benefit from a priority review, which we will have. So we ultimately got a PDUFA date now of March 10th. One of the things we were obviously wondering about, given that we're the first example, was whether or not there would be a need for an advisory committee. But the FDA has said that that's not something that they're currently planning on doing. And we'd, at this point, I think, be surprised if that were to come. So from a confidence level, we think we've got a very, very strong package. The data are there for anyone to see. It's, you know, the compound has just excellent efficacy and a very very clean safety profile. So we look forward to the questions and, you know, that's what lies between now and March 10. Yep. What, and how do you think about, like, the scope of the label, like age monitoring? Any tidbits yet at this point? And again, I think there's obviously some more to do here, but just what is our baseline? Yeah. We tried to develop the program as essentially an all-comers program minus the pediatric patient population below age 16. So there were no restrictions based on prior therapy, type of therapy, degree of disease, that kind of thing. And, in fact, the patient population that ultimately came into the Phase III program largely represents what is the market in the United States, 70% LTP, 30% on-demand therapy, patients with varying degrees of control, and, importantly, 20% of the patients in that Phase III trial with complete control. So we think that the product has broad appeal, and we would expect that the label will reflect that. Okay. Maybe talk to us about just kind of some of the market access work you guys have done as you prepare for the launch, any early insights from some of the payer conversations, and then just remind us as you kind of scale your commercial footprint, what is that going to look like? I'm going to turn to Ed to speak to the market piece. Yeah, I'll talk to that. Maybe we'll start with the clinical data since that's the basis of a lot of these conversations. And we've all been trained to talk about attack rate reduction. We had 87%. That's sort of table stakes for today's LTP market, as we like to refer to it. But as importantly is the data that we have in terms of how many patients have an attack-free state at the 28-week primary observation period. And in our case, that also is accompanied by no therapy by definition. So we had 62% attack- free status. In both cases, that's as good or better than anything that's been reported. I'd like to extend that, though, because I think there's two other bits of information as we think about the opportunity ahead that we're really excited about. If you take a big step back and you look at all patients we've treated, phase one, phase two, phase three, that's in excess of 100 patients. All patients eventually get to an LTP-free state. I'll just say it again. Every single patient has gotten to LTP free, and none have gone back to LDP. So as you think about health care resource utilization, that's an important consideration. It is already a very expensive disease to treat, The reason being, for the most part, that LTP therapy, which can be in excess of $700,000 annually. So when we show up to a payer conversation, it's very interesting because their question is, well, what is the right multiple to think about, right? And so we will test things like two, three, four, five times multiple. Not surprisingly, when you get to the upper end, you're going to face a lot of resistance. So we haven't decided a price. We're obviously not going to communicate any price today, But somewhere within that range is precedent for a one-time therapy that is highly effective. But that's the other important part here, the durability of clinical benefit. We now have already shown three-plus years of data. Those patients continue to mature. We're at four-plus year in the earliest Phase I and II patients, and we're going to continue to follow the Phase III patient population. So we think in a relatively small market that relies on patient switches, we have an extremely differentiated profile. And the one thing I would say is that this is somewhat of a unique market in that we all talk to physicians. Their perception is, my patients are pretty adequately served. There are lots of treatment options, and there are. The patient voice is the one to really focus on. They are actually uniquely educated. There's an advocacy group that they all participate in. They know what studies have been run. They know the clinical data. And they're very much a part of that conversation. So it's usually more joint decision-making. When you talk to the patient's perspective, they see a high degree of unmet need. In fact, go to our phase three patient population and 70% were LTP users, 30% were on demand, which we think is really important, so it's more of an all-comer patient population opportunity. 20% of the patients, though, Terrence, had complete control of their disease. So think about that for a second. They are adequately controlled on their existing therapy, are willing to wash off that therapy, establish a baseline number of attacks, and run the risk of getting placebo in the hopes that they can get a definitive treatment option. So we're really encouraged by the setup, and we've been working with payers for quite some time, doing it all again in essence now that we have the Phase 3 data. We've had very constructive conversations. Okay, that's great. Maybe just remind us kind of the mix, like how much commercial, Medicare, Medicaid, what to expect here, and then, again, sizing of the commercial footprint. Again, it seems like this will likely be a very small, you know, targeted sales force. It's the perfect starter indication for us doing this for the first time. To answer your first question, about 70% of all covered lives are commercially insured, about 20% Medicare and 10% Medicaid. That's pretty important as you think about covered lives and what the curve looks like post-approval. You can typically get to 60-plus percent in the first six months and then continue to advance it from there. So we've got a lot of folks in the field already. The medical team has been out there for quite some time, educating on the unmet need, educating on CRISPR, of course, and now that we have our Phase III data for Lambo Z, talking about that. But we also have liaisons focused on authorized treatment centers, do they have the right capabilities, making sure that they're prepared. We've been looking at, obviously, the market access continuum, thinking about distribution, how do different institutions prefer to get the product, do they want to buy and build, do they Want to Specialty Pharmacy options. So we're doing a ton of work. Now, a lot of this stuff will have to come post-approval, which we can talk about. But you're right, the footprint is relatively concentrated. 