Q2 2019 Earnings Call
Hi, Please go ahead.
Thanks, So much for taking my question I have one and a follow up if I may 1st in the past when you've described the blinded safety looks you've always mention that it's tracking at least as favorable as the data from phase two and I noticed today Youve added on language to include its tracking at least as favorable as data from phase two and the Orion Phase three open label extension studies should we be reading into that that youve expanded the scope of what you were referencing as.
What it's tracking a favorable relative to that's one and the second one is maybe one for mark when when it says no material safety issues, how should we think about that as we are heading into the press release. Thank you very much.
Hey, what is this a theater and so when we announced the alliance waivers helps we we made it.
A clear in our in our disclosure that there was also seen in alliance. We are consistent with it will be seen in Hawaii and one just for the longer term follow up will hold up to three years. So I don't think you need to read anything more than that at this is consistent from a wine one two and three and what we're seeing and blinded review of two phase three program.
Oh that handle for the the safety no material safety issues as well Peter.
Straightforward yeah, it's sort of the same things we have established the safety profile in phase two.
Oh I am one of its now extended out to three years with Hawaiian three.
Again, we look at the blinded safety information from Phase three so you look at the aggregate event rates that you see there and again, we are consistent with what we have seen in Hawaii and one of the line three.
And what is sort of expected with the background of the cardiovascular disease and these patients have so thats whats the fine no material safety as we said before.
Got it thank you very much and good luck into the press release.
Thanks, Jim.
Our next question Mr. Joseph Schwartz from Leerink. Please go ahead.
Good morning, I appreciate you taking my questions insisted on dialing in for Joe So.
One question and one follow up for me as well just based on our conversations with investors. Other several recurring questions I wanted to get your take so first question is on your prior call in Miami held with Dr. Doncaster line.
I remember you, saying he predicted about 54% LDL reduction on day 510, and the consequent improvement in many ways.
So since Ryan for data on expected for several more years and we're expecting a sequential date on third quarter wondering what is the lower bar in your view on the LDL reduction that could materialize and what is it from the Cana wells that they would like to see as a bare minimum and as a follow up were still hearing investors' cautious on the Tcs canine markets. So can you frame for us based on either commercial pcsknine monoclonal sales or your own market research that.
Mark you alluded to in your prepared remarks, what is the industry's appetite for six monthly subcu drug liking inquests ramp. Thanks.
Thanks, Sarah and I'll, let Peter handle the first part and then I'll I'll continue with the second.
Yes, Thanks, Joe So if you go back to the alliance Threed data that we presented at analyst day.
This is sort of a combined with the line three six years three years of follow up and up to six doses open Glenn.
Given in individual patients and what was striking of the line three data one we got consistently more than 50% of LDL C reductions.
And to the LDL C response was identical or consistent every single time, you gave him closer.
So we anticipate that consistency is maintained.
Over the long term in the population that we had an alliance we had on average 60 milligrams per deciliter absolute reduction in LDL C. Because it's different by the baseline that this particular population had but that this disorder. The number that you have to keep in mind. If you want to extrapolate that to what you could expect in an outcome studies in the long term.
If I can Oh I'll cover the.
The couple of questions, which are more around the commercial impact when you think about.
I'm sort of the lower bar certainly our in our research we presented a profile which is.
50% or greater.
And I'll make a market research in terms of LDL C lowering.
That is being received extremely positively however, it's much more around the whole profile, where where are we getting feedback.
The twice a year dosing actually putting the control back into the hands of the physician is coming across is very very positive.
And I think this speaks to the second part of your question around the six month dosing.
The beauty of this and what we're hearing in the research is that these high risque ASCVD patients.
Saying that their health care practitioners twice a year routinely in the majority of them anyway.
And we're seeing that as very positive not only for the physician.
Again, who feels that they've got to control and also giving a purpose for the visit.
But its sort of guarantees their adherence, but also for the patient.
They feeling a reassurance that they know they've got LDL C lowering on board.
As they try to achieve these treatment goals also.
Great. Thanks for taking my questions and good luck.
Thank you.
Our next question is from Jessica Fye from Jpmorgan. Please go ahead.
Great. Good morning, Thanks for taking my question Theyre building, a little bit on the last topic.
