Q3 2020 Alnylam Pharmaceuticals Inc Earnings Call
<unk> revenue.
Delivering 24% growth versus Q2, primarily driven by increased patient demand.
As of September Thirtyth over 1100, 50 patients were on commercial on Petro treatment worldwide.
Turning to the U.S.
We saw notable increases in demand and new patients starting therapy.
Also with many patients now having successfully transitioned to alternate sites of care, including home care, we benefited from strong patient compliance, which also contributed to the rebound in revenues.
We continue to see progress with new prescribers in the us with cardiologists, making up more than half of new prescribing physicians in.
In the United States. We also continue to see a steady rate of concomitant use of on Petro with TTR stabilizers and expect this trend to continue to grow.
Turning to the rest of the World, we made very encouraging progress with on Petro in the third quarter with $43.5 million in revenues from ex us markets.
As noted last quarter, we have secured access and all priority markets in Western Europe, including Portugal, following our Q3 launch.
We're also pleased with the continued growth in Japan, a country of strength for on Petro.
An important dynamic you observed in ex US is patient switching to on Petrochem stabilizers for the potential to halt or reverse disease progression and AJ TTR patients with Polyneuropathy.
This dynamic represents greater than 50% of new on Petro patients outside the U.S.
Our medical Affairs team also remains committed to addressing the challenge of raising disease awareness and improving diagnosis rates of HIV TTR amyloidosis.
Including with Alnylam Act, our third party genetic screening initiative in the Us Canada and Brazil.
As of October greater than 30000 samples have been submitted out of which approximately 1800 have tested positive for a pathogenic TTR mutation.
We are encouraged by the recovery in Allomap genetic testing volumes, we've seen in recent months and we believe these volumes will continue into the fourth quarter.
Weve also seen continued recovery in the number of piece by piece cans conducted for detection of cardiac amyloid.
As you know ha TTR amyloidosis is a multi systemic disease and in the U.S. detection of cardiac amyloid is often the first step in an overall diagnosis of the disease as many of these patients also have polyneuropathy.
On Tatro continues to be recognized as a breakthrough for patients with AK TTR amyloidosis with Polyneuropathy and we're honored to have received the highly prestigious pre value in USA Award just last week.
Moving on to give Laurie we achieved a $16.7 million and global net product revenues in the quarter with over 150 patients now on commercial drug.
Our progress with patient accessing the U.S. has been strong having now finalized 10 value based agreements for VA days with us payers.
We currently have confirmed access for over 90% of covered us lives.
We have not experienced any payer headwinds would give laurie to date and we're pleased to see the majority of plans adopt medical policies without restrictions to the number of baseline attacks.
The CEMEA region saw great progress as well with a successful ongoing good Laurie launch in Germany, and named patient sales in other countries, including France.
We're off to a very strong start for market access in CEMEA and.
In France, we have Laurie received an improvement of medical benefit or a S. M. R score to concluding it offers significant additional therapeutic value.
Additionally, give already obtained a considerable added benefit grading, Germany with only 15% of all orphan drugs, achieving such a high rating.
And we secured a strong ha rating in Italy.
We're also excited to soon after launch underway in Canada. Following the recent approval and look forward to the completion of the ongoing review of our India, and Japan, which was submitted in September.
Finally, our commercial full affairs teams are prepared for the upcoming launch of Bucks Loulo. The brand name for do mass around with.
With a positive see HMP opinion in hand in the EU and an FDA PDUFA date, just weeks away on December Threerd, we look forward to soon bringing our third R&D therapeutics to patients around the world.
[noise] label for the treatment of cutting off the in both hereditary and wild type 80 timely doses patients to this end we've conducting the Apollo B phase three study.
We continue to enroll patients in Apollo B and continue to expect completion of enrollment in Twentytwenty, one due to impacts from the COVID-19 pandemic.
During Q3, we saw a pickup in the pace of enrollment and are still aiming to make up for lost time that we experienced during Q2 due to the pandemic.
We're also thrilled to received last month positive see HMP opinion recommending approval of Lemass ran into the treatment of ph one in all age groups Reece.
Recently, we presented full results from eliminate B study awfully mass friend pediatric patients lessons six years old.
In this study treatment lemass friend led to a 71% mean reduction and spot during oxalate craton ratio from baseline two months six this was the primary endpoint in the study.
Master and also demonstrated positive results across secondhand points, including 50% of patients that achieved during August late levels at or below 1.5 times, the upper limit of normal and.
