Insmed Inc (INSM) 2015 Q3 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Insmed third quarter 2015 financial results conference call.

(Operator Instructions). As a reminder, this conference call is being recorded.

I would now like to introduce your host for today's conference, Susan Mesco, Head of Investor Relations at Insmed. Please go ahead.

Thank you, Charlotte, and welcome to our third quarter conference call.

Before we start, let me remind you that today's call will include forward-looking statements based on current expectations. Such statements represent our judgment as of today, and may involves risks and uncertainties that may cause actual results to differ from the results discussed in the forward-looking statements. Please refer to our filings with the SEC, which are available from the SEC or our website, for information concerning the risk factors that could affect the Company.

Joining me on today's call are members of our executive management team, including Will Lewis, President and Chief Executive Officer; and Andy Drechsler, Chief Financial Officer.

At this time, let me pass the call over to Will.

Good morning, and thank you for joining us today. On today's call, I'd like to give you an update on the important progress we've made advancing our ambitious agenda for 2015, which centers around five key goals.

First, enrolling our global Phase III of ARIKAYCE in NTM lung disease; second, advancing our European marketing application; third, bringing a second-source contract manufacturer on line; fourth filing our IND and launching a Phase I study of INS 1009, and fifth, broadening our pipeline through corporate development.

Let me start today's update on our global Phase III CONVERT study. To date, we have secured approvals in 12 of our 16 targeted countries, and more than 80 of our planned 100-plus sties are open. While we've made good progress based on our observations to date, we expect to achieve our enrollment objective 6 to 12 months later than our initial end of the year expectations going forward, as the remaining countries come on line, which contain more than 30 targeted sites, and enrollment continues to ramp, we will narrow this estimated timeline, and provide updates on future calls.

With respect to enrollment, we are seeing steady progress. The study's design is rigorous, particularly insofar as quality is concerned. We are enrolling a very specific subset of NTM patients who we believe will be the most responsive, based on our experience in Phase II.

It is important to note that the anticipated commercial experience will be quite different from the demands of this global registration study that is taking place in 16 countries. While the primary end point will read out after six months, the overall study will run for much longer, and regularly collect data for more than two years. It is important for the study to capture valuable data on the disease, the treatment regimen currently used, and our investigational drug.

We believe, when completed, it will satisfy regulatory needs from around the world.

Our experience during the 112 study took 18 months to enroll, taught us that the demands placed on patients create some challenges, but the results from our enrollment efforts to date are, again, proving that by applying best practices at each site, these challenges can be overcome.

At this stage, the performance of our sites is a mix. At many sites, we're actually enrolling more patients than expected, but at other sites we need to focus on applying what we've learned to accelerate enrollment. While it is apparent that our estimated timing for completing enrollment was too ambitious, we believe the focus on quality strategy remains the right approach, and the additional time and effort will pay valuable dividends over the medium term.

A byproduct of having most of the countries and sites online, or in the final stages of coming online, is a greater sense of what it will take from here to be successful. I'd like to share some of our observations to date.

We are gaining valuable insight into the regulatory process in certain regions. Each country has its own questions, comments, and time lines, and there are valuable lessons from that process that will all benefit us when it comes time to commercialize ARIKAYCE.

One specific example is Japan. We secured protocol approval with PDMA faster than expected, which was an important achievement. At the same time, completing some of the logistical details, such as shipment and delivery of the nebulizer device, required more time than expected, and Japan came online later than we had planned.

Another observation we made along the way is that we would benefit from more firepower and experience in our clinical operations team, so we added some tremendous talent, most notably Dr. Reinilde Heyrman. Dr. Heyrman brings extensively clinical operations expertise to Insmed, and we are thrilled that she will be driving best practices across the study and others. Not only does she have experience directly relevant to the CONVERT study, she also has experience in pulmonary arterial hypertension studies, which we hope will become of increasing importance at Insmed in the coming years.

However, her first charge is the CONVERT study, and Dr. Heyrman's team is armed with global recruitment expertise to help expand our patient support mechanisms, accelerate enrollment, and ensure long-term compliance and retention of patients.

We have created a strong global infrastructure. This is serving us well, not only with respect to the CONVERT study, it also advanced our parallel objective of driving disease awareness in important markets around the world. This should help accelerate the regulatory process, and if approved, eventual commercial success.

What is clear to us today is that we will reach our goal with quality. As a remind everyone at the Company and our CRO partner, we must be able to look back in a few years' time, when we are selling the drug around the world, upon a first-class study and results that support the use of ARIKAYCE.

As with any landmark study of this nature, there are challenges to overcome. These are simply delaying the progress, not derailing it.

To date, we have not unearthed anything that is of material concern to us about the prevalence, the interest of physicians, or the potential clinical impact of ARIKAYCE. If anything, there is a striking consistency around the world when it comes to the recognition of need, the regulatory engagement, the physician enthusiasm, and the desire of patients for a new therapy.

This truly is a global opportunity.

Turning to our second goal, we remain on track with our regulatory process in Europe. We are finalizing our responses to the EMA's 120-day questions, and we still expect to submit these by the end of this year. This timing support a potential