Q2 2025 Intellia Therapeutics Inc Earnings Call
Good morning and welcome to intellia Therapeutics is second quarter 2025 Financial results conference call. My name is Drew and I will be your conference operator today.
Following formal remarks, we will open the call up for a question-and-answer session. This conference is being recorded at the company's request and will be available on the company's website following the end of the call. As a reminder, all participants are currently in listen-only mode. If anyone requires operator assistance during the conference, please press star zero on your telephone keypad. I will now turn the conference over to Brittany Chaves.
Thank you, operator. And good morning, everyone. Welcome to intellia Therapeutics second quarter 2025 earnings call earlier this morning and tell you issued a press release outlining, the company's progress. This quarter as well as topics for discussion on today's call, this release can be found on the investors and media section of intellia website at intellia tx.com.
This call is being broadcast live and a replay will be archived on the company's website.
At this time, I would like to take a minute to remind listeners that during this call and tell you management may make certain forward-looking statements and ask you refer to our SEC filings available at sec.gov for discussion of potential risks and uncertainties all information presented on this call, is current as of today and until you undertakes. No duty to update this information unless required by law.
Joining me from intellia are John Leonard chief executive officer, David lebwohl chief medical officer, Ed dulac Chief Financial Officer and bear. Get Schultz our chief scientific officer who will join for Q&A. John will begin with recent business highlights? David will then provide updates on our clinical pipeline progress and Ed will review our financials before we open the call for questions with that. I will now turn the call over to John our chief executive officer.
Thanks Brittany. Good morning, everyone and thank you all for joining us today.
2025 is proving to be a year of excellent execution and exciting clinical updates.
Thus far we're meeting or exceeding all the objectives, we set for ourselves, which sets us up well, for the second half of the year.
Financially. Our restructuring is delivering the benefits that we expected which support a Runway through several major milestones. And into the first half of 20207, when we expect to be launching Longbow, Z for Hae
clinically presentations of the longer term. Follow-up data, presented from our ongoing trials, suggest our lead programs have the potential to set new standards for the treatment of Hae and for both the pollen neuropathy and cardiomyopathy manifestations of attr amaly. Doses, also from an operational perspective, all 3 phase 3 studies across Lan vosi and Mexi are enrolling faster than we expected.
We're benefiting from strong interest from both patients and physicians, coupled with their teams. Excellent execution positions us to accelerate guidance. We said at the beginning of the year,
We now anticipate completing enrollment earlier in our Hae and ATR power. Neuropathy programs than previously thought. And we expect that we will enroll more patients this year in our career, myopathy program than originally planned.
Among the many favorable updates. We provided across our programs. Today is our decision to increase enrollment to approximately 1,200 patients in magnitude or phase 3, study evaluating nexi in attr, cardiomyopathy subject to help Authority review.
Expanding the patient number in the study, will provide a more robust data set, particularly in the stabilizer stratum which we know will be very important to patients clinicians and payors.
We believe nexi in combination with a stabilizer will provide meaningful clinical benefits Beyond treating with only a stabilizer, which will be a key differentiator in the commercial setting.
it's also important to note that the improvements gained from a larger study size, do not impact either, our previously, projected enrollment or our cash Runway,
When we initially designed our study we recognized that the TTR treatment landscape could change as new agents became available during their phase 3 program. We also knew that we were well positioned to adapt to changes in TTR treatments because of the timing of our program.
Now with the benefit of recent clinical readouts, we know how to best capitalize on the rapid deep and consistent TTR reduction achieved with nexi to make it into a formidable and differentiated competitor in this large and growing Market.
Based on the strong enrollment magnitude. We also said this morning, that we are now targeting. At least 650 patients cumulatively by year end.
Again, we believe this increase relative to our prior guidance. For more than 550 patients is made possible by the operational excellence of our team, but importantly, it also reflects the enthusiasm for investigators and significant demand from patients to participate in the trial.
Let's turn the magnitude 2 for the treatment of hereditary attr. Poly, neuropathy.
High level engagement from patients and physicians in response to the promising data and potential of nexi.
Enrollment continues to track ahead of our initial projections, and we've refined our guidance. Now expecting to complete enrollment of a trial in the first half of 2026,
We are also equally excited about our phase 3 Halo study of lanoi.
Formerly known as ntla, 2002.
Today we announced, we have ended Recruitment and expect to complete randomization. During the third quarter, this Milestone consistent with our market research, reflects the high unmet need in the Hae Community despite existing treatment options.
