Q1 2025 Intellia Therapeutics Inc Earnings Call
Drew: Good morning and welcome to the Intellia First 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.
Antonio: I will now turn the conference over to Brittany Chavez Senior manager of Investor Relations Antonio. Please proceed.
Speaker Change: Thank you operator, and good morning, everyone. Welcome to <unk> Therapeutics first quarter 2025 earnings call earlier. This morning, and tell you issued a press release outlining the companys 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 Italians website and tell your T X.
Speaker Change: Dot Com this call is being broadcast live and a replay will be archived on the company's website.
Speaker Change: At this time I would like to take a minute to remind listeners that during this call and Italian management may make certain forward looking statements and ask that you refer to our SEC filings available at SEC Gov for a discussion of potential risks and uncertainties. All information presented on this call is current as of today and then tell you undertakes no.
Speaker Change: I need to update this information unless required by law joining.
Speaker Change: Joining me from Italia are John Leonard Chief Executive Officer, David Lebel, Chief Medical Officer, Ed Do last Chief Financial Officer, and Dr gets Schultz, our Chief Scientific officer, who will join for Q&A.
Speaker Change: 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 <unk>, Our Chief Executive Officer.
Speaker Change: Thank you Britney good morning, everyone and thank you all for joining us today.
Speaker Change: We entered the year with clear priorities and a plan for operational excellence, we've already made tremendous progress in the first quarter.
Speaker Change: We're on a mission to offer life changing benefits with one time therapies for people living with severe diseases.
Speaker Change: Progress is fueled by the core values of the company one team exploring possibilities delivering yourselves and disrupting the status quo.
Speaker Change: We are committed to changing the treatment paradigm for patients suffering from hereditary angioedema and <unk> amyloidosis.
Speaker Change: Of the six milestones we outlined for 2025, we have accomplished two critical ones in the first three months of the year.
Speaker Change: Dosing the first patient in our phase III study for H E and dosing the first patient in our phase III study for hereditary <unk> polyneuropathy.
Speaker Change: We continue to see significant interest from both investigators and patients across our programs enrolled.
Speaker Change: Enrollment in our global Phase III Halo study for HIV is progressing rapidly and reinforces our market research.
Speaker Change: Need remains high.
Speaker Change: Despite existing treatment options patients.
Speaker Change: Patients are eager to pursue more convenient and more effective therapies. The transformational potential from a single infusion of <unk> 20 O to resonate strongly with patients and physicians.
Speaker Change: Our global Phase III magnitude studied create GTR with cardiomyopathy continues to be ahead of schedule. We now have over 90 sites actively enrolling and we continue to benefit from interest in our emerging profile for Nike guaranteed Coumarin, which we also referred to as next three from our phase one data presented.
Speaker Change: November.
Speaker Change: In the first quarter, the FDA granted until the <unk> designation for <unk> for the treatment of <unk> cardiomyopathy, which follows prior are met Assignations received for next year for <unk> with Polyneuropathy and forensic late 'twenty up to N H E E.
Speaker Change: In parallel to the great execution of our phase III studies, we've been building critical commercial foundations in order to bring their promising therapies to patients as quickly as possible.
Speaker Change: For the past few months, our commercial team has broadened its leadership capabilities and includes extensive experience with one time therapies and in disease areas of interest we're increasingly confident in our ability to evolving towards strong commercially ready company.
Speaker Change: We're excited to share multiple clinical updates throughout the year, we expect longer follow up to further solidify emerging and highly differentiated safety and efficacy profiles of our lead programs.
Speaker Change: In the case of HCA E will present, new data from patients who have crossed over in our phase II portion of our phase one two studies later this year.
Speaker Change: This expansion of patients receiving the 50 milligram dose will provide a more robust perspective with more than 30 patients in total on unique and valuable profile afforded by a one time therapy like into late 'twenty or two more.
Speaker Change: More immediately and you will have two year follow up data from our ongoing phase one study of until late 'twenty two at the European Academy of allergy and clinical Immunology Congress.
Speaker Change: Great GTR with Polyneuropathy will extend the durability window out to at least three is further extending our leadership position in in vivo gene editing.
Speaker Change: We're confident in our plans.
Speaker Change: And our execution and excited by the value creating opportunities that lie ahead.
Speaker Change: Before I hand, the call over to David Loeb Wall, our CMO.
Speaker Change: Wanted to take a moment to address how we're thinking about the regulatory environment, given the leadership changes and developments at the FDA.
Speaker Change: Like everyone else, we will monitor the situation closely.
Speaker Change: And at this point, we've experienced no tangible changes to our interactions with the agency or timelines associated with her programs. We remain on track to meet or exceed our stated regulatory timeline and objectives.
Speaker Change: We remain in close communication with her review teams and continue to move our programs toward approval as per our original plan.
Speaker Change: We have a strong active relationship with the FDA as we can.
Speaker Change: Simplified by the two prior art designations and our most recent and Atg RCM.
Speaker Change: We remain on course to file our first BLA in 2020 such.
Speaker Change: Similarly, we continue to monitor potential implications of pending pharmaceutical tariffs.
Well established manufacturing and distribution capabilities and are confident in our ability to manufacture and deliver supply for our clinical trials and eventually commercial products upon approval.
