Q3 2023 Alnylam Pharmaceuticals Inc Earnings Call
Good day and thank you for standing by welcome to the in Ireland Pharmaceuticals, Q3, 2023 earnings Conference call.
At this time participants are in a listen only mode. After the speaker's presentation there'll be a question and answer session.
Please be advised that today's conference is being recorded.
I would now like to hand, the conference call over to the company.
Good morning, I'm, Christine <unk> senior Vice President of Investor Relations and corporate communications that on an island with me today are are on Green Street, Chief Executive Officer until the Taylor commercial lobster Physical Guard Chief Medical Officer, <unk>, Chief Financial Officer.
For those of you participating via conference calls the accompanying files can be accessed by going to the events section of the investors page of our website investor's Dot on island Dot Com slash events.
Today's call is out.
Two one will offer introductory remarks bright general contact.
Oh that will provide an update on our global commercial progress.
Quick overview pipeline updates and clinical progress.
Just to review our financial some guidance followed by summary, according milestones before we open the call to your question.
I would like to remind you that today's call will contain remark concerning an island feature expectations plans and prospect, which constitute forward looking statements for the purposes of the safe Harbor provision under the private Securities Litigation Reform Act of 1995.
Actual results may differ materially from those indicated by these forward looking statements as a result of various important factor, including those discussed in our most recent periodically report on file with the S. A C.
In addition, any sport that can statements represent our views only have the date of this recording it should not be relied upon as representing our views as if any subsequent date.
Typically disclaim any obligation to update such statements with that I'd like to turn the call over and it was on <unk>.
Thanks, Christine and thank you everyone for joining the call today.
In the third quarter of 2023, we continue to make great progress across our business.
Experiencing at this appointment.
He announced the.
The U S food and drug administration declined to approve the supplemental new drug application for <unk>.
An investigation.
Therapeutic there within development for the treatment of the cardiomyopathy of a T T R amyloidosis.
We have conveyed we are extremely disappointed with this outcome, particularly with regard to the needs of patients many of whom spoke at the Advisory Committee meeting in September.
We have been steadfastly committed to this on the phone.
<unk> and <unk>.
The main comforter and it's been a long term strategy to building a leading T T. All French fries with with Theresa and but he gets piece study describing as a very important for the next step in this journey.
We look forward to sharing the top line results, which remain on track for the 2024.
As we continue to progress all plans and teeth in ATT, all cardiomyopathy, a commercial strength in the third quarter was driven by the ongoing successful launch of <unk> in patients with hereditary a T. T. R amyloidosis would probably be welcomed.
This contributed to a 35 per cent yeah, it'll be a growth in total net product revenues compared to the third quarter of 2022.
We also collaborates important clinical updates from key pipeline programs in the third quarter.
September we announced positive topline results.
Cardio one phase two dose ranging study <unk>.
Which demonstrates that greater than 15 millimeters of Mercury reduction.
Pollack blood pressure at three months of treatment compared to placebo.
Is it encouraging safety and Tolerability profile in adult patients with mild to moderate hypertension.
Additionally, the results also reflects a sustained reductions as the stomach blood pressure a six month.
The potential for quarterly or biannual Thursday.
We also share the updated positive results from the phase one study of a L. M. A P. P. In patients with early onset Alzheimer's disease, we should record and robust targets engagement with sustained affects out to 10 months with a single dose Anthony encouraging clinical safety until.
But the profile.
Additionally, we presented to is it going to be a part of this study <unk>. It's H F. S. A showing that the effects with the police were on treatment on six minute walks aspirin Casey C. Q what maintains through 24 months of treatment.
This type of relative stabilization and what is otherwise a steadily progressive disease is very encouraging.
Both with a confidence in periods b.
We're thrilled to have had this was published in the New England Journal of Medicine, just a few weeks ago, which was accompanied by a favorable editorial highlighting the step forward represented by army or therapy six if this disease.
Lastly, we're excited to have achieved a third grade <unk> science magazines top employer survey the 2023.
<unk> that are not I'm was featured as one of the top three companies in that annual survey of industry professionals.
Boys to deliver a couple more pipeline updates by the end of the year, including top lines Craig's one results for a O M. T. T. R. S. C O for its whereas N K H K, our investigation will army like therapeutic the type two diabetes.