I know you can't comment on any ongoing discussions or strategic interests, but can you just give us a sense of the types of players who could be interested in owning this asset and what specific attributes been close ran you think they might find attractive whether it be the revenue potential potential Cogs advantage.
Et cetera, just sort of hoping you could get us give us a sense of whether you think there could be a competitive process to own this asset.
Hi, Jessica.
Thanks for the question up obviously I can't comment on any sort of speculation.
As you know we've we've always said that we would seek to have strategic optionality and flexibility in whatever we're doing and obviously, having a range of options is very important to us.
What what we can say is that if you look at the profile.
And if you think about the profile of Inclisiran that is going to give you potency durability.
Sort of that consistent lowering of LDL C.
Then you have on top of that the fact that Youre also going to put the control back into the hands of the healthcare practitioner, which will help.
Well, certainly with adherents and obviously the reduction in the amount of times that you have to take this medication.
You start to get a very different different profile.
Coupled with that you will it was starting to have conversations which have very different with payers that I've experienced before around in LDL C lowering medication, where they're starting to look at specific patient types in groups of populations.
Which is being.
You know quite this is this is why we talk about it being game changing because they are starting to consider is.
In around day, the discussion turns to population health very quickly.
So I mean, you are probably answered the question yourself.
Is he gave you examples you've got a differentiated profile you have got a very attractive cogs.
And so therefore, you have got the flexibility in how you position they certainly from patient affordability.
It's it's very very exciting for I would imagine a range of companies.
Great. Thank you and maybe just one follow up on just the cadence of news flow. We can think about it over the back half of the year. So based on the projected completion of these phase three trials do you anticipate all three of them will be presented at conferences by yearend or is it possible we might have to wait until HCC for example to see some of the data details.
Hi, Jessica this is Peter again as we have stated the first one will be presented at AMC and the second one following nine and 10 as you remember enrollment was finished in a short time span of the three started six weeks.
Earlier last year, we anticipate those results to come out sort of the same sequence in roughly about the same time span. So there would be ready for a major conferences later in the year.
Obviously, we will have to go through the process of except abstract submission and acceptance. So that's the part we don't know yet.
Great. Thank you.
Our next question is from Joel Beatty from Citi. Please go ahead.
Hi, Thanks for taking the question. The first one is on the topline data from the first trial reading out.
Let's see if there are any potential for topline data to come on that sometime before you see and then the second follow up question is can you discuss.
Where are you currently a in terms of hiring for commercialization and any plan on that.
To wrap that up in the near term. Thanks.
Hey, you too much to handle timing.
Yes, yes I can.
To answer the first part of your question Joel as we said in the in the call earlier as well as previously we will report topline data from the three studies as they come available to us. So also align 11 will become available. This was before he has c. So we will do a top line announcement prior to easy, but fooled results will be done disclosed as you see in the late breaking scientific session on Monday September the second.
With regards to Joe Joe. Thanks for the question with regards to commercialization planning whereabouts, you know really six seven months into it now.
Everything that's ongoing is as you would expect in a normal.
Pharma company were doing extensive work around.
Research when doing extensive work around the scientific platform.
It really is pre commercialization.
We're very early in that process.
And it's all going to plan and it's and as I said.
On the call were very very excited about what's coming back in terms of our.
Our research and its really affirming the competitive profile that we have for in cluster I'm very excited.
Great. Thank you.
Our next question is from Chris Shibutani from Cowen and company. Please go ahead.
Great. Thank you very much two questions. If I may on the outcome study I think you mentioned that there was potential for a range of enrollment completion in one or two years can you comment on what the rate limiting factors are for that and then number two you discuss some of the feedback that you have from payers us Europe and Japan.
Can you comment about what kind of assumptions the payers were contemplating from a pricing standpoint, and is well how they thought about the potential for patients using inclisiran, either new to therapy versus the possibility of benefit of switching over patients on monoclonals, which may be more.
Priced higher.
If you could comment on the considerations that went into the thinking of the payers that you've been discussing with that'd be helpful.
Great. Thanks, Chris I'll, let Peter will talk to you about the outcomes and they'll take the commercial questions.
Yes, Thanks, Chris. So you you probably remember that align to four is being conducted in two countries the UK and the U.S.
We're using a streamlined approach to two in the two conducting this study.
