Q2 2024 Ionis Pharmaceuticals Inc Earnings Call

Participants

Wade Walke; Senior Vice President, Investor Relations; Ionis Pharmaceuticals Inc

Brett Monia; Chief Executive Officer, Director; Ionis Pharmaceuticals Inc

Richard Geary; Executive Vice President, Chief Development Officer; Ionis Pharmaceuticals Inc

Kyle Jenne; Executive Vice President, Chief Global Product Strategy Officer; Ionis Pharmaceuticals Inc

Elizabeth Hougen; Chief Financial Officer, Executive Vice President - Finance; Ionis Pharmaceuticals Inc

Eugene Schneider; Executive Vice President, Chief Clinical Development Officer; Ionis Pharmaceuticals Inc

Eric Swayze; Executive Vice President - Research; Ionis Pharmaceuticals Inc

Jonathan Birchall; Chief Commercial Officer; Ionis Pharmaceuticals Inc

Myles Minter; Analyst; William Blair & Company, LLC

Yanan Zhu; Analyst; Wells Fargo Securities, LLC

Jessica Fye; Analyst; JPMorgan Chase & Co

Allison Bratzel; Analyst; Piper Sandler & Co.

Yaron Werber; Analyst; TD Cowen

Jason Gerberry; Analyst; BofA Securities

Jay Olson; Analyst; Oppenheimer & Co. Inc.

Mike Ulz; Analyst; Morgan Stanley

Gary, Nachman; Analyst; Raymond James

Salveen Richter; Analyst; Goldman Sachs

Konstantinos Biliouris; Analyst; BMO Capital Markets Equity Research

Presentation

Operator

Good morning, and welcome to the Ionis second-quarter 2024 financial results conference call. As a reminder, this call is being recorded. At this time, I would like to turn the call over to Wade Walke, Senior Vice President of Investor Relations to lead off the call. Please begin.

Wade Walke

Thank you, [Danielle]. Before we begin, I encourage everyone to go to the Investors section of the Ionis website to view the press release and related financial tables that we will be discussing today, including a reconciliation of GAAP to non-GAAP financials. We believe non-GAAP financial results better represent the economics of our business and how we manage our business. We've also posted slides on our website that accompany today's call.
With me on this morning's call are Brett Monia, our Chief Executive Officer; Richard Geary, Chief Development Officer; Kyle Jenne, Chief Global Project Strategy Officer; and Beth Hougen, our Chief Financial Officer; Eric Swayze, Executive Vice President, Research; Eugene Schneider, Chief Clinical Development Officer; and Jonathan Birchall, Chief Commercial Officer, will also join us for the Q&A portion of our call.
I'd like to draw your attention to slide 3 in our presentation, which contains our forward-looking language statements. During this call, we will be making forward-looking language statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors contained in our SEC filings for additional detail. And with that, I'll turn the call over to Brett.

Brett Monia

Thanks, Wade. Good morning, everyone, and thanks for joining us on today's call. We've achieved a great deal during the first half of this year, delivering on many significant milestones as we continue to execute on our vision to bring better features to people with serious diseases. Today, Ionis discover and developed medicines are reaching more and more people, hosed by two recent launches.
We newer for people with hereditary ATTR polyneuropathy in the US and outside of the first approved treatment for a genetic QALSODY of ALS currently available in the US and now approved and available in Europe. And with the progress we're making across our pipeline, our medicines are well positioned to continue reaching more and more patients for years to come.
US launch of our first Ionis co-branded medicine WAINUA is progressing well with AstraZeneca, and we expect to bring WAINUA even more patients across the globe with the recent approval in Canada, an anticipated approval decision in Europe later this year and with additional regulatory submissions completed in many other geographies with more coming.
Today, we are even more confident in the potential of WAINUA to address the larger ATTR cardiomyopathy population. As the largest study ever conducted in this patient group, our ongoing landmark cardio transform trial is on track to deliver the most comprehensive and the most robust data set in this patient population.
We believe, when you (inaudible) has the potential to be the treatment of choice for the global ATTR population. Our confidence is based on WAINUA a strong efficacy profile as demonstrated in hereditary ATTR polyneuropathy and the freedom of simple at-home self-administration, together with AstraZeneca's global cardiovascular commercialization leadership along with our leadership in ATTR amyloidosis.
As WAINUA want to accelerate, we're also preparing for the launch of Olezarsen in FCS later this year. Our first independent launch of a wholly owned medicine for Ionis. All those Olezarsen represents one of the most meaningful opportunities in our pipeline today as we prepare to first launch in FCS, a severe rare disease with no approved treatments in the US and then to expand to the much larger SHTG patient population.
Our NDA submission for Olezarsen was recently accepted with priority review. Our PDUFA date is set for December 19, and we're ready to bring this groundbreaking medicine to people with FCS. We also recently completed enrollment for our SHTG Phase 3 program and keeping us on track for data in the second half next year.
Based on our significant first-mover advantage and our positive results demonstrated to date, if approved, we believe Olezarsen could be the standard of care for both FCS and SHTG. We're building on the capabilities we've established for newer and Olezarsen in preparation for our anticipated launch of Donidalorsen for HAE prophylaxis next year.
In our comprehensive clinical program Donidalorsen has demonstrated strong evidence of meaningful benefit across multiple measures of disease for the favorable safety and tolerability profile. These data together with the potential for monthly or every two months of administration using an autoinjector, strengthen our belief that if approved, Donidalorsen has the potential to advance the treatment paradigm for people living with HAV.
With positive Phase 3 data in hand, we expect to submit the NDA for Donidalorsen soon as we look to independently bring down the lawson to patients in the US. Outside the US, our commercial partner, Otsuka, is preparing to file for marketing approval in Europe later this year and with our recently expanded license agreement, Otsuka is also working to bring down version to people with AJE in Asia Pacific region.
Following the WAINUA, Olezarsen, and Donidalorsen, our next wave of wholly owned opportunities includes our program for Angelman syndrome. Based on the positive results from the HALOS Phase 1, 2 study that we presented last week, we are advancing this potentially transformational medicine into a Phase 3 study, which we anticipate will begin in the first half of next year.
ION582 is positioned to become the cornerstone of our wholly-owned neurology franchise with today -- which today includes five wholly owned medicines in clinical development with more to come by the end of the year. Our accomplishments so far this year and the investments we're making move us closer to achieving our goal bringing a steady cadence of new transformational medicines to patients for years to come and generating next-level value for all Ionis stakeholders.
With that, I'll turn the call over to Richard to discuss our recent pipeline progress and preview key upcoming events.
Next, Kyle will review the WAINUA launch and our launch plans and progress for all those are some inbound Olezarsen. And Beth will review our financial results. I'll then wrap up things before taking your questions. With that over to Richard.

