Q2 2020 MyoKardia Inc Earnings Call

Good afternoon, everyone.

Michelle Corral Myokardia had a corporate communications and Investor Relations welcome today's call treat you second quarter results <unk> business update a press release summarizing Q2 results have been posted to the Investor section of the myocardial website.

Leading today's call is my cardio CEO tacos young.

That's always joined today by Dr., Jay Albarn, our Chief Medical Officer, Bill, Sorry, our Chief Commercial Officer, and Taylor Harris, our Chief Financial Officer. Following their prepared remarks, well open the lines acuity well. We will also be joined budgets, our chief business Officer before we begin let me remind you that the information discussed during this call wasn't paid for.

Looking statements, which represent the company's view as of today I guess for 2020, we undertake no obligation to update or revise any forward looking statements to reflect new information or future events, except as required by law. Please refer to today's press release as well as our filings with the FCC for information concerning factors that could cause actual result.

Could differ materially from those expressed or implied by these statements.

I'd like to now hand, the call over Tracy Uh Huh.

Okay.

Good afternoon, everyone. This has really been an incredible quarter I couldn't be prouder of the team at Myokardia, especially during these unique M unpredictable times.

Second quarter accomplishments should be remarkable under any circumstances, even more so we'll be.

So I'd like to start today with the thank you. Thank you to our employees and their families to the people who haven't continue to participate in our studies in their loved ones who support them.

For the study investigators in their staff, who are working harder than ever right now.

The resoundingly positive explore read I was a massive inflection for myocardium, some obvious and perhaps some less obvious wage.

These data extend our position as the leader in the science in the treatment of HCM and put us on a clear and urgent path to registering ADVATE canton as the first targeted therapy unobstructed HCM.

Underscored by its recent breakthrough designation, which is rare for cardiovascular drugs.

Explore results reinforce our aspirations beyond HCM, a being the world's leading cardiovascular medicines company, whose mission is to change the lives for the millions of people around the world suffering from cardiovascular disease, too bold and innovative science.

Of course, we remain laser focused first and foremost on the U.S. regulatory approval and launch of matter Kimpton for obstructed Betsy.

Our relationships and commitment to the HCM community, who had been with best friend to start continue to deepen.

And we're anxious to enable the physicians caring for people when they seem to be able to prescribed another counted.

So with our confidence hi, coming out of explore let's inventories over the top questions that we are concentrating on right now.

First what's the likelihood of matter captains U.S. approval and win what could the label look like.

We do went to be ready to successfully launch our company's first drug perhaps in a kobin impacted environment.

What do we think the potential value is now the canton as an approved therapy might be.

Do we think about the addressable patient population over time, and how do we improved on the low diagnosis rate.

What could the adoption could look like and what are the key factors that we think will influence adoption overtime.

How are we approaching axis and availability of magic camped out what do we think therapy might be priced out.

And finally looking outside the U.S. what are our plans in Europe Asia and beyond.

Rest assured will be addressing this entire list of questions between now and watch.

Today's call will focus on the March towards the U.S. regulatory approval in obstructive HCM as one of the ways, we're thinking of expanding matter campaigns availability globally.

Well not the focus today, we plan on discussing details around our preparations for the U.S. introduction of now the captain during a call on the time part you see presentation of explored data on August 31st.

Do you want to take a moment I would emphasize our growing belief that magic has it has the potential to be a backbone therapy in HCM and maybe even beyond we're working hard to extend our disease area leadership across multiple dimensions that you should be aware of.

First within obstructive HCM continue generation of clinically valuable evidence from ongoing in future clinical trials.

Next outside obstructive HCM. The continued exploration of additional disease profiles are we believe NAV account that may have benefit nondestructive HCM and targeted has passed being too we have discussed.

Third the deliberate and thoughtful expansion of our geographic reach aimed at increasing the number of people would HCM, who can access maverick camp and globally.

And finally, the expansion of clinical value within next generation therapies, including and why K two to four.

Introducing naveh campaign for the treatment of obstructive HCM in the U.S. is just the beginning.

As compelling as we think that the campaign is we are not a one therapeutic companies you know our cardiovascular R&D platform continues to generate important potential therapies, including the three that are currently in clinical study.

What's been time today on Dan I can't do but I do want to highlight the unique and differentiated effects. Then accounts is shown by directly activating the left atrium along with the left ventricle.

It's finding has generated a lot of enthusiasm as a novel approach to potentially reduce the burden of h. real fibrillation in people with heart failure.

As a very challenging condition, which is growing at a significant rate across the globe.

Are advancing program we've done a captive is another great example of my all parties R&D approach, yielding valuable novel Absolves learning about our molecules first in well defined patient populations and thoughtfully expanding into additional patient subgroups in a scientifically rigorous inefficient way, which we've also done successfully now with mab accounts in Indiana Cantor.

With that let's get into today's discussion right now the canteens U.S. regulatory update in high level Global strategy for my colleagues Dr., Jay Boyle, Chief Medical Officer, and Bill Ferry Chief Commercial Officer Taylor Harris, Our Chief Financial Officer will then walk through ours to Q financials and provide an update on the timing of several important milestones.

We'd like you to be thinking about.

Jay over to you.

Thank you talk so.

I'm excited to share the refund meaningful progress per member count.

That's helpful Imagine following <unk> results for much more moving forward quickly apparel for submission of a planned new drug application or India.

Okay, and the first quarter of 2021.

We're also moving quickly extraordinary value H.

First of several plants that is intended to build evidence promoted counted as a backbone therapy afes here.

