Ionis Pharmaceuticals, Inc. (IONS) Earnings Call Transcript & Summary

Good afternoon, and welcome to Ionis conference call to discuss the FDA approval of DAWNZERA. As a reminder, this call is being recorded. At this time, I would like to turn the call over to Wade Walke, Senior Vice President of Investor Relations, to lead off the call. Please begin.

Thank you, Constantine, and thank you to everyone who's joined us today as we discuss the FDA approval of DAWNZERA now approved in the U.S. for adult and pediatric patients 12 years of age and older to prevent attacks of hereditary angioedema, or HAE. Please be sure to visit the Investors section of the Ionis website to see the press release that Ionis issued, that we issued earlier this morning, along with the slides accompanying today's webcast. Before we begin, I would like to remind you that our discussion today will contain forward-looking statements based on our current expectations and beliefs. Such statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors contained in our SEC filings for additional detail. With me on the call today are Brett Monia, Chief Executive Officer; Kenneth Newman, Senior Vice President of Clinical Development; and Kyle Jenne, Chief Global Product Strategy Officer. On our agenda today, Brett will provide opening remarks, and then Ken will discuss HAE the need for new treatment options and the positive data supporting the DAWNZERA approval. Kyle will review our strategy to achieve launch success with DAWNZERA and after Brett's brief conclusion, we will open the call for questions. And with that, I'll turn the call over to Brett.

Thanks, Wade, and thanks to everybody for joining us today. Earlier this morning, we received FDA approval of DAWNZERA, marking an important milestone for people with hereditary angioedema or HAE. DAWNZERA is approved as a prophylaxis to prevent HAE attacks in patients aged 12 years and older, as the first and only RNA targeted therapy for HAE. DAWNZERA represents a significant advance for people living with HAE. It offers strong efficacy with long-term durability and the longest dosing interval option available with dosing as infrequently as every 8 weeks using a simple low-volume autoinjectors. This approval underscores the strength of Ionis' science and the impact we're making as a fully integrated biotechnology company. In just 9 months, we have achieved approval for 2 important medicines: TRYNGOLZA for people living with FCS with a successful launch underway, and now DAWNZERA for people living with HAE. These achievements demonstrate how we're delivering on our commitment to transform groundbreaking science into life-changing medicines. They are a direct result of the passion, expertise and relentless commitment of all Ionis' employees working together to discover, develop and bring forward transformational medicines to people living with serious diseases. And this is just a start. Next year, we're planning for two additional independent launches, assuming approval, of course. These include a second indication for olezarsen, severe hypertriglyceridemia or sHTG, a large population with high unmet need and Zilganersen for Alexander disease, a severe rare leukodystrophy with no approved disease-modifying therapies. Collectively, these four programs represent much needed breakthroughs for patients and multibillion dollar revenue potential for Ionis. And beyond these launches, we have many more wholly owned medicines advancing towards the market, setting us up for a steady cadence of independent product launches well into the future. This includes ION582 advancing Phase III development for Angelman syndrome, which has transformational potential for the tens of thousands of people living with this serious rare disorder. But today, we're here to celebrate DAWNZERA. The approval of DAWNZERA was based on robust clinical results demonstrating substantial and sustained reductions in the rate of HAE attacks, long-term disease control and a favorable safety and tolerability profile. Further, DAWNZERA's unique profile provides meaningful differentiation that we believe positions it to transform the treatment paradigm for people with HAE. DAWNZERA is the first and only RNA targeted treatment for HAE, offering an entirely new mechanism of action to prevent attacks. It works by limiting the production of PKK, a protein that plays a key role in the cascade that triggers HAE attacks. DAWNZERA offers the longest dosing interval, dosing option for a prophylactic HAE treatment together with a low 0.8 ml volume patient-friendly autoinjector that takes just 10 seconds to self-administer. Additionally, the switch results from our OASIS-Plus study are the first ever clinical data to guide patients and physicians in transitioning from a previous prophylactic therapy, offering valuable insights to support informed treatment decisions. Together, we believe these attributes will result in the positive experience that people with HAE are looking for in a new prophylactic treatment option. Before I pass it off to Ken, I want to extend my heartfelt thanks to the patients, families, advocates, investigators and research partners who made this approval possible. Especially those who participate in our clinical trials. And with that, I'll turn the call over to Ken.

