Q2 2023 Ionis Pharmaceuticals Inc Earnings Call
[music].
Good morning, and welcome to I honestly second quarter 2023 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.
Thank you Sanjay.
Before we begin I encourage everyone to go to the investors section of this website to view the press release and related financial tables, we will be discussing today.
The 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 have also posted slides on our website that accompany today's call.
With me on the call. This morning are Brent ammonia, our Chief Executive Officer, Richard Geary, Chief Development Officer, and Beth Hougen, our Chief Financial Officer.
Eric Swayze Executive Vice President of Research Eugene Schneider, Chief Clinical Development Officer, <unk>, Chief Global product strategy and operations Officer will also join us for the Q&A portion of the call.
I would like to draw your attention to slide three which contains our forward looking 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.
With that I'll turn the call over to Brett.
Thanks, Wade and good morning, everybody and thanks for joining us today.
We achieved a great deal in the first half of 2023 as we continued to focus on our most important strategic priorities.
We advanced our pipeline in many important ways, we made great progress in building our commercial capabilities.
We are writing the next chapter for Aon as we transform <unk> into a highly successful.
Fully integrated biopharma, focusing on delivering an abundance of new medicines to patients.
Launch preparations for our three near term commercial opportunities FY <unk> <unk> and <unk> are right on track.
<unk> is currently under regulatory review for <unk> Polyneuropathy in the U S and we're on track to submit additional filings outside the U S. Before the end of the year.
We and Astrazeneca share the goal of bringing F. One person to <unk> patients globally, who today have limited treatment options.
We're also pleased with the longer term with 85 data for <unk> from the phase III Neuro <unk> transform study that we reported last month.
These longer term data showed continued improvements from baseline out to 19 months, highlighting our sponsors and durable efficacy and contributing further towards overall attractive profile.
And in a few minutes Richard will deep dive deeper into the importance of these data.
And just last week, we reported that our landmark cardio transform study of <unk> in patients with <unk> cardiomyopathy completed full enrollment with more than 1400 patients. This is the largest study ever conducted in this patient population.
Our next major late stage milestone as the top line readout of the <unk> phase III balanced study in FCS in the second half of this year.
We expect those <unk> and FCS to be the first independent commercial launch for Aon.
And we're well prepared.
In parallel we are advancing our <unk> phase III pivotal studies in the much larger patient population severe hyper triglycerides, EMEA SAP hcg, which were also well prepared for it.
We also completed enrollment in the phase III <unk> study of <unk> earlier this year.
This important milestone keeps us on track for data in the first half of next year.
We continue to be encouraged by the efficacy data <unk> generated to date.
Recently announced two year open label extension data that showed consistent and sustained protection against HAE attacks in line with what we previously reported from our randomized phase II study and our open label extension study at one year.
I also want to highlight the continued success, we have achieved developing medicines for patients with neurological diseases spin Rozzer continues to be the global market leader for the treatment of all types of SMA and.
And just recently, it's been Rogers proven strong efficacy was reinforced further with highly encouraging new data from the ongoing response study in SMA patients, who had a suboptimal response to gene therapy.
And with the recent approval of <unk> in the U S. We now have two breakthrough commercial medicines on the market to treat two severe neuro degenerative diseases.
The fda's accelerated approval of <unk>, Saudi brings hope and a breakthrough treatment to people with <unk> ALS and their families.
And Cal Saudis approval further validates our capabilities to treat intractable neurological diseases.
Today, we have 12 medicines in clinical development for neurological diseases, including treatments for other forms of ALS Dementias neurodevelopmental diseases and much more.
Our industry, leading neurology research team is also making remarkable achievements to further advance our leadership in neural neurology therapeutics.
With a track record of driving innovation, we are focused and making great progress in advancing new cutting edge medicines into development to address severe neuro neurological diseases for patients in need.
Additionally for the second quarter in a row, a robust late stage phase III pipeline has expanded.
Yeah.
Roche recently initiated phase III development of <unk> ft, L Rx and Iga nephropathy, increasing our late stage phase III pipeline to eight drugs being developed for 10 separate indications.
A robust late stage pipeline sets us up for a steady cadence of phase III data readouts over the next few years positioning <unk> to deliver many new important transformational products to the market for years to come.
And just last week, we were pleased to announce our expanded collaboration with novartis demonstrating their confidence in ion has capabilities to create a next generation compounds targeting LP little a as a potential follow on to pellet cars utilizing our latest cutting edge technologies.
As a reminder, pellet Carson is in an ongoing phase III cardiovascular outcome study called LP Little a horizon, which is fully enrolled with more than 8000 patients.
The Horizon study is progressing well with data and a potential filing planned for 2025.
We also recently expanded our cardiovascular franchise, when we advanced our first cardiac muscle Leica.
First cardiac muscle like a drug into preclinical development. This muscle targeting drug is our first to enter development utilizing our in license bicycle technology.
This achievement further highlights the potential for us to expand our drug discovery capabilities for cardiovascular and neuromuscular diseases.
And importantly, we remain on track to accomplish our other key strategic closed across the business, including achieving our 2023 financial guidance.
And with that I'll turn the call over to Richard to discuss our recent pipeline progress in preview upcoming key events.
