Good afternoon. Welcome to Ionis Pharmaceuticals Annual Meeting of Stockholders for 2022. My name is Brett Monia. I'm the Chief Executive Officer of Ionis, and I'm really thrilled to provide you an update on the great progress we're making at Ionis today. These are my forward-looking statements that I recommend to you to review at your convenience. Today, Ionis is a leading, fully integrated biotechnology company, well-positioned for substantial growth in the near term and in the long term. The evidence for this is compelling and clear. Today, we have a commercial portfolio of three medicines in our commercial portfolio, led, of course, by our blockbuster medicine, Spinraza, for spinal muscular atrophy. That portfolio is expected to grow and grow fast and substantially based on our industry-leading rich mid- and late-stage pipeline.
A pipeline chock-full of many potential transformational medicines that are rapidly advancing to market. In addition, our technology is advancing at a rapid pace based on the investments we have made over the last several years that is allowing us to tackle diseases tomorrow that we cannot tackle today and extending our leadership position in RNA-targeted therapeutics. We have a compelling financial profile. The financial strength to invest in all of our priorities here at Ionis to ensure we maximize substantial growth for our shareholders, for Ionis, for our patients, and to achieve our vision of becoming one of the best, greatest, most productive biotechnology companies of all time. Today, we have two leading therapeutic franchises and one rapidly emerging therapeutic franchise. Our leading therapeutic franchises are in cardiovascular diseases and in neurological diseases.
In cardiovascular diseases, we are addressing many of the major cardiovascular disease risk factors today. We have four ongoing phase III trials and nine medicines in clinical development in our cardiovascular pipeline today. Our neurological disease franchise is addressing many major severe neurological diseases. Three ongoing phase III trials in progress and 11 medicines in clinical development tackling neurological diseases. We have a specialty rare pipeline that's emerging, led by our phase III drug donidalorsen for the treatment of hereditary angioedema. We have a very rich phase III pipeline today, six medicines in phase III development across eight different indications. These medicines are being developed for severe rare diseases as well as severe broad indications with prevalence estimated in the millions for some of these indications.
These drugs are expected to read out from their phase III pivotal studies in a steady cadence of readouts starting this year, next year, and as far as we can see from this phase III pipeline through 2025. We also have a rich mid-stage pipeline that will be supplementing many of these phase II drugs that will be moving into phase III development to continue phase III readouts for many years to come. This is what our phase III neurology pipeline looks like today. There are three medicines in development for neurological diseases. They're all targeting severe rare neurological diseases. Tofersen, our lead drug for amyotrophic lateral sclerosis, ALS, targeting a genetic form of ALS due to mutations in the SOD1 gene.
Our ION363 targeting another genetic form of ALS, in which patients develop ALS due to mutations in the FUS gene. Eplontersen for hereditary TTR amyloidosis with polyneuropathy. Before I do a deeper dive into several of our phase III programs, I wanna provide a brief update on our SOD1 ALS drug, tofersen. Last year, as many of you I'm sure know, we were disappointed that the phase III VALOR study in SOD1 ALS did not hit its primary endpoint. However, there was from that VALOR phase III study as well as from limited open label extension data encouraging signs that patients were doing better. Clinical signs, several clinical endpoints appeared to be trending in the right direction that was suggesting that tofersen was truly benefiting patients with SOD1 ALS.
In addition, there were substantial decreases in a biomarker called neurofilament light chain or in patients treated with tofersen. NfL is a key well-recognized biomarker of axonal injury and neurodegeneration, giving us further encouragement that tofersen was truly benefiting patients with SOD1 ALS. Based on these results, our partner, Biogen, opened up an expanded access program which has gone very well. Today, there's 133 patients in the EAP across 31 countries in which patients are receiving tofersen. Very importantly, tomorrow, new data from longer treatment open label extension from the phase III VALOR study in which patients have been treated for a minimum of 12 months will be presented at the European ALS meeting called ENCALS, and I point you to that for an update on tofersen.
Based on all of this progress, Biogen remains actively engaged with regulators on potential next steps for tofersen. We at Ionis remain committed to treating all forms of ALS. Genetic causes such as tofersen for SOD1 ALS, our ION363 for ALS due to mutations in the FUS gene, as well as for broad ALS, non-genetic ALS, if you will, or sometimes referred to as sporadic ALS. Our drug ION541 targeting ATXN2 is in a phase I/II study in non-genetic ALS and is enrolling very well. We're expecting additional programs targeting ALS, sporadic ALS, to reach development in the near term. Our cardiovascular phase III pipeline is equally exciting. Today, we have three medicines in development in phase III studies. olezarsen, eplontersen, and pelacarsen.
