Please provide an update on Ionis for you today. I'm very pleased that all of you are joining us for today's presentation. Before I get started, I would like to first announce for our shareholders some changes to the Ionis Board of Directors, starting with Stan Crooke. Stan Crooke, after today, will be stepping down from the Ionis Board of Directors. Stan, of course, is the founder of Ionis Pharmaceuticals and has served as the CEO and Executive Chairman for over 30 years at Ionis, and more than that, he provided 30 years of outstanding leadership to the company. We will very much miss Stan going forward, but we're very pleased by the fact that Stan will be continuing to serve on Ionis as a scientific advisor going forward.
In addition, Breaux Castleman, after eight years of outstanding contributions to Ionis as a board director and as a member of the audit committee, will also be stepping down off the board after today, and we'll very much miss him as well. Other changes to the board include the following. Joseph Loscalzo has now been appointed Chairman of the Board for Ionis Pharmaceuticals. Joe has served on the board for seven years now, and I've very much enjoyed working with him over that time, and I'm very much looking forward to continuing to work with Joe going forward. In addition, we're adding a new board member, Allene M. Diaz.
Allene M. Diaz is coming to Ionis Pharmaceuticals' board of directors with extensive experience in the building of commercial organizations in the pharmaceutical industry and in the marketing of such products, capabilities that we're very much looking forward to complement the rest of our talents on the board. Joseph Wender, recently appointed as Lead Independent Director of the board, will continue in this role, and these three individuals round out a truly outstanding group of directors on our board, a group that I very much enjoy working with, but more than that, look forward to working with to bring Ionis even greater success well into the future. These are my forward-looking statements, which I recommend to you review at your convenience.
My presentation today will focus on Ionis Pharmaceuticals today, where we are today, as well as the future of the company, a future that we believe is incredibly bright, and a future that we will continue to deliver transformational medicines to patients on and bring new marketed products to patients for a very long time. However, before I focus on where Ionis is today and where we're headed, I did want to spend just a moment on the past, and in fact, the recent past, and more specifically, the recent announcement in March when Roche informed us that they were terminating the phase III study for the Huntington's disease trial involving our drug, tominersen, due to the conclusion that they came to that the drug was not providing benefit to patients and would not provide benefit to patients if the study continued to its natural completion.
We were disappointed by this setback, but it's a setback that Ionis can certainly absorb considering our rich mid-stage and late-stage pipeline that I'm going to take you through in a few moments. It was of course a very big disappointment for the patients who were depending on tominersen to change their lives and provide a treatment for this devastating disease going forward. We continue to work with Roche to work through the data, and we believe that the learnings from this phase III study will teach us a great deal about the disease and also increase our probability for success in developing new drugs for Huntington's disease going forward, including potentially drugs from our own pipeline. Now for the future and the present for Ionis Pharmaceuticals.
Ionis today is a leading biotech company delivering transformational medicines to patients in great need and will continue to do so for many years to come. Ionis was built today on a commitment to innovation. 30 years of innovation at our core, innovation in science, in research, in drug development, and in innovation in conducting our business activities over that period of time. Innovation will always be at the core of Ionis Pharmaceuticals, and we're going to use these 30 years of what we built with a focus on innovation to bring Ionis to even greater successes. We're going to focus on going forward on three key objectives. The first objective is launching of a new business model for Ionis to bring even greater value to the company.
This business model will allow us to now commercialize drugs from our own pipeline, our wholly-owned pipeline, and deliver these drugs to the market, drugs that we choose to commercialize ourselves, bringing even greater value to the company. By doing this, we will also be expanding our commercial capabilities, which we're well along the way on doing, and prioritizing the Ionis wholly-owned pipeline. The second key objective for the company will be to expand and enhance the scope of our drug discovery capabilities. That is to be able to build out our technologies and our platforms so that we can tackle diseases that are very difficult to tackle or even impossible to tackle with our current platform today. Thirdly, we're going to deliver a large number of new transformational medicines to the market for many years to come.
Our goal and what we're projecting are 12-plus marketed medicines on the market by in 2026. How are we doing against these three key objectives? First, in the evolution of our business model, we will strive to create an excellent commercial organization that matches the excellence we've created over the years in research, drug development, and in our business. We've made many key steps along the way already to achieve this goal. First, we reacquired our commercial affiliate, Akcea Therapeutics. This was important for several reasons, most notably because it allowed us to bring in excellent, highly talented individuals to commercialize and build out our wholly-owned pipeline and get us ready for commercialization of drugs that we choose to bring to the market ourselves.
In addition, the acquisition of Akcea allows us to bring in full value for the pipeline of drugs that we're very excited about, drugs that we discovered and put into Akcea years ago. This includes partnered drugs as well as drugs that are now Ionis wholly owned. We're also well on our way in building out our commercial capabilities and building out and prioritizing our wholly-owned pipeline and expanding our infrastructure to set us up for successful commercialization activities in the future. How are we doing in expanding and enhancing the scope of our drug discovery capabilities? Well, we're doing very well, actually. We have made a priority of strengthening our internal efforts on human genomics, and we've also established partnerships in human genomics.