Next Beth will review, our second quarter and first half financial results and then I'll wrap things up before taking your questions.
Richard.
Thank you Brett.
Well as Brent just mentioned, we've made important pipeline progress in the first half of this year, bringing us even closer to our goal to deliver an abundance of new medicines to patients and to the market.
We believe that the positive data we have reported to date from the neuro <unk> transform study demonstrated <unk> potential to provide substantial benefit for patients with <unk> Polyneuropathy. The recent 85 week data further strengthened our confidence in <unk> competitive profile.
<unk> hundred 85 weeks <unk> continued to demonstrate a sustained and substantial reduction in serum GTR concentration pace compared to baseline.
As you can see from both the <unk>, plus seven and Norfolk quality of life grafts.
The changes from baseline through 85 weeks of treatment are very encouraging.
Importantly, a substantial number of patients treated with <unk> continue to demonstrate improvement in neuropathy impairment and quality of life through the 85 weeks treatment.
These data further add to the totality of data supporting <unk> differentiated profile, we plan to report the full data set at a medical conference later this year.
Couple of interesting is currently under review in the U S with additional filings outside the U S, including the EU plan for the end of this year.
We and Astrazeneca recently expanded our agreement to include Latin America.
Further underscoring our and Astrazeneca is commitment to bringing <unk> to patients around the world.
Positive efficacy and safety results, we've seen from neuro <unk> transform study also support our confidence in <unk> for <unk> cardiomyopathy, notably, we recently completed enrollment in our phase III Cardio T transform study with more than 1400 patients. This is the largest.
Study ever conducted in this indication.
We designed the study to demonstrate benefit on cardiovascular outcomes in a broad set of patients.
Now that enrollment is complete and cardio T transform we expect to report data as early in the first half of 2025.
As with most outcome trials, our timelines are based on a variety of factors, including event rates and the evolving clinical landscape.
Following up on <unk> <unk> is the next drop we expect to bring to the market and is the first we will commercialize ourselves.
We are developing all the sourcing for two indications FCS and S. H T G and while SCS is a rare indication and <unk> represents a much broader population.
Both indications are characterized by severely elevated triglycerides, which can lead to fatal pancreatitis and atherosclerosis and both are poorly managed by the current standard of care.
We remain on track to report data from the Phase III balance FCS study in the second half of this year.
Our development program to support the broader <unk> indication is also progressing well with over 3 million patients in the U S with severe hypo triglyceride EMEA and first mover advantage. We believe <unk> represents a blockbuster opportunity for ion is.
Following closely behind <unk> as our next wholly owned medicine dining Dawson.
Treat patients with hereditary angioedema a.
A recently completed enrollment in the phase III <unk> study for Dani Dolores and keeping us on track for data in the first half of next year.
In June we reported top line two year results from the Phase two open label extension study of <unk>, showing an overall sustained mean reduction in attack rates of 96% from baseline.
Two years across dosing groups, we plan to present these data at a medical conference later this year.
Based on the totality of the data generated to date.
<unk> continues to demonstrate sustained protection and preventing potentially fatal HAE attacks. As a result, we are confident in <unk> competitive profile, providing us with a meaningful commercial opportunity.
Our industry, leading neurology franchise continues to deliver groundbreaking medicines in April the FDA approved <unk> for patients with <unk>, making it the first approved treatment to <unk>.
Target genetic cause of ALS and.
In addition, we have 12 medicines in clinical development to treat neurological diseases, including two in phase III studies and eight in phase II one of our highest priorities is to expand our wholly owned franchises in neurology and cardiology.
We currently have several wholly owned medicines that are moving quickly to the clinic are world class Neurology research team is working to turn great science, great medicines that we plan to develop and commercialize ourselves.
As a result, we expect a steady cadence of new clinical study starts over the next several years from sharing our neurology franchise continues to lead in innovation and positioning us to deliver a growing number of new medicines to patients and the market for years to come.
Now I would like to briefly touch on the recent positive interim results from the response study of spin Roslyn respond as an ongoing two year phase four open label study evaluating spin rozzer and SMA infants and toddlers.
With suboptimal response to gene therapy.
The results from the interim analysis showed that most patients improved and measures of motor function with spinner asset treatment spin Roswell also continued to demonstrate a favorable safety profile in these patients.
<unk> treated with gene therapy.
These data add to the extensive body of evidence demonstrating <unk> benefit for SMA patients and that includes treating more than 14000 patients with a well established safety profile based on data in patients treated up to eight years.
In addition to respond Biogen is conducting the ascend and devote studies that together aimed to address the remaining unmet need and informed treatment decisions for the SMA community.
Our late stage pipeline expanded for the second consecutive quarter with the start of a pivotal program for <unk> Rx in patients with Iga nephropathy.
We now have eight drugs in late stage development advancing in a total of 10 separate indications GSK recently presented new data for <unk> in chronic HBV patients.
Our other medicine that started a robust phase III development program earlier this year.
The data presented at easel showed that the payer versus treatment resulted in a durable response in responders from the be clear phase <unk> study GSK plans to present, new data later this year from the B together study, which is evaluating the peer version in combination with <unk> interferon.
In totality, we have had an eventful first half with many important positive data events in clinical advancements in.
