Intellia Therapeutics at TD Cowen Conference: Strategic Advances and Challenges

On Tuesday, 03 March 2026, Intellia Therapeutics (NASDAQ:NTLA) presented at the TD Cowen 46th Annual Health Care Conference. The company detailed its clinical progress and financial strategies, highlighting promising developments in treatments for hereditary angioedema (HAE) and transthyretin amyloidosis (ATTR). While optimism surrounded their innovative therapies, challenges remain in the competitive landscape and regulatory pathways.

Key Takeaways

• Intellia plans to file a Biologics License Application (BLA) for its HAE treatment, lonvo-z, in the second half of 2026.
• The company anticipates a potential launch of lonvo-z in 2027, targeting a mid-single-digit market share in the U.S.
• Financially, Intellia expects to maintain a cash usage of approximately $400 million annually.
• The ATTR program is back on track with resumed patient accrual for key studies.
• Intellia is preparing for commercial readiness, focusing on infrastructure and engagement with stakeholders.

Financial Results

Intellia’s financial strategy is centered on maintaining a stable cash usage of about $100 million per quarter, totaling $400 million annually. The company has restructured to prioritize research and development while creating capacity for sales and marketing investments. With a focus on commercial readiness, Intellia is eyeing revenue potential from lonvo-z, which is positioned as a high-margin product in a premium-priced setting. A mid-single-digit market share in the U.S. could cover the company’s operating costs.

Operational Updates

The phase 3 trial for lonvo-z in HAE is fully enrolled, with top-line results expected mid-2026. Intellia plans to file a BLA in the second half of the year, aiming for a U.S. market launch in 2027. The company’s TTR programs have resumed, with the polyneuropathy study expected to complete enrollment by the end of 2026. Enhanced protocols have been implemented to monitor safety in these studies. Commercial readiness efforts include building infrastructure, engaging with patient advocacy groups, and developing a distribution strategy.

Future Outlook

Intellia is optimistic about its HAE treatment, projecting attack rate reductions that could surpass current market leaders. The company aims to demonstrate the quality of its data to payers, focusing on durable attack-free results. For the ATTR program, Intellia plans to complete the polyneuropathy study by year-end, with data potentially sufficient for regulatory filing. The company is exploring value-based agreements with payers to enhance its commercial strategy.

Q&A Highlights

The HAE market, valued at $6 billion, presents significant opportunities for Intellia, particularly in the U.S. The company targets patients dissatisfied with current therapies, with a high likelihood of switching to lonvo-z. In the ATTR market, the cardiomyopathy study includes a high proportion of patients with wild-type genes, indicating a broader disease prevalence. Intellia’s executives expressed confidence in their ability to meet significant unmet needs and establish new standards of care.

For more details, please refer to the full transcript below.

Full transcript - TD Cowen 46th Annual Health Care Conference:

Joe Thome, Senior Biotech Analyst, TD Cowen: All righty. I think we’ll go ahead and get started. Everyone, thank you for joining us in the room and online, at the second day of TD Cowen’s 2026 46th Annual Healthcare Conference. I’m Joe Thome, one of the senior biotech analysts here on the team at TD Cowen, and it’s our pleasure to have with us today the team from Intellia Therapeutics. Up here with me today is CEO John Leonard. We have CFO Ed Dulac as well. Thanks, guys. Maybe to kick things off before we go into the individual programs, obviously, a lot’s been happening, a lot of, you know, new data coming up this year. Maybe a brief state of the company and kinda what should investors be looking for during 2026, then we can kinda dive into the programs.

John Leonard, CEO, Intellia Therapeutics: Sure. Good to be here and see you again, Joe. It’s 2026 is a really important year for us, as you’ve mentioned. lonvo-z, the treatment for HAE, is completing its phase 3 work. We’ve said that we’ll have top-line results here mid this year, be filing a BLA in the second half and onto a launch next year. Lots of things are gonna happen. Of course, we’ll be updating the ongoing phase 1, 2 patient population, which people have been paying a lot of attention to. As I’m sure you saw, yesterday we announced that we’re back accruing patients for the MAGNITUDE study, which is a CM cardiomyopathy study for TTR. We came off hold for the polyneuropathy study at just a few weeks ago.

