Q3 2020 Insmed Inc Earnings Call

Our successful.

Consequently, the error rate to be preserved for two trial.

Each at 0.05 is 0.01252 side.

So the correct comparison is point or one for Aspen compared two point or one to five for a two trial program.

In addition, Aspen as a single study has 90% power various a program with two trials each having 90% power would have a smaller overall power at 81%.

So when the number of trials is accounted for we have more power for the X X the treatment effect, a 30% reduction.

And an order of magnitude difference in type one error rate to preserve that is acceptable for FDA and EMA.

Similar to will the Aspen study will enroll patients with at least two documented from expenses acceleration that were treated in the past 12 months.

For this single study approximately 540 patients will receive each of 10 milligram friends for captive 25 milligram price attempted or placebo once a day for 52 weeks for a total of approximately 1600 20 patients.

For full details of the study design. Please access our R&D day presentation available on our website.

We plan to enroll patients across approximately 480 sales in 40 countries to.

To drive enrollment, we're fast tracking several countries with the U.S. and Australia already approved and we expect to add sites activated by year end.

We are also targeting sales that were involved in the will study.

We are encouraged by our progress as we are tracking ahead of our internal benchmarks.

We look forward to providing updates as the trial progresses.

Beyond Funky excesses, we believe that venkat that have broader potential application as a novel neutrophil immunomodulator weak.

We plan to prioritize and capitalize on this potential opportunity and work towards building an industry leading portfolio around friends for CAD.

In the near term, we will be working with regulators on exploring an appropriate path forward and determining next steps for development in cystic fibrosis.

At the same time, we continue to advance our research efforts to support expansion to other indication light.

Nice GP ITD, our eight oncology or lupus nephritis.

Let's now move onto our Registrational programs to pursue FDA approval of airing case as a frontline therapy and our overarching goal to establish a new standard of care for patients suffering from NTM lung disease.

This effort involves the planned clinical program that includes two separate but interrelated clinical trial that will be conducted in parallel with staggered EPS.

First is the advise trial, which is targeting enrollment of approximately 100 patients with newly diagnosed neck lung disease.

This will be an interventional study designed to validate longitudinal characteristics of the patient reported outcome or Piero tools that will be used in the second study.

The encore study.

The anchor study will be the pivotal trial designed to establish the clinical benefit of Erra case in this new patient population.

We expect to enroll approximately 250 patients.

The anchor study is intended to fulfill the post marketing requirement to allow for full approval of aerospace in the U.S. and to support the supplemental Andy for the use of Erra case, as a frontline treatment for patients with neck lung disease.

We plan to initiate both trials by the end of this year.

Since our R&D day, we've already made progress towards this goal and have conducted numerous site initiation visits.

In summary, we are very excited about the development across our pipeline and potential overlap among our program.

We look forward to sharing our continued progress with you.

Let me now turn the call over to Roger to discuss some key operational update Roger.

Thanks, Mark and good morning, everyone.

I am pleased to report that from an operational perspective, we had a very solid third quarter with.

We continue to experience strong uptake in the growing air case franchise with growth in new prescribers during the third quarter that we believe is in part due to the arrival of the new NTM treatment guidelines.

Additionally, we were very pleased to receive approval of a supplemental new drug application or San Diego that allowed important new updates to our us label.

We also continue to make excellent progress internationally as we further the global expansion of the aggregates franchise, which we expect to be a meaningful growth driver for us in 2021.

Let's begin with the FDA approval of our EPS, India, which we received just last week.

We are pleased to report that this approval as important efficacy data regarding durability and sustainability of culture conversion to the arc is label.

In preparation for this approval, we tested the new durability and sustainability data in market research with healthcare professionals.

Across both infectious disease, and Pulmonologist positions our market research revealed that these see these new data as very promising, particularly culture conversion three months after ending all treatment.

We anticipate that this update may motivate new prescribers to try our pace for the first time.

And increase the confidence of existing prescribers to prescribe advocates for additional indicated refractory Mac patients.

These new data in the Sndk, along with a strong recommendation in the new NCCN guidelines just published in July give us important information and tools to build momentum for aerospace.

Turning specifically to Eric is performance as Sarah mentioned, we had revenue of $43.6 million in the third quarter, resulting from our continued success engaging both healthcare preferred providers and patients in this largely virtual setting.