This is important because our focus here is to continue to identify drug targets that have a human genetic linkage to them to enhance our probability for success and to continue to replenish our pipeline of genetically validated targets well into the future. In addition, we have strengthened our targeted delivery capabilities internal by significant investments internally as well as through external partnerships and collaborations, and we expect possibly to even do more collaborations in the future. Thirdly, we've launched additional initiatives in medicinal chemistry and new routes of delivery that will continue to allow us to tackle new diseases going forward, and we're prioritizing these activities today. We've begun now to explore potential new platforms to diversify our platform capabilities for drug discovery in the future and to complement what we're doing in the antisense platform.
Our third objective is to deliver 12-plus new-to-market medicines in 2026, and we're very much well on our way in achieving this goal. Today, we have six ongoing phase III studies at Ionis, and by the end of this year, we expect to have seven, possibly eight phase III studies in progress. Tofersen, our phase III program in ALS, is due to read out in the fall of this year, and we have additional phase III starts that are planned for the second half of this year, as I mentioned, and also well into 2022, additional phase III starts are expected. All of this sets us up for a steady cadence of phase III readouts every year, with some years having more than one readout, including this year with our tofersen SOD1 ALS drug.
These 12-plus medicines that we're projecting to be on the market in 2026 will primarily come from two leading franchises from the Ionis drug discovery and development pipeline, neurological diseases as well as cardiometabolic drug discovery activities. In our neurological franchise, today we have three ongoing phase III studies, 11 medicines in clinical development, three of which are wholly-owned Ionis drugs today. Our cardiometabolic franchise is as equally productive with three ongoing phase III studies, 14 medicines in clinical development, six of which are wholly owned medicines. Disease indication for neurological disease, of course, is led by SPINRAZA, our transformational medicine for all forms of spinal muscular atrophy. SPINRAZA continues to perform very well on the marketplace today as a blockbuster.
In the first quarter of this year, we achieved greater than $500 million in revenue, which exceeded the fourth quarter of 2020. We expect continued growth for SPINRAZA well into the future. Today, there are more than 11,000 patients on SPINRAZA today. The prevalence is higher than we originally thought it was when we first started our SMA program. Because of that, there's a lot of room for growth. In addition, we continue to enhance with our partner, Biogen, the profile of SPINRAZA by conducting post-marketing studies that will further enhance the profile of this drug, giving it an even greater competitive edge against the competition. For example, the DEVOTE study, in which we're examining higher doses of SPINRAZA in patients with SMA, is well underway. The objective there is to demonstrate even greater efficacy by examining these higher doses.
In addition, the post-marketing RESPONSE study is in progress. This is a study in which we're evaluating SPINRAZA in patients that are doing suboptimally. They're not doing as well as had hoped who went on gene therapy. They're being converted over to SPINRAZA. The objective there is to demonstrate that these patients will benefit from SPINRAZA after suboptimal treatment with gene therapy. SMA is our leading indication in neurological diseases, but it's only one of many in the clinical pipeline today from our neurology franchise. Today, we have four drugs in amyotrophic lateral sclerosis in development, and I'll be taking you through these drugs in a little bit. We also have drugs in development for dementias, such as Alzheimer's disease and frontotemporal dementia. We also have drugs for Parkinson's disease and synucleinopathies in clinical development and leukodystrophies.
I can tell you that even by the end of this year, there'll be more neurological disease drugs in the clinic for other indications as well, and more to come in the years to come. Our cardiometabolic franchise is equally impressive. Today, we're addressing all major cardiovascular disease risk factors that are essentially known today that cause cardiovascular and cardiometabolic diseases, including drugs that manage lipids that cause atherosclerosis or other cardiovascular types of diseases. Our PCSK9 program is moving very nicely to manage LDL cholesterol, our ApoC-III franchise for the management of triglycerides, and vupanorsen for the treatment of mixed dyslipidemias, as for an example. Our antithrombotic drug, Factor XI LICA, Factor XI LRx, is in a phase II-B study for the prevention of thrombosis in patients at risk for thrombosis.
In addition, we are targeting other risk factors such as transthyretin for the treatment of heart failure or cardiomyopathy, pelacarsen, which targets another risk factor, Lipoprotein(a), which causes atherosclerosis, stroke, and heart attacks. Finally, we have two drugs in development today that are being developed for the treatment of refractory hypertension. Now what I would like to do is take you through our phase III programs, provide you an update on these programs, what their status is, and where we see them headed. Today, we have five drugs in phase III development being tested and evaluated in six phase III studies. The drugs are listed here on this slide. What you can see also on this slide are the disease indications and the prevalence.
The prevalence is worth noting because it demonstrates that not only are we targeting in these phase III studies severe rare diseases such as ALS, but also very highly prevalent diseases such as Lp(a), cardiovascular disease, which is affecting millions of people around the globe. What you can also see on the right is when the data readouts are expected for these phase III studies. As I said earlier, we're expecting phase III data readouts every year for as far as the eye can see from our late-stage and mid-stage pipeline, including this year with our tofersen phase III readout in the fall. Now what I'd like to do is focus first on our neurological disease franchise, phase III programs, tofersen and ION363.
tofersen is being developed for the treatment of a form of ALS called, due to mutations in a gene called SOD1 ALS. I think everybody recognizes the fact that amyotrophic lateral sclerosis or Lou Gehrig's disease is a fatal disease with a very large unmet medical need. It's a severe disease that occurs due to a functional decline in motor function, paralysis, respiratory function due to degeneration of neuronal cells and glial cells in the central nervous system. It's a rapidly progressing form of neurodegenerative diseases, with survival lasting only a few years after symptom onset, typically. In addition, there are several different causes of ALS that have been identified today, several different genetic causes due to mutations in genes that cause ALS. There's also the broad ALS, in which no known genetic linkage to this form of ALS has been identified to date.