For that, it’s really a matter of operationalizing the changes we’ve made, and I’m sure we’ll be talking about that a little bit, and resuming the just wonderful momentum that we had at the end of last year. Very much heading into the commercial side of the equation for us this year and laying the groundwork for, you know, the second product.

Joe Thome, Senior Biotech Analyst, TD Cowen: Awesome. Maybe we’ll start with lonvo-z for HAE. Maybe if you could touch on a little bit of the high points of the Phase 2 data that gave you confidence to advance this into the Phase 3 program. As you look, obviously, we have data coming up soon. Maybe your confidence that the patients that you enrolled in the pivotal program, you know, kinda look relatively similar to what you had seen previously in the earlier parts of the program.

John Leonard, CEO, Intellia Therapeutics: I mean, with respect to the patient population, we’ve been trying to have a very general, kind of broad-based HAE patient population. We’ve not skewed it one way or the other. Starting at late adolescence on up and no particular type of disease manifestations, and we’ve seen that in terms of the patients that have come into the Phase 3 study, which is pretty reflective of what we also saw in Phase 2. I guess if you’re gonna draw some distinctions, Phase 2 was done outside the United States, and we’ve made up for that with a lot of American patients coming into our Phase 3 program. Why do we believe the drug’s gonna work well? I mean, we’ve had just phenomenal, I think, outcomes in terms of what we’ve. You’ve seen this all.

It’s been presented most recently in November with this pooled analysis that we shared, which is any patient that’s received the Phase 3 dose of 50 milligrams, whether coming from the Phase 1 or 2 study. What we see is just really excellent efficacy for the patient population. The safety profile’s been excellent as well. The effect size is so profound that, you know, I, I think there’s really little doubt that, you know, we’ll have a favorable study. In terms of expectations, you know, when we think of the primary outcome, which is attack rate reductions, we think we’re gonna be in the 80s, which is, you know, I think the high watermark for the field in general.

What we’re really excited about is the attack-free domain, where the market leader is about 45%. We would expect that we would be, you know, in the ballpark or better than what is the best, which is about 60%. As is clear, I think, in the data we presented that as you move away from a blinded study and have patients, you know, be aware that they received a drug, the results even tend to improve with time.

Joe Thome, Senior Biotech Analyst, TD Cowen: Can you go into a little bit of that? Is it that at the beginning, they’re just still nervous that what they’re feeling is anything they’re feeling is an attack, and they tend to just kind of report because they don’t know, and then over time, they get comfortable kind of knowing what’s a real attack and what’s not? Why does that phenomenon kinda happen?

John Leonard, CEO, Intellia Therapeutics: Yeah. I mean, in these studies, the question is what’s an attack?

Joe Thome, Senior Biotech Analyst, TD Cowen: Yeah.

John Leonard, CEO, Intellia Therapeutics: Right? An attack either can be visible swelling where, you know, there’s no question about it. Use of an on-demand therapy is scored as an attack, whether there’s, you know, a actual swelling that takes place. Medical practice, and appropriately so, for this patient population is if you believe that you’re about to have an attack, to act on that. The idea is to get ahead of that. What’s interesting and I think sort of a mind game in a, in a way, if you’re participating in these studies, you’re, you know, naked, if you will, with respect to whatever you were taking previously. These patients have all washed out and gotten a baseline attack rate and then are randomized to either drug or placebo, and they don’t know.

If something doesn’t feel right, the right thing for them to do is to act on that. That’s why I was saying earlier, when patients are aware that they’ve received drug, they have a little bit more confidence instead of. I like to say, instead of counting to two before they act on whatever, maybe they’ll count to 20, and then they build confidence over time.

Joe Thome, Senior Biotech Analyst, TD Cowen: Obviously, the benefit of the one-time therapy, and you’ve seen it in the earlier data, is sort of this longer-term attack freedom after basically the drug kinda settles in and when we get past some of the observations that you’re talking about right now. When you think about the update for the phase 3, I guess what are you gonna be able to share with investors? Is it gonna be everyone through the primary observation period? Is it gonna be the primary observation period plus the duration that some patients may be beyond the primary observation period? Kinda how are you thinking about the amount of data you wanna share?