Thank you, Brett. Like Brett, I am so excited about today's approval and what this can mean for patients with HAE. HAE is a rare chronic genetic disease that causes unpredictable, debilitating and potentially life-threatening swelling despite available treatments, many people living with HAE still with each day and fear that they will have an attack. Swelling can occur in various parts of the body, including hands, the feet, the face, the throat and the abdomen. The unpredictable and recurrent nature of HAE attacks can take a considerable toll impacting daily life and well-being for patients living with HAE. HAE affects roughly 1 in 50,000 people around the world with an estimated 7,000 people affected in the United States. On average, it takes 5 years to receive a proper diagnosis and since it's a genetic disease, it can run in families. However, approximately 25% of patients do not have a family history. Attacks often begin in childhood with about half of people with HAE experiencing their first attack before their tenth birthday and the majority before they turn 18. This means people with HAE will spend most of their lives, managing a disease that is marked by unpredictable attacks. HAE is usually caused by inadequate C1 esterase inhibitor activity. When this protein doesn't work properly, it leads to a chain reaction involving the kallikrein-kinin system that ultimately produces too much bradykinin. When bradykinin levels get too high, they cause blood vessels to open up and leak fluid, which results in the painful and potentially fatal swellings experienced during HAE attacks. And here, you can see that DAWNZERA targets a novel mechanism of action, pre-kallikrein or PKK, which is at the start of the kallikrein kinin pathway. We designed DAWNZERA to work by selectively blocking the production of PKK in the liver, helping to keep bradykinin levels under control, which prevent swelling. What makes DAWNZERA unique is that the first and only medicine to reduce PKK production at the source by selectively targeting PKK messenger RNA in the liver offering patients a brand-new approach for the prevention of HAE attacks. And this new mechanism is demonstrated by our Phase III data, is highly effective and durable. Data from DAWNZERA has been published in the New England Journal of Medicine, not once, but three separate times. These publications includes our Phase I data, our Phase II data and our Phase III data, this level of validation from one of the most prestigious medical journals underscores the scientific rigor and clinical importance of the DAWNZERA program. DAWNZERA's approval was based on positive data from the Phase III OASIS HAE study, which showed that treatment with DAWNZERA results in substantial and durable benefit for HAE patients. The strength of DAWNZERA was further reinforced by the positive data generated from OASIS-Plus, our ongoing Phase III open-label extension study. Across both the double-blind study period and the open-label extension, DAWNZERA substantially reduced HAE attacks. Reduction in HAE attacks translated into substantial and clinically meaningful improvement in quality of life across key subdomains and DAWNZERA treatment also resulted in high levels of disease control and a vast majority of patients as measured on the angioedema control test or AECT. Notably, as of our last data cut in January of this year, patients who had been on DAWNZERA treatment for one year in the Phase III open-label extension experienced a mean HAE attack rate reduction of 94% across both 4-week and 8-week dosing groups. Additionally, OASIS-Plus included a switch cohort, which utilized a specific protocol that patients followed when switching from their prior prophylactic HAE medication to DAWNZERA. These results which were recently published in the Journal of Allergy and Clinical Immunology or JACI in practice, showed that DAWNZERA treatment resulted in an overall mean reduction of 62% in HAE attack rate from their prior prophylactic treatment. This reduction was seen despite the fact that these patients were previously maintained on prophylactic treatment for a sustained period of time before even entering the study. Switching to DAWNZERA also resulted in improved quality of life measure and improved disease control from prior prophylactic treatment. And here is more detailed data on the reduction in HAE attacks seen when patients switched to DAWNZERA from prior prophylactic therapy. At the bottom of the graph, you can see mean baseline attack rates for patients during the screening period, which was up to 10 weeks while on their prior prophylactic treatment. The bar graph shows the reduction in HAE attack rates seen over 16 weeks when patients switched to DAWNZERA treatment, demonstrating that mean HAE attack rates in each group improved substantially. Additionally, 84% of switch patients surveyed preferred DAWNZERA over their prior prophylactic treatment. Rounding out DAWNZERA clinical data is a favorable long-term safety and tolerability profile. The safety data contained in the DAWNZERA label is across OASIS HAE and OASIS-Plus including both the OLE and the switch cohorts. We have also presented additional favorable safety and tolerability data at recent medical conferences from our Phase II OLE data in which patients were treated with DAWNZERA for up to 4 years. Taken together, the clinical profile is clear. DAWNZERA delivers strong efficacy, durable outcomes long-term safety and tolerability and the longest dosing interval option available to prevent HAE attacks. As a result, we believe DAWNZERA sets a new bar for prophylactic HAE treatment. I'll now turn the call over to Kyle.