Speaker Change: And that we're convinced our products will yield significant value for patients and the health care system.
Speaker Change: We're continuing to monitor the environment, but amidst all the changes there is one thing that remains the same and that's our dedication to bringing highly differentiated therapies that have the ability to reset the treatment standards for patients with H H E and ATR.
Speaker Change: Now I'll hand, the call over to David Lebel, who will provide an update on our clinical programs.
Speaker Change: David.
Speaker Change: Thanks, John I'll begin with 'twenty or two in development for H E S.
Speaker Change: As John noted, we dosed the first patient with 20 or two in our Halo phase III study in the first quarter.
Speaker Change: Hello, It's a 60 patient global randomized double blind placebo controlled study.
Speaker Change: Patients are randomized two to one to either a single 50 milligram infusion of 'twenty or two or placebo after washing out their long term prophylaxis therapy.
Speaker Change: They are then followed for 28 week primary observation period.
Speaker Change: A total of 104 weeks in the study.
Speaker Change: Enrollment is going very well and progressing ahead of our projections.
Speaker Change: We are motivated by the early progress and excited by this patient and investigator interest.
Speaker Change: The team is executing well and we are in a position to go from the first patient to last patient dosed in less than nine months.
Speaker Change: The speed of enrollment confirms our market research and speaks to the high unmet need and demand in the age of your community.
Speaker Change: As well as the significant room for improvement.
Speaker Change: We expect to complete enrollment by the end of the third quarter of this year.
Speaker Change: We are pleased to share that new 20 O. Two data were accepted for an oral presentation at the European Academy of allergy and clinical Immunology Congress on Sunday June 15th and Glasgow.
Speaker Change: This update will include at least two years of follow up in patients in the phase one portion of the phase one two study.
Speaker Change: Later this year, we plan to present longer term data from patients in the phase two portion of the study.
Speaker Change: <unk> those who initially received a 25 milligram dose or placebo and was subsequently given the 50 milligram dose of 20 O. Two selected for the Phase III study.
Speaker Change: As John mentioned this phase two update will more than double the total patients have received the 50 milligram phase III dose to more than 30 patients.
Speaker Change: I'm, telling you is committed to ending the burden of HCA your tax and chronic treatment for H I G.
Speaker Change: The emerging profile of 20 O two from our phase one two study suggests that many HIV patients can be free from attacks and free from the medications that are currently used to treat this disease.
Speaker Change: We believe our market research shows that 'twenty or two will bring significant value to patients physicians and payors.
Speaker Change: The value proposition for 'twenty or two is comprehensive and compelling.
Frank: Frank patients freedom from HEU attacks and chronic treatment.
Frank: Physicians freedom from persistent administrative burdens and managing chronic HCV therapies.
And material Pharmacodynamic benefits for payers.
Frank: 'twenty two is poised to be the first ever one time treatment for people living with HIV and the first approved therapy using in vivo CRISPR gene editing.
Frank: Let's move onto the next C and development for the treatment of H T. T. R amyloidosis.
In March the first patient was dosed in the global Phase III Bagger, two two study for the treatment of hereditary <unk> amyloidosis with Polyneuropathy.
Frank: This pivotal study is a placebo controlled study with expected enrollment of 50 patients patients are randomized to either a single 55 milligram infusion ups next day or placebo.
Frank: Plan to measure M. This plus seven at 18 months and serum <unk> levels as key endpoints in the study.
Frank: Full study enrollment is expected to be completed in 2020 six to enable our second BLA filing by early 2028.
Frank: Also in March we announced the FDA granted <unk> designation to <unk> for the treatment of H T. T R amyloidosis with cardiomyopathy.
Frank: As John mentioned with the granting of a third arm that designation all of our lead programs and indications will benefit from earlier and more frequent engagement with the FDA.
Frank: This is a testament to the potential of our therapies to reset the standard of care and the impact they can have on patients.
Frank: We continue to be very pleased by the enrollment in the global Phase III magnitude study in H T. T. R amyloidosis with cardiomyopathy, which is ahead of our projections.
Frank: We expect cumulative enrollment to exceed 550 patients by year end.
Frank: Later this year, we will present longer term data from patients with either ATT, our polyneuropathy or cardiomyopathy in the phase one study, which will include updated measures of clinical efficacy and safety.
Frank: We will have a median follow up of two years in cardiomyopathy and three years in Polyneuropathy.
Frank: We look forward to sharing these updates in the second half of 'twenty 'twenty five.
Frank: I'll now hand over the call to Ed Our Chief Financial Officer, who will provide an update on our financial results as our first quarter 'twenty to 'twenty five.
Ed Do: Thank you David good morning, everyone.
Ed Do: Kelly continues to maintain a solid balance sheet that allows us to execute on our pipeline and platform.
Ed Do: Our cash cash equivalents and marketable securities were approximately $707 $1 million as of March 31, 2025.
Ed Do: Compared to $861 $7 million as of December 31, 2024.
Ed Do: Our balance sheet evolution reflects normal expenses from operations during the first quarter and nonrecurring costs associated with decisions, we took to prioritize our portfolio and reduce our real estate footprint and workforce all of which diminished the medium and long term capital needs for the company.
Ed Do: These outcomes represent positive developments and allow our current balance sheet could bridge to our expected launch for N. P. L. A 20 O two in <unk> during the first half of 2027.