John Leonard, CEO, Intellia Therapeutics: I think the base case I would assume at this time is you’ll see top-line data for, you know, the cohort that has got the full 28-week observation period. Attack rate reduction, attack free, any headline sorta safety that needs to be reported. I mean, what we’re most excited about is what you’re referring to, is this notion that you can get to a no attack and no therapy outcome, which we think just defines a new category. In the end, I think that’s gonna be the fundamental differentiator for the product.

Joe Thome, Senior Biotech Analyst, TD Cowen: Obviously, you mentioned filing the BLA later this year. I guess can you just talk a little bit about your confidence that this data package is gonna be sufficient for filing? Kinda what have your conversations looked like with the FDA regarding, like, CMC and overall safety database as well?

John Leonard, CEO, Intellia Therapeutics: Yeah. I mean, I think we’re in really good state with the FDA. We have, you know, some of these very favorable and helpful regulatory designations, RMAT, which allows us to interact on an ongoing basis, and we participated in some of the, you know, projects that they’ve had with respect to some of the unique aspects of CMC for, you know, LNP and RNA-based therapy. We think we have a really good agreement, and we have a good understanding what they’re looking for, whether it’s clinical, preclinical, the CMC work. I would point out with respect to the CMC, what we’re using is essentially a commercial product.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

John Leonard, CEO, Intellia Therapeutics: There’s no, you know, last-minute comparability things or anything like that. You know, it’s what we’re waiting for is the clinical work.

Joe Thome, Senior Biotech Analyst, TD Cowen: Yeah

John Leonard, CEO, Intellia Therapeutics: to finish the package.

Joe Thome, Senior Biotech Analyst, TD Cowen: Have you had any conversations with ex-U.S. regulators if there would be any large differences between the package or even if you’re open to filing ex-U.S.? How you think about that?

John Leonard, CEO, Intellia Therapeutics: We’re doing a multinational study. The notion is that we’d be in a position to address, the regulatory requirements outside the U.S. Our focus for the launch, 2027 will be the United States.

Joe Thome, Senior Biotech Analyst, TD Cowen: You’ve presented some data kind of on, I think the slide is you tell people a profile like lonvo-z and kinda get their relative level of interest. I guess, can you talk first about the unmet need that remains in HAE and maybe the highlights from that data as to, you know, kind of excitement and adoption for something like lonvo-z?

Ed Dulac, CFO, Intellia Therapeutics: Yeah. I’ll take that. Thanks, Joe. I’ll say that we really like what we see in terms of the setup, so we’re super excited about it. We see a total addressable market of $6 billion, most of that coming from the U.S., which is where we are intending to launch initially. We also see a trend towards more LTP use. It’s already the majority of the market with more and better options. We see that trend continuing. That plays very well in our favor. Patients do have treatment options, so actually are accustomed to switching. There are a few dynamics that just as a backdrop for a market entrant like us that we’re very excited about. We see lots of potential. What John is referencing, particularly in the real-world profile, is what we feel is a best-in-class product.

I mean, we’re talking about patients not just having attack rate reductions. Being attack-free and doing that in a durable way that does not require drug therapy is not a profile that exists today. It’s not gonna exist in the future, but for lonvo-z. When we ask patients what their interests are, they’re not necessarily caught up in the modality. They want the outcome.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

Ed Dulac, CFO, Intellia Therapeutics: These are relatively young, otherwise healthy patients that struggle with HAE. They want an intervention that essentially allows them not to have HAE.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

Ed Dulac, CFO, Intellia Therapeutics: This is a profile that resonates with patients, but also physicians and payers. We could talk a little bit about that. The one thing I wanna mention just to wrap up this is I think we underestimate how significant HAE is.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

Ed Dulac, CFO, Intellia Therapeutics: We talk about attack rates, and there is anxiety about having that next attack, but there’s also anxiety about going on vacation, switching a job, things that you and I might do pretty readily. That is not the lifestyle that an HAE patient has. So they’ve got significant issues around, you know, psychosocial aspects of things. So they’re looking for freedom of attacks, but really a return to normalcy, if you will, and we think we’ve got the therapy to enable that to occur.