As average they are using pre screening methodologies to identify patients.
Potentially eligible for the study and then they will be going to the trial sites to be screened and ultimately if fulfilling the inclusion and exclusion criteria that will be involved in into the study and then follow up for the duration of the study.
So there's no typical or any different rate limiting factors that you would have in any of these types of trial. It it comes down to identifying the sites, which we have already done activating them and then having the patients come to the schedule visits for the screening procedures and if selected positively than can be enrolled and treated in this study.
So fairly standard and Thats why we based the one to two years open enrollment period on.
Thanks, Peter and with regards to the commercial question with regards to pay as Chris.
Is it said we've secured the input from senior decision makers that health plans health systems in the U.S.
The European top five countries and also in Japan.
Strong general agreement among payers in several important areas that supporting cluster and strong value proposition.
For patients who do require this additional lift but lowering therapy.
I can.
I can say that.
Whilst we do not at this stage, it's very early we do not disclose any pricing.
The pay is a very receptive to our focus on patient affordability.
And all of our teams really to create that environment that responsibly response supports access.
To all the patients who can benefit from Inclisiran.
With regard to the types of patients that that.
We would be targeting all and again very early.
In our work.
However, the early feedback is very clear to us that suggests that includes sirona is essentially its a new new product and the new class and will be a market of one.
It's a highly differentiated and very clear to us that we should not just be positioned.
With regards to the monoclonal antibodies.
And that the opportunity is much greater.
Great. Thank you.
Our next question here is how much do Kumar from Robert W. Baird. Please go ahead.
Yeah. Thanks for taking our questions. So we're just curious in kind of a big picture perspective.
What do you think oligo manufacturing capacity it looks like now and over the next two years, so recognizing that maybe a long term cogs benefit pretty close right.
Do you think kind of manufacturing capacity for all of your jokes like includes Iran is often not for that kinda like first few years of a potentially because around lunch.
Yes, I do this this is mark thanks for the question.
We've obviously, we buy third quarter, we will have our commercial scale in place we've got a very strong partnership in place with agile and.
We've obviously got very clear plans and pathway to our initial launch and then two two subs subsequent scaling.
We believe we've we've got.
Sufficient access and a runway for.
Large numbers of patients, which we believe will be applicable.
Two.
To have access for Inclisiran.
We've we've focused very clearly on a on a target number of patients.
In the very early years, which we would like to gain access to.
And with that we've got.
Contracts and assurances and a brand new site, which is just opened for enrollment in Frederick Colorado, which essentially will be dedicated to to our manufacturing.
But to do that and would that kind of target number you envision stayed within the ballpark of where surpass and probably wait are selling today or is it because it could be larger than that I mean, obviously give hard numbers, but kind of what are you thinking as an initial target number for the current rounds of manufacturing capacity.
Yes, let let let let me answer that similarly to the way I answered Chriss question, it's very clear in the feedback that.
We've got a very differentiated profile lending plus around we will be seen as a market of one.
Therefore, our our numbers in terms of manufacturing capacity, a substantially different as to what you would see with with the antibodies.
Okay. Thank you.
Our next question is from Paul Troy from Goldman Sachs. Please go ahead.
Great. Good morning, and thank you for taking our questions.
Recognizing that the political landscape is shifting almost on a daily basis here could you maybe comment on how you're thinking about potential on theoretical or exposure to opt to Medicare, particularly in part B exposure.
As you think about the U.S.
Dispensing prescribing within the physician office going forward and just how you're thinking about sort of sort of pricing buckets for that particular population.
Yes. Thanks, Thanks for the question Paul I mean look obviously, a very a very sensitive area and there is lots of moving parts in this space at the moment.
That.
The beauty for explicit around it is it's going to be a applicable for a range of different types of reimbursement and access.
That provides us with tremendous tremendous flexibility.
However, I would say for us it's very early.
First to be thinking about all of the changes that are taking place.
In DC at the moment as you know many of these will not come to fruition and some will.
We're working very closely with policy advisors down in DC and sort of keeping track of the changes that would affect in plus around.
But it's very early for us to be able to to actually say anything since we really were 18 months for launch and do you have a high degree of flexibility to anticipate and respond to those changes.
That's the beauty of being a a one product.
Company, we can position that.
In however way we want.