Tofersen is targeting a genetic form of ALS due to mutations in the gene SOD1 or superoxide dismutase type 1. This is a toxic gain-of-function disease, which means that the overproduction or the production of the protein is what's causing this form of ALS. This is the second most common genetic form of ALS. We know that ALS has over 100 mutations have been identified today in the SOD1 gene, many of which have been linked to SOD1 ALS, some of these mutations cause a very rapidly progressing form of ALS. Tofersen targets the root cause of SOD1 ALS. It blocks the production of SOD1 in the CNS. The prevalence of this rare disease is shown here, 1,400 patients estimated in G7 countries. Again, this is a severe form of ALS. It's invariably fatal, with no treatment options available for really any form of ALS today.
This has the potential to be the first in-class product and certainly transformational for families and patients suffering from this genetic form of ALS. Tofersen targets the root cause of SOD1 ALS, SOD1. We've demonstrated in phase I/II studies in patients with SOD1 ALS, robust reductions in SOD1 with strong trends in improving outcomes, slowing down progression of this disease. This led to the initiation of the phase III study called VALOR, which is now fully enrolled and due to read out in the fall of this year. In addition, our partner Biogen and Ionis have also initiated this year a second phase III study called ATLAS. ATLAS is a study in which tofersen is being tested in patients with SOD1 mutations who have yet to develop symptoms of ALS, so they're pre-symptomatic.
Of course, the goal here for this study is to prevent the disease onset from ever occurring. To fersen is one of two drugs in development today for ALS that is in phase III development. Our second phase III drug for ALS is ION363, which targets FUS ALS and is a wholly owned product of Ionis Pharmaceuticals. FUS ALS, like SOD1, is due to a mutation in a gene called FUS, which is a toxic gain of function disease. It is the third most common genetic form of ALS and is a very fast-progressing form of ALS. Like SOD1, FUS mutations cause motor neuron degeneration through a toxic gain of function mechanism, as I mentioned, causing destruction of neuronal cells, glial cells, and rapid deterioration of the motor function of the central nervous system. ION363 is a wholly owned phase III program targeting FUS ALS.
We're targeting the root cause of ALS mutations in FUS. We're targeting the FUS gene and blocking the production of this toxic gain of function protein. We've shown in animal models that we can halt the progression of the disease and prevent motor neuron loss in models of FUS-ALS. We also have supported in a compassionate use study with an investigator at Columbia University with our FUS-ALS drug ION363 in patients with FUS-ALS. Based on encouraging results from that study, it supported our decision to move into phase III development. We have a very innovative pivotal study design designed to achieve potentially rapid acceleration to the market. As I mentioned, the phase III study is now enrolling. We are committed to treating all forms of ALS. tofersen and ION363 are two drugs in our ALS pipeline today.
We also have IONIS-C9Rx, which is a phase I/II study in patients with another genetic form of ALS due to mutations in the gene called C9orf72. This is the most common genetic form of ALS. Data is expected to read out in the first half of next year for this program. Fourthly, we also have ION541, which is in phase I/II development for broad ALS. This drug targets ATXN2 for the broad ALS population, and this phase I/II study is well along the way. We're looking forward to additional programs for the treatment of ALS coming to the clinic in the future. Now I'd like to focus on three phase III drugs that were developed from our cardiometabolic franchise, eplontersen, IONIS-APOCIII-LRx, and pelacarsen.
These three drugs utilize our most advanced targeted delivery chemistry called LICA chemistry, which confers to these drugs excellent potency, excellent tolerability with the convenience of once-a-month administration or even less frequent. Let me take you through these three drugs, starting with eplontersen, which was previously referred to as IONIS-TTR-LRx. This is a fatal disease characterized by the formation of TTR amyloid deposits in various organ systems, which causes multi-organ failure, typically dominated by the failure of the heart system, causing cardiomyopathy or the peripheral nervous system, or both. This is a progressive disease that results in a rapid decline in quality of life and quite often death. Depending on the individual and other circumstances, life expectancy can be very short, or it could be longer.
This is a highly prevalent disease when you look at the entire population of patients suffering from TTR amyloidosis, estimated with a prevalence of greater than 250,000 around the globe. It is often fatal, as I mentioned, and certainly our LICA medicine, eplontersen, has the potential to be the best-in-class medicine for the treatment of all forms of TTR amyloidosis, thereby being transformational for patients and truly changing, in a beneficial manner, the standard of care for patients suffering from TTR amyloidosis. As I mentioned, eplontersen utilizes our most advanced chemistry, our targeted delivery chemistry called LICA chemistry with high potency, excellent tolerability, targets the root cause of TTR amyloidosis. In phase I development in normal volunteers, we demonstrated greater than 90% reductions in transthyretin, the TTR protein, the cause of this disease, in these normal volunteers with excellent safety and tolerability.