Thank you, Ken. The approval of DAWNZERA marks a major milestone for Ionis. The team is energized and focused on executing a successful launch. We have a top-tier team with extensive experience in allergy and immunology and specifically with the HAE community. They have been enthusiastically preparing for this moment, including engaging with treating physicians since late spring. We believe DAWNZERA's differentiated profile positions it to transform the HAE treatment paradigm, and we expect to have product in channel in the coming days. U.S. prophylactic HAE market is well established, but patients are still largely unsatisfied. With a compelling profile and our targeted launch strategy, we believe DAWNZERA can become the preferred prophylactic treatment for many people living with HAE. There are an estimated 7,000 people in the U.S. with HAE and about 75% are on prophylactic treatment. Approximately 1,000 allergists and immunologists are treating 90% of people with HAE. This is an established space with a concentrated prescriber base, which enables us to reach treating physicians with an optimally sized team. And while most patients are on prophylactic treatment, many patients are seeking new options. Up to 20% of patients switched treatments each year, a clear indicator that current treatments aren't meeting patients' needs. Additionally, recent Harris Poll results found that 9 in 10 HAE patients surveyed are interested in trying new prophylactic therapies, reinforcing persistent unmet needs remain within the HAE community. Patients have routinely said that they're looking for three important attributes in a new HAE prophylactic treatment. They want strong durable efficacy that results in overall disease control. Many people at HAE still experience breakthrough attacks, which can impact daily life, including their ability to work, travel and attend personal events. They want to improve tolerability, fewer side effects, including less injection pain and a treatment experience that doesn't include additional burdens like gastrointestinal issues, and they want a convenient therapy. Less frequent dosing can reduce the overall treatment burden and improve compliance, plus a treatment that can be stored at room temperature offers added convenience for patients, whether at home or on the go. DAWNZERA has demonstrated that it can deliver on all of these unmet needs that people with HAE are looking for and more with its compelling profile. First, DAWNZERA delivers strong durable efficacy. As Ken went over, the data generated from our pivotal and long-term extension studies is extensive and the reduction of HAE attacks is substantial and sustained with a 94% mean HAE attack rate reduction seen in patients treated for one year in the Phase III OASIS-Plus OLE, across both dosing groups. The results demonstrate that an attack free year is possible with DAWNZERA. Second, DAWNZERA is very well tolerated. It's self-administered with an auto-injector, the injection is low volume at only 8 ml and it contains no citric acid, which is associated with injection site pain. Third, DAWNZERA makes dosing simple and convenient. It offers the longest dosing option to prevent HAE attacks with every 4- or 8-week dosing. There's no loading dose required. It takes just 10 seconds to self-administer and it can be stored at room temperature up to 6 weeks. As a result of these key attributes, we believe DAWNZERA checks all the boxes that people with HAE are looking for in a new prophylactic treatment. Our switch data confirm that DAWNZERA's compelling profile resonates with patients. 84% of surveyed patients from our Switch study indicated that they preferred DAWNZERA over their prior prophylactic treatment. There are reasons aligned closely with the key attributes people with HAE tell us they're looking for: efficacy, tolerability and convenience. Additionally, with these data, HCPs have a clear road map to switch their patients to a new treatment without fear of breakthrough HAE attacks during the transition. Our switch results clearly set DAWNZERA apart and have been especially well received and presented at key medical meetings. Importantly, we expect DAWNZERA's compelling profile to empower health care providers to switch patients with confidence. These same attributes also reinforce our value story and ongoing payer engagements. Our DAWNZERA launch strategy is built for success, driven by a unified team committed to one goal, helping as many people with HAE as possible to better manage their disease. Our medical affairs team has laid important groundwork at key medical conferences showcasing DAWNZERA's robust clinical data and the power of Ionis' RNA-targeted technology. Additionally, our commercial team has been active in the field, well ahead of launch, engaging with treating physicians. Now with approval in hand, the team is fully equipped to communicate DAWNZERA's compelling profile while ensuring a seamless prescribing experience for physicians and their staff. In parallel, our market access and reimbursement teams have proactively engaged a broad set of U.S. payers in advance of launch to ensure timely access and coverage. And to amplify the impact and reach of our commercial team will leverage our omnichannel marketing capabilities we have built to connect with both patients and physicians. Supporting patients throughout their treatment journey is central to our commercial strategy. Ionis Every Step, our patient support program staffed with Ionis employees was first launched for the FCS community, and now we have expanded it to address the needs of people with HAE. In the heart of Ionis' Every Step is a team of dedicated patient education managers who provide personal support to help patients start and stay on treatment. For HCPs, Ionis Every Step streamlines the prescribing process by offering assistance with insurance authorization, reimbursement, reauthorizations and refills for patients. We are also deploying DAWNZERA Direct, a new digital companion, that gives patients access to various resources aimed at making treatment as seamless as possible. And we were rolling out a free trial program to patients starting DAWNZERA that will allow them in coordination with their health care providers to determine if DAWNZERA is right for them. DAWNZERA is being launched with a price of $57,462 per dose, reflecting its clinical value in the rare HAE patient population. We are committed to ensuring DAWNZERA's accessible for patients who need it. To that end, we have established financial assistance and reimbursement support programs for patients. For eligible commercially insured patients, these programs can reduce out-of-pocket costs to as little as $0 per dose. Additionally, we're offering a quick start program for patients who experience a coverage delay. Before I turn the call back to Brett, I want to underscore our excitement about today's approval and the opportunity it brings to make a meaningful difference in the lives of people living with HAE. While we recognize that educating patients and physicians and facilitating switches from existing therapies will take time, we are confident that DAWNZERA's compelling profile positions it to become the preferred prophylactic treatment for many people living with HAE. Combined with our highly experienced commercial team, we are confident in our ability to successfully execute on Ionis' second independent launch. Looking ahead with two additional launches anticipated next year, we are well positioned to sustain this momentum. With that, I'll turn the call back over to Brett.