In the second half of this year, we remain on track for a number of key additional events, including USF, one person approval and regulatory filings outside the U S as well as phase III data for <unk> in FCS Our next potential medicine to launch after implantation.
We will keep you updated on our progress on these events and more throughout the rest of the year and with that I'll turn the call over to Beth.
In the second quarter, we continued to make progress on our goal to further strengthen our financial foundation in support of our strategic priority.
Financial results for the second quarter reflect our ability to generate meaningful revenue to fund investments in key growth opportunities across our business.
We earned revenues of $188 million and $319 million for the second quarter and first half of this year respectively.
Our revenues increased 40% for the quarter and 16% year to date over the same period last year driven by significant partner payments.
As anticipated our operating expenses and operating loss for the second quarter and first half of this year increased over the same period last year as we advanced our commercial readiness activities and our pipeline, especially our late stage programs.
We remain well capitalized with $2 4 billion in cash and investments at the end of June innate.
Enabling us to continue deploying our financial resources to bring transformational medicine to the market.
In the second quarter, we Opportunistically refinanced our 2024 convertible notes and we're able to accomplish all our objectives. We retained our cash to continue making key value driving investments in our pipeline.
We extended the maturity of our 2024 notes to 2028, while maintaining a low coupon.
And importantly, we retained the flexibility to repay the new notes with cash.
<unk> are a combination of the two enabling us to mitigate potential equity dilution.
We retired approximately 80% of the 2024 convertible notes and as a result, our cash balance at the end of June included approximately $115 million, we have earmarked to address the remaining 2024 notes.
And Rod this global sales were $437 million for the second quarter and $880 million year to date.
As a result, we earned $61 million and $111 million in royalty revenue for the corresponding period.
And Ron just global sales were essentially flat compared to the same periods last year.
Reflecting spin ross's resilience against emerging competition in the U S and abroad.
By working to expand existing markets, while also generating important efficacy data from spin rises robust lifecycle management program.
Biogen is making good progress on their call of returning <unk> to consistent crowd.
We earned R&D revenue of $110 million in the second quarter and $173 million year to date.
Both of which increased substantially compared to the same period last year.
Our significant R&D revenue reflects the value ion as this technology is creating as numerous partnered programs advance.
Notable payments earned in the second quarter included $40 million from Astrazeneca for Avalon person, which included development cost sharing payments and the $20 million license fee for Latin America right.
$20 million also from Astrazeneca for advancing ion 839 into a phase <unk> study for Nash.
And a $60 million milestone payment from Biogen for <unk> U S approval.
As planned and aligned with our goal to invest for revenue growth or.
Our non-GAAP operating expenses increased in the second quarter and year to date compared to last year.
As most of our ongoing phase III studies are either fully enrolled.
We're approaching full enrollment as you would expect our clinical study costs increase which resulted in higher R&D expenses.
Additionally, as we prepare to launch <unk> and to needle Larson, our SG&A expenses also increased modestly year over year.
Our results for the first half of this year keep us on track to meet our 2023 financial guidance, including our P&L and cash guidance.
Looking ahead with many partnered programs advancing we continue to have numerous opportunities to earn additional R&D revenue.
We anticipate revenue in the second half will be weighted towards the back end of the year. For example, we are eligible to earn a $50 million milestone payment for the U S approval of that one person.
And we expect to recognize additional amortization revenue from our recently expanded collaboration with Novartis.
We project operating expenses to continue to gradually increase over the course of this year.
Consistent with our guidance, which includes expenses related to our capital intensive phase III studies.
We estimate our full year R&D expenses will increase between 20% and 25% year over year.
Excluding the manager know me upfront payment from last year.
We also continue to project, our full year SG&A expenses to increase approximately $35 million year over year.
As we prepare to bring Apple interest in <unk>.
And the needle north into the market.
For example, as we move closer to launching F. One person.
Assuming an approval in late December our SG&A expenses will include our share of the cost to build out the App on trust and sales for us.
As far as additional launch readiness expenses.
Over the next few years, we are poised to launch several Madison as.
The result, we are in a period of investment we project, our operating expenses to grow modestly and importantly, keeping more programs for our style. We are positioned to deliver significant revenue growth.
Additionally, we continue to expect our substantial base of R&D revenues to contribute meaningfully to our overall revenue as our partners continue to advance numerous programs.
And with three near term commercial opportunities that have a combined multibillion dollar peak sales potential.
On a steady cadence of medicine poised to follow closely behind we are well positioned to drive substantial revenue growth and long term value for shareholders and with that I'll turn the call back over to Brad.
Thanks Beth.
Looking forward to the rest of this year, we're laser focused on advancing our key priorities with additional important regulatory and late stage pipeline events planned for the second half.
We are well on our way to achieving our goal of delivering an abundance of new medicines to patients. We now have two breakthrough medicines to treat devastating neurological diseases on the market.
And with a December <unk> date.
We could also add.
<unk> to our commercial portfolio late this year.
We're on track with our go to market activities for each of our near term commercial opportunities.
Our first planned launch of upon person with Astrazeneca in patients with <unk> Polyneuropathy is quickly approaching.
With our independent launches for <unk> and Donna diverse and following closely behind.
And with our rich late stage pipeline, we are well positioned to bring additional medicines to patients for many years to come.