Corporate related restrictions continue to result in regional variability.

The most important metric we're tracking is in person patient visit volumes.

These track closely and inversely the presence of cobot surges.

For example, in the second quarter, the East Coast was down but began trending back in the third quarter.

Where's the south and west were less affected in the second quarter, but faced significant challenges in the third quarter.

Overall doctors across the country are learning how to operate in the corporate environment and despite the challenges of Cobiz. We continue to see a recognition of the importance by physicians for the use of our case in appropriate patients.

As one might expect we're seeing stronger trends in enrollment forms in regions, where officers have higher reopening rates and consequently higher in person patient visit volumes.

Notably we saw an increase in new prescribers this quarter, which we attribute in part to the new guidelines potentially helping physicians identify refractory patients given the recommendation to add Eric case to the standard treatment regimen, if a patient has not culture converted after six months.

We are hopeful this clear and strong recommendation helps physicians determine when to add Eric case to the frontline triple therapy recommended by the guidelines.

Importantly, the guidelines also recommend the treatment should be continued for 12 months after culture conversion.

This trend of new prescriber growth is very encouraging as it lays the groundwork for future growth as regions impacted by cobot return to something approaching normal.

Overall, we believe that as offices reopened and as NTM patients return to physician offices, we will see growth accelerating from current levels.

In addition to growth in the U.S.. We are also making exciting progress internationally as we work towards global expansion of the Eric is franchise.

Let's begin with our efforts in Europe.

As will mentioned we are pleased to announce that we received marketing authorization for our case in the EU for the treatment of Mac lung infection as part of a combination antibacterial drug regimen in adults with limited treatment options, who do not have cystic fibrosis.

As you heard about R&D day, our infrastructure in Europe is in place.

Modeled combined building our own commercial entities and field force in major markets, while utilizing distributor models where appropriate.

We expect that by the end of this year, we will have 24 customer facing personnel.

We anticipate grown to a team of 50 by 2022, reflecting the anticipated phase launch and receipt of a reimbursement approvals.

Overall, we remain on track to commercially launch our case first in Germany, where the United Kingdom and other emerging markets to follow subject to local reimbursement processes.

In addition to our recent success with European regulators. We are also excited about the potential opportunity in Japan.

As we discussed at the R&D day intimate decided to register add if approved commercialize our case in Japan ourselves.

We believe that building a high quality team in Japan to bring Eric is the Japanese patients. Initially in refractory population followed by frontline therapy is the right strategy that leverages, our global infrastructure and can be accomplished with a modest local footprint.

To support our anticipated mid 2021 launch we've built a strong presence in Japan with plans to have 19 customer facing personnel by the end of this year.

More broadly given the overlap between brought the emphasis and NTM lung disease.

The investments, we are making now positioned us extremely well for potential future Lontra brenzel captive in Japan.

We are excited to expand their case brand and pursue the long term potential of the franchise in the us Japan and Europe.

I want to sincerely. Thank the entire team for their continued commitment to the NCM community as we work to achieve these milestones.

From a supply perspective, we continue to have a robust supply of aric case and have not experienced any cobra related or other interruptions, preventing us from serving our patients.

As we prepare for the potential forthcoming international launches, we have on hand sufficient apiay for Eric case to meet anticipated global demand through the end of 2022.

For parental Kathy we have ample supply to meet the clinical trial requirements of a global phase three program.

We also have clinical trial supplies manufactured for our phase one and phase two ATP IP programs.

With that let me turn the call back to will.

Thanks, Roger let me close out our prepared remarks by reiterating our focus on continued execution. During this next important chapter of growth for instead as.

As you just heard we are making significant progress across our pipeline and commercial program and we will carry that momentum forward through the rest of this year and into 2021.

We have a demonstrated track record strong balance sheet and a clear pathway to potentially advance our exciting pipeline, while also expanding the market opportunity for Eric.

I am confident in the engineering teams ability to execute on our goals.

Grateful for the entire team's hard work dedication and commitment to patients and healthcare providers with that I'd like to open the call to questions. Operator can we take the first question. Please.

At this time I'd like to remind everyone in order to ask your questions. Please press star followed by the number one on your telephone keypad.

Our first question comes from the line of Ritu Baral from Cowen.