Let's start with all regulatory body.

Following the explore data read out.

Thanks, Good luck to the agency to range pretty.

The data.

Questions regarding I understand.

Based on her colleagues tour pretty material.

Clear, but the das yet we're working toward isn't alignment with the agency expectations and the data is sufficient worthwhile.

The reason for C. O rig therapy designation provides further validation that we are on the right track.

A reminder, brick.

Good.

The development and we do have a cabinet don't clinical evidence of substantially all of them for existing therapies.

This could assignation recognizes the.

Hypertrophic cardiomyopathy and leave no therapeutic options.

It's you know all reason who subject.

Oh Oh development.

<unk> worksheet up here.

Good morning, Archer offered Carlson testimonials from individuals living with it.

Talking about the burden of their disease, and it's in Paris daily living family Y and their long term health.

We are proud to be able to partner with the HCM on this important event for patients encouraging all come visit the website could you.

Why don't you got.

These events.

I'm going commitment.

Just a very encouraged the development of novel cardiovascular Therapeutics.

Well breakthrough designation become increasingly common uncertain disease areas, such as oncology they remain exceedingly rare.

Cardiovascular Nephrology division, where there's been only one therapy approved the granted breakthrough.

Designation was introduced in 20.

2012.

Based on our data the prevailing feedback received on the ramping a breakthrough designation, we didn't feel was necessary.

Due to the point.

We have a clear path ahead of us breakthrough ensures ongoing ARX <unk> agency for advice from feedback throughout the submission process.

We'll continue to work closely with her counterparts with the appealing preparation submission born rolling over India.

We anticipate submitting our mdna in the first quarter of Twentys when do you want.

Last September we announced a partnership with Cleveland clinics, C.R. Bard academic research organization, who can dark phase three study evaluating you should mother count as an alternative supply induction therapy.

After being delayed due to the pandemic, we're excited to be gone patient dosing in the value each to your phase three clinical trial.

The <unk> power.

Got a once daily dose.

Medication.

The need Werner Brandt from surgical procedure.

It's a unique study design and we believe will exciting evident for Medicare patients ability to make a dramatic different lots of the patient.

The Valor study is just our next step in our commitment to HCM disease area leadership.

We look to build further value not accounting program.

One part of this strategy is to conduct supplemental studies beyond those needed for our initial submission package that could ultimately expand.

That's good.

Let me the medical need Sheehan community.

No wonder account.

No Sir likely as the first such supplemental data sets, because ultimately expand never count them obstructive HCM label.

Oh enables us to work with several important issue I'm, sorry, but are new to the most kimpton program, including largest volume from Cleveland clinic, and middle class, but on a month, a dozen or so site committed boozy obstacle to participating to test the ability of Melba captain.

What is the need for surgery, an important outcome for patients.

The study expand you always see I'm.

Beyond explore including New York Heart Association class for patients and allows us to tour [laughter] remotely dosing approach based solely on clinically based criteria.

Did we look forward given the results valor, that's a future supplement to the India. We're currently preparing.

In closing, we're extremely well positioned as we move forward for submission.

India application for regulatory approval in the U.S.

And would be similar we start looking beyond our initial label to provide another counseling to as many patients as possible for whom its distinct mechanism they provide benefit.

Starting with a constructive HCM and the prospect be able to point to a once daily oral okay. The funnel.

Dr ballpark procedure will be compelling doctors.

And patients.

<unk> U.S. another component, we're thinking about bringing about because people being on the balance.

Our global strategy, let me turn call over now to Bill.

Bill.

Thanks Jay.

The strength that the explore data coupled with our breakthrough therapy designation reinforce our belief that now the captain has the potential to be a significant advancement in the treatment of obstructed each yeah.

We are keenly focused on U.S. pre commercial and medical education activities and we look forward to sharing more of these details on some of this work is part of our planned call around do you see that also alluded to a bit earlier today I'm excited to be able to discuss our value creative strategy to bring other camped into patients around the world and build and the.

Build up our commercial footprint.

Footprint that will include territories in which we establish our own infrastructure and territories for which we will engage partners for the majority of the work.

Our ultimate objective is to be the global leader in the treatment of each.

With the aim of ensuring that 80% of the world's population at least with HCM have access to Napa Kimpton by 2026.

Accomplishes school, we're currently investigating the opportunity to launch now the captain ourselves in certain regions, such as Europe and in order to provide access to patients as quickly and efficiently as possible. We know that we'll be working with partners in at least some parts of the world.

Here's how we're thinking about the core tenets of our global approach.

As well as how we'll be evaluating to decision on a region by region and sometimes country by country basis.

First matter captain should be a clear priority at the organization does is launching the brand in a given country or region. This disease requires focused effort to both foster and partner with the local HCM community as well as to optimize the uptake of the brand.

Second we will establish a global brands reflective of our products distinct characteristics and our Companys core values and we intend to control the image at that brand everywhere.

Next we will take a global perspective on pricing and lead the pricing strategy by territory. As you know many countries. She's a reference based model to negotiate price our launch sequencing will be crucial to managing these dynamics.

We will be the all decisions regarding the development America capping beyond its initial indication and finally, we will establish a local presence in territories that are strategically important and where we believe we can optimize long term value from myokardia as well as our shareholders.

We know the worldwide opportunity is significant HCM just not discriminate it's estimated that one in every 500 people will have HCM and a significant number of those will go onto developed instructive form the disease. This translates into a worldwide HCM prevalence estimated.

At 14 million.

