Q3 2019 Earnings Call

Greetings and welcome to the medicines company third quarter 2019 earnings call webcast.

This time, all participants will be listen only mode.

A question answer session will follow the fall presentation.

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Please note this conference is being recorded.

At this time I'll turn the call over to Krishna Gorti, Vice President Investor Relations. Please go ahead.

Rob Good morning, everyone and welcome to the Medicine Company third quarter 2019 earnings Conference call I'm joined today by our Chief Executive Officer, Mark <unk>, Our Chief Financial Officer, Christopher video Lee.

Chief Development Officer, Peter Weingarten.

Earlier. This morning, we issued a press release reporting our current quarter 2019 financial and operating results. The press releases are available in the Investor and media relations section of website.

Before we begin I'd like to remind you that our discussion during the call will include forward looking statements.

Subject to risks and uncertainties that could cause actual results to differ materially from those indicated by those forward looking statements.

Additional information regarding these risks and uncertainties is discussed under the forward looking statements legend in this mornings press release as well as in our periodic reports filed with the Securities Exchange Commission, which can be obtained from the T C or by visiting the Investor Relations section of our website. During today's call. We will also discuss certain.

Financial measures that were not prepared in accordance with the U.S. generally accepted accounting principles. Please refer to this mornings press release for the cancellation of these non-GAAP measures to the most directly comparable GAAP financial measures with that I'll now turn the call over to Mark Mark.

Thank you Christian good morning, everyone and thank you for joining us today.

Before I discuss the quarter I'd like to remind us all why we're here.

More than 47000 people worldwide will die today as the results of the world's number one kyla cardiovascular disease.

Atherosclerotic cardiovascular disease already asked CBD is the leading contributed to morbidity and death and its root cause cumulative exposure to elevated LDL cholesterol is also the most readily modifiable risk factor.

We are aligned with the increasing recognition by thought leaders of the importance of addressing cumulative exposure to LDL C.

Patient management should consider both lowering LDL C levels and keeping them low for the remainder of one's life.

Despite the widespread availability and use a proven LDL lowering therapies, notably Stanton many people when they see the day, it's still not meeting treatment goals.

We know from my research that health care professionals around the world are concerned about the inability to get and maintain patients on therapy, and they're seeking different ways to achieve durable and potent LDL C reductions that address cumulative exposure to LDL C.

It's the first and only LDL C therapy that would be at men be administered by a healthcare professional twice yearly. We believe that includes around is a game changer that addresses to critical unmet needs.

First additional LDL C. Lowering is needed so that A.S. CVD patients consistently reach that goal and avoid cardiovascular events.

Second underlying this first need these poor patient adherence to LDL C lowering therapy.

Based on the exceptional data presented so far we believe in class Ryan is well positioned to address the significant unmet need in s. CVD setting the stage for substantial commercial opportunity and shareholder value.

We continue to make steady progress keeping a sharp focus on highly disciplined execution and we believe the existing cash provides us with runway into the second half with 2020 and enable significant strategic financial flexibility.

Now, let me focus on a very busy an exciting third quarter, where the performance that was defined by flawless execution.

I'll begin with our clinical development program, where we successfully completed in close surrounds pivotal phase three LDL C lowering trials.

Each of those three studies met all primary and secondary endpoints, showing durable and potent efficacy with twice yearly dosing, giving place around an excellent safety with no treatment related lever Arenal laboratory abnormalities.

At the European Society of Cardiology meeting in Paris in September we presented the results from a Ryan 11 inclement runs first pivotal phase three clinical study.

In a rising 11 twice daily dosing within closer on sodium 300 milligrams met all primary and secondary efficacy endpoints.

Well I was well tolerated and demonstrated an excellent safety profile.

For the primary endpoints in klystron delivered a placebo adjusted LDL C reductions of 54% a day 510 and demonstrated time average placebo adjusted LDL C reductions a 50% from days 90 through 540.

The overall ADVATE adverse event profiles of the placebo and cluster on treated groups in a rising 11 with similar with no treatment related hepatic or renal abnormalities. The results of the Orion 11 trial support the unprecedented potential living close around to deliver assurance to combinations.

In patients that LDL C can be low it in a sustained fashion over the long term within infrequent dosing regimen and an excellent safety profile.

In addition to EUR 911, we topline the two remaining pivotal trials Ryan nine and 10 in late September .