250 prescribers, the top 250 in the U.S. cover about half of all U.K. U.S. patients, so we can be very targeted, and we think that's a good place for us to start. There will be a referral component to this for folks in the community or institutions that are not willing to take it on directly, and what we have were plans for that underway. Okay, and again, have you started to build out, I know you probably have your leadership in place, some of the MSLs, but you started hiring yet for the regular field force, or is that kind of more early next year? We have, and so we have not, we wanted to make sure we use the lead time we've had. If you look at 2025 last year was really the foundation leadership, really experienced people that have both HAE and one-time therapy experience. This year in 2026 has been more of the field build-out. So beyond medical, some of these liaisons to do the ATC assessments, for example, have been in place. But we've also actually hired the field reps that will be promotional in the market post-approval, assuming that comes around that March 10th timeline. So there's training required, but we're in a really good position. And should the agency surprises to the upside with even earlier approval, we would be prepared to do that. Same to be said for manufacturing. We're in a really good spot there as well. Okay. Okay, great. I guess as we think about the early launch analogs, should we look at the Ionis product as kind of the most relevant one just because it's a more recent launch? And again, I know it's different technology platform, but is that the way we should think about kind of early ramp of patient numbers or what's the right analog to think about here for the early part of launch. Be disingenuous if I said we're so unique and different and then say there's a natural analog for that. I do think it's an opportunity, though, to realize where we are different. In this case, I think it is important to know when you have a highly effective one-time therapy, we have no ability to take those patients on clinical supply to commercial. We don't have that same playbook. If you have small molecule or self-at-home injectable, that's a different paradigm. We do not have that. What you're hearing us saying is making sure we're going to great length to make sure we understand all the stakeholder needs, be in a really good position so that if and when we receive approval, we can quickly operationalize it. What that means, though, is we're not going to have that overnight flip to revenue. So you're going to start judging us early on on things like ATC and our penetration there, probably things like patient start forms. We're still working our way through all that. The revenue will ultimately be captured downstream, but it's going to take a little bit of time out of the gate for that to mature. So I'd be looking for a couple quarters of revenue so you can get a better sense of what the real projections would look like for us in HAE. Yeah. Okay. Makes sense. Any other considerations for the launch that we should keep in mind here as we look forward to March? I think the way I look at it, and John can chime in, it is a small market. It's a switch market, and we look like we have a very different profile in that. To go back to some of my earlier comments that I don't want to repeat, so we think this is going to be very transformational for the treatment of HAE, I don' t think every patient shows up on day one. I also don't think there's a huge delay, and we see reasonably that there's a nice curve associated with it. As a company, though, doing this, this could be profoundly impactful for capital needs and our ability to reinvest in the business. I'm sure we'll talk about TTR next, but we also have active research. We look at, even if we had a mediocre launch, quite frankly, we are in the possibility of covering the operating costs of the company. So as we think about how well we're funded today, what the future capital needs, the real question we ask ourselves and what investors need to come to terms with is, what is the Lambo Z opportunity? It's going to be a premium price product in an already premium price market with very attractive margins, which gives us the possibility of really bending the curve in terms of the capital needs. So there's many things going on, including for us as a company, and that would allow us then to allocate capital to the TTR program, but also the early research priorities that we've outlined. Okay, great. Maybe we'll pivot to NEXE for TTR. A lot of focus, obviously, on the ongoing magnitude Phase 3 program here. Maybe just any more details on, you know, timing, interims, our events tracking. Help us think about when we'll be able to see data here from this trial. Well, I'd start with the data that's come out recently and how we think about that with respect to ESC, EPLON-THURSON, and even going back to Voutry, some of the things that we've learned about that, because that guides how we think about endpoints and accrual, et cetera, et cetera. I make the point that based on what we've seen, we think we're in a really good position. What we've earned from the recent disclosures is the relationship between degree of knockdown and stage of disease and how that patient mix affects the ability to see an effect in an all-commerce patient population, especially with the widespread use of stabilizers now. And so as we look at the study as it's currently designed, we think we've got the right set of endpoints. We've got a right patient mix. We will encourage investigators to think very, very carefully about the patients that they bring in, recognizing that there's more and more information that suggests that patients who are early in their stages of disease will benefit from