It's in the U.S. current treatment options are limited and geared toward alleviating symptoms rather than addressing the disease directly and we know that's the diagnostic rich vary widely around the world.

Consequently, the pressing needs for new treatment alternatives that we see here in the U.S., it's similar across other regions.

Europe is the first region, where we anticipate seeking approval outside the U.S. and as a reminder, over 50% of you explore trial population from Europe, representing 37 treatment centers and 11 European countries.

So we've been directly engaged with the HCM community over there.

For many many years in February this year, you heard Willem van footprint as our head of Europe and establish an office in Amsterdam, He and his team our task was continuing to develop and more thoroughly assess each sim opportunity.

In both you and the UK.

What we've done so far is that the region.

In HCM care is highly centralized slight differences between countries. All major countries have centers of excellence decay wells in these sensors often fall large patient groups on a regular basis in some cases several hundreds per center. We expect these centers to drive treatment initiation while community cardiology.

Just like we play in many instances and maintenance roll into treatment at these patients.

As in the U.S.K. wells strongly agree that there was an unmet need in HCM and they expressed the desire to treat the underlying disease.

They also acknowledge that HCM is under diagnosed and are willing to educate their community cardiology colleagues.

The European explore investigators as a subgroup of this group are eager and interested in increasing the attention.

Two HCM among their national colleagues, particularly now there's a potential new therapy on the horizon today in Europe, we're preparing interactions with regulatory authorities in anticipation of a potential you and UK filing in 2021.

We're also engaging country specific market access expertise to determine optimal routes to now the kimpton reimbursement.

We're working with supply chain experts to prepare the pan European distribution strategy.

We're assessing the each market with regard to prevalence eligible patient pool patient journey inpatient segmentation and finally, we're engaging with the key opinion leaders to better understand local treatment patterns treatment guidelines and opportunities for medical education.

Next steps for us in Europe include requesting meetings with the regulatory authorities in the fourth quarter of this year, completing our assessment or commercial assessment, including our launch sequencing and go to market strategy for the region.

We anticipate following a similar model for Japan.

Japan is the third largest pharma market behind the U.S. and Europe is a highly developed health care system that encompasses care for both genetic and rare disease patients.

HCM has been designated as an attractive will disease, a classification for rare disease in Japan, which means the government for most research and financially supports patients but these diseases.

We believe that the diagnosed obstructive you'd see in population today in Japan.

It's 30000.

We've had discussions with Japan's pharmaceuticals, and medical devices agency and have aligned on our development pathway that could enable now the captains registration for obstructive HCM, we plan to conduct the phase three study in partnership with the local clinical research organization and anticipate beginning that study in the first half of next year.

Over the course, but that phase three program, we will further assess the opportunity in Japan and ascertain whether value is best arrived from independent commercialization efforts or in a partnership.

Now I'd like to briefly turn to China were HCM is estimated to effect over a million people.

There were inclined to partner with the locally based entity that meets some of the criteria that I mentioned earlier.

We would expect command control maintain control over the brand pricing and development programs, but we also feel very strongly that for original partner in the area to be successful it must be willing to make never campton, a clear and or number one priority and while there are numerous pharmaceutical companies in the region.

Do you have the experience with novel Therapeutics that we're looking for and so we're being quite thoughtful to ensure that as we go forward in China, we do so so right partner and the correct model.

Look forward to keeping you all updated on our global efforts for now the captain to patients worldwide.

As well as the activities were undertaking here to set the stage from other captains anticipated U.S. launch with that I'll hand, it over to tailor for an update on the Companys financial results the second quarter Taylor.

Thanks, Bill and good afternoon, everyone.

We ended the second quarter of 2020, and a strong financial position with cash and investments totaling $918 million.

Geared to 430 million at the start of the year.

Increasing our cash balance came from our successful financing during the second quarter. Following the announcement of positive explore results in which we raised approximately $605 million net proceeds.

So let me pause there to express our deep appreciation for the support of all of our shareholders and in particular the participation of so many new and longstanding investors in our offering on behalf of the Myokardia team, we take our responsibilities to deliver on our mission very seriously and we're thrilled to have so many of you share in our excitement for the.

The opportunities that lie ahead, as we bring that camps into patients in need and apply our precision medicine approach to additional cardio My office see at heart failure conditions.

Well much of today's focus has been on efforts to bring maverick camps into as many obstructive HCM patience as we can our progress across the portfolio remained steady with several milestones anticipated between now and year end or early next year.

Starting with Maverick Hampton Inn, obstructive HG young Dr. Yakubu only votto, we'll be presenting the explored data late breaker presentation at the upcoming yes see virtual scientific Congress.

We're planning a virtual IR have done on August 31st to review those data with Dr. Olive auto the principal investigator for explore.

We expect to also discuss some of the Precommercial activities currently underway to support matter Kimptons introduction.

Of course, a major driver of our obstructive HCM program will be the submission of our first new drug application in the first quarter of next year.

The American Hampton Inn diseases of diastolic dysfunction, we anticipate beginning or phase two study in a subset of health past patients before year end. Additionally, we plan to meet with the agency later this year to review Maverick results and discuss magic Hamptons regulatory pathway and non obstructive HCM.

Lastly, with respect to Dan a captive we're gearing up for two clinical studies following encouraging clinical and preclinical results presented during the second quarter, which pointed to a unique mechanism of action.

Phase two study of data camped it for genetic dilated cardio my off the fees is expected to begin enrollment in the second half of this year.

