Q3 2022 Ionis Pharmaceuticals Inc Earnings Call
Pipeline to our portfolio next year.
These are of course at one person for <unk>, Polyneuropathy and <unk> Prasad one AOS.
In addition, we have made excellent progress advancing our late and mid stage pipeline with.
With eight positive key data readouts. So far this year, our rich phase III pipeline is poised to expand with two new phase III starts expected in the first half of next year.
And based on all our pipeline progress, we're well positioned to continue delivering a steady cadence of phase III data Readouts in 2023, 2020 for 2025 and beyond.
This year, we have also advanced our commitment to deliver transformative medicines to the market with our go to market commercial preparations for our near term product opportunities FY <unk> <unk> and <unk>.
We have also made great progress expanding and diversifying our technology with the recent advancement of three new programs into IND, enabling development activities. These programs involve our first medicines, incorporating leica technology for enhanced delivery to muscle and our Measle fazer emanate, our MSP a backbone chemistry designed to.
Improved both efficacy and durability.
These advancements further enhance and expand our drug discovery capabilities for both our new our new programs and our follow on programs.
We've also taken additional steps to support our future growth.
We recently began work on a new state of the art manufacturing facility. This facility will ensure we have the capacity we need to continue to successfully deliver our medicines to patients and continue to expand into new chemistries.
We also recently capitalize under record demand for life Science real estate assets by monetizing several of our facilities through a sale leaseback transaction with <unk>.
Transaction further strengthens our balance sheet to support our plans for accelerated growth.
With that I'll turn the call over to Richard to discuss our recent key data readouts pipeline updates and preview our upcoming catalysts.
Then <unk> will review, our third quarter financial results the financial impacts of our recent real estate transactions as well as review our full year financial guidance and after Beth I'll wrap up our prepared remarks before.
Taking your questions so now over to Richard.
Thank you Brad.
While our pipeline has certainly performed extremely well this year, we reported eight positive data readouts so far this year.
As a result, we are looking forward to potentially having two new medicines on the market and expanding our rich phase III pipeline next year.
Over the next few minutes I will review, our recent achievements and then preview our upcoming catalysts.
Our next potential medicine to reach the market as <unk> or.
Our medicine for patients with <unk> ALS.
<unk> is currently under priority review with the FDA has the potential to become the first approved disease modifying medicine for the treatment of a genetic form of ALS until.
<unk> has a <unk> date of April 25, two.
Thousand 23.
In September we presented positive Epsilon tertiary data from the phase III neuro <unk> transform study in patients with <unk> Polyneuropathy at the international Symposium on amyloidosis.
And the eight month interim analysis, <unk> achieved highly statistically significant and clinically meaningful change compared to historical placebo for its co primary and key secondary efficacy endpoints, including demonstrating robust ctr reduction from baseline.
With improvements in neuropathy impairment and quality of life relative to baseline and a substantial portion of patients.
Yes.
With these very positive data, we and Astrazeneca I look forward to filing for regulatory approval in patients with TCR polyneuropathy in the U S. Before the end of the year.
Additionally, we are extremely pleased with the continued progress of cardio T transform our largest and longest study in patients with <unk> cardiomyopathy to date.
Since we initiated cardio T transform in late 2019 patients are being diagnosed much earlier in the course of their disease as a result of greater disease awareness and improve disease detection methods.
Evolution in the ATR cm landscape is supported by new published and presented data from the scientific community.
Based on these new findings along with careful monitoring of patient demographics and blinded event breaks in our study with.
We increased target enrollment goal 2500 patients.
This increase will ensure our study fully reflects the entire population of patients including patients with less severe disease.
We believe this further increases our probability of delivering a highly positive study outcome that best position <unk> to successfully compete and lead in this growing dynamic.
And global market.
Importantly, based on our current rate of enrollment and the added power from additional patients we.
We remain on track to report data in the first half of 2025.
Our broad <unk> development program in FCS and severe high triglycerides is also progressing nicely the phase III balance FCS study is fully enrolled as planned to read out mid next year.
Our broad clinical program supporting the larger severe high triglycerides or S. H T. G. Indication also continues to progress well core our pivotal our first pivotal study in patients with <unk> remains on track for data in 'twenty four.
Core to our confirmatory pivotal study in the same population is now underway with data also expected in 2024.
We recently initiated essence, a supportive phase III study is designed to build out the safety database for the much larger house hcg indication with first mover advantage, we remain very confident in the potential of <unk> to be a substantial driver of future growth.
Now are done at Dolores in the Oasis Phase III program in patients with hereditary angioedema remains on track for data also in 2024, we will report new longer term data from the phase II <unk> study. This Sunday November 13 at the American College of allergy asthma.
And immunology annual scientific meeting.
The goal of the study is to reinforced under the license.