All three of these medicines benefit from our transformationally advanced LICA chemical platform that provides high potency, great efficacy, and with very attractive safety and tolerability. These drugs are targeting rare indications as well as very broad indications with prevalences upwards in the millions. olezarsen is in phase III development for two indications, a rare genetic form of high triglycerides or severe hypertriglyceridemia due to genetic causes called familial chylomicronemia syndrome or FCS. Then a very large triglyceride patient population, severe hypertriglyceridemia, SHTG, that's estimated with a prevalence in the millions in the United States. Eplontersen, as I said earlier, is in phase III development for hereditary TTR polyneuropathy. That same drug is in phase III development for a much broader indication, much broader prevalence in cardiomyopathy, patients suffering from amyloid, TTR amyloid buildup in cardiac tissue.
Pelacarsen, our drug that's partnered with Novartis, targeting a cardiovascular disease risk factor called lipoprotein(a), is in phase III development and going very well. This is a prevalence of more than 8 million patients suffering from cardiovascular disease due to high levels of Lp(a). We're expecting Novartis to complete enrollment in this cardiovascular outcome trial involving upwards of 8,000 patients in this phase III study to complete enrollment this year. From our emerging specialty rare pipeline, donidalorsen in phase III development as a prophylactic treatment for hereditary angioedema. Enrolling well. A prevalence estimated to be more than 20,000 patients with this rare genetic disease in the U.S. and E.U., with data expected from this phase III study in 2024. Ionis' business model has evolved.
Today we are building and working and preparing for the 1st commercial launches from Ionis ever, from drugs that we deem appropriate to bring forward to the market ourselves to maximize value to our shareholders, to our patients, to Ionis, to all stakeholders. Last year, about six months ago, we presented at our investor day our strategy for moving and advancing to the market here at Ionis. That strategy will focus on two core franchises, our cardiovascular franchise and our neurology franchise. In addition, we will also take advantage of other opportunities if it makes sense to do so outside of our core assets. Assets that have high probability of success or and attractive markets and are within our capabilities.
We will focus our commercialization efforts in the United States for both rare and broad indications, and we will build commercial excellence globally to ensure that our drugs through distributorships or other types of partnerships are reaching our patients on a global scale. We will expand in a disciplined manner over time. Our pipeline, our wholly owned pipeline, will expand beyond our near-term commercial assets, and we will expand our infrastructure at the right time outside the United States. We will continue to partner strategically. We will co-commercialize when appropriate to enable greater patient access and availability and out-license assets outright at times, if it makes sense to do so, if those assets are outside of our core areas or strip our capabilities. Today, we have three near-term commercial opportunities. Eplontersen, olezarsen, and Donidalorsen.
All three of these medicines benefit from our highly advanced and attractive LICA chemical platform. Eplontersen is being developed for TTR amyloidosis. All forms of TTR amyloidosis is in phase III, as I already said, with a high prevalence for this disease in the hundreds of thousands of patients, especially suffering from cardiomyopathy. Based on the data that's been generated to date with Eplontersen, this drug really has the possibility, it has the potential to change the standard of care in a very meaningful way for patients suffering from TTR amyloidosis. With a very attractive market opportunity, Eplontersen has blockbuster multibillion-dollar market potential. Our 2nd near-term commercial opportunity is olezarsen. olezarsen being developed for patients suffering from severe, severely elevated triglycerides for two indications.
The 1st phase III data readout is expected next year, and we're ahead in this market, this very attractive market, in patients suffering from very high triglycerides. Potential 1st-in-class treatment and best-in-class treatment for patients suffering from different types of diseases with severely elevated triglycerides. This drug also has blockbuster market potential. There's our 3rd near-term commercial opportunity, donidalorsen. Donidalorsen is being developed in phase III as a potential best-in-class prophylactic treatment for patients suffering with a rare genetic disease called hereditary angioedema. Prevalence is shown here on this slide. Phase III data expected in 2024, and the market opportunity for donidalorsen is very attractive for Ionis.
Now I'd like to do a deeper dive into our three near-term commercial opportunities, starting with eplontersen, our lead medicine for the treatment of TTR amyloidosis. TTR amyloidosis remains a very rare disease that has a very high unmet medical need. It's a progressive disease due to the production of misfolded TTR protein from the liver, which deposits and forms amyloid in various organ systems, causing organ system destruction and rapid decline in quality of life. Eventually it is a fatal disease. There are two indications we're pursuing, a rare genetic form of the disease called hereditary TTR polyneuropathy, with the prevalence of approximately 40,000 patients globally.