Thanks, Kyle. We are delivering on our promise to directly bring a steady cadence of new medicines to people with serious diseases. Importantly, our commercial organization is successfully executing TRYNGOLZA launch for FCS and is well positioned to repeat this success with DAWNZERA. Beyond our U.S. launches, we're also committed to ensuring our medicines are available broadly. Accordingly, donidalorsen for HAE is under regulatory review in Europe with an approval decision expected next year. Additionally, we are pleased that olezarsen recently received a positive CHMP opinion for FCS, paving the way for anticipated approval in Europe later this year. Our OUS commercial partners will be ready to bring both of these medicines to patients as quickly as possible, assuming approval. We expect to continue our momentum as we look to the next wave of innovative medicines nearing commercialization. Olezarsen for severe hypertriglyceridemia represents our first opportunity to address a large patient population. We are eagerly awaiting results from the Core and Core 2 Phase III studies in sHTG and remain on track to report the results of both studies at one time in September. Additionally, Zilganersen for Alexander's disease is on track for Phase III data later this year. Combined, these four launches provide multibillion-dollar revenue potential marking a pivotal next chapter for Ionis. Following these anticipated launches, we have a rich pipeline of wholly owned medicines that position us for commercial success well into the future. Before I open up the call to questions, I need to remind everyone to keep your questions limited to DAWNZERA since continue -- since we continue to be in a quiet period. And with that, we'll open the call for questions.

[Operator Instructions] Your first question comes from the line of Yanan Zhu from Wells Fargo Securities.

Congrats on this exciting news. I was wondering, I think I heard you mentioned the per dose price for DAWNZERA. I was wondering, could you make a comparison to the pricing for TAKHZYRO and also the recently approved CSL drug ANDEMBRY. Given that patients could either get treated for every 1 month or 2 months, how do you think the pricing combined with that treatment or average treatment frequency translate into either incentive for payers or any other implications?

Thanks, Yanan, and this is Kyle. I appreciate the question. Obviously, we're really excited about the approval of DAWNZERA today. and we're very optimistic about the launch and getting off to a strong start. Related to the price at $57,462 that is on par and competitive with what you see with garetosmab as well as TAKHZYRO. We priced DAWNZERA based on the efficacy and the data and the supporting evidence. We've worked very closely with payers on this, and the payers are what we believe will be very accepting of the price since it's in line with the other products that are in the HAE space today. Regarding the dosing expectation, we expect that the majority of patients will start on every 4-week dosing with the option to transition to 8-week dosing if they're doing well. And obviously, payers will work with us to make sure that we understand that dynamic, and we expect very favorable coverage as we work to establish open access for patients as we move forward.

Sorry, if I may ask a clarifying question. When you say the pricing is comparable or competitive, is that referring to the Q4W on a whole year basis or Q8W on a whole year basis or a blended proportion of the two that you expect on average patient will be on?

Yes. Thanks, Yanan. So the price per dose is in line with what other products are competitively priced. When we annualize that at an every 4-week schedule that takes us to approximately $747,000 annually. And then obviously, if some patients are on 8-week dosing, there will be a reduced amount that the payer will be responsible for.

Your next question is from the line of Akash Tewari from Jefferies.