Hi, guys good morning.

Well.

Hi, guys. Thanks, so much for taking the question good morning.

Well, let's talk about how.

Persistence in duration right now appear to you is that increasing yes. The NAV is the guidelines have been out or for some time and no any change in trends on discontinuation.

Okay, and then I've got Oh, yes.

Sure well I'll ask Roger to comment I think one of the most exciting aspects of this quarter and in fact, a recent week as the number of elements that are leading to wind in our sales and momentum behind your case refractory franchise in the US which of course will now pay dividends in Europe, and if approved in Japan as well.

Roger do you want to take that.

Yes, Thanks will thanks for the question.

We are too so.

I don't think we've seen a significant change in the in the sustainability or the duration of therapy at this point, but you're absolutely right to point out.

That there's the guidelines recommend.

Recommending 12 additional months of therapy beyond culture conversion and.

And we see that resonating with physicians as we go out and discussed the guidelines and just a reminder, that we've been talking about the guidelines for for quite a long time awaiting the issuance.

They only came out in July so we are able to actually engage with physicians to talk with them about the guidelines and Theres. Two factors that I think are really resonating. The first is a very clear and strong recommendation as to where to use erra case and that gives physicians who are perhaps wondering should I continue to persist with the frontline.

Triple therapy as per the guidelines beyond six months it gives them a very clear direction that after six months of these patients are not culture converted you need to then move to Eric is a very strong recommendation and then once you pass culture conversion that that then you would need to.

T to treat for for the 12 months. So we expect that to be a very positive tailwind.

The other thing I know that you're aware of this as well that we're very pleased about is the.

The impact we're seeing from the practical management of adverse events for our case and this is a peer review paper that came out in March that helps physicians manage patients through that first few weeks, where the airways adapting to Eric is so helping patients manage through that and we think that thats going to.

Help patients space to stay on that Oh, Americas therapy, and then be able to complete that full.

Triple therapy go into culture conversion plus an additional 12 months. So we remain pleased with the persistence and the duration and we expect to be able to leverage the godines to further improve that going forward.

And Richard just to add to that we didnt really make a big deal out of it to be very blunt, we weren't sure we were going to get it but the recent approval of the SMB brings.

Brings additional clinical data into the label that allows us to point to physicians in conjunction with the arrival of a guidelines benefits that patients can expect to obtain as a result of using our therapy. So it's a it's a powerful combination and non approval the EPS and da happened only a week ago.

No I don't.

I think your question you guys to Roger as well one.

Moving to the UK reimbursement how are you guys.

We'll be facing.

Facing I know there is much different than I am.

Hoping for a little more clarity to.

Q you mentioned that.

You have all the T. Rowe price.

We continue to bottom.

You are expecting that the top five markets will be generally secured reimbursement will be generally secured at the topline site and once it too.

Roger what their dose yeah sure. So I'll take the first question.

You asked about the United Kingdom, and the reimbursement process and and.

I guess more specifically about around the around England. So the pricing. It's as you know it's a it's a free pricing market, but there are procedures that have to be follow before the the price actually gets published and officially reimbursed we expect that to to occur over the.

The first half of 2021, the timelines very in the meantime, there our reimbursement processes that can be follow to secure reimbursement for UK patients on an individual basis within within the UK, but it takes a little a little bit longer. So I would say that in that first half probably by the second quarter as well.

We'll see full reimbursement that will allow us to have a.

The robust launch in the UK.

And as we have mentioned previously Germany will be first to launch and and has that free pricing and doesn't have the same sort of procedural process that.

The UK does.

And then as far as the top five markets.

Timings will vary and as we're estimating as what they look like I think the we will have probably by 2021, we're anticipating based on the the benchmarks and how long these usually take to get reimbursement, we're anticipating the Germany, the Netherlands UK.

Italy will we'll have approval and reimbursement in by 2021, we think that based on benchmarks, France will likely take longer so I'm a big market for sure.

Work continue to work with the authorities there and there's flexibility around the timeline potentially but I think France is probably the market that will take the longest based on history and benchmarks.

And just one final clarification for the UK just to be Crystal clear, we do not have to go through a nice that's an important point.

Yep.

Got it thanks, so much.

Helpful.

Okay.

Our next question comes from the line of Matthew Harrison with Morgan Stanley Go ahead. Please your line is open.

