Q3 2023 Ionis Pharmaceuticals Inc Earnings Call
Two filings for additional detail with that I'll turn the call over to Brett.
Thanks, Wade and good morning, everyone and thanks for joining us on today's call.
He has taken the helm and I honest nearly four years ago, we have executed on our strategy to deliver next level value.
And we've done so with a clear vision and laser focus on our strategic objectives to bring our medicines directly to patients.
Build our wholly owned pipeline and to extend our leadership in Oregon nucleotide therapeutics.
Our successes this year, which are a direct result of our efforts in these key areas move us closer to achieving our ultimate goal to deliver a steady cadence of new transformational medicines to patients and to generate next level of value for all I own stakeholders.
We are on the cusp of delivering our near term commercial medicines to patients starting with the first potential approval of <unk>. This year.
We and our co commercialization partner Astrazeneca are prepared to launch up on tariffs and following U S approvals for.
We're also executing on our global regulatory strategy with potential approvals in the EU and Canada next year.
Additional filings are also planned positioning us for a steady cadence of approvals around the world.
We recently achieved another of our key objectives for upon tourists and with the publication of a comprehensive review of the phase III Neuro <unk> transform study results in Jamba.
Publishing our results in a highly respected journal like charmer reflects the importance of our phase three neuro <unk> transform study for the treatment of ATT, our poly neuropathy and showcases the strength and quality of our results.
Based on its strong overall profile, including highly positive phase III data together with the freedom of a simple at home monthly self administration profile. We believe <unk> is well positioned to become the therapy of choice for ATT, our patients who remain underserved by current therapies.
Following closely behind <unk>, and Donny Dolores and our wholly owned near term commercial opportunities.
We were very pleased with the positive top line data, we reported last month from our <unk> phase III balanced study in patients with Fcs.
<unk> showed significant triglyceride reductions, which was the study's primary efficacy endpoint, along with a favorable safety and Tolerability profile.
But most importantly for patients Ozarks and demonstrated substantial reductions in acute pancreatitis events.
Making <unk> the first lipid lowering therapy to achieve this result in the clinical setting.
With these highly positive results we are on track to file for marketing approval in the U S and EU early next year positioning <unk> for its first potential approval as early as the end of next year, assuming priority review in the U S.
We also continue to be encouraged by the performance of Donnie doors, our medicine for the prophylactic treatment of HAE.
We recently reported two year open label extension data, which demonstrated favorable safety and tolerability, along with durable and sustained protection against HAE attacks consistent with the previously reported one year OLED results and our phase II results.
We're getting closer and are looking forward to a phase III readout with data expected in the first half of next year for Donegal worsen.
We also made significant progress recently and further strengthening our wholly owned neurology pipeline by advancing <unk>, our treatment for Alexander disease into Phase III development.
Advancing zildjian nurse and further expanded our rich phase III pipeline to a total of nine drugs in development for 11 separate indications and importantly, we remain on track to accomplish our other key strategic goals across the business, including achieving our 2023 financial guidance.
With that I'll turn the call over to in Asia to discuss our expectations for the <unk> launch and to briefly review the status of our go to market activities for <unk> and Donegal worsen.
After our Naser, Richard Richard who will discuss our recent pipeline progress.
And after that Beth will review, our third quarter financial results and then I'll wrap things up before taking your questions and with that over to Nathan.
Thank you Brad.
As Brian outlined and as you will hear from Richard in more detail in a moment Ione pipeline holds tremendous promise.
And today, we are ready to begin delivering our medicines to patients.
With an estimated 40000 patients worldwide and fewer than 20% of patients on an approved treatment hereditary <unk> polyneuropathy remains significantly under diagnosed and are largely underserved disease.
In large part the low rate of diagnosis is driven by the systemic nature and heterogeneous presentation at <unk>.
Cloud peripheral neuropathy may be the most important symptom and many patients others may present, with cardiomyopathy, and still others with symptoms Gi disease, leading to muscle wasting.
Leveraging <unk> deep knowledge of H, TR and Astrazeneca significant commercial reach we are uniquely positioned to recognize <unk> in time diagnose patients and get them on treatment early in their disease progress.
And in doing so we are well positioned to grow this largely untapped market.
Our field team has built and deployed and already executing on our strategy to drive a contrast in growth to a disease education and brand awareness.
Additionally, we recently launched our unbranded disease education campaign called C. The patterns.
Aimed at accelerating diagnosis by helping HCP spot potential <unk> in patients with seemingly disparate.
We also recently launched our health care professional website aimed at driving disease and brand awareness among atti traders.
Additionally, we are investing in which data sources with the potential to identify agent TRP and patient and support the field team's effectiveness to improve the diagnosis.
And treatment.
With its potential approval in about six weeks, we and Astrazeneca are ready to deliver upon trust into patients with <unk> Polyneuropathy and as our launch gets underway a key measure of our success will be in achieving our goal of upon trusting becoming the preferred choice for newly diagnosed patients with <unk>.
Dr Polyneuropathy.
We expect <unk> to be the first medicine relaunch independently we are developing <unk> in two indications the rare Fcs indication and the broader S. H T G indication with potential first mover advantage in both settings.
Additionally, the fast track designation, we have for FCS gives us the potential for an expedited review and together with the extremely positive results. We reported from the phase III study in patients with Fcs.
And hand, we are moving forward with our launch preparations with even greater pace.
With the capabilities established for the person launch we are in strong position to build upon this foundation and enable stronger launch readiness for Fcs.
And as we prepare for the follow on S. T. S. Http indication we plan to further scale these capabilities to realize the full potential of the product pending phase III trial results and FDA approval.
We expect our next independent wants to be withdrawn until or send for the prophylactic treatment of <unk>.