We also continue to make innovative technological advancements to enhance our leadership position in RNA therapeutics positioning us to a steady cadence of new transformational medicines well into the future.
And our strong financial foundation that enables us to invest in areas with the greatest potential to drive increasing value.
Look forward to sharing our progress as we advance our priorities with that.
I'll now open it up for questions operator.
Thank you.
We will now begin the question and answer session to ask a question you May Press Star then one on your telephone keypad.
Using a speakerphone please pick up your handset before pressing the keys.
Withdraw from the question queue. Please press Star then two.
At this time, we will pause momentarily to assemble our roster.
Today's first question comes from Myles Minter with William Blair. Please go ahead.
Hi, Thanks for taking the question congrats on the quarter.
First one is on all of those Austin.
And I noted that your stance.
<unk> Harper truck was for Dania trials is that you wouldn't need to conduct an outcome study or not looking too.
Theres been some language put out there from one of the PR comp.
Companies developing in the space as well that they would be doing an outcome study has that language sort of change your viewpoint on the nature of conduct an outcome study in that population. Thanks.
Thanks miles absolutely not.
We're focused on.
Patients with severely elevated triglycerides and genetically caused Fcs for.
Severely elevated triglycerides, where theres no known.
Genetic causes of disease. These are patients that suffer from severe metabolic diseases.
Particularly acute pancreatitis.
Evolve to chronic pancreatitis diabetes, and all kinds of other morbidities. There is also a cardiovascular component to severely elevated triglycerides, but our focus is on getting patients out of harm's way.
The hubs are suffering from severely elevated triglycerides.
We've done a lot of research we are preparing the market and we're really preparing for launching our sourcing process message to June I'd like to just maybe.
So in Asia to expand.
Meiosis question.
Sure Hi, Myles yeah.
Yes.
<unk> spoken before we see a great unmet need for severely elevated triglycerides in the marketplace over 500.
This is a market, where we have over $3 5 million patients.
The standard of care is.
Just <unk>.
<unk> not sufficient to actually meet the goals that these patients are required to meet our the medical guidelines, which is to get them below 500 are as close to 500 as possible to get them out of harm's way for the risks that Brexit highlight in particular.
Pancreatitis risk.
So we have we're really looking forward to getting the drug on market for that both for the rare disease genetically defined as FCS, we expect to see the balance data by the.
By the end of the year and then looking forward to launching into that and then and ultimately in Q.
The severe hypo triglycerides in this space.
Second question is just on the wake 85 data for a contest in Polyneuropathy.
To also understand that there was some vitamin deficiency related ocular events that were discovered in that trial.
Obviously I would take you outright auction that you get fed out inefficiency and you can supplement that but my question is have you submitted that data to the FDA just for safety purposes, only I I don't think you've submitted it with the efficacy data, but we will say that safety data.
Eugene.
Yes. Thanks for your question Myles So we submitted.
All of the comprehensive safety and information, including information that was routine with the day 128.
As part of the NDA. So all of the safety data that was available at the time as well as the updates related to the de 120 update were submitted to the FDA and are under review.
And everything is on track records and Everything's on track absolutely.
Beautiful thanks for the questions.
The next question comes from Deb Jet Charter <unk> with Guggenheim Securities. Please go ahead.
Hi, James This is Robert on for Doug Thanks for taking our question.
How does <unk> plan to compete against SA RNA options in the <unk> market.
<unk> presents potential a blood person to be first approval. So let me say difficult global markets. Thank you.
Thanks, Robert <unk>.
Yes, sure Robert we're very excited with the data that we're seeing the week 85 data was very encouraging.
We saw and duration of effect.
Sustained GTR suppression for GTR, and then obviously halting disease progression and seeing improved bank in a substantial number of patients in both <unk> seven and Norfolk quality of life. We've got a really great efficacy data package, we have from.
From all of the research we've done the more preferred administration profile, which is self administration at home allows patients to be empowered and taking control of their disease and taking the medication wherever they are with them and not relying on them going into the Hcp's office.
The efficacy combined with this self administration profile gives us a really strong way to enter the marketplace.
As I've said before.
This is a market, where we still have 40000 patients and less than 20% of those patients had been either identified diagnosed and treated.
Sure.
We're a polyneuropathy, including mixed phenotype, so our ability to get to.
These patients are identify them and get to the offices outside of the centers of excellence, where they're presenting is going to be really important and those are some of the strategies, we're working on with Astrazeneca.
And then as to your question on whether we will be first in many global markets. Yes that is that is the goal we are planning to file an.
And different markets outside of the U S. In the second half of the year, particularly in Europe .
But as you know we're also looking at expanding into markets, such as Eastern Europe , Russia, China, Japan and again. These are places where astrazeneca has global scale will bring the ability to really penetrate and get these patients are in.
Care when there's need it.
And as you know Robert.
We're very pleased that Astrazeneca also.
Enthusiastically.
Licensed of Latam Latin America rights to for <unk>.
Of course for all indications neuropathy, as well as cardiomyopathy and demonstrates there.
Their enthusiasm for <unk>, and our partnership and their enthusiasm for the data has been generated to date.
Thanks, Tim.
The next question comes from cost Us <unk> <unk> with BMO. Please go ahead.
Thanks for taking our question.