Question comes from the line of Matthew Harrison with Morgan Stanley Go ahead. Please your line is open.

Our next question comes from the line of Matthew Harrison with Morgan Stanley. Please go ahead.

I think we probably have an issue with why don't we just go to the next person in the queue. Please.

Oh, sorry, one moment please.

You can jump back again, Matt you're in there.

And our next question comes from the line of Marty Ouster with Credit Suisse go ahead. Please.

Hey, guys. Thanks for taking the question I had a couple of I guess I wanted to follow up on you mentioned marketing, but the 44 dosing cohorts have been completed the TPP study I was curious if you could comment on how many doses you are going to evaluate and all and also if you could sort of maybe frame the doses studied relative to kind of.

The data that was put out on the Nebulized version.

Precursor of no form of a wonderful nine from a couple of years ago, I'm, just kind of a freeway.

And where you're at and that kind of goes Ascension and then secondly, just on expenses the EPS Phoenix, that's been pretty flat so far through through 2020 versus 2019, and you talked a little bit about kind of some increased hiring in Europe is perfect for Japan launch those curious kind of for this year how much of this one.

It is an intended.

Going forward kind of a pro.

Two commercial expenses in the U.S. market how much of it is maybe there is some kind of one time reduction because of covance in travel restrictions and lack of access to take when she walks into that's just want to get a little color on that.

Sure. So I'll invite Kevin to comment on the first question going into two VIP and Sarah can take the question on this today.

Great. Thanks worldwide sales Kevin.

Kevin Man, So we're quite pleased.

Pleased with the progress that we've made in that study.

For dosing strengths that we.

We did today 10.

In terms of where we're headed based on the modeling work on the animal data as we've got several more strength that we are able to continue to dose escalate through and healthy volunteers, but as with any sad Mad study.

We expect at some point, we will reach a tolerability dosing strikes. So again, we're happy with how far we've progressed and with respect to the prior nebulized formulation.

We are and an exposure of Austin will that is above what we saw in that.

Earlier stage as well, but I think right now although we're looking at data were still blinded to the dosage strengths as we see those in that off but again I think in summary things are progressing very nicely and we're very pleased with how it's going.

A real quick.

Kevin can you confirm whether whether or not you hit those comparability limits that you are looking for so far for the bill for those kind words or do you continue to see your desk right those from here.

We're still going through dose escalation.

Perfect. Thanks.

And then Marty on the expense question. So thanks for the question.

So as Roger mentioned, we've added appropriately a modestly in Europe.

Continue to add slowly there to support the launch, but we sales infrastructure, there you're seeing that extent international.

Expenses to date.

Hey, I'm, we did see some savings this year from corporate related on obviously folks aren't traveling as much and those types of things that we will look to continue to see how can we leverage the learnings that we had in 2020 and bring those forward into 2021 as we look to Q.

Keep questioning expenses.

As stable and in line as well as possible. So that we can best in R&D and.

Oh, yes.

Okay I appreciate the color. Thank you.

Uh huh.

Our next question comes from the line of Steven Willey with Stifel. Go ahead. Please your line is open.

Yeah. Good morning, Thanks for taking the questions.

I guess.

There were some comments made with respect to new enrollment forms and just.

Just on the new patient starts front just wondering if you can kind of provide any kind of directional qualitative commentary I think I think there was.

Previously mentioned not too long ago that you guys had started to kind of see quarter over quarter growth from a monthly perspective is that is that a trend that you're continuing to see now.

So I'll I'll preface to the answer that I'm going to give Roger the opportunity to take in a minute with the comment that as a general rule, we're not going to dig into the weeds of ita.

<unk>.

Within the within the profile of the launch just because at this stage, we feel like what matters. The most is the ability to generate the revenue we feel really good about what we've been able to do but we didnt know the shift in the concentration of Cowen cases from the east to the south and the west in the second quarter to the third quarter, but there are a number of drivers.

Is that are positive that we think are going to be curious to future growth from here with regard to any trends or qualitative comments. Roger do you want to address that I don't know if you want to make any statements about that yeah.

Yeah, no thanks will and I think you.

Characterized it well so we continue to see new prescribers and new patients and new enrollment forms Oh.