Ed Do: During this time until it will achieve several important value, creating clinical development and regulatory milestones, which we expect will help us further capitalize the company.
Ed Do: And aggressively pursue our plans for next week and a T T R with Polyneuropathy and cardiomyopathy.
Ed Do: Our collaboration revenue was $16 $6 million during the first quarter of 2025 <unk>.
Ed Do: Compared to $28 $9 million during the first quarter of 2024.
Ed Do: $12 3 million dollar decrease was mainly driven by a decrease in collaboration revenue under the <unk> license and collaboration agreements.
Ed Do: Recall that during the first quarter of 2024.
Ed Do: There was a transition to equity method accounting for Evansville, which resulted in a one time recognition of revenue for approximately $21 million.
Ed Do: Yeah.
Ed Do: R&D expenses were $108 $4 million during the first quarter of 2025 compared to $111 $8 million during the first quarter of 2024.
Ed Do: $3 4 million dollar decrease was primarily driven by employee related expenses.
Ed Do: Stock based compensation research materials and contract services offset by an increase in the advancement of our lead programs.
Ed Do: Stock based compensation included in R&D expenses was $12 $6 million for the first quarter.
Ed Do: G&A expenses were $29 million during the first quarter of 2025 compared to 31 $1 million during the first quarter of 2024.
Ed Do: $2 $1 million decrease was primarily related to lower employee related expenses due to a workforce reduction in January 2025, and lower stock based compensation parsed.
Ed Do: Partially offset by increases related to severance expenses recorded in the first quarter.
Ed Do: Stock based compensation included in G&A expense was $9 $2 million for the first quarter.
Ed Do: As guided previously we continue to expect a year over year decline in GAAP operating expenses of between five and 10% this year.
Ed Do: And that our cash balance is sufficient to fund our operating plans into the first half of 2027.
Speaker Change: Thanks, Ed in conclusion, and tell you continues to meet and even exceed our goals in all programs and we're excited to report on our progress in the months ahead.
Speaker Change: 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 one question per caller.
Speaker Change: Operator, you May now open the call for Q&A.
Speaker Change: We will now begin the question and answer session to ask a question you May Press Star then one on your Touchtone phone if youre using a speakerphone. Please pick up your handset before pressing the keys to withdraw your question. Please press Star then two.
Speaker Change: Please limit yourself to one question.
Speaker Change: At this time, we will pause momentarily to assemble our roster.
Speaker Change: The first question comes from Gena Wang with Barclays. Please go ahead.
Speaker Change: Thank you.
Speaker Change: So.
Speaker Change: So if any updates all the different programs, but I would live in my questions to one so since that's the most pressing questions. So I'll ask about the mechanisms like a phase.
Speaker Change: Phase III trial enrollment I seems like ongoing very well and if you can't give them out.
You know your updated Ah metrics regarding the patient baseline characteristics, which includes like percentage of patient who had a baseline stabilizer and then also the silencer dropping rate what are these rates and I'd each Bates and.
Speaker Change: All right.
Speaker Change: Languished or internal expectation.
Speaker Change: David do you want to speak to the evolving characteristics at baseline in patients and thank you for that Gina VIX and the exciting thing is the rate at which this is enrolling.
Speaker Change: And.
Speaker Change: In terms of the patients around the world to families is becoming more commonly used in including the U K recently.
Speaker Change: So as we've said really from the beginning we do expect more than 50% of the patients to be on trucks and most of the study and that we're monitoring that.
Speaker Change: And we do think it's important to show a benefit over to families that hasnt been shown yet with the silencers and this is also valuable than to have a large group of families patients on the study.
Speaker Change: In terms of silence here of course. This has just been approved in the U S. Recently.
Speaker Change: We don't expect many patients to crossover though.
Speaker Change: At this point there are no patients, but over time, we do anticipate.
Speaker Change: Our statistics that a percentage of the patients will be going over to violence or.
Speaker Change: And we're ready for that in terms of.
Speaker Change: The results.
Speaker Change: Thank you.
Manny: The next question comes from Manny <unk> with Leerink partners. Please go ahead.
Speaker Change: Hi, This is living in a single on for money. Thank you for taking my question I just had a question regarding cash burn and OPEC. So you just mentioned that you were expecting a 5% to 10% year over year decreasing opex, but could you maybe give us a little more in terms of what we should expect in terms of cash burn in the next 12 to 24 months.
Manny: Especially as the restructuring progresses. So are there any notable.
Manny: Nonrecurring cost story, then that we should be taking into consideration.
Manny: Thanks for the question.
Ed Do: Ed do you want to walk through there's a lot of details, but I think it's really important to understand what was going to be the baseline running rate going forwards and Ed can take you through that Ed.
Ed Do: Yes. Thank you. Thanks for the question. This is an important focus for the company.
Ed Do: The key point I want to make for investors that we estimate that our average cash use over 2025, and 2026 will be about $95 million per quarter.
Ed Do: So this is consistent with the guidance that we reiterated today. This morning that our current cash will fund our operating plans into the first half of 'twenty seven.
Ed Do: As I indicated during the fourth quarter call a few months ago, we expect in the first quarter results continue to be pretty noisy just given the broad restructuring decisions that we made at the company earlier in the year. So.