As as those changes unfold.
Great. Thanks for that and then as a follow up can you maybe just confirm for us.
Either on the clinical or non clinical side, whether you have any other outstanding CMC or manufacturing validation.
Processors or tests, you need to do before you estimate your anda filing.
Peter.
And as we said before so obviously, we will have a full.
And the a file which includes manufacturing and non clinical activities, including the Validations you refer to he said before for the program to complete two Nd a the clinical program is on critical parts not to CMC, but not Nonclinical Park. So were on track for.
For the totality of the NDA for submission by the EPS for the FDA by the end of the year and for the M&A for Europe in Q1 of 2020.
Great Thanks for that and good luck.
Thank you I suppose.
Our next question is from Yasmeen, how many from Roth Capital Partners. Please go ahead.
Hi seem odd two questions to your question one is for Peter Peter We know that the Orion 11 study.
At 12, and a half patients at high risk acquired one how do you think they're trying to stability will be with that you won from the old Ryan 11 data to arrive on time and then the follow up is congrats on getting eaten into the European Society of Cardiology meeting for your presentation on why it's so critical that you needed to really secure a presentation at that time.
Deadline for age a police barricades August 14th so should we expect that to be all data potentially at the upcoming H.C. meeting and then what is sort of the feedback you're getting from physicians there are different between U.S. safe position like European and thank you for taking the question.
Oh, Okay, let me start with your your Middle question.
All they say, Hey, say, yes, you're correct. The after Dec line is all good for 14, so were working.
Towards the abstract submissions in a similar way that we did that for full year see but as I said before it's dependent on whether the FX will be accepted by the review committee of the society's whether we will be able to present the data at the conferences later in the year I can't comment on that specifically.
He is C is a is the first one after we have.
The first study read out as we have noted this close.
We felt it was important to to present the results as early as possible as they come known to US. That's why we executed the plan in that particular way.
And with respect to your first question.
So those regulatory guidance, both from from actually and from Europe with respect to the various populations.
As has been done in previous liquid loading development programs, we essentially followed that cadence and therefore, we did the study in the wine 11 in Europe , but the two populations as CVD an assay for the whiskey equivalent because they have essentially the same risk.
Of of cardiovascular risk and subsequent events to that so both populations are important.
And then to US the guidance is more focused on air CVD, Hence we did a entirely dedicated as CVD study in the U.S. its standard procedures that we followed here.
We executing accordingly, and we will make the submissions to regulators in the same standard way.
Hi, as mean, let me sort of.
Touching on some of that first question and then I'll go to the second part of your question I will just say as Peter said it I've been highly consistent since I came into the company that I would like to get this data are out as quickly as possible.
That that our objective is not changed this is very important data for a very high risk group of patients and the sooner we can communicate that the better.
I would say and in terms of research that we're seeing across the U.S. as.
Compared to the EU and the rest of the world. The only subtle difference that we're really saying only this high consistency about the differentiated profile high consistency about the value of twice your dosing physician administered health care practitioner administered on also the adherence benefits.
Coupled with the juror ability the ability to stay low over that six month period that that is sort of garnering it the feedbacks coming back of confidence of reassurance, it's very very reassuring.
However, I will say the subtle difference is the way that they think about their populations.
The the majority certainly ex us think of.
Population health how does this work within for example, our country.
When we've got X hundred thousand Lorex million patients, who could be applicable how do we think about gaining access and what does that look like and obviously that is much more fragmented within the U.S. system.
Thank you team and best of luck has not getting into the data readout.
Our next question here, So mccosh story from Wolfe Research. Please go ahead.
Hi, Ah so can you expand a bit on the E U opportunity for increased rent and how payers would view your asset versus the traditional Pcsknine and then also outside of the <unk> initially high whack, what other commercial commercialization areas, you feel Amgen and regeneron made when launching other products. Thanks.
Thanks, <expletive> Thanks for the question the cash.
So the I will caveat this and it probably will form the majority of my response here the E U on any of our commercial research is still it's still early.
The early feedback has said is very positive we havent really dug into the size of the opportunity yet as we're working our way through.
We have payer and system research, we're very early in our physician research within the EU, but I'll just reiterate the differentiated profile is coming on strong and that conversation quickly turns to what is that patient population, we have deeper understanding in various countries, which for competitive reasons I will not go into.