But not at the pre corporate levels, yet as you might expect and that's driven really by that regional variability, but I think look if I look forward first of all I really pleased with how the commercial team and particularly our field based personnel have been able to adapt to the ebbs and flows of of of cobot and what's happening in the different regions regions, you really have to be.

Quite flexible pivoting between in person and virtual interactions of the team has done an exceptional job.

We talked about the guidelines in some of the number of catalysts that we see going forward.

We have seen for sure the impact of the guidelines and that clear strong recommendation as to when to use our case that has already started to have an influence and we've seen new prescribers.

Initiate therapy, we believe that that will will continue in the future and and also encourage existing prescribers to to prescribe Erra case further we will mention and I want to just reiterate how power.

Powerful and potentially if the impact of the San Diego and the update the label could be in establishing a new patients and getting new prescriptions.

Adding in the sustainability and durability of culture conversion into our label, allowing us to have that conversation.

Physicians, who are then able to relate that to the patience I think is very powerful in their market research the.

The physician has told us how important that was that.

They can offer that to patients if they stick with the therapy. There is it a good likelihood that they will be able to sustain culture conversion awful awful therapy.

And so we feel very positive and I feel very positive about the future of the franchise moving forward.

And certainly as we monitor the in person patient visits from from a corporate perspective, that's going to be a key factor, but the long term health of Erivedge franchise I feel very good about.

Understood and I I totally get it on the qualitative militia front.

When you just think about Europe, right, there's obviously, a big big discrepancy between.

The addressable patient numbers that have at least been reported.

Relative to the U.S. and I guess.

How much of that you actually think is is it's just implicit NTM at BBB ALG versus.

They're just be.

More generalized lack of awareness and diagnosis and I guess to what extent you feel like you can close the gap on the latter via this commercial launch.

Yes, that's that's at the heart of the Governor were making Roger you want to dig into that a little bit.

Absolutely I I think it's a combination of both right. So I I do believe that the prevalence and the epidemiology has been done has been quite thin prior to the launch and given the increasing tension is now being turned to NTM. We are seeing publications, where theres potentially the prevalence has been has been underway.

Reported and that certainly makes sense. If you think about the characteristics and way. If you think about the prevalence of NTM the proximity to the water history of lung disease elderly population. All those factors are in place in Europe as they are in the U.S. So.

So I think it is a combination of just understanding digging into the data little bit better and actually looking for that but then driving awareness and an often with rare diseases, you will see that with the approval of the other therapy for the rare disease and it actually an effective treatment option.

You will see those diagnoses of those patients a rise and that's certainly our efforts will be focused on driving that awareness.

And establishing the treatment pathways for these patients to get to get that the medication in the treatment that they require.

So it'll take some time for sure to drive that awareness, but we believe that the opportunity is there.

And with the support of the guidelines with the support of the sales in Europe, We think that we have a great opportunity to impact the diagnosis of these patients in Europe, and the ultimate treatment of them.

Okay, and then just one quick clinical question a bunch of cabinet.

So so.

I know you want to you had been kind of listed as an opportunity of interest previously just wondering how you're thinking about where that kind of sits in the hierarchy of needs to pursue coast CF I know theres, obviously been a lot of interest in the space and.

The competitive dynamic is getting a little bit more interesting on on the development side is this is this an indication where you kind of feel like you need to sit back and see what happens over the course of the next couple of years before you plot of course forward or is this.

Just not an opportunity that sits but higher and higher.

Sorry, Steve I missed the indication you were talking about.

US Alpha one antitrypsin.

Oh Alpha one Jeff So I think.

Just generally what I would tell you is were still doing an awful lot of work on brands a cat.

Specifically and on the GBP, one pathway generally and the ways in which we think we can exploiting that for the benefit of patients in a variety of disease. There's a lot more to be learned I would say that as I think this year to a certain degree at our R&D day, and we continue to see in preclinical models. There is a lot.

Got a promising data out there for this pathway as a potential.

Mechanism of action for treating a number of different diseases and the early data looks good I think there is some some real.

This year, we are going to have to make some prioritization choices, where we stand right now is that while more work still needs to be done. Our current thinking is the CF is probably out front.

And it's important to dig into that opportunity and understand that even.

Even with the operation of the.