This is an attractive market for us because it involves a fairly concentrated set of prescribers, allowing us to deliver accounted to listen to <unk> patients, we can efficiently sized field team.
With the compelling phase II and early data we have seen to date together with a once monthly self administration profile. We believe <unk> is positioned to be an important new prophylactic treatment for <unk> patients once approved.
I am pleased to say that we are right, where we should be preparing for our first independent launches of <unk> and Donna to worsen.
Our commercial infrastructure is in place and we are ready to begin delivering our medicines to people in need as they come to the market.
This is a very exciting time for Anna.
I am proud to be part of it and I look forward to keeping you up to date as our next important steps unfolds.
Now over to Patrick.
Thank you Nathan.
We could not be more pleased with the performance of our pipeline Epsilon person has continued to perform exceptionally well demonstrating durable and sustained efficacy and safety through 85 weeks of treatment in patients with <unk> Polyneuropathy. Just this morning, we presented new data at the European <unk> amyloidosis.
This meeting.
Are there any enforces these results demonstrating improvements in measures of neuropathy impairment and quality of life.
That we're seeing in a substantial number of patients at 35% and 66 weeks and were sustained through the 85 week analysis.
And benefit across secondary endpoints at 85 weeks showed improve neuropathy specific and physical health related patient quality of life stabilized or improved ambulatory status and stabilized nutritional status with epsilon tourist and treatment.
And last month at <unk>, we showed data demonstrating improvement in cardiac function and structure in a predefined cardiac subpopulation population of polyneuropathy patients from.
From the neuro <unk> transform study.
The positive results from neuro <unk> transform also support our confidence in the potential for Epsilon person to benefit patients in the larger <unk>.
<unk> cardiomyopathy indication.
With Carty ups transform fully enrolled we remain on track for data as early as the first half of 2025.
As a reminder, with over 1500 patients cardio T. Transform is the largest study in this patient population to date designed to generate the data physicians and payers want and need to understand the value upon person offers for patients and to enable the best possible treatment decisions for.
Patients.
Following up on tariffs and all the sourcing is the next drug we expect to bring to the market and is the first we expect to commercialize independently.
And the balance study the 80 milligram dose of <unk> demonstrated statistically significant reductions in triglycerides robust target engagement.
A favorable safety and Tolerability profile consistent with the profile seen with our other like medicines.
In addition, <unk> demonstrated unprecedented substantial and clinically meaningful reductions in acute pancreatitis attacks.
This is remarkable because it's the first time, a lipid lowering therapy has ever achieved this result in a clinical trial setting.
Based on the positive data, we reported from the Phase III balanced study, we believe the debt <unk>.
<unk> is poised to become the standard of care for patients with FCS. Our next step will be to file for marketing approval in the U S and EU in the first half of next year positioning <unk> for its first potential approval in late 2024, assuming priority review in the U S.
In addition to our clinical development program for FCS. We also have an ongoing program for patients with severe hypo triglyceride EMEA.
Or S. H T G phase III studies in <unk> patients are ongoing and we expect those studies to readout in late 2024 or early 2025, depending on enrollment.
Following closely behind <unk> as our next totally owned medicine on at Dolores and to treat patients with hereditary angioedema.
Several treatments are already on the market Hey.
Continues to represent a significant unmet need.
For example in a study recently conducted by their hereditary Angioedema Association of over 500 patients with H E. Only 13% of these patients reported having good control of their disease with more than 85% reporting two or more attacks per year.
Data reported from the ongoing phase two open label extension study of Ghana divorce and show sustained and durable reductions in HAE attacks and favorable safety and Tolerability over two years and support <unk> potential to address the unmet need we look forward to presenting a comprehensive look at.
The two year OLED data next week at the AC AI conference.
With enrollment complete into phase III.
Places Hae's study, we remain on track for data in the first half of next year.
And from a robust late stage pipeline, we look forward to updates from a peer version and I honest FBL Rx.
Last week at AAN, <unk> GSK plans to present, new data from our phase <unk> study of the pier versus and in combination with regulated industry.
And this weekend at kidney week, we plan to present, new interim results from our ongoing phase II study of our Roche partnered medicine, I honest FBL Rx in patients with Iga nephropathy.
We also made significant advances with our industry, leading neurology franchise this year.
We have to improve breakthrough medicines for neurological disease on the market spin Rosa and Cal Saudi and we have another 12 in clinical development and more than 10, new programs in preclinical development of our lead optimization.
Among our partnered neurology programs, we recently completed enrollment in the phase one two study of Ireland 582 in patients with Angelman syndrome.
Putting us on track for data around the middle of next year and we were encouraged by the positive data our partner Biogen recently reported from the phase one be in long term extension studies have Iona snap T. Rx in patients with early Alzheimer's disease.
Data presented at the clinical trials on Alzheimer's disease Conference show numerical improvements on multiple cognitive and functional scales and continued favorable safety and tolerability in this small early stage study.
And data published in Jama Neurology showed a rapid substantial and sustained reduction in Pal and phosphorylated Tau in CSF as well as reduce Tau pathology on pet imaging with up to 100 weeks of ion us and map T Rx treatments.
And we're particularly excited with the progress we're making in building and advancing our wholly owned neurology pipeline, which represents one of our highest priorities as Brett mentioned.
We advanced <unk> into phase III development in patients with Alexander disease, a rare debilitating pediatric Luca dystrophy with no approved treatment.
We're on track to advance ions 707 into phase one two first in human study in patients with prion disease before the end of the year and following eye on 707, we expect to advance three more wholly owned neurological disease medicines into the clinic next year.