And I encourage you to save the day you can see it into our annual R&D date, which will be held virtually on December the 13th where we will discuss all of the exciting progress across our pipeline and platform.
We believe all of this purchase on track with our modern piece of fish by 25 calls, making <unk> developing and commercializing transformative medicines of patients around the world with rare diseases and beyond driven by a high yielding pipeline of first Andrew best in cloud support our candidates.
From our organic product answered all while delivering exceptional financial results.
With that let me now turn the call over to Tolga for review bar commercial performance toga.
Thanks for your call and good morning, everyone.
Q3 was another strong quarter for our commercial portfolio.
Both are two TR franchise, driven by another robust quarter of what's your performance in the U S market.
And our ultra rare franchise delivering growth in excess of 30 per cent compared with the prior year.
Continue to steadily increase the number of patients on all of our therapies.
Told him that product revenues route 35% year over year for the third quarter or 33 per cent at a constant exchange rate.
Let me now turn to a summary of our third quarter Ctr performance.
R. T T R franchise achieved $230 million in global net product revenues on petrovietnam bookshop represented get three per cent increase compared with the second chord Sir.
35 per cent growth compared with the third quarter of 2022.
At the end of the third quarter more than 30 790 patients were on commercial on petrol all of them, which are treatments worldwide upfront over 3400 90 patients at the end of the second quarter, representing 8% quarterly patient growth.
Now, let me provide highlights so far U S and international Ctr performance.
In the U S combined sales of petrol and what's your increased by 11% compared with the second quarter and a robust 47% year over year, driven by what's yours launch.
The U S growth was primarily driven by the following.
It's six per cent increase in demand, which was driven by the strength of ongoing which are patient uptake more than offsetting a decrease in on Patrick patients that switched <unk>.
At the end of the third quarter more than 80% of all the item Usdt occupations are now on a workshop at positive side, indicating how well the product profile has been received by both prescribing physicians and patients.
In addition to the demand growth reported growth was also favorably impacted by approximately 5% due to an increase in on what's your inventory and the distribution channels.
Now, let me turn to our international markets, where TCR franchise growth decreased by seven per cent compared with the second quarter.
Although there was growth in patients on terror for you during the quarter. This growth was offset by a variety of factors.
<unk> price adjustments in Germany. Following the end of the six months free pricing period.
Inventory Destocking in Japan.
And the timing of orders in emerging and partner markets.
It is worth noting that we have now launched <unk> in all major international markets. Following recent launches in Spain and Italy.
I'm proud of the effort so far market access team as we have made on which are available to patients and security reimbursements significantly faster that industry the X box.
Now moving to our ultra rare products and the performance of <unk>, which delivered $83 million and combined product sales during the third quarter, representing a 1% increase compared with the second quarter and it's solid 33 per cent growth compared with the third quarter of.
2000 2022.
We ended the quarter with more than 1000 patients on our two alternative products and exciting milestone with more than 625 patients I'll give lori commercial therapy add more than 375 patients on <unk> commercial therapy.
Representing 8% combined quarterly growth in patients on our alternative products compared with the second quarter 2023.
Forgive Laurie product sales declines six per cent in Q3, compared with the second quarter with the following regional dynamics.
Five per cent increase in demand in the U S market driven by an increase in patients on therapy.
At 25% decrease in our international markets.
By this time in golf orders in in Orange again partner markets, whereas with previously indicated.
Two two results benefited from a large order and higher gross to net deductions.
Four of <unk>, we delivered a robust 19% increase in product sales compared with the second quarter, which was driven by the following.
At 10% increase in the U S driven by 16% demand growth.
Partially offset by a reduction of inventory and the distribution channel at 23% increase in our international markets.
Driven by increased demand and the timing of orders are emerging and partner markets.
We were pleased with the results in the quarter, particularly strong patient broke with both of our T. T R and alter their franchises delivering an 8% increase in patients on therapy during the closer as well as delivering robust year over year growth in revenues with both franchises Grove.
Going in excess of 30%.
As we look ahead to the end of the year, we anticipate a strong fourthquarter positioning us to the end of the year at the approximate mid point of our net product revenue guidance range.
With that I will now turn it over to push call to review, our recent R&D and pipeline progress.
Cough.
Thanks, Tolga and good morning, everyone let.
Let me start with our TCR franchise as you know we have two products approved for the Polyneuropathy of hereditary ATT or Emily doses Tatro.