therapy, and we want to make sure that physicians understand that. We may tweak at the margins here somewhat as we go and look at all the numbers, et cetera, But generally speaking, as we look at, you know, coming back on after the clinical hold that we had, we feel really good about the ability to fully enroll the study, again, with the right set of patients. The more challenging point is that it's an endpoint-driven study. So it really comes down to that patient mix and getting the right number of endpoints that will set the ultimate time frame for this. I will say that as we've looked at the accumulating endpoints, because, you know, this has been going on for some time now, and even during the hold, we continued to accrue them, were largely in line with the assumptions that we made in the beginning. So that was gratifying, especially as we's gotten access to this additional data. So, again, I would just make the point that I think we're in a really good position. and because a few hundred patients remain to accrue, we can still benefit additionally from the insights. Okay. And are you able to share anything about those tweaks at the margins that you might make? I think it really, yeah. I mean, it's a study that looks at standard of care, increasingly stabilizers are that around the world. and this is a study that's superimposed on top of that. So the proportion of patients that are unstabilized is something we're probably not going to affect that much, but stage of disease, the degree of advancement and the progression of disease as measured by NT-PRO-BNP is something that we can think about doing. And there may be things that we do to ultimately cap the distribution and different subsets of NT-PRO-BMP, that remains to be seen. We're working through those numbers now. Okay. When do you expect to have that finalized? Soon. I mean, you know, timeliness is really important to, you know, influence patients coming in. The other point I would make is that we've learned a lot about the endpoints themselves and those that are more discerning for the benefit than others, and that's something that we take into consideration how to measure it, which can, I think, increase the power of the study. Yep. And anything you can share in terms of that, you know, powering at this point? Well, we've powered the study to, with a high degree of power, we think, to have success in, again, for all comers, which is the primary endpoint or objective of the study. I mean, when you think about the proportion of patients that are on stabilizers coming in, And it's almost effectively an on-top-of-taff study, if you want to think of it in those terms. But, yeah, we think we're, again, we have the right statistics. Okay. Okay, great. How should we think about potential companion diagnostics, just given the HLA data? Is that something that is on the table? Yeah, just for the audience. And we learned after we went back on track after the clinical hold with additional analyses that there's an association between the liver findings that we had in an HLA allele that is strongly statistically significant. And that's important information. We've made that available to physicians and patients, and we're putting in place the ability to actually know an HLA type as patients come in. My anticipation at this time is that that probably will wind up from a commercial point of view, although we're not there yet, and that's obviously conversations that will take place when we get to labeling and that sort of thing. But we're using a CLIA-approved laboratory and the ability to go directly to a commercial sort of setting is something that I think we'll be in a really good position to do. Okay. And you think that would have to be for pretty much everyone done across the board, and it's pretty straightforward to do that? It's very straightforward. And it's something that, you know, now in the study is part of the screening procedures. Again, it's not to screen patients out. Right. It's to have an informed discussion that patients choose to self-exclude or based on their own priorities to participate as a study. And my expectation is it'll look like that later on as well. And just remind us, what percentage of people would have that HLA subtype that would be impacted? It really depends on ethnicity. If you look back in the trial population, it's about 12% of patients that have the allele. that's reflective of a European sort of Caucasian makeup, which is the predominant patient type in the patient population. But as you move increasingly into an Asian ethnicity or into African Americans, the prevalence really falls to as low as 1% to 2% in African Americans. So it really depends on the patient type. Okay, understood. I guess as you think about the competitive landscape, again, it's a similar question to, you know, the HAE discussion we're having. It's just where do you envision this fitting in the paradigm? Again, it is, you Know, I'd say it's not as crowded as HAE. Again, this is not the prophylaxis versus on-demand dynamic different here. You have, you Now, cardio versus PN. But, again where do envision this in that new paradigm? Well, we know that ATTR amyloidosis, whether it's polyneuropathy or cardiomyopathy, is a progressive disease. And we know, at least of the currently approved agents, the patient populations progress on those agents. I don't think experts in the field, certainly the ones that we talk to who know all the drugs and participate in all the trials and write all the papers, basically, that any of them believes that we're at the end point here with the pharmacopoeia as it exists in approved therapies today. So what we learn from our study and the L-nylam study, which I think has many similarities, is really, I think, going to set the stage for how these drugs are used. Cardiologists don't want to have a succession of drugs where you're chasing failures because as you fail, it becomes increasingly difficult to get the benefit. The cardiologists that we work with want to stop the disease in its tracks, and it's best to do that with the most effective therapy as early as possible. Again, I think that that's the patient population that we're trying to make sure we have plenty of examples of to show that, in fact, it will work that way. As we think about the pricing dynamic, Is it the