Richard Geary

Thank you, Brett. We are pleased that our pipeline delivered many important achievements to date this year. With WAINUA reaching more and more people with hereditary ATTR polyneuropathy. I am proud of all that Ionis team has accomplished to discover and develop this important new medicine and bring it to patients in need.
Recent ATTR cardiomyopathy data further reinforce our confidence in the potential of WAINUA to improve cardiovascular outcomes in this estimated worldwide patient population of approximately 300,000 to 500,000. With over 1,400 patients enrolled in our ongoing Cardio TTRansform study is the largest and most comprehensive study ever conducted at HTTE -- in ATTR cardiomyopathy. And as a result, we expect the data we generate will enable physicians and payers to make informed treatment decisions in this dynamic treatment landscape.
In addition, as part of our Phase 3 program where conducting advanced cardiac imaging sub-studies, including an MRI substudy and a scintigraphy sub study, which will generate valuable data about the potential benefits of WAINUA in cardiomyopathy patients. We were delighted that our recent Olezarsen NDA submission was accepted by the FDA for priority review, highlighting the potential of this medicine to make a profound difference in the lives of patients.
Our submission was based on the positive Phase 3 results in FCS that we presented and published earlier this year. In the Phase 3 Balance study in patients with FCS, all the sources showed substantial and durable triglyceride reductions and importantly for patients, physicians and payers alike, our size and demonstrated substantial and clinically meaningful reductions in acute pancreatitis attacks, our remarkable 84% reduction in hospitalizations and a favorable safety and tolerability profile.
We look forward to our upcoming December PDUFA date and assuming approval bringing to Olezarsen to people with FCS who currently have no approved treatments in the US. We are also developing Donidalorsen for the much larger, severe high triglyceride patient population. And we recently completed enrollment in our extensive Phase 3 program for SHTG with more than 2,500 patients enrolled across three studies.
This puts us on track for data in the second half of next year, maintaining our multiyear first-mover advantage and this wholly owned blockbuster opportunity. Following closely behind our Olezarsen is done at Donidalorsen for the prophylactic treatment of hereditary angioedema, we recently presented and published in the New England Journal of Medicine, positive Phase 3 data from a ways of HAE, our placebo-controlled trial.
Additionally, we also presented positive data from OASIS plus our trial that includes an open label cohort for patients rolling over from the Phase 3 study and a separate cohort that we refer to as the switch study Donidalorsen treatment significantly reduced HAE attacks. The reduction in HAE attacks translated into significant and clinically meaningful improvements in quality of life across multiple validated measures and high levels of disease control in a vast majority patients.
And with longer term treatment patients improved further on all these measures. Additionally, as of our most recent data cut off in February [98%] of OLE patients remain in the study. These positive data were further bolstered by the encouraging switch results. The switch study through week 17 patients showed a substantial reduction in their HAE attack rate with Donidalorsen treatment compared to baseline on their previous treatment.
Now, the Olezarsen treatment also resulted in improved quality of life measures and increased disease control. Importantly, more than 80% of patients surveyed reported a preference for Donidalorsen over their prior prophylactic treatment and nearly 90% of switch study patients remained in the study as of the data cutoff in February.
In addition, to strong clinical results, Donidalorsen offers the potential for simple monthly or every two months self-administration via an autoinjector. Based on these data, we believe Donidalorsen could become a preferred prophylactic treatment for people with HAE. Our NDA, which we plan to submit soon will include data from OASIS, HAE, OASIS plus, OLE study switch and our Phase 2 study.
Outside the US, Otsuka is preparing to submit for marketing approval in Europe later this year. And with the recent expansion of our license agreement, Otsuka also plans to bring Donidalorsen into patients in the Asia Pacific region. The rest of our rich Phase 3 pipeline is also advancing positioning us to continue delivering a steady cadence of potentially transformational medicines to patients.
We recently completed enrollment in the pivotal arm [Ulefnersen] study for Alexander disease, keeping us on track for a Phase 3 readout next year. And GSK recently completed enrollment in the Phase 3 program for the parent person for chronic hepatitis B, which keeps the program on track for data in 2026. Coming right behind these programs, we have our next wave of medicines, including a number of medicines to treat both rare and broad neurological diseases, five of which are wholly owned and we expect our wholly owned pipeline to expand later this year when two more medicines from our neuro disease franchise enter clinical development.
ION582, our medicine for Angelman syndrome has transformational potential for the 100,000 of people living with this serious rare disorder who are in need of disease-modifying treatments. For this reason ION582 is poised to become the cornerstone of our wholly-owned neurology pipeline. We're encouraged by the recently presented positive early results from the HALOS study of ION582, and people with Angelman syndrome.
In this study, we demonstrated evidence of consistent and meaningful improvement on all key functional areas across multiple assessments. This included 97% of participants showing clinically meaningful improvement in overall Angelman syndrome symptoms on the SAS, CGI assessment. Improvements in measures of communication, cognition and motor function exceeded natural history on the Bayley-4, Vineland-3 and Orca assessments.
Additionally, we observed consistent improvements across ages and genotypes. And we saw favorable safety and tolerability at all dose levels, including no discontinuations for adverse events that were considered related to study drug. Based on these positive data, we plan to advance ION582 and do a well-controlled Phase 3 study in the first half of next year.
Alongside the positive Phase 1,2 data for Angelman syndrome several recent events have also occurred in our mid-stage pipeline. We were pleased to present positive Phase 2 data at EASL for ION224, our medicine targeting began to for the treatment of metabolic dysfunction associated steatohepatitis or MASH.
Additionally, based on the encouraging Phase IB data, from ONIS-MAPTRX also known as debating that were presented late last year by (inaudible) recently announced, they amended the ongoing Phase 2 Steleus study with the goal to accelerate a potential proof of concept outcome as a result of this change, they are now projecting data in 2026?
Also, we and our partners recently discontinued development for ION541 targeting Ataxin 2 for ALS and [IONIS-FB-LRX] for geographic atrophy. Both programs showed good target engagement and favorable safety, but did not meet their primary efficacy endpoints. Importantly, (inaudible) continues to advance the IONIS-FB-LRX IgA nephropathy Phase 3 study that they initiated last year based on positive Phase 2 data.
Looking ahead, we have several important milestones still to come this year. These include presenting new Phase 2 open-label extension data for Donidalorsen and data from the devote study, which is evaluating a higher dose of SPINRAZA as well as anticipated regulatory approvals and launches for WAINUA and Olezarsen and regulatory filings for Donidalorsen. With that, I'll turn the call over to Kyle.