Vertex drugs in correcting patients those that haven't been treated before to see these 16 are already bracketing panic on the damage as a result of curing disease for as long as they did and so they're going to need to be treated for sometime into the future and for those that are being treated at a much earlier age we're hopeful that there without any issue but to the extent.

But that is partially effective they will need to be treated so that suggests as an obvious patient population up one I don't know Kevin if you want to talk anymore.

All about what we May know at this stage.

Net or are we still in the midst of doing work I think it's as you said I do I think is it something that's worth considering and exploring as we are on and Thats certainly see EPS is I think alcantara NASCAR alliances after Aspen.

Got it thanks.

Your second question.

Our next question comes from the line of Joseph Schwartz with SVB Mirror, leaving my apologies.

Andrew Some shows your line is open.

And our next question comes from the line of Matthew Harrison with Morgan Stanley Go ahead. Please your line is open.

Hi can you hear me.

No we welcome Clare.

Great. Thanks for coming back to me on this is that corner on for Matthew Thanks for taking the question. So so just a couple from US. So the first one I guess is it sort of like Inelasticity question relating to our case and you guys have touched on this with regard to the San Diego and the guidelines and whatnot, but it it for instance.

The case counts in this brand is to become as bad as it was in the second quarter would you expect similar impacts to through our case or do you see.

The physician indication of.

Uh-huh prescribing.

Stronger than that.

Yes, so I appreciate that question I think.

If you look back at what happened in Q2 in Q3, which you see is that these were first time very intense surges of coal that initially the eastern in the south and the west and I'm I'm generalizing a bid there, but the impact was quite dramatic and I think it's defined by the.

Significant reaction that those regions had in responding to the presence of the carbon surge. We think we're seeing now and we'll see going forward. Although it's it's hard to predict as you can appreciate is that the hospitals that physicians and patients. We're all learning better how to deal with the right.

Level of our new surgeon Covidien and you see that even now as people think about more targeted restriction methods and.

The use of a better social distancing and maps and that sort of thing and for those reasons I don't think that necessarily what we saw in Q2 or Q3 was shutdown of major densely populated areas is going to be repeated in the future. So.

What we're seeing now are areas like in the middle of the U.S., but haven't seen those surges before and even there they're doing a better job with getting in front of the possibilities and the medical system in hospital system, recognizing that they have to find a way to treat these other conditions the patients need the treatment. These are these treatments are now.

Not optional and frankly and very practically the medical system financially cannot support myopic focus on covered 90.

Does that answer your question.

Yeah, Yeah that makes sense. Thank you and then just two other quick ones, which are mostly on timing and just some more background you don't so.

Can you just give some more detail on what what the path forward is in CF and you guys mentioned that that might be your primary focus after asking for Brent you got that.

And so just like your general plan with the App and then.

When can we expect some of the or I guess, the first frontline David Vargas.

Yes, so on C. I would say that we're in the process right now working up what we think would be the appropriate protocol. There is a very well trodden path for drug development in this area and as you may recall from our distant past.

When I was at Insmed, we actually brought Erra case forwarded a pan European study of cystic fibrosis.

Gross just so we know the space extremely well I think.

But we want to make sure. We have is the best possible and most efficient path for bringing that rolling forward and just to perhaps dig in a little bit there.

In which the drug is metabolized in the cystic fibrosis patient is different than that of other patients and so it's important to understand the PK elements of different doses of the drug and so that will be a first step we think that we want to get our arms around before we advance into a more.

As for clinical program.

More work to be done there for sure I will say that I think effectively and effectively treated cystic fibrosis patients.

Is who has been carrying cystic fibrosis for a while is.

Effectively by definition broadcast this patient so the probability of impact here is quite high based on the strength of the Willow data and that's one of the reasons. Why this suggests itself for use in that population exacerbations remain an issue for these patients even after they are effectively treated.

By the vertex drugs and I think what's exciting about that for us in terms of clear unmet medical need is that our drug is directly responsive to that need and we believe based on willow data can be quite helpful and really taking away one of the last remaining challenges that cystic fibrosis patients face.

So I think your your second question was on aerospace and the rise trial and when we think that data will read out we're not giving any forward forecasts yet on data availability I think that our.

Message today is we are off and running with a rise encore and Aspen and I am incredibly excited and frankly, just impressed by what the team has been able to accomplish in terms of getting sites open getting ourselves ready to enroll patients and as we see how that unfolds in the coming months will be.