Then a much larger indication that involves both hereditary causes of the disease, as well as non-hereditary forms of the disease that produce cardiomyopathy in a much larger patient population, as I said. We have a comprehensive phase III program in process that to maximize the value of eplontersen on the market today. Our NEURO-TTRansform study is a multicenter open label study, phase III study with 168 patients enrolled, with the primary endpoint being mNIS+7, which is an instrument to measure neurological disease, peripheral neurological disease progression. In addition, we have a co-primary endpoint of TTR, the target TTR lowering at week III5. We're expecting data from this phase III study mid-year this year.
Our CARDIO-TTRansform study focused on patients suffering from TTR cardiomyopathy, both hereditary patients as well as wild type patients. This is a global randomized, double-blind, placebo-controlled cardiovascular outcome trial involving 140 weeks of treatment in up to 1,000 patients to be enrolled with data expected in the 1st half of 2025. We also have several other studies in process as well as being planned that we collectively refer to as TRANSFORM Beyond. These are studies to further enhance the profile of eplontersen, to generate data to show that this drug truly is a leading class molecule for the treatment of amyloidosis and to win on a very competitive, very attractive market. Last year, we announced a strategic partnership for eplontersen with our partner, AstraZeneca. Our long-standing partner, AstraZeneca.
It's a very important partnership for eplontersen to set it up to win in a very competitive but yet very large market opportunity. It's a partnership that is very complementary. Both sides are bringing complementary skills to the table to maximize the success for eplontersen. At Ionis, we're bringing our industry-leading experience in development of antisense drugs as well as our vast experience in TTR amyloidosis. We also have a very important and substantial seat at the table for commercialization of eplontersen in the United States. AstraZeneca, of course, brings with it its global capabilities, its global leadership in the commercialization of cardiovascular diseases. Together, we believe that this partnership will maximize success for eplontersen in a very compelling market. As I said before, a market that's compelling but is also competitive.
Where are we with eplontersen, current status and next steps? Well, the NEURO-TTRansform study had completed enrollment last year. We actually exceeded enrollment in the phase III study, with data expected mid-year this year. If the data supports, we will file for marketing authorization this year as well and launch the drug next year. Our CARDIO-TTRansform study is the largest TTR cardiomyopathy study ever conducted, and it's large because it's designed to demonstrate benefit in a very broad patient population that suffers from TTR amyloidosis. Diverse patient population that's really gonna position this drug as a best in class molecule for TTR cardiomyopathy. It's on track to complete enrollment in 2022 and this year. For data readout in the 1st half of 2025.
Our 2nd near-term commercial opportunity that we're preparing to launch here at Ionis is olezarsen for the management treatment of patients suffering from severely elevated triglycerides. olezarsen really has the potential to be a transformationally new approach for the treatment of patients suffering from severely elevated triglycerides. We know that elevated triglycerides are associated with many major medical issues, including acute pancreatitis that can be fatal, high risk of cardiovascular disease, and there are no good treatment options available to manage severe hypertriglyceridemia today. The target for olezarsen is APOCIII. It is a liver-derived protein that is the master regulator of triglyceride metabolism in the body. We have shown in phase II with olezarsen that olezarsen is highly effective in reducing triglyceride levels in patients with very elevated, highly elevated triglycerides with excellent safety and tolerability.
APOCIII is also a validated cardiovascular disease risk factor. As I mentioned before, we are targeting two patient populations, FCS and the broader indication, severe hypertriglyceridemia. Like eplontersen, we have a very broad, comprehensive phase III program for olezarsen to maximize its success on the market. We have the Balance study targeting the rare genetic cause of severely elevated triglycerides called familial chylomicronemia syndrome, FCS. This is a global randomized, double-blind, placebo-controlled study involving about 60 patients with FCS. Primary endpoint is triglyceride reduction compared to baseline at six months. We expect data, as I said, early next year. Then for the broad population, the population that affects millions of people is severely elevated triglycerides. We have two studies that are planned or in progress. The CORE study is in progress.
This is a global pivotal study in up to 540 patients with severely elevated triglycerides, about 500 mg per deciliter. Primary endpoint is same as Balance. Triglyceride lowering at six months with data expected in 2024. Then we're about to initiate a 2nd supportive confirmatory pivotal study called CORE 2.0, involving a somewhat smaller sample size, 390 patients. Same primary endpoint, same time frame for the primary endpoint to read out and for its data to read out, from the CORE 2.0 to coincide with the readout of CORE. Our go-to-market strategy and our plans for commercializing olezarsen in the market is a plan that will evolve with time. We will start and focus on the 1st readout from our FCS phase III study, focusing on FCS patients, triglycerides.