One on the pillar <unk> follow on molecules that you recently announced and discussed the potential technologies that you could elaborate there to improve the efficacy of the dosing frequency of the first generation molecule and approximately how many years do you expect these follow on molecule to enter.
The cleaning after fill up to enter the market. So the offset from Watson. Thank you.
Yeah.
Sure. Thanks.
Very excited.
Novartis.
Came to us with a.
Proposal two.
On with them.
Follow on strategy follow on program for pellet cars, let me just say right from the outset that power Carson Pellekar. Some phase III program is going well very well on track.
And it's on track for data readout and potential filing in 2025.
Okay.
That novartis came to us really demonstrates their enthusiasm their added enthusiasm.
For this.
The mineral acres.
Our opportunity for ultimately cardiovascular disease.
To be assuming.
Crude oil for pellet cars from the first to the market.
And to have a substantial global reach and the follow on program is to extend that reach the purpose is to reach more and more patients with the follow on program.
Novartis recognizes our expanded and vast capabilities in RNA targeted therapeutics, and we're bringing our full arsenal to the table and they appreciate that and that's why the pause.
With us on.
That includes all the great work that our research organization has begun doing over the last few years and expanding our medicinal chemistry capabilities, including MSP a backbone that we've talked a lot about in the past and other chemistries as well as our rapidly emerging capabilities in the RNA.
Technology.
And combinations of both we can utilize chemistries that will utilize <unk> technology as well as for RNA platforms.
It's tough to beat the efficacy the pellet Carson has demonstrated in phase two cost us.
I mean with 90, 899% of patients.
With with CBD due to high LP Little a we were able to get their LP little a levels down below that threshold associate with CBD.
So really we want to we want to maintain that efficacy. We wanted we wanted to reproduce that efficacy and a potential pharma molecule, but what we're really focused on is less frequent dosing.
We're very confident in our ability to deliver a molecule with semiannual dosing maybe annual dosing.
Utilizing a mixture of our of our technology capabilities and that is that is the focus with novartis and we're gonna be working hand in hand with them to bring the best molecules forward to follow on.
As a follow on to pellet Carson.
The next one.
Oh.
Please go ahead sorry.
Hello.
Sorry, no I was going to ask approximately how many years behind as a follow on to our liquidity.
Compare that to like Hudson.
Yeah, we haven't we haven't stated.
First by publicly cost base from what the timelines are and obviously the molecule that we're selling research phase so it'd be a little risky to actually speculate on that right now.
Very helpful. Thank you.
Okay.
The next question comes from Michael <unk> with Morgan Stanley . Please go ahead.
Hey, guys. Thanks for taking the question.
Just on Epsilon person in cardiomyopathy.
Maybe you can comment on the recent bridge data and sort of how that impacts your thinking in terms of the cardio.
<unk> transformed study.
And then maybe second secondly to that is there a potential for you to maybe stop the study earlier or is the thinking still to go through sort of.
The full results there thanks.
Right.
So.
Bridge Biodata.
Good for patients to have another.
A potential option for <unk> cardiomyopathy.
To state the obvious.
Get a lot more data we need to see more data looking forward to seeing more detailed data.
And I think they are planning to present later this year.
The demographics of the studies supports our trial design and further reinforces our trial design gives us even greater confidence in our in our expanded trial design in which were going down and which we're going to have we have now as we have completed enrollment very good balance between the families.
Patients, who have one personal copper firmness as growers naive patients.
So it supports that.
CEVA mortality.
Overall mortality is very important in this population and maybe I'll ask Vanessa to just really expand.
<unk>.
The importance of this from a physician standpoint from a payer perspective.
So as you know.
Epsilon Trust and Michael that.
We loved the breath of our trial, we believe we're going to it's a landmark trial.
Going to generate a.
Significant amount of data to really go in and arm the physicians with the data that they need to actually treat these patients. This means anything from anyhow class one two and three from mild to severe hereditary and wild type naive to silence their therapy naive to <unk>.
Cardiomyopathy therapies in <unk> as well as on top of standard of care to feminists as well, we really love our endpoints.
<unk> done a fair amount of work in recent times to really understand the.
The difference.
In terms of how physicians view, all cause mortality versus cardiovascular death, and that is actually a more meaningful cardiovascular endpoint along with the richness of our cardiovascular hospitalizations and then some of our secondary endpoints, obviously in six minute walk in and other measures that are going to be at play but.
The endpoints just actually really meaningful so.
All in all we are really excited about our dataset our trial design and looking forward to seeing the output of that in the coming up coming.
Coming time.
And Michael.
There's no plans to change our.
No changes to our plans for when the study will complete.
Based on any new emerging data that has come out recently, we love our trial design.
There are several factors that will impact when we read the study out the first of course was to complete enrollment.
We've now achieved that and we've achieved it very successfully we have the demographics and the study that we intended to.
Have a.
<unk> actually.
I actually have the greatest dataset when the study reads out.
We'll also be looking at changing.
Petitor landscape, new data as it emerges that could potentially affect the time, we read the study out we don't think that final data is going to impact that but there may be other data that comes out and thirdly.
Our blended event rates will be very important for us to continue to monitor.
We decide when and especially free but there is no change in the currently there is no change in the timing of when that study.