Potential best in class profile by demonstrating long term protection from Hai attacks, along with longer term safety and tolerability in patients treated for one year.
We look forward to sharing our OLED data with you on Sunday.
Recently, we and our partners presented positive data from several of our mid stage programs further advancing our rich pipeline.
We recently presented positive and competitive phase II data from <unk> FB <unk> in patients with Iga nephropathy at the American Society of Nephrology kidney week.
This study was designed to demonstrate clinical proof of concept for the potential to treat Iga nephropathy by targeting complement factor b and the alternative complement pathway and of course to evaluate safety and Tolerability.
<unk> met the primary endpoint, demonstrating substantial and clinically meaningful reductions in 24 hour urinary protein in patients with Iga nephropathy with a mean reduction of 44%.
Additionally, patients effectively maintained their egfr throughout the study.
And together with this achieved a favorable safety and Tolerability profile.
Based on these positive data Roche already announced their plan to advance <unk> into phase III development by mid next year.
Also at kidney week, Bayer reported positive phase <unk> study for <unk>, our factor 11, like a medicine for the treatment of thrombosis.
The goals of the rethink ESR. This study were to demonstrate dose dependent substantial reductions in factor 11 levels.
And no increase in bleeding risk compared to placebo in patients with end stage renal disease safety and Tolerability were also key outcomes.
We were pleased that <unk> exceeded all of the goals of the study <unk> achieved dose dependent and sustained median reductions in steady state factor 11 levels exceeded 85% at the top dose and with no imbalances and major bleeding or non major bleeding compared to placebo.
Additionally, incidences of dialysis circuit clotting, and Avi access thrombosis diminished significantly.
With decreasing factor 11 levels, both of which were exploratory efficacy endpoints.
And as <unk> demonstrated favorable safety and Tolerability in this study.
Despite these highly positive results spare made the decision to only advance their small molecule factor 11 medicines in phase III, and therefore return <unk> to high <unk>, while we understand bayers decision not to move the second factor 11 drug forward.
We and our clinical advisors believe that these positive data support advancing <unk> into pivotal studies, given the large potential addressable patient population and numerous potential indications to explore we are focused on getting customers into the hands of the right partner to deliver it to the market has.
As possible.
Turning now to the exciting appear averse and data GSK reported at <unk>.
<unk> as a potentially transformative treatment for people living with chronic hepatitis b.
<unk> is responsible for approximately 900000 deaths annually.
The goal of the Phase <unk> study was to assess efficacy safety and tolerability in HBV patients treated with <unk>.
This one is an important study because it demonstrated for the first time that <unk>.
<unk> alone or in combination with anti <unk> anti viral nuclear tighter nucleoside inhibitors can deliver a sustained and substantial reduction in both viral DNA and HBV surface antigen, which together are key measures of efficacy.
The results showed that 9% of patients on nucleoside nucleotide analog treatment, 10% of patients on <unk> versus <unk> alone achieved the primary outcome of viral DNA and HBV surface antigen below the limit.
Lower limit of quantification at 24 weeks after by peer versus treatment.
These data strongly support.
The potential for a payer version to achieve functional cures in people suffering with chronic HBV infection.
Based on these encouraging data GSK is currently in discussions with regulators on the design of the phase III studies with plans to initiate a robust phase III program in the first half of next year.
While it has been an eventful and catalyst rich year, and we anticipate continuing the momentum with the remainder of the year and in the year ahead.
We're looking forward to presenting our upcoming HCA data this coming Sunday and we are on track to file the NDA for <unk> by the end of the year.
Next year, we're looking forward to more key catalysts, including the potential approval of <unk> in the first half of the year.
Both 66 week data from the neuro <unk> transform.
Study of Epsilon person the potential FDA approval of <unk> later in the year.
Phase III data from <unk> in FCS patients along with the initiation of two new phase III programs among other important advances.
With that I will turn the call over to Beth.
Thank you Richie.
I'll provide a summary of our third quarter results discuss our recent real estate transactions and then touch on our full year guidance.
We earned revenues of $160 million and $435 million for the third quarter and year to date, respectively, and approximately 20% increase over last year.
Our revenue continues to be derived from numerous diverse sources with approximately half from our marketed products and the balance from numerous partnered programs.
Our operating expenses for the quarter and year to date reflect our continuing investments in advancing our rich pipeline and commercial readiness activities.
Notably we continued to maintain our healthy balance sheet with cash and investments staying steady at approximately $2 billion.
Through the end of Q3.
<unk> global sales were $431 million for the third quarter and one 3 billion year to date as a result, we earned $62 million and $179 million in royalty revenue for the corresponding periods.
In the U S. <unk> sales continued to stabilize in the third quarter.
Additionally, we continued to see positive trends in discontinuation rate.
We expect to see the same dynamics play out in markets outside the U S.
Which we see as the path or spin Roberts returned to growth.