These are patients, again, with triglycerides above 1,500 mg per deciliter and a genetic cause of the disease. That has a prevalence estimated about3 ,000-5,000 patients or so. As the CORE study reads out, we will then move to a patient population that we refer to as the early adopter population. These are patients with triglycerides above 1,000 mg per deciliter at high risk for pancreatitis, potentially fatal pancreatitis. A prevalence that's estimated to be about a million people in the United States. With time, we will move forward to the broader, even broader population, the SHTG population, with triglycerides about 500 mg per deciliter associated with cardiovascular disease with a prevalence estimated above 2 million patients in the United States. The current status of olezarsen, the next steps.
First, I want to point out that we published our really, attractive or impressive phase II data in the European Heart Journal earlier this year of the BALANCE study in FCS. We're expecting full enrollment soon with data expected next year. The CORE studies are progressing very nicely. CORE is rapidly, actively enrolling with data expected in 2024. The confirmatory, supportive study CORE 2.0 is expected to start soon with data readout again in 2024. Our next near-term commercial opportunity that we're preparing to launch here at Ionis is donidalorsen. Donidalorsen for the prophylactic treatment for hereditary angioedema, with a profile that has the potential to be a best-in-class prophylactic treatment for this disease. Hereditary angioedema or HAE is characterized by unpredictable, painful, and potentially fatal attacks.
It's a severe, rare genetic disease that's caused by a dysfunctional gene called C1 inhibitor. The lack of C1 inhibitor causes hyperactivation or overactivation, if you will, of a pathway called the kallikrein pathway, the prekallikrein pathway, which leads to excessive production of a chemokine called bradykinin, which leads to angioedema, massive swelling of various tissue beds, including the arms, legs, face, and throat, and this can be a fatal event. This is also an unpredictable event for patients. These patients live their lives in constant anxiety and fear that an attack can happen at any time. Donidalorsen targets the root cause of hereditary angioedema, bradykinin overproduction by targeting prekallikrein. We reported last year some very exciting, very compelling phase II data in patients with HAE with donidalorsen. We demonstrated substantial reductions in HAE attacks that were rapid and sustained.
Reductions over the 17-week treatment period that were 90% lower versus placebo in that full 17-week treatment period. If you look at weeks 5 to 17, after the 1st dose or the 2nd dose when the drug gets fully on board, we actually upped that to 97% reduction in monthly HAE attacks versus placebo. What was really remarkable and unprecedented for a prophylactic treatment was that more than 90% of patients during this treatment period were completely attack-free, compared to zero patients on placebo that were attack-free. Truly a potential best-in-class HAE profile. Based on this data, we rapidly moved donidalorsen to a phase III development. The phase III study that's underway, the pivotal study, the registration supporting study is OASIS.
It's a global pivotal study, in which we're targeting approximately 84 HAE patients, in which we're dosing monthly with donidalorsen as well as every two months over a 24-week period. The primary endpoint for this phase III study is the same as the phase II study. Time-normalized HAE attacks, with data expected in 2024. We also have a collection of studies that are in progress and planned to further enhance, further promote the profile for donidalorsen in the HAE community, in the HAE market to win and to maximize success on the market. We call these collection of studies OASIS+. This includes the global open-label extension study in which patients from OASIS will roll over into to demonstrate and to establish durable protection over longer periods of time against HAE attacks.
In addition, we're about to begin a new study we sometimes refer to as the switch study, that is open to HAE patients that were previously treated with other prophylactic therapies and then are moving over to donidalorsen to demonstrate, maintain, and maybe even improved efficacy with good safety and tolerability. This is a very exciting market, the HAE market. It's an established and growing market, a market in that has a potential of more than. Let's say that today is more than $1.5 billion and growing, especially prophylactic treatments are growing here. It's a well-defined U.S. patient population and a well-defined prescriber base. It's estimated to be about 6,000 HAE patients in the United States, and there's a large unmet need that remains despite the availability of prophylactic treatments. These patients continue to suffer from breakthrough unpredictable, severe attacks despite being treated.
We think donidalorsen is the answer for those patients. Of course, these patients continue to experience significant fear and anxiety because these attacks, again, are highly unpredictable. Donidalorsen has the potential to be a best-in-class, has the best-in-class profile based on our phase II data, based on efficacy, its onset of action, its safety tolerability, and its convenience as a once-per-month or less frequent at-home self-administered agent. Where are we with donidalorsen? We were very proud to have published our phase II data in the New England Journal of Medicine earlier this year. The OASIS pivotal phase III study is actively enrolling and on track for data readout in 2024. The collection of studies, the supportive studies, OASIS+, are also moving forward nicely on track.