Our cardio transform studies due to read out.
Let me just address one other question, which was on the payer reimbursement that I missed so just to make sure that we've done a fair amount of testing with payers on the trial design and again, if we show the cardiovascular risk reduction on top of <unk>.
There is clinical meaningfulness in that from physicians and they are not going to be kind of standing in the way in terms of reimbursing our combo product here.
The data will bear out and they are very favorable and making sure. These patients who are highly at risk. It's a terminal disease are getting the best medication and care possible. So.
We're really pleased to see them thinking about the disease and the patients display and thinking about the landscape of reimbursement as either mono or combo in the space.
Got it thank you.
The next question comes from Liana <unk> with Wells Fargo. Please go ahead.
Hi, Thanks for taking our question.
I was wondering if you could share your thoughts.
Some recent development in <unk> syndrome field, where Roche decided not to move their ASR program into the next stage of clinical development and I'm wondering if you could share any update from your end demand syndrome clinical.
Clinical study.
That is.
Ongoing.
And any.
Thoughts around.
The program or the.
Product candidates efficacy and safety profile and also if you could also talk about your <unk> program.
And it's ongoing study that would be great I think the data are expected at around the same time as the anchor Mexico program. Thanks.
Sure happy to Ian and thanks for the question so the Angelman program.
My honest Biogen England's program is going very well were operationalized the phase one two study and we're continuing to enroll patients in this study.
We are in with Biogen are planning to have data around mid year next year from the Angelman.
Program.
And as I said, it's going very well so far.
We haven't disclosed are we really don't have any insights into the reasoning behind why Roche ended their study obviously you have said.
That it wasn't a safety issue. They said they didn't meet their minimum target product profile or the minimum criteria I assume on efficacy, we really don't have an shouldnt.
We're not disclosing anything we may think honestly, we're really focused on our program.
So if you expect a readout from that study next year, we may be able to provide an update on the status of the program late this year or there's a we have a standing invitation to an angelman is meaningful fast and which.
We always have a podium slots and I'm sure we'll be present this year to boot.
We're not necessarily expecting data new data at the meeting, but we haven't decided what we're going to present at that meeting.
As far as a Texan to this of course is another one of our AOS drugs. This drug is particularly exciting because it's targeting.
Sporadic ALS, so no known genetic cause of ALS.
Studies enrolling this.
Study in which we're examining four dose cohorts with the highest dose cohort having expanded to add more patients to have the most robust data set to inform a potential phase III study. This study is successful.
That as you mentioned is also due to read out around the same time next year around mid year next year.
And all indications are that it seems that it's going well.
Great. Thanks for all the answers.
The next question comes from David Leibowitz with Citi. Please go ahead.
Thank you very much for taking my question given the H eight data is coming up earlier next year could you and assuming the phase II data is replicated could you tell us.
What your efforts will look like for launching the therapy and trying to convince physicians to move to a new modality.
Sure David Nathan Hey, David Yeah, No we're very excited about.
Preparations for a <unk> launch and waiting for the phase III data next year.
We are thinking about the market in a variety of ways. As you know this is going to be pretty much a switch market. So we do actually have a switch study that's going alongside our phase III, which will be very informative and give confidence for physicians to switch.
Patients.
At the confidence piece, it's going to come from the ability to make sure. They are no breakthrough attacks in the process of the switch and given our rapid onset.
I believe we will be able to demonstrate that on the patient side. I think you can see the switching behavior already in the marketplace with Orlando.
And fighting more switches from text IRA which is the standard of care. So we see that patients are willing to try new treatments and they want they want to zero attack rates and they want more convenience and we offer both with our profile as well.
So.
The teams are very active in understanding kind of what will drive some of the switching behavior and their go to market strategies alongside of that.
Thank you for that and one additional question.
Moving towards potential Epsilon person launch do.
Do you have any thoughts on how.
Market growth has shifted since the sub Q was watched by al in Ireland.
And how that might.
Apply to upon tariffs and how you're thinking about the launch going forward.
Yeah, I'm, taking a look at how and who trust uptake is going on in the marketplace I mean, they've got a good start.
And it's just important to note that they are working through a lot of on Patrick's switches right now right. So we're really trying to understand how much market growth. There is as I said this continues to be an underpenetrated marketplace lots of patients that are still not identified diagnosed.
For treated.
And I think you know Alan.
Alan Island gained their job of getting most of their patients onto their next generation silencer.
And we have a lot of work to get new patients to just filings for therapy overall in this marketplace. So we expect it to grow rapidly. This is when you have a couple of players in the marketplace. It's always a good thing for patients.
Looking forward to getting in in January and starting that's starting to work.
<unk> as I said earlier, we have a very exciting product profile of efficacy as well as the self administration profile, which we believe will do.
Do very well in the market.
Thank you very much.
Thank you.
The next question comes from Allison <unk> with Piper Sandler. Please go ahead.
Hi, good morning, and thank you for taking the question.
Just one for me on the <unk>.
Phase two golden trial in.
Just curious is there any update on your view of the geographic atrophy space and potential opportunity for a therapy targeting complement factor B just given some of the recent safety and regulatory updates in the GI space in recent weeks could you just frame what youre looking for in the phase II readout next year.
Further investment in that space. Thanks.