And a new study looking at then a captive in patients with this dollar to function and atrial fibrillation is expected to begin in the first half of 2021.

In order to provide a deeper look at our ongoing efforts across research or develop plans for Maverick Hampton Inn, Danna captive and preparations for the commercial launch of Maverick Hampton Obstructive HCM, We're planning a series of Webinars starting in the fourth quarter, we look forward to rolling out detailed through these events in the coming weeks.

Let me now open the call up to your questions operator.

Jeff for you there were ready to start the acuity period.

Yes first question from the line of Jin.

I'm in for a new Palm Roma.

Your line is now open Sir.

Oh, great. Thanks, Thanks, so much for taking the quick question guys.

Two quick ones from me.

Any new analyses at yet from the explore trial that we should be looking for beyond what we know.

On the topline data and.

The other question that we get it a lot is it just the timelines on the explore.

Filing in one Q. So what are the gating factors to getting that done and are there any.

Things that could expedite or efficiencies that can be gained it to expedite the.

Filing given you had some of preclinical data and the pioneer results already in hand, thanks much.

Sure Hey on a bomb its Taylor so for yes, see we there will be some additional data that that will be presented these are the.

The the complete results from explore now I will say, we had a fairly extensive release at top line.

And and so there's a it's not that for sure was the most material set of information. So you should expect some additional analysis.

To be provided and we'll have that it yes see but then keep in mind, we have a long term extension.

Ponant of of explore that we have resumed enrollment in its continuing to accrue patient years, and so there's going to be additional analysis that comes out over time. So.

Yes, the isn't the final stop on the journey of.

The data set that we're generating here with the study on on timing, we feel good about the submission timing in the first quarter of next year I think that's the right expectation for people to have you can certainly rest assured we're pushing.

As hard as we can.

And but but Q1 I think should be to write expectation I'll turn it over to Jay just to talk about the process with the agency, which certainly been Super collaborative.

And is and has aided by the by the breakthrough designation that we received Jay.

Yes, so with breakthrough we have the opportunity for multiple interactions with the agency. We know that were on the right track with won't be actually Oh, I have already show modem and we're now.

All the integrated documents, there with the csrs et cetera to be able to actually I told us with them and we now have the opportunity for us to be able to have this interaction through our preparation through the submission the eventual filings.

Great. Thanks, so much for taking my question.

Thanks all of them.

Next question comes on line and the thing Ahmad.

Sir Your line is now open.

Hi, guys.

Good afternoon. Thanks for taking my questions tops I wanted to get a little bit of your thoughts on how are you thinking about the paradigm shift that that might be needed at least initially when I'm stuck in HCM lunches and the U.S., we've talked in the past in detail about the potential of Nava to that.

Only delay surgical ablation for example, but in some patients maybe even completely eliminate the need for it and as you think about the the ramp expectations. How do you think doctors at least initially will need to be educated in order to better understand that particular aspect of it and then.

Follow up that I have is how much can the valor study based on its design potentially increase the market opportunity from Alba overtime.

Hey disease good to hear from you. So let me start maybe given a big picture view of your question and that have bill add some specifics around the educational efforts that the team has been working on now for some time.

Keep in mind in terms of dynamics at launch we've got.

A reasonable number of prescribers in the diagnosed population with who are familiarity with Maverick Hampton through its four so this is great. So generally speaking the education, there is going to be a little that.

There are educated and we're building on that and they see sort of the benefits. The good news for US is we this study was designed.

To measure the things that really matter to the physicians and we're stepping into a relatively old standard of care context. So.

For us we have essentially demonstrated that NAV accounting is hitting all the elements that physicians are interested in and so we feel pretty good about their willingness to want to use it.

Improving of symptoms improving a function the safety profile was great.

And so I'll come back to your Valor question, maybe after given bill an opportunity here too.

To elaborate a little on the educational piece and adoption.

Yeah. Thanks, Thanks to also.

We we estimate a diagnostic rate today somewhere in the 15% to 20% range and we fully expect that diagnostic rate to double.

Over a certain period of time as we approach and get into into launch so and to drive that are a couple of things are more than a couple of things I mean, the data clearly I think its doctors recognize.

How good this drug is in treating substructure form they're going to start looking more for for the disease, but we've already identified some kind of barriers that exist today, one of those happens to be.

Quality.

And interoperability of echoes when we talk to doctors and centers around what are some of the barriers to an accurate diagnosis they point to.

Cardiac refuse it's a rate limiting step so we're in the process of working with the American Society of choreography Ha C C.

On ways to help improve the quality.

And interpretation.

That goes we've also as you've heard US talk about we launched a disease state campaign, which is geared at this point toward HCP watch that November last year, and we're continually adding this is the expose HCM DCC can cover continually adding content.

To that.

We're working with advocacy groups et cetera, we're doing we're doing quite a bit.

Working with the major medical associations GCG campaigner RMS sales are working with with the field as well.

So there's a lot that we've done and there's a lot to be done, but I think the key point here is that we fully expected diagnostic rates to improve dramatically.

Over over the launch.

But the drug.

If I may have on dollar you asked how we expect the dollar to impact.

Thank you asked how we expect dollar impact uptick and when we were running the market risk. When we were running in the market research. We do these share calls and we see through different ppps for physicians and it's clear that the TPP with valor does give us a lift.

A lot of doctors believe that based on explorer alone.

We would expect to to reduce the need for surgery, but I think valor.

It's going to be an important addition to the evidence behind behind Melba, Captain and addresses a subgroup that we didn't get a chance to explore thoroughly and explore which has to the sicker patients right to the kind of late functional class III functional costs for population so.