But.
It's it's let's just say it's substantial opportunities that we have to try to help governments figured through for the amount of patients that they have.
In terms of the antibodies, obviously you know that.
I I don't want to comment.
About what they did what they did right and what they did well.
I think for us.
And I want to be very clear is that the feedback supports exactly our positioning that.
In cliffs around is going to be a market of one.
It's a totally different value proposition.
The which has advantages and can be thought about very very differently. So.
We are in you touched on obviously their initial pricing but for me. This is this is about as we think about patient affordability, but then with there is much more to this you've got to be able to gain access for that to the right group of patients.
So there is theres, a whole spectrum and how any company should think about launching.
Such a product as inclisiran.
Which is.
This is.
It you have to understand how.
Beneficial the product could be for a large group of patients.
So therefore, our our launch structure is and thoughts and thinking and pre commercialization work would be vastly different to to to what the antibodies would have been thinking.
Got it thanks, so much.
Our next question here is a man I'm Tammy from B. Riley FBR. Please go ahead.
Good morning. Thanks, so much for taking my question I have two for Peter and just one for Mark.
Just a follow up to the.
Got questions that have been asked before just understanding that Ryan 11 topline release that precedes E C.
Is there a different than the embargo rules relative to HCC earlier today, which may allow you to have more or less granularity, particularly on the baseline characteristics. If you me and then second on the clinical side.
As I understand it 911, obviously closely mimics the line one baseline given the European side focus.
But but I think you made a comment that it lacks the more renally impaired group. So anything else you could compare comment on combating the difference in baseline characteristics for 911 relative to it and Dan and planned for in terms of underlying liver or renal disease and then for Mark.
I I know you talked a lot about part b versus body, but just on the characteristics of poorly adherent patients.
Is there anything you are identifying that is maybe unique to the sub growth maybe across the U.S. and you win.
And how maybe the antibodies are doing in that in that particular segment.
Thanks.
Hi, I'm a bit your first two questions. So generally the embargo rules that the major societies has like PSC KCC and aid say are very similar.
And obviously they recognize the need that we are in as a public in a small company. So we will be discussing with them, what we can and will be cannot say and the topline results.
Once we have the data and then we will decide what exactly will be it will be included but I think you can look up the rules of the bulk of them on the web site.
Of the societies and that will give you sort of the general guidance of where they are going with what kind of a couldn't be said.
With respect to the baseline characteristics. The only thing that we have disclosed on that so far.
As pointed out by you correctly 111 has done in Europe and has a ASCVD patient population an assay for the Misc equivalent which was similar to the way in one.
We have disclosed the baseline LDL C level of all the phase three studies in our analyst presentation in May and there was 110 112 and hundred 16, respectively. The larger one for for line. Nine. This is a heterozygous FH study, where you expect to have a higher baseline.
So 10, and 11 or similar even though they have slightly different patient populations.
And I may point out that that baseline in the line 11 and align 10 is also slightly lower.
Baseline he has an aligned one.
Which was allowed to 125 foot cluster dosing groups that we tested in a way in one.
The only other thing that we have this close to your point that you made to the comments yourself already is that he aligned seven study allowed us to include.
Severe renal impairment patients in the phase three program towards the end.
Once the lines have almost completed that was not possible in a line one because we didnt have to data at that point in time.
And that's.
All the things that we have sort of said publicly.
On the baseline characteristics of the studies.
Thanks, Peter and.
Thank let's thank you. Thanks for the question. So the if if I understand it correctly is there anything sort of unique in that patient. So group, who are who were not here and.
Or anything that we're seeing in the U.S. or across the rest of the world.
That the short answer in terms of certainly the feedback that we've received in our research firm from patients is very clear.
They want to get to go.
Even the non adherent patients they are frustrated.
Dave Hadnt the CV event.
It's pretty clear that the majority understand the risk that they are at but they frustrated they are frustrated that they can't get to go are they're frustrated in terms of getting access to the right medications.
And that's that's that's a real challenge so that comes through really strongly.
Now I'm not saying that is all patients because it's very clear to us in the research we see two thirds of patients regardless will stop taking their medication.
Oral medications.
Stands after one year.
That's two thirds of patients that's that's a very very significant number.