We believe lanoi is maturing data and unique profile. As a 1-time therapy administered in an outpatient setting, resonates with patients and Physicians.
Building further on our strong momentum, we shared positive interim data throughout the quarter that continues to support the growing body of evidence for both Onvoy and Nexi.
David will expand on that in a moment.
We also look forward to sharing more clinical and operational Milestones from our lead programs later this year.
The positive developments within our studies have been matched by the progress we've made in building our commercial and medical teams required for a successful launch.
Senior leadership positions hired within the commercial and medical Affairs organizations, during the first half of the Year include head of Us sales and head of commercial operations, as well as several additional senior Leaders with responsibilities for a commercial data and field operations marketing pricing patient services, Market access forecasting and medical Communications.
We've now largely completed our buildout of the commercial and medical affairs leadership teams.
We're well underway to becoming a strong commercial ready company. We're confident in our plans, diligent in our execution and excited by the value of creating opportunities that lie in the not so distant. Future
Lastly, I want to take this time to announce the future retirement of David Lebwohl, our Chief Medical Officer, which will go into effect a year from now in August.
David will continue to serve as CMO until a successor is appointed and will remain on as a medical advice to work closely with intellia and his successor during the transition period to ensure a seamless Handover.
This is part of our routine succession planning. We've already begun to search for his successor; we are committed to finding a highly qualified candidate who can continue to build on the strong foundation that David established. In the meantime, David will continue to lead Intellia through the important clinical milestones ahead. David's leadership has been instrumental in advancing our pipeline and positioning Intellia for future success.
I'll now hand the call over to David, who will provide a more detailed update on our clinical programs?
David.
Thanks John. I'll begin with longevo Z in development for Hae.
as John mentioned, we are very pleased about the enrollment in our phase 3 study in Hae
patient and investigator interest has been strong in study initiation and enrollment has exceeded our expectations.
When you consider that the Halo study requires, 60 patients to complete enrollment, it is notable that we screened 41 patients in April alone.
This degree of demand in our study is remarkable and is enabled us to stop recruiting during the second quarter a mere 4 months after dosing the first patient.
A majority of these patients are coming off of leading therapies. Including Lana, Dela mab, which we believe supports the underappreciated degree of unmet need.
The rapid enrollment in the Halo study Echoes. What we see clearly in our market research patients and Physicians value, a therapy like lamboi
We find they are looking for a therapy that has a potential to give freedom from attacks and freedom from ongoing Therapies.
The percentage reduction in attacks is 1 measure of therapies for Hae, but our goal is to go beyond that standard.
We aspire to reset expectations and the standard of care for patients living with this debilitating disease, to achieve zero attacks in most of the patients without the need for any Hae medication.
We look forward to sharing additional data from our ongoing Phase 1 to trial later this year.
After just a single dose. Patients, remain a tax-free and treatment free for median of 23 months.
This underscores the unique value proposition of Longbow Z: the potential to offer freedom from attacks and freedom from chronic treatment.
Rhonda Z was well tolerated and showed a safety profile consistent with earlier data presented at Yaki in 2024.
The most frequent Adverse Events. During the study period were infusion related reactions. That were mostly grade 1 and resolved with all patients, receiving the full dose.
With up to 3 years of follow-up, no treatment related Adverse Events were observed after the first 28 days, and those serious Adverse Events reported in any patient.
Later. This year, we plan to present longer term data from patients in the phase. 2 portion of the study, including those who initially received the 25 milligram dose or Placebo and were subsequently given the 50 milligram dose of lanbo Z selected for the phase 3 study.
This Phase 2 update will more than double the total number of patients who have received a 50 milligram dose to more than 30 patients.
Italia is committed to transforming the treatment landscape for Hae.
We believe that the value proposition for Longboat is compelling and centered on 3 pillars.
First Freedom for people living with Hae.
Freedom from both Hae attacks and the need for chronic prophylaxis second relief for Physicians. The administrative complexity of managing insurance coverage for chronic Hae therapies is vastly underappreciated.
And third meaningful pharmacoeconomic advantages for payers.
LV is well positioned become the first ever 1-time treatment for people living with Hae and the first approved therapy to take advantage of in Vivo crispr Gene editing.
We'll now turn to nexi in development for the treatment of attr. Emily doses.
