Great. Good morning, everyone. Welcome. My name's Jessica Fye. I'm a Biotech Analyst at J.P. Morgan, and we're continuing the 43rd Annual Healthcare Conference today with Ionis. First, you're going to hear a presentation from the company, and then we're going to go into some Q&A. If you're in the audience and you've got a question, raise your hand and someone will bring you a microphone. Or alternatively, you can send them to me via the portal, and I'll get them on the iPad up here. So with that, let me pass it over to Ionis' CEO, Brett Monia.
Thank you, Jess. Good morning, everybody. Thanks for joining today for my presentation. I'm really, really thrilled to be presenting to you today the remarkable progress we're making at Ionis and a vision towards an even more remarkable and exciting future for the company. I will be making forward-looking statements during the course of my presentation, and although I will be focusing my presentation on the current state of Ionis, a really exciting time for the company and a vision forward, I will also be touching in the beginning of my presentation on a little touching back to a little bit of history for the company to provide context, but in that vein, let me start here. Ionis was pioneered to create a new field based on RNA-targeting therapeutics, targeting RNA using oligonucleotides, antisense oligonucleotides originally, and then this has expanded to be so much more.
And we were highly successful, highly successful. And we did that by investigating all aspects of oligonucleotide therapeutics, including creating the industry-leading capabilities in medicinal chemistry that gave these products their drug-like properties that allow them to be attractive and effective medicines for patients. And we also led and continue to lead the way in manufacturing capabilities. We optimized and validated distribution, understanding of how these drugs get into cells, how they're distributed, what are the most sensitive cell types. And in that way, in that manner, we actually were the first to validate the liver hepatocyte as a highly sensitive organ for oligonucleotide therapeutics. And then that followed with our ability and our validation of the central nervous system, CNS delivery using oligonucleotide therapeutics.
We optimized and validated multiple mechanisms of action for oligonucleotide therapeutics, including the RNase H mechanism of action, which is basically a mechanism that involves the reduction of targeted RNA to block the production of toxic proteins. That mechanism has been utilized by breakthrough treatments like Qalsody for SOD1-ALS, like Tryngolza for familial chylomicronemia syndrome, and Wainua for hereditary TTR polyneuropathy. Then, of course, we've also been able to validate other mechanisms like splicing, control splicing, which led to the breakthrough treatment that we conceived and discovered at Ionis Spinraza for spinal muscular atrophy. All of this has led to, based on all of this, we have led the way in discovering and developing first-in-class medicines for a whole range of diseases, having provided benefit to tens and tens of thousands of patients already today. We're positioned, we're poised to help millions of people globally.
Five years ago, I assumed the role as CEO of Ionis, and that was in January. And I gave my presentation right here at the J.P. Morgan Healthcare Conference in January 2020. And what I said at that presentation during that, in my initial presentation as CEO, was that Ionis is highly recognized as a highly innovative company, research, well known for cutting-edge research and early development. And I also emphasized that that would not change for the company. That's our bread and butter. That's our strength. However, I also recognized that we needed to do more to drive value, value for shareholders, for patients, for stakeholders. And I outlined four key objectives to achieve that value, and they're shown here. First, to move beyond our original business model, which is a model that we partnered all of our programs.
We partnered in early development, research phase, and we let other companies take our drugs that we conceive and discover to commercialization. I felt we needed to change that. We needed to prioritize and advance our wholly owned pipeline, keep these drugs for commercial success ourselves. We needed to build our commercial capabilities to eventually launch our own products. We needed to expand and diversify our technology. A lot of competition emerged after we pioneered this field and created this field of oligonucleotide therapeutics. We needed to address that competition by expanding and diversifying our technology to extend our leadership position in the field we created. And then finally, we needed to commercialize our own products, products that we conceived, that we discover ourselves to bring those medicines to market to retain the full value, the full value of the medicines we had discovered.