The most common drug related adverse events with a mild and try an injection side reactions reported and 17% of patients.
Efficacy and safety profile awfully mass friend was consistent with that observed in adults and children six years older and illuminate a study.
And both illuminate a and B studies be continued seen causing evidence towards certain clinical events, such as network Calcinosis and regional stone events or Rsc's.
And eliminate a we previously reported on encouraging results with improvements in network Calcinosis. The next poetry endpoint.
At S. N. We showed some initial results from illuminate a an improved odyssey's with continued dosing base.
218 with interferon in a phase two study in patients with chronic hepatitis b infection.
We're very excited about the clinical data already presented for this molecule as a reminder, alnylams retain the right to opt into a 50 50 shaft program prior to the start of phase three.
Lastly, turning.
Turning now to a summary of our full PNM results for the quarter net.
Net revenue from collaborations for the third quarter was $26.6 million, primarily due to revenue recognized from our beer and regeneron collaborations.
Gross margin as a percentage of total revenue was 83% for the quarter down from 93% in Q3 2019, primarily due to the current utilization of on Pactual full cost inventory, while last year benefited from zero cost on Petro inventory.
As well as having a higher proportion of sales in the third quarter of 2020 coming from lower margin international markets and a write off of on Petro inventory at our contract manufacturer.
It happens in our guidance range for combined non-GAAP R&D SG&A expenses remain unchanged. However, we are expecting our combined non-GAAP R&D SG&A expenses the end of the year towards the upper end of our guidance range driven by an expected increase in queue for in both R&D expense as we continue to make good progress in advancing key click.
Stage programs and SG&A expense, primarily driven by increased spend in support of our planned launch a box limo.
Please note we have revised the midpoint of our gap combined R&D SG&A operating expense guidance range upward by 30 million, primarily reflecting an increase associated with a contingent liability related to arbitration with illness.
Operator, we will now open the call for questions to those dialed in we would like to ask you to limit yourself to one question each and then get back in the queue. If you have additional questions.
Okay.
Thank you if you would like to ask a question. Please press star one other telephone keypad.
We are using a speakerphone just make sure that your mute function is turned off slow your signal to reach our acquired with again that is star one to ask a question, we'll pause for just a brief moment hello, everyone an opportunity to signal for questions.
Two co that impact in Q4, we expect the growth to come primarily from net net new patient demand.
And I'll turn it over to Jeff here on the inventory side.
Yes, hi, everybody.
In terms of where we are in inventory gene at the end of the third quarter from Potrero were less than two weeks and based on the distribution agreements. We have that that range is typically in the one to three weeks right.
Range. So again, we're right maybe right in the middle of that at this point.
Okay, great. Thank you very much.
Thanks Dana.
We'll now take our next question.
Oh Pezim Abbott from Bank of America. Please go ahead your line is open.
Because I think it was that I cant isn't my question [noise] <unk>.
I'm looking at it.
I just have one estimation or we should expect to see one of the top line readout Kinda Humana. They study early next year.
And whenever that data does show should we have any reason to think that there would be read through into the population that you guys are spending a cardium my off at the end of Healios B study. Thanks.
Yeah, that's a great question to Jean and all that I'll, let oxaydo handle it let me just start by saying, we're very excited about which ran up because it is obviously you know that enable a once quarterly subcutaneous dose.
Dose administration at potentially with additional work, we believe that we can introduce a bi annual dosing regimen for patients with AJ TTR. Initially it will be for the Polyneuropathy setting with the Helio say study and then obviously with the focus will be in heliosphere, Cardium uppity, both hereditary and wild type.
So akshay do you want to comment specifically on PC and questions around what will be available at the top line and what potential read through there will be on on the cardium opposite from Healios a.
Your Ah can you is it possible that the day that would be in January or you know providing that level of granularity.
Yeah, we're not we're not gonna provide that level of granularity <unk>. Our early period is you know is Q1 or Q too, but I think it's gonna be early.
Okay. Thank you.
What I would take our next question from Paul tests from Seinfeld. Please go ahead.
Her name is open eight.
Alright, thanks, so much and congrats on record at two questions. One on nutritional in do you think you could bridge to the six months.
Just T T R data safety and if so what's the status of that clinical work and then second on the master in on the Wall Street side explication through this drug or materially lower than that of get votes around but I think some of the prevalence data.