Ed Do: So I wanted to just unpack a little bit the cash what drove our cash use during the quarter.
Ed Do: The first key driver was our normal company operations, we spent $86 million to run the business, which again is very consistent with sort of that $95 million per average cash use per quarter that I mentioned previously so normal operations, we spent 86 million in the quarter.
Ed Do: <unk> bonuses of course this is something we routinely do but that was $18 million and we did use that to pay and bonuses to existing employees, but also those that were impacted by the restructuring that we announced in January.
Ed Do: And the last driver of cash used for the quarter was sort of nonrecurring costs.
Ed Do: That was about $51 million in the quarter.
Ed Do: We used some of this to pay employee severance and related costs, but primarily we use these cash too.
Ed Do: Enter into payments associated with real estate transactions that we disclosed in February as part of our 10-K filing.
Ed Do: And I'll talk a little bit about our real estate transactions that I just referenced.
Ed Do: We're actually very excited about the development in the evolution of our real estate portfolio.
Ed Do: Just to remind folks in February we entered into a cash neutral transaction to reduce our portfolio.
Ed Do: Oh fire operations and identify additional and significant savings.
Ed Do: The cash neutrality to that transaction is really important for us. So we essentially took cash that we had budgeted for the company's real estate portfolio through 2026, and we use that to pay agreed upon lease modification payments.
Ed Do: So if I see that a little bit differently, the near term cash outlays associated with the real estate transaction will be fully recouped from the absence of cash payments that we informed we expected to pay for the real estate portfolio. So the bottom line, our real estate portfolio really better aligns with the focus and the needs of the company.
Ed Do: And it does bring us a few important benefits. The first one is what we will simply have a new corporate headquarters that the company is excited about so by the end of 2026, we'll have a new headquarters located in Cambridge or do you plan to consolidate most if not the entire company and we expect this will support the growth and the support and grow our collaboration.
Ed Do: Innovation.
Ed Do: Culture at the company. So we're very excited about those prospects.
Ed Do: The operational perspective, we're just going to have to run a very smaller simpler portfolio. So we'll have about 30% reduction in the real estate capacity over the next couple of years, including the release of all the obligation from a long term lease that we had in Waltham, Massachusetts for more than 140000 square feet.
Ed Do: And the last thing I'll say on the real estate portfolio.
Ed Do: According to our estimates, we'll expect nearly $50 million in cash savings from operating our smaller footprint there'll be other synergies and cost savings associated with the management of our portfolio.
Ed Do: And there is potential companies income from the smaller buildings that will remain in the portfolio. So I covered a lot of ground there, but I think it's such an important topic I wanted to spend a little bit of time on it and just to reiterate we will use an average of $95 million of cash per quarter grew this year in 2025 and in 2026 and this.
Ed Do: Importantly will allow us to do three three very critical thing first one fully invest in our three phase III studies, we provided an update this morning.
Ed Do: And we will continue to build the commercial infrastructure in the U S to capture the.
Ed Do: Significant value that we see across both of our lead programs.
Ed Do: And importantly, we created a financial bridge too.
Ed Do: Our first anticipated launch.
Ed Do: In the first half of <unk> 27 per <unk> and <unk>.
Speaker Change: The next question comes from Andy Chien with Wolfe Research. Please go ahead.
Hannah: This is hannah.
Speaker Change: Calling on behalf of Andy Thanks for taking our question and just honing in on that.
Hannah: Yeah.
Hannah: We see thank you guide to a cash runway into the first half of 2027, but post 2027 have you considered non diluted financing and if so what options and how feasible would they be to obtain.
Ed Do: Ed do you want to keep on going from that.
Ed Do: The prior question just talking about.
Ed Do: Look further down the road and some of the options that we're actively thinking through.
Ed Do: Yeah I appreciate the question I'll just start with what we kind of indicated this morning in January we made some difficult decisions on the restructuring we've already seen I think it's early and encouraging signs in the first quarter, our operating expenses were down 4% versus the year ago quarter and down 7% already from.
Ed Do: The fourth quarter of last year. So for the things that are immediately in our control. We're definitely focused on making sure that we are operating very efficiently and that will continue over the next few years.
Ed Do: As it relates to capital raising going forward.
We have clearly built in opportunity for the company to quick through a number of important milestones, we think they will be value, creating for shareholders and we would think about how do we raise additional capital on the back of some of those catalysts that the company has over the next 12 months to 24 months.
Ed Do: We are big believers in building the company and so we're going to continue the evolution to a commercial stage company. We also don't talk much about our research pipeline, but we do have one and we continue to invest there. So we're looking to build the company over the long term and I think a number of different levers are on the table for US one would be collaborations. We currently have a cloud.
Ed Do: And with Regeneron, our GTR asset there are opportunities to think about that cliff collaboration protect potentially differently, but we do have wholly owned assets like <unk> that we can consider partnership and then we have pipeline assets that are also hoping for potential collaboration.
Ed Do: Another option that it becomes increasingly more available to a company that I can tell you as we approach commercialization funding options like royalty transactions could make sense. The other option that you mentioned and we sort of a term debt prevention that sort of a structure that also could make sense as we think about commercialization the revenue generation and the profit.