Kyle Jenne

Thank you, Richard, we are pleased with the initial results of the WAINUA new launch with AstraZeneca following US approval at the end of last year, including the significant growth quarter over quarter with an estimated 40,000 patients worldwide and fewer than 20% of patients on approved treatment, people with hereditary ATTR polyneuropathy remain underdiagnosed and largely underserved.
As a result, a high unmet need remains that we and AstraZeneca are uniquely positioned to address. The combined team is working together seamlessly with shared goal to make WAINUA, the preferred choice for patients with ATTR polyneuropathy.
We continue to see good uptake among patients in the second quarter with an encouraging mix of new patient starts, including some who are new to this class of medicine, some switching from other treatments and some using WAINUA as an add-on treatment to their existing therapy. Prescribers and patients are recognizing the newest strong clinical profile and patients value the ability to easily self-administer window up from their home.
We expect to reach a growing number of patients as we continue to educate prescribers about the value that WAINUA brings. With our increased confidence in our ongoing cardio transform study for ATTR cardiomyopathy, we and AstraZeneca are progressing our pre-commercialization activities and investments to support the potential substantial opportunity WAINUA represents. We are leveraging and building upon our efforts for the WAINUA launch to prepare for our upcoming independent launches of Olezarsen and Donidalorsen.
As Richard mentioned, we are developing Olezarsen for two indications, the rare FCS indication and the broader SHTG indication with anticipated first mover advantage in both settings. We are pleased to receive positive feedback from key opinion leaders on the Phase 3 FCS data that we presented at ACC. They were particularly impressed with the reduction in acute pancreatitis attacks and the substantial reductions in hospitalizations and in-patient hospital days.
We expect that these data will also be important in securing access from payers. In addition, the US expanded access program for Olezarsen is in place, enabling patients to have access to treatment ahead of potential approval. We are putting the final touches on our independent launch plans to bring Olezarsen to patients as soon as possible after anticipated approval.
Our medical affairs team has been meeting with physicians and working to improve disease awareness through disease education. Earlier this year, we hired our first Ionis national sales director and now with the December 19 PDUFA date set, we have recently hired and are now training our customer facing team with extensive rare disease experience in preparation for the FCS launch. To bolster our field teams efforts, we are deploying a tailored omnichannel strategy to further enhance our relationships with patients and health care professionals.
Finally, we are building a world-class patient and caregiver support team to provide a seamless customer experience to help patients initiate treatment and remain on therapy long term. We plan to further scale our commercial capabilities as we prepare for the SHTG indication to realize the full blockbuster potential of Olezarsen.
Donidalorsen for the prophylactic treatment of HAE is our next planned launch after Olezarsen. And based on the positive results we have seen in the comprehensive development program, we are excited with what Donidalorsen could mean for people with HAE. HAE is a well-defined patient population with an estimated 20,000 people affected in the US and Europe, while prophylactic treatment in the US is well accepted by patients and physicians.
There continues to be a need and the market continues to grow. Outside the US acute therapies have historically been the standard of care. However, prophylactic treatments are gaining ground, especially in Europe. Many people in HAE are unsatisfied with current treatments and are looking for the option that reduces frequency and severity of attacks that also offers good tolerability and convenience.
This is a disease that typically appears in childhood, so patients have to manage their disease throughout most of their life. As a result, patients have a history of switching treatments seeking to find the best therapy for them. We believe Donidalorsen could be a preferred prophylactic treatment for both patients new to therapy and patients currently on available therapies.
With strong clinical data, including switch data and the simplicity of monthly or every two months self-administration be an autoinjector, we believe Donidalorsen combines the attributes that people with HAE are looking for in a single attractive treatment, assuming approval. Today, I'm pleased to share that we are right where we should be in preparing for upcoming launches. Our infrastructure to support commercialization is in place, and we will be ready to begin delivering our medicines to people in need as these new therapies come to the market.
Now, I'll turn it over to Beth.