I'm pleased to report today that we've achieved essentially all of these core objectives over this past five years. We have one of the most exciting wholly owned pipelines today at Ionis with 10 wholly owned medicines, all of which have transformational potential that are in our mid- and late-stage pipeline. We've built a highly innovative, highly experienced, and scalable commercial organization that is in place to launch our products from our wholly owned pipeline. We've expanded and diversified our technology in many ways through medicinal chemistry and in other ways, and a lot of the advancements we've made in technology are now bearing fruit. A lot of the medicines that have been recently approved over the last two years bear the benefits of the advancements, the investments we've made in science and technology.
We are now a fully integrated commercial-stage biotechnology company with our first independent commercial launch, Tryngolza for familial chylomicronemia syndrome, now underway following the December 19th approval, the first ever medicine approved by the FDA in the United States for FCS. We anticipate three additional launches, independent launches over the next three years. As I said, we built a commercial organization. That commercial organization is in place. It is an innovative commercial organization with a lot of experience. Of course, we have now achieved. We have put in place all of the necessary functions that are required for successfully commercializing your own products. That includes, of course, market access, analytics, and so on.
Patient service program that we call at Ionis, the Ionis Every Step program, supporting patients from diagnosis to understanding their disease to treatment, getting on drug and getting reimbursed, operations, new product strategy to prioritize our pipelines ourselves, innovative tools to reach patients and HCPs like omni-channel marketing. And of course, now we have our first customer-facing team in the field that is delivering Tryngolza for familial chylomicronemia syndrome. As we set out on this journey in 2020, we set out on a planned, measured approach to become a fully integrated commercial-stage biotechnology company, step by step, building on the success that we had in our rich history on discovering and developing transformational medicines like Spinraza for SMA, like Qalsody, the first ever approved medicine for a genetic cause of ALS.
Building on that innovation, our first step to full integration was to complete a transaction that involved a co-commercialization partnership with a trusted partner. And that first medicine was Wainua for TTR amyloidosis, the first indication, hereditary TTR amyloidosis for polyneuropathy. And that co-commercialization partner is AstraZeneca. It's our first Ionis-branded medicine launched in 2023, and that launch is off to a great, great start. And then our first independent launch, Tryngolza, first independent launch, first FDA-approved medicine for familial chylomicronemia syndrome, approved in December of last year and now launched in 2024. And now that launch is underway and going very well. And there's so much more to come from our wholly owned pipeline and our partnered pipeline, putting us in position for substantial, substantial revenue growth. And when I say there's a whole lot more coming, I'm not kidding.
This is what the potential near-term commercial launches look like for Ionis' wholly owned pipeline as well as our partnered pipeline. Shown in orange stars are programs that are wholly owned. In blue are partnered programs, and those that have both gold and blue represent our co-commercialization partnership. The anchor program is Wainua for TTR polyneuropathy. As I mentioned, the launch is off to a great start in our first ever co-commercialization partnership. Tryngolza, our first independent commercial launch, now underway in the United States with an anticipated launch in Europe later this year. Coming quickly behind Tryngolza is our second independent commercial launch, donidalorsen, as a potential highly preferred prophylactic treatment for hereditary angioedema with a PDUFA date of August 21st of this year and assuming an on-time approval launch this year.
Following right behind donidalorsen from our wholly owned pipeline is the second indication for olezarsen, the generic name olezarsen, for a much more highly prevalent disease called severe hypertriglyceridemia, a disease in which there are no effective treatment options available today, a disease that afflicts millions of people in the United States alone, with phase III data from that phase III SHTG program anticipated for the second half of this year, and then more, particularly from our leading CNS platform, our wholly owned CNS platform, Alexander disease, and then our Angelman syndrome program, which we anticipate to start, we expect to start and will start in the first half of phase III development in the first half of this year.