Eplontersen today is in phase III development, and in fact, it is in two phase III studies today, one for the hereditary polyneuropathy indication, the same indication as TEGSEDI, as well as the broader indication, the cardiomyopathy indication, due to TTR amyloidosis. Like our other drugs, we're targeting the root cause of this disease, TTR. It utilizes our LICA chemistry, which brings tremendous advantages to the profile of the drugs. We've shown very nice reductions in TTR protein in phase I, and the two ongoing phase III studies are well on their way in enrolling with the polyneuropathy phase III study due to read out next year. Our second drug in phase III development from our cardiometabolic franchise is IONIS-APOCIII-LRx. APOCIII-LRx is being developed for the management of diseases related to high triglycerides.
We all know that elevated triglyceride levels are associated with many major medical issues, including an increased risk for cardiovascular disease, as well as metabolic disorders such as diabetes and acute pancreatitis, which often can be fatal. ApoC-III is the master regulator of triglyceride levels in the body, and has also, not surprisingly, been identified as an independent cardiovascular risk factor. There are several different populations that have been bucketed, if you will, patient populations that suffer from high triglycerides. This includes the familial chylomicronemia syndrome patient population, or FCS, which is a rare population. These patients suffer from metabolic diseases due to very high triglycerides, well above 1,000 milligrams per deciliter. A second bucket involves patients suffering from triglycerides above 500 milligrams per deciliter. This is referred to as severe hypertriglyceridemia, or SHTG, and this is not a rare disease.
In fact, in the United States alone, this disease is estimated to have a prevalence of more than 3 million people in the U.S. Patients with triglyceride elevations on the order of 150-500 milligrams per deciliter or so, suffer from a high risk for cardiovascular disease. This is a very large population of patients that suffer from a risk for cardiovascular disease due to high triglycerides, estimated in the tens of millions. We are focusing APOCIII LICA on two patient populations today in development, the rare patient population, the FCS patient population, as well as now the severe hypertriglyceridemia patient population, SHTG. This drug, APOCIII LICA, based on its mechanism of action and based on its chemistry, our LICA chemistry, has the potential to be the very best in class for the management of triglyceride disorders of all forms, including FCS and SHTG.
Certainly, has the potential to be transformational for patients suffering from these diseases. APOCIII-LRx, a wholly-owned pipeline product for Ionis Pharmaceuticals, has shown very potent reductions in triglyceride levels, including in a phase II study that we conducted. This was in patients with cardiovascular disease and that had very high triglycerides. In fact, in this study, we were able to achieve potent reductions in triglycerides in these patients. In fact, we were able to get more than 90% of these patients' triglyceride levels below the threshold associated with metabolic diseases and cardiovascular diseases. The phase III study in FCS called BALANCE is now actively enrolling patients and is underway, and we're planning to initiate a phase III study in severe hypertriglyceridemia patients, SHTG, in the second half of this year.
Our third drug from our cardiometabolic franchise that's in phase III development today is Pelacarsen, formerly known as IONIS-APO LRx. Pelacarsen targets a risk factor called Lipoprotein(a). This is a risk factor that's highly prevalent. Lp levels are genetically determined at birth. If you have abnormally high Lp levels, you're at risk for cardiovascular disease such as stroke, heart attack, and atherosclerosis. In fact, the higher the level of Lp, the greater the risk of cardiovascular disease that you have. Not surprisingly, Lp is recognized as a major independent risk factor for cardiovascular disease. There are no ways to manage Lp levels. There are no approved pharmacological therapies that can control Lp levels in the body. The prevalence of this disease is very large.
As I mentioned earlier, greater than 8 million people around the globe are estimated to have Lp(a)-driven cardiovascular disease. As I mentioned earlier, there are no treatments to manage this disease. It is commonly fatal due to heart attacks and strokes, and certainly this drug has the potential to be another first-in-class product to reach the market, and certainly transformational for patients suffering from Lp(a)-driven cardiovascular disease. Pelacarsen targets, like the other drugs that we're developing, a root cause of disease, Lp(a)-driven cardiovascular disease. In a phase II study, I'll remind you that in which we tested pelacarsen in patients with cardiovascular disease and high Lp(a) levels, we were able to normalize Lp(a) levels in those patients.
Approximately 98% of the patients in that study, we were able to normalize their Lp levels in the phase II study, giving us great confidence that we're certainly hitting the target that we want to hit and giving us confidence in our phase III study. The phase III study is referred to as HORIZON, which is now well underway and enrolling rapidly with phase III data expected in 2024. Those are our five phase III drugs in development today being tested in six phase III studies. Now I'd just like to give you a glimpse into what we believe will be our next phase III drug, and that drug is IONIS-PKK-LRx. PKK-LRx is being developed to treat a rare genetic disease referred to as hereditary angioedema. This is a severe genetic disease. It's caused by insufficiency of a protein called C1 inhibitor.