I'll begin with attr cardiomyopathy. As John mentioned, due to strong demand and magnitude. We're now targeting at least 650 patients cumulatively by year end, and we plan to expand the study from 765 patients to 12200. Patients subject, to health authority review,
This decision is driven by our desire to increase the likelihood of achieving statistically significant outcomes that are clinically relevant for patients, clinicians and payors.
This is made possible by the strong demand, participate in our study.
Increasing the sample size to 1200 patients offers a critical Advantage enhanced statistical power within the stabilizer stratum.
This will strengthen our ability to generate robust data for next. The alone as well as next Z in combination with a stabilizer.
We anticipate both approaches will be compelling based on promising Phase 1 results observed to date.
The expansion and sample size will also accelerate the approval of clinical events.
As John mentioned, our guidance remains unchanged, we will complete magnitude enrollment by early 2027.
In may we presented wild type and hereditary attr Kona myopathy data from our ongoing. Phase 1, study at the World Congress on acute, heart failure.
Participants who received nexi and reduced TTR production and improved outcomes for both wild type and variant attr cardiomyopathy patients.
Absolute TTR levels dropped from 225 to 17 micrograms for ml in the wild type group and 1, 132 to 17 micrograms per ml in the inherited disease group.
Functional capacity and clinical biomarkers were favorably. Impacted in both patient groups and evidence of stability or Improvement. In disease, progression markers, was observed across both populations at similar rates?
The most commonly reported treatment related Adverse Events were infusion related reactions which were mild or moderate and did not result in any discontinuation.
Later this year, we will present longer term data, from patients with attr cardiomyopathy and the phase 1 Study, which will include updated measures of clinical efficacy and safety. Extending our promising data presented last year at aha.
The first few months with our Global phase, we magnitude to study after randomizing the first patient in the first quarter.
This pivotal study is a placebo controlled study with planned enrollment of approximately 50 patients.
Patients are randomized to either a single 55 milligram infusion of nexi or placebo.
We will measure M, plus 7, at 18 months and serum TTR levels as key endpoints in the study.
Enrollment is expected to be completed in the first half of 2026 to enable our second dla filing in, or before 2028.
We also presented positive 2-year, follow-up data from the ongoing, Phase 1, study of Maxi and hereditary attr poly. Neuropathy at the peripheral nerve Society annual meeting in May.
This data showed ongoing persistent declines in TTR at 24 months, following a one-time dose of nexi.
Among the patients in whom and and this for 7 assessment was completed at 24 months. As of the date of cut off 13 of the 18 had an improvement from Baseline greater than the 4 point threshold, which is considered clinically meaningful.
Most of the patients in the cohort were progressed on patisiran improved and only a single patient. Among the 18 had a deterioration of greater than 4 Points.
Lexi has been generally, well, tolerated across all patients and had all those levels tested
Treatment related Adverse Events were consistent with those described for the cardiomyopathy population.
This supports our growing body of evidence, as single dose of nexi may lead to disease, stability and clinically meaningful improvements in neuropathic impairment measures.
stay tuned for a symposium in September where we plan to present extended interim, Phase 1, power neuropathy data at the international aptr and more doses meeting for patients and doctors
We're poised to complete enrollment across all of our Studies. By early 2027 and Achieve, several important clinical and Regulatory Milestones before the end of 2026,
I'll now hand over the call to heed our Chief Financial Officer, who will provide an update on our financial results as of the second quarter of 2025.
Thank you, David. Good morning, 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 approximately 630.5 million as of June 3020.
Compared to 861.7 million as of December 312022.
Our collaboration Revenue was 14.2 million during the second quarter of 2025 compared to 6.9 million during the prior year quarter.
The 7.3 million increase was mainly driven by cost reimbursements related to our collaboration, with your general and pharmaceuticals.
R&D expenses or 97 million during the second quarter of 2025.
Compared to 114.22%.
The 17.2 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 in R&D. Expenses was 14.1 million for the second quarter of 2025.
GMA expenses were 27.2 million during the second quarter, 2025 compared to 31.8 million during the prior year quarter.
The 4.6 million decrease was primarily related to lower stock based compensation.
Offset in part by increased expenses related to the ongoing buildout of our commercial infrastructure.
stock based compensation, expense included in G&A expenses with 84 quarter of 2025
We continue to expect a year-over-year decline in GAAP operating expenses and are now guiding to an approximately 10% decline this year.
To fund our operating plans into the first half of 2027.
Thanks Ed.
Our continued progress is fueled by the core values of the company 1 team, exploring possibilities, delivering results and disrupting the status quo.