And then you can see from our partnered program, pelacarsen for Lp(a)-driven cardiovascular disease, a very, very large unmet need, chronic HBV, our bepirovirsen program with GSK, IgA nephropathy, and more. These anticipated approvals, these anticipated launches are exciting in their own right. We anticipate four independent commercial launches over the next three years from the wholly owned pipeline, four key partner launches over the next three years. Remarkable in their own right, but what's really, really remarkable is the millions of people that we are positioned to benefit globally from the medicines that we conceive, discover, and we bring to the market through partnerships and from our wholly owned pipeline.
Diseases that are for severe rare indications like ALS, like FCS, like hereditary angioedema and more, and for highly, highly prevalent diseases like severe hypertriglyceridemia, Lp(a)-driven cardiovascular disease and chronic hep B, millions of people waiting for the treatments that we bring forward to the market. And not only are we helping millions of people, not only anticipate all of these approvals and launches over the next few years, this also sets us up remarkably well for substantial revenue growth in the next few years. This is what the partner pipeline looks like today in the anticipated launches anchored by Spinraza for spinal muscular atrophy, a breakthrough treatment for SMA, Qalsody for SOD1-ALS, and now Wainua for hereditary TTR polyneuropathy.
Following these programs, we're looking forward to the anticipated launch of other programs, Wainua for the much larger indication TTR cardiomyopathy with phase III data in the second half of 2026, our IgA nephropathy program, Factor B targeting with our partner Roche, and then bepirovirsen for chronic hep B, and then our tau program, a really exciting program for Alzheimer's disease, which we showed in our phase II study that we could actually reverse the pathology and provide evidence of improved cognition by targeting intracellular and extracellular tau with our, in our, for the medicine we've brought forward and now have partnered with Biogen. All of this from our partner program, from our partner programs are anticipated to drive in excess of $2 billion of annual peak royalties from these programs alone.
And that doesn't even include the milestones that are associated with these programs that are substantial in excess of $3 billion for pelacarsen and Wainua alone. And what's really exciting is what's coming from the wholly owned pipeline shown here in red. Again, Tryngolza is now launched and it sets the stage for the rest of the anticipated launches coming forward. Donidalorsen for hereditary angioedema, again with a PDUFA date in August of this year and anticipated launch, our second independent launch for which will be for hereditary angioedema. And then Tryngolza for the much larger indication, as I mentioned, for severe hypertriglyceridemia with phase III data this year.
And then a whole host of medicines that we anticipate to be launched in the next few years from our industry-leading CNS platform that delivered medicines like Spinraza and Qalsody and tau for Alzheimer's disease and so much more anchored by our Angelman syndrome program, which we expect to start phase III development this year. Shown on this slide are the anticipated revenue that we expect from our wholly owned pipeline for just the next few years in excess of $3 billion in peak revenue potential. And when you combine this, you can do the math. What we're looking at is in excess of $5 billion in anticipated peak product revenue based on our internal programs as well as on the royalties from our partnered programs. This is what's going to drive our goal to achieve positive cash flow in the next few years.
What you can see on this slide are the three components that is going to drive positive cash flow. First, we have a steady stream of R&D revenue from our partners, milestones and so forth. That's significant and that will continue, that's shown in light blue on this slide. And then shown in dark blue are the royalties and sales milestones that we anticipate from our partner pipeline over the next few years. And then product revenue, product revenue from the Ionis wholly owned pipeline. We're looking forward to this. This is a top objective for the company to achieve cash flow positive and sustained top-line revenue growth over and over again on an annual basis. In the beginning of my presentation, I highlighted the importance of Ionis to get to accelerate value for all stakeholders by building our wholly owned pipeline, by building our commercial capabilities.
I also highlighted that we were going to and have invested heavily in research and development to expand and diversify our technology to extend our leadership position in RNA targeted therapeutics, and that's going exceptionally well. We have now new chemistries using antisense oligonucleotide mechanisms that are new backbone chemistries, for example, that are improving potency and durability so that we can dose far less frequently than we have in the past. Also, Ionis invented chemistries for Ionis siRNAs have now reached clinical testing and there's a lot more coming, and we're making great progress in gene editing. Targeted delivery is going exceptionally well, opening up new tissues like cardiac myocytes for heart failure indications, skeletal muscle for neuromuscular diseases.