And that the the.
Research that runs beside that is that's the healthcare practitioner. The fact that they are then taking control and taking this issue away from patients who were trying to do the right thing is is where the benefit applies.
Is there anything that the beers could potentially also do in your view.
That could allow for maybe earlier utilization over other options just recognizing proactively there's a there's a subgroup.
That is going to be very poorly adherent in hands to this the economic burden on the on the system group.
Yes, that's it's a great point, it's certainly come through in our research from payers.
They identify this group regardless.
Of really their risk profile that there is just a group of non out here in patients that they also want to get under control. They understand the benefit of that they've they've spoken to us about it and it's very clear.
That they are looking for solutions. So I do think there is a role for for all stakeholders.
And that's that's sort of the approach that we're taking in pre commercialization.
Great. Thanks for taking my question and good luck for the data release.
Our next question here, So Jay Olson from Oppenheimer. Please go ahead.
Good morning, and thanks for taking my question.
I'm curious if you saw a recent publication in age journals AJ journals.
That analyzes patients with limited access to Pcsknine therapy. It shows increased risk of cardiovascular events and I was wondering if that type of analysis could be used to strengthen the value proposition for and closer in and.
Potentially help you create a more compelling argument a with payers. Thank you.
Thanks for the question Jay and yes, we saw the article.
A recent article I think it was I think we only saw it yesterday or the day prior.
Very.
I mean for us, obviously, very very timely and it obviously it dovetails, so well into our existing research that's that's coming back.
I think you answered the question yourself I think it would it's it's certainly beneficial however.
For for US this is.
It's.
It's so important to have the understanding that this is a different product to water Tim's PCSK nine inhibitors and and I.
The monoclonal antibodies have wonderful science, it's great science, and it's validated and it validated the target Inquests runs differentiated profile is coming through is so different.
Therefore, where we are.
Certainly and our research with picking that up and I think access is a critical component. When you have a large number of patients who could be applicable to the street.
So we can have different discussions but.
It's it's certainly the easy you make those that access or the better it can be calm.
Then you have to solve the adherence issue.
You can get 100% access for a product, but if the patients is still not going to take the product.
You still don't get the benefit and thats wearing plus or it comes it.
Great. Thanks for taking the question.
Our next question is a follow up from a more rapid from Evercore ISI. Please go ahead.
Hi, Thanks, so much for allowing the follow up my question was I just wanted to confirm this so Ryan 11 was had the last patient randomized on 29th of January So Dave 510 for that patient would have meant June 23rd for the primary endpoint. So is it safe to assume that trial has read out internally in the statisticians are working on it.
Yes.
Thanks, So much for your your math your math is not exactly.
Correct, there is always a little bit of flexibility in the visit Windows that you have to factor. In then you have to factor in database cleaning.
Before you can lock the database and when the analysis as we said before the trials are on track and our ongoing so.
We are.
Where we are and we will release the data as it becomes available to us in the topline and presented at Monday morning, 920 to September 2nd in Paris at the assay.
Got it but just to be clear Peter the trial has it maybe in a database cleanup stage, but the trial has officially met that frankly, we're past the primary endpoint correct, meaning management's not aware, but internally there might be a cleanup.
As I said just before the trial is ongoing and on track I can't specifically comment on where we are exactly on an individual lost patients on.
Got it thank you very much.
This concludes the question and answer session I'd like to turn the floor back to management for any closing comments.
Okay. Thank you, Matt and thank you all for your questions and which is of a of of good luck.
Influenza unique profile.
Last global market opportunity, coupled with the medicines company full on encumbered commercial Reits doing plus around in all markets.
And market exclusivity to mid 2034 with expected extension into 2035.
Do you set the stage for significant shareholder value creation.
In place around is moving very quickly through phase three trials, we're encouraged by the emerging clinical and safety profile and expect the phase three data to start rating out in the second half of the third quarter.
In parallel our pre commercialization work is ongoing.
And it affirms the highly competitive profile, having plus around.
The board and the management team of fully aligned and committed to unlocking the value in plus around for its shareholders and ultimately people who would benefit from this unique therapy.
So with that I'll close the call and I wish you all a very good day. Thank you.
This concludes today's teleconference. You may disconnect your lines at this time. Thank you again for your participation.