This is Anastasia on for Akash. Congrats on the approval today. I was just wondering about the anaphylaxis warning language. Is there anything in the OASIS data that suggested that you should kind of specifically include that? I don't think I saw that language for TAKHZYRO, but please let me know if I'm wrong on that?

Yes. Thank you for the question. This is Ken Newman. There were two episodes of hypersensitivity reactions that did not occur in OASIS they occurred in the OASIS open-label extension. Both of these hypersensitivity reactions resolved quickly did not have any long-term implications. So we don't believe this will have any meaningful impact. And with regard to the label for lanadelumab that's all -- they also have a hypersensitivity warning. It's obviously not uncommon.

Yes, Ken, I'll just add from a commercial viewpoint. We don't believe that this is going to have a meaningful impact on the DAWNZERA launch. We have a very strong data set here. And we believe that the label as well as the proven efficacy and safety behind the product that we'll be off to a really good start with the launch of DAWNZERA.

Your next question is from the line of Mike Ulz from Morgan Stanley.

It's Avi Novick on the line for Mike. I saw that you guys guided to peak sales a little greater than $500 million, but some of your competitors have guided to more than $1 billion peak sales for their prophylactic AG offering. So I was wondering if you can maybe add a little color to what's driving that expectation? And maybe touch a little bit upon what you see as the competitive dynamics?

Yes, great question. Thanks for that. This is Kyle again. Greater than $500 million is what we've guided to. We believe, based on the number of competitive launches that are happening in the United States, that it's reasonable to penetrate this market and have this product be established as one of the preferred treatment options for HAE. Obviously, we're also looking to launch this product globally as we referenced in the opening comments Otsuka will be building the market in Europe and elsewhere. And we believe that this is a tremendous program with an opportunity of greater than $500 million in peak sales.

The next question is from Debjit Chattopadhyay from Guggenheim Securities.

So where do you expect to capture the greatest market share? Is that going to be from the orals or the injectables, which are currently in market? And I have a follow-up.

Yes. Thanks for the question. So there are about 6,000 patients in the United States that are currently on prophylactic treatment. This is a switch market ultimately. What we do know from the data sets is that about 20% of patients are moving between these therapies, regardless if it's an injectable or if it's an oral treatment today. We also know through the Harris Poll data, as I mentioned, that 9 out of 10 of patients would be interested in trying a new prophylactic therapy. So there's a lot of motivation, a lot of dissatisfaction from patients that are currently on existing treatments. So we expect that over time, patients will be switching, and we believe that DAWNZERA is an excellent choice for these patients based on the profile that we've outlined. The efficacy data is very strong, as Ken mentioned, even with our 1-year data. The ability to self-administer this with an easy-to-use auto-injector that is low dose, low volume that can be stored at room temperature and self-administered by the patient is really, really important. And having the longest dosing option here, I think, is really going to make a difference in this space. We know the three things that patients are looking for, which is: efficacy, tolerability and convenience. And the profile of DAWNZERA supports all of those attributes that patients are looking for.

Got it. And for the follow-up, I know you sort of highlighted greater than $500 million in peak sales potential. So how is the company thinking about the durability of the DAWNZERA franchise in light of future longer-acting prophy? So it's more of a life cycle management question. I know it's -- you're literally launching this product. But obviously, there is going to be focus on the future competitive launches, especially if they come in with once every 3 months or once every 6 months dosing?

I'll take that, Debjit. Thank you for that. So we believe that DAWNZERA is going to be extremely durable in the -- on the market for HAE for all the -- for compelling profile for all the reasons Kyle outlined on efficacy, convenience and tolerability. It's going to be -- we believe it can be established. It's going to establish itself very well in the HAE community and patients are going to be very satisfied and they're not going to want to move off of DAWNZERA because they're going to be satisfied. Now with that said, and Debjit you know this as well, we're making me tremendous advancements across our platform. new chemistries, new mechanisms of action, so forth and so on. And rest assured that if we believe that we can make an even better treatment for HAE for FCS, for sHTG, you name it, because we can make patients even more satisfied we'll bring forward a new molecule. And we're working on all that for all of our Ionis own programs today. So stay tuned.

Your next question is from the line of Gary Nachman from Raymond James.

And my congrats as well on the approval of DAWNZERA. So it sounds like you're expecting most of the DAWNZERA used to be switches from other prophy treatments. But do you think there will be opportunities for first-line use with some new patients at some point, given the favorable profile and that there's still some undiagnosed patients out there? And then, Kyle, just how big is the sales force? And are they detailing Justice products for the launch? And how many of the targeted physicians will you be able to reach, I guess, in the early days? And just what have been some of your key learnings with TRYNGOLZA that you think will help you with the launch of DAWNZERA?