<unk> and <unk>, we've also been pursuing expansion into a T. G. R cardiomyopathy through two large studies Apollo.
Apollo B for <unk> and Helio speak for <unk>.
As previously announced while Apollo be delivered positive results not just on the primary endpoint, but consistently across additional secondary and exploratory endpoints as well all with a positive safety profile <unk>.
P. A declined to approve the S N da for <unk>, citing insufficient evidence of clinical meaningful us.
As a result of this decision and with the top line read out from Helios be expected in early 2024, we have elected not to invest further into additional development to secure approval for <unk> and ATT or cardiomyopathy in the United States.
A positive data on multiple aspects of ATT or cardiomyopathy coming out of the Apollo B study reaffirm our confidence and success appeal Yospe.
In particular, the 24 month data show that both six minute walk test and Casey C Q relatively stable over the entire period.
In contrast to the large expected decline expected in this disease and suggests the potential that RNA and I immediately tcr's silencing may result, in a differentiated efficacy profile and this disease.
Heliotherapy study is designed empowered to demonstrate a benefit of <unk> patients very similar to those studied in the <unk>.
The composite outcome of all cause mortality and recurrent cardiovascular events over a 30% to 36 month period.
The study is on track to read out in early 2024, and assuming positive data. We then plan to seek a label expansion <unk> and if approved ultimately launch that medicine into the growing market of patients around the world with wild type or hereditary ATT or Emily doses with cardiomyopathy.
We believe that the convenient quarterly subcutaneous dosing regimen with a therapeutic profile that includes cardiovascular outcomes data in its label could.
Could potentially position <unk> as a transformative therapy with a market leading profile for patients with this disease.
Moving on following announcement of initial human proof of concept data on Alan a P. P. R. First Ernie I therapeutic designed for CNS delivery, which is in development for the treatment of Alzheimer's disease and cerebral amyloid Angiopathy. We're excited by the positive results. We've seen from the phase one study to date.
At the clinical trials on Alzheimer's disease Conference a few weeks ago, we presented additional positive interim results from the phase one study in patients with early onset Alzheimer's disease.
The time of this interim look 20 patients had been enrolled in three single dose cohort and part of the ongoing phase one study.
To date, we've studied three dose levels 25, 50, and 75 milligrams with four to six patients dose in each cohort.
Excitingly Ellen E. P. P treatment resulted in rapid dose dependent and sustained reductions both soluble AVP alpha and beta.
Markers of target engagement in the CSM.
We saw rapid knock down as early as 815 and observed peak mean reduction of 69, and 82% respectively for Seibel, APB Alpha and valuable APB beta.
Reduction was sustained for the main reduction of 33 and 39% respectively for.
For soluble AVP Alpha and beta 10 months after single 75 milligram dose.
We also presented clinical data that for the first time showed marked reductions.
<unk> 42, and a beta 40, the soluble forms of the Emily Dot <unk> peptide that aggregate into amyloid deposits in Alzheimer's disease in Caa.
Specifically at two months after a single dose of 75 milligrams of alien AVP mean reductions of CSS, Amy 42, and 40 or 49 and 71% respectively.
These peptides are directly implicated in disease pathogenesis. These findings are encouraging as I suggested treatment with an army and I therapeutic can potentially interrupt relentless progression of these two devastating diseases.
The safety of single doses of Alan AVP has been encouraging as well all adverse events were mild or moderate severity and CSF parameters have not revealed any significant abnormality today.
Further exploration of single doses avail, an a P. P is ongoing and party. In addition, part b. The multiple dose part of this study has been initiated in Canada and has now also received all required approval to proceed in the United Kingdom, and the Netherlands Mulch.
Multiple dose part of the study remains on partial clinical hold in the United States do to findings observed in Pryor Nonclinical chronic toxicology studies.
In some I'm thrilled about these impressive human data showing the potential for on and I, just started disease, causing transcription the CNS and look forward to providing additional program updates in the future.
Let me now turn to recent progress was <unk> and development for the treatment of hypertension.
We're very excited to have reported positive topline results from the cardio one phase two dose ranging study.
And Cardi, one <unk> met the primary endpoint demonstrating a dose dependent clinically significant reduction in 24 hour mean systolic blood pressure measured by ambulatory blood pressure monitoring it month three.