H, one and two or three that you've outlined are not that dissimilar K H T. So do you think it boatswain as realistic analog for this thing it's or if not can you give any contacts tanks.
Primary function outcome of such an analysis. Thank you.
Great well I'm going to I'm going to have Oxaydo as answered the second part second question.
But regarding the regarding the the first question I'll, Let me just give a high level that Andy you can comment.
Look at a high level, it's our belief that the medical system.
Again, we eat this study is not orientated towards kind of myopathy. So I don't know exactly how many of those events would have a cat, but we'll certainly be sharing them in due course.
Right does that answer your question.
Yeah. Thank you.
Fantastic.
Moving on to our next question.
Alicia Young from Cantor Fitzgerald. Please go ahead Atlanta's open.
Great. Thanks that says I'm only on currently yeah. Thanks for taking my question it might have some of the recent contract and challenges and a T.
Okay, let's see how you're thinking about plans going forward, but that's my sense of iron AI and do you think that combinations, an American army I T as in Thomas.
Kind of a long range Bowl here.
So I'm I'm I'm not I'm not sure I.
Hurt you clearly on the first pocket Emily could you.
Repeat what area are you a common thing I specifically.
A T.
Especially thank you have a difficult time really incredible cause she just how over the years the distance come together and how you're treating patients so effectively bell.
My question that that there was recently and a lot of the others were answered but kind of what's the latest.
We haven't really talked about that one as much recently interest because there's been such a focus on the success what the other programs, but kind of how have you seen that market changed a little bit over the last year and where do you think that fits for <unk> for you guys calling for it. Thanks.
Yeah. Thanks, Thanks Tad. Thanks, Thanks for the first of all for the common.
Graduate Tori comments at the beginning but it on for two strikes specifically as you know this is partnered and as you mentioned this has partnered with atopy. It's an army at therapeutic of targets antithrombin with the goal of increasing I'm a generation to improve our hemostasis inpatient Smith hemophilia a.
[noise] hemophilia be with them without inhibitor. So it it it really isn't attractive target proud of profile that we constructed for the molecule. The the program is in phase three it's being led by sanity and you know we really rely on their continued execution of the program. So we we hope to learn more.
More in in the next period and so that's where it is but you know I think for the most part sad if he really has been the driver of the program and it's it's ultimately their call in terms of how they advance it I don't know akshay or of on anything else to add to that from your perspective.
I I think the anything on that as to the the hemophilia landscape. You know continues to need innovation. The adoption of him deeper shows that people are keen to find therapies other than multiple times, a week intravenous factor replacement and so I.
Alright, so I've got to Tucson, Hershey was a great home for advice and hemophilia N b with and without inhibitors uhm, but as John set you know fantasy Wood Wood guide you. So the progress with the program.
Yeah, great. Thanks, and can you just from under strict commercial interest there. Thanks guys.
Yeah. So we have is very important point. So so we have reciprocal we have royalties off the to surround that range from 15% to 30%. It's here to sales. So we have we do have a significant attractive financial interest in in the product success no question about it.
Well you know the target H S. B doesn't circulate in the blood so like a lot of our programs, we won't have direct by them all day too.
The target itself, but there are a number of other downstream in fact that we're looking at in terms of my mom because we believe will be highly informative Lucia Moore on that as the the program progressive in the study progressed as next year and ultimately I think what guys always deliver in the Nash patients will be of great importance bye bye chemically as well as radiological and we'll shove.
That.
The materials.
Yeah, I'll, just I'll just add to that I'll, just add to that that that you know we also have our upcoming R&D day in December and that'll be an opportunity for us to do more of a deep dive on V. H S T opportunity and and the political plans for that program, but it is an exciting program because it is a genetically validated target.
For for Nash, and we think it obviously hold great promise in that important indication.
Thanks to.
And they'll take our next question from.
Murray Raycroft from Jeffries. Please go ahead.
Is open.
Hi, everyone. The morning does that sound of progress and thanks for taking my question Uhm first one is also on a L. M. A G. T program for the data and next week I'm just wondering if you're gonna have some data from the additional exploratory cohorts, including the obese patients has all control cohort and.
Ah combo called his wall and if not I guess, what's the latest status with those cohorts, how how meaningful all day and then uhm, what our next steps with the program.
[noise] APTP when can you expect like data there.
Yeah, Thanks, Sonia well I'm I'm glad to get a question like this and I'm sure Akshay is as well you know let me just say at the start and remind everybody that one of the exciting breakthroughs that we achieved over the last couple of years is the delivery the efficient then and and highly.