Now I've taken you through our rich phase III pipeline. I've also taken you through three phase III drugs that we're preparing to launch here at Ionis over the next several years. Right behind that phase III rich pipeline is a large phase II pipeline, a pipeline that has many drugs from our cardiovascular franchise, our neurology franchise, and our emerging specialty rare franchise that has the potential to be transformational agents and if successful in phase , has this highly likely potential to move into phase III, further enhancing our phase III pipeline and providing a continuous supply of phase III assets in the long term. All this sets us up for substantial revenue growth for the near term, medium term, and well into the future.
Our revenue growth, of course, also receives contributions from our partnerships. We refer to this revenue as R&D revenue. We will continue to gain revenue from our existing commercial products, of course, led by SPINRAZA, our blockbuster medicine for SMA. In the near term, we're expecting a very large number of molecules, products, assets to reach the market to substantially increase the growth of Ionis, our revenue growth. In the medium to longer term, you can see a tidal wave of new products that we're projecting to potentially reach the market to really maximize our revenue growth, maximize growth of Ionis, maximize success for our shareholders and all stakeholders. We're also continuing to invest in our technology, and it's paying off in many, many important ways.
Investments in medicinal chemistry, for example, are having an impact on extending our dosing intervals, enhancing our therapeutic profile, even beyond the attractive profiles that we're generating today. We plan to incorporate these new medicines into new drugs that will enter the pipeline, but also into existing programs for lifecycle management for existing therapeutic areas or drugs that are on the market today or in development. A great example of this is our follow-on to SPINRAZA, which is expected to reach clinical testing soon for SMA. We're also developing new LICA strategies that go beyond liver LICA, opening up LICA strategies for muscle and pancreas and maybe even lung, opening up diseases like neuromuscular diseases, heart failure by targeting the heart directly, and metabolic diseases. We'll continue to validate new routes of delivery, just like we validated intrathecal delivery for CNS.
We're well on our way to validating additional routes of delivery to open up new disease areas, new organ cell types, further strengthening our leadership position in RNA-targeted therapeutics. This is a really exciting year for Ionis. We have a lot of pipeline events, a lot of pipeline readouts. We've already had quite a few in the 1st half of the year, as you can see on this slide. Tomorrow, we're expecting another pipeline update, tofersen, as I mentioned earlier, in which Biogen will present at ENCALS an update on the open-label extension for tofersen in SOD1 ALS. We're very much looking forward to the phase III interim readout for eplontersen in TTR polyneuropathy midyear this year.
You can see in the 2nd half of the year, we have a whole host of phase II readouts and phase II-B readouts that we're very much looking forward to, as well as key study initiations and technology advancements that we expect to reach development this year. We are very strong financially, and this is so important. Today, we are well-capitalized with multiple sources of revenue that allow us to make all the investments we need to make in the company across our business to maximize success for Ionis, for our shareholders, for all stakeholders. Building out the Ionis wholly owned commercial portfolio, building out our commercial organization, expanding and diversifying our technology, and getting our drugs to the market and winning on the market, all of this is expected to lead to substantial growth for Ionis.
We're doing all this with corporate responsibility in mind, focused on our employees, our people. A fantastic group of employees who are highly dedicated to developing drugs and helping patients. Of course, we're devoted to our patients and dedicated to our patients, our environment, our communities, and continuous innovation. We're very proud of the fact that we published our corporate responsibility report in December last year. We're looking forward to providing further updates in this report in the future. To conclude, Ionis is indeed a leading fully integrated biotechnology company today, well-positioned for accelerated growth, maximizing success for all stakeholders. We have many attractive product opportunities rapidly approaching the market, a growing and advancing phase III pipeline, and we are now fully integrated. Research excellence, development excellence, and now a commercial organization of excellence all coinciding together.
We're making substantial investments in our technology that's paying off. Advancements are extending our leadership position and expanding our ability to tackle diseases tomorrow that we can't tackle today. All of this leading to a sustained delivery of transformational medicines in the near term and in the long term. Thank you for listening. With that, I would now stop. I will now pause and take a short pause and then open it up for a question and answer session. The instructions for the question and answer session are shown on this slide, and we look forward to seeing you back for the Q&A period in about five minutes or so. Thank you. Welcome back. Again, my name is Brett Monia, CEO of Ionis, and we are now in the question and answer session for the 2022 Ionis stockholder meeting. Joining me to my left is Beth Hougen, and to my right, Onaiza Cadoret-Manier. Beth, you wanna briefly introduce yourself?
Sure. Thank you for having us. My name is Beth Hougen, and I'm Ionis's Chief Financial Officer. I've been with the company for over 20 years now.
Onaiza Cadoret-Manier.
Sure. Good afternoon, everyone. Onaiza Cadoret-Manier. I'm the Chief Product Strategy and Operations Officer for Ionis.
Great. Well, let's start with some questions. Do we have any?