Shaving a placebo subtracted reduction greater than 15 millimeters of Mercury with both 300 milligrams and 600 milligram doses.
The study also met Keith secondary endpoints, including significant change in 24 hour mean systolic blood pressure is measured by a b pm that months six.
As well as significant change in office sit down blood pressure at months, three and six for all of that will be sent arms compared to placebo.
The study results indicate there'll be San was associated with dose dependent potent and durable knockdown of CRA G. T levels three months six <unk>.
Importantly, so I'll be saran demonstrated encouraging safety and Tolerability profile.
We look forward to sharing complete results for party won at the upcoming H a scientific sessions. This month and we remain on track to deliver topline results from the cardio to phase two combination studied <unk> in early 2024.
Before I wrap up I'd like to briefly update on one of our partners programs for two strength, which is in development for the treatment of hemophilia, a or b with or without inhibitors.
Santa Fe, just reported encouraging safety and efficacy data for the antithrombin based dosing regimen and a phase III study and indicated they are currently in discussions with the FDA.
Regarding filing an NDA in 2024.
These are just a few highlights from abroad and innovative pipeline driven by our underlying organic product engine that we expect will deliver sustainable innovation and represents a key growth driver per hour an island in the years to come.
With that let me now turn it over to Jeff to review, our financial results in upcoming milestones Jeff.
Thanks pushed call and good morning, everyone I'm pleased to be presenting a summary of elm items Q3, 2023 financial results and discussing our full year guidance.
Starting with a summary of our P&L results for Q3 2023.
Total product revenue for the quarter were $313 million or 35% growth versus Q3 2022.
Told the previously mentioned the increase was driven by strong growth from our GTR, an ultra rare franchises with both reporting growth greater than 30% during the quarter compared with the prior year.
Ah report results in the quarter benefited modestly from foreign exchange is constant exchange rate product sales growth was two per cent lower at 33 per cent.
Net revenue from collaborations for the third quarter was $427 million, representing nearly a $400 million increase from Q3 2022.
Primarily due to increases in revenue from our resolve these saran co development and co commercialization collaboration will gross.
Which included full recognition of the $310 million upfront payment received in the third quarter.
As well as $65 million in revenue in connection with our Regeneron collaboration.
$65 million represents the portion of revenue recognized from a 100 million dollar milestone earned from achieving certain criteria during early clinical development for our CNS program.
A P P.
Royalty revenue during the quarter was $10 million, which was driven by Novartis a sales of <unk>, which continued to increase following launch in the U S and the first quarter of 2022.
Gross margin on product sales was 75 per cent in Q3, representing a 10% decrease compared with the third quarter of 2022, primarily due to Q3 right off on Petro inventory that had been manufactured for future demand associated with the a T. T R cardiomyopathy indication for <unk> for what.
We did not receive regulatory approval.
Recall that I mentioned on our Unpacks wrote CRM Investor call on October 9th that we expect on petrol demand a decrease on a go forward basis as <unk> continues to cannibalize existing Unpacks wrote Polyneuropathy business and markets, where <unk> has launched.
As a result for 2024, we anticipate on petrol product sales will be in the 200 to 225 million dollar range.
A non-GAAP R&D expenses increased 16% in the third quarter compared to the same period in 2022, primarily due to higher costs related to clinical activities and increased head count the support our R&D pipeline and an expense for achievement of certain milestones payable to a partner.
Or non-GAAP SG&A expenses increased 2% in the third quarter compared to the same period in 2022, primarily due to increased head count and other investments supporting our strategic growth, including the global launch of <unk>.
For the first time in Q3, we generated non-GAAP operating profit during the quarter equal to $278 million driven by the significant revenue recognized during the quarter from our collaborations with Roshan Regeneron.
We anticipate that in future quarters, we will revert to a non-GAAP operating loss as we have not yet achieved sustainable profitability.
Finally, we ended the quarter with cash cash equivalents and marketable securities of $2.4 billion compared to 2.2 billion at the end of 2022 with the increased primarily related to the $310 million upfront payment from Roche.
Set by our operating last year to date.
We continue to believe our current cash balances sufficient to bridges to a self sustainable financial profile.
Now I'd like to turn to our full year 2023 financial guidance we.
We are increasing our collaboration royalty revenue guidance from $100 million to $175 million to $575 million to $625 million.