Yes. Thanks, Gary. So first, I'll say, in the U.S. market, it's a switch market, as I highlighted. Obviously, they're going to be newly diagnosed patients. And we do believe that DAWNZERA will appropriately be used for newly diagnosed patients. And then we also believe that over time as it becomes the preferred prophylactic treatment out there that this will be the place for physicians to start first line and move patients over to -- but we believe patients will stay on as Brett alluded to as well. And we've got long-term data that's forthcoming to be able to support all of those positions. In terms of the sales force size, we're competitively sized. We've got approximately 70 team members in the field that are responsible for DAWNZERA. They are specifically assigned our sales organization, specifically dedicated to DAWNZERA as a product. And they will be targeting all of the prescribers of current HAE prophylactic treatments. The concentrated prescriber base is about 1,000 physicians that treat approximately 90% of these patients. So you can have a very efficiently sized organization to be able to get out to the prescriber base. In terms of key learnings for us, there are a number of things that I'll highlight here. First is the ability to get product and channel very quickly. We expect to have a product and channel in the coming days, so that prescriptions that are written here very early on or are able to be fulfilled and we can get product to patients as soon as possible. The second thing that I'll highlight is our Ionis Every Step program. We really are, I believe, leading the way in terms of the way that we are navigating the patient journey in the different disease areas that we've been responsible for, be it in the TTR space, our ATTR space with WAINUA. Obviously, TRYNGOLZA with FCS and now with DAWNZERA in HAE. But we have a really strong strategy behind patient services and the way that we've designed our program, the way that we interact with patients. And I believe that, that's something that's been a key learning that we'll be able to take away and really help these patients get on and stay on treatment effectively long term.

Thanks, Kyle. And Ken, as I recall, I think we had quite a number of naive patients new to treatment in our Phase III OASIS study. Is that right?

Yes, the majority of patients in the OASIS HAE study were new to prophylactic therapy showing that the medication is equally effective in patients who are new to prophylactics or transferring from other prophylactic agents.

Your next question is from the line of Jason Gerberry from Bank of America.

This is Chi on for Jason. I have a couple from us. The first one is going back to your prior comment about script written early. Have you already identified an initial pent-up demand that is ready to switch from existing therapy to DAWNZERA? And quantitative -- either quantitatively or qualitatively speaking, what are you guys thinking about patient adoption and revenue conversion in the next 6 months? Do you expect most of the script will be free or subsidized or would you expect to have paid script as well? And then the second question is, given what we know about the label, what do you -- what's your current strategy in terms of educating physicians on the Switch data?

Kyle, why don't you take the first part and then I could jump into the Switch -- the Switch question.

Yes. Thanks, Chi. The -- in terms of early adoption here, we've had our field teams out since late spring profiling accounts, interacting with physicians and treaters of HAE that the team has experience already either in allergy and immunology or specifically within HAE as well. So it's been going very well to have preapproval compliant discussions around the disease area and some of the needs of the patients that these prescribers have. We've also done a great job with our medical affairs team presenting at medical congresses and sharing, obviously, the information from all the New England Journal publications and all of the other data that's been generated on this program. So that's been really an ongoing effort. We are hearing that there are patients that are, again, unsatisfied and looking for better treatment options. And obviously, we'll be communicating with them starting immediately around the approved label, making sure that they have access to our start forms and that they can begin writing prescriptions as early as today. So that the team is ready and anxious to get out there and make all of that happen. In terms of revenue conversion as we look at the launch, as I mentioned, this is predominantly a Switch market. There are going to be naive patients that will be getting prescriptions but it's going to take a little time for physicians and patients to be educated on donidalorsen. And we believe that this will be a launch uptake that will be successful long term with $500 million plus in peak revenue. For 2025, I think we feel comfortable with where consensus is at today, if that's helpful from a guidance standpoint for you. In terms of free drug versus paid drug, it will be a combination of that. We do, and we intentionally designed our program to have a free drug program so that patients can get on treatment very quickly. This is a severe and devastating potentially fatal disease. And we want to make sure that patients have access to DAWNZERA as quickly as possible. So there is the free 30-day start for patients. And then we also have our QuickStart program. So if there is by chance an approval delay from the payer, we'll be able to move those patients through on to our QuickStart program. That being said, there are established criteria that are in place. This is an established market with other competitors that are in the space. So payers have policies in place today. And we believe that we'll be able to help physicians and their staff follow the policies of those respective plans in order to get DAWNZERA approved fairly efficiently. So it's going to be a blend of free drug combined with paid drug as we move forward. And then the last piece was kind of strategy around educating on switch. And I'll turn that back over to Brett.