Topline data for Ryan nine which is the phase three clinical study in patients with heterozygous familial hypercholesterolemia or H E. F. H show that the study met all primary and secondary endpoints inclisiran demonstrated durable important efficacy and was what.

Well tolerated with excellent safety that was generally well balanced between the treatment groups with no treatment related liver Arenal laboratory abnormalities.

Ryan 10 phase three clinical study in patients with I see the day Mark the successful conclusion of the pivotal phase three LDL C lowering studies of in place around.

Ryan 10 met all primary and secondary endpoints, and then clustered around demonstrated efficacy and tolerability and safety that where at least as favorable as observed in Orion 11, with no treatment related liver Oriental laboratory abnormalities.

Detailed efficacy Tolerability and safety data from a Ryan 10 will be presented at a late breaking science session at the American Heart Association annual meeting in Philadelphia on Saturday November 16.

11, Oh Stakes Eastern standard time.

The company will also present data from the Orion nine study in patients with Eightci FH at a separate late breaking science session of the A.J. Congress on Monday November the 18 at 924 Hiestand Stantec standard time.

Without clinical development program is also a ryan for our cardiovascular outcomes trial.

Enrollment of patients into a rainforests is ongoing and remains on track, we expect to complete enrollment within one to two years from the beginning of enrollment.

During the quarter. We also completed manufacturing validation of includes ran and achieve commercial scale.

With this validation and the completion of the pivotal phase three studies, we are progressing rapidly towards anticipated regulatory submissions, we expect to file in India by the end of this year.

And then M. A in Europe during quarter, one next year.

In parallel we continue with our robust precommercialization work that reinforces the transformational profile and potential living plus around.

Our phase three data routes further fuel our excitement in the product profile. This enthusiasm is matched by thought leaders and stay called is keen to change the trajectory of cardiovascular disease.

Our planning has been informed by a wealth of insight driven analysis centered on patients health care professionals health systems and pay is that comprise the health care ecosystem.

We've been working with industry, leading partners to conduct several rounds of qualitative and quantitative market research globally.

Early feedback on the target product profile for Inquests around has been very positive across stakeholders, who see the game changing potential for these first in class cholesterol lowering small interfering irony therapy to deliver durable important lowering of LDL cholesterol and is they bought thereby ideally suited.

Good to address the risk of cumulative exposure to LDL C.

[noise] across all stakeholders patients providers health plans and health systems around the world. The feedback is remarkably consistent.

Messaging related to disease burden as well as clinical efficacy and safety for Inclisiran has resonated well with decision makers across all markets. They see how our product within cluster runs profile can help address the overwhelming unmet needs that contribute to the world's leading cause of death.

Low adherence to existing therapies is seen as a significant driver of unmet need and a cluster Ryan's dosing profile is viewed as a potential solution to help to circumvent the challenges of treatment that hearings by improving therapeutic coverage and persistence.

There is strong feedback on the possibility for includes run to deliver a positive treatment experience through twice a year dosing administered to the patient by healthcare professional which aligns with common approaches to care for patients with they ASCVD, including the frequency of follow up office visits.

Looking a little deeper into what differentiates includes surrounds the pay is this important stakeholder group fuse twice a year dosing.

Healthcare professional administration and the ability to significantly lower LDL C over a long period of time as call value drivers.

All stakeholders are also receptive to our focus on patient affordability and attempts to create an environment that responsibly supports access to all patients who could benefit from it plus around.

These consistent and continued insights and stakeholders around the world reinforce our confidence in plus around is the first in class cholesterol lowering center that offering a vastly different value proposition compared to any other LDL C lowering option.

The opportunity to help patients simply and dramatically lower LDL C. Therefore live healthier lives and the magnitude of the unmet need and health challenges speak to the potential market opportunity for in place around.

The number of high risk under treated patients requiring lippitt lowering therapies is staggering.

We believe there is an opportunity for mplus Ron to provide durable important LDL C. Lowering among the more than 40 million people, where they ASCVD RF h. across the U.S. the largest European countries, China, and Japan, Youre currently treated with LDL cholesterol lowering therapies, but are not act.

Oh.

Were confident in the promise of in place around is the first and only cholesterol lowering center with the potential to deliver durable and potent lowering of LDL C levels via twice yearly dosing that can help address the two critical unmet needs additional LDL C lowering and poor adherence to therapy.