We're committed to changing the treatment paradigm for patients suffering from HAE and ATTR amyloidosis. We look forward to meeting and exceeding our goals from these programs before the end of the year.
With that. We'll now open the call for your questions to do our best to address as many questions as possible. We will only be able to take 1 question per caller.
Operator. You may now open the call for Q&A.
We will now begin the question and answer session to ask you a question. You may press star then 1 on your touchtone phone. If you're using a speaker-phone please pick up your handset before pressing the keys to withdraw your question. Please. Press star. Then 2. Please limit yourself to 1 question.
At this time, we will pause momentarily to assemble our roster.
The first question comes from Manny fuhar with Ling. Please go ahead.
Hi. Good morning. Uh, this is so on, formati, thanks for taking a question. Um, so I wanted to ask so now that you've increased the target number for the ftse CM study. Um, do you have a Target proportion of patient? You would like to be on stabilizers, um, to be able to see the um, the work to be powered to see the benefit in combination. Thank you.
So thanks for the question. Uh, as we start the study, we estimated that we would have 50 to 60% of the patients on stabilizers. Uh, it's become apparent. Uh, over the course of the study that uh, the use of stabilizers has become more and more the standard of care, we estimate that we may have 70ish percent of patients who are on stabilizers. That's not a target number that we've Set. Uh, this is a study that looks at the addition of uh, nexi on top of standard of care. And that's essentially what's uh, the rate of use out there.
Uh, uh, around the world that we're seeing. So as we made clear with the, uh, adaptation of the study, we want to have a highly statistically significant finding, not only for the overall, uh, a group of the study. But also, for the combination of nexi, with stabilizers, which we think is an important clinical differentiator, uh, in the market.
Market as we see it today and expected to evolve
The next question comes from, Jina Hwang with Barkley's, please go ahead.
Hi. This is hankou from Blay's on behalf of Gina Huynh, thanks for taking our questions. So I want to follow up with this. So could you walk us through how cash Runway won't have a major change after this trial expansion?
So, we'll turn to Ed. But I would just start by saying, as I hope it's become apparent over the years, we're very thoughtful about how we peer into the future and take a very conservative view to the guidance we give and to our financial planning. But maybe Ed, you can give a little bit more detail to that. Yep. Thanks, John. Thanks for the question. Yeah, generally we do take a conservative approach to our long-range planning and for significant investments like clinical studies so that we can run the business with confidence.
For our late stage clinical programs, which may last years from planning, to execution and completion, we always assess different scenarios, different potential timelines, different potential investment needs. Uh, that's pretty standard practice for us here at intellia for magnitude. Um, specifically we consider the possibility of increasing enrollment within our scenario planning, based on, you know, the emerging data from our peers in the TTR space, our own maturing Phase 1 data from RT.
TTR program and then we have increasingly more market research that we are getting from physicians and payers to inform our thinking here. And so, we've only recently made the decision to increase to 12,200 patients, which, relative to our 3-year plan, represented a modest uptick—an immaterial uptick in costs that we can absorb without impacting our cash runway or our net cash burn guidance that we provided through 2025 and 2026.
The next question comes from Mari roft with Jeffries.
Please go ahead.
Thank you for taking our question for next year while you're accruing longer term Phase, 1 2 Data. What is the latest regarding your assumptions? On phase 3 events acral rate and if that also prompted you to extend the study to 1200 patients,
Thanks for the question. We're not talking about specific event rates but obviously, we look at information that's become available from a variety of sources, as we said in our comments, uh to open the call. Uh we've seen information has come from competitors in the space which we think provides uh useful information in terms of the current standard of care and how patients are treated and the rate of their disease progression. Uh, we supplement that with databases that comes from other sources that again, we think gives us contemporaneous information in terms of how patients with the disease uh progress. But also of significant importance is the information. We're collecting from our own Phase 1 patients which we've reported on previously and we will extend uh the reports later this year. And what we've seen uh in work that was published in New England Journal and presented elsewhere.
That the very deep rapid and sustained levels in TTR, reduction translate into what we've long expected to be, uh, a lower event rate. And so as we continue to monitor those patients that also figures into our calculations. So when you step back and look at, uh, the changes in Toto, uh, we expect that we will have an even more robust outcome than we expected before, not only for the overall, but for patients, on stabilizer will be able to have uh enrollment fall within the original guidance, which we're very excited about and being in a position to uh, March towards what we think will be 3 uh prospective launches by 2030. So, all in all we think, uh, we're increasing the overall likelihood of success for the program in a way that fits within the guidance that we've long, uh, uh, put out.