Substantial increases primarily attributable to two factors that were not included in our previous guidance.
First recognition of the full $310 million upfront payment received from Roche in the third quarter in conjunction with the <unk> collaboration.
I would also like to note that our accounting conclusions associated with the rose collaboration are summarized on slide 27 in the appendix of today's presentation.
And secondly achievement of the $100 million Aline ACP milestone from Regeneron during the third quarter.
Majority of which will be recognized as revenue during 2023.
All other elements of our 2023 financial guidance remained unchanged.
Let me now turn from financials and discuss some key goals in the upcoming milestones slated for the remainder of 2023.
We will of course be executing on global commercialization of our products on petrol and Blue Trust give Lori <unk> limo.
We intend to report topline results from Phase one studies of <unk> and development for the treatment of ACP are amyloidosis, and al Encage K and development for the treatment of type two diabetes.
With our partner programs Veer expects to report further results from Phase II combination trials of Allen HBV O two and development for the treatment of chronic hepatitis b.
Let me now turn it back to Christine to coordinate our Q&A session Christine Thanks.
Thank you, Jeff Operator will now open the call for your questions to the Taliban we'd like to ask you to let me look up to one question each and then get back in the queue. If you have additional questions.
Thank you at this time, we will conduct a question and answer session. As a reminder to ask a question you'll need to press star one one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one one again, please stand by while we compile the Q&A roster.
Our first question comes from <unk> of T. D. Cohen. Your line is now open.
Good morning, guys. Thanks for taking the question I wanted to ask a little bit about the helium B statistical <unk>.
Sorry, the statistical plan I understand that you're using.
The Anderson killed method mmm.
Which are statistical consultant any <unk> any kind of C. D. And then would be analyzed since a recurring event and and would count and at first is what has been used by other developers where they had ranks they had to rank sense within this anderson.
<unk> R a Z.
Types in the composite weighted equally or are certain events.
<unk> hospitalization waited more uhm such that the analysis, maybe more meaningful to to doctors for serious events and regulators as well. Thank you.
Thanks for its own good morning kind of a great question is you know.
The focused on delivering a successful PSP study and feel confident just given a track record in the air and all the.
Studies that we've delivered that have been costs up to date.
Regards to your specific question around and how we're thinking about specifics <unk>, maybe you could provider.
Two perspectives.
Yeah. Thanks for it to look I think there's lots of ways that people look at these types of data.
As you mentioned our focus is really on Ah definitely current hospitalizations.
And both are Finkelstein schoenfeld, and and Anderson can do that I think one of the unique aspects of the study. So we've done to sort of increase in maximize power is actually have differential follow up for patients. So we'll follow up that can range from 30 to 36 months.
And the Anderson Gil allows us to actually incorporate that that variable follow up whereas in the finkelstein schoenfeld.
That's followed passed to sort of be aligned to.
To the lowest common denominator, so it actually gives us some additional power.
That's why our statisticians and our team is.
Prioritize that in the statistical analysis plan, so certainly if we.
AIDS deaths, but we look at all of those deaths into hospitalization events just about three current events that you talked about it. So we think that's really optimize the power for the study.
Great. Thank you.
Thank you and one moment for our next question.
<unk> Ah Stefan your line is now open.
Great. Thanks, so much for taking the question I appreciate it.
We've been trying to think about what if any learning there are from the recent advisory Committee Yospe, we fully understand right that is generating outcomes data, but issues with the policy be at the F. D. A level are related to a lack of that to some extent that said I was curious if you think from a regulatory perspective, it's important that.
You show some level of added outcomes benefit on top of Tafamidis and mysterious that he's not really powered for a key value, but how would you kind of delineate what the line is on a clinically meaningful effect in the combo therapy subset of Yoyo state. Thanks, so much.
That's probably a question Sir.
<unk> yeah. Thanks, Paul look I think maybe a couple of points.
As reflected previously obviously, we're disappointed in the decision that was made but as we look at the.
Apollo B results with regard to tap in non tab.
The add on task was very small group moly 91 patient study wasn't designed to characterize that subgroup, but we are encouraged him. When we looked at the data that were presented at the AD communists at various congresses that the outcomes data in both groups actually are trending favorably for the <unk> arm and that bodes well.
For Helio speed.
The other point I would just make around that is that we.