I'll now turn the call over to our Chief Financial Officer, Chris Videolink will cover our financial results for the quarter over to you Chris.

Thank you Mark and good morning, everyone.

During the third quarter of 2019, we continue to execute to our operational and financial plan.

Research and development expenses were 42.8 million, including 1.9 million in stock based compensation expense and approximately 12 million related to the release of three manufacturing validation lots in the third quarter of 2019 compared to 32.7 million, including 1.4 million in stock based compensation.

Expense for the same period in 2018.

In addition to the manufacturing validation work R&D expenses for the third quarter of 2019, including costs associated with the pivotal Orion phase three clinical programs.

Progression of enrollment in the Orion for CVR T program.

The continued transition to patients from the pivotal programs into your Ryan eight extension study.

And headcount associated with R&D.

The manufacturing validation lots will be part of our NDA filing and will be used for clinical and commercial supply pending approval.

SGN a expense was 18.6 million, including 2.6 million in stock based compensation expense in the third quarter of 2019, compared to 6.8 million, including 2.7 million in stock based compensation expense and a $7 million gain from the sale of the company's rates the branded angiomax in the United States.

Sandoz for the same period in 2018.

Our cash and cash equivalents at the end of the third quarter was 265.9 million, which we anticipate will enable us to fund operating expenses into the second half of 2020.

With that I'll turn the call back over to Mark Mark.

Thanks, Chris So in summary, the medicines company is entered an exciting period, fearing plus around which we believe is a class of won the therapeutic profile that offers a vastly different value proposition compared to any other LDL C lowering option.

It is a product with substantial possibility to fundamentally reshape the landscape of cardiovascular care.

Looking ahead to the rest of the year, we have a number of important upcoming catalysts that include a Rhine nine and Orion 10 presentations at the Ha conference in November .

Publications of data from Phase three studies and pay review journals and the anticipated U.S. San Diego filing in the fourth quarter.

In parallel Precommercialization work is ongoing and affirms the highly competitive profile living plus around.

The board and the management team of fully aligned and we committed to unlocking the full potential living plus around for its shareholders and ultimately patients who would benefit from this unique therapy.

We are more confident than ever in our belief that interest around could become a game changer in cardiovascular care and help to overcome many of the existing barriers in the fight against cardiovascular disease, the world's leading cause of death.

With that we thank you for listening and I'll turn the call back over to Rob So that we can take some questions.

Thank you will now be conducting a question answer session.

So that we may address questions from as many participants as possible. We ask the you. Please limit yourself to one question and one follow up if you have additional questions. You may recall, you and time permitting this questions will be addressed.

If you like to ask a question. Please press star one on your telephone keypad and the confirmation tome indicate your line is in the question Q.

The press star to if you'd like to remove your question from the Q.

For positions that are using speaker equipment, you may be necessary to pick up your handset before pressing the star Keith.

Our first question comes from the line of Humar refine with Evercore. Please proceed with your question.

Hi, Thanks, so much for taking my question Mark can you speak to any contracting work you guys have already been doing potentially.

With any with any government agencies U.S. Forex U.S., what the size of that looks like what the volume of that looks like and what's the dollar pricing for that looked like thank you very much.

I am a and thanks. Thanks for the question as you can imagine we've been in deep discussions with payers and health systems around the world.

We have tremendous optionality as we speak to them.

It's too early for for me to disclose any of those conversations at this point in time.

Our ongoing.

It's suffice to say that there is tremendous.

Excitement around the possibility of trading large populations with a product with the profile liking plus around.

And let let me leave it there, but it's very exciting times.

Thank you very much.

Our next question, let's turn to line up Joseph Schwartz with SVB. Please proceed with your question.

Hi, Good morning, Thanks for taking my question Congrats on all the progress this is Dave.

So mark two questions on the.

Back to you comment.

Prepared remarks first question is.

Attention for cluster.

Yep.

<unk>.

Or population health approaches provide you with any strategic flexibility relative to the monoclonal antibodies.

Patients where market opportunity and second question kind of related to that.

Can you share some of your market research with payers specifically are you getting the most traction.

And what does it imply both for the potential markets.

Yes.

The overall.

If you will be just market. Thanks.

Yeah. Thanks, Thanks to the question, Doug and let me let me answer the second one first obviously paces are very important stakeholder group for us.

It's very clear in the market research that we've done that they viewed twice a year dosing healthcare professional administration and the durability and the potency lowering of LDL C is called value drivers.