I understand what our enrollment rate is and then report out to community. What we think timelines are likely to be but we're super excited because as you've seen from our.

Description of the number of sites, we are going to activate around the world. We are resourcing. This fully to try and get this done as rapidly as possible and since we have prior experience in recruiting patients with NTM.

These centers are expecting this trial everyone's ready for their frankly very excited about it and the same is true for Brunswick County to the non CF bronchiectasis, especially on the heels of the New England Journal paper.

Understood. Thanks, Thanks for the clarity there.

Yeah.

Our next question comes from the line of John Mcneill with Goldman Sachs. Go ahead. Please your line is open.

Hi, everyone I'm actually calling in on behalf of them you Greg on a bed.

So maybe first of all I wanted to ask you know what do you think is driving the difference in sequential growth when you look at Q.

Q1 versus Q2 and Q2 into Q3 is that.

Hi, there was obviously a doughnut hole impact in Q1, so when you think about the trend ex that sort of what we're looking at for Q4.

And then maybe on the forward me now.

What would you need to see to think about providing guidance for 2021.

Yes, sure. So I think when we talk about.

The the progression of revenue growth, what I would say is the.

First quarter was the arrival of covert and everything coming to a screeching halt.

Second quarter was the adaptation of some regions effectively to the presence of cobot and its threat. While other regions were completely shut down and we were more specific in the comments on the call to say that really was the east coast largely that was driving that shutdown and the pressures we face.

The second quarter.

While the south and west were performing very effectively as we move into the third quarter. It was the south and west that shutdown on the east coast that came back and I think as Roger said you know did.

The degree to which those.

Region anywhere opens up again.

The patients come back rapidly and so we see a very dramatic shifts regionally and the responsiveness to the presence of the Covance search and I think whats encouraging as we look forward just in the Cobas dynamic is the adaptability of physicians and hospitals to the presence of this.

Realizing that they need to continue their treatment of conditions outside of coated and and we are as close to this is anybody we're calling on the front line position in the covert battle Pulmonologists and infectious disease specialists and so I think we are uniquely positioned to understand how these pressures unfold and what we saw.

Shifting from Q2 to Q3 and in color.

Modest growth or parity quarter to quarter Q2 to Q3, I think really reflects the severe arrival of covance in high density populations a.

Centers in the us in different areas.

Going forward I am hopeful that that will not be the case and that we'll be able to do is take advantage of this long list of accomplishments that weve been able to make that set us up for additional growth in the future remember that we think there are 12 to 17000 diagnosed refractory population.

Population in the U.S. eligible for treatment today, and if you were to some of the numbers that we had stated historically would be around 3000 patients that had initiated therapy. So there is a lot left for us to go after and I think what we've heard from physicians that there is real interest in treating these.

Patients we now have the guidelines the treatment paper can he has said da to augment the efforts to go out and educate so that appropriate patients get treated by the physicians.

Okay. Thanks, and then.

And as well on spending.

You talk more about the thought process on the testing to dose up there and that can be.

Do you think that might kind of give you insight into.

Me, neither other indications or whether you think multiple dose levels might be commercially viable.

Sure. So I'll ask Kevin to comment on that in some greater detail I'll just remind you that the simple reason for going after tenant 25 as they both worked in phase two but beyond that I think there's opportunity certainly to learn of potential application in other areas and that's something we're reflecting on perhaps you might comment a little bit on this.

Think about other disease states.

Thanks also.

As will said very nicely we are testing both the doses that we.

Had animal study in both us as for successful meeting the primary endpoint and so we've taken the key elements from Willow, including these doses into Aspen.

Which are two very viable doses on.

And in that population from the.

The efficacy relationships, we see with the exposure in those doses and Willow and.

Well like we see in the Aspen study.

That information does have relevance to other indications such as cystic fibrosis, and what we may ultimately taken today or as we understand.

The pharmacokinetics in that population so to see if that does have a unique set so so.

So the multiple doses or what we consider a highly.

Highly viable does this standard take or the windows into a phase three top line.

Yes, and so how we proceed and happy with the progress, we're making that opening the sites for the study.

Great. Thank you very much.

Sure.

Our next question comes from the line of Joseph Schwartz with SVB Leerink go ahead. Please your line is open.