The durable delivery of Arnie I therapeutics to the CNS and other tissues as well, including the API and more recently the long. So we are obviously quite.
Excited about that because it opens up you know.
New prospects for our pipeline growth outside of the liver.
And in the setting of the CNS itself of course, it is really an opportunity to go after the many many neurodegenerative diseases that are caused by gain of function.
Mutations or gain of function expression of proteins in the CNS.
With a dose regiment that we think interest equally can be given once every six months if not less frequently. So it is it is a great opportunity for the company and we're partnered with Regeneron on a 50 50 basis in that regard I actually do you want to specifically talk about ATP on the next steps.
Yeah. So speaking of Regeneron that APTP is great at the.
The problem with US we'll be taking the program would that mean to phase one next year, we continue to guide to.
Will enter phase when the middle next year also.
And you know sort of guidance on on when we'll actually see data.
We'll be given once weve got any without phase one study and the other thing is because it is a very interesting time data can you map review ongoing and there's a lot of excitement around what those data showing so be missing CV outcome, a ban on Friday, but.
But we continue to believe in a P.T. as a very important target for Alzheimer's disease, and beyond and not only can we task so they pay.
Pay the deposits, we believe in the extra settlement space, but to attaching to a target outsource and turning off the top so to speak and all the intra erodible effects of.
Hey, Beta will also be impacted so we think this could have a really significant contribution to play so excited to games phase one next year and we'll update on base expectations off.
And if I do you want to comment a little bit on that thank you. Yeah. It's about you want to comment a little bit on how this works within our regeneron relationship. It's a v., our lead et cetera that might be useful context.
Yeah, No. That's that's great I'm really delighted that some regenerative opted in we're actually going to be leading the programming and we're very excited about that and obviously you know the shabby economics with regeneron, but some were very excited to be leading the CNS program out to bomb that's my problem.
Good.
And we'll take our next question comes.
So Alan Carr from Needham <unk> Company. Please go ahead.
Hi, Thanks for taking my questions I'm getting.
Can you give a more detailed around the your calls the candidate well.
Well exactly where things stand with well what can you do around that I'm kind of curious about where things stand and where you were looking at.
Other candidates to another targets around that 19 can you give us an email.
Comprehensive update around that program yeah.
Yeah happy to Alan and let me start and then Akshay you can you can comment as well yeah. We're work we continue to be committed to advancing our cobot program. Obviously, there's the opportunity of targeting the Sars koby to genome, which is an art.
[noise] genome directly with an already out there pick is is is is certainly inappropriate.
Thing to do from a technology perspective at our recent advances in lung delivery.
Obviously have come just in time to help us help us advance this program.
We've done some work into searing hamster model, which is an established model for Sars koby to infection and we have seen a antiviral activity in in the model specifically and we're encouraged by that but we want to do more model work before we commit to specific.
I'd timing and specific clinical development plans. So that we can understand the best place to position this molecule in the context of the emerging therapies.
For the treatment of a of COVID-19.
And you know we're going to play the long game on this program as it relates to how we could play into.
You know the management of COVID-19 in the future, which we think will there will be an opportunity longer term.
For for therapies, just like it was for disease like flu, but that's how we're thinking about it and those are the specific results and we look forward to presenting those at some point in the future akshay anything to add to that.
No I think you covered it John.
Actually right.
Right all right. Thanks for taking my questions and congratulations on the progress.
Thanks Alan.
[noise] [laughter] well now take our next question from Paul.
Patrick to kill.
Hey, C. Wainwright. Please go ahead your line is open.
Thanks, Hi, Good morning, you know with the understanding that the closure in the U.S. election, maybe it may take some time I'm wondering if you can comment how a potential change in the administration [noise].
Could impact health care policy, and what impact if any that could have on islands R&D or commercial execution in the U.S. and 2021 and beyond.
Okay, great. So yeah, obviously it it you know we are hoping that there is a completion and clarity on on the election here in the coming coming days are coming weeks and months.
I think it's it's great to see our democracy, you know going through the process of counting counting all the votes, which is the way democracies.
Need to work and so it's great to see that happening.
And we certainly stand standby to sort of see how it emerges overall, but I think that regardless of the outcome, whether trop or or bought in get elected.
You know, we believe that there's going to be a dialogue it continue to be a dialogue around drug.
Drug pricing.
Politically.