For them, it's clear in the research that low adherence to existing therapies is seen as a significant driver the unmet need.

And then cluster ends profile is really viewed as a solution to help circumvent some of those challenges of treatment adherents.

If we look a little bit deeper into some of that research.

At this stage, it's an important stakeholder group, but they do say that twice a year dosing is is the critical piece for them.

There is really strong feedback that there isn't prompted link to.

Improved adherence and that leads to the possibility to deliver a differentiated treatment experience, which is very exciting for them.

I think finally, there they're all they've also been very receptive to our focus on patient affordability.

And our attempts to create an environment that responsibly.

Supports access for patients.

With regards to your first question it really is.

Our opportunity is really very broad because of our differentiated product profile.

We do have.

A unique product and therefore, we are having very different types of discussions. It's early for us to talk about those setting in greater detail, but it does leave us with with Optionality and great Optionality and whether that's around.

Part B.

Medical benefit all pharmacy benefit we have options in both which have very exciting for us.

Great. Thanks for taking my question.

Our next question comes from the line of Jessica Hi, with JP Morgan. Please proceed with your question.

Hey, guys. Good morning, Thanks for taking my question first on those commercial scale validation batches to those now need to step first ability or do you have stability data already.

Hi, this is that they'd just be the movie do have stability data already because I would also be hard to off to file both for the pie as well as Jeff pointed to of product.

Okay, Great and then separately on the outcomes trial that you mentioned was enrolling I think you said it would complete.

Enrollment at once two years from when it started can you remind me when that trial started enrolling.

And then related to that how much of the cost of the C. D. O T has already been incurred and how much still remains in front of the company.

No we announced its first patients enrolled in a lie in Fourq and late last year I believe it was October .

So did the timeframe from the 123 years has to be seen from that time point on this.

Chris do you want to under yeah on the cost yes, yeah. As we stated a the total program would cost approximately $150 million in that would roll out over four to five years of.

Of the trial and we're tracking towards that we said it on a fairly linear basis. So we're tracking within that range.

Thank you.

The next questions from the line of Tazeen Ahmad with Bank of America. Please proceed with your question.

Hi, guys. Good morning, Thanks for taking my questions I'm, just a couple on Hum I'll comment that you made about.

Your financials. So you said that you have enough cash to take you through two I think you sat around the middle of 2020 as that assumption inclusive of having to build out of sales force. That's question. One question number two is what are your thoughts about partnering the program that lease on the X.U.S. front is that your assumption that.

It will be partner by the time, you launch or do you have expectations that you will at least start the line checks U.S. Thanks.

Yeah. So on the this is Chris on the on the runway a it would include we said we have cash that takes us into the second half of next year and it would include the work necessary to the Precommercialization work necessary in R&D work necessary.

So there.

As you think about sort of the build out of any commercial team that wouldn't really begin until a third quarter. Today. So I think you can factor that into into what Chris is saying.

With regards to.

Pondering, obviously it we are not if and when we have anything to announce will obviously announced that it at the appropriate time all strategic Optionality is is in front of us a I'm we're excited by those options.

And then just one follow up do you have a sense of how big of a commercial sales force you would need any you asked.

Yeah. It's a this is a common question that I do get asked states, it's a little bit early for us at the moment and the reason being is our extensive research continues.

And as our discussions with with payers and providers alike.

That's the bill that goes back to some of the earlier questions about how you actually would launch a product with such a differentiated profile so little bit early first to comment on that it at this stage.

Okay. Thanks.

The next questions from the line of Yasmeen Rahimi with Roth Capital. Please proceed with your question.

Hi team looking for taking my question.

Yeah. The first one <unk> or Peter Peter can you walk me through what type of Zentri data are you planning to share with your parents to really link improved confined to reduce event rate in the absence of TV. OTI result, and then I should want it's just a little bit deep held in regards to.

Sorry, packaging, maybe remind us with the needle DSIC required we understand what the volume.

Ministries.

Okay. Thank you.

Thanks, Yes main for your question I'll start with a second to questions, So and cluster and this code to be and administered as soon as a subcutaneous injection of 1.5.

Mills this will be in a pre filled syringe has a needle gauge of 27, so it's a very fine needle.

Your first question, but that type of events around inhalants, obviously, we have started Englishman sofa only in clinical trials setting and as you probably know from the results. He presented before do you Havent seen clinical trials has is extremely high we had 95% or more often.