And Ross has potential to return to growth is further supported by Biogen continued geographic expansion and their robust lifecycle management program.
This includes the word biogen is undertaking to further characterize the remaining unmet medical need of patients with SMA with <unk> respond and devote study.
We earned R&D revenue of $87 million in the third quarter and $212 million year to date.
Both of which increased substantially compared to the same period last year.
Year to date, we earned $85 million from Biogen for advancing neurological disease programs under our strategic collaboration.
We also earned $63 million from Roche for licensing and advancing ion and SP dash sell our ax.
$55 million in cash payments from Astrazeneca for their portion of Avalon test development.
Our non-GAAP operating expenses increased in the third quarter and year to date compared to last year.
We are in line with expectations.
The increase was driven by higher R&D expenses from advancing the six phase III studies, we are currently conducting.
Epsilon testing comprising our largest investment.
Our R&D expenses also included increased spending for CMC and medical affairs activities to support our near term commercial opportunity.
SG&A expenses increased in the third quarter compared to last year as we ramped up our go to market preparations.
Year to date SG&A expenses were below the same period last year continuing to reflect the substantial savings we realized from the <unk> integration and steadily transaction.
As Brent mentioned, we recently took two important steps to support our future growth we.
We entered into a long term lease to construct a state of the art manufacturing facility.
Significantly increasing our capacity to bring our medicines to the market and to expand into new chemistry.
We will oversee the design and construction of the facility and it will incorporate advanced sustainability and environmental protection features.
For example, we expect that approximately 50% of the new facilities power requirements will come from renewable energy sources.
We anticipate completing this project in 2025.
Based on our early design work, we expected to cost us approximately $350 million.
We also entered into a sale leaseback transaction, which took advantage of the record demand for high quality life Science real estate assets.
This transaction bolstered our cash balance was approximately 250 $240 million in net proceeds plus funding to expand our R&D campus.
It also enabled us to retain control over the operation of that facility.
We used a portion of the proceeds to pay off.
Our existing mortgage on the property and doing steadily reduced our long term debt.
By putting this cash to work, we believe we can generate substantially more value advancing our growth initiatives.
Including expanding and advancing our pipeline and technology preparing for multiple product launches and building our new manufacturing facility.
Our Q3 results keep us on track to meet our 2022 revenue operating expense and net loss guidance.
We continue to expect revenues of more than $575 million with commercial and R&D revenue roughly split 50 50.
As our phase III study is continuing to progress we expect our R&D expenses to increase between 25% and 30% this year compared to last year.
We project, our SG&A expenses to be in line with last year, even while we increase our investments and preparing to bring our near term opportunities to the market.
In total we expect our non-GAAP operating expense to come in at the lower end of our guidance, which is between $825 million and $850 million.
And since our recent sale lease back transaction was not contemplated in our guidance. We are increasing our 2022 cash guidance from $1 7 billion to $2 billion.
Looking to the future beyond 2022, we expect our strong financial foundation to continue to serve us well.
And as we continue to invest in advancing our strategic priority. We are pleased to deliver significant future growth and with that I'll turn the call back over to Brad.
Thanks Beth.
To summarize this morning, we made great progress this year in advancing our key priorities to grow our commercial pipeline.
To deliver an abundance of new transformational medicines to the market in.
And expand and diversify our technology.
We're on track to file the <unk> NDA by the end of this year and with 12% currently under priority review with the FDA, we're positioned to add these two new medicines to our commercial portfolio next year assuming approval.
Our late stage pipeline continues to advance and expand sitting and stuff to extend our phase three data Readouts next year and for many many years to come.
We've made important advancement in advances to expand and diversify our technology with more advanced <unk> still to come and.
And we've taken additional steps to support our growth.
Importantly, we have the resources to continue executing on our priorities to drive substantial value for all stakeholders.
This has been a great year for Iona, So far and I think next year and the years to come are going to be even better.
Looking forward to sharing more on our progress in the coming months with that I will now open the call up for questions.
Greater if you could open up the queue. Please.
We will do we will now begin the question and answer session to ask a question you May Press Star then one on your telephone keypad, if youre using a speakerphone. Please pick up your handset before pressing the keys and to withdraw your question. Please press Star then two and at this time, we'll pause momentarily to assemble our roster.
And the first question will come from Gary Nachman with BMO capital markets. Please go ahead.
Hi, good morning.
So first one up on tourists.
Explain a little bit more of the rationale for further expanding the cardiomyopathy study, where you were seeing in terms of having too many earlier stage patients.
Did you consider extending the duration of the study at all beyond what you did previously and.
And just how you're confident that the timeline won't change in terms of getting those data.
So that's one and then just on the so first an NDA with extended three months.
Why.
The FDA asked for any additional information.
And if you guys are still anticipating a panel.