We have an experienced now in that study was we've mentioned that we targeted operationally about 50 per cent of patients we've come in somewhat less than that which certainly adds in the overall powering of the study.
While we over enrolled as well by 10% <unk>.
I think with regard to the add on fat factor that you were mentioning from a regulatory perspective, I think one of the points that probably is worth noting is that at.
That point was was was raised in particular, because <unk> has has a mortality claim and what Apollo be with <unk> was coming forward with was with a functional claim in terms of six minute walk Beth and Casey C. Q and so that raises questions about how these drugs are going to be used in combination or in sequence et cetera.
In contrast is you've just highlighted USB is going to deliver outcomes results and so that issue becomes much less of an issue. The other point is that we have a much larger experienced in this study and much longer follow up so I do think that we're gonna be able to look at the consistency of effect across both the mono therapy and the base.
<unk> group and that's really what we'll be focusing on when you look at that subgroup as well as a number of other subgroups in this study.
Excellent. Thank you <unk>. Thank.
Thank you.
Thank you and one moment for our next question.
Alright next question comes from Luca E. C. F. R. B C. Your line is now open.
Oh, great. Thanks for taking our questions. This is Lisa <unk> I just wanted to touch base on Helios E is it possible that you all have a N T. P. B M P and text minute locked test as part of the accomplice at primary and plant you obviously have Sean Thomas.
Results from both of those I'm, calling from the policy and and that way. If the elevator you would have the primary endpoint that ended up replicating page bio. So you couldn't get you use that as a regulatory precedent.
Take your conversation with a broken arm and Stockbridge.
Would that be fair way to think about it uhm any color that would be much appreciated. Thanks.
Thanks, Lisa your question look I think.
What you're pointing out in raising is the fact that when we looked at the Apollo B data, we did see really pretty much every endpoint lining up in favor of teach are lowering whether it was functional like six minute Bob test your quality of life echocardiographic parameters and biomarkers like anti appropriate P.
And so I appreciate the point that you're raising and and certainly is Yvonne highlighted where laser focused on delivering a successful study we're very confident in the overall design of the study the execution of this study.
To your point about the bridge by our results I think they point to the fact that in the modern era.
But this is still a progressive disease, despite patients being caught earlier and their disease process and then and then an effective therapy can show a benefit on top of that and so in that setting so.
We're overall really encouraged by what the study is and how it's designing out and as we've mentioned laser focused on this if there are any tweaks adjustments that he makes the statistical analysis plan will follow up in due course.
Alright.
Thanks.
Thank you one moment sorry next question.
Ellie morale of UBS. Your line is now open.
Hey, guys. Thanks, so much for taking my question, just again kind of on the potential of our company said just commercially how are you thinking about the proportion at atti cardiomyopathy patience that and will be treated with mono therapy versus say a combination with the <unk>.
<unk> and then just from a commercial perspective, what do you think parents want to see in terms of the benefit as a treat to add on top of.
In terms of mortality hospitalization anything coming out at.
Any kind of initial conversations back and then just a quick question what data can we expect from the <unk> K data does here.
<unk> included late last year.
Alright, So maybe we'll we'll we'll take your first question.
We believe that I'm pretty sure is getting theory important option for patients with a potential threat differentiate your profile give it it's infrequent administration.
Minimal co pays uhm and if you look at the progressive toga highlighted earlier with respect to the growth in patient demand for <unk> patients poly neuropathy.
We believe that this is going to be a really important.
Addition to the treatments Allen Terrace.
Physicians talk or maybe you could speak specifically to how we're thinking about.
Alright, you spell Sir.
Yeah, I mean, I think one of the points that we really we need to make it clear as innovation really rules. The day in <unk> has been a game changed it already pulling neuropathy and I believe we believe very strongly based on our research on which was available and cardiomyopathy is going to be important, especially if you look at our track records.
And price sensitive markets, where actually <unk> is available.
In Europe for <unk>, we've been able to actually build an attractive business tablets versus infusion tablets versus then subcutaneous and be able to build a business not just by net patients, but also with switches 90 U S, which is similar to sort of the the profile that you.
Eluded to in terms of how we would actually think about in combination.
Is our business is already built about with the <unk> with the with the mixed ferrotype patients about 30 per cent of our patients already logged onto fabulous granted where indicated for Colorado apathy.
Antifeminist has now indicated for for cardiomyopathy.