Actions in Hawaii, and 11, completing the trial and receive into four doses out to the 18 months durations. So first study.

That's great of course, it will be very useful in those discussions you referred to but ultimately it's more important to look at the the market research, we're doing how to perception if the profile of the glisten twice yearly administration.

And in administration by the health care provider, what I would translate into a real setting often havens would do bits, we do anticipate to be much higher than typical deluxe at an admin is much more frequently.

And how aware our the chair of the lack of compliance, resulting in a high inventory.

Yeah, that's that's coming through very strongly in our research.

He has made its it's.

It's clear that they understand the challenges without hearing some many companies have and I've tried to solve there's some many systems of try to solve this so over periods of time.

We are actually coming through the research, we're starting to see health systems Hana how much.

Actually spending on trying to solve this per patient.

Which is a it's been fairly dramatic for first is to see that the lengths that they going to to try to change adherence because they know obviously it has such an impact on outcomes. So the awareness levels a very high.

And as Peter said this there's tremendous excitement around a product which can be delivered.

By a health care practitioner.

Which and basically guarantees that the drug is onboard for for a long period of time.

Thank you team keep up the good work.

<unk>.

Our next question is from Atlanta, Paul Choi with Goldman Sachs. Please proceed with your question.

Thank you and good morning, and thanks for taking your questions.

My first question is on the regulatory side and or we were just wondering what are the remaining steps that you have to do before filing the NDA and then if you could lay out for US you know what are your base case expectations with regard to the.

Timing and potential topics for for a potential advisory committee meeting foreign cost trend given that it could be the first in class a Florida for LTL management.

Thanks, Bill I'll take the those questions so wherever youre ready and D.A., we've always had the clinical program being the driver of timelines towards the end the eight as a non silicon CMC part is essentially finished early in the year.

So the lighting of the idea of that part is also very advanced and what drives the oval timelines in terms of the final steps towards the end. The submission is dividing up off the phase three clinical data in this in this study reports in the integrated analysis.

We are on track so has that completed by year end and submission to the FDA by the same time.

And with respect to your second question so about questions of the outcome.

First of all the don't anticipate together that have come at this point in time, we will be and we have performed and a LDL C loan program, which is unique in one sense because of the profile of English, but on the other side. This is standard as has been for other LDL C loan program somebody being held to the.

Same standard.

The decision is ultimately in the hands of the FDA it will be speculative for less to make any statements on that but from what we know today, we don't anticipate we will be having an outcome.

Great. Thank you for that.

Our next questions from the line of Chris Shibutani It with Cowen. Please proceed with your question.

Thanks, very much a couple of questions in terms of thinking about potential commercial partners I think.

We've had a discussion previously.

About how the current commercializing companies monoclonal antibody.

Might have quote and difficult time getting their heads around the idea of also having within their portfolio of product like yours is that something that you continue to feel that way and would you for instance thing that there any anti trust related issues, if one of the existing players.

Considered partnering or commercializing or even owning the assets.

And Chris It's Mark I'll I'll answer that obviously.

Where we can't speculate on our comments on the any sort of potential partners.

I think you've you took a third party view I think you'd have to say.

You know the the FTC. It's at this point in time at taking quite a quite a strict.

Approach to these types of.

Let's say close collaborations I think it's it would be difficult certainly I would think I think in my mind, but.

Thats I wouldn't want to speculate.

And then when you commercialized potentially a group of patients would be those who are already taking the monoclonal antibodies can you remind us I believe number one what studies you are actually doing I think there was a study that was looking at transitioning patients number two would you think that you would be needing.

Color data from a regulatory standpoint too.

We have something in the labels for that instruct physicians what to do for instance, if you're on a monoclonal would you need to do that initial sort of dose three months and then go to six month and then finally have you having discussions with payers about what they think they need to know or understand in a situation where they have a patient on a monoclonal antibody we'd like to transition.

And over so it's really clinical studies regulatory and sort of the commercial discussions with payers for that potentially attractive subgroup of patients.

Yes, let me, let let me start and I'll ask Peter to comment on a Ryan three so we expect the Inclisiran label at launch to be in combination with maximally tolerated status in patients with they ASCVD or HCCI FH.

Frankly, we see cardiovascular diseases our competitor.