And how you and Biogen are preparing for that what you think the.
It might be discussed if there is a panel.
Sure thing Gary.
Maybe I'll, maybe I'll take a stab at the till for some question and then I'll turn it over to Eugene.
Discuss the rationale.
Reasoning behind the <unk>.
Protocol Cardiomyopathy protocol amendments so for Tofacitinib.
Yes, there was an extension.
The timeline for the NDA <unk> date to April .
25, three months delay major amendment.
Primarily because of the FDA has communicated that they just need more time to review all of the data, it's really not a request for any substantial or significant additional data they needed to do the review it was really a bandwidth issue principally.
They have a lot going on in the Neuro division, especially this past fall.
For similar indications and we suspect will go not definitive that that probably caused them to have to take more time to review the data set we're very much looking forward to the data readout.
The decision.
The outcome from that.
The review by the FDA.
No new nothing new on the.
Physician by the FDA on.
Outcome. We've heard if you are still assuming that they are planning to have an outcome at some point and we're very much looking forward to that as well using money to take us through the rationale.
And also the importance of the amendment.
The change to the cardiomyopathy.
Phase III trial for GTR.
Sure Brad Thanks for the question so as Richard already mentioned in his remarks.
It is clear to us too.
Many of the advisors, we've been talking to the population was <unk> cardiomyopathy has changed substantially over the past several years.
And as you recall the primary source for us too.
To power. The study the original study that we started back in 2019 was via trucks dataset, which.
The study that Pfizer conducted quite a few years back and the more.
Data became available to us internally as well as externally.
Importantly.
Quite a few publications.
But now endorsed the patient population has changed in a meaningful way specifically they come to a definitive diagnosis earlier than they used to and as a result of that sort.
Dr drove greater disease awareness.
Diagnostic measures.
And that results in the patient journey.
The relatively.
Different to what it used to be so.
Okay.
One attract was conducted patients came to attention leads in there.
Clinical presentation and have multiple early events or again as I said were used or the original powering of the study so as we.
Assimilated all of the data externally.
Internal where youre coming from our study.
Study it.
It became clear that the study was not.
Powered properly based on those updated assumptions and we needed to resize the study accordingly.
Of course, the question about duration is an important one and we've looked at that as well we've considered against the <unk>.
Extending the duration even further because.
Substantially delayed timing of the readout and we felt that become the upsizing of the study alone was sufficient to ensure that it is properly powered.
Without taking a significant penalty.
Okay.
Ended up thank you gene and I'll just add of course, we also have patients in the open label extension of the phase III cardio transform study.
<unk> now completed the 140 weeks, so we wouldn't want to lose those patients. So we can accomplish the same objective is the same goal by increase in sample size, which we did.
And we think that this is a strategic strategic importance.
Move.
The study to really help ensure for the most successful outcome.
Possible for cardio transform.
Okay. That's very helpful. Just to confirm you don't need to increase the number of sites.
Enrollment has been going quite well, maybe just comment on that thank you.
Right.
Adding a 100 patients not changing the timing for the readout means that we're well ahead in enrollments of enrollments going very well.
And we're not needing to open up new sites.
Studies, some existing sites and we're just.
Moving ahead rapidly to get to the 1400 number.
Okay, great. Thanks.
Alright.
The next question will come from <unk> <unk> with Wells Fargo. Please go ahead.
Hi, Thanks for taking my questions and congrats on the progress.
Quarter I have a follow up on cardio transform transform study and also a question on LP little a for cardio transform how does.
The changing demographics teams tend to your powering assumption in terms of event rate in the control arm and the effect size and what proportion of <unk> patients did you assume in your <unk>.
Howard assumption.
For LP the <unk>.
<unk>.
How do you and your partner Novartis view that data for.
Passerine presented at the meeting.
Where they filled up to a 100% L P little a reduction.
Does that affect your outlook for kind of a carson. Thank you.
Thanks Shannon.
Great questions.
Eugene to share with you can share about powering assumptions and so on and then Richard to talk about.
Sure. Thanks again, thanks for your question so related to our original assumptions.
You may recall we.
We did.
What we thought was responsible and conservative.
Thing to do which was assuming that all of our placebo patients will be on a background of us. So we took the essentially the sum of those arm evaporate in our original power calculations.
Even given that rate turns out to be overly.
<unk>.
Quite quite a bit different from what we're seeing.
And what's been published recently to be the case and patients in general in two days and two based care so even that rate was.
Was overly.
Pi relative to the population of available today.
We haven't really changed any of our other.
Assumptions on the treatment effect of <unk> as you know the treatment between treatment effect does not know them or not.
There are two changes.
But our assumptions nor have we commented on what specifically we used other than to say that we use both our advisors. So that would be considered clinically meaningful for them.
Thank you Jane and I will just add.
We're focused on.
The cardio transform study of course.
But.