It's a small group.

And we believe that that doing the work there was the right thing to do for a company that intensively.

In this space and help it will very much help round out we think the utility.

Now the captain in that population.

To Zeena would I would add just at a overarching level. This is the allover is the first study we're talking about here in a bigger strategy for us to just continue to generate evidence that we believe is clinically valuable says in addition to adding some of the more sicker patients we are engaging Cleveland clinic and Mayo here along with.

You know dozen or so other sites in Cleveland and May or the number one HCM sites in terms of patient volumes that they see the and they were not a part of explore so there are various aspects to this study beyond the impact, let's say to the label that might influence uptake. So we're thrilled to be getting that study going look for more.

Efforts like that from us beyond let's say the initial label based on explore that we'll continue to elaborate on as we hopefully look to continue to increase the standard of care for patients with more and more evidence of clinical benefit from from our work.

Operator next question.

Next question from the line of reaches Robyn.

Your line is now open.

Hi, guys. Thanks for taking the question I wanted to follow up on the MRI cohort from Xplore can you comment on how data capture.

From that cohort is going, especially if there's any.

David Confounding and what are you guys thinking now as far as.

Yes.

[noise] data, especially in comparison to valor tightening.

I've got a follow up.

Yes so.

You know that there was a sub study with and explore which patients actually got.

Life cardiac Amar.

We will actually be reporting that data out.

In the future.

As we get all the data analyzed but cobot wasnt negative impact to that philosophy. We've continued to follow patients from the long term extension and have the opportunity to extend on these data but updates on the on the timing of the presentation to little bit later on.

Got it and if that later like.

Later than the and the filing later than no I guess.

Wondering like rough timeframe I'll be talking 2021, 2022 or even further.

The totality of the day that we've gotten from explore will be part of the filing so specific Congress that will present data.

Needs to be defined.

Understood. Okay, and then I wanted to follow up on your comments about your Sta interactions you indicated you didnt try to precise on the meeting.

That said you are moving forward just on common.

No I just keep on the beach the status quo just comment on.

What you got that gave you such confidence on that you don't need to pursue a meeting, especially with the reorganized the.

I mean, the investors it had a really rough road with new just.

If it had over there in CV right now so you know how confident are you with the reorganization new personnel.

What you have we've had a great relationship with the agency in this division.

Throughout the development.

Okay, even before it gotten to the clock.

So with the.

Breakthrough designation.

On the pre read materials that we submitted for our.

It's a leading the feedback that we got was extraordinarily clear it told us that we do that what we were prepared was inline with.

Affectations work.

What would be good.

Our submission and with breakthrough would we have the opportunity to come back in house additional dialogues with them throughout the process third so we didnt actually need them either because the result, because the feedback was so clear.

Next question from the line and Jim Besch enough.

Your line is now open.

Yes, hi, guys. Congrats on all the progress on the breakthrough designation. So maybe starting with that was there one aspect of explore data that was the focus of the breakthrough designation in one part of the endpoint was it Pico to New York Heart Association classification to compensate or just a sense of what was valued by FDA.

In granting the breakthrough designation.

Well I think the FDA.

Value would be the totality of the evidence obviously the primary endpoint.

And all the key secondary so clinically meaningful to patient and physician there.

Hi level of statistical significance, how well it was done I think are important element on top of the fact that there is incredible on that.

In HCM, so that all told we built a strong case breakthrough and we're very very pleased to have received.

And then just following up on valor with the goal of obviating the need for septal ablation.

Surgery.

What is the criteria for septal ablation, Chris surgery, and what level of LDL t. reduction or other improvements would obviate the need just trying to understand what do you need to do that actually obviate the need for for surgery and what's the indication for surgery.

So.

Hi, good lines.

Recommend considering patients for production therapy, when they continued to be highly symptomatic despite medical therapy.

Now a gradient over 50 millimeters of Mercury.

For these patients then the only option for getting symptomatic.

Really functional improvement.

Didn't open heart seizure, where the ventricles opened and actually we move part.

Up.

Part of traction or Alternatively go to the California, and actually inject alcohol into coronary artery.

With member Count them, we can give them once daily medicine, which we think based on explore we'll be able to reduce the gradients majority of these patients you give them symptomatic improvement as well and replaced the need for these patients need to go onto acceptable induction therapy to get the.

Symptomatic and functional improvement.

And take them below what guidelines the guideline criteria quite readily.

You know in the explore trial.

Over three quarters of the patients were able to get the great. It's below 50 millimeters of Mercury.

And over half the patients were able to get below the criteria for the diagnosis of obstruction getting bluecore millimeters from Mercury. So we're very confident in this trial going forward.

And just one final question just in terms of.

Launch preparation cardiology in general seems very guideline driven and so how important are getting onto the guidelines. What are the important groups that you know decide guidelines for obstructive HCM and is there anything you can do now you get in front of those guideline committees.

Hi, its Phil.

Great question. So the guidelines are driven and HCM by ha.

Which we have a longstanding kind of relationship in partnership with as well as HCC and.

We're keeping an eye on on their guideline slow their timing.

Working with them so that.

When the opportunity presents we're well positioned to.

To get matter camps and explore data represented in those guidelines.

Great far as an important question Oh, sorry go ahead.

I'd say as far as importance.

In the long run guidelines are important.

For sure.

We don't have any doubt that that we're going to be included there in a short term, whether we're going to be as part of the guideline that launch or not.