Joe Thome, Senior Biotech Analyst, TD Cowen: Awesome. Yeah, so the trial enrolled really quickly. It seems like you had a lot of interest kind of broadly across sites in order to get this in pretty quickly. I guess when you do the commercial launch, obviously you indicated, you know, some younger people. Do you get a sense of who these kind of quote-unquote, I guess, like, low-hanging fruit patients are the most ideal for a gene-edited therapy? ’Cause this is gonna be the first, you know, in vivo gene-edited treatment. How do we think about that?

Ed Dulac, CFO, Intellia Therapeutics: Our market research we just presented in January, very encouraging, right? We’re pretty transparent about the degree of efficacy that we will have, some of the safety considerations, and we are very clear that this is a gene editing approach. With pretty full disclosure, we’ve got patients 99% of whom are very or somewhat likely, and almost 65% that are very likely or extremely likely to take the therapy. We think there’s a lot of interest. Now, that’s unlikely to happen on day one, and so it wouldn’t be surprising to your low-hanging fruit question.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

Ed Dulac, CFO, Intellia Therapeutics: Patients that are not satisfied, that have a lot of breakthrough attacks, that are not doing well on therapy, they are probably the most motivated. That’s an important point about the HAE community, maybe a little bit differently. We talk a lot about physicians. These patients are pretty sophisticated. There’s great advocacy groups. They know what’s available. They talk quite a bit. They are very much a part of the conversation, if not leading the conversation in terms of choice of therapy. It’s a really good group to be working with, you know, they’re really responding well to the profile.

Joe Thome, Senior Biotech Analyst, TD Cowen: Can you talk a little bit just about the administration? You know, once a physician writes lonvo-z for a patient, what does the patient do? Administer it in an outpatient setting? What kind of prophylaxis do they do? I guess, what kind of, you know, when you think about, I guess, quote-unquote, the treatment burden, even though it doesn’t seem very burdensome, can you kind of walk us through the administration?

Ed Dulac, CFO, Intellia Therapeutics: Sure. It’s an outpatient drug, and preparation really consists of a single dose of dexamethasone the day before. Patients come into the outpatient setting, doctor’s office or infusion room. They’ll get another dose of dexamethasone, some antihistamines, and then it’s a 2-to-4-hour infusion. At the end of that, they go home. I mean, it’s that simple.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm. Then in terms of your go-to-market strategy, how are you thinking about targeting physicians or these patients kind of concentrated at, you know, major academic centers, and then they’ll be referred to sort of these outpatient settings? How do you think about how large of a footprint you’ll need?

Ed Dulac, CFO, Intellia Therapeutics: Yeah, we’ll talk about a little bit now, more in the future. Just take a step back, already in 2025, 2 years ahead of expected potential FDA approval, we’ve been building the infrastructure. We’ve had a field medical team out there talking to investigators, talking with KOLs. We’ve also been very active in these patient advocacy groups. There’s a couple, one in the U.S., one outside the U.S. We’ve been very engaged there. We’ve been doing probably earlier than expected payer work. We really wanna understand all the customers-

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

Ed Dulac, CFO, Intellia Therapeutics: -not just the prescribing physicians. People have to pay for this. There’s a lot of work to be done. We’ve already been doing that through the course of 2025. As we flip to this year, this is more about enacting some of that plan. We’re talking about sales and reimbursement reps that we need to put in place. We’re thinking about our distribution strategy, our pricing and contracting strategy. There’s a lot left to be done, but we’ve got a very clear plan that we’re executing upon. For a company like us, this is our first undertaking.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

Ed Dulac, CFO, Intellia Therapeutics: It’s a relatively digestible opportunity for us. We’re not talking a massive infrastructure. We’ve got some very capable people, senior leadership that have direct HAE experience, direct one-time therapy experience. We’re leveraging all of that to make sure that we capitalize on the value creation that we have with this asset.