Thank you. The next question comes from Luca EC, with RBC Capital. Please go ahead.
Oh great, thanks so much for taking my question, maybe David can you just talk about enrolling Pace between your trial for TTR card and myopathy versus the the leaders. Um, it looks that astroica started their period trial around the same time as your trial, and they have now, enrolled 1,200 patients versus your obviously, guiding for 650 patients by the end of the year.
So that reflect the higher appetite for patients and physician to choose the Peter versus Gene editing. Or are there any other factors like differences in inclusion exclusion criteria that we should keep in mind here and then maybe bigger picture has the availability of 3 commercial option. Uh, in DTR economic slowdown, the pace of enrollment in any capacity. Thanks so much.
David, you want to take that?
Yeah, what we've seen in the pace of our trial is we think is pretty astounding, um, to get to more than 650 patients at the end of this year. And 12200 patients by the first quarter of 200, uh, 2027 is really unprecedented and and, and very exciting. The there are differences from the depleted study. They took basically, uh, all patients, um, including some very thick, patience, patience on, uh, any type of therapy including um, uh, TTR reducers. So it is a, it is a very different trial. Uh, when you look at our trial in the in a period in which routine is coming out, acarus is coming out. Um our enrollment is actually increased during the period that the new drugs are available.
What we see is a a strong interest from both patients and Physicians uh to get onto our trials and and we feel very good about that.
So much.
The next question comes from June Lee with truist cities. Excuse me, please go ahead.
Hi, good morning. Thanks for taking our question. This is Mary on, uh, for June, uh, given almost binary response to longer z. Uh, how would you um, maintain the study blindness? Um, and um, for for the patients that's still might show some breakthrough attack. Would that have or full? Those redosing be able to ensure complete responders. Uh thank you.
Standard procedures and there's nothing inherent about the design that should lead to unbinding. But if you want to expand on that, David be my guest.
Yeah. Our our trial is very similar in design to other pivotal trials in this disease. Um, patients will get an infusion that is uh it it's it's actually the um it's unknown to them what that infusion is.
Um, The Physician doesn't know what the infusion is. So it's it really is a a very well blinded study. Of course, the patients may experience different things, whether they, uh, have a response to the, you know, with with the drug they receiving or not. But that is not uh, considered un blinding because they really don't know if they've received the drug or not.
uh, as you know, there is also a strong placebo effect that that can take place, um, in every trial
So um, we are a confident that the trial has a great deal of Integrity in terms of blinding and um, you know it's it's uh really in good shape moving forward.
I would just add uh to that that uh the 1 of the very valuable aspects of this particular trial is that we're actually measuring clinical events. There's not much subjectivity involved patients, you know, either have an attack or believe they're having an attack and act on that with, on demand therapies. So we measured discreet.
Outcomes and uh, that is why these studies are so ugh effective at, uh, finding the effects of drugs. It's true that based on our earlier data patients respond, very well who get the drug and we're looking forward to hopefully replicating those results in our phase 3 study, as that becomes available,
The next question comes from Alec Stranahan with Bank of America. Please go ahead.
Hey guys, this is Matthew entra. Alex. Appreciate you taking our questions. Uh, maybe double clicking on a previous 1, I guess. Can you speak to whether it changes to your enrollment expectations and magnitude or stabilizer percentage? Uh, have changed your thoughts around the likelihood or timing of a potential long-term readout?
Thanks.
I would say that, uh, as we've made the adjustments, uh, we are increasing the overall power of the study, not only for the, uh, primary outcome, which is the addition of drug, on top of standard of care. But presumably also for the tap subgroup, which was a lot of the thinking that went into this. Uh, our expectations is that, uh, at some point, we will do an interim analysis and we would expect, uh, that, that these changes would favorably affect the ability to find an effect that, that, that the point that we do that.
The next question comes from Andy Chen, with wolf research, please go ahead.
Hey this is Brandon on for Andy um in regards to the expansion of magnitude you mentioned increasing the likelihood of seeing stat Sig um what were the specific data that you're trying to generate um for you to show compelling information to payers and Physicians to repair some? Thank you.
Uh, without getting into specific statistics, maybe David, you could just talk about the importance of showing profound clinical benefit in ways that are unambiguous.
Feel free to enlarge on that.