But I think that Alnylam is very well positioned in that dialogue because of the type of innovation that we consistently deliver from our from our platform and I think you know the type of medicine. So we bring forward the type of ways that we've engaged with payers around you know sharing of sharing of risk and.
And obviously delivery a valuable ultimately these.
These are the type of approaches that we think will will will bode well for continued success and continued ability to get the value of our innovation recognize bye bye.
By governments and payers around the world I'm. So we do think that you know we're in a good position to regardless of the outcome, regardless of the policies that emerge to be able to continue to do what's right for patients first and foremost.
Obviously deliver on the value of that from a more platforms. So we think we're in a good place Patrick on the overall, but we certainly have been active in helping different stakeholders. In this discussion and we will remain active as a as a company in this discussion.
But we we are generally optimistic and yes, maybe there will be some changes that the comp that that occur, but we think we're very well equipped to to do well through through all of that.
That's helpful. Thank you very much.
Thanks, Patrick.
Well now take our next question from Yeah, Leland Gershell from open Haywood. Please go ahead.
Hey, good morning, Thanks for taking my questions and I see no. Other his comments on the on its own occasions, just a question on the reimbursement progress where consumer now.
Having been through that period or discussions with others on the floor. We recently just want to ask if you have any comments on any differences you're seeing in their progress and if we would expect it to be pretty quickly on pace with where you were who are good Laurie as you as you execute on to something else.
Yeah. That's that's a great great question Leyland, let me just start by saying.
How I'm proud I am of our access teams around the world with the great job they've done with our Petro a the great job. They are doing right now with give Laurie.
And you know right now we have over 30.
Just about actually just about 30, but value based agreements that we've signed with commercial payers in the U.S. and we continue to work you know with with with in global markets very effectively with the payer stakeholders and we've shown a lot of we've demonstrated and brought a lot of innovation forward on these on D.C.B.A.S both the.
General structure of them, then I'll be share risk around performance of the product.
But also on some of the new.
New features that we've introduced like the prevalence based just a model that will be introduced on on on give Laurie so with that as context, Andy do you want to get more specific on obviously low and and obviously, we can't share all the details that will share when we launched the product, but maybe you can give some context on how our discussions are going.
Yeah sure sure so similar to on Petro and give lorries, we will and are pursuing an aggressive value based agenda with all payers globally and feedback from early days on that Sun has been exceptionally positive. So we expect similar results in terms of open access for actually more as we as we had with the block.
Again, I'm, Patrick would really really strong so.
We will continue our industry leadership here.
Yeah. Thanks, Andy Thank you.
Moving on to our next question comes from money for all Huh.
Spivak. Please go ahead your line is open.
Hi, Thanks for taking the questions guys. A quick one I guess starting on for Jeff I'm kind of little about increasing compliance as a driver of our magic performance I presume some of that is from patient hesitant to come in for their eyes need during the height of the pandemic.
Has that compliance trend to reverse the entirely or there's still a little bit excuse.
Next quarter and beyond.
And then for Akshay Akshay, there's been a lot of talk about what Healios age. How this about healios be I'm inclined to agree that maybe Apollo. He is the more useful lead forward. Just can you give us a little bit on how you think about taking the optional healios be interim is Islam is the most.
<unk> approach to wait until you have Apollo be data to inform that.
Or do you think that just data that you've got it on a blinded basis from healios be itself.
The study proceeds will provide you the information to you to decide if and when to take that interim.
Okay. Those are great. Those are two great questions. Many why don't we why don't we start with Jeff and then we'll have Akshay talk about the the Carty b as we call them collectively strategically and and how that relates to the interim so Jeff you want to start first on the compliance question.
And.
Yeah sure. So just a reminder on on the results that Andy commented on earlier and I did as well. We we grew 21% in Q3 in the U.S. front Pachou versus Q2, 14% in that was demand related and that was a mix of new patients coming on to therapy and the IND.
Creased compliance that we saw in Q3 and that returned in the U.S. to pre pandemic levels money. So I don't see no, but sort of a big in pack and hold that on growth going forward and just a reminder, outside the U.S. We didn't see the same impact on on compliance in Q2 that we saw in the U.S. so outside the u.
You asked the health care system seem to do a better job of maintaining patients on therapy and compliance wasn't impacted so again I don't see a big impact of increased compliance going forward on our growth rates.