Ed Do: The ability that this company could have on a three of your three year view and in reality, we may consider one or more of those over the next two to three years. So we've been talking about this just given the current macro economic situation in geopolitical situation for quite some time I think we have some clear plans in place.
Ed Do: They tune, but we feel really good about the balance sheet, where we're heading and I think we have multiple levers to capitalize the company over the next couple of years.
Speaker Change: The next question comes from cost just for Lewis with BMO capital markets. Please go ahead.
Speaker Change: Good morning, everybody and congrats on the progress and thanks for taking our question a question for my son, a day given that you plan to file in 2020 seats and these will potentially be the first ever commercial in vivo gene editing therapy.
Speaker Change: Can you help us.
Speaker Change: How does that how should we be thinking about the launch dynamics. They add in terms of activating sites for PSTN St. Jude in Calvert AIDS and Theyre potentially time required from patient disease Gentoo received it cannot be.
Speaker Change: Two infusion time and should we expect similar timeline dynamics to in vivo gene set up piece that we have today in the market changes.
Speaker Change: Thank you for the question it's it's.
Speaker Change: I think really a very important one.
Speaker Change: As you pointed out <unk> he will be not only our first in vivo gene editing launch, but the world's first CRISPR <unk> gene editing launched and it's something that we're paying.
Speaker Change: Great attention to.
Speaker Change: In our phase III program, which as David commented earlier.
Speaker Change: Things have been progressing extremely well, we're ahead of our timeline and learning much about how to deal with sites only make the drug available.
Speaker Change: In parallel.
Speaker Change: We've been building our commercial organization.
Speaker Change: And have staffed it with people with deep insights into prior onetime therapies.
Speaker Change: From which we can certainly learned a lot many of those one time therapies. However are not good analogs to what we're doing.
Speaker Change: The reason for that is <unk>.
Speaker Change: Ours is a very straightforward outpatient infusion where patients received a dose of dexamethasone the day before therapy come sit in the clinic for two to four hours.
Speaker Change: With another repeat dose of dexamethasone in some anti Histamines and they go home.
Speaker Change: So.
Speaker Change: To provide that versus some of the priory examples that have been made available it's Dan.
Speaker Change: With respect to switching from therapies that patients may already be taking as you might imagine as we carry out our phase III trial, we're learning a lot about that and in many instances is a simple matter of looking at the pharmacokinetics of the drugs that patients currently taking.
Speaker Change: And compensating for how those will wash out over time, while the effect of the gene edit.
Speaker Change: So we think we're in really excellent position from.
Speaker Change: <unk>.
Speaker Change: Profile point of view and we presented some of that data and you'll see more of this year.
Speaker Change: We're very excited about.
Speaker Change: How patients do and how that profile evolves over time and are really looking forward to sharing that soon and from the standpoint of getting into the marketplace. Once drug is approved we think that we can progress extremely efficiently.
Speaker Change: And bring a drug to many many patients which has been what we've been learning from our market search so.
Speaker Change: We're in a very very good position at this point.
Speaker Change: Yeah.
Speaker Change: The next question comes from Luca <unk> with RBC. Please go ahead.
Luca: Oh, great. Thanks, so much for taking my question and congrats on all the progress maybe a quick one on pricing what was your reaction when you saw the myeloma actually not lowering their price and to get the label expanded from just your airport neuropathy or cardiomyopathy.
Luca: Are you surprised by it and just maybe bigger picture, how youre thinking about pricing for your molecules more broadly given the.
Luca: The nature of them. Thanks, so much.
Luca: Thank you.
Speaker Change: Obviously, we're paying attention to the TCR market broadly and it's not just on the island winter as you know.
Luca: They're all participants, including a recent entrant.
Luca: And we watch the uptake and the performance of those different drugs, but we see as an increasingly large and rapidly growing marketplace diagnostic procedures are improving the disease is more widely recognized and across the board. This translates into an opportunity for all entrants, but we.
Luca: With the profile that we've seen thus far from our drug this is going to be a very.
Luca: Exciting market for us to participate in.
Luca: With respect to all the islands price.
Luca: Obviously, they are responding to what they see in the marketplace.
Luca: The dynamics that they've observed already polyneuropathy in the prior experience with on Petro.
Luca: We think that translates into very significant opportunity for us.
Luca: And.
Luca: As we get down the road.
Luca: Further home, how we think about that in the Meanwhile, it's all about getting our clinical trials enrolled which we're doing very very aggressively and it's David has said.
Luca: Especially with the progress of those programs were well ahead of schedule and if anything we see enrollment.
Luca: Accelerating so we're looking forward to participating in that marketplace and we're quite confident that we will do very very well.
Speaker Change: Got it thanks, so much.
Maury Raycroft: The next question comes from Maury Raycroft with Jefferies.
Speaker Change: Please go ahead.
Maury Raycroft: Hi, good morning, Congrats on the progress and thanks for taking my question.
Maury Raycroft: Going back to enrollment for the Halo phase III in late March we changed that minimum age from 18 years old to 16 years old on Cte Dot Gov. Just wondering if that's driven by patient interest or demand or was it to accelerate enrollment or for other reasons and then based on cardiomyopathy enrollment continuing to track rather than <unk>.
Maury Raycroft: <unk>.
Maury Raycroft: Can you say more on on where do you expect enrollment to land by the end of the year could it be greater than 100 patients on study or 600 patients on study.