This has been an eventful year, so far and we're looking forward to several additional key events in the coming months, including the U S. Upon <unk> approval launch and additional regulatory filings and approvals outside the U S. All of sorts in regulatory filings in FCS and <unk> phase III data.
We will keep you updated on our progress on these events and more throughout the coming year.
And with that over to Beth.
Richard.
Our year to date financial results keep us on track to achieve our 2023 financial guidance, while we continue to execute on our strategy to unlock next level value.
Revenue continued to be substantial and sustained with revenues of $144 million and $463 million in the three and nine months ended September 32023.
<unk>, a 10% decrease and a 6% increase respectively.
<unk> to the same periods last year and driven by the timing of certain partner payments.
As anticipated our operating expenses and operating loss for the third quarter and year to date.
Increased over the same period last year as we advanced our commercial readiness activities and our pipeline, especially our late stage program.
We remain well capitalized with $2 $2 billion in cash and investments at the end of September enabling us to continue investing in our strategic goals.
Our commercial revenue from spin Roset royalties was $67 million and $179 million in the third quarter and year to date, respectively.
Reflecting its been rises resilience against emerging competition in the U S and abroad spin rises global sales in the third quarter demonstrated a low single digit increase compared to last quarter and compared to the same quarter last year.
As a result, our revenue from spin RASM royalties increased by 9% compared to last quarter and 8% compared to the same quarter last year.
We earned R&D revenue of $60 million in the third quarter and $233 million year to date.
Significant R&D revenue, we continued to generate.
Next the values that I own as this technology is creating as numerous partnered programs advance.
In line with our goal to invest for revenue growth.
Our non-GAAP operating expenses increased in the third quarter and year to date compared to last year.
With most of our ongoing phase III studies fully enrolled our study costs increased as expected, which resulted in higher R&D expenses.
And as we prepare to launch upon person always are thin and they need to learn our SG&A expenses also increased modestly year over year.
Our year to date results keep us on track to meet our 2023 financial guidance.
We continue to project revenues of more than $575 million.
We expect our fourth quarter R&D revenue to be driven by the potential $50 million milestone payment from Astrazeneca for the U S approval of alpine person.
R&D revenue from continued development about Athlon person.
And additional revenue from Biogen and from our recently expanded collaboration with Novartis and Roche.
We project, our 2023 non-GAAP operating expenses to come in at the higher end of our guidance.
It is between $970 million and $995 million.
And looking ahead, we expect to generate a substantial and sustained base of R&D revenue from multiple sources in 2024 as our partnered programs advance and.
And we expect that blood test and we will continue to be an important source of revenue in 2024.
We have the potential to earn a milestone payment for an additional app on tourist and approval outside the U S.
We also expect to begin generating modest royalty revenue next year with growth expected as the launch ramps up.
We project our expenses to grow modestly next year with our R&D expenses approaching steady state as our late stage programs are fully enrolled.
And our SG&A expenses to ramp up in line with the planned launches of Athlon person Elisa thin and they need a lot of time.
We have a strong financial foundation substantial recurring R&D revenues was substantial and sustainable royalty revenue that can continue to grow and.
And we expect to add new product revenue from our advancing and expanding wholly owned pipeline.
Together with our prolific technology. We believe we are on a path to successfully bring our medicines to patients and to unlock next level value.
That I will turn the call back over to Brad.
Thanks Beth.
We are very proud of the remarkable progress we've made this year.
We believe that the successes we've achieved so far this year position us to drive substantial value for patients.
Our shareholders and all stakeholders.
Strategically we have arrived where we are today have been focused on a clear vision.
And by being focused on all our supporting strategic objectives necessary to achieve our vision.
We have now established all of the functional capabilities, we need to deliver a steady cadence of new and potentially transformational medicines to the market.
We are advancing and growing our wholly owned pipeline and have established <unk> as a leader in cardiovascular and neurology drug development we.
We continue to extend our leadership position in Oregon nucleotide therapeutics by expanding and diversifying our technology further optimizing our capabilities for existing therapeutic areas and opening up new areas for drug discovery.
And we continue to strengthen our financial foundation, providing the means to support all our strategic objectives.
And today with one of the most robust late stage pipelines in the industry with nine medicines in development for 11 indications returning that promise into new medicines for patients in need.
And not just one or two but a steady and growing cadence of new transformational medicines over the mid and long term.
And in achieving this goal we are positioned to drive great value for all stakeholders.
Stakeholders.
With that I'll now open the call 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 Touchtone phone.
If youre using a speakerphone please pick up your handset before pressing the keys if at anytime. Your question has been addressing you would like to withdraw. Your question. Please press Star then two and at this time, we'll pause momentarily to assemble our roster.
Okay.
Yes.
And the first question will come from Gary Nachman with Raymond James. Please go ahead.
Okay.
Hi, Thanks for taking the question so on <unk> for <unk> any additional updates regarding your interactions with the FDA and.
And how everything is progressing in front of the producer they requested any additional data in our label discussions progressing in the way you would like them to.
And then just on the commercial plans.
Given the competitive dynamics in this space with a good trend on Petro Paolo payers be viewing up on Charleston, Whats your work telling you there.
Well all of these drugs will be covered on most formulary and whereas astrazeneca on the hiring of the sales force just give us a sense of how big you think that'll be thanks.
Thank you Gary I'll take the first one and.
Briefly give you an update on regulatory and then I'll ask <unk> to cover the second part of your question on competitive dynamics. So.
It's.
We don't comment on ongoing regulatory discussions for drugs under review for potential approval, but what I can say.
With high confidence is that we're very pleased with the progress we're making with the FDA.
And bringing up an <unk> to an on time.
A potential approval either <unk> day on December 22nd.
So theres been really no.