And just before I hand, it over to Akshay I would just add that the site of care adjustments that we made in Q2 have have I think bolstered any potential downside of pandemic resurgence the third wave that might happen to the U.S. et cetera. So I think that we're very we're better sheltered in Q.
For beyond two you know not if things get much worse did not have any significant impact from what we saw like in Q2.
Akshay do you want to know handle the more complicated.
Complicated, but interesting question that many has asked.
Would love to do.
The question Manny you know focused on a polar b and the read through to Healios B and I agreed that that's a very important aspect to the work we're doing and insights we clean that will be very important for us.
I would also say that you know continue work with patients from Apollo itself from nuclear and extension study gives us important insights into long term outcomes on neuropsych and caught him up see we've.
We've had a number of studies on being out in the field and don't forget them. All from the UK grew just published a paper in Jack imaging on a reversal.
Oh amyloid deposition.
In teach out how democracy patients so the inherited type.
And I think that's just something important and then we continue to work groups like not to understand what they're seeing and the outcomes that dosing puts clinically and ready logically.
He'll does he will say as we discussed earlier.
To your point, it's not as Richard they've set for democracy, but then there could be some employee information there and.
And then a polar be itself and and I I think.
Ultimately, we'll just have to see on the timings of Oh, all these data points on how they factor in and as we get greater insight into the Apollo be read out I think we can decide on what the exact he must be in trend will be.
And use all these points of information to guide that but I think where we were fortunate because there's so much to teach us about what to expect ultimately something you'll see in that should lead to a very soon and structure around the interim.
Yeah, absolutely agree does that answer your question many.
Yeah. That's great. Thanks, guys also Carter you would have been a great trial, Manchukuo dot noise [laughter] agree [laughter].
Thanks, guys.
Well now take it thank you.
Well take our next question from Navon Chico from <unk>. Please go ahead.
Hi, everyone. This is John on for Kevin. Thank you for taking our question. So with respect you've alluded to covert recovery across geographies and were insurance coverage has caused any shift in payer mix for your assets get blurry, an untapped channels are also curious as to how.
As to which analog might be better for us as we prepare for the Ocs Lumos launch would it be more like kids Lora, you went a bit more medicaid or perhaps more like on Petro any color would be appreciated.
Well those are great questions I'm going to hand them right over to Andy to answer.
[laughter]. Thanks.
So let's start with the first ones or changes in payer mix, specifically in the United States, We're seeing little to no changes in payer mix. Remember then on Petro is the vast majority Medicare I mean at this point in time cutlery is you know pretty early days here, but largely commercial and we're not seeing any any material.
Rule changes to those due to profit.
And then the second question with Ox Pneumo in terms of payer mix analog I'm actually neither are perfect, but over the two it's certainly going to be less of a Medicare population right. We think talk to him. It was more of a commercial and door on Medicaid insurance. One so that's I guess, a little bit more similar to.
Good Laurie if that helps.
Certainly thank you.
Sure. Thank you.
And moving on to our next question comes from Vincent Chen.
Vern seemed. Please go ahead your line is open.
Okay. Thanks, Thanks for taking the question well, probably a little far out but going over to the CNS side of things for me when I say that before so your latest thoughts on the L. in H.T.T. in Huntingtons and how that might offer advantages over competitive programs. This space, most notably Roche sounds as someone there are some.
Other reasons to expect the airline hcg and B S. I learn a lot from the CNS will outperform the erosion in this program from the perspective of.
Degree of knockdown achieved leap.
Brett who already the ultimate ultimately the efficacy.
So let me, let me hand, it over to auction <unk>. Thanks for the question Vincent I'll, just start by saying that obviously the the what we've seen with our platform in the CNS has been pretty consistent with what we've seen in the platform with liver and when you compare a minority.
Therapeutic approach in liver compared to an antisense oligo based approach what you see is you see deeper better knockdown and much greater durability in the liver, we've seen that all the way through marketed products.
And we see similar profiles in non human primates between antisense, Oligos and ER and Arnie I therapeutics. So by all accounts, we expect.
A deeper knockdown potential with with our platform and a much more durable approach that would allow for less frequent Intrathecal administration, which of course is a important or is it is a burden in the in the administration of Allah goes into CNS, but there's some more to that there's more to the A.C.T.
Opportunity that will lead to oxaydo to comment on specifically on X on one okay.
Yeah, and you're probably gonna take someone joking or add to what you said in terms of Splunk logic attributes show potency durability of course, but also just much better distribution. It's not preclinical findings, we think that the Ani approach is much better than old kind of deeper brain structures like the Oh.