Maury Raycroft: I guarantee you it will be more than 100 patients.
Maury Raycroft: Yeah.
Mark: Alright, Thank you for the question Mark.
Maury Raycroft: Yeah, Let me start with the Halo study first.
Maury Raycroft: Basically our interest is in having the broadest possible label, whether it's from age or disease severity.
Maury Raycroft: Designed program that should permit that.
Maury Raycroft: Patients coming into the phase III study resemble to a great extent those have come into the.
Maury Raycroft: The phase two and phase one studies and we see a range of disease severity and we think that that's very very helpful. In terms of assessing how the drug performs and should augur well for the label that we expect to get.
Maury Raycroft: With respect to enrollment of that study.
Maury Raycroft: We've been extremely gratified by interest across the board United States outside the United States, where we've had patients essentially lined up and that is not an exaggeration at all sites and we are well ahead of what we projected so well.
Maury Raycroft: Have some opportunity to further refine exactly what that looks like.
Maury Raycroft: But as we look down the road into how we think uptake will go.
Maury Raycroft: In the marketplace. Many of the comments that we've seen others offer where this is a well satisfied space.
Maury Raycroft: We see that that's not correct patients and physicians tell us that there are significant remaining need or desire to get to a state of no attacks and no further therapy, which we've seen the majority of patients. Thus far is very very compelling to patients and we actively see people.
Maury Raycroft: Very very act.
Maury Raycroft: Actively seeking that out.
Maury Raycroft: With respect to the cardiomyopathy enrollment similarly, we've been very gratified by the very rapid enrollment there.
Maury Raycroft: We guided we expect to have cumulative enrollments beyond 550 patients.
Maury Raycroft: And typically we under promise and over deliver and that may be a further instance of that and as we get down through the year, we will give some additional details there, but we like where we are and as we look at comparator.
Maury Raycroft: From prior experience.
Maury Raycroft: We've been very pleased because we're well ahead of those projections.
Maury Raycroft: Got it thank you.
Speaker Change: The next question comes from Alec Stranahan with Bank of America. Please go ahead.
Speaker Change: Hey, guys. This is Matthew on for Alex. Thanks for taking my question, maybe just one looking forward from US I know that you said, you're still developing other in vivo and ex vivo candidates, maybe just some color on it.
Speaker Change: The timeline of piece, whether they're likely to come after the potential approval and H H slash GTR.
Speaker Change: You are referring to our pipeline.
Speaker Change: Yes.
Speaker Change: We.
Speaker Change: You talked about some things in the past that we've been working on.
Speaker Change: But what we've been focusing on since the end of last year and throughout this year is very much the clinical programs and.
Speaker Change: That will be what we spend most of our time talking about because that's what's going to be the near term driver of significant value.
Speaker Change: To separate us from other companies in the space.
Speaker Change: Well beyond the proof of concept phase.
Speaker Change: Where we've demonstrated clinical activity with these drugs and what we're doing now is building a label with pivotal trials in gaining approval. So that's where the focus is going.
Speaker Change: We do have very significant efforts underway for additional in vivo candidates were talking about most of those at this point in.
Speaker Change: In the past we've spoken some about alpha one and you may hear about that.
Speaker Change: Same goes on very excited about the progress, we're making with our gene writer, we can imagine areas, where that can bring real utility and from an ex vivo point. We think we have some insights that can significantly open up that space and as time goes on we'll be talking more about that but these are competitive areas. So we will focus on the clinical.
Speaker Change: Sure.
Speaker Change: Thanks.
Moderator: The next question comes from Mitchell Kapoor with H C. Wainwright. Please go ahead.
Moderator: It is in fact, the situation I would expect from a pair point of view that that will not be a significant point of discussion I think we'll get some early insights in terms of how payers behave in the most stringent circumstances with.
Moderator: Shouldn't look for examples where yeah, topamidus may or may not be used together again, the clinical circumstances are a little different in that case, where the clinical benefit was not shown in a statistically said.
Moderator: Are designing our trial in such a way and have sufficient patients coming in onto Faminist to in fact demonstrate an expected benefit when the two drugs are used on top of Familist alone so regardless of pairs and.
Moderator: And have it in the label so that's where the situation stands as as we speak today.
Speaker Change: The next question comes from J Olsen with Oppenheimer. Please go ahead, Oh, hey, Thanks for taking the question maybe just to follow up on the previous question about the patient baseline characteristics. Ignoring in magnitude can you talk about these characteristics will impact you estimate for the time.
J Olsen: Transfer the primary endpoint and whether that would happen before or after the first half of 2027. Thank you.
J Olsen: I don't know if we're gonna be talking about timelines, but you want to talk about baseline characteristics and how you're thinking about that David with respect to.
J Olsen: The study progression yeah. So the patients in the study are looking very similar to the other phase three studies other than what I mentioned that there's more and more use of to Familis. So if you look at the number of patients with variant disease, which is a more aggressive disease.
J Olsen: Based on patients, who Mo you know obviously more patients on Tofamitis and again the timing as we get obviously get closer to analyses will we'll be able to tell you more about the timing of that.
Rick Winkowski: The next que the next question comes from Rick Winkowski with cancer Fitzgerald. Please go ahead.