Yeah. So what we're very interested in as the trial went forward is that, um, the family, this is becoming a standard of care around the world. We're seeing an increasing percentage of patients who are receiving tofacitinib in our trial. And of course, we hear it in the commercial world as well.
Um, this this seems like it will be a baseline going forward and we thought it was very important to show A major benefit over that a significant benefit and a clinically meaningful benefit. This has not been shown with any other drugs, the ability to add to stabilizers, but looking at our Phase 1 data, it looks um, that we do have that possibility. Uh, we have very strong data related.
As John mentioned, we get deeper and more rapid reductions, uh, than other drugs. And that seems to translate based on our aha data we showed last year, into better clinical results.
Eventual accumulate more rapidly, by having more patience.
I think it's important to add that all in at the end of the study, we want the data to be absolutely unambiguous across the spectrum of treatment of the disease. Whether it's, uh, nexi attitude, standard of care whether it's nexi alone, uh, or nexi in any way that may be used. And the study has increased uh with number of patients gives us the power to demonstrate those how it comes which will be very very important to differentiate the product and have it be successful in the marketplace.
The next question comes from Troy Langford. With TD Cowen, please go ahead.
Hey! Congrats on all the progress in this quarter and thanks for taking our question. Um, with respect to the phase 1 attr-cm update later this year. Can you all just give us a little bit more color around? What level of progression you all would normally expect to see on the various functional measures and patience just giving the patient population enrolled in that study and the amount of follow-up.
Are you asking about uh within the within the phase, 1, Study, I guess so David. Do you want to speak about the clinical results? That we've reported thus far and what would otherwise have been expected.
Yeah, let's talk about that as mentioned. The first thing is to look at the effect on TTR. So the levels come down within a month, and they come down to levels of about a 90% reduction in all patients, very consistently. No patient is left behind with that.
With that. What we showed at, aha last year, was that there is, uh, when you have the measures of progression such as probnp, such as 6, minute walk, unlike, uh, Placebo patients. And unlike patients on some other agents, uh, they do not show the the worsening that those, uh, in those trends that we've seen historically, and there's now a lot of data available for multiple phase 3 trials.
But we do see is stabilization and in some cases Improvement in the patients in those measures. Uh, so this is unprecedented, um, really with any drug
Um, based on that, uh, We've also looked at as John mentioned at events rates and the event rates in this group of patients, uh, who are actually at high risk of of worsening, because they're, uh, 50% class, free patient for high percentage of variant patients. Despite all that the event rate is very low relative to what we see historically uh in other settings.
So all that comes together to say that in the state update um we look forward to you seeing it uh we have more extended data in this group of patients and uh as we said we're excited about what we're seeing. Um in those Phase 1 patients,
The next question comes from Costas Billy Urus with BMO Capital Markets. Please go ahead.
Hi. This is Yuri on for Kostas. Congrats on the progress and thanks for taking our questions. So we have 1 on next Dean attr, cardio myopathy and and so what are your latest thoughts, around potential drivers of grade 4. Lfp changes following an treatment treatment given the signals occurred, roughly 3 to 4 weeks post dosing. Thank you.
Yeah, you're referring to a patient that we reported on back in May where a patient had a Trans Am salvation. I would point out that with respect to drug induced Livery scores, this was a grade 1 which is mild. The patient was asymptomatic required. No therapy, has returned to Baseline continues in the study and is otherwise doing well, where unaware of other instances of that uh, in study. And uh, at this point, our belief is that this is unlikely to be directly related to lnps. Uh, and
As we consider other alternative explanations at this point.
that's under investigation and we're not in a position to attribute, any particular uh, mechanism to the finding
The next question comes from Brian. Brian Chang with JP Morgan. Please go ahead.
Hey guys, thanks for taking a questions this morning. Uh, just maybe you want to confirm, uh, 1 Thing uh, with the expansion in magnitude, uh, is the study now powered to show statistical, significant difference in the subset who are on stabilizer background. Thank you.
The answer is yes.
The next question comes from Mitchell, Kapoor with HC Wayne Wright. Please go ahead.
Hey everyone! Thanks for taking the question, can you speak to the qualities of patients, who are coming onto your Gene, editing studies, who are comfortable with a permanent treatment? What are you learning about these patients in particular? That could help with commercial launch, positioning for Gene, editing options, in both ha and attr. And based on these learnings, What proportion of these patients, uh, from the total addressable Market standpoint, might be open to a permanent option versus the proportion, who would like likely not opt for a permanent option. What are your your findings on that?