Where obviously for us to be able to really elucidate how the positioning is gonna work out we need to helio speed data, that's gonna be a really important and that will obviously inform the best way, we got a position to send the best way, we're gonna engage with the with the with the payers, but again just to give you a sense about.
The unmet medical need if you look at the early access program that we have we've already being able to enroll 200 patients.
Because patients do progress and we believe this is gonna be an important alternative.
Thanks Soccer.
That was kind of great Sir with respect to your final question about K. It's K well, obviously, you know I'm trying to avoid taking a multipart question to Nicole to give everybody a chance to uhm ask the question in respect to K, It's K.
Look forward to seeing more data as prescribed.
<unk> at the end of the year.
Next question please.
Thank you one moment for our next question.
Our next question comes from David Leibowitz City. Your line is now open.
Thank you very much for taking my question you spoke earlier about talking to heal Yospe can.
Allow for a very differentiated profile versus the other therapies in the space.
And my question is regarding Somerset linked to some of the earlier questions.
Given the trial differences they have different populations with different levels of severity their hair and points are slightly different from each other with slightly modified statistical analysis.
Easier as it can be to actually demonstrate to physicians that a profile is actually differentiated and what aspects of the data would you focus upon.
So I think maybe you can start off.
You know maybe also reflecting on some of the day so within a ready for <unk> for 24 months later that Sir.
<unk> actually sort of stabilization Sir this is <unk>.
Medications, yeah, absolutely thanks, Ivan and thanks for your question look I think.
Your <unk>.
Important knowledge first of all there aren't any head to head data in this field right. So what we're looking at though is a field that's evolving fairly rapidly right with because of the growing recognition of the unmet need and you have to bear.
Benefit of patients multiple therapies coming forth and you are right to point out that everyone is using you know there are some variations for example in the way that end points and statistical analysis done.
But I think what you have to do is think about it from the way the clinician thinks about it when they step back and they looked at a patients coming in and.
They are progressing with this the present with this disease at various stages.
Marked by Disney up by exercise foot fatigue poor quality of life and you are seeing a decline over time, they're echocardiographic parameters are worsening their hardest thickening, they're anti probie N. P is rising they may develop arrhythmia is et cetera, and that's what clinicians are looking at and when they look at clinical.
Data I think what they're looking at then is I believe is looking at all of the data that are coming forward in terms of how is this drug power. These various drugs affecting the disease process.
And I think.
While I was alluding to I think what we're starting to see coming out of Apollo B.
Really indicates the potential.
For a very unique profile when you silence T. T. R upstream using an RNA mechanism of action, where we are seeing really favorable effects across all of these different parameters that we've looked at whether it's functional quality of life, whether it's echocardiographic, whether it's biomarker base and that.
In a disease, that's otherwise steadily progressive to see stability Alpha two years on both six minute walk test and Casey C. Q.
Stands out.
And I think that's what's quite remarkable so look I think over time as clinicians will get experienced and I think this is again where conditions are having experiences toga highlighted it within <unk>, both on <unk> and now I'm <unk> for now many years taken care of Pn patients phenotype patients I think they're also getting a <unk>.
<unk> <unk> <unk>.
The efficacy profile the Tolerability to safety profile. These medicine, so all of that.
Helps I think in terms of physicians understanding of how to use medicines for their patients.
Great. Thank you <unk> alright pressure.
Thank you one moment for our next question.
Oh.
Our next question comes from solving rector of Goldman Sachs. Your line is now open.
Thanks for taking our question. This is Tommy on for solving so on E. S. P. How similar do you expect to your policy and he'll ask the patient populations to be in terms of genotype and baseline characteristics in the <unk>.
I see him at the higher cap on Helios P for baseline task you sorry are there any other notable differences.
Do you have the flexibility to potentially pushback top line data from hearing S. P until all patients Getcha 36 months of follow up if that was seen as necessary. Thank you.
Great question. Thank you that's cool yeah, Tammy I think what I'd say is that in general I would think about a patient populations in Apollo b and he'll yospe as being fairly similar right. There. We started these studies around the same time the entry criteria in general are the same.
As you talked about the one exception is that we allowed for a higher baseline.
Proportion of patients to come in on on to fan minutes, but by and large I would think about these similar and I think that's you know again what helps US here is the fact that we've seen the positive results out of Apollo be across all the different measures that we've talked about this study has the benefit of being you know twice as large and three times as long to follow.