We see real opportunity at the top of the funnel. When you think about the number of more than 40 million people would they have CVD or FH across those major markets, including the U.S. European countries, China, Japan that who all need additional LDL C lowering.

And then not to go so you know it's it's.

It's clear to me there is a much larger opportunity out there than.

Yes that small number of patients are actually taking.

The monoclonal antibodies. So we expect to source patients from all lines of therapy.

And that's being consistent within our research as well, whether that's being with pay as healthcare providers and patients, but basically it's a any any all who are in need of durable potent lowering of LDL C and wed twice yearly dosing will improve adherence Peter would you like to talk about the studies.

Yes, as Chris said your line three studies the extension study of the safe to align one study we presented data from the face of maintain therapy on that list or an earlier in the and the late.

But the placebo patients that were in a line one transitioned into a line three first by a year of treatment that after locum up and then they are have been switched to it to in Cleveland.

In two different ways by two different transitions modality concomitant administration of the lost those softening of Evolocumab combined with Inglis win or by an interval of two to three weeks, which sort of typical dozing until 40 antibodies.

That data will be forthcoming and be able to of course have information from that study that will provide guidance on how to switch from them on a client 42, and plus one and obviously at the appropriate time, we will try to have that also reflected in the label that they'll be possible will depend on the suitability of the data that we have and the ace opinion on that.

As far as all the records in the World of the certainly intend to have that ultimately in the label.

Great and then last quick detail the previous wording into second quarter with cash well into the second half. This quarter, you say into the second half am I being too specific about that was that a deliberate change of wording or.

No it's not deliberate yeah, you're just you're being too specific Chris.

Okay.

Looking for Q in a thank you thanks and good question go ahead.

Our next question is from the line of Mike Montani with B. Riley. Please proceed with your question.

Good morning, Thanks for taking my question and congrats on the flawless execution.

Interesting to hear him I'm Jim's management team commentary last evening audit. This rod Mark wondering if you could comment what you already when Diane might be heading from your industry peers or should I say settled amex colleagues in case, you how to John's to invalidate of you just add ons overall profile or or maybe you run into some of them at the Ajay.

Just curious.

From the industry side, who folks committed to cardiovascular what you're getting dead.

Thanks for the question my own and.

Obviously, I I can't comment on any any strategic discussions or any speculation I will state, it's well known and we saw this it S. C. There is tremendous excitement around inclisiran.

And I think that's across all stakeholder groups. It's it's a well known product I think the the data speak for themselves and that's only.

Built around the excitement.

Of the product profile that is that is now coming to bear so very exciting and I don't think that's changed.

Okay, great if they could do little follow up so now you have all the data in house in Oh. This year, you talked about your pre commercial lines and you think about the different patient profiles that any cholesterol lowering company considered as part of the large Glenn maybe could you comment on what that ideal patient <unk> looks like floating listed on until.

How that longer dumped safety exposure in of course, the outcome data just across the different patient profiles.

Yeah, it's a it's it's remarkably consistent with with what I said I mean, we do expect the label to have a launch to be with maximally tolerated status in patients with a CVD.

Our AG FH and and really it is those patients who are struggling to get to go those secondary prevention. The high risk patients that will really form the basis of the patient group that will be left will really benefit from in place around at launch obviously, we would have.

Have a full lifecycle management plan that will expand that that patient population over time as we learn more about it we don't even though we will not have outcomes.

Cardiovascular outcomes at launch, we don't expect that to be a barrier for any of our major stakeholder groups.

The question like whenever I pose this question and whether whether we posted in research what consistently comes back to US is well did any body weight for outcomes when received Staten launched.

The clear answer is no I am PC SK nine is a well validated target we've got outstanding data over a long period of time, we've done some of the longest.

LDL C studies.

In the history of cardiovascular medicine, and that all supports a very strong profile in a will support a strong launch.

Excellent and if I can squeeze one in for Peter Peter any color you could provide an emerging cardiovascular targets such as PD L. Three.

Which according to some again early but could be a competitive threat to the easiest canine lots of the whole any any thoughts there.

Yes.

Of course, there early programs right now so it's hard to add to predict what exactly that dataset will be by the end of phase three but the only thing I would add to that is is that most of those opportunities do not touched a patient populations at loss that we are targeting who is a as CVD and FH with patients who LDL C not that target.

Coal most of those opportunities you're talking about either.

The specific sub populations like the FHLB homozygous FH.