This change of changing demographics and CTO cardiomyopathy, we think applies to all contemporary studies evaluating investigational medicines and we're in a very strategic position and made a very strategic move to ensure.
For a very successful outcome in this study. So we think this is a very important move and it gives us even greater confidence in a successful outcome.
Hello Carson Richard.
Yeah. So.
Speaking directly to the question how does it.
<unk> change our view on <unk>.
It doesn't change it at all and just to take.
Take you back to a remembrance of phase two.
For pellet Carson.
Dose that we took into phase III achieved.
98, plus percent of the patients the goal and the goal is to get below that threshold of 50 milligrams, it's not to get to zero.
So.
It's a little bit different than LDL, its different way of thinking lowers not better but getting below that threshold is the goal.
So we're going into phase three with <unk>.
A product that gets nearly a 100% of the patients to where they need to be out of risk.
And we are well ahead of the competition there is competition and that just.
It gives us all the urgency that we've had all along to get this thing to the market as quickly as possible.
Yes.
Thanks Richard.
It's probably worth noting too that the epidemiology data is substantial and continues to grow really enforcing.
<unk> reinforcing our conclusion that thresholds, where you need to be below that threshold, where you need to be to get out of harm's way.
As Richard said, Hello, Carson delivers on that based on it.
Very significant large phase III study, which we are extending the same patient population same phase II dose, but also there is now emerging data.
<unk> data, indicating that if you go too low and LP Little a you can also.
Of course the problems there are publications now out there that says if you can go very low on LP little a.
That you can actually have an increased risk for diabetes sets associated not causal not proven but theres no need to go that low and all it does is bring burner risk.
I also want to add this.
<unk>.
The study is fully enrolled the study is well on its way to reading out. This study gets reviewed by oversight committees independent oversight Committee regularly.
That drives risk down.
Right.
Competitors are going from a small phase II study to a large phase III outcome trial that brings risk we'd like our risk profile today fully enrolled on our way to readout well ahead of the competition and to getting virtually all of the patients into the safe zone for LP little a level. So.
Alright.
It answers your question.
Yes, yes. Thank you for all the helpful color and congrats again on the progress of this quarter.
Thank you Sir.
The next question will come from Myles Minter with William Blair. Please go ahead.
Hey, just a quick question on <unk>.
Just with your new partner can considering you did show the data in Saudi with dialysis and it looks to be hitting everything that you set out to do.
Demonstrate.
What sort of indications with you encourage a new sponsor that ties with that asset versus the oral inhibitor competitors that look to be guiding for a more acute setting.
Thanks miles.
As I think we've been very.
Transparent with over the last.
I think really last year.
We were hoping <unk> was going to take <unk> forward based on positive phase III really positive phase II data, which ended up being very positive.
But we're also anticipating preparing for the eventual potential return.
Of course bear had three independent modalities being developed firm targeting factor 11 their own homegrown small molecule in licensed monoclonal antibody in licensed <unk>.
As I said as you know.
The some of the small molecule that has been presented already at ESC.
A lot of aspects look good I think it's the biggest kind of a mixed bag there.
Very pleased with the phase II data for <unk> in the antibody that has not yet.
So they've made that they made the decision to go forward with one drew.
Drug forward.
And there was focused on end stage renal disease as a potential population for <unk> medicine.
We believe that Thats too limited we believe that.
Once a month highly effective factor 11 inhibitor that achieve knockdown of factor 11 beyond 85%.
It can be used for any prophylactic treatment to prevent thrombosis atrial.
Atrial fibrillation secondary stroke prevention.
End stage renal dialysis. So on so we think that this is.
<unk> has the potential to be used broadly and thats where were going to be looking for in a partner a partner that can bring as Richard said in his statements to bring to the market.
Quickly as possible, but also to really maximize.
The opportunity is a pharma prophylactic treatment for thrombosis.
Okay Cool and then a quick one on cardio <unk> study just with the 400 patients that <unk> gone to additionally, enroll that going to be.
<unk> balanced across the patient subgroups like wildfire versus hereditary to feminists experience versus naive.
Or are they specific subpopulations as you've seen the demographics of the 1000 patients currently that you might want to bolster with the addition of these 400 patients coming into the shop.
Yeah. Thanks, Thanks for the question miles with CGM. So.
Clearly the opportunity here is due to be fairly intentional with the remaining portion of the population that we're enrolling.
We're in a position where all sites are open we have an ability to be kind of.
More targeted in the types of patients that are being brought in.
What we're doing.
As you said of course, if you look at the epidemiology data and the risk is different for certain types of patients with regards to outcomes.
What we're trying to maximize here of course, bringing them more hereditary patients.
For patients who are on <unk> therapy.
Submissions at later stages of their cardiomyopathy compression.
Is going to be a priority and that's what we're trying to do with the remainder of enrolled population.