There's uh, several levels to the question. You're posing.
The quality of our patients. Uh, if I understand the question is hi. These are patients who, uh, meet the inclusion exclusion criteria that are Set, uh, for these studies, which is, you know, representative of all studies typically done in these different conditions.
Uh, patience. Uh, if, if I understand your question, do not have their back against the wall or anything like that. They consider the treatment options that are available to them otherwise and, uh, we encourage them to discuss that with their physician and uh, you see the results. I mean, the clinical trials are all enrolling robustly.
And as we've said several times today, uh, all are ahead of what we thought were already. Very aggressive enrollment criteria uh, and plan. So we've been very, very enthusiastic about that as David said in his comments, uh, earlier. Uh, it's interesting to look at how patients act when, uh, in the case of lavoi they're receiving, uh, standard of care that is widely used in, for example, the United States Lennard Deli map, many of the patients uh, have chosen to come off that therapy and enter into our study. What that means is they wash out of the drug. They expose themselves to the opportunity of getting drug or Placebo and uh, subject themselves to what happens during net observation period. That suggests to us that they're strongly. Motivated to find uh, the outcomes possible with uh what we think may be a permanent Improvement in their disease. Same thing is true with
Cardiomyopathy, these are patients who are not denied any other therapy. That is otherwise available to them up to this point and patients have come into the study. Uh, uh, in a very robust fashion, independent of, where they're located the United States or elsewhere around the world. So we've been very enthusiastic about the response of the patients to, uh, the study and to, uh, how they think about, uh, options for care. So, you know, I think the, the notion of a permanent,
Uh, fix if you will for their disease is something that we find patients and Physicians embracing when they consider the alternatives for the particular diseases that we're studying.
The next question comes from Jay Olsen with Oppenheimer. Please go ahead.
Oh, hey. This is John online for J. Thanks for taking the question, and congrats on the quarter. Uh, just back to the method to, um, study. I'm wondering why the 1200 number is the right 1 and, uh, it is a final number. Where you think you may further adjust the talking Bowman down the road, if any assumptions may change over time. Thank you.
uh we're not planning on adjusting the numbers going forward but David maybe you can give a little more information just in terms of what 12200 does for the study and why it's uh uh what we think is an optimal uh approach
Yeah, what we looked at here? Uh, are several things, 1 again, as I talked about are the phase 1 results. We saw there based on the outstanding results were reported that there's an opportunity to show a benefit in the stabilizer population.
Uh this is not an opportunity that uh we think of the drugs have had um seen that there have been that has not been a significant difference for example in in some of the leading drugs going forward. But we see in our data that that possibility.
Based on that we start we felt it was very important to show that statistically significant as well as clinically meaningful benefit in that subpopulation.
With the very brisk enrollment to the trial. We also saw that we could enroll 1200 patients in the time frame in, which we've guided uh, to complete enrollment.
Really looked optimal in terms of the timing of both the final analysis and an interim analysis. Uh, that will be taking place that this, this is, um, gets us there, uh, to to analysis faster because you have more patience more event securing, but also, it's not, uh, so many patients that you're, uh, you're waiting a long time, uh, for the enrollment period.
So that that's where we got to. Um and we think this will be um and and as you've also heard it, it maintains our our um Runway
So, putting that all together, this is a number we chose. We actually see the size is similar to other studies that are out there, so it's not that unusual. The differences that we do believe, based on our efficacy, we can show a benefit to specific benefits in the task group. It doesn't seem like that would be possible with a lesser effect on TTR.
Thank you.
The next question comes from Jana Anjou with Wells. Fargo Securities. Please go ahead.
Oh, great. Thanks for taking the questions. I was wondering, uh, in your statistical planning. Did you, uh, allow any, uh, did you consider any difference in between the first generation stabilizer and the nuity approved stabilizer? Um, and perhaps also, uh, any updated thinking on the percentage.
Patients on silencers uh in the study. And what uh do you expect to learn uh from those patients, thank you.
Yeah, I I can start us off in David can deal with the silencers I mean, as we look at the clinical data for the second generation stabilized, we don't really see much of a difference between that and tammis.
uh,
That that's how we approaching that with respect to the study, David, if you want to talk about silence or any other uh, comments on stabilizers, be my guest.
Yeah, we did anticipate, that silencers would become available during the period of the trial. Um based on the phase 3 trial and based on what um an island is saying the main usage of that would be upfront. Um or a switch from a stabilizer to uh, a TTR reducing drug.