Sure. So Chi, first off, we couldn't be more thrilled with the label for DAWNZERA. We believe it reflects a truly compelling profile. And as Ken outlined in his remarks earlier, we're very proud of the data we generated in the prospective Switch study. The only study of its kind ever conducted in where we not only enrolled the study quickly, amplifying Kyle's points earlier that patients are looking for better treatment options. They're willing to switch and try donidalorsen DAWNZERA in a clinical trial, we further improved their efficacy beyond their baseline prophylactic HAE attack rates. And as Ken highlighted, patients strongly -- more than 80% of patients preferred donidalorsen DAWNZERA over their previous treatment prophylactic treatment option. We're going to utilize all this information. It's been so incredibly well received by the HCP community already, and we're going to continue to double down on that. What really matters is our ability to market the switch data through the publications and presentations that we've given on the Switch data already, and we're going to definitely do that. And that's really going to be our strategy to double down all the news that we put out on the Switch data already.

Congrats on the approval, and we look forward to the approval data.

The next question is from the line of Myles Minter from William Blair.

This is John on for Myles. Congrats on the approval. So I was wondering if you have any idea of what proportion of current TAKHZYRO patients are currently on the once every 2 weeks dosing versus the once every 4 weeks dosing? And for those patients that are currently on once every 4 weeks TAKHZYRO, would they be eligible to directly switch to a once every 8-week dose of DAWNZERA? Or would they need to transition to a once every 4 weeks dose first?

So the TAKHZYRO breakdown that, as we understand it, is about 75% are on every 2 week and about 25% are on every 4-week today. The recommended dose for DAWNZERA is going to be every 4 weeks. They have the option of going to every 8 weeks, if they're stable and doing well. And I think once the product is launched and physicians and patients start to gain experience with that, we will begin to better understand what the treatment dynamic looks like and what that split ultimately will be.

Yes. John, there's no restrictions on whether a patient was on every 2 weeks or every 4 week TAKHZYRO, whether they can go on to every 4 weeks or every 8 week DAWNZERA. But as Kyle mentioned, our recommendation would be for patients to start with every 4-week dosing with DAWNZERA from whatever dosing regimen they're on with a previous prophylactic treatment.

Your next question is from the line of David Lebowitz from Citi.

This is [indiscernible] on for David Lebowitz. Congrats on the approval. I noticed in the label, the Switch study data is not there as expected. Could you give us any color or commentary on our discussions with the FDA went with regards to that? What does a potential pathway look like for eventually getting the Switch study in there? And if it's not in the label, how does that impede at all, if any, your efforts on educating physicians and being able to market DAWNZERA?

Sure, Mike. So again, we're very pleased with the DAWNZERA label. We believe it reflects a truly compelling product profile. I don't want to get into discussions with FDA, but consistent with FDA practice, the efficacy data, including the label is from the Phase III randomized placebo-controlled trial. And that's traditional FDA practice. It does also include safety data from the OASIS-Plus study, the open-label extension and the switch data and mentioned earlier, we couldn't be more proud of the Switch data that really provides the instructions, the road map for safely and effectively transitioning patients from prior prophylactic treatments to DAWNZERA. And we're going to utilize this in our marketing -- in all of our marketing strategies because the data is now published and have been presented several times. It has been very well received. Right, Kyle?

That's correct. So our team can educate HCPs on the data that's been generated from all of our studies on donidalorsen. This would include the data published in the New England Journal as well as the Switch data that was published in JACI in practice. The Switch data is very compelling, and it's very helpful from a safety standpoint and from an execution standpoint, to be able to demonstrate 62% overall mean HAE attack reduction after moving to DAWNZERA compared to a baseline with patients on prior prophylactic treatment. This really does help HCPs make decisions around how to move over successfully and not increase attacks. And then I know the other number that Ken shared was 84% of those surveyed indicated that they preferred DAWNZERA over their prior prophylactic treatment. And I think that's important as well for patients to understand not only how they're doing on treatment, but how they feel once they're on and also the ability to tolerate the treatment in a very convenient way.

The next question is from the line of Luca Issi from RBC Capital.