During their which is very easy to get to fulfil or something that was predominantly.
The those homes logic attributes and then does the took the actual target strategy itself and you know, there's an abundance of mixture now or or significant mix, just suggesting that excellent want it so he.
As a very important role to play in the pathology of the disease and the truncates transcripts that can affect someone.
It appears you know themselves to be you know toxic and that are approaching I guess I'm, a little pitching aid from the truncated exome and transferred that aggregates includes pathology. So you know going for an x. someone agnostic approach may not be the strongest and we focused on the mix on one approach so.
Oh, we can have the best approach the target publix, or Conversely would support and which I also cool and that along with some closing actually as we've discussed I think really sets us up for a very attractive product profile look towards getting to the clinic.
Thank you.
Does that answer your question Vincent.
Yes, thank you very much.
Thank you. Thank you.
Well now take our next question comes from Luca.
From RBC. Please go ahead.
Terrific. Thanks for taking my question and congrats on the commercial execution here I'm, just going back to car he be for a second but maybe with a little bit more of a commercial angle here I'm using it actually a poll they'd be would be sufficient for Dr change their prescribing habits from Dekalb to Potrero.
What do you think the most dock will actually need to wait for Sealy us be given that again apologies just power for six minutes walking are still dealing with the Ivy drugs any thoughts there would be helpful. Maybe second question. We've seen a few of your competitors actually going after he snacks for cystic fibrosis wondering if one you have any thoughts on that approach and to watch.
Your appetite to potentially entered that race. Thank you.
Okay, well well great questions I think obviously the first one Andy I'd like you to answer I'll just start by reminding everybody that obviously you know the Apollo B study is a study of the T. SRAM, which is a non branded name for a for a petro which is an investigational agent right now.
No and it's in being studied in patients with both wild type and hereditary TTR amyloidosis with Cardium apathy and that input that study uses the six minute walk distance as the primary endpoint at 12 months and then and then the Helios B study with Patrice Rad uses the uses CB hospitalization mortality as the primary endpoint.
<unk> 30 months to treat that and Ah. So there that that's an important distinction, but in general and then Andy you should comment we do feel very I'm encouraged that if Apollo b is positive and if.
We're able to get an approval with the FDA based on the study.
The other regulators that this would be a very attractive alternative for the cardiology community to treat their patients with both hereditary and wild type.
TTR and while the while the ultimate presentation of a TTR silence or with a quarterly or six monthly subcu approach will be you know certainly much more exciting in the future in the meantime, our petro with his broader label will be an important treatment option for.
Patients Andy do you want to comment a little bit on on or perspective on that more in more detail.
Sure John Happy too so.
We're very excited about the Apollo be potential here and the launch into hereditary and wild type Cardium apathy to note in the United States. Today Cardiologists are currently having very strong experience with on Petro I'm in treating the polyneuropathy and upon.
An approval, we do expect a meaningful amount of physicians to choose a TTR silence or versus the stabilizer and Furthermore, there also will be physicians, who don't decide to choose and frankly, they use both and so reimbursement will be a little something will be proactively looking to solve on that side.
So as well.
Terrific and then okay do you or maybe evolved do you want to comment a little bit on from a portfolio standpoint, how we think about programs and in that for example, and is that.
And whether or not that's an area that we would consider.
Yeah, I'm not sure John look I think I think what's been incredible about Tom platform is actually they kind of productivity that we had and you know we went well increase to be demonstrating our ability to access tissues. In addition to the liver CNS and not color and many of you may be aware that some you know I'm not inside of him.
Street.
With lung to Liberty as well with you know an RSV program. Many years ago. So we have a tremendous amount of opportunity in front of us and you know Katie we need to think how we prioritize the best opportunities for Oh, we have a lot on our plate subset to move forward from an execution perspective.
But you know we remain open about considering to explore the the poor do you put a t. as a platform going forward, but but nothing to shop, specifically on cystic fibrosis at this time.
So one thing I didn't hear it no.
No no I don't know Akshay anything you want to add to that.
No I mean part of the you know Alan Cole good assets, obviously lung deliveries come front and center, we have about preliminary dataset about a year ago now showing we've achieved long delivery, which is very exciting and you know just as we've done with many of the settings.
An old guns.
I'd of genetically validated targets comes into the mix and we have knowledge of you know a number of very interesting genetically validated targets do you own.