What's really exciting is the work we're doing, and we're on the precipice of advancing new programs for CNS diseases, not just by infrequent intrathecal dosing, which is how we're dosing now, but now maybe even systemic dosing using subcutaneous or intravenous administration by overcoming the blood-brain barrier. Stay tuned for that. All of this is positioned to strengthen our leadership in cardiovascular and neurological diseases and potentially other areas. Now, after these years of investment over the last few years, we're now going to see the benefits of these investments reaching or on the precipice of reaching clinical testing. We expect to achieve clinical process and present proof of concept for our first Ionis MsPA backbone chemistry this year. It's a part of our APP program in Down syndrome patients with dementia. Our first siRNA proof of concept will come out of the clinic this year.
And we're expecting to advance our first Bicycle siRNAs into clinical testing this year for muscle targets, particularly cardiac myocyte, and to initiate IND enabling studies for neuromuscular targets, skeletal muscle, and our first blood-brain barrier candidate with others overcoming the blood-brain barrier to follow. Not surprisingly, with all this progress that we're making and all the investments we've made to advance our technology and to commercialize our own drugs, 2025 is set up to be an exciting year, a year full of key value, key value-driving events. Pipeline, phase III development. We're anticipating three phase III readouts this year. I already highlighted Tryngolza for severe hypertriglyceridemia in the second half of this year, zilganersen to address a rare neurodevelopmental leukodystrophy called Alexander disease, phase III data in the second half of this year, and pelacarsen for Lp(a)-driven cardiovascular disease, phase III data this year.
We expect to expand our phase III pipeline this year as well when we initiate phase III development for our Angelman syndrome program, ION 582, which will get started in the first half of this year. We also have mid-stage pipeline readouts. On the regulatory front, we're looking at the FDA approval of donidalorsen for hereditary angioedema, the European approval of Tryngolza for FCS, and European and other territory approvals for Wainua. That's the name for Wainua in Europe for hereditary ATTR polyneuropathy. Of course, the product launches, donidalorsen for hereditary angioedema, Tryngolza launch in the U.S. for FCS and in Europe for FCS, and Wainua the full year launch for Wainua for ATTR variant polyneuropathy.
So in closing, I think you see now why we're so excited at Ionis about all the great progress we've made over the last few years to drive accelerated value for the company and our vision for the future, which is very exciting. And we're very much looking forward to achieve that vision. And we're in a great position to do so. We have a proven and prolific discovery and development engine. Our pipeline is delivering across the board at all stages, CNS, cardiovascular, and more. We have a scalable, highly experienced, innovative commercial organization now in place that's launched Tryngolza and is going to launch the next wave of Ionis products. I've laid out for you a clear path to positive cash flow with top-line revenue growth anticipated in the next few years.
And importantly, very importantly, of course, we are positioned to improve the lives of millions of people globally for rare diseases, for highly prevalent diseases in which there are no meaningful treatment options available today. Before closing, I just want to acknowledge it takes a great deal of many people to achieve everything we've achieved at Ionis over the last few years. I want to acknowledge the collaborators and research that we've done so much work with over the years, the investigators that run our clinical trials and are devoted to Ionis, the patients who participate in our clinical trials, and very importantly, all of the people at Ionis who work painstakingly or persevere to drive value for all stakeholders, to drive value for Ionis, for patients and so on who work around the clock to do so. Thank you very much.
Great. Thanks. Maybe first I'll take a question from the audience here. You talked at the beginning of the presentation about how the strategy of the company has changed under your leadership. So how are you thinking today about what assets you would still partner out versus keep in-house? And kind of what are the pros and cons of partnering assets outward?