Alright, thanks for the questions.
Thanks miles.
The next question will come from Jessica Fye with Jpmorgan. Please go ahead.
Hi, there good afternoon. Thanks for taking my question can you give us an update on the Angelman program, where does that stand and when can we expect an update.
Thank you.
So unfortunately, we don't have a whole lot new to <unk>.
Fine.
We were.
We're enrolling the study as you know it's an open label extension study.
And.
Sure.
We're looking forward to completing the studies as rapidly as possible, we're not really planning to share any data rate Eugene.
Like you know.
Anecdotal observational data as we go forward, we want to get this study completed it's dose ranging and it's intended to set us up for a phase III start as quickly as possible, we absolutely and Thats also partnered programs. So because of the open label nature of the fact that it's at.
Really in the early stages of dose escalation, we're not really commenting on the timing of MSA has gone. According to the plan going according to plan, it's enrolling well.
Theres moving alone.
Thank you.
Alright, Thanks Jess.
The next question will come from Luca <unk> with RBC. Please go ahead.
Oh, great. Thanks for taking our questions. This is Lisa answer Luca.
For Brian just a bigger picture I know you've talked in the past about broadening your reach to technologies beyond antisense oligonucleotide. So I was wondering if you can comment.
Your latest thinking is there thanks.
Sure.
Thanks for the question so.
We.
As I as I meant mentioned in my prepared remarks today, we're making great progress in advancing.
Our technology in many different ways.
We've now moved with a partner a new program using of new Leica targeting muscle.
More about the target or the indication at this point, because it's highly competitive area, but we're looking forward to providing an update maybe next year.
That is a potential open up new diseases for <unk> as well as for partners targeting targets I'm going off of targeting muscle.
We are also now.
Brought forward, a new backbone chemistry column MSP.
We brought into development now.
Supporting toxicology studies.
For two CNS targets.
Using that backbone.
That backbone is intended to do to increase efficacy potency as well as durability. So less frequent dosing and we expect that to translate to both the CNS as well as.
Systemic applications, so stay tuned for that Theyre, both for broad indications for one with partner one by one is wholly owned and we expect to keep gallon ourselves as well.
As far as.
Other other approaches have been safe now for quite some time.
We are.
We will continue as we have been now for the last couple of years.
Evaluating ESI strategies as well as DSO strategies will move our philosophies, let the best drug win based on preclinical data for each of them to the clinic.
Speaking to move our first ESI into.
Into development.
Talks that you probably early next year early this year.
And there are specific applications, where we see advantages for our centers specific advantages or areas, where we see advantages for <unk>.
We're going to be multi modal here as far as new platforms go.
<unk>.
We're in sort of seeking evaluation phase right now about diversifying our platform capabilities.
And I really can't say much more about it than that Lisa except to stay tuned we hope too.
Do you have to make some progress.
In the future about some some of our thoughts ideas in that area.
Excellent. Thanks for taking my question.
Thank you Lisa.
The next question will come from Gena Wang with Barclays. Please go ahead.
Thank you for taking my questions I, just have one regarding the itchy yesterday.
Sunday.
So do you already feel pretty impressive early efficacy so with this early data.
Should we expect further improvement in that.
<unk> reduction given the longer follow up and also which data point will be more important regarding percentage of patient attack free versus percentage of a reduction in attacks.
I'll start at the beginning but then I'd like to talk from a commercial standpoint, maybe what she she views since we're planning to launch this drug ourselves, but most important to patients and prescribers for a prophylactic for HIV. So.
You can't get ahead of the presentation on Sunday.
Be fair.
<unk>.
We're expecting our plan is to show I mean, it's hard to get better in the phase II data right. I mean, these patients where essentially attack free once we got to steady state after five weeks after one dose.
It's hard to get better what we really looking to do is what shows whether that debt unprecedented efficacy is actually sustained per year right as well.
As compliance as well as the.
Along with long term tolerability. So those go hand in hand from an approval to separate as you know Gina.
Tolerability as well as sustained efficacy. So that's what really I don't think we can go beyond I mean, maybe.
But it's really onesies and twosies of patients percentage points I should say because you can't get much better than the efficacy we showed in phase III.
What are you thinking is it from what's what's most important to patients.
Yes, I would say keep us positioned to MTA patient ciena.
Efficacy is first and foremost we tested.
Hierarchy in order of efficacy.
Just to kind of clean like what's most important and the theory on the cap rate is the number one.
Efficacy measure then followed by.
Attack reduction and then followed by how much are actually withdrawing them off the acute treatment said those are that's the order of hierarchy bacteria attack rates basically the name of the game here.
And as Brett said, we in our phase III <unk> already seen showed a mean.
Our Max clinical efficacy of 97% zero Tac rates that we achieved.
In week five to 17 as quickly as after your first Ken.