Joe Thome, Senior Biotech Analyst, TD Cowen: Maybe I understand that you might not be able to go into too much detail, but obviously launches for genetic medicines, obviously not necessarily gene-edited treatments, but, you know, gene therapies and others have been a little tricky. It is kind of aligning the right effective therapy with the right reimbursement model. I guess, what do you think is the right reimbursement model? Is this gonna be a, you know, pay over time? There’s some sort of performance metric? I guess, what will be easy or best for you? Yeah.

Ed Dulac, CFO, Intellia Therapeutics: Yeah. I’ll say a couple of things without committing to doing anything right now.

Joe Thome, Senior Biotech Analyst, TD Cowen: Yeah.

Ed Dulac, CFO, Intellia Therapeutics: We’re not giving our strategy at the moment. It’s a commercial market. Let’s start there, right? Reimbursement tends to come a little bit more quickly, roughly 70% of this in the U.S. is gonna be a commercial market. We’re trying to understand who’s gonna be, you know, paying for these types of therapies. The quality of data really matters, right? What we present in top line and some of the follow-on data that we’ll eventually be using in promotional activities, I think is gonna be extremely important, right? To the extent that you are having results like we did in our pooled analysis with the vast majority of patients getting to attack free in a durable manner after a single infusion. We’ve seen no effect waning in these patients now out to 3-plus years.

That’s a really strong position to be in. I think what payers are trying to guard against is mediocre results, not knowing who’s gonna respond or what the duration is. In many ways, we struck the right balance between a one-time therapy, which is simple-

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

Ed Dulac, CFO, Intellia Therapeutics: the outpatient stuff that John mentioned, with a long-term durable treatment effect.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

Ed Dulac, CFO, Intellia Therapeutics: That’s a good position to be in as we talk about payers. There have been some experience with payers in terms of value-based agreements and other such things, so we’re thinking about that.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

Ed Dulac, CFO, Intellia Therapeutics: We don’t expect it to be really a common occurrence, in part because of the profile of the product that we’re dealing with.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

Ed Dulac, CFO, Intellia Therapeutics: You know, to the extent that we deliver the Phase 3 results that we expect, I think we’re very in an advantaged position there.

Joe Thome, Senior Biotech Analyst, TD Cowen: Ed, maybe ’cause you’re here, I guess, how are you thinking about the necessary sort of transition from R&D for the HAE program over to sort of the sgRNA build-out component? How should we be thinking about modeling that and, you know, given your financial position, kinda your comfort level in being able to do that efficiently?

Ed Dulac, CFO, Intellia Therapeutics: What we’ve said and, you know, go back to 2025, we restructured a company in a meaningful way in January.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

Ed Dulac, CFO, Intellia Therapeutics: That, of course, brought cost reductions. The real plan was thinking about the phasing of our clinical expenses. Our OpEx for quite some time has been driven primarily by clinical costs, headcount and clinical costs. That’s what it is in biotech. When you have three phase 3 programs, you have meaningful costs. What we did is prioritize things in R&D a little bit differently so that we could create capacity to invest significantly in the sales, marketing, leadership, and organization. The mix has changed over time. The visibility, though, that we had in 25 still applies to 26. We kinda used, on a net basis, about $100 million per quarter in cash. We’ll call it $400 million annually. I don’t know that that changes substantially. I’m not providing long-term guidance. It’s a reasonable basis to think about it.

What will happen, though, is you have an increased presence of sales and marketing that will grow substantially in 2026 and into the launch in 2027.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

Ed Dulac, CFO, Intellia Therapeutics: We’re fortunate in that we have some natural sun-setting of costs, right?