<unk> is moving on track with that and I also want to remind you.
Everybody that we are now under review.
Our filings accepted in Canada, and in Europe with potential approvals for those markets as well for next year for <unk> Polyneuropathy.
Hi, Nathan.
Hi, Gary Yeah launch plans are I really underway I would say they are actually in place we have hired all the necessary people for.
Very very effective launch the salespeople as you know is being led by Astrazeneca are hired and deployed in the market. They are in the field, they're working on disease and brand awareness really given that this is a very growth market identifying with different physician.
<unk> said the types of symptoms that agent TRP and patient high bandwidth is very much underway you've seen some of the campaigns on you now.
See the patterns. So they are out there really.
Last month in field and we are just awaiting approval for defense December 22nd and all things are in motion.
Our nurse case managers on their own side are hired and have been trained and sit there mostly post approval because we would deploy them right after and as you know the field medical team that's been in place for the last you know.
18 months to two years so.
All signals are ready to go from a payer perspective, I think we have a very strong payer strategy. We've done a lot of research with the majority of the payers in the U S. We don't expect anything different than other other kind of pn agents that had been priced on the analog something weird.
Disease pricing again, we believe this is a really active rare disease, we do not expect tons of.
Uh huh.
Beyond the normal prior authorization for a rare disease to get through we haven't seen much shift in the landscape here.
Alright, great. Thank you.
The next question will come from Luca <unk> with RBC capital. Please go ahead.
Oh, great. Thanks, so much for taking my questions, maybe two quick ones one on hepatitis B.
What was your reaction to GSK in licensing DSI RNA from Arrowhead and J&J given to date already had is balancing agent would you.
Why do you think they need a second one.
And then maybe circling back on the prior question Tcl put neuropathy that could do for us.
Any color on manufacturing has the tech transferred to Astrazeneca have been successfully completed has the FDA inspected the facility that will provide commercial supply just trying to understand if there is anything that keeps you up at night.
Thanks, so much.
Thanks Luca so.
We have a we have a very good relationship with GSK. So.
We were aware of what was coming and what was announced this week.
The way to think about it is that.
Acquisition of the RNA Arnie I molecule from dance and really represents a double down and triple down if you will on debit person.
<unk>.
Is the only treatment that has produced a meaningful.
Yes.
Meaningful.
Percentage of patients receiving achieving a functional cure patients with HBV chronic HBV.
And in the phase.
And the phase to be clearer and the clear study what.
What we demonstrated with GSK was about a 10% functional cure rate.
However in patients with a lower HBV burden.
<unk> thousand I use per mill.
I think per milliliter.
That functional cure rate was well into the 20% plus range.
<unk>, which is which is really impressive.
And so the the strategy.
GSK has stated and.
We're bringing in the RNA molecule, which has not shown functional cures, but what it has shown as reductions in H B b antigen levels.
Two levels.
Which is a substantial percentage of patients could get below that 1000 are you level is to do a sequential treatment to reach even more patients to achieve even greater percentage of functional cures by bringing.
<unk> down to a level, maybe below 1000 more patients below 1000 I used per milliliter.
And then coming in with a person.
So this is an added dimension through a very comprehensive.
Clinical program for <unk> to reach as many patients as possible and to achieve the highest percentage possible for functional cures for <unk> and it's also consistent with everything that GSK has been saying in which they will be exploring different combinations for better comparison to maximize success on this market, which as you know is one.
Hundreds of millions of people suffering from chronic chronic HBV.
We're very pleased we're very pleased about about this.
About this.
This new outcome with GSK for <unk>.
Maybe you could talk a little bit about the where we are with the <unk>.
And then our launch preparations for commercial supply sure absolutely. We are we are already to go just as we are on the commercial side and the medical affairs side all.
All of the products needed for launch has been manufactured it was manufactured through the registration process regulatory process.
Has been reviewed.
<unk>, we just are waiting for a final label to do label and packaging and get product into channel shortly after approval.
And all of the tech transfer necessary from ion is to Astrazeneca with the with the commercial manufacturer of the contract manufacturer is done.
And all of that has gone extremely well. So we are we are.
Our systems ready to go.
Great. Thanks, so much.
The next question will come from Yale Jen with Laidlaw <unk> Company. Please go ahead.
Good morning, guys. Thanks for taking the questions.
Two quick ones.
The first one is what it's been the raws.
I believe that will be automated and up by about.
Biogen, but nevertheless, you indicated that the growth.
Loan growth quarter over quarter should we anticipate it leave that the business again, because it's the way the stabilization.
The franchise.
Larger SME space, then I have a quick follow up.
So.
What I would say is we're very pleased with the low single digit growth in against last quarter and against the previous quarter the same quarter last year.
We believe that demonstrates <unk> continued resiliency, even in the face of emerging competition.
Beyond that I really need to respect Biogen earnings call next week and I really can't go any further.
Okay, Great that's helpful and in terms of again came up application.
Uh huh.
But on Thursday, the thing the band it.
How should we think about that to incorporate into the marketing strategy, particularly for.
Uh huh.
<unk> Neal.
It'd be treated or treated patients and thanks.
The publication specifically.
That's going to be a really effective tool right. Yeah, I think we'd be promotional and regulatory kind of you know a guidance.
Looking at the Jama publication, and where are our promotional messages are are headed as it can be highly supported the jama publication is also very consistent with the label that we expect so that will allow for use by both the medical teams as well as the sales team as well and that's what we expect.
Yeah. So.
In other words.
Although our.
Our our package that's under review at the FDA is based on the week 35 interim data that we reported last year.
Having this publication for weeks 66, and week 85 is very very helpful from a marketing standpoint, and we expect to utilize that at.