Elizabeth Hougen

Thanks, Kyle. Our results in the second quarter and first half of this year reflect the excellent progress we've made toward our goal to bring a steady cadence of medicines to the market. We continue to generate meaningful revenue while investing our capital to independently launch several new medicines over the next few years, that have a combined multi-billion dollar peak sales potential. We are also investing into advancing our next wave of wholly owned medicines, which continued to make great progress in the first half of this year.
In addition to our recent pipeline achievements, we've delivered strong financial results, keeping us on track to achieve our financial guidance. We earned revenues of $225 million, $345 million for the second quarter and first half of this year, respectively. As we remain the primary source of our commercial revenue was $57 million and $95 million of royalties in the second quarter and year to date.
Notably, SPINRAZA product sales increased 25% from the first quarter to the second quarter due to growth from both the US and ex-US markets. Additionally, in the second quarter of the WAINUA launch products sales were $16 million, bringing year-to-date sales to $21 million. As a result, our WAINUA royalty revenue increased quarter over quarter to $4 million for the second quarter and $5 million for the year to date period.
R&D revenue also increased in the second quarter and year to date, reflecting the value that our pipeline and technology continue to generate. As planned, our non-GAAP operating expenses for the second quarter and year to date increased over the same periods last year, driven by higher SG&A expenses. Our SG&A expenses increased 46% and 31% for the second quarter and first half of this year, respectively, as we continued to make investments to prepare for our upcoming independent launches of Olezarsen and Donidalorsen.
Notably, we built out our commercial team, including our field organization, and they are enthusiastically preparing for FCS launch. Our SG&A expenses also included our minority portion of WAINUA US launch expenses. And as planned, our R&D expenses decreased slightly for the second quarter and were flat for the first half of this year compared to the same periods last year.
Our results for the first half of the year keep us on track to meet our 2024 financial guidance, including revenue of more than $575 million, of which approximately $175 million will come from non-cash amortization of partner payments we received in prior years. Looking to the second half of this year, we expect our total revenue to be slightly lower compared to the first half and weighted more to Q4.
We expect commercial revenue to increase as the launch of the ramp for renewal and counterparty and from higher anticipated SPINRAZA royalties as our tiered royalty rate increases. Additionally, we expect our R&D revenue, which often fluctuates from quarter to quarter due to the timing of achieving various collaboration milestones to be lower in the second half of the year.
Importantly, however, we still have the opportunity to earn sizable payments, including a $30 million milestone payment from AstraZeneca, if we knew is approved in the EU. We continue to project our full year 2024 operating expenses to increase by a mid to high single digit percentage compared to 2023, excluding the impact of onetime costs last year.
And similar to the first half of this year, the increase will be driven primarily from sales and marketing expenses as we prepare for our back-to-back independent launches of Olezarsen and Donidalorsen. We are on track to end the year with $1.7 billion in cash as we continue to make strategic investments in the substantial opportunities before us today, including our late-stage program and our next wave of innovative medicine. So as you can see, we delivered a strong second quarter and first half.
Before I turn it back to Brett, I'd like to provide you with a look beyond this year to our path to revenue growth and increasing value as we deliver on our goal to bring more medicines to more people. With our strong development and regulatory progress, Ionis is at a critical inflection point. We have several near-term commercial opportunities with significant potential to help patients in need.
In parallel, we are advancing our next wave of potentially transformational medicines and our technology. As a result, we plan to continue to strategically invest our capital resources to ensure we unlock the full potential of our promising near and longer-term portfolio. Our investments are focused in four key areas.
First, in our go-to-market activities, enabling us to realize the full value of our medicines, which includes investing in our upcoming independent launches for Olezarsen and Donidalorsen. Our expenses in this area also include our newer cost share with AstraZeneca for the hereditary ATTR polyneuropathy launch in the US.
As we approach the anticipated Olezarsen launch for the broader severe high triglyceride population. We will scale our capabilities and increase our go-to-market expenses to support the larger opportunity. And as we and AstraZeneca approach a potential ATTR cardiomyopathy launch for WAINUA, our expenses will increase consistent with the much larger cardiomyopathy opportunity. Importantly, our planned investments are right sized for the combined multi-billion dollar revenue potential that these important medicines represent.
Second, we continue to advance our late-stage pipeline. All of our ongoing large Phase 3 studies are fully enrolled with more than 4,000 patients in all and are currently in the heaviest period of investment. We expect these investments to fuel our continued value generation and revenue growth as the data readouts, and we bring new medicines to patients over the next couple of years.
Third, we are increasing our investments and our next wave of medicines, including development and pre-commercialization expenses for our growing wholly owned pipeline of potentially groundbreaking neurology medicines, such as ION582 for Angelman syndrome.
And finally, we are investing in cutting-edge technologies to ensure we continue to deliver innovative medicines with competitive profiles well into the future. As you can see, we are strategically investing our capital towards growth opportunities. Importantly, we expect our investments to power strong revenue growth and positive cash flow as our medicines reach more and more patients in need, positioning us to deliver next-level value for all Ionis stakeholders for years to come.
And with that, I'll turn the call back over to Brett.