Is it is still something that we're trying to evaluate right. We're trying to work with the those two organizations to find out theres an opportunity for some kind of supplemental.

Publication that that we might be able to drive I don't see guidelines as being a critical barrier or lack of being in context as being a critical barrier.

To the launch of Melba, there's there's there's so many patients out there already that a bit on background therapy that are still symptomatic that are being referred to surgery that I think.

I think there's enough pent up demand there is it just this drug is going to be used.

At launch whether rent a guideline or not.

Got it thanks, Thanks again guys.

Thanks, Jim.

Next question for the line ALLETE young.

[noise] Your line is now open.

Yeah.

At some of the progress.

I guess two questions I'm just one.

I think bases I know, it's early can you just kind of help frame I kind of how the market dynamics differ how you know kind of doctors think about on the treatment landscape and then second question as it's like maybe for Tom 17.

Big picture watching for that the hundred K claims are you onto from that kind of it a bigger opportunity set and I guess I'm curious in relation to your comments around kind of.

Partnering aspirations and interest around the globe. Thanks.

[noise] highly kids spill again, let me start and maybe maybe torso can that can close off I missed some of your points. I think your first question was you know what do we learning about about to various geographies and the nuances around the market dynamics.

So what what we're learning is that.

There is an unmet need just about everywhere we look.

We're getting fairly deep into into Europe, but we've also explored some of the other regions as well and there's there's clearly an unmet need there there's clearly a desire.

Of it, particularly in Europe, where we've done they actually kind of hard core research.

From physicians for something that addresses the underlying.

Disease that that can help.

These stations that are already and continued to be systematic despite despite standard of care.

Some countries have a more centralized approach to the way they managed to patients where patients are referred only two centers of excellence, whereas.

You case, maybe an example of that whereas there are countries like Germany for example, where.

It's not as centralize there are centers.

And they clearly we'll treat a number of patients but the community based cardiologists will also initiate therapy. So we're working through.

We're working through those dynamics, so I think that kind of the upshot. Other dessert there seems to be more similarities across these countries and regions and just similarities in.

In terms of pent up demand and opportunity, obviously pricing and those types of things are going to vary.

So I hope so here, yes that was exactly thank you.

Yes and question I was just philosophically are you locked in for you know kind of a smaller the 100 K claims are for the bigger kind of true diagnosis, they really exists.

Well, you're super kind to repeat the question I didn't have it this time to only to the thanks. Yeah. We you know US we are in this for the long haul and we're looking to build I mean, our strategy is to be the world's leading cardiovascular medicines company and we want it and that starts with HCM. So this is about.

Really disease area leadership build relationships around the globe with our quote unquote customers, who are the patients. The physician health authorities insurers are central to us. So we're going to build those relationships directly I think you heard from bill some tenants that are really consistent with that.

And then kind of operationally how to let's say optimize the.

Our ability to get them get the therapy to patients and improve access on a region by region basis, we might need to customize. So it's it we are a very much a global company. This is a global disease and when you when you want to.

Bring a transformative therapies that take on diseases, I think you've got to be prepared to.

Good to play that way.

Great. Thank you.

Next question from the line of Nike Austin.

And is now open.

Well thanks for taking the question I wanted to go back to something that I think with Bill is talking about before when you. When you were introducing a different target product profile to clinicians and getting feedback around potential share.

Opportunities with different different kind of pictures are all novel curious if you've done the same sort of work either with with payers or with the kind of cost effective analysis groups like ice or things like I'm curious if.

Things like Bell or other studies complimentary studies.

I would say market that you're planning down the road, how much influence and residents those have in terms of either.

Supporting supporting pricing are confirming pricing, if they're likely to kind of read out.

Post kind of post approval by consistently and then my second question, but just the.

Curious, if there's any update or and timing of of two to four and just kind of your strategic thoughts about that asset going forward at this point. Thanks.

Hey, Marty as Phil I'll take the first one and then maybe kick it over.

To to Jay or Taylor for two to four.

We're doing a lot of work on our modeling so we've kicked off burden of illness works with our health economics now comes through.

We're in the midst of building out our cost effectiveness model and we've got some preliminary information there.

We're building on and we're kind of all this rolls into the overall value proper devalue dose here that we're going to be taking forward to to payers.

In the U.S. and abroad, ultimately so doing a lot of work there and the c. the signs.

The initial work are quite encouraging.

What we've learned specifically in the U.S. is as we started to engage now so we let me back up we did some market research with payers testing different price points.

Around restrictions and access about two years ago.

And we're comfortable as we think about our pricing framework, we're comfortable that were.

Going to be pricing the drug at a price yeah were pairs are going to be intervening in a significant way.

So.

We're not overly concerned about about payers being the rate limiting step two patients getting getting the drug based on based on price we've begun to share the export data with a lot of the key.

Payors DMC goes in the in the PBM is out there and they're quite interested in it and there there are returning our calls in there they're very interested in learning more and so we'll continue to build those relationships as we get as we get closer to launch.

So I look I feel like we're.

Getting close to two aligning around I wrote the pricing is going to look like based on work. We've described not yet ready are prepared to kind of guide you are the others more than we have been we've been talking about.

And orphaned orphan disease type pricing not ultra orphan disease type pricing. So we're still.

In this 20000 to 100000 dollar per annual.

Range.

I think valor.

Will help.

The cost of you surgeries are expensive and we're modeling.

Today.

With that will look like so I think dollar only gets us upside.

I don't I don't really see any downside to dollar at all it regardless of the way it reads out.