Thanks Allison.
Yes, we are.
And our partner Roche are very enthusiastic about our <unk>.
<unk> study our factor B L Rx.
Geographic atrophy study Goldman.
We're pleased that.
There is a benchmark to get drugs approved for <unk>. It sets. This helps set a path forward for all drugs that are being developed for <unk>, including ours.
We like our drug we like our profile so far the Golden study is.
<unk>.
Quite a large study.
300 patients to dose dose cohorts dosing groups.
And which patients are going to be treated for about 15 months. So it's a good start in and what we're looking for is the primary change changes in geographic atrophy area.
So you know, it's an efficacy study in proof of concept.
And that study is due to read out next year.
We like this or we like the target factor B <unk>.
Alternative pathway, we think is the right target for GE, we think systemic approaches to the complement pathway, particularly factor D is the right approach.
For for treating G E.
And we think that the overall safety profile and Tolerability profile that we're going to have with factor B L. Rx is going to be a very significant advantage.
Versus IDT drugs, which are administered.
And directly to the eye and have side effects as a consequence of that we expect that to be Rx fabric excellent safety profile much like the rest of our like a platform that had Stefan first intolerant carcinoma in sourcing Don in the worst.
So.
That's that is in phase III.
We're seeking to achieve proof of concept for next year.
If the data strong data and.
Support so I should say.
Roche is preparing to go to phase III.
And they're equally enthusiastic for the program as we are.
The next question comes from Paul Matteis with Stifel. Please go ahead.
Thanks, so much for taking my questions.
And congrats on all the progress I wanted to ask about <unk>.
In light of how much the cardio metabolic space has really changed since you initiated the pivotal program just specifically looking back at the phase two baseline characteristics I think most patients in the study.
Hi type two diabetes.
Most patients had comorbid hypertension.
BMI was overweight on average I guess, how do you think about the impact of this recent wake Obi data and more broadly the take off of these weight loss drugs on the market for <unk> and I guess what percent of patients with <unk> above 500 would you say demographically.
Wouldn't actually qualify for one of those drugs on label. Thanks, So much.
And you want to yeah I ball.
<unk> been on a lot of good data for a further slip one recently as well. So a couple of important things to note first of all they're not going to be ended indicated rate for triglyceride lowering.
And if you looked at some of their key G. Just their TG lowering Ada it's very much in line with what current standard of care. It. So if they're not getting to the really high level of TG lowering that apoc III target can actually deliver here. So that's kind of the first thing.
If physicians do use it off label.
Very important reminder, and I think most of the endocrinologists notice that the glick plans or have a warning in their label for not being used in patients with.
With risk or a history of acute pancreatitis.
And as you know in the 500, plus severely elevated triglycerides, where <unk> is being studied we have many many patients who at risk for AP. So we do think both the both the magnitude of triglyceride reduction along with the with the risk for these patients for over five.
<unk> hundred four <unk>, we do not expect that to be.
Direct or indirect competitor.
Okay. Thanks for the thoughtful.
The next question comes from Yaron Werber with Cowen. Please go ahead.
Great. Thanks for taking my question I, just want to otherwise.
The response by the interim results are definitely encouraging can you give us a sense of are these potentially label, enabling like how do you. How do you think about it just given your broad label vehicle need sort of a label, enabling or is this just for standard of care sort of change.
And then secondly, just in terms of some of the B.
The attacks in two program and the attack and three programs I know you've touched a little bit on the <unk>. We also have a fourth program.
For you, let's just maybe give us a little bit of a sense. What's the next data timing and would you expect from that data.
The first AOS as a pivotal in 2025.
Thank you.
Thanks, Sharon so.
It's our understanding that ascend or respond.
Responding.
When youre talking about very encouraging data of patients that haven't done.
That well on gene therapy moved onto spin rods.
And really showing really good strong signs are doing very well.
Proving muscle strength.
Neuromuscular function.
Not surprisingly there's been a lot of anecdotal data out there over the years. This is the case, but it's very helpful to Biogen actually their study demonstrates that the studies ongoing.
Our understanding that the studies in patients for.
<unk> sub optimally.
Gene therapy or on.
Diversity.
That remove us from RASM would be more for publication purposes, and those sorts of things and which are certainly in line with.
Promotion.
It's the devote study.
That has the potential to actually expand label.
The devote study is a randomized controlled phase three study looking at higher doses.
And rod and demonstrate even greater efficacy.
SMA patients of all kinds. So that's my understanding and I'm, sorry, I'm getting head nods from my clinical folks here soon.
The next question comes from Luca <unk> RBC cap.
Hey, Scott jump.
<unk>.
Eric just reminded me I Didnt answer the attacks in two questions. So the attraction to.
Is enrolling four dose cohorts the proptosis, an expanded cohort to have more patients in the Thursday. It has the potential to be the dose that goes to the phase III that data is due to read out midyear next year, a tax and two for non genetic AOS I'm sorry.
The next question comes from Luca <unk> with RBC capital markets. Please go ahead.
Great.
Thank you so much for taking my question. So on the progress maybe all else Cumulation of maybe following up on a prior question. A breath you may have already in two weeks, but I'm wondering insurance.
Yes.