All patients with elevated triglycerides suites kind of come secondary to LDL C.

Great. Thanks for taking my question Dan.

The next questions from the line of I fashion jewelry with Wolfe Research. Please proceed with your question.

Hey, thanks, so much so maybe just going a bit on the phase threes that are gonna get the full data can you compare and contrast, like the baseline severity in CBD burden on the line nine population versus a Ryan 11, and have you seen any change in the net reduction of LDL C. S patients base.

Nine LDL C increases and it also looks like you're mentioning.

The Japanese in China market a bit more in your prepared comments is it fair to assume that those are markets you'd likely look to partner and how would you kind of characterize decides is the commercial opportunity in those markets versus let's say the U.S. Thanks a lot.

They did you want to take the first phone.

Yes, obviously I can't comment on specific data points from nine and 10 as they will be presented at age say on this on Saturday for wind tenant on Monday for why nine but I can't speak to the difference in the patient populations of those trials why in 11.

Well, let's say European and South African study in air CVD patients and assay for the Vickery equivalents, who should have the same risk over <unk> of of cardiovascular events and need for LDL C. Lowering the ratio between the two populations in Hawaii 11 was approximately 85% to 15% of a safety.

This concludes blunt.

My intent is a U.S. only study and only included assay for the so it's highly similar then align 11, but there's some fine difference in the exact composition of the patient population and of course, the geography that would also discuss leverages conducted.

Why a nine on the other hand is a dedicated study and heterozygous FH patients that was conducted.

Globally.

Now how does that have each patient is an early manifestation of a CVD so patients at risk at the earliest states in life and largely in totality of consider the have a high risk of assay lead because of that early manifestation and it's all driven by the genetic background of the mutations that they carry that causes them to have the disease of.

Fades so in that context, though at a higher risk over their life costs, but then ask specifically different individually populations. In this study we will show you that data when we eventually get to it to ha.

Let me, let me just touch on the.

The question around Japan, and China. This we are receiving significant interest in the profile of Inclisiran within those countries.

Whether that's with.

The payers or with.

The key opinion leaders.

As you you would well no there is significant CVD in those regions of the world.

And therefore, it's incumbent of us to ensure that.

There is a robust planned for how that those regions would actually be accessed.

We've said and that we continue to believe that.

If we ought to do anything within Japan, we would do that with a partner.

And we have regulatory pathways to what type of bridging studies would need to be conducted in both markets.

Great. Thanks, so much.

Next question comes from the line of my do Kumar with Robert W. Baird. Please proceed with your question.

Yeah. So thanks for taking our question so thinking about the mace observation that you made guys. They.

11, and see if there if there weren't I must say, whether there are not in the IRI intend data set an A.J. would that be similarly presented in the presentation or how should we think about kind of mace observations in the in the USA ASCVD trial.

Thanks, Matt do Hawaiian 910, 11 for that matter led designed with the exact same.

Concept of the protocol so the endpoints, we collected the 11 or the same endpoints we collected in tenant nine.

10 is about the same sizes are line 11, so yes, we will be able to provide to that that data.

In in the upcoming presentations nine is a much smaller study so I would not read too much in that particular endpoint for white Knight.

Yes. It for me thanks, very much yes.

The next questions from the line of jails and with Oppenheimer. Please proceed with your question.

Oh you guys. Thanks for taking my questions I wanted to ask about your discussions.

With payers that you commented on earlier I was wondering if you're considering any innovative approaches with payers such as performance based reimbursement repairs may pull pay more or less depending on patients getting to go.

And then as a follow up just wanted to circle back on some of the comments you made about Europe , where I think you mentioned it all options are still on the table I was wondering if that meant you are in fact, considering building a commercial infrastructure in Europe . Thank you.

Hi, Jay Thanks for the questions.

With regards to to the pay as I said the research is very clear for us and they are very excited about the differentiated profile.

It's it's fair to say for for US all options is still on the table, it's very early within our research.

I would say is the data become available.

Not only our outreach, but inbound.

Questions around and closer on how best to create access.

A leading us to really think very carefully about that and hence to my earlier comment that really has an impact on how we think about commercial.

Planning and infrastructure going forward.

That's not dissimilar to to how we see it within a Europe is a differentiated profile you have an opportunity to do something very different and all strategic options is still on the table for us.

Great. Thank you.

Our next questions from the line of beer and I've been with Jefferies. Please proceed with your questions.