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

Ed Dulac, CFO, Intellia Therapeutics: Our Phase 3 HAELO study enrolled in September of last year. The PN study, MAGNITUDE-2, that we lifted the hold in January. We have a few more patients. We just announced that we intend to fully enroll that by the end of this year in the second half. What remains is the CM study, which is event-driven and a little less well-known.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

Ed Dulac, CFO, Intellia Therapeutics: On a 2-3-year basis, we’ve got pretty good visibility into OpEx. It’s just the mix that’s going to change. The last thing, ’cause I can’t resist, ’cause I’m CFO, is we’ve always thought ways to finance the company. For the first time, we’re really thinking about what revenue could mean from a product like lonvo-z.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

Ed Dulac, CFO, Intellia Therapeutics: It’s gonna be a high-margin product in a premium price setting. We’ll do the right thing to maximize access. We do wanna create value for all the stakeholders involved.

John Leonard, CEO, Intellia Therapeutics: Little goes such a long way for us. If we’re talking mid-single-digit market share in the U.S. in a given year, that covers the operating cost of the entire company.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm.

John Leonard, CEO, Intellia Therapeutics: I’m thinking about that in terms of financing plan, but it could meaningfully move the needle and allow a whole bunch of exciting things beyond that.

Joe Thome, Senior Biotech Analyst, TD Cowen: Great. Maybe last question on lonvo-z, then we’ll transition to the TTR programs. I guess when we see the full phase 3 data, how should we think about the relative safety profile of the therapy? Maybe what have you seen in phase 1/2 and phase 2, that gives you confidence that, you know, when we see this final profile, it’s gonna be one that, you know, a large portion of the population is gonna be comfortable kinda taking?

John Leonard, CEO, Intellia Therapeutics: I can take that. I mean, we’ve shared our safety profile, what we’ve seen thus far is really something that’s exceptionally clean. As we had the TTR results with the safety event that led to the clinical hold, we, as you might imagine, looked very, very carefully through the lonvo-z program. We just have not seen what we reported out for TTR, that goes through the HAELO study. No Grade 3s, no Grade 4s in terms of transaminase elevations, the rest of it is really extremely well-tolerated. I think we have outstanding efficacy, from the standpoint of safety, I think it’s gonna be a very, very attractive profile.

Joe Thome, Senior Biotech Analyst, TD Cowen: Great. Obviously you kinda led into the next question, but maybe just to hit on the safety event that did happen in the TTR program. Obviously you’re off hold on both of those studies.

John Leonard, CEO, Intellia Therapeutics: Right.

Joe Thome, Senior Biotech Analyst, TD Cowen: That’s a great outcome. Maybe if you could just kinda walk us through the, you know, the patient course there and anything the company has done to, as much as you can, figure out, you know, why this might have happened in that patient.

John Leonard, CEO, Intellia Therapeutics: Sure. At the end of October, we had an individual, an 82-year-old man, who presented with abdominal pain, called his investigator, was sent to an emergency room. There, he was found to have high transaminase levels. He was admitted for observation in a hospital, and so he was followed there, had a course that was actually unremarkable, with liver enzymes that began to improve, much like we’ve seen with any other cases that have had some elevations. That’s when things got a little bit more complicated. The patient turned out to develop a perforated duodenal ulcer, went to surgery, and never really recovered after that. The liver findings were, you know, do not cause perforated duodenal ulcers.

Whether they interacted somehow is something I don’t think we’re really ever gonna know. That patient, I think, is an outlier with respect to what we’ve seen elsewhere. We do have an incidence of LFT elevations, primarily in the form of transaminase. When it occurs, which is in a small single-digit % of patients across the entire study, it tends to occur in what is a very stereotypical fashion. When we see it’s usually, you know, week three to five following dosing. Patients will have either a modest excursion or, in these unusual cases, a higher one, which with the exception of this gentleman who passed away, everybody’s, you know, convalesced and recovered fully back to where they began, really with no sequela in essentially all cases not requiring any intervention at all.

What we’re doing in the study going forward, as we’ve worked with the FDA, whether it’s for the polyneuropathy study or the cardiomyopathy study, we’ve implemented some enhanced collection of blood in the period immediately after the dosing, especially in that window. The idea is that if we see an excursion, call it above a Grade 2 transaminase elevation, we ask that the patient take a short course of steroids. If you look back at the 650 patients we’ve already enrolled and say, "Okay, what does that apply to?" We’re talking to a very small number of patients, and we would expect that the steroid course would be, in essentially all cases, probably less than a week.