This insufficiency in C1 inhibitor causes hyperactivation of a pathway called the prekallikrein-bradykinin pathway. The symptoms of this disease, as I said, are very severe, resulting in excess swelling of various organs and systems in the body, including the arms, legs, face, intestinal tract, and throat. If you get excess swelling in the throat, it can be fatal due to suffocation. Furthermore, the onset of these HAE attacks are unpredictable. There are no known linked causes of these attacks, therefore patients live their life with the uncertainty of having an attack at any moment in their life. There are approved prophylactic treatments for HAE. However, there still remains a very large unmet medical need for better efficacy. Many of these patients on these drugs continue to experience breakthroughs and certainly a strong desire for more convenient drugs, easier to tolerate drugs.
We believe IONIS-PKK-LRx fits that bill to be a potential best-in-class medicine for HAE. We're targeting the pathway with IONIS-PKK-LRx that is responsible for HAE, the prekallikrein-bradykinin pathway. IONIS-PKK-LRx is designed to block the production of prekallikrein, lowering the levels of kallikrein and bradykinin, bringing them to normal levels and resulting in prevention of HAE. Like our other phase III drugs in our cardiometabolic pipeline, IONIS-PKK-LRx is another LICA medicine that benefits from all the benefits of the LICA platform. It's estimated to be more than 20,000 in the U.S. and in Europe. It's certainly a potentially fatal disease resulting from, as an example, suffocation due to edema in the throat. Certainly, IONIS-PKK-LRx has the potential to be the best-in-class product for the treatment and prophylactic management of HAE. Today, we believe it does, and certainly, if so, it has the potential to be transformational.
We draw this conclusion not just because of the wealth of preclinical data that we have and the phase I data that we have, but also the phase II data that we reported top line data for earlier this year. This was a phase II placebo-controlled study in patients with HAE, in which patients were treated with either placebo or IONIS-PKK-LRx over a 17-week period of time. What we showed in this study was that we demonstrated a 90% mean reduction in monthly HAE attacks compared to placebo, which was highly statistically significant. In addition, if we look at the time period between weeks five and 17 in this study, that's relevant because it takes a few weeks for the drug to get on board and get to steady-state concentrations.
If we look at when the drug is fully on board between weeks 5 and 17, we were able to actually achieve 97% mean reduction in monthly HAE attacks versus placebo. Moreover, during this time period, 92% of the patients in this phase II study had zero attacks compared to 0% of patients in placebo having zero attacks during this time period. Very exciting and impressive phase II data that sets us up very nicely to move into phase III development. PKK-LRx targets the pathway that's at the root cause of HAE. It's a very conveniently used drug as a once-a-month, low-volume subcu self-administered injectable. It utilizes our highly advanced LICA chemistry with the potencies and the tolerability advantages that it offers. Certainly, the phase II data, we believe, supports the potential for a best-in-class product for the management of HAE.
As I said, the phase III study is in planning, and we're hoping to get that study underway soon, potentially by the end of the year, if not in the early part of next year. We have a very exciting, rich late-stage pipeline of phase III drugs that I just took you through. That's a rich agenda for Ionis and our partners who are developing these drugs alongside the drugs that we're developing in phase III. This year, in 2021, we also set out with a very aggressive agenda on pipeline readouts that we said we were going to have throughout the course of this year. I'd just like to take you through, if you will, a report card, a scorecard on how we're doing against those planned pipeline events. These events include data readouts as well as key study initiations from the pipeline.
We've already had several phase II readouts or several pipeline readouts from various studies in the first half of this year. The second half of the year is looking to be a very rich part of the year for additional pipeline readouts, including the full data set for PKK-LRx in HAE, the MAPT data in patients with Alzheimer's disease, and of course, the tofersen phase III data in patients with SOD1-ALS in the fall of this year. We're also well on our way to achieving our goals for study initiations. Many study initiations have already occurred this year, as you can see on this slide, including the post-marketing studies for SPINRAZA, the ATLAS tofersen presymptomatic study in SOD1-ALS, and there's more coming. Our phase III study for APOCIII-LRx and SHTG, severe hypertriglyceridemia, our Angelman syndrome phase I/II study to start in the second half of this year.
As I mentioned earlier, potentially Ionis PKK-LRx phase III in HAE. The performance of this pipeline this year, as well as the phase III pipeline that I just took you through for the last little bit, sets us up very nicely to achieve our objective of 12 or more marketed medicines in 2026. Again, as a reminder, most of these medicines will come from two leading franchises in the industry, our neurological disease franchise, both wholly-owned and partnered, our cardiometabolic franchise, wholly-owned and partnered, as well as some drugs outside of these two franchises, such as PKK-LRx for HAE. Today at Ionis, the pipeline is advancing at an accelerated pace. In addition, our technology is advancing and expanding to tackle diseases today that were unapproachable in the past.
We are certainly pioneering new markets with drugs like tofersen for SOD1-ALS and pelacarsen for Lp(a) driven cardiovascular disease. We're changing the standards of care for patients in a beneficial manner with new drugs to reach the market like PKK-LRx for HAE and eplontersen for TTR amyloidosis. We're investing in all aspects of the business to ensure that Ionis is as successful and grows with accelerated pace of growth in the future, including investments in our research organization, our wholly-owned pipeline, building out our commercial capabilities, and more. All of this being permitted because of the strong financial position that we are in at Ionis today. All of this sets us up very nicely, perfectly for accelerated growth for the company well into the future. With that, I think I'll stop there.