Yeah, sure. First question is, as you highlighted today, you clearly have a rich phase III pipeline. We hear a lot about eplontersen for TTR amyloidosis and donidalorsen for HAE, but much, much less about olezarsen. Well, you referenced it today. Can you expand a little bit on the commercial case, the unmet medical need for lowering triglycerides, the olezarsen program and the general commercial opportunity for the program?
Yeah, that's a great question. Thank you for that. Indeed, olezarsen, despite our great efforts, seems to continue to fly under the radar. We do think it's a great drug, as I tried to highlight in my presentation. It has potential for a blockbuster. I'd really like for Onaiza to speak to the potential for to really have a big impact on the market, if you will.
Yeah. I'll be happy to. I think whoever asked the question, it's a great one because we do actually see it's somewhat under the radar. It has, you know, blockbuster potential, as Brett said. Importantly, actually, we always start as we do in all of our commercialization processes to understand what the unmet need is out there. You know, this is actually significant, and it's multifactorial. There are multiple sets of population that I'll talk about in a minute, but important to know in an unmet need marketplace, it's really critical to see what is already in place. The standard of care is actually suboptimal for these patients, right? They have severe elevated triglycerides, which give them several different types of conditions. What is available to physicians right now in their armamentarium, in their toolbox for them is really niacin, fibrates, very old agents. Even the newer agents, such as
There's a couple of questions on the thrombosis programs, somewhat related. Ionis has a phase I study of factor twelve inhibitor ION 547, and also the phase II program on fesomersen for factor eleven. Questions are how those programs related? Are they complementary competing drugs? How are the two differentiated?
Very exciting programs. Thank you for the question. Factor eleven is much further along than factor twelve. Both are coagulation factors, of course, produced by the liver. We were 1st to validate factor eleven in humans as a potent antithrombotic agent that provides minimal risk of bleeding. We were 1st to do it in a knee surgery surgical setting in the clinic. That was our non-LICA drug. We then brought forward our LICA version of that drug called fesomersen, and that study is about to read out soon in a phase II-B study with our partner Bayer. Based on that data, fesomersen is gonna be a phase III ready asset. It's gonna be ready to go. We validated factor eleven, and it's very far along in development.
Very exciting. It really is the future of antithrombotic therapy, in my view. Factor XII isn't as far along. It's wholly owned by Ionis, so it's not partnered and, but we have some validation to do with Factor XII. We have to prove that Factor XII is a good and safe antithrombotic. We're confident that inhibition of Factor XII will not produce bleeding. We have to show that it has a potent antithrombotic effect. Once we do that, we'll know whether or not these two programs will compete or differentiate or whether Factor XII just is not as good as Factor XI. We have some clinical validation to do with Factor XII, and we're well on our way. We're about to start phase II development for Factor XII in a thrombosis setting. Stay tuned. Very exciting.
There's a follow-up question, if you will, on Lp(a). Is there an interim look in the phase III olezarsen trial and a possible earlier timeframe to submit for approval?
Yeah, that's really a great question for Novartis. Novartis, they have said that there is the potential for an interim analysis in that CVOT study. That's all they've said. I assume it's baked into their statistical analysis plan, and they can pull that trigger if they choose to, based on a collection of data that they'll make that call on. Really beyond that, it's a question for Novartis.
There's a couple follow-ups to the olezarsen program and discussion. One is what the progress of Waylivra and what's happening with Waylivra and how that fits in, and then also how the commercialization of olezarsen and thoughts on that with regard to 1st a rare indication, then expanding into a much broader indication of the strategies for that.
Thank you for the question. I'll take the 1st one, maybe Onaiza you can talk about the plan to execute olezarsen through the market. Waylivra is on the market for FCS in certain countries in Europe and in Latin America. Sobi is our distribution partner, is distributing Waylivra in Europe and our partner, PTC, in Latin America. We decided a couple years ago to not advance Waylivra in the United States through the FDA because we had olezarsen coming. We had a much better drug. It's a LICA medicine, and eventually olezarsen will cannibalize Waylivra in the markets where Waylivra is today. Of course, we expect to be fully approved for rare and broad indications in the U.S.
Yeah. On the pricing issue, really we understand there's a, you know, big difference between rare disease pricing and pricing in more prevalent diseases. We fully expect that as we launch into FCS. We know that it's really important to think about bringing this to patients as quickly as possible. It is the 1st indication, but we also expect that we're gonna go into pricing from a, you know, more prevalent disease perspective that you can expect for all of the cardiovascular diseases that have sizes and prevalences of in the millions as well. We would, the FCS patients would actually get that at that prevalent disease price.
Next question is about FUS. How is enrollment going, and is it still on track to read out in 2024?