Americans so some cystic fibrosis. So it's really the new best assuming before us than they will be exciting to take you know beyond because enough itself.
Great terrific. Thanks, guys. Thanks.
Thanks Luca.
We will now take our next question from Shang Shu. Please go ahead.
Your line is open thank you very much.
Thank you very much good morning, congrats on the strong quarter here claims.
A quick question on.
Just around I guess Apollo be have you guys looked at any I guess clinical or translational data in terms of the correlation between baseline disease severity and the potential response to the drug no six minutes walk or hospitalization hybrid car.
On the <unk>.
Yeah.
Stabilize it actually has a.
Different trend to win win comes defined patient population and then second question quickly on HGTV program.
Given the drive to a beach potentially target a large population patient population I think I started.
So how do you think about partnership opportunity there.
Thank you.
Right well, let me start with let me just actually you should take the Apollo the very interesting Apollo B question, but let me let me just on the AG Ti.
Comment real quickly our our intent with the H.T. program is to advance it to the market. You know, we certainly are a company that as we.
Bring a medicine like agency forward, we're going to have an opportunity to to you know at that stage of our growth and company to commercialize medicine like that if we and at that point in the future choose to bring on a promotional partner we may do they do that.
But our key goals is to retain the program and develop it ourselves and that's how we're focused on it and Ah. So that's that's that's what we're doing there, but actually do you want to answer the Apollo the question that was asked.
Sure actually John if I can just come in really quickly on the point you made I think the other thing to remember it was off sort of you know TTR suite of opportunities we are actually building out.
You know a favorite bust commercial footprints in the cardiovascular arena, it's not something else that we can consider as we as we plan on AG team Yeah, Yeah, absolutely agree completely thanks for thanks for jumping in on that Saddam Akshay do you want US then you will get a policy change.
<unk> good question about a pull it be now of course is an ongoing blinded study so we don't.
You know.
Sort of look at little bit <unk>, Oh, currently and that that's as it should be to maintain study integrity side I can comment on.
You know relationships to embarrass parameters.
I can tell you that.
You know that there aren't very good associations between Neocart Association, the stage and six minute walk distance.
We know that from from current work hours on other People's work.
And we know how that relates to garner amount because such as BNP and none of the imaging pharma because you know in terms of the other answer to your question was outcomes with or without tried so some of this and they are we kind of looked at older information from a polar itself. The original study from Israel.
<unk> for the Phase three study and what was very clear that actually is whether patients who had previously been on a stabilized or whether it was to five missiles, Iceland as a whole has never been on stabilizing their outcome wants equivalent and that is on average then I missed a seven year old standpoint improve the quality of life.
Food. So that's that's very encouraging for us, but our mechanism of action seems to be present and loved it wasn't a head to head study everything pointed to you know perhaps are really having a profound impact resulting in improvement of disease in the context of being pulled this study.
And we believe that's one of the very attractive feature of the drug.
You know, we know from to five minutes from the phase three attract study that was clearly there was a benefit in terms of hospitalization mortality. He always test went down is just because the performance didn't go down as much as it did so placebo, which is a good thing for patients, but sadly disease progress is clear.
Clearly chevron when you looked at including six minute walk distance and you know walk distance declined over time in the active group as opposed to see but.
So if we can stabilize six minute walk distance I think that's great. If we can actually improve six minute walk distance even better. The recently published study by the.
Just doesn't go more in orders from the Sacred and Jack imaging, where they took a cohort of coded maps. The patients that were given to trend at one year comparing to sorry control they sort of stabilization.
Oh six minute walk distance, there and regression of amyloid something is neither of those things are busy with their families up till now so you know.
We think the fundamental mechanism action to remove the constant it protein to a great extent.
How come the neuropathy that we know well.
And so some of the preliminary evidence emerging around uncoated biopsy and use them on pump trend investigational study suggests that.
We look forward to stabilizing disease, hopefully improving outcomes.
Thank you very much changes that does that answer your question.
Yes, thanks very much thank you.
Thank you.
I just have a little bit I would like to turn the conference back to the company for any additional or closing remarks.
Okay. Thank you and thanks, everyone for joining us on this call look El Nio them. It's a very exciting stage of its continued growth and development as a leading biotech we're really pleased with our Q3 results and our execution from our commercial and R&D teams. We look forward to updating you on our continued progress at our R&D day in December.
Her until then I hope you all stay safe and healthy and have a great day Bye bye now.