Publication, very effectively I think that was the basis of your question.
Okay, great Thanks, and congrats.
The next question will come from Paul Matteis with Stifel. Please go ahead.
Hi, This is James on for Paul Thanks for taking our question.
Just one on <unk> quickly.
I guess.
As we get ready for the FCS launch I guess, how are you thinking about pricing just given that.
The higher triggs opportunity may be coming behind it and assuming they will be different price points there and.
I guess, just as you've kind of put some of this commercial infrastructure in place for the FCS launch.
How much I guess leverage either from like Salesforce or or spend perspective, do you anticipate getting from this FCS infrastructure as you think about launching the higher triggs opportunity. Thanks, so much.
Sure.
So we've done some extensive work with payers to understand kind of this dual indication that we're going after and prevalent in rare diseases that actually really make a shift in your pricing strategy do we we know that once we.
Once we have the more prevalent.
Evelyn indications pricing will obviously be in line with good kind of cardiovascular premium priced products.
C building new indication in terms of.
Am I thinking about this differently as a result of the two indications if they were.
Two single indications in different molecules with price for rare disease, along rare disease pricing corridors and that broader indication along the corners of cardiovascular.
Cardiovascular premium priced benchmark as well so you should think about it that way.
I would.
I would say that the Fcs.
<unk>.
Account sales team will be calling on obviously, a much smaller portion than the total universe of physicians you would call on for S. H T T. It.
It will be more focused on on the lipid dollar chest, but extend out a bit beyond that as well.
For where we believe the FCS patient population is we're doing a lot of work from our integrated data analysis and qualifying where those physicians are that actually have FCS patients and then as we get into the progress indication. The sales teams will obviously stay on board and we will extend the size of it.
<unk> team for the broader S. H T G market to incorporate some of the other physician specialties that we believe will be very important for the uptake of that product.
Makes sense. Thank you.
The next question will come from Allison <unk> with Piper Sandler. Please go ahead.
Hi, Thanks for taking my question.
So first I guess I just wanted to ask on the anti Tau update last week.
Forgive me.
I know Biogen is responsible for development of the asset, but I just would be curious just to get your thoughts on how that approach could could fit into the alzheimers treatment paradigm.
And combo arm or monotherapy or what have you and then hoping you could also just describe how that that data may be influences your conference and the wholly owned neurology assets.
And then second on a second Brian just on the complement factor B program.
Looking at that that interim phase two data being presented at ASN and a couple of days is there any update just on your view of the Iga nephropathy market.
And potential opportunity and again just given the.
Context of an evolving competitive landscape there. Thank you.
Thank you Allison so.
The phase two study evaluating Tao.
Patients with Alzheimers.
Alzheimer's disease is underway and enrolling and it's a very.
It's a really quite a quite a extensive study with more than 700 patients to be treated for well over a year with the primary endpoint really mean efficacy improvement in cognition.
And the purpose of that phase III study.
Is to really make a decision to set up in support of our forward to go to phase III development for a pivotal study.
And in this study we are exploring.
A different dose levels as well as different dose regimens, including twice a year dosing and thats based on the.
The data that you're referring to which is the phase one two study that is now published in Jama neurology and was presented at <unk>.
Last week and.
It is incredibly supportive of that phase II study in the towel program overall.
We and our partner Biogen could not be more thrilled with the data that was generated from the long term extension of the.
Phase one two study in patients with Alzheimer's disease Tau is considered by expediting essentially all the experts in the field as being the most important target for all centers disease based on.
Nor February tangles that appear just before cognition impairment occurs.
Downstream and beta amyloid, which which can be present long before cognition deficits occur.
But it's difficult to drug targets because.
Whats matters, most is intracellular tau and that causes the nerf entertainment nor degeneration.
But we've shown for the first time is not only can we substantially lowered our all forms of Tau in CSF, we can actually reverse tau pathology and that long term and the long term extension data.
In patients by pet imaging, but now we also have from a long term extension data actually signs trends that patients are actually improving in cognition.
So we couldnt be more thrilled about the data and this has built on the confidence.
From the Sealy a phase II study, that's underway that I referred to earlier.
As far as combination monotherapy that kind of thing Thats. You know this is the start of a.
Development program for a drug is leading the way to target Tau.
The phase II study is intended to assess the benefits of tower in cognition as a monotherapy.
Not preclude future studies looking at different combinations as the field evolves, whether it be with a bad beta amyloid treatment in combination with a talent driven so on that will require further development and.
But it can make sense, we can see how those two mechanisms can actually.
Complement each other maybe even synergize with each other so all of that is on the table, but right now.
Jim and I owners are focused on the phase two study to bring that forward as quickly as possible.
And as far as confidence in neuro.
This is just another piece of data evidence validation of our leading neurology platform.
I would start with spin Rosa.
And Cal Saudi to approve breakthrough treatments for a nerve.
Neurodegenerative diseases.
Using the same platform.
<unk> Tau using the same platform as our Angelman program using the same platform as all of our 12 drugs that are currently in clinical development for all kinds of different Neurodegenerative neurodevelopmental disorders, and as Richard highlighted in his earlier remarks.
We expect to start a prime program OEM program by the end of this year.
And three more.
Next year that are wholly owned neurology programs for for diseases that have a high unmet medical need for both rare and large indications.
So.
It just adds to our confidence in our leading.
Neurology platform as far as.
Again, <unk> X to be presented at kidney week.
Coming up.
This will be a.
An additional data cut that was presented at kidney week last year in patients with Iga nephropathy, I'm, just showing you know more data more and more patients longer treatment showing reductions in proteinuria.
And that study as far as the competitive landscape. It's crowded there's no question. We're glad Roche has has taken the lead on this because they have a tremendous global's might global strength.