In licensed a next generation molecule informed in any sort of formal shaped by the blinded event training. They are seeing in a cardiovascular outcome trial Carsten.
Is this just truly lifecycle management.
So maybe Eugene if I may.
TCR cardiomyopathy wondering if you could comment on what's statistical methodology are you using for the phase III for <unk> myopathy or using just <unk> sure.
So much of which bio and Pfizer or are using the Anderson Gil method, which is similar to <unk> and maybe why you choose one versus the other and then lastly, maybe at Agg what was your reaction to our island Roche deal and how are you.
Thinking about BD for your molecule. Thank you.
Sure Luca.
Before turning it over to Eugene I'll take two of those and then you can talk about the statistical plan for them.
Our new transform so LP little ways entirely lifecycle management propeller Carson Phase III study is going very well on track for data in 2025 with a potential filing in 2025 has nothing to do with any particular data from this study except to say that the study is going very well so that.
Rents, even greater confidence by Novartis too to pursue lifecycle management.
We're focused Luke on our own programs are really don't have a reaction to any competitors in the agency space or anywhere else partnering strategies.
We are our plans haven't changed.
We are planning to share.
New agency data in the second half of this year at a medical meeting.
We've said all along that we think.
A drug like this.
For indications like hypertension, and heart failure are best suited.
With a partner.
To reach as many patients globally around them.
Around the world.
And we.
We havent provided any details on the timing when we're going to.
Part of the program, nor with whom of course, but stay tuned for that down the road.
Could you talk a little bit about the.
Lucas question about on our stats plan from.
Cardio transform.
Sure. So if I understood. Your question it was related to the analysis of the primary endpoint is that right.
That's correct yes.
That's correct.
Yes, so as we said the methodologies that were utilizing or planning to utilize for that analysis.
Driving through.
Using Congress and beyond method to look at it.
Both CV mortality and CV events required events.
Or was that.
So again there is nothing.
Nothing fancy about this model has been tried and done multiple outcome studies since early classic way of looking at these events.
Got it thanks, so much.
Okay.
The next question is from Yale Jen with Laidlaw and company. Please go ahead.
<unk>.
Good.
Good afternoon, and thanks for taking the question.
The first question is for Apple in person.
If you get approved later towards the end of this year in the apartment.
Holy Neuropathy.
You anticipate the drug will also be useful for treating the mixed pipe patients than that.
Another follow up.
Absolutely we do provided they have detectable polyneuropathy Yale yes, this drug would be suitable for pure pn patients as well as mixed phenotype.
Patients.
Okay.
And Mike.
No question is the formula.
Dawson.
In terms of the.
T T enrollment can you provide any color in terms of the status and do you anticipate completing enrollment later this year.
Okay.
Okay.
I missed the specific.
How are we doing on <unk> enrollment.
And that's going very very well.
And.
If either very late this year or very early next year, it's kind of the guidance we've been giving.
Okay, great. Thanks, a lot I appreciate it.
You see how many time for one more question.
The last question today comes from Joseph Stringer with Needham <unk> Company. Please go ahead.
Hi, Thanks for taking my question just a quick one on <unk> phase III readout. Later this year can you just frame expectations on what type of outcome it would need to see to be successful commercially.
What type of key metrics should we be looking at beyond the.
Primary endpoint from wood.
That would be important from a physician or a O perspective. Thanks.
You want to take that I mean, obviously the primary endpoint is pregnancy rate lowering for century, what's right lowering compared to placebo and thats important and we expect.
What will really drive this market substantial TG lowering in this patient population.
Eugene.
And maybe you can talk about the commercial so what additional endpoints, we're looking to see.
Sure.
Happy to.
So you're going to also look at responder a variety of responder analysis, so looking at it.
Proportions of patients, but below a particular clinical.
Clinically meaningful threshold thresholds like.
<unk> for instance.
The classic one or 500, so again achieving those.
Those reductions that are thought to be meaningful in terms of the risk for having acute pancreatitis events.
Something that we're in.
Prescribe future prescribers will be very keen to see we're also looking at quality of life measures, but a gamble will indicate whether these patients are actually feeling better or people could function better.
<unk> again are included in this call.
Lithium we've yes, no that's great I think we've done obviously some good.
Market understanding on this as well is this just a reminder, this is a.
Rare disease population for FCS They really have no chose at their disposal leases this is where the.
The first line treatment is restricted diet and it's.
It's just not.
I mean, they just can't.
And continue on that level of restrictive diet that they're on for a while so just a huge unmet need I really do think that this is going to be let's get the product that's efficacious.
But also really safe and easy to use and I think getting some of the safety Tolerability and here. It is going to be really important versus first generation.
It's going to be a real and got a lot of lot of lipid dollar Jason a lot of patients are waiting.
Thanks, Joe.
Sure.
Thank you thanks, everybody for joining us today for today's call.
We're well on our way we are planning to continue on.
Strong momentum second half of this year are delivering across all over all aspect key aspects of our business commercial pipeline technology and so on.
Also I want to highlight that we're looking forward to providing a comprehensive update on.
All the great progress, we're making around this at our Investor day on October 4th.
We really hope that.
Many of you can join us in person.
Our meeting.
See you there until then thanks and have a great day everybody.
The conference has now concluded. Thank you for your participation you may now disconnect your line.