Yeah. The FUS phase III study is enrolling well, and it continues to be on track in 2024. You know, we're very pleased with the enrollment that's happening so far in that ultra-rare form of ALS. I also want to mention, it was on my slides, but I didn't highlight it, I don't think. You know, we started that program with an investigator at Columbia University and in a compassionate use basis before we took it back and developed it now for phase III. Some of that data was published earlier this year, including autopsy data from a patient that was treated with that drug.
The results, the overall results, both for the patient while she was alive as well as, the autopsy data was very compelling, very providing a lot of encouragement that, we're getting to the target. We're lowering the target and potentially, patients will do better. It's not a lot of data, but it's very encouraging, nonetheless. Take a look. If you're interested in the FUS program, take a look at that data. It's very interesting.
Another question about the neurology programs. Any update you can provide regarding the Huntington program with Roche, specifically tominersen and when can we expect to see any news on that program?
We're committed to developing treatments for Huntington's disease. We were disappointed early last year when the GENERATION HD1 study was terminated early. Although patients continued to be followed, we stopped dosing based on, let's say, the oversight committee or DSMB or what have you. An oversight committee at Roche concluding that patients weren't gonna do better if the study continued through 25 months, I think it was. Nevertheless, Roche continues to follow those patients, and very importantly, they continued to analyze all the data from the phase III study, and that is the largest study by far of a therapeutic in Huntington's disease. They have a wealth of data.
Earlier this year, Roche presented at a medical meeting findings that suggested in a post-hoc analysis of that data that patients with less disease burden that were younger with Huntington's disease were potentially doing better with tominersen. Quite encouraging post-hoc data analysis, take it with a, you know, take it that way. But all or not all, I should say, but many, most, potentially all of the clinical endpoints that were evaluated in that post-hoc analysis were all trending in the right direction, as was neurofilament light chain, a marker of nerve degeneration. Based on that analysis, Roche is planning to initiate a phase two study in a similar patient population that appears to be getting benefit soon. They haven't put specific timelines on when they're gonna start that study, but they're great partners.
They're very committed as we are to bring medicines to the market, to patients with Huntington's disease, so they're moving as urgently as possible, so stay tuned for that. It's quite encouraging.
There's a couple questions on the MAPT program. What is the status of the Biogen Ionis drug for MAPT for Alzheimer's? When will the phase I, II-A data be released? When you get to that, I'll have one more.
The phase I/II data that Biogen presented last year at the Alzheimer's meeting last summer was very impressive. We demonstrated in that study. The study was in mild Alzheimer's patients, so it wasn't designed to show, you know, improvements in cognition. What it was designed to do was to select a dose for a follow-up phase II, a much broader follow-up phase II study, based on safety tolerability but also based on tau reductions. The reductions we saw in tau in the CSF, which are of course reflective of what's happening in the CNS, were substantial. Tremendous reductions in tau levels in the CSF. These reductions were durable, that lasted many months following cessation of dosing. That data was presented at the Alzheimer's meeting last summer.
I believe our partner, Biogen, is planning to prepare a publication with that data and, then the next step is for them to initiate a, much larger, phase two study in patients with Alzheimer's disease. They haven't put out timing on that yet, but stay tuned. It's moving forward very well.
The next question was regarding the phase II. It says, "Biogen plans to dose every III or 6 months in the phase II MAPT trial. That is less frequent than the phase I, and could you comment on that?
Love to. Good question. You know, we're learning a lot about how to optimally dose our drugs in for CNS applications. Remember, we were the ones that pioneered the administration of oligonucleotide therapies to the CNS. Well, that of course with Spinraza in babies and then SMA adults and then so much more experience that we've done over time. We continue to refine our molecules, our chemistries, as well as understanding how best to dose, focus on dosing frequency, if you will. Many, most of our molecules that are moving into development nowadays are showing a similar profile as MAPT that we believe will now allow us to dose biannually with existing chemistries. For example, potentially, we're seeing long-lasting effects for several of our drugs in the CNS.
I believe that that's gonna become the norm, not the exception. I also wanna remind you that we also have new chemistries coming forward for CNS applications, right? In January this year, Biogen licensed from us an Ionis discovered, invented chemistry for a follow-on molecule of the Spinraza that we are hopeful will get us to every nine-month dosing or once a year dosing. That study has not started by Biogen in SMA yet, but it will start soon. I guess the short answer is the technology continues to advance and we continue to optimize applications for CNS for systemic applications and more.
Another question on technology. Ionis has a few job postings related to gene editing. What's the status of Ionis' gene editing programs? If they exist, what would be unique about them as compared to some competitors' programs?