We'll present to you know to get the drug is successful.
To bring it to as many patients as possible, but you know.
I really think that that's to be determined once we see the phase.
Phase III data and to see how this positions itself, but really we couldn't be more pleased to have.
When you're in a competitive market like this with a high unmet need it's great to have a global the global strength of a partner like Roche.
The next question will come from Yun on view with Wells Fargo Wells Fargo. Please go ahead.
Great. Thanks for taking the questions three questions if I may.
One person what launch metrics would you provide so that we can have an understanding of how the drug is performing in the market in the early launch quarters.
On the Tau program can you talk about how you see the visibility of the infancy core route of administration and its a very large indication.
Lastly on the Enckelman syndrome program following the recent updated data from <unk>.
Any insights you could share regarding.
How your program could be differentiated from that program as we look forward to data in mid 2024. Thank you.
Thanks, again, and maybe we'll start with.
Launch metrics checkers.
So yeah, and I think the way to think about this market as I said is it's a growth market.
And we have a lot of patients too.
To get diagnosed and get treated on an iPhone <unk> and.
And I think the phenomenon that you might be seeing now with switches as very temporary and I think we will have them.
They will have worked through that.
We're squarely focused on growth.
And growth mindset on newly diagnosed patients as such our launch success will be measured on getting up onto our send out the preferred choice for newly diagnosed patients new to filings.
Got it.
Next year, we will be providing some metrics and we'll see how it.
So stay tuned for that.
Regarding the.
Tau program, so all timers disease. Despite the you know.
Really remarkable progress.
That's the main recently.
Living medicines to the market to patients for a dealer this is Stuart.
Severe neurodegenerative disease with.
With a very high unmet medical need.
And.
Like I touched on earlier, we think that was the best target for treating this disease broadly.
And with that comes the need for treatments and we don't we believe the interest equal delivery.
Will be well accepted if the drug is efficacious and is as efficacious as we expect it to be.
With that said.
The Tau program is an example of the great progress, we're making in further optimizing and advancing our neuro neurological disease drug discovery capabilities with through medicinal chemistry, and just just experience.
In the Tau program, we actually have a treatment arm that we expect will be efficacious.
With twice a year dosing. So we've moved from monthly to every three months for many programs and now we've been moving some programs to twice per year dosing interest equal that is part of the.
Our program that's in phase II development today.
In addition, as we highlighted at our innovation day, a few weeks ago, we're making great progress on.
From our research organization.
And and overcoming the blood brain barrier is an obstacle for delivery of our treatments are drugs for using subcutaneous or intravenous administration.
And you know.
Obviously programs like tower.
Our on our radar as our other programs so.
We also think that that could be in the future for a large population chronic disease indication they call centers disease. So no promises there yet, but we're very pleased with the promised progress we're making there.
Regarding angelman syndrome.
Prefer not to comment on other people's programs of the Companys programs.
What I will say is that.
We are fully enrolled and our Angelman program, we're actually over enrolled the study a bit.
We expect data in mid year next year, we expect data on.
Efficacy as well as of course safety and biomarker data.
From that trial and that trial is designed to set up a potential phase III decision.
Based on all of that and then what I'll also say is that.
And it's kind of related to <unk>.
Earlier question that I got.
But I tried to address which is we have a vast amount of experience with our platform and neurological diseases, thousands and thousands and thousands of patients have been treated for a very extended periods of time with our chemical platform with our knowhow with everything.
And we think that that bodes very well for the angelman patient community, because they're going to be able to take it they're going to benefit from the vast experience that we have.
And I honest with delivering neuro.
Drugs for the treatment of severe neurological diseases like Angelman syndrome, so stay tuned for all that.
We're very much looking forward to the data next year.
Great very helpful. Thank you.
The next question will come from <unk> <unk>.
<unk> with Guggenheim. Please go ahead.
Hey, good morning team. This is Robert on for Doug.
Thanks for taking our questions two for both this morning.
First could you share any pricing thoughts on application, specifically would you anticipate large price.
So it's Kurt Pn treatments on the high end <unk>.
<unk> treatments on the low end.
For the hours that their program.
Or what would you hope to see in the phase III.
Subsequently.
When would you potentially anticipate a phase II readout based on those tablets.
Thank you.
Our neighborhood.
The north <unk> yeah.
So Robert I think that you know we would.
We would expect that again for two indications are both rare disease indications, but they they are priced differently. If you looked at analogs in the marketplace.
You know you based on all the work that we've done we don't believe there is any reason to kind of shift from.
From that from that in terms of our pricing strategy. So I would expect that.
As the price is set by AZ that we would expect poly neuropathy to be priced according to the sea analogs and benchmarks of either a polyneuropathy products.
And regarding our.
Our newest phase III program.
Our Alexander disease program.
Sometimes not sometimes most of the time for enrolling a rare disease indications.
Can be challenging because they are rare and finding patients to get into your study.
Obviously, it can present challenges, but what's unique about our phase III program per Alexander disease is that we.
Designed a seamless phase one through three design such that it's all the same sites. It's all the same products the same protocols already been baked and everything like that.
And after our phase II results.
Which was which.
<unk> reviewed it we had two decisions to make a really one was to dose escalate or to move into phase III development and during that review process. When you go through all the data youre collecting the data cleaning the data and before we actually review the data.
Enrolment is put on pause right because we don't know or the next step will be for the program.
Happen in this situation is that patients were on the sideline waiting to get into the.
Dose escalation phase of the next step or.
The phase III.
Part of the program.
So with that said, we think actually enrollment will go well for the Alexander program, because we have patients on the sideline.