Also important to note that in this marketplace. We also just completed some market research to say, okay, well where are the patients that currently.
<unk> being the market leader.
And the number one prophylactic H embedded eased out there again.
Yes.
With with a pretty significant zero Tac rate, we're still seeing patients have put it on average there are about three HIV attacks happening in a year and in <unk>.
And thats pretty substantial scale. So we do believe that we're going to really fulfill this unmet need that still exists in the market.
Thank you very much.
The next question will come from Joseph Stringer with Needham <unk> Company. Please go ahead.
Hi, Thanks for taking our questions a quick one on the GSK partnered HBV program, the peer of yours and <unk>.
Just wondering if you could talk about the.
Differentiation of your approach from a.
Competitor approaches.
That are using dual or even triple combo therapy, some of which are.
RNA inhibitory knockdown based.
Great question, Joey Thanks, I'm going to ask.
Eric.
Comment on that sure.
Really I think the.
The key differentiator is the peer Pearson as a single agent was able to do things that other approaches really haven't been able to accomplish.
And that was evidenced by the be clear results showing around 30% Hbf antigen.
Below the limit of detection level at the end of treatment and then.
Maintaining that for about 10% of the patients.
24 weeks post study and this highlights the potential of that drug to achieve.
The ever elusive functional cure in HBV, where patients are being able to remove from therapy.
I think GSK is doing a great job with this program and thinking about combination approaches they have to be together study ongoing right now which is adding interfering on top of that and I think some of those competitive studies, you're referring to are using HP re RNA lowering agents in combination with interferon and showed.
Some S antigen loss, but that was at the end of study.
Not after removal of treatment so.
I think the field is moving forward it's actually.
Great to talk about HBV functional cures and having the buzz around at the recent meeting that that's happening and I think it's good for patients and ultimately.
We and GSK to think that that would be will be a foundation for treatment of HBV, including combinations involving battery that will hopefully increase the rate of patients that can remain therapy free.
I think thats something I just want to emphasize that Eric just closed on is that the the 90, 10% functional are undetectable levels 24 weeks after completing dosing. So often all drugs 24 weeks later undetectable and about 10% of patients whether monotherapy or on nukes.
Really is unprecedented and is the foundation.
To build from that alone. We believe is an approvable mark benchmark that's a.
Marketing as a marketable and.
The endpoint.
And it's the beginning once we get into combination treatments and solar.
Subpopulations, we know that the.
The undetectable levels were.
Greater in patients that had less HBV burden coming into the study in 2030% range right.
All of this is just the beginning and still really impressive but.
We go and GSK is going to be taking a comprehensive approach phase III approach to looking at various combination immunotherapy.
Interferon combinations and so on.
To maximize the value of <unk> for HBV patients.
Great. Thanks for taking the question.
Thanks Jerry.
Yes.
The next question will come from Paul Matteis with Stifel. Please go ahead.
This is James on for Paul Thanks for taking our question, maybe just one on <unk>.
It looks like it could potentially be <unk> first kind of independent drug launch and I guess, one is that how you are thinking about it today to launch it yourself.
And if so what the investment there look like.
And then maybe just separately quickly it'd be great to just get your thoughts on what you would want to see efficacy and safety wise to have confidence in our competitive drug profile. There. Thanks, so much.
Sure on anything you want to take that sure.
Yes that is a very correct assumption that this will be the first ious.
Self commercialization outside of our cocoa Athlon tillerson being the first one.
And we are looking at two indications as you know the first one is in FCS and then the second one in severe hypo triglyceride EMEA.
Severe hypo triglyceride Dena is a large patient population in the U S with close to 3 million patients available for treatment over here with elevated S. Http.
This is the investment that's required is actually going to be a pretty focused I would say it would seem on the face of it because of a large patient population youre going to go out and you don't have to call on GP and staff, but we've done a fair amount of work to see where the referral patterns are for these patients and they are coming into a couple of spec.
<unk>, so we're going to be an extra very targeted there and we're also been employee just really good.
More innovative tools, such as omni channel and.
Just a lot of AI to identify where the patients are from predictive analytics to be able to manage our investments to get to this large patient population. So we are working very actively.
In terms of preparing as these trials are all in phase III right now the two core trials, which are the pivotal and confirmatory trials in any essence, which is safety trial that just got initiated that as well.
As to what's a competitive profile listen the standard of care or <unk>, and niacin and Vascepa and their triglyceride reductions were in the 20% to 30% range. So we're doing we expect to do about two and half to three X more of that we have a real good confidence that we will get there based on our phase twos, which as a reminder.
The phase two for substantial but we're not in these really high elevated at <unk>. They were in that 200 to 500 milligram range and in that we already showed a 62% placebo corrected TG.
TG lowering <unk>.
If you take a look at what we expect.