same framework that we should think about here, you know, multiples of existing therapies given your same idea, your one and done here, or is there a different framework here for some? It's certainly a consideration, you Know, and I think the current silence, well, it's a very extremely highly priced market right now, at least from a cardiology point of view. So we think that this patient population, which is elderly and very much a Medicare patient population in the United States and outside the United States, I mean, these are mainly central payer type populations, that that plays to our strong suit from a pharmacoeconomic point of view. So presuming an efficacy that is not surpassed by other agents, and I think that that's the likely outcome here, we think we're going to have a very competitive economic offering that will be very attractive to the group of payers that serves those patients. And, Ed, what does the commercial footprint look like here relative to HAE? We haven't scoped it out to the same extent as you might imagine, and we've done with HAE, it's, you know, there's more cardiologists for sure than, you know, physicians who treat HAE. So it's a bigger footprint, and here's where we have other options, and we sort of have our colleagues at Regeneron who are part of the mix here. So as we get a little further into that, I'm sure we'll be talking more about it, but it will be a bigger undertaking for sure. Okay. And I'll just add in between HAE and CM is this PN indication that gets lost in the mix. It's a little bit smaller, but it should unfold that PN will be first. We will have the benefit of learning things from HAE in a population that's older, but not quite as significantly older as the CM population. And so I think there's some synergies there on the near term. But, yeah, ultimately there's a bigger build-out. And, again, we have that collaboration with Regeneron that could help as well. Okay. And just remind us how the split works there in terms of economics. and are there any, like, opt-ins or that decision was already made? Yes, from the outset, it's been 75%, 25% sort of in our favor. In terms of just decision-making, it is Intelia's ultimate decision, and we support 75% of the economics. That will hold true. Commercialization will be essentially a 75%, 25% profit split. There is a opt-in decision. It's sort of non-consequential from an economic perspective. We don't get an opt-In payment, for example, but they do have a right to co-promote in a minority fashion in the U.S. for the TTR asset. And the way to simply think about that is if, you know, for every 100 reps, they'll have some proportion that's actually Regeneron employees instead of Intelli employees. Net-net, it's still the same cost, still the SameSplit, but that comes roughly about two years before anticipated approval. So that is on the horizon, but, again, not all that consequential from the overall collaboration perspective. Okay. So they have to make that two years bevor approval? Roughly, yes. Okay. got it um okay um the i guess just you mentioned this ed before just as you think about the hae launch and what that means from you know a capital perspective for the company and having maybe more flexibility to um invest in in the broader pipeline and so maybe just talk through like what that would look like and you guys already have like opportunities that you're thinking about like rolling out or is that going to be staged like how do you think about capital deployment in the event that you do have a successful HAE launch? Yeah, so we have a pretty clear five-year plan. I mean, the good thing about running these studies in the case of CM, which really drives a lot of our operating expenses, you've got good visibility over the next few years. So we've been planning on that for quite some time. If we take a step back into the second quarter, we had about $630 million in cash, and we've be very conservative with our guidance, where we just exclude MAMBO-Z revenue altogether. We still have cash to run the company into 2028. And that's intentional, right? We want to make sure we not just get approval, but the key question investors have is, are you going to sell it? Can a one-time therapy be successful? We think the answer is yes. We need time for that to play out for the reasons we talked about. Just last week as well, we announced now a debt facility with OrbMed, which gives us $300 million in committed capital. We took down the initial $75 million of that, and we've given disclosures. But in a nutshell, we get another $75 available to us at Lama Zee approval. There's three distinct $40 million payments that we can get linked to sales performance of Lombo Z, but that gives us even more optionality and flexibility. We've also preserved the opportunity to do converts or synthetic royalties, so we want to make sure we have a lot of options just given everything that's going on at the company. But the thing that's most fun for us to think about, which really transforms if we need capital, how much and when, will be the performance of Blumbo Z. So we've given ourselves enough runway to see that through. But in many ways, there's been a lot of stuff that's happened in the TTR landscape, as we just talked about in particular. The goal was always do really well with Lambo Z, but that gives us capital to then redeploy against much larger opportunities, particularly in CM. And so despite some of the noise and the challenges and opportunities that come with the recent data sets, there's now a really big and growing market and probably one less competitor. So just think about the possibilities there. That's what we're really playing for. The other part we'll eventually talk about, not today, will be the pipeline. We do have active research going on. It is a competitive world out there. Given everything else the company has, we're not going to get credit, so we don't talk about that. But we do have very active, viable programs that we will in due course. So we've thought about all that on a five-plus-year view. We feel really good about where we are, but we really want to execute and deliver on the LOMBO-Z opportunity for good reason. Okay. Well, thank you so much both for being here. Really appreciate it, and best of luck. Thank you. Appreciate it. Thank you, man. Thank you.