Great. Thanks for coming back to me can you hear me okay.

Loans were.

Okay, great. Thanks so.

So two questions one on Brent Academy and one on Europe first.

First of all I know, you're not giving guidance on when exactly we'll see arise.

Encore data, but I was wondering if you can talk speak to whether or not you will be able to I know you're running these in parallel to what extent will you be able to course.

Course, correct based on findings that you observe in arise and will you report data publicly on arrives before at any point before.

Encore data become available.

So I'll take the second question first I think once we have an understanding of what that trial.

Means and to remind everyone. Its an open label trial.

Our expectation is that we'll be able to share that publicly.

Although I don't want to commit to that yet because.

As always when you're looking at do you want to make sure you understand it fully before you Sharon.

My intention today to share and be transparent with that once we have an understanding of it.

In regards to those two trials in their interaction I'll ask Kevin to comment on the design. The one is really specifically designed for the other.

Right. Thanks also for Erra case for this program for a rise in encore, we signed it.

In such a way that although they are running in parallel and the studies are staggered arises.

Through seven months and on power is through 15 months and so to your question. We will have data at the end of arise.

That is specifically designed to decide to help inform ultimately.

What's the how.

How the primary endpoint for encore will be computed so there is that opportunity to take those data.

Digested work with the FDA to come to a final statistical analysis plan for encore and in that step wise approach. We think is the best way to take.

The approach the overall program and give us the greatest chances of success at the end of the day for encore.

Okay, Great. Thanks, and then my question on Europe is.

You guys have been very thoughtful with your use of novel tools and strategies to be Bush's for patients in the U.S., where you had suspicions that there were patients that were not being diagnosed.

Properly with NTM can you talk about the extent to which you can deploy a similar or.

Maybe different tactics in Europe.

And whether at this point, you've seen any signs that.

Would lead you to believe that there could be some sizable pockets of NTM patients.

The European Union that are being misdiagnosed or not diagnosed or otherwise overlooked.

And then any insights at this point into like how that Jesus.

Geographic distribution in Europe.

The true geographic distribution of where these patients where patients potentially could be hiding I guess, what I'm getting at is some of the prevalence numbers.

Don't really look that believable just given the overall population.

Most line and other factors, which seemed important he.

Here in Denver and in places like Japan.

Yes sure appreciate the question, Joe and I would just say.

Ill refer to comment on it in a second but remember that whatever the prevalence numbers they have to be set against the timeline for reimbursement approval, which is uniquely European country by country, and so that necessarily limits the degree of.

Aggressive ramp that will that might come from understated populations.

If we were to discover that but the AI and machine learning and all that sort of stuff. Roger maybe you can talk about what we've done what we might do there what else you've learned.

Yeah sure. Thank you so I think you're spot on in asking the question in thinking about the true prevalence of NTM in Europe compared to the U.S. and I would say that as we apply that same sort of methodology with machine learning in a slightly different way.

In Europe that were.

We are seeing the same sort of things that you might suspect so.

For example, there was a publication in the European respiratory Journal, where we looked at apply those machine learning algorithms to national databases, and that's a little different in Europe is different data availability different privacy laws. So you can't really get down to the granular level you can in the U.S., but we're doing a country by country and that theres different timelines associated.

She added with that.

But for example in RJ, we looked at.

The population in the UK, which would seem to indicate that there was a significant untapped NTM patient population in the UK, We think thats, probably the same in Germany, and we'll find out about other areas as well now a lot of these patients reside with.

Decisions, who are still struggling to diagnose them as.

Much of sales in the U.S., so raising that awareness and then providing.

Providing.

Treatment pathways and treatment options is an important part of this but as we really see.

Across Europe as you might suspect elderly populations history is smoking.

Proximity to order those risk factors are universal and so you might expect to see the higher pockets of NTM in those areas that have those characteristics and we think as we go through this in and do the data mining that were that that is bearing out so longer term, we think the opportunity perhaps larger than what the initial epidemiology had indicated.

Okay. That's helpful. Thank you.

And there are no further questions in queue at this time.

I'd like to turn the call back over to will lose for some closing remarks.

Thank you all again for joining us today.

And this concludes today's conference call you may now disconnect.

[music].

[noise] [noise] [laughter].

[noise].