Uh, we do not allow the patients who come on, uh, to the drug as a first-line agent onto a silencer, the first line agent.
And um The Physicians around the world are are obviously very aware of that that the patient would need to choose it. Uh, between 1 or the other. What we're hearing from Physicians are excited about the possibility of getting both a stabilizer and a TTR, reducing agent in combination as they can on our trial. So that um as you see, we still have very good enrollment of patients joining the trial despite the availability of um silent.
At this point.
We also anticipated that some patients might switch from to feminists to patrakar during the trial. That is uh, figured out in our our statistical analysis and we find um, the the um predictions that were able to get a positive result.
Despite that, despite these crossovers uh, seems quite clear based on our analysis.
The difference between a true b and a feminist, uh, in your statistical considerations.
No, they are considered to be the same based on the data that we have available.
Great, thanks.
The next question comes from Jonathan Miller with evercore, isi, please go ahead.
Uh, hi guys. Congrats on the progress. And thanks so much for taking my question. Uh, since you've had so many on magnitude. Maybe I wanted to switch over to the upcoming commercials, uh, uh, commercial side of things. I know you've been building a commercial team and Market access Etc. I'd love to get updated feedback from those folks on how you think players are going to react uh, to Gene editing. Obviously in the Hae setting uh is there uh quote unquote cure rate that the there is a bar for payers uh at particular price points. I just want to get a sense of how you're viewing commercial, uh, setup,
Products that will be win-win for the clinical setting and for the payer, uh, side as well. Uh, We've uh, been interacting with payers, uh, as our commercial team has come uh, into being here and by and large have corroborated our early thinking, it really comes down to the nature of the outcome. Which, uh, as has been commented on here, several instances, whether it's lamboi or the, uh, treatment effects that we're seeing with TTR, both in PN, the cardiomyopathy, uh, those effects uh, with the studies that were designing should make the clinical benefit very apparent. Uh, to the payers, uh, 1 time, therapies are easily confused. Uh, there are precedents out there that don't directly apply plus and you know, the ease of use of the uh, outpatient and fusion approach that we have coupled with the excellent outcome.
We think are going to offer a real uh, positive opportunity for the payers. Uh and as as that story, becomes clear, we'll share more results. Uh, perhaps even later this year,
The next question comes from saline Richter. With Goldman Sachs. Please go ahead.
Hi. Uh, this is Mark on for salvian, congrats on the progress and thanks for taking our question. So, uh, our questions on the competitive landscape for nexi. So I'm sure you saw that, uh, you know, the competing rnai therapy post is really strong results, this quarter. And I wanted to get your thoughts here on how this impacts the overall Market. Uh, patient physician awareness as a payer Dynamics and your views on Nexus commercial positioning in the space. Thanks.
Yeah. Well, as we said at the, uh, throughout the call, we expect to have a product, that will be a very formidable competitor for ambra, or any of the other agents that are in the space and we're taking actions in the study to give us, uh, a label that we expect will uh, position us very, very favorably. But overall with respect to the performance of these other drugs, it confirms our long-held belief uh which has been corroborated by market research, talking to Physicians and leaders in the space. That this is a large growing uh significantly underdiagnosed Marketplace. That is frequently misunderstood uh, while it's true that patients with peripheral, neuropathy typically have a heritable form of the disease, and the case of cardiomyopathy, the vast majority of these patients on the order of 90% or so, uh, have wild type disease. That means these patients are
Have the results of their TTR code of myopathy, caused by aging and not by an underlying genetic disease. There is a large supply of these patients that we will compete for very aggressively when the product becomes available, and we're excited about our prospects.
The next question comes from David. Liu with City. Please go ahead.
Uh, thank you for taking my question. Um, curious. Given that there's a, uh, another therapy that does catering knock down, um, potentially entering the market soon, obviously. Um, a different overall modality. But is there anything that you would be looking for in their launch to help inform? How you think about a potential launch for yourselves with Lonzo
Well, we pay close attention to how all of the other products and new entrance are doing. Uh, we believe that the profile that we're bringing forward is unique in the space. While there are ways to knock down kallikrein, uh, we're aware of only a single agent longboi, which knocks it down on, what we believe will be a permanent basis, that yields outcomes that are truly unique.
This concludes our question and answer session and intellia Therapeutics is second quarter 2025 Financial results conference call. Thank you for attending today's conference, you may now disconnect your line.