Rick Winkowski: Hey, good morning, and thanks for taking the question for 20 O. Two I was hoping you could expand on the value proposition in H AE and thoughts on the degree of flexibility you'll have for pricing. This given the competitive landscape here I'd like to know your thoughts on how.
Rick Winkowski: Uticans chronic treatments and what potential cost offsets could be realized by payers over time, yeah. It's very important question.
Rick Winkowski: I I think it's important to start with the clinical profile that we've seen thus far where in addition to attack rate reduction, which we see across the board and patients. The vast majority of patients reach a point of tax.
Rick Winkowski: I'll repeat no attacks without any other therapy and that is a very important distinction and it's a category that of outcomes. That's unique to 20 O. Two so that clearly brings value to patients if they can beha.
Rick Winkowski: That's what they want they don't want faster you know on demand therapy or longer term prophylaxis, they want to get rid of their disease. If they can that's what's driving interest and that's true for the physicians as well who in many cases.
Rick Winkowski: U and a payer's perspective is substantial and very very significant these patients in the United States start at over a quarter of a million dollars a year with many of them costing over a million dollars a year in drug therapy alone that provide.
Rick Winkowski: Stanial window for us to price the drug in a way that can be very competitive with any other existing therapies that can be very very resource sparing for the health care system generally and.
Rick Winkowski: Company, and we're refining that work today, where.
Rick Winkowski: Prior precedence are taken into consideration and relationships between.
Rick Winkowski: Calls will provide more insights.
Speaker Change: Great. Thank you. The next question comes from Yanju with Wells Fargo. Please go ahead.
Speaker Change: Hi, Thanks for taking our question. Our question is also around actually in a T. T. R. C. M. So we know overall the phase three study enrollment is progressing well can you specifically talk about the enrollment in the U S and are you seeing any impact from the.
Speaker Change: Atrobi and Rocha and are you, allowing drop in of those two drugs. Thank you. David you want to speak to have you seen any impact from the new drugs and the make the tune enrollment United States first speaking to the.
Speaker Change: What we saw I think what you saw at H a last year is that the drugs is doing something different from what's been seen with other drugs for this disease. We've seen that the progression is is really stopped and patients even improvement.
Speaker Change: And this seems to have touched the investigators looking at this and really pushed forward the enrollment.
Speaker Change: That includes the U S and really all over the world, we have to really have sights pretty much everywhere, where the disease or there are specialists for this disease. What we've seen in terms of Voutre you've heard from long island. They don't expect there to be significant combination of.
Speaker Change: In the U S. Registering is approved virtually every patient is onto Famitus right now so.
Speaker Change: Though there is a chance to go on there is the possibility of patients being able to get through Tricerin, it's not expected to be a common event based on the data that that Onlylem has provided.
Speaker Change: So far we have we have been able to keep up obviously, it's early for brute tree. So we don't know a lot, but we we so far have been able to maintain the enrollment and even accelerate and recent months. Despite the fact that lutresin is coming out and the physician.
Speaker Change: Initially and with our trial it gives them the chance not only to get to Faminists, if they're undefamists, but also to get a drug that may add substantially to the famous effect. So that's what we're seeing so far and obviously keeping close T.
Speaker Change: In terms of being able to cross over the protocol, we're telling physicians if they intend to use retriserin. They should not enroll in the study right now obviously that would be their decision and the patient's decision, but if they are enrolling and the study.
Speaker Change: We don't expect them to to go over to Betricerin. During the initial year or two I think it's also the case that most physicians in our experience don't see much of a difference between two family.
Speaker Change: Getting very brisk enrollment despite the availability of Patricia.
Speaker Change: Got it the next.
Speaker Change: The next question comes from Troy Langford with TV Cowen. Please go ahead, hi, there congratulations this quarter and thanks for taking our questions I just want to follow up on one of the comments that you actually just made about recent 20 O one phase one data.
Speaker Change: Functional data from last November so when when you all show that data to physicians. Since you presented it can you just talk a little more about maybe like what one data point stands out most of them or seems to resonate most of them.
Speaker Change: What retricerin is shown in the recent new journal is that they take about nine months to get to the Nader. So it's a very delayed reduction in T. T R and they reach a level about 50. So it's a very big difference in terms of what's happening with TR.
Speaker Change: Three nine even that that's what drives efficacy and all the results are consistent with that from from last November. The we don't see increases in pro B N T. We don't see decreases in six minute walk and all those things are seen in populations of patients.
Speaker Change: Stabilizer drug and recent phase three studies that are available in a in a similar group of patients.
Speaker Change: The other thing I see is we've recently presented the time to first event and that also looks very different from what we've seen in those phase three studies. So we think when we do talk to physicians most of them are quite impressed by the data we're seeing with nex.
Speaker Change: I said I think this isn't driving enrollment and also obviously will be important in our trial results that this will drive a successful phase through trial.
Speaker Change: Great. Thanks for the color.
Speaker Change: The next question comes from miles Mitcher with William Blair. Please go ahead.
Speaker Change: Hi, This is Jake on for miles. Thank you. So much for taking our question. We had a question about you know some changes that have recently happened at Seabur and whether this is influencing your plans for timing of your B L a submission or or plans for hiring on a sales potential.