Brett Monia

Thank you, Beth. As just summarized, we have made great progress in the first half of this year. And in the second quarter alone, we've achieved a great deal with many important successes, which include continued strong start to the renewal launch for hereditary ATTR polyneuropathy in the United States, approval in Canada and submissions under review in many additional territories.
Positive FCS data for Olezarsen which we presented at ACC, which were the basis for our NDA submission, which was recently accepted by the FDA with priority review. Positive HAE data for Donidalorsen presented at Yaki. It will be the basis of our upcoming regulatory submissions, and we completed enrollment for the Phase 3 Olezarsen and SHTG program this past quarter.
Keeping us on track for data next year. We also presented positive data from the HALOS Phase 1, 2 study in people with Angelman syndrome, and we are well along in preparing for our end-of-Phase 2 meeting with the FDA scheduled for this fall with plans to advance this important medicine for Phase 3 development next year. And we delivered solid second quarter and first half financial results, keeping us on track to achieve our 2024 financial guidance.
Based on the strong progress we've made across our business this year, we are well positioned to continue building on our positive momentum as we execute towards achieving all of our strategic priorities. We've aligned where we are today by being focused on a clear vision and a clear set of strategic objectives, which include building and advancing our pipeline and delivering medicines that we can see discover and develop directly to patients.
Our pipeline is delivering, we achieved multiple marketing approvals and positive key data readouts over the past year, and we are poised to build on the strong momentum in the near term. We have prioritized building our wholly owned pipeline and are now advancing several of these medicines towards the market.
In parallel, our partnered programs are progressing on track with important Phase 3 readouts next year and beyond. We are also focused on extending our leadership position in (inaudible) type therapeutics by expanding and diversifying our technology, further optimizing our capabilities for existing therapeutic areas and opening of new areas for drug discovery.
All of this sets us up to continue bringing a steady cadence of new medicines to patients for years to come. And we're looking forward to sharing our progress as we build on our recent achievements and accomplish our strategic objectives.
And with that, I'll now open the call up for questions before moving into the Q&A portion of our meeting, I just ask that our analysts please limit yourselves to a single question as we have quite a long, long queue, and we'd like to get as many people in into the queue and ask their questions as much as possible. So with that, Danielle, we can open it up for questions.

Question and Answer Session

Operator

Thank you. We will now begin the question-and-answer session. (Operator Instructions)
Akash Tewari, Jefferies.

Hey, this is Ami on for Akash. Thanks so much for taking your questions. So one on ATTR-CM, there's been some debate on If you need a certain level of TTR to have a cardioprotective effect. Have you seen anything in your own data around this theory? And do you expect any differences with the silencer approach using an all-cause mortality versus the CBD mortality composite primary endpoint. Finally, do you have the flexibility to change your primary endpoint if needed? Thanks so much.

Brett Monia

Thank you, Amy. So we have seen that we don't believe that there's any evidence of a threshold effect for TTR lowering to achieve benefit in either polyneuropathy or on or in cardiomyopathy endpoints. We're very pleased with the magnitude of TTR reductions that we have seen in our in all of our studies for renewal on for polyneuropathy, I'm very pleased with the level of magnitude of TTR lowering we're getting.
But I don't believe that there's any believable evidence out there that suggest a specific threshold effect for our TTR lowering to produce benefit either in polyneuropathy or in cardiomyopathy, we believe our primary endpoint isn't all in cardio vascular mortality and hospitalizations, and that's what we're laser focused on. We also have as secondary endpoints specifically CV mortality as well as all-cause mortality. And we think they're both very important, our next question.

Operator

Myles Minter, William Blair.

Myles Minter

Hi, just on the timing of the cardio TTR transform readout, I mean, is it fair to say that you're at least waiting for data at ASA in London that might have read through to your trial? And if that is the case, what exactly would you be looking for out of that dataset to stick with the decision that you write that out early or just wait until the full 140 weeks are up in that study? Thanks very much.

Brett Monia

Thanks, Miles. And so we're very pleased with the way the cardio transform study is advancing. We are particularly pleased with the blinded events that we're continuing to evaluate both CV hospitalizations as well as mortality.
It's going very well right on track. As the first silencer readout in this indication, we're very much looking forward to any and all additional data that we can see, which we think will be very nice read-through to our cardio transform study.
As you know, the we have the largest by far study ever conducted in this patient population. And we think that anything we see from other molecules in the silencer trials are going to be very, very good read-throughs to what we expect to see in our study. So we're very much looking forward to any and all data that comes from future presentations on the silencer class. Next question, please.

Operator

Mani Foroohar, Leerink Partners.

Hey, guys, you have Ryan on for Manny. Thanks for taking our question. Can you just talk a little bit about any early insights from the when you will launch and how you see that in forming a potential launch strategy in cardiomyopathy and kind of alongside that, maybe what pre-commercialization activities you guys are undertaking in cardiomyopathy? Thanks.

Brett Monia

Well, I'm sorry, Jonathan.

Richard Geary

Yes, we're thanks for your question. We're very pleased with the early insights regarding with the PN launch and as Kyle referenced, we're seeing patients are new to treatment. We're seeing patients or restrict switching from existing treatments, and we're seeing patients having we know are added on to their current treatment. And so we receive are pleased with what we're seeing. It's very early days.
This is a foundation year for the launch of WAINUA, but we think there's certainly significant opportunity here with you think through the potential patient population of both PN and CM and the number of patients who are potentially underdiagnosed and fundamentally, the relatively small numbers today who were actually treated.
And what we're pleased with is that we seeing prescribing from both neurology and cardiology and both centers of excellence as well as in the community and that I think (inaudible) well, not just for the PM launch a nice progression, but also the transition obviously into future indications. Obviously, when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We will have to wait. So for future data readouts of our own pretty comprehensive programs.

Kyle Jenne

Yeah two quick things. To add first on the payer access side of things, we're seeing payers cover window up very quickly. So that the prescription process, the patients actually starting on drug is going very, very well. That tells us that the right types of patients are being identified. And it's also telling us that physicians are justifying the prior authorization process with the sense of urgency, which tells you that these patients need treatment and they see the value in WAINUA
The second thing I'll just mention is around our patient engagement team. Our [PEM] team is directly interacting with these patients and getting feedback on a real-time basis, how patients are extremely pleased at when they start WAINUA at the ability to self-inject with the autoinjector. Very well-tolerated, very easy to use, a very convenient for those patients and the profile of WAINUA is really playing out there, we expected it to the market.

Brett Monia

Next question, please.

Operator

Yanan Zhu, Wells Fargo Securities.

Yanan Zhu

Great. Thanks for taking our questions. Wondering about what's your takeaway from Roche's recent presentation there? Engemann syndrome Phase 2 data at the ASF. meeting? And also separately, given the similar development time line of your Angelman syndrome program and Ultragenyx program, do you think FDA will want to apply the same pivotal endpoint to both programs? Or is there a possibility that the agency could allow different primary endpoints based on strength of data? Thank you.