Joe Thome, Senior Biotech Analyst, TD Cowen: I don’t know if you’re able to share, but, you know, if you could just give us an idea of kinda how the conversations went with the FDA, what kind of information.

John Leonard, CEO, Intellia Therapeutics: Mm-hmm

Joe Thome, Senior Biotech Analyst, TD Cowen: ... requested to get comfort. Obviously, they ended up getting comfort to release the holds, which was great. Kinda anything around that that gave them-

John Leonard, CEO, Intellia Therapeutics: Right

Joe Thome, Senior Biotech Analyst, TD Cowen: ... the, go ahead.

John Leonard, CEO, Intellia Therapeutics: Excuse me. The list of things that we wanted to look into pretty much matched the list of things that they wanted to look into. You spend a lot of time looking for demographic clues. Is there some attribute, et cetera, that seems to correlate, to predict? To be perfectly frank, we did not find one. What we see is a pattern that is very reminiscent of what would be an immune-mediated kind of process. People ask us, "Well, what’s the inciting event?" We don’t know yet.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

John Leonard, CEO, Intellia Therapeutics: There’s really not enough cases for us to be able to tease that out. If we do have additional cases, we will collect information and try to, you know, have more visibility into that. We’d very much like to know if there is one thing, because I think then we could take action, exclude or modify, you know, the, say, prophylaxis, for example, in that patient population. As far as interacting with the FDA, I can only say positive things. They’ve been very responsive. They beat their timelines.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm

John Leonard, CEO, Intellia Therapeutics: ... you know, which we really appreciated. The interactions were about data, and I think we were able to pretty quickly satisfy them. If you look at, you know, the list of studies that go on hold, the PN study came off from the, kind of the upper quartile...

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm

John Leonard, CEO, Intellia Therapeutics: ... If you will, you know, CM study was shortly thereafter. We were happy.

Joe Thome, Senior Biotech Analyst, TD Cowen: Yeah. Maybe we’ll start with PN, because that was the first one to come off hold, and you only have a few more patients to kind of get through that study. Where do you see the unmet need in ATTR PN right now that an editor can address, and when should we expect data from the phase III program, you think?

John Leonard, CEO, Intellia Therapeutics: Yeah. As Ed said with HAE, it’s about the outcome.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

John Leonard, CEO, Intellia Therapeutics: What we see at least when we look at the current choices that are available for patients with ATTR amyloidosis, we believe that there’s efficacy that’s been left on the table. If you look at, you know, the leading drugs that are out there, you know, as a patient population, they progress.

Joe Thome, Senior Biotech Analyst, TD Cowen: Mm-hmm.

John Leonard, CEO, Intellia Therapeutics: This is a disease where it’s becoming increasingly clear that TTR, the protein, is the pathogenic agent. I think Alnylam did a really nice job early on showing that the lower you go, the better your outcomes. What we see is in the patients that we’ve treated with essentially without fail, everybody responds. When I say respond, I mean, I’m talking about not a range of reductions, but everybody pretty much collapses to absolute values of less than 20 micrograms per mil, which no one has presented data that is in that domain thus far in a patient population. That’s the answer. I mean patients, you know, want the best possible outcome, and if you can stop the progression, that’s ideal.

We’ve reported that with the extended follow-up of the Phase 1 patient populations, be it in polyneuropathy or in the cardiomyopathy patients don’t progress as a group. In fact, several of them actually regress. I mean, they go back and are better off than their baseline. Maybe with extended follow-up, which, you know, we’re continuing to observe these patients, we’ll see even further improvement.

Joe Thome, Senior Biotech Analyst, TD Cowen: Great. In terms of if this study completes before, MAGNITUDE, which it sounds like probably it might, would this be a sufficient package to file on its own for nex-z? Would you wait for cardiomyopathy and do kind of a combo package? I guess, how are you thinking about the filing strategy?