Hi, guys. Thanks for taking my questions Mark I want to get your views on what you think continues the l. that Pcsknine class you know historically the criticism spend that the class was priced too high attendant 13000, but you know now that the prices and cut the lessons 6000, we still continue see you know sales growth being flat.

You know yesterday last night for example, Amgen reported for path at about 80, 85 million, which is basically where they've been stuck at the last few quarters. So yeah I just want to get your impression on what you think you know triggers the class and causes the trajectory that we've been expecting.

Yeah. Thanks. Thanks. So the question I think it's you know I think the.

The issues of around pricing, a well known and not for me to to comment on.

I think that what was a real positive and certainly what we see it and our research and in multiples.

Is that you did hear on the call that there is increasing volume or certainly coming from from or a path or an amgen and I think that only speaks to the opportunity that we certainly see in there and the research.

I still keep anchoring back to the size of the treatment population that that could benefit from a product lighting plus around which as I talked about in these major markets is around about 40 million patients.

And therefore for US the opportunity is much larger I think in order to take advantage of that opportunity you have to do a number of things you have to be able to clearly understand the research.

Find and define that CLIA patient population that a ASCVD secondary prevention population, who were really benefit of getting.

Additional LDL C lowering but also the patient populations, who just struggle with adherence.

And that just increases the risk, especially around cumulative exposure to LDL C.

No the product and can do the types of studies that we've been able to do around cumulative exposure and that for me is it's a very exciting possibility. So as I as I do think about it I think you gave you know it's we obviously watch we watch closely.

It's it's not a competitive set that is really where we would encourage itself because we think of product profile is so differentiated a much more suitable to a chronic indications.

Got it and then maybe a couple of follow ups I think the company's previously mentioned that you plan to target not just cardiologists, but also general practitioners. So I guess my question is what percentage of eligible patients are treated by GE piece compared to cardio isn't what type of salesforce, which would be necessary to cover Gpus.

Yeah, It's a it's a great question I'll I'll.

I, let let me because I don't want to to get too much into what would see a potential commercial strategy here, but it's fair to say that is you think about the management of or a cardiovascular patient the cardiovascular patients is monies within the GP setting.

There's no doubt that cardiologists have a however, clearly a very important role to play but that day to day management.

It is clearly done through the GP side. So there's there's a real blend here and I think both both stakeholder groups are very very important.

And then I guess on the question on the sales force size that you'd need to cover the Gpus.

Yeah, that's still we're still looking at that it's very early for us to to comment I think in some way shape or form we will be engaging with that important state stakeholder group, but how and what that looks like it's still yet to be determined.

Great. Thank you.

The next question is from the line of Joel Beatty with Citi. Please proceed with your question.

Hi, Thanks for taking the questions.

Can you go into a little more detail on which types of health care providers are most likely to be administering closer and no and then also what types of sidings administration is most likely to occur.

Thanks for the question, Joe We've got tremendous Optionality around this and again, it's very much part of our our current work and current thinking.

Obviously, a healthcare practitioners comes in many many guys is.

I think the setting our focus is it is making the setting the one which is most appropriate. We're obviously we have the great benefit that a substantial amount of the patients a same their healthcare provider.

At least twice a year, so it's very consistent with the dosing schedule.

But again it comes back to how do we make this is simple than is accessible as possible for the patients to get it and that's part of our planning.

Thanks, and one follow up.

Talk about the potential timing of publications for the Ryan Phase three data sets you know enough that could come in the same time.

And we're working together with the principal investigators in the steering committee to get the data of all the three phase three studies published as soon as we possibly can.

Okay. Thank you.

Thank you we've reached the end of our question answer session I'll turn the call over to management for closing remarks.

Okay. Thank you Robyn. Thank you all for your questions. So we've successfully completed plus runs pivotal phase three trials and presented exceptional safety and efficacy data for the Orion 11 study at the see conference in Paris, and we look forward to presenting IRI and nine and 10 studies at the A.J. conferencing.

November .

Include surrounds highly differentiated profile vast global market opportunity coupled with the medicines company full on encumbered commercial rights to Inclisiran in all markets and market exclusivity to mid 2034 with expected extension into 2035 sets the stage for six.

Terrific and shareholder value creation.

With that I'll close the call them wish you all have very good day. Thank you.

This concludes today's conference you may disconnect. Your lines. This time, thank you for your participation.