In the severe hypo triglyceride range, we expect that it's going to be higher and as a reminder, we are also studying two doses 50 milligrams and 80.
And our original phase II testing.
So we havent very competitive profile and a reminder, we are well ahead of the.
The competition.
And we have a first mover advantage over here by a substantial margin. So we'll get to really prepare the market shape the market and price the market.
Very helpful. Thank you.
Okay.
The next question will come from Sal <unk> with Goldman Sachs. Please go ahead.
Thanks for taking a question this is tommy on for solving.
Our question is on of one person in Polyneuropathy could you envision them sharing detailed functional data over time, such as <unk> plus seven trajectories at one one and half two years. So that people can see the the benefit that youre getting on these measures over time.
Thank you.
Yes so.
Thanks for your question we are.
Anticipating.
Providing a pretty thorough and wholesome update on all of the co primary and key secondary endpoints.
We look at our primary endpoint, we have 66 data.
Next year around mid next year.
As we said until that point.
The key results have been disclosed.
Obviously.
Not able to share additional details, but once a week.
<unk> 66 data become available.
Study results will be shared more broadly anymore.
<unk>.
Yes.
Expect.
To present that have that data by midyear next year and we will also prepare publication and presentation. So we very much look forward to sharing the full dataset.
The week 66 data at that time, when we have it when we have the data.
Thank you.
Okay.
The next question will come from your own Werber with Cowen. Please go ahead.
Hi, This is brendon on for Aram, Thanks for taking the questions quick ones from a firsthand.
Eriksson for Acromegaly I know you guys have so many things advanced and we can't wait to get to all of them here, but.
But just wanted to see what the latest thinking is for timing and presentation of that data and maybe whether youre targeting a medical meeting, but the release or not.
And then just quickly wanted to see if there are any new update on the Huntington's program with Roche neither on the timing or just the overall clinical plan with Temodar sitting there. Thanks.
So far the our acromegaly program.
We're still planning to review the data.
Safety data from the monotherapy data this year right Richard.
I don't know if were going to have the opportunity to present the data because the year is rapidly coming to a close certainly medical meeting gets out of the question. We'll see what we can do it's a relatively small phase II study, but probably not going to able to get to get that data out until next year.
But we're going to we'll try to get it out as quickly as we can.
For Huntington's Roche.
Roche has done a pretty good job of sharing a lot of data from the post hoc analysis recently.
<unk> is post hoc, but it's compelling.
Patients with less less disease burden, we're doing better.
And we're doing better with less frequent dosing of <unk> and they are also laid out the trial design right. Their phase II trial design pretty detailed the big studies as I recall.
Thank you Hey, Richard there's three cohorts.
About 120 patients per cohort two doses, one placebo is that right.
Right, yes, so its a big step it's a big study.
We haven't given timing on exact first patient dosed, but it's not far out there.
Alright, great. Thanks, very much guys.
The next question will come from Yale Jen with Laidlaw <unk> Company. Please go ahead.
Great. Thanks for taking the questions.
GSK as well as the Roche <unk>.
The program, Paul where two.
Two pivotal phase III study do we anticipate any milestone payment.
To give it to the company later this year already next year.
You were asking about the GSK HBV program yet.
Yes as well.
For the wrong by Roche.
The FTE in the property.
Yes, so on the milestones.
I think with the license fee and milestones we've already earned in the second and third quarter. This year.
We will be looking forward to regulatory approval milestones for that trend going forward and then potentially milestones as the.
Geographic atrophy study continues to advance.
With that same drag with the Sps.
Okay. That's very helpful. Maybe one more question here, which is for the ATT.
For the.
Premium resistant hypertension, you will have the data readout could we get a little bit more color on what to expect later this year.
Thanks.
Thanks, Joe.
We.
We have three studies in progress right.
The refractory hypertension with Gen. Two like a molecule. We also have the heart failure study Gen. Two bite molecule, which is which is still <unk>.
Process at both studies are in process and we have the gen two five and hypertension patients.
We're probably going to present the data we're going to pull all the data together and probably have a presentation in some form or another where announcements probably early next year. We want we really want to look at the full dataset.
Both indications as well as both drugs because the next question that we're going to get once we present. This data if we do it in pieces will be what are the next steps right and we don't know what the next steps will be but we look at all the data from two drugs in two indications so.
We'll certainly have completed at least one of those studies this year, but we'll probably which will all the studies are complete.
For getting the data out there.
Okay great.
Thanks, Neal and thanks, everybody.
Yes.
To close it out thank you.
Thanks, everybody for your for joining us participating on today's call. We're really really pleased with the quarterly results.
I'm very much looking forward to.
The rest of the year as well as moving into next year as well and continuing to provide you with updates on the progress we're making.
Again and have a great day.
The conference has now concluded. Thank you for attending today's presentation you may now disconnect.
[music].
Yes.