Speaker Change: It's well generally speaking changes at the FDA have been much commoned on by others in for good reason, we all have to work with the FDA in our experience thus far.
Speaker Change: Directly affected us we've established strong working relationships with our review teams as David mentioned in his comments during the earlier part call.
Speaker Change: Just recently received our third of three instances of Armat designation. So we know people are working hard on looking at the merits of the drug et cetera. Our team has been reviewing engaged we have meetings with.
Speaker Change: We we say for a good shape with respect to the most recent change at Seabur. What we see is a strong interest in actual clinical data as opposed to.
Speaker Change: S areas, where we're not active whether it's vaccines or single arm studies surrogate markers you know oncology all of the programs that we're running are randomized comparative trials that are controlled and they have clinical I.
Speaker Change: In wells standardized in the field. So we thank that we're speaking the same language as the new participants at the FDA and we look forward to sharing our data on time or ahead of time, given the enrollment and the our.
Brian Cheng: Thanks for next question comes from Brian Cheng with Jpmorgan. Please go ahead.
Brian Cheng: I got thanks for taking out question. This morning, I'm curious if you can elaborate a little bit more about your latest thinking on just a timeline for a T. T. R. Cardiomyopathy since that during a call you said that the enrollment is progressing ahead of projection what should be our base.
Brian Cheng: To get to events you to have a first interim look for this phase three and just just given that the reason trials have been taking a little bit longer than expected. Yeah. So can you elabor a little bit more on the timeline. Thanks.
Speaker Change: Groundwork and David can deal with the details, but you're right enrollment as we've said is going extremely well and we're very pleased with where we are and the progression of the study around the world Us.
Speaker Change: Interim analysis, the first timing would be after enrollment is complete so in 2027 as you as you say the idea of an interim analysis is that you have a drug with outstanding efficacy that you can stop a trial early because you see something at that early point.
Speaker Change: As I just talked about we do think we have outstanding efficacy with this drug we will continue to follow closely the long term results in the phase one we'll be looking at the event rate obviously in magnitude as well as well as looking back at at other trials.
Speaker Change: We do think we certainly possible that this trial could stop at an interim analysis based on the efficacy. We're seeing the exact timing you know as I said you need to be following these other things events to know when that is.
Speaker Change: The next question comes from William Pickering with Bernstein. Please go ahead hi, Thank you for taking my question for the magnitude two P. M study could you talk about your expectations for the enrollment rate I know you said.
William Pickering: And 2026, which is understandably a pretty wide range just given it fairly early in the study, but you know do you think the al nylon and Ionis P. In study's a reasonable benchmarks and just any color you can share on early interest in the study. Thanks so much.
William Pickering: Take your date yeah. So this is different from the earlier studies and that of course, the widespread use of Lutrisin has has required us to go to country that don't yet have utricer available. However, because those studies don't have the modern therapies.
William Pickering: There's a very large interest from the investigators in this therapy.
William Pickering: It will enroll briskly and I said into 26 as we get closer we could give you more details on when that enrollment ends, but it does give us the possibility of a submission in 28 using standard timelines.
William Pickering: For the high high level of efficacy, we're seeing in P. N and we'll be talking more about this just in June at P. N S. Because of that this also could stop at an interim analysis or even an accelerated approval type situation. So.
William Pickering: Touch look for the data in June and and you'll you know you'll get more and where this timeline may go.
William Pickering: Thank you.
Speaker Change: And the last question today will come from David Lebowitz with city. Please go ahead.
David Lebowitz: Thank you very much for taking my question in terms of the the primary endpoint to the magnitude trial, given the range and for the events from I think 18 months to 18 weeks to 18 months to 48 months.
David Lebowitz: What are the dynamics relative to I guess costs number one if the events were to come in slower does it change at all your thoughts on what type of cash you have in need and additionally, when looking at the alum.
David Lebowitz: Because they had shuffled their primary endpoint one of their endpoints from 30 to 36 weeks to 36 to 42, but in the labeling. It ultimately was pulled to being 30 to 36 weeks for all the endpoints how do you think the FDA would.
David Lebowitz: At your primary point with such a wide range on on timing two points first of all from a runway point of view, we've taken a conservative view that considers the scenario the you touched on.
David Lebowitz: And adding additional patients should that be the case. So we think from a runway point of view, where a good shape.
David Lebowitz: With respect to.
David Lebowitz: C. Prior work that was done by on a contrast in the design of our study with Heliosphere is that from the get go a helio. Our study magnitude has been and study it's not dictated by time, it's dictated by when.
David Lebowitz: Experience any of the various endpoints are included in the composite list.
David Lebowitz: So we don't see ourselves patching it up at the end of the study to get to some sort of average duration to get two endpoints by its design. It should accomplish that so we think that overall, we're in good shape we have.
Ed Do: Enrollment in the trial and as Ed said in his earlier comments. The bridge that we've built takes us into the launch of 20 O. Two so in contrast, with other companies in the space, we're talking about commercialization and.
Ed Do: Company, and we're well beyond the proof of concept stage. So we're on well on our way to being a the fully integrated pharmaceutical company that we've always intended to be thank you very much appreciate it.
Ed Do: This concludes the question and answer session and Untilyotherapeutics's first quarter 2025 financial results Conference call. Thank you for attending today's conference you May now disconnect your line.