I'll just take a couple of minutes to set up for the question session of the presentation. I'm going to ask Beth Hougen, our Chief Financial Officer, to join me, as well as Onaiza Cadoret-Manier, Chief Corporate Development and Commercial Officer, to join me as well. Stay tuned and we'll be back in a moment. Welcome back to the question and answer session of today's Ionis shareholder meeting. Filtering the questions and taking the questions will be Wade Walke, Vice President of Investor Relations, and Wade will be feeding us the questions here to Beth, Onaiza, and myself, Brett P. Monia. Wade, do we have some questions?
We do. For those of you that are on the platform and you want to ask a question, please click on the Q&A button down at the bottom of the screen and type in a question. Our first question involves the PKK LRx program, the question is, you released or only reported data from patients with Type 1 or Type 2 HAE, but the study also enrolled patients with HAE with normal C1 inhibitor. Why wasn't this data released when you talked about the Type 1 and Type 2 data, will it be released? Do your plans for phase III include HAE patients with normal C1 inhibitor?
That's absolutely correct that our phase III study included Type 1, 2, and 3, but there were really one or two Type 3 patients in that study. It really just wasn't much to be able to draw a definitive conclusion on. We will share the full data set in the second half of this year. We're targeting a publication and potentially also a presentation in the second half of the year, and we'll certainly share all that data when we present the full data set.
I'd also remind investors who are interested that a paper was published with investigator-initiated study of two patients. One of them had normal C1 inhibitor.
That's right.
The patient showed significant reduction in attack rates.
Okay. That was a Type 3 patient in that one journal paper.
Next question is about the Huntington program. Does Ionis Roche have any plans to move an allele-specific ASO to the clinic to treat Huntington's patients?
Yeah, it's a great question. We're still working through a massive data set from the phase III study with Roche. Roche is taking the lead on that work. We have a lot to learn before we start deciding on what will be the next step with respect to drug development. Certainly, one potential path forward for the Huntington program, once we get through all the data, will be to develop an allele-selective inhibitor, potentially. We certainly have a lot of experience in developing allele-selective inhibitors for HD. We published on this, and we certainly have a drug pretty much ready to go if we choose to go that path. Stay tuned. I suspect by the end of the year, we will know the next steps for the Huntington program.
Next question is about our TTR-LICA and APOCIII LICA programs.
Question is, will you consider out-licensing ex-U.S. rights in order to shift risk and fund commercial rollout in the United States? TTR-LICA and APOCIII-LICA are two drugs in our wholly-owned pipeline that we're building out our commercial plans for today. What we do, how we manage partnerships for those programs is to be determined still. This is a work in process. What I can assure you is that we're working hard to develop the markets for these two assets ourselves today. Whatever we choose to do for these two drugs with respect to partnerships in the future, whether it be commercialization or what have you, to bring the maximum value to the company that we possibly can bring. It's a work in process.
Next question is about business development. Are there merger, new partnerships, or acquisitions possible in the future?
We don't comment on mergers or acquisitions. That would be inappropriate. Sorry.
There's a couple of questions on this particular topic, so we'll just ask this one question, and I think it'll cover the others. This is from a shareholder who also has shareholder clients. Says you have a robust pipeline of drug development in various stages of process. Given the stock price has dropped recently in the past few months, what is the market missing? Outside of potential positive clinical trials, how do you think you can change Wall Street's outlook to have a more positive outlook on the company's future financially?
Thank you for that question. We know we are disappointed, frustrated by the performance of the stock price. Trust me when I say that the senior team at Ionis pays a great deal of attention to how to turn this around all the time, every day. I think we've suffered a little bit from the tominersen Phase III outcome. That was a big setback in the eyes of many. What we're pleased about is we see no read-through to the neurological platform. As I took you through, we think that it's one of the richest, one of the most robust platforms, and we're very much looking forward to the tofersen Phase III data later this year to really demonstrate that again from our platform. I think that was a key setback in the stock price.
Other than that, I wish I knew, other than the fact that we did have a bit of a quiet period with key clinical readouts over the last year and a half or so. That's all changing now. Our clinical pipeline, as I took you through, is going to have clinical readouts from our mid-stage pipeline and our phase III pipeline this year, more this year, next year, and for many years to come. I really do think that that is what's going to get people's attention and turn things around.
The next question is about the PCSK9 program. The question is, I noticed that the PCSK9 drug partnered with AZ could be a best-in-class profile drug based on the phase II data. This drug uses the LICA delivery and gen 2.5 chemistry. The rest of the pipeline uses LICA plus gen 2 or gen 2.5 alone.
Do you have a strategy to upgrade the pipeline drugs with LICA plus 2.5 chemistry so they could be more competitive in the marketplace? Indeed. Our PCSK9 gen 2.5 LICA medicine with AZ does have the potential to be the best PCSK9 inhibitor that's out there today. We say that not only based on our preclinical data, more importantly, based on real clinical data, some of which was presented at the AHA last year. We have more data. phase II-B study is ongoing to select those, potentially move that drug into phase III development later this year. It was really the gen 2.5 component to that LICA medicine that allowed it to really put out that profile of a potential best-in-class in a very crowded area, PCSK9, with PCSK9 inhibitors based on its added potency.