Waiting to qualify to enter our phase III program now that we've activated it so.
You know enrollment is going is ongoing and we expect data.
In 2025.
The next question will come from your own Werber with Cowen. Please go ahead.
Hi, guys. This is brendan on for your own. Thanks, So much for taking the question a couple of quick ones from US just another one on mapped out Nazi excuse me sorry, if I missed this but.
Just wondering if theres any planned for.
Any interim look at the phase II study or any possibility of any additional data updates there before the full phase III readout, assuming maybe 2026 for the full phase two so just wondering if we can expect anything new there in the meantime, and then quickly on <unk>. Obviously, you have a few different studies ongoing there and I think youre planning to incur.
Corporate into one filing maybe including the switching study et cetera. So.
Can you just maybe give us a sense of timing for data beyond the top line readout in the first half of next year, maybe how long Theyre up do you think you'd need to collect and analyze data.
And if you're thinking to maybe file in second half of next year, if that's fair to us. So thanks very much.
Sure.
No.
There is no plan for an interim look in the phase II study for the.
<unk> Tau program at this time.
Short answer a quick answer.
It's very important to get this study right and get the richest data set as you, possibly can and as I mentioned earlier.
This is what we're looking for here is actually.
Evidence to support a phase III decision that we're improving.
Cognition cognizant impairment.
So that's going to take time that studies over a year long as I mentioned earlier more than 700 patients.
So no interim look at this time for Dan and Lewis and I.
I don't think we've said that we're expecting to include switch data in the filing.
For the NDA.
Really the phase III data along with all the other data that we've generated from phase one and phase two will be sufficient to support a filing assuming positive outcome with that said, we expect a switch data.
From our Switzerland from our switch study, which as a reminders.
Our knowledge, we're the only we were the only sponsor that is actually conducted a true switch study.
And which patients that are on an existing treatment therapy prophylactic treatment are switched over to our investigational medicine Donegal awesome.
And investigates mentioned, which in our case as Don indoors.
And then we assess.
Everything.
Including protection against HAE attacks on identifying.
Demonstrating that there's no gaps between one treatment switching to another treatment tolerability sustained efficacy and actually be able to generate.
The information that prescribers are going to want to have to understand how do I do this okay I want to switch to your drug I want my patient to go on your drug, but how should I do this and that's really the that's really the goal of the switch study.
We expect that data to be out next year or at least a cut into that data next year, that's going to really allow us to actually demonstrate the value of down at a worse than us in this market, which is the switch market, but we have no plans to include that at this time to my knowledge.
In the NDA filing either.
Yes.
We believe that the publication will be more than sufficient to be consistent with the label to be used actively bye bye.
By our sales team and promotion.
And to the extent that fits all ready along side of it we could actually add it in but it's really not a requirement noted we think its really necessary for commercial uptake, we like it into publication and that's what we're looking for is our strategy going forward.
Okay, great. Thanks very much.
The next question will come from Jessica Fye with JP Morgan. Please go ahead.
Hey, guys. Good afternoon, thanks for taking my questions.
Remind me of your expectations around weather in addition to a clear impact on triglycerides whether.
Do you believe you could show an impact on pancreatitis for Ozarks in S. H T G.
Then second forgive.
Forgive me if he stated this but for cardio transform I believe the follow up is up 240 weeks I. Just wanted to clarify is there a minimum planned follow up for those who do not reach 140 weeks.
I noticed some of the endpoints are as I said I think 121 is that the minimum assuming the study is not stopped early.
Yeah.
Eugene you want to take those.
Sure happy to maybe I'll start with the last one so.
You said.
Of course, the further squishy and level of detail and.
Analysis, one, but just to summarize it.
The exposure on the study is up to 140 weeks, which means that in some patients.
If the study readout early exposure will be less than that.
We've defined the minimal exposure.
The time point specific time points.
For those early looks in our safety and I don't think that we have.
Have come out.
Included specific timelines on those other than sort of the general.
General statement about early opportunity for closing the study earlier based on some specific conditions being met.
And then there was that in any event you don't stop the study early what the minimum would be.
Well, if we don't stop the study early we go all patients will be well.
Be treated for 140 weeks.
The double blind period.
Okay.
And then.
Likelihood of achieving AP and S. H D. G. Yes, so S. H D. G again, it's it's.
Of course, a very different population from FCS in terms of risk for AP events, having said that again the program that we've designed the two very large studies are certainly we believe we will.
How about an opportunity to show an effect and what we are also going to be looking at is combination of those two studies. So looking at sort of integrated analysis of efficacy.
Combining those two large studies, which together amounted to about almost 1000 patients.
So we're fairly confident of course today, we don't know what the data will show what we can say is that we were extremely pleased with it.
The effect on AP events in our FCS population, so we do.
Well I believe that the thesis is very strong, but we need to wait until the data readout, yes.
The next question will come from <unk> <unk> with BMO capital markets. Please go ahead.
Hi, everyone. Thanks for taking our question one quick question from Us on a DTI.
Morning entirely or presented data from the literature demonstrating that in addition to the percentage of P. P added back soon the absolute serum <unk> levels. After treatment. Although I'd also very important as they can contribute to the ongoing fibril formation and they actually have an impact on survival.
Got it.
That said I'm wondering whether you have any thoughts around that given that most of the discussions in this space focus on the percentage of PPI redact soon but I bet upon the absolute levels of TPI post treatment. Thank you.
Thanks Cosmos.
Not a not a lot of.
Thoughts on.
Gene editing efforts in the TCR space I mean, the progress that they're making.
As you know.
Steady.
For percent reductions in T. T are absolutely important for efficacy I don't think there's a I think we've known for a long time that theres not a threshold effect. If that's your question that there's a specific magnitude three.