Yeah. So when we made the strategic decision to become a fully integrated commercial stage biotech company in 2020, we also inherited a big pipeline, right? And it was clear that to be successful, we were going to have to move in this direction in a measured manner, carefully. We weren't going to, all the programs that were not partnered yet, we weren't going to keep. So we were going to have to focus. Focus is a key objective for the company and for us to in the programs we prioritize in our wholly owned pipeline. So partnering had to happen. And we've been very successful in partnering programs that we choose not to keep today.
As we continue to do that and to prioritize our pipeline and focus it down to the programs that we think we're going to bring the greatest value to the company, we also have to recognize that we have a highly prolific research organization. That research organization is focused on bringing forward programs that are intended to be kept, right? They're intended to be kept. So you're going to see less partnering in the future as our pipeline gets focused down and as our research organization brings forward new medicines that are intended to be kept by Ionis. With that said, there are always exceptions and life is uncertain. And sometimes there are reasons to partner a program or not. And I think the key thing is that what we really want to do is to build those synergies, right?
To build common call points for medicines we bring forward ourselves. And if we don't feel that a medicine that is going to achieve a synergy with programs coming behind it, we may choose to partner those programs. But those will certainly be the exception more than the rule.
And then you talked about the goal of becoming cash flow positive over the coming years. And based on the slide, it looks like that's going to be very top-line driven. How do you see the company's cost structure evolving now that you do have multiple wholly owned products that you're going to be launching?
As I outlined, we are in a great position with the anticipation of several launches, four independent launches over the next three years for our wholly owned pipeline and four key launches from our partnered pipeline. We're also in a good capital position. Our capital position today is strong. But we still remain in a period of investment. Research and development is essentially at steady state. We don't see the need to grow that organization and still maintain a highly prolific R&D organization. But we are going to have to grow our commercial organization in anticipation of the next launch, for example. We have everything in place for the Tryngolza FCS launch now. We are going to have to invest a bit more for the donidalorsen launch later this year in HAE.
Then, of course, we're going to have to invest in the much larger disease indication, severe hypertriglyceridemia, which we anticipate to launch next year. With that said, we don't really, we expect modest growth in expenses, single-digit growth. That's mostly driven by the commercial investments we're going to need to make to ensure that these launches are successful.
You talked about a desire for new pipeline products to ideally have synergy with the portfolio ahead of them. How much synergy do you see across the kind of the first wave of commercial launches?
Synergy is coming in different forms. We have a great deal of synergy with what I refer to as sort of the backroom internal investments you need that supports all commercial launches, whether that's market access or patient service hubs and the like. From a therapeutic standpoint, call points, those kinds of things, where do we see synergies? Well, there's a very significant synergy as we transition from FCS to severe hypertriglyceridemia, right? This is a disease that is caused by severely elevated triglycerides in both cases. And FCS is a launchpad to get us out there and exposed and get Tryngolza exposed for severe hypertriglyceridemia. These are patients in both cases that are treated by common call points, endocrinologists, lipidologists, pancreatologists, in some cases cardiologists. But these are patients that are managed essentially by a similar physician segment. Great synergies there.
Our neurology pipeline that's growing rapidly, our wholly owned neurology pipeline is also offering significant synergies. For example, we have four drugs for pediatric neurology in our pipeline today, including Angelman syndrome, about to start phase III in Alexander disease with phase III data this year. And then we have others for pediatric neurology, common call point, and then in dementia. We have several programs advancing forward in dementia. Our first program is in prion disease, which is a form of dementia, a rapidly progressing neurodegenerative disease that's really a cause of a form of dementia. And then we have our amyloid precursor protein program that's now in phase II development for in dementia associated with Down syndrome. And we have more dementia programs. There will always be one-off opportunities that may not be a perfect fit for some of those synergies that I just described.
We are focused on building those synergies to maximize efficiency.
Okay. There's a lot kind of going on with the commercial organization this year. But in terms of kind of earlier mid-stage pipeline readouts, what would you focus investors on this year?