Only see upside.

Also.

Or Taylor, Hey, Marty on the <unk>, yes.

Hey, Marty tailored so thanks for the question on why K two to four this is a program were in phase one and we have resumed enrollment in that phase one study to do for our study was one of those that had to be put on pause due to covert but we have resumed we.

Other reset a timing guidance on when we'll have phase one data just because.

There are still challenges due to cold that and we want to make sure that we fully understand enrollment rates before we we give affirmed guidance, but it's moving along and we would expect that in a relatively near future no strategically.

We're still thinking about two to four very similarly to to the way. We've described it in the past I guess what has changed over the last few months is that we've delivered data on Maverick Hampton and it's really hard to find the gaps in the Maverick Hampton data. So we're we're super excited about that.

But we acknowledge that we're still we're still early in the us and our goal as a company is to be the disease area leader for individuals who have H.C. alma to meet the full set of unmet needs and to continue to raise the bar on standard of care.

For these people and so we want to be the company to do that we think we're we're absolutely on a path to doing that with Maverick Hampton and as we go forward, we're going to learn more about what the residual need is.

And we'll see as we deliver on phase one where subsequent datasets from two to four if there is indeed that it can uniquely Phil similar like we have lose one we've got other programs earlier in the pipeline that we would hope could continue to round out the the care for.

For for HCM patient so that's the way we're thinking about it.

The only thing that's changed is obviously majdic Hampton is setting a super high bar for any therapy that comes behind in the HCM space.

Great. Thanks for your insights on the appreciate it.

Next question from the line at Sir.

So.

[noise] lending is now open.

Thank you for taking the question congrats on the progress I'm just a couple of questions on value I, just wondered if you could maybe discuss and the powering assumptions around the treatment effect for the plan at or above the 50 patients.

For Valor and then secondly, just wondered you know that 15 HCM centers highlighted them the press release.

If you could maybe talk about what what percentage of sort of.

Scepter reduction procedures in the U.S. does does those HCM centers represent thank you.

[noise] so.

Okay.

Hey, powering assumptions for the study will get all.

Manage now and likely design paper.

And im not too distant future will talk time later, but.

The fact is powered off of what you've seen him explore with the ability to scale.

Okay.

Hello 50.

If we do very well getting below 30 in the Tolerability you've seen.

So that's what what is taken into consideration important powering assumptions then we'll get all the details.

When we think about the.

Sites that we actually how.

[laughter] facing this these are the site that actually.

Sort of surgical Oh, well I'll call.

Stage participating or trial, so it's a great opportunity to engage.

Additional centers that were.

Well the explore.

Hey answer that was Jay he'd battling with the the east coast Hurricanes nowhere, so apologies for his line being choppy, but what are you saying is.

And this atossa here what are you, saying is the the 15 sites represent the majority of the simple reduction treatments and that's both of my up demand the alcohol subpopulations that are done in the U.S.

Okay last answer yes, perfect. Thank you Jeff.

Two questions on the line of Jeff Hum.

Please now open.

Thanks for taking the question had some questions on one of your earlier programs can you remind us what are the gating factors out for Dancing Act one into clinic and it is still on track to begin in the first half next year.

Yes, Hey, Jeff. It's also here thanks for asking about the pipeline and I think it's it's both we haven't talked a lot about danna captive, which were excited about and is moving forward.

Act one to remind the audience is a program that is also activator of the proteins in the cardiac muscle cells. It still advancing very well and research phase and in terms of our guidance I'm Taylor I do you have that at the tip of your tongue here.

Yeah, we haven't Jeff we haven't updated our guidance on preclinical programs in a while that is something we we mentioned on the call. We're planning a series of Webinars events, starting here in the fourth quarter.

And so we will have one that's dedicated to our research efforts and will be covering that in more detail.

Okay, great and how might that targeted half rest syndications frac one differ from those after danna captive are there any learnings from dentek enter that you can apply to ask one given that there does appear to be some overlap in potential patient population. Thanks.

Yeah, Hey, tailor it faster here, if you don't mind I think what you're getting a at their Jeff is really central to our whole philosophies why we think the platform so powerful and efficient at Myokardia. So.

Rather than sort of describe to you today, where you want to venn diagram of patient profiles with systemic dysfunction I think the thing to think about is we're generating evidence and we do this across all of our molecules that really helps refinements as we go and we're in new territory, we've got very thoughtful strategy.

He is about how to map the patient profiles relative to Biomarkers imaging markers like echocardiography.

Clinical history symptom and function because what you know I think in most of the audience at least as hurt us. If we think about 3 million people in the country that have systemic dysfunction. The way they get to that suspect. This function is different that is likely going to need different treatments different approaches different doses. So if you think of our programs we now.

We've got act one we've got Danna captive Dan a captive is aiming now at genetic DCM and then a second group of half breadth with a fair. So we're going to learn a lot about the differences in these patients their underlying biology, and what they need and so act one definitely bring something different to the table so standby.

On that just your I know that we are collecting really important insights probably proprietary that have not been unearthed before that are going to give us a real leg up in matching drug mechanism to disease mechanism and I think what we're hoping to see and I think what happened is and maybe five to 10 years, we're no longer talking about three.

<unk> million people would have graph that we categorize with one crude measurement objection fraction, but we're really talking about you know a handful of different disease profiles that are framed much more thoughtfully and robustly.

Thanks, Jonathan.

Your next question operator law here.

Your next question from the line of modest themselves.

Let's now open Sir.