As you know is designed to allow for differential follow up and really to maximize the.
The follow up that we have on the patients. So I think that is was asked earlier as well I think this really <unk>.
Maximize or optimize the power that we can sort of game on some of the endpoint. So we're looking forward to presenting the results are in early 2004.
Thank you and one moment for my next question.
Jessica I F. G. P. M changed your line is now open.
Hey, guys. This is <unk> on for Jessica Fi.
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Assuming he kneeled B is <unk> you have a.
Vision does that price of advil for changing from the current poly neuropathy.
I'll just call me on my opposite.
Why or why not thank you.
Alright, so it's pretty early days yet.
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And add a 2024 and unlimited at this point in time.
Think it's appropriate to make any specific comments about pricing other than to say obviously.
Once by <unk>, Sir patients physicians that mucus, it's the magenta according to our.
A patient access principles. So I think that's that's about all we can say it.
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Thank you and one moment for the next question.
Yeah.
Murray right craft I've Jeffries your line is now open.
Hi, Good morning. Thank you for taking my question I think it was mentioned on a recent conference call that you have the opportunity to make tweaks to the Helios B statistical.
Alex's plan up until the database locks.
Can you elaborate more on what that could entail would it require FDA by N and how this flexibility factors into your chances of success for Helio speed.
Yeah I know that's.
Great question, Uhm Prisco any comments you'd like to make them. The restaurant, Yeah, Maria I think I'm gonna probably three.
<unk>, what we've talked about previously which is it's.
Our teams are looking obviously a data in the study were looking at external datasets et cetera N. As is normal in the industry has been known practice here on an island.
There are two weeks that can be made and.
In past instances, we've looked and changed from parametric to nonparametric statistical tests et cetera, we've added subgroups et cetera. So there are things that that can be done that can help either the primary analysis or the overall data set that are being done in terms of maybe you know in terms of pre specified analysis methodologies that are applied.
Yeah, I'm not going to speculate or hypothesize about what's going to be aligned with agencies or not so I think but you know if there's material information there will certainly share that with you in due course.
Thank you next question.
My next question.
Okay, just one moment.
<unk> at Barclays. Your line is now open.
Thank you maybe just follow Alright, alright question. So are you planning to add see any additional follow up time flexibility regarding because right now when I look at your slides to Saint.
<unk> follow up each month 30, and do you have the flexibility and willingness of plan to extend to 36 months and then I had a very quick question regarding <unk> just wanted to make sure I heard correctly prescribed I think that you've mentioned 50 per cent of the patient baseline.
<unk> was that correct or was a close to 50 per cent and it also regarding the <unk>.
<unk> four 2% is a good benchmark Fortunately no fee.
Yeah. Thanks, Gina maybe a couple of points just to clarify so look in terms of the study design. The study design has variable follow up 30 to 36 months.
And so we will be following the majority of the patients out to 36 months because of the way that enrollment occurred.
But there is variable follow up in the context of the study.
Blinded portion of the study.
In terms of baseline <unk>, we had an operational target a 50%, but as we have stated previously we came in under that.
Under that number and.
And then with regard to drop ins what.
What we've said is that the dropping rate remains below.
The assumptions that we had when we design. The study so again all of these offer tailwinds in terms of what we believe in the overall powering of this study.
So hopefully that helps.
Okay great.
Any other.
Questions.
Yes. We are next question give me one moment.
Our next question comes from Mike off of Morgan Stanley. Your line is time open.
Good morning, and thanks for taking the question maybe just another follow up on Chelios B. When you share. The data early next year can you give us a sense of what level of detail and data that you will include in the top line results. For example, what we see that the feminist combo subgroup analysis.
Thanks.
Yeah. Thanks for the question, Mike look I think as as our norm during a topline results. We will present, the pre specified hierarchical and points along with P values, along with an update on safety and then with subsequent data presented at a scientific Congress.
Great.
Next question.
This concludes the question and answer session I'd like to now turn it back to the company for closing remarks.
Great. Thank you everyone for joining us on this call. We're very pleased with our progress in the third 2023 across the business and we look forward to sharing will progress with you in the coming months. So if we could have an uncle's. Thank you very much and have a good day.
Okay.
Thank you for your participation in today's conference. This does conclude the program you may now disconnect.
Mmm.
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