On the mid-stage pipeline side, we are focused, of course, on the mid-stage pipeline. We are also laser focused on the four phase III readouts that we plan for this year, which represent potential near-term launches for those programs. On the mid-stage pipeline, it's going to be very prolific as well. We're expecting phase II data from our alpha-synuclein program for multiple system atrophy, a very aggressive form, if you will, of a movement disorder, Parkinson's disease. Proof of concept could lead to a phase III triggering for that program. That's wholly owned, by the way. And then our polycythemia vera drug, sapablursen, we're planning to present and get out there phase II data for that program, which also would trigger, if positive, a decision to go to phase III development.
As I mentioned in my prepared remarks, we're also expecting some initial proof of concept data from our first clinical Ionis-discovered using Ionis chemistry siRNA program in the clinic to validate our approach to siRNA drug development and also our first MsPA backbone chemistry in the APP Down syndrome study this year as well. There could be more. Some of these studies are enrolling now. So it's difficult to project whether they'll complete enrollment and we'll have data in time. But that's certainly, it's going to be an exciting year for the mid-stage pipeline as it will be for the phase III pipeline as well.
So you mentioned kind of the first proof of concept for an Ionis siRNA. How are you prioritizing target selection and choosing between leveraging an ASO versus siRNA?
Yeah. I have to say, maybe I'm a little biased. We have the strongest research organization in any company, not even close in oligonucleotide therapeutics with medicinal chemistry as the foundation. When I made the decision to expand and diversify our technology to include ASOs, new chemistries for ASOs, siRNA, now even gene editing, it was like unleashing an incredible amount of talent on all aspects of oligonucleotide therapeutics. We make some fundamental decisions right out of the gate on whether to pursue a siRNA or an ASO, for example, for programs in which we're intending to modulate splicing, splicing to produce a drug to correct splicing or to modulate it in a beneficial manner. It has to be an ASO. You cannot develop a siRNA to modulate splicing.
Nuclear RNAs like Angelman syndrome, UBE3A and Angelman syndrome work much better with ASOs versus siRNAs in the nucleus, other nuclear retained RNAs as well. For programs in which siRNA and ASOs have the potential to be the best for a particular target, we advance both platforms, both technologies forward within Ionis, and we let the best drug win. We let the best drug win based on potency, based on off-target potential, off-target risk, as well as durability so we can dose more conveniently for patients, so it's a dynamic environment, and we are well positioned to bring forward the best possible drug for a given target for a given indication.
So maybe turning to some specific products. Last year, you launched Wainua. How should we think about growth for that asset in 2025?
Sorry. Let me just start with this. The Wainua launch is off to a great start. We didn't have a full year last year. We launched in February with our co-commercialization partner, AstraZeneca. Our focus is on patients that are new to treatment. More than 80% of people with ATTR polyneuropathy are not on treatment today. So that's obviously our focus, and we're doing very well there. I think we reported in our Q3 earnings last year that more than 40% of patients that are new to treatment are on Wainua after only eight or nine months. That's pretty good. We're also seeing switches from existing treatments that are moving on to Wainua. That's nice to see, of course, but our focus is on newly diagnosed patients. We're seeing a nice mix of cardiologists prescribing Wainua and neurologists prescribing Wainua, which is good to see as well.
We expect the momentum we had in the 2024 launch to continue. We expect steady continued growth for the Wainua launch in 2025.
When you're thinking about cardiomyopathy, following the HELIOS-B results, can you talk about any changes that were made to the phase III CARDIO-TTRansform trial, for example, on variable follow-up? How should we think about timing for that study? And is it powered for the TAF and non-TAF subgroups?
Yeah. Just as a level set for everybody listening in, our CARDIO-TTRansform phase III study in ATTR cardiomyopathy is the largest study ever conducted by far in this patient population. And that positions it to have the richest, deepest data set ever produced for this disease indication, in which it's a big indication. More than 500,000 people are estimated to have TTR cardiomyopathy. And treatment options, although some exist, are still by far insufficient to really address this disease. We want to run this study to the finish line, which is the second half of 2026, to take advantage of the trial design that I just summarized to obtain the richest, most deepest data set possible to make sure that the benefits that Wainua can offer to TTR cardiomyopathy patients is fully realized. It's fully realized by a rich data set.