Thanks, operator, and congratulations on the quarter. This is Keith on for Mohit just had one question regarding Uh huh.

So we're all looking at the FDA decision Entresto in half.

On the Novartis has filed on the sub group analysis of Paragon HF trial can you help us understand the significance of the outcome from your point of view since you're also working on the syndication and then also where do you think the FDA stands on improving drugs in these indications on biomarkers as opposed to win for functional and play.

Thank you.

So that's the first part.

As the fts potential approval for health, so based on Biomarkers and we've seen I think that Theres, a government openness to using feel function endpoints as something that they're open to so I think that this is from FDA has clearly signal.

Openness to this with their position paper last year, we really applaud them for that but very much in line with where we're going.

In terms of.

Being able to develop a program that complements.

Where we see our program with how we're clearly targeting patients with yeah that are at the higher end, where we think we'll be able to actually build would be able to benefit that's really quite distinct pretty healthy male population. There I think that we really need to be able to start to drill down much more.

Typically.

Into eating.

Oh targeted diastolic dysfunction and stop lumping half of heart failure is just preserved ejection fraction. So I think that we'll be able to be become leaders in the space to be able to really define who has actually been able to.

Benefit from different therapies recategorized the disease this way.

Keith it's possible here that was that was Jay on the line there.

Just for the transcript purposes, the interest though.

Event here on has to just keep in mind that we have had nothing approved and how that's so it's it's one of them more major unmet medical needs around on the planet.

Diastolic dysfunction is affecting you over 10 million people around the world.

But what we're doing has is fundamentally different than what interest or does some different mechanistically annual back maybe to my previous answer on a previous call. A question. It's important for us to think about designing and developing drugs that are going to have this transformative effect.

Eventually hopefully our goal is to get to disease modification. Our view is as we're matching drug mechanism to underlying disease biology and disease driver you stand the greatest opportunity the fundamentally disrupted disease progression and effect of the totality of what patients and clinicians are looked.

For quality of life improved symptom burden.

Improved function as well as hospitalization mortality and so that is something that would we design our molecules and the Mavericks camping endemic Emptive absolutely decided with this mine we believe they have that potential.

My view is that's not how interest there has been designed there might be and there could be benefit and that benefit and have pets is gonna be really welcome because we need some thing, but there will be in my estimation.

More work to be done in half for molecules that are really mechanistically targeted.

Operator.

Next question from the line of government site.

Let's now open.

Hi, this is going on for Georgia, Congrats founded BTD into the late breaker, just we had a few question.

If I remember correctly, I think explore with about 30% population that with class three.

How representative of that is of the overall like obstructive population that gets referred or some sort of surgical correction and then.

Did I think about it the other way around I'm wondering.

There are.

Popular and what percentage is not a candidate for steptoe ablation or surgical correction because the problems not actually at the September I'm trying to figure out is that.

That might be something I'm wondering that would be amenable to NAV account them.

Maybe to surgical and I'm thinking about this all wrong, but when you would be great to hear your thoughts on that.

So I think there we have good results.

Both our class two and our class three patients and explore so we got good benefit in terms of symptom reduction.

Our.

Overall primary endpoint.

I think that this will translate pretty well into valor.

We're seeing an increasing number of patients who are class too.

Being referred for sub production therapy. This had previously been mostly class three and four but the trend has been for more cost too, but overall, we think that the explore results will then be able to model.

And be able to be predictive of really beneficial recall.

Yeah. It's it's Bill let me just let me just add one thing here.

We think explore is highly representative of of the population.

Here in the us in Europe, given that yeah.

We think about the symptomatic population to break out between functional class two functional class III is is about 70 30, it's probably a little closer to 60 40, but highly representative.

Next question from David Nierengarten.

Your line is now open.

Hi, Thanks for squeezing man I couple of questions on the dollar first off maybe I'm, maybe I missed something but.

Could you explain how that randomization works with the surgery versus a.

Pharmaceutical.

And how do you avoid bias of yeah of the surgeon or physician and then second what's the what's the time point.

For that you know given that presumably surge or surgery patients as I recall experience improvements immediately and that it might taper over time, where the converse is true for a metric after that seems more improvements continue to strengthen overtime what's the.

So what's the choice on the endpoint.

For timing purposes. Thanks.

Okay, Let me clarify in the Valor study patients, Iran, who are being referred for SRT.

Who come into the trial or randomized to either received placebo or member caps.

For the six times correct.

And then at the end of that.

To be deemed whether they are either get start they elect to get elsewhere or their guideline eligible for us starting at the end of the study.

One will be allowed to continue.

Open label extension.

And.

So during that open label, well I guess that they meet the guideline, but if they could subsalt placement for the open label extension I guess, that's really more of the point is for that extension study.

You know it to to support the findings that.

On a monthly amount of captain as attractive you would.

You just follow them for for how long or is there an additional time point there kind of how.

Constructed.

Yeah. So we'll be can genuine does any of them for a prolonged period of time, it's not only to be able to avoid the need for surgery over the first 16 weeks, but it's to actually be able to have a durable benefit.

That these patients would not need need.

Sircy for a prolonged period of time.

Okay.

Hi, This is okay got it.

Okay. There are no for the question at this time please continue.

Great. Thanks, Jess and thanks to everybody for joining US today, just a reminder, that we will have our data being presented at yes see.

At the end of August and we'll be hosting an investor event. Shortly after that so stay tuned for more details we look for it to speaking with you then thanks again for joining us today.

Thank you and that concludes today's conference. Thank you everyone for participating you may now disconnect.

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