Thank you for that question. We have an industry-leading research organization here at Ionis that is continuously evaluating many different technologies, many different platforms. You know, our goal is to become the leading genetic medicines company of all time. That includes antisense, that includes RNAi, that includes other platforms that we, if we deem are worthy of us conducting drug development in, we will do so. We're working in DNA editing. We're working in other areas too.
This is all consistent with the strategic imperatives that I laid out in 2020 when I said our three key objectives are to bring drugs to the market ourselves and to become a fully integrated biotech company, to diversify our technology base, our platform technology base, including DNA editing, and to maximize, bring an abundance in molecules, medicines to the market, in the near term and in a sustainable manner. I can't hold these researchers back here at Ionis. They'll pursue all kinds of things, and that's just one area that they're pursuing. We're looking to hire some experts in DNA editing. We'll see where it goes.
Question. Couple questions about LICA. One is relating to some competitors who have LICA targeting the CNS and other competitor targeting the lung. The question is, does Ionis have any LICAs for these tissue types?
Yeah. It's another technology question, like you said. Great question. Thank you. We have a broad comprehensive LICA program, as I'm sure you all know. You know, with a lot of experience in the liver with LICA. More than 5,000 patients now treated with liver LICA. Reproducibly excellent safety, potency, tolerability, efficacy. Based on everything we've learned about liver LICA, we're expanding that to other tissues, such as skeletal muscle, cardiac muscle, lung tissue, pancreas. We've had good success in pancreas and muscle already. We're also looking at LICA strategies for the CNS and in the lung too. I can't comment on competitors' programs. There actually hasn't been a lot of data.
I think there's been things written in some, you know, announcements in here and there, but there hasn't been anything published in a scientific peer-reviewed journal. It's hard for me to comment on that. Let me assure you that I believe we have the most comprehensive LICA platform for anybody in RNA-targeted therapeutics, and I believe that we're advancing new LICAs for new organ systems into development, hopefully by the end of this year.
Continuing on LICA, can you describe some of the potential benefits of your muscle LICA program, particularly relating to the Bicycle and potentially Arrowhead collaborations?
We are very pleased with our Bicycle Therapeutics and Arrowhead Pharmaceuticals collaborations. These collaborations are focused on developing novel ligands targeting cell surface receptors using a LICA strategy to enhance drug delivery to specific cell types. Both of these strategies offer the potential to use ligands, that is, molecules attached to our oligonucleotides to drive them into the cells we wanna drive them to. Ligands are very low molecular weight, okay, compared to, for example, large molecule monoclonal antibodies or other things that are using molecule LICA strategies. We believe that there are lots of advantages to this strategy including more convenient dosing regimens. We strongly believe that the subcu route using our low molecular weight LICA strategies for muscle are well within reach, so we don't have to go intravenous.
Easier to manufacture, simple medicinal chemistry, so that we can do chemical modifications to enhance the drug-like properties, reduce cost of goods, easier manufacturing, and so on. We're really focused on low molecular weight ligands that can deliver our drugs to various tissues and cell types, and that's what Arrowhead and Bicycle brings to the table. The collaborations are going exceptionally well, and we're very pleased with the progress we're making.
This is the last question. Why are you so confident that you can successfully penetrate the established HAE market that appears to be relatively, well served by several currently marketed products?
That's a great question for you, Onaiza.
Sounds good. I'll wrap it up. First I'll say I don't think it's well served. We tested our TPP just when we got our phase II data, and I have done a lot of these in my lifetime. I've never seen a set of physicians and patients so excited to have this product. There is an unmet need that is unequivocally on zero attack rates, which is the efficacy marker in the marketplace. There are multiple dimensions of efficacy, but that one seems to be the most important. If you see our phase III data, which is published in The New England Journal of Medicine, you will see that and we get there with a 97% attack rate in a very fast period of time.
Which is the other efficacy dimension because you're taking this medication from a prophylactic perspective. You wanna get there as fast as possible, and we get there in about one dose. So it's very meaningful. It's very meaningful to patients. It's very meaningful to give them the confidence and the freedom to be able to do this prophylactically. And then, you know, if you take a look at what's in the marketplace right now, you have a lot of agents, which is true in the prophylactic market, as Brett said, is growing pretty rapidly. But the unmet need is also around the ability to take a low volume, very easy to use, injectable, and self-help administration as well, again, to kind of speak to the freedom that it brings.
That actually isn't available to all the patients right now. We have the market's more in the every two-week stage versus every month. You know, it's a very strong profile that we bring together with efficacy, with safety, tolerability, as well as the package on the self-administration and the dosing.
Yeah. Thank you. Thanks, everybody, for participating. This has been a great set of questions. Very thoughtful, and we hope we addressed your questions sufficiently. Thanks again for joining us for our stockholder meeting this year, and we look forward to seeing you again down the road. Have a really great day. Take care.