The second half of 2026 is the plan to complete the study, more than 1,400 patients over 140 weeks. We've made no trial changes, no trial design changes. We're sticking with the trial design we came up with. We think that that's a big, big opportunity, a big advantage for the program. The trials, of course, it's powered for the primary endpoint, which is cardiovascular mortality and cardiovascular hospitalizations. But because of the size of our study, we think we're going to have, based on pure numbers and, of course, the demographics, which has worked out very well for us, the richest data set as monotherapy, Wainua alone for treating cardiomyopathy and Wainua in combination with tafamidis, the only treatment approved for TTR cardiomyopathy. But it's still the primary treatment for TTR cardiomyopathy today.
We're going to have the richest data set that could support advocating for combination usage of a silencer or Wainua with tafamidis, for example, or a stabilizer, if you will. That data will come in the form of mortality, hospitalizations, functional endpoints like six-minute walk distance. In addition, we're conducting the most intensive imaging studies ever conducted in TTR cardiomyopathy, MRI and scintigraphy, longitudinal assessments so that we're actually going to be able to look at what the amyloid burden is over time when we look at combination versus monotherapy. Is there a faster clearance of amyloid, for example, in combination? Can we reverse it more effectively? Is the heart function better? All of this is going to be very, very important to inform cardiologists on how to use Wainua, combination, monotherapy, and so on. So we're well positioned to have the richest data set.
We're committed to running the study out to completion.
Maybe turning to another one of your near-term launches for donidalorsen. Where are you envisioning that product kind of initially picking up patients? Will it be those who are new to HAE prophylaxis? Will it be switchers? And if they're switching, would you expect to get them more from the existing injectables or oral treatment?
Donidalorsen has the potential to be the preferred prophylactic treatment for many, many patients for hereditary angioedema to prevent attacks from these severe, potentially fatal attacks from happening. Treatments today that are prophylactic treatments for HAE in the United States are available. But there's a strong desire for more effective treatments, better tolerated treatments, and more convenience for patients that are on existing Prophy treatments today. In the United States, 70% plus patients today are on one of the prophylactic treatments. Not surprisingly, this is a severe, potentially fatal disease. So they tolerate what they can tolerate. But they do switch. They do switch back and forth from treatments because they are seeking better treatments for the reasons I said.
Donidalorsen, based on our phase II data, our phase II data that is now elevated to be a pivotal study in our submission to the FDA and our phase III data, is positioned to satisfy the needs of these patients: better efficacy, reduction of HAE attacks, better convenience, and better tolerability. So we think it's going to be the preferred treatment for many of these patients. And we're going to see switch. We're set up. And our focus is to promote the switches from existing therapies to donidalorsen because the U.S. is a switch market. And you know what else?
We actually proactively, prospectively conducted a switch study, the only study ever done prospectively in HAE to ask the question whether patients are willing to switch from an existing marketed product to our investigational medicine, how that goes, are we able to protect those patients from HAE attacks, and ask the patients what they prefer at the end of the trial. Not surprisingly, patients, we were able to enroll the study quickly. Patients are looking for better treatment options based on the reasons I said. Not only did they enroll the study, we enrolled the study quickly. We were able to keep patients on drug. They liked being on donidalorsen.
And when we read the study out last year at the EAACI conference, we actually showed that not only were we able to protect patients from HAE attacks, we were able to improve their HAE attack rate compared to their baseline values of their existing prophylactic treatments by more than 60%. We improved reductions in HAE attacks. And then the patient survey, which was conducted independently, more than 80% of patients said that they preferred donidalorsen over their previous treatment options. Why? Better efficacy, better tolerability, and better convenience were the reasons. So we think we have a really good program. And we have a really good opportunity to switch patients from existing therapies, whether it's oral or subQ.
Great. Well, with that, I think we're out of time. So thank you.
Thanks, Jess.