Our Gen 2 LICAs are outstanding drugs in their own right, and they're performing exceptionally well in the clinic and are far along, and as I took you through three, soon to be four, drugs with Gen 2 LICAs are in phase III development, soon to read out and be first, if not first best in class, potentially best in class medicines. If we were to convert those drugs over to Gen 2.5 down the road, we would have to factor in lots of different things. What will a 2.5 give us over Gen 2? Is it worth it because the Gen 2s are performing very well? Do we need it? We probably needed it for PCSK9 because it was a highly competitive field to further advance our competitive edge. Should we do it for life cycle management to continue the franchise for much longer periods of time?
That's a long, convoluted answer to a very good question that we'll have to see what we need and what 2.5 would bring to these other drugs. These two Generation 2 LICAs are performing exceptionally well. The next question is regarding potential share buyback. The question is, have you considered a share buyback with cash on hand? We did a share buyback a year and a half ago, Beth, and we've talked about it, but why don't you take that?
Sure. Happy to. As Brett said, we had done one in the past. We've looked at that, obviously, with where our share price is today. We believe really firmly that the best allocation of our cash right now is internally, in our pipeline. I think Brett took you through a really nice overview of what value there is in the late-stage pipeline, as well as in the mid-stage pipeline, investing as deeply as necessary to bring those medicines forward to the market to ensure that they're commercially successful, building out our commercial capabilities, and expanding the reach of the technology so that we can continue to retain our leading position in this field.
I think those are the places where ultimately we're going to see the greatest value for the company, and particularly as we start to see those phase III readouts year after year after year, beginning, we hope, with tofersen later this year, reaching our goal of 12 or more marketed medicines in 2026. That's really where I think there's true value for the company.
The next question is again about the PKK program, but is asking if there's an update about the drug helping COVID patients, specifically the trial in Brazil.
Yeah, this was a real flyer, an investigator study that was conducted in Brazil. We were contacted by an investigator in Brazil who was experiencing the pandemic in very bad ways. The bradykinin pathway has been linked to poor outcomes in patients with COVID infections. He asked if he can do a single-site investigator study. We provided the drug to him. The data still is being analyzed, so we should have data by the second half of the year.
The next question is two parts related to delivery of antisense drugs. One is there an update on oral delivery of ASOs and specifically PCSK9, but also in general? Also, what's the status of lung delivery for ASOs?
We continue to develop a platform that potentially will allow us to achieve commercially viable oral delivery for antisense drugs. We're putting quite a bit of resources internally on this to increase the bioavailability, improve bioavailability so that we're at the bioavailability that we want to achieve, that we think is necessary to be commercially viable. We're also working with our partner, AstraZeneca, to help develop this platform going forward. Can't say right now whether we will be for sure successful in achieving this, but we're certainly encouraged by the learnings we made from the phase I study that AstraZeneca did with the PCSK9 inhibitor using the oral route of delivery, we learned a lot from it, like I said, and we're building on that. We're encouraged, we're continuing to work on that. Stay tuned.
In 2022, we'll have an update on the oral platform. With respect to lung delivery, this is a very exciting area for the company that we're continuing to pioneer and advance our technology, another example of that. We had a setback earlier last month in our EMAC program, in which based on a finding in a chronic monkey toxicology study, we thought it was prudent to stop clinical development of that drug for the safety of the patients in the clinical trial while we better understood the finding, a local effect in the lung, nothing systemic, no read-through to the Gen 2.5 class, nothing like that at all. It was just an effect in the lung in monkeys. We think we'll be able to work through that.
We're working hard on that now to come up with different chemical designs, molecules that we think can avoid the observations we've made. Stay tuned, but we're feeling good that the pulmonary franchise is certainly in our future. We just have to sort out what's the best design for a pulmonary-delivered antisense drug.
We've had a couple of questions asking about how our eplontersen differs from Alnylam's patisiran.
Very different. Patisiran is an unmodified double-stranded RNA molecule that is delivered intravenously every three weeks and requires pre-medication with steroids to dampen pro-inflammatory effects, infusion reactions in patients that get this nanoparticle-formulated siRNA. Very different. It's subcutaneously administered like a medicine. It's a single-stranded molecule, an antisense molecule, single-stranded. It's administered very low volume, subcutaneously, auto-injector, patients self-administer at home once per month. So you can see how ONPATTRO and eplontersen differ. They differ quite a bit with respect to the profile for the patient and the route of administration, convenience, and so on.
Next question is, what can you do to move even more quickly to advance the pipeline?
Well, we have that conversation pretty much every day at Ionis. What can we do to get drugs into phase III? How can we speed up enrollment? How do we get phase II drugs moving faster and so forth and so on. I think we're doing everything we can today to advance the pipeline to late-stage development into the market as quickly as we can. As I mentioned, we have the financial wherewithal, the strength to be able to invest in all aspects of the business, including the pipeline. I can assure you that we are investing significantly in the development organization to expand the development organization, to expand the whole Ionis pipeline, to move these drugs forward as rapidly as possible.
I would say that being a very nimble, relatively small organization like Ionis, gives us the ability to move drugs faster through development and onto the market. It's the nature of a small company like Ionis. That is another aspect of hanging on to some of the drugs, many of the drugs from our whole Ionis pipeline ourselves and bringing them through phase III. That represents significant advantages, efficiency, and speed, and that's another factor. We'll certainly never let a drug sit, because we don't have the resources for a drug. Every drug should move, and that's why we partner. We partner if we decide that we don't want to necessarily prioritize a drug for our own pipeline to bring it to the market.