John Leonard, CEO, Intellia Therapeutics: How those two studies interact, we’ll see as things play out. You know, with the clinical hold, we’ve added some time in the middle of the cardiomyopathy study. They are two separate INDs and, you know, filings. Undoubtedly some of the safety will come from the cardiomyopathy if whether it’s the completed study or some subset thereof. You know, they’re the same underlying, you know, gene that’s edited. It’s the same underlying disease just with a manifestation’s primarily one form or the other. You asked me about when we’ll be in a position to complete the polyneuropathy study. We enrolled 47 of the intended 50 when we paused the study. As we started up again, we said we would enroll up to 60. We’re trying to accommodate patients that had presented themselves for screening.

We will fully enroll the study before the end of the year, and my guess is perhaps beat that, and we’ll speak to that as the year goes on, but it’s an 18-month observation period. A patient has a baseline result, and then after 18 months, you have where that patient wound up, and that serves as the basis of the evaluation.

Joe Thome, Senior Biotech Analyst, TD Cowen: Great. Then maybe jumping over to cardiomyopathy, obviously was enrolling ahead of expectations, before the hold. I guess, can you talk a little bit about the level of interest that you were getting before the hold and maybe already some interest again, you know, when the study’s reinitiating?

John Leonard, CEO, Intellia Therapeutics: Yeah. The study’s been ongoing. We just have not accrued additional patients. Anybody who had been treated, they continue to come to the clinics. We’re collecting endpoints, we’re collecting safety information, et cetera. We’re progressing as we go. We were really very pleased with the rate of enrollment. The guidance that we had issued at the beginning of last year was to, you know, aim for a total of 550 patients in by the end of last year. When the study paused, we were already at 650, and I believe that had we continued to the end of the year, we probably would’ve had 750 patients. In fact, enrollment was actually accelerating as we were going on.

I think what we learned was that patients were excited by the simplicity of it, and doctors actually saw a lot of simplicity to it as well. Will we recover that same enrollment rate? I think it’s gonna take a little while to know that. There’s some operational things that we have to do immediately now with respect to IRBs and protocol amendments. That’ll happen reasonably quickly, I think. We have sites outside the United States. Some of them may have some additional things that we have to do depending on their particular locales. We’ll know here in a few months, you know, what kind of a slope we have, and my hope is that as quickly as possible, we can get up to something that’s reminiscent of what we were seeing last year.

Joe Thome, Senior Biotech Analyst, TD Cowen: Great.

Ed Dulac, CFO, Intellia Therapeutics: Joe, maybe I’ll just add, I mean, I think we’ve been focused on safety for good reason recently. What people are responding to is the early efficacy side. We look at our Phase 1 data. This is a potential, another standard-setting opportunity that we have. The speed, the depth, the consistency of reduction is not available today, and patients and physicians are responding.

Joe Thome, Senior Biotech Analyst, TD Cowen: In the studies, I guess what proportion of patients do you think are gonna be on some sort of other background therapy? Kind of off the back of that, with the strong efficacy that you’re seeing, how big of an opportunity do you think nex-z could be across these indications?

John Leonard, CEO, Intellia Therapeutics: Well, it’s a standard of care study, so patients take the drug on top of whatever they’re taking for their heart disease. The relevant therapy in most cases is Tafamidis, a stabilizer, and we would estimate that maybe up to 80% or so of patients will be on that drug. We look for an outcome that’s favorable for the entire patient population, and then on top of Tafamidis, we also wanna see a favorable outcome. How big a commercial opportunity? I mean, if we get the results that we’ve seen thus far and the safety profile holds up with the mitigation strategies that we put in place, this is a large and growing market.

I think what many people misunderstand is that while the polyneuropathy form of the disease tends to be heritable, the cardiomyopathy tends to have a wild-type gene. If you look at these Phase 3 studies, sometimes up to 90% of the patients are wild-type genes. It’s a disease of aging, we have an aging patient population, you know, just across the world at this point. As doctors learn to better recognize the disease and make the diagnosis faster, we think this could be a very, very, very substantial opportunity for us.

Joe Thome, Senior Biotech Analyst, TD Cowen: Awesome. Well, great to see the news this week and, best of luck.

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