Congrats on the approval. Maybe a couple of quick ones here. Kyle, if I can circle back on pricing and please correct me if I'm wrong here, but the $750,000 a year that you cited is actually higher than the current gross price for ORLADEYO. So I wonder if you could comment on why you decided to price the drug at a premium versus an oral? And what do you think the payers start putting any hurdle in place that maybe start favoring orals ahead of injectables or anything on those lines? So any color there, much appreciated. And then second, what is the internal expectations for what proportion of patients will be on Q4W versus Q8W? Is it 90-10? Is it 80-20? Like any color there will be very helpful for us to think about their blending in price there.

Yes. Thanks, Luca. So when you look at the launch price of some of the competitors recently, they're right in the same range that we are on an annual basis and the fact that we price this on a Q4 week basis, annualized at the $747,000. So I think we're right in line with where the market is today. In discussions with payers, the payers are actually going to look at their existing patient population, they will not only assess the annualized price of Q4 week. But to your second question, I think they're going to ask what do we anticipate the split going to be between 4 weeks and 8 weeks and that's to be determined at this point, right? As I mentioned, we expect the majority of HCPs to start patients at every 4 weeks. And then if they're performing well and well controlled, they could potentially have the option of moving them to every 8 weeks. So we'll have to see what that split looks like over time, I think, within the marketplace and see how that happens. But I don't expect additional payer restrictions. I don't expect payers to look at the orals and try to prefer those over the injectables. When you look at the efficacy of the orals, there are some challenges there, I think, compared to the injectables. And then there are also side effect dynamics that happen. So what we've largely seen from payers up to this point is creating a policy for all of these HAE therapies and it's really up to the physician and patients to make the determination around which treatment is most appropriate for them. And as we've been talking about, we believe DAWNZERA is going to be a very attractive treatment option based on the efficacy, tolerability and convenience of the treatment.

Your next question is from the line of Yaron Werber from TD Securities.

This is Steven on for Yaron. Congratulations on the approval. That $500 million annual sales that we are hearing corresponds to about 700 or so patients. And I'm wondering if you could give a little bit more color on how much of that you expect to get in the first year, first 2 years? Is this going to be a steady ramp and kind of help us model how growth is going to look in the near and long-term future?

Yes, Steven, that's -- those are some details that we're not prepared to provide at this time. We're just getting started. But Kyle, if you want to add any general comments, feel free.

Yes. Just my comment around -- this is a Switch market largely in the U.S. It's going to take some time, right, to educate physicians and patients around the profile of DAWNZERA, and we expect this to become a very attractive treatment option over time. I don't think this is going to be a hockey stick inflection point right off the bat, but we expect this to be a growth over time and to be able to get appropriate patients on treatment and keep them on treatment long term.

Your last question for today comes from Yale Jen from Laidlaw & Company.

Congrats on the approval. Just from a practical perspective, how do you anticipate the patient and the physician to switch from Q4W to Q8W? Would they start to maybe getting the treatment in the 6 weeks instead of 4 weeks and eventually to see what happened and maybe automate to the 8 weeks interval? And then maybe one more add to that is that based on your open-label study at this point, do you get a general sense of maybe what might be that duration might be from 4 to 8 weeks?

So Kyle, do you want to start with the -- how you think the process will go from -- for patients from transition from every 4 weeks to every 8 weeks?

Yes. According to the label and what was -- what just came out is Q4 week is dosing with the option to move to every 8 weeks. So we expect the majority of physicians to start their patients on every 4 weeks, see how they perform and then make a decision over time if they want to move them to every 8 weeks. We don't foresee and based on what we -- in the clinical trial and the way that it was conducted, they moved from 4 directly to 8. They didn't go to 5 and 6 and do it in a sequential order. So we believe, according to the label that they will follow either a 4- or 8-week dosing regimen as is outlined.

Yes. And I'll ask Ken to just give you his perspective on what we're seeing in the long-term open-label extension studies. But in short, we couldn't be more pleased the durability of DAWNZERA is remarkable and with no emerging safety or tolerability issues with long-term treatment. But Ken, you are the expert.

Yes, absolutely. So the 8-week dosing is performing very well in the open-label extension, so that we know over the first year that they've been in the open-label extension that there was a 94% reduction in attack regardless of you were on 4-week dosing or 8-week dosing. So it seems to be very well tolerated for the 8-week dosing and also it seems to be quite durable in terms of its efficacy.

Thanks, Ken. Thanks, Yale. Thanks, everybody, for joining us today. We're at the end of the webcast now. We're making tremendous momentum. Our tremendous progress at Ionis is -- we're going to build on this momentum for the rest of this year and well into next year. And I look forward -- we look forward to sharing all of our achievements and the progress along the way. So until then, thanks, everybody, for joining again, and have a great day.