Next question is regarding muscle-targeting LICAs. Where do things stand with respect to such technology, how far is muscle-targeting LICA drug from the clinic? Will your first muscle-targeting LICA drug treat myotonic dystrophy?
This is a highly competitive space, as I'm sure the person who asked the question knows. It's a very good question. There are various approaches to develop RNAi molecules, antisense molecules for muscle delivery. We're in there, too. We're working hard in various workstreams, research workstreams, I believe that we're getting close to identify a lead molecule, a lead ligand for targeted delivery to muscle, which we're hoping will enter development by the end of this year.
When I say this, what I was referring to just now includes both work that we're doing ourselves for the whole Ionis pipeline with targeted delivery to muscle, as well as with our partner Biogen who also obviously has tremendous capabilities in protein therapeutics that we can leverage, and we are leveraging as well. As far as myotonic dystrophy or Duchenne muscular dystrophy or other forms of muscle diseases, this is, again, a highly competitive space. We're going to keep that one to ourselves for now.
This one relates to the TTR LICA program. How much will it cost to build an organization to sell TTR LICA, given that you will be competing with Pfizer, Alnylam, and others, and how many sales reps do you anticipate having in the field?
That's a good question for you, Onaiza.
Good. Okay, I'll take that one.
I ask you that every day.
Yeah. If one person for polyneuropathy and for cardiomyopathy will obviously be very different indications, will require different ones. We'll take the larger one, which is cardiomyopathy, well over a $10 billion market. As you know you already have Pfizer on there. I think your biggest gauge for what to require it is just taking a look at the number of salespeople that they have. It's still a rare disease. It's not tremendously that large. This is not going after a lipid category or anything like that. We're not looking at kind of reaching GPs. It's pretty much still treated by cardiologists. You're not talking about a tremendous size of field force and still relatively very targeted as well. I hate to put out numbers on there, so I think you can guess it's kind of specialty field force type of sizing.
That's the way I think about it, if that gives you a gauge. Certainly not PCP or GP type of sizing as well. Exciting indications in both PN and cardiomyopathy, and then obviously we also have the mixed disease phenotype in there that allows you to go to both neurologists and cardiologists over time. We're looking forward to getting out there and serving patients in a very attractive market.
Next question is a financial one. At what point would you consider initiating a dividend? Onaiza.
I'd like that one. Sure. I think when you look across the biotech field and you look at even the big biotech companies they rarely will issue dividends. As we think about capital allocation, thinking about share buybacks, dividends, those types of investment opportunities, if you will. It's just really not where we see the growth for the company. Being able to invest, as I had said earlier, internally in the pipeline, in the technology, in the commercial capabilities that are critical for the success of these drugs, that's where the real growth opportunity is.
I would say a dividend is not something I see in our near-term future and probably not in the longer-term future either at this point.
Thanks, Beth. Next question is on the GHR LRx program. "Can you give more color on your acromegaly asset that will read out in the second half of this year? What type of data do you need to see to move this asset to phase III?
The data to expect in the second half of this year from our acromegaly program. Let me back up. The patients that we're studying in this phase II proof of mechanism study really are patients with acromegaly who have uncontrolled disease despite being on somatostatin analogs. Our objective in this study is to control their IGF-1 levels, a biomarker, an approval biomarker for the management of acromegaly. That's what we're focused on, as well as some other measures of quality of life. We're also focused on proof of mechanism, as I mentioned, looking at growth hormone binding protein levels, which demonstrates that we're hitting the target very nicely if we can demonstrate that.
The data to look for in the second half of the year is the phase II data, along with quite a bit of open label extension data, where patients have continued to be treated with our acromegaly drug, cimdelirsen, well after the phase II study completed. Safety, tolerability, proof of mechanism, and we're also hoping for good indication of effects on the biomarker IGF-1.
We're running low on time, so I'm going to ask one more question. I think we've covered most of them in general topics. Can you say something about your expectations for the growth of TEGSEDI and WAYLIVRA in the second half of the year?
Sure. Beth, would you like to jump on?
Sure, absolutely. I think what's important to remember with TEGSEDI and WAYLIVRA is that we have entered into distribution agreements with Sobi for Europe, for TEGSEDI and WAYLIVRA, and recently with TEGSEDI in North America. We're looking forward to Sobi really taking over and marketing these drugs putting forward their field force and their expertise and their reach for both of those drugs. From a revenue perspective, we'll be getting a distribution fee rather than product revenues. You could expect to see revenues probably decline as a result of that. That doesn't necessarily mean that product sales are declining. It just means that our portion of those sales is a portion, not 100%. We still see the TEGSEDI and WAYLIVRA having a future and possibly getting into new markets.
I would say be mindful of the fact that from a revenue perspective, we get distribution fees, not the full product sales.
Thanks, Beth.
For those that have questions that we didn't get to or have questions that we've run out of time to answer, please contact Investor Relations Group, and we'd be happy to answer those questions.
Thank you, everybody, for all the great questions. Thanks for joining us on today's shareholder meeting, and have a great evening.
Thank you.