Threshold by which if you lower T T R that you'll achieve benefit in neuropathy or cardiomyopathy or whatever.
But then it's actually individualized per patient and per cent reductions.
It is very important and we're very pleased with the mid 80% mean reductions that we've achieved in the neuro transform study for EB one person in Polyneuropathy patients mid <unk> 85 per cent range.
As you know we've actually substantial.
Number of patients actually improve.
And this was evident in.
Quality of life So I.
I don't want to say about those other programs, except that they have a long way to go.
No cardio <unk>.
But the indications are going to require an outcome trial in our view.
To not just be approvable, but to actually compete and.
It's going to take a long time to get there.
And it's a new platform that.
You never know what will come up.
So anyone.
I don't know what else to say about it other than that caused this.
But we love our program and we're very much of a head.
Thank you very much.
The next question will come from Joseph Stringer with Needham <unk> Company. Please go ahead.
Hi, Thanks for taking our question just a quick one on.
Thanks, Steve Golden trial in geographic atrophy, what can we expect topline data and given some of the competitor data that's out there can you handicap expectations on what.
Successful phase III outcome looks like and if the results are sufficiently positive what would be the next steps in the program collaboration with Roche.
The only thing that Richard.
Yeah, I'll take a stab at it I think of course, we want a positive trial.
On geographic atrophy.
<unk>.
And comparable if not better results than that and have been presented by our competitors.
So that's the goal we have no insight.
Into.
But what that is today, but the data will be out next year second half yeah.
So second.
Second half as Richard said second half next year.
What I could add to that Joey is that.
We also had a interim look in this phase III study that allowed us to select the doses to complete. This study right. We started with a number of dose and then where it all goes down to two doses to complete the Golden Phase two study and bring it to the finish line.
<unk> seen excellent tolerability.
We're seeing a profound reductions in factor b and in downstream effects like split products.
Exactly where we expect to be so we're getting great target engagement.
Not seeing any risk associated with that target engagement by block by block in the alternative complement pathway, it's going great.
And what we expect to see is what we hope to see as you know.
A slowing down of lesion.
Formation and improvement in visual acuity.
These are the outcomes that we're expecting to support a decision whether to go to phase III or.
We're not as far as competitive landscape. This is a sub Q once per month drug using which could use an auto injector once it got to the market. If it gets there is simple at home.
Auto injector like upon person.
Whereas the drugs that are.
Our under review have recently been approved or interim vitriol.
And they have side effects as you well know so I think I think.
Although there has been progress made in G&A I think patients are desperately waiting for a drug that's not not so invasive and simple and convenient might be so cute or at home administration.
Great. Thank you for taking our questions.
The next question will come from Myles Minter with William Blair. Please go ahead.
Uh huh.
On <unk> four I think you've got an upcoming presentation at American Heart Association.
Just wondering whether we should be thinking about similar I'd say take knockdowns to the previous locker molecule and just more infrequent dosing or is that potential to get more than that sort of 75% that was signed with that molecule. Thanks very much.
You got it Myles.
So our.
Our presentation on our ADT.
Graham IHA will really focus on.
You know the dose dependent reductions in HGT.
The.
We start to achieve in our in the phase II study.
If this is a molecule that is being dosed monthly our earlier generation molecule that you mentioned was weekly.
And we expect to see greater reductions to our earlier generation molecule because it's a more advanced chemistry.
That's where we are.
Cool thanks for the question.
Yeah.
The last question will come from David Lebowitz with Citi. Please go ahead.
Thank you very much for taking my question with respect to all of US are some given the recent pivotal data.
As you look forward to severe that hyper triglycerides anemia.
How I know that you achieved benefits with respect to paint with Titus you achieved reductions, but given the dynamics in different differences in that population.
Easy do you think it's going to be the show of pancreatitis benefit.
Okay.
That's a great question, David and it's a it's a question that are answered today is a lot different than it would've been earlier this year the Fcs data.
<unk>.
Our wildest dreams, we hoped to see the AP reductions that we saw in SCS.
And those would want wildest dreams turned into reality.
So.
You know and as we mentioned in our in our remarks earlier.
And there have been more pleased and this is the first time anyone has demonstrated that lowering of lipid Mike triglycerides can actually.
And positive outcome in AP.
My point is that our confidence has grown because the efficacy with silver marketable on reduction in AP events and.
And that that could eat lends confidence to the SHT G population, which although it's not a genetic form of severely elevated triglycerides no known genetic causes.
A monogenic disease like S. Yes.
These patients still suffer from a highly elevated triglycerides much like FCS patients I'm sure some of those patients could be in the above 500 range to 1000 range for many many of these patients are in the multiple thousands or at least above 1000, which are which puts them at very high risk for AEP. So I think we're going to get a P events and.
In the phase three <unk> study and based on the effect size or the effect that we saw with outsourcing NFC, yes, our confidence has grown but we have to see that.
Even.
And despite the fact that the.
Number of events per patient may be less in Ace H T G versus FC Yes, it's such a bigger study. It's a much bigger studies, we're going to have much more data that we're going to collect and as Eugene said, we have the ability to combine two phase III studies core amcor too to really look at them overall.
Overall, the impact of <unk> <unk>.
And S H T G. So.
Thanks, so much for taking my question.
Thank you David and thanks, everybody for joining us today.
Everyone, who has participated in our in our call.
We really are proud of all the progress we've made this year and and and we don't we believe that the future has never been brighter.
Here I don't want it and we plan to continue our momentum by delivering an additional key commercial updates pipeline updates technology updates objectives as we as we go forward and we very much look forward to it but until then thank you again and everybody have a great day.
[music].
Yeah.