Brett Monia

Thanks Yanan, and I'll take the first question, then I'll ask Eugene to comment on the primary endpoint in any harm and harmonization in primary endpoints arrangements. So we are very pleased to see the data that Roche presented on their Angelman's program. And particularly, we were pleased with the fact that the data are further supported our confidence in our Phase 1, 2 data that we presented at ASF specifically that the rank order of improvements that they reported with respect to the magnitude of improvement was exactly what we reported.
The biggest magnitude that they reported was intercept was an expressive communication, followed by expressive, receptive communication, followed by cognition, followed by motor function and so on. And that's exactly what we reported, which get bolsters it further confidence in our results to date.
We are also pleased with the magnitude of benefit we're seeing compared to their program, which really looks like when you really compare apples to apples and you convert fairly treated daily for outcomes both very well. We will likely have even better efficacy at lower doses compared to what was presented, but we were pleased to see what they say, but they showed because of the consistency in sub domain benefit between the two programs.

Eugene Schneider

Yeah well, regarding our primary endpoint and conversations to be had with the agency, of course, we're looking forward to updating you after we've had our discussions. There's from our standpoint, there's this will be data driven. We certainly do believe that the data and consistency of what we see in our Phase 1, 2.
So it gives us pretty good idea what we would like to see in a pivotal study, but it's still to be seen what the specific primary endpoint will end up being. We'll certainly give you an update. yes, is there a precedence to have a slightly different or different primary endpoint? Of course, there's plenty of precedent in neurology space as well as type. I mean, if you look at ATTR-CM that's another example where primary endpoint is not identical for two very similar program. Stay tuned, we will certainly we'll be happy to provide you an update.

Brett Monia

Thank you (multiple speakers)

Operator

Jessica Fye, JPMorgan.

Jessica Fye

Hey there, thanks for taking my question. On the back of the top line, (inaudible) data, what's your latest expectation for whether silencers and TTR cardiomyopathy will mainly be used in combination with stabilizers versus as monotherapy? Thank you.

Kyle Jenne

Yes, I'd be happy to talk to that. this is Kyle. Thanks, Jessica. The data that ultimately is going to drive this, we believe that as a starting point, I think ultimately it will come down to physicians and patients making a decision around the profile of treatment that they want in that decision. But we see it right now, we are seeing new or used in combination, obviously, as [HATTR] polyneuropathy indication combined with cardiomyopathy indication for the stabilizers currently.
So we're seeing it happen now. We think that will continue to progress over time, and we also believe that based on the data and the way that data plays out will be justification for physicians to be able to justify that to the payers whenever they submit these requests and trying to get the drugs approved. So I think it's ultimately data in driven by physicians and patients.

Brett Monia

And just add to that, as you know, Jeff, we have -- we're positioned to have the richest data set across the board on a primary or secondary and some endpoints and subgroups. And we're going to have a great deal of data in combination usage as well as a monotherapy. Second to none and that includes data on -- no key endpoints, clinical endpoints such as hospitalizations, mortality, six-minute walk test, biomarkers and so on.
But also in the imaging studies, we have several imaging studies in process. And we think that if anyone's been able to show meaningful improvements in combination versus monotherapy across the board. But at the imaging or clinical endpoints, we're going to be the best in the best position to do so. And we think that doubled, as Kyle said, because this is a data driven environment, we're going to invest position to actually have data to support combination usage.
Next question, please.

Operator

Allison Bratzel, Piper Sandler.

Allison Bratzel

Hey, good morning, guys, and thanks for taking my question. Maybe one on Pelacarsen, since that Phase 3 data and regulatory filing are coming up next year. Could you just talk to or frame like what you'd like to see in that readout? And maybe in broad strokes, what gives you confidence in the differentiation of this asset in what could be a competitive space, color on that or the next-gen program would be helpful. Thank you.

Brett Monia

Yeah, Allison so, there's not the only the only news on Pelacarsen is really that the study is on track to read out on has scheduled next year. Everything is going very well. And our partner Novartis is well positioned with first mover advantage in this first to market patient population. This enormous patient population, everything we're seeing in the Phase 3 study is very supportive of this being set have been set up for a successful and outcome. First mover advantage is really important, and we would Novartis are has substantially to the market.
Yeah, the program, our follow-on program to Novartis with Novartis on the follow-on program is advancing well, maybe I'll ask Eric Swayze to comment on how the how things are going.

Eric Swayze

Things are going great. We've been working closely with Novartis, looking at a variety of ways to extend the dosing interval and make a great (inaudible) lowering drug. And I'm sure we'll discuss it in some time as the program advances further. But I can't say more than that at this time, but very pleased with the progress we've been making on new technologies, SIRNAs in particular and a broad range of other things beyond what would be minimal for the LPA permanent group.

Brett Monia

Where we feel very comfortable that we're going to achieve our objectives with Novartis on a follow-on molecule, things are going very well. There's obviously a lot of benchmarks out there today, there's a lot left to compare to please. Next question, please.

Operator

Yaron Werber, TD Cowen.

Yaron Werber

Great, also thanks for taking my question. I also have just a quick follow up on WAINUA. And as you look at the [Healios B] data and I'm totally obviously you're aware that the you're probably going to be waiting for the full Helios B results.
But as you think about with a much powered trial design, where could you potentially differentiate? And how important will that combo data be just given that overall and butcher will get a broad label for TTR. Thank you.

Brett Monia

Well, thank you Yaron. As the largest study ever conducted in this patient population. By far, we think we have the opportunity to differentiate in several different areas, but it will be very interesting to see the onset of action for silencers and whether or not our onset of action is going to be similar or faster. It could be very interesting to see the combination data, as you alluded to just now, as we touched on earlier, combination data, it can be very important patient population.
And despite having a broad label, which we expect to have as well, cardiologists are data-driven and they're going to need to see data before advocating for combination usage. I think we're well positioned to have that data.
As New York health class categories are very, very important to see how mild patients are doing moderately ill patients in severely ill patients are doing all of this. When you have a well-powered study at rich data and provide set up have the rich dataset you have the potential ability to differentiate across the board. Anything to add to that Eugene?

Eugene Schneider

No, not really about how to characterize it. I think the power really comes from the size of the study and also an ability to look at subpopulations, which were really well positioned to do.

Brett Monia

Thank you Yaron. Next question please.

Operator

Jason Gerberry, Bank of America.

Jason Gerberry

Thanks for taking my question. I wanted to come back to the cardio transform timing question. So it sounds like we're going to get pretty deep, detailed and granular data from our (inaudible) How do you see in terms of multiple curves on overall mono? I've groups with famous background, including mortality.
So it seems like you'll have everything you need to know post ESC on whether or not the 2025 interim is in the cards. So is it fair for investors to get or expect maybe a clear message as of the third quarter update on which way you're going to go as the base case 2026 or whether or not you're look to 2025 interim?

Brett Monia

Yeah, thanks, Jason. So Ionis and our partner, AstraZeneca had been thinking about this quite a bit on our base case remains sound or 40 weeks of treatment, which brings it to mid-2026. The study were to go to completion. But we are committed to bringing renewal to patients as fast as possible if it makes sense to do so.
And certainly, as I mentioned earlier, following upon our blinded events and following up on the studies that we're running is most important for any new information that we get from other treatments in this in our -- in the same class, the silencer class is going to be informative on what we do.
With that said, we can't get ahead of regulators, we're going to want to get on buy-in on anything we do with respect to an earlier readout with the FDA EMA before I make any proclamations out there publicly. So timing is a bit uncertain right now, but rest assured that we and AstraZeneca are working on this on very thoughtfully.

Jason Gerberry

Thanks so much.

Operator

Jay Olson, Oppenheimer.

Jay Olson

Hey, congrats on all the progress and thanks for taking the question. Can you talk about your launch preparation for Olezarsen in FCS.? And how should we expect the launch uptake and eventual opportunity in FCS and also the early access program, how many patients you have? And will those patients switch over to commercial product as soon after approval? Thank you.

Richard Geary

Yes, thanks for your question. We're really pleased with the progress we're making and have continued to make obviously a preparation started a couple of years ago with the medical affairs team and subsequent to that, we built out all the commercial functions that you would expect, whether that's in our mark to market access patient support that Kyle referenced with return of build-out and in our industry leading support that effort for our patients and to bring you right up to date, we've now started hiring and training, our field teams ready to engage with customers.
So the (inaudible) has gone very well and is certainly on track aligned with our regulatory progress, which with breakthrough designation has been at this point very timely and that we think sets us up for a positive launch.
And to you -- to your question, specifically about the expanded access program with all patients, let's be honest before that who've been in our pivotal registration studies that are obviously patients that at launch. We hope to provide the opportunity to move on to commercial drug. And the EAP is now in the hands of our medical team and they're talking to customers today and patients are progressing through the administration or the administrative side of getting access to all Assante through that program.
So all in all, we are doing a lot of work, as you can imagine, but very much on track to be ready to launch just as soon as the FDA provides approval, things cross.

Brett Monia

Next question, please.

Operator

Mike Ulz, Morgan Stanley.

Mike Ulz

Hey, guys, thanks for taking the question. Maybe just one on the neurology pipeline with Angelman sort of emerging as your lead programs. Can you maybe highlight what do you view as the next key opportunity there? And if there's any potential read-through from what you learned in Angelmans? Thanks.

Eugene Schneider

Yes, sure. Happy to. Thanks for your questions. Certainly because we are delighted to have annual maintenance service kind of the linchpin of the neuroscience portfolio, but it is a very rich portfolio following the Angelman Phase 3 program (inaudible) just to name a few Paramount, the balance currently, certainly the nursing home, which is now fully enrolled and its pivotal study.
As we recently announced, this is the next molecule that we're super excited about. It's an ultra-rare disease. It fits very well with our neurology portfolio. Those studies progressing while there's great feedback from sites and investigators on kind of the quality of the study conduct and behind. So the nurse and of course, we are delighted to have our thoughts (inaudible) program progressing well.
Our pre-owned program really kind of making great strides in first in human experiments that are now conducting. So we're looking forward to sharing lots of data with you over the coming months and certainly years in that rich area of research and development for us, our wholly-owned neurology pipeline.

Brett Monia

Thanks, Eugene is positioned to grow and expand. In addition to the programs that are in the clinic today, we expect to start two additional wholly-owned neurology programs by end of this year and more next year for both rare as well as larger indications, more highly prevalent indications.
I also want to highlight the great progress we're making to extend our leadership technologically in neurology our most advanced backbone chemistry MSPA will enter is expected to clinical development and C for a CNS indication later this year, which is focused on reducing dose frequency of very meaningfully.
We're also making great progress in traversing the blood-brain barrier using subcutaneous or intravenous administration in frequent administration. And we're looking forward to maybe our first candidate overcome the BBB, early 2025, and we're looking forward to talking about that as well.
So CNS is here now and we're we lead in this space, and we continue to expect to extend our leadership position in CNS going forward.
Thanks, Mike. Next question please.

Operator

Marie -- I'm sorry excuse me, Gary, Nachman, Raymond James.

Gary, Nachman

Great, thanks, guys. For Donnie, when you submit the NDA, what indication will you be looking for in the label and are you optimistic the switch data will actually be included on the label, which will be so important for these HAE patients.
Any chance you could get a priority review? Or is that likely a standard review? And when will you start building out that commercial team? How much could you fully leverage what you're doing currently with over resources? Thanks.

Brett Monia

Thanks, Gary. Eugene, I'll take the first couple of questions and then Jonathan could touch on the build-out of the commercial team.

Eugene Schneider

With regard to the indication, of course, we're seeking a broad indication for prophylaxis of attacks in hereditary angioedema, and we're pretty comfortable with how things are progressing. Obviously, it is have you determined what the final label looks like and the indications and we are some -- sorry, what was the second part of the sub-question. (multiple speakers)
And yes, along the same line, again, it's really early to speculate on what the final label is, we will do our best to. We believe our program, our pivotal program is very comprehensive and we also believe that the data that we collected and the switch populations. It's important for physicians to be aware of. So we'll make sure that this is shared broadly, whether it's publication or it ends up in the label, we can't really speculate today.

Brett Monia

Yeah, and I'll just touch on that a little bit more, Gary, on the switch data is very important we believe from a safety standpoint, which we think boths very well for, including in the label. I mean, these patients switch over time, right? And actually having data that informs physicians on how to safely switch patients such that they avoid getting our GAAP and our protection against HAE attacks is going to be very important and we think that will and of course, the FDA is focused on safety and protection against disease progression.
So we think that both very well for us to get in the label. But as Eugene said, if it's some risky to get ahead of the regulators on what the label will look like. But we think that we have a pretty good shot at that.
Jonathan, how like how much prep count?

Jonathan Birchall

Launch prep is going well. And as you could imagine, this is coming so hot on the heels of the potential as the launch that we talked about it. But the launch prep on the commercial side for Donnie is well advanced or a lot of capabilities that we built and for all of us and we can leverage for Donnie, whether that's the medical affairs function.
First and foremost, that's been done established product trials, and that's now leading in the HAE space, we've got brand teams, access teams, building out the value dossiers and patient services is also well advanced to ready to support patients in HAE space and omnichannel as well as a capability that we feel very confident that we will built well at Ionis now and is a capability that's very applicable close to the FCS launch, but also the HAE launch service.
And there's a lot of synergy going on the commercial side, albeit a lot of that is being appropriately built and to best serve each of those launches in the markets and the challenges that they present.

Brett Monia

We're also very pleased with the progress actually because making for submission and preparing for launch in Europe. So stay tuned for that as well. Next question, please.

Operator

Salveen Richter, Goldman Sachs.

Salveen Richter

Good morning. Thanks for taking -- or good afternoon thanks for taking my question. Could you just speak to the work you're doing here on oligos with next-generation backbones and the other modalities you're looking at and when these programs might enter the clinic? Thank you.

Eric Swayze

Sure. So as Brett mentioned, earlier, the first compound that incorporates our MSPA backbone will enter the clinic for a neurology indication later this year. And the objectives there are to trying to extend the dosing interval with the enhanced stability of that backbone, which it provides, and we'll see how it performs on. We all we also have a compound in development with a partner, AstraZeneca that uses our buy cycle program to deliver our drug to the cardiac muscle.
In this case, that program is moving forward and we look to start (inaudible) this year, and that's progressing nicely. And that's an (inaudible) coupled to the buy cycle program. And we also have it in internal SI RNA program for a follow-on indication for liver targets that we anticipate getting headed towards development this year.
And then beyond that, we've been making some really nice progress in our blood-brain worth, both with our lifecycle collaboration and also the Vectura's collaboration, which we announced earlier this year or very late last year.
And we had some scientists from the team present some of that data at a recent tides meeting with early mouse data in Vectura's collaboration, it looks fantastic and we'll continue to provide some more data updates. And hopefully, if everything goes according to plan, we can get some molecules that cross the blood-brain barrier program for our new wholly-owned neurology pipeline into development or early next year.

Brett Monia

Thank Eric, and I'll just add to that. So I mean, you can expect to see in the not-too-distant future, a new programs advancing towards development pod, focused on neuromuscular diseases, skeletal muscle, specifically to further extend our leadership in neurology. And also, we're pleased with the progress we're making with Meta genomics on gene editing.
We have several programs there that are advancing very nicely preclinically, and I think next year could be a very informative year, very interesting year and in our gene editing program with respect to new information coming out as to what our strategy is and what our first molecules will be. So stay tuned for that. We're making great progress across the board in diversifying and expanding our technological capabilities.
And with that, I think we have time for one more question.

Operator

Konstant Biliouris, BMO Capital Markets.

Konstantinos Biliouris

Hello. Thanks for taking our question and congrats on the progress. Can you talk a little bit about the cardio transform enrolled population and specifically the differences between the geographies and the follow up from the originally enrolled population and the population who were enrolled after the changes you made to the statistical design and if you expect any impact from the differences between these two populations? Thank you.

Brett Monia

Thanks, Cassidy. So we, of course, haven't shared the demographics for our cardio transform study yet. We look forward to doing that in the future. We really are pleased with the enrollment in this study and as we've said, we have a nice balance in this big study, the largest study ever conducted in TTR cardiomyopathy, nice balance between monotherapy patients as well as patients on combination treatment.
We're also very pleased with very small percentages are dropping in families and study. It's going exactly as planned. We're pleased with the (inaudible) equity percentages of patients we have with New York health Class one, two and three in the study. And we everything we have seen that has come out in this space with respect to other people's patient demographics supports our decision to expand our study to take to account for a patient population that's been diagnosed much earlier in their disease. So we couldn't be more pleased with the way the study is going, including our patient demographics.
So thanks for the question, Konstant and I think we have that it's time to wrap things up. I'm really, really want to thank everybody who joined us today for your participation and your questions. We're very proud of everything we've accomplished this past quarter, first half of this year, and we plan to build on this momentum to achieve even greater successes in the second half of this year.
And we're very much looking forward to providing updates on the progress we continue to make this year as well as into next year. So thank you very much, everybody, and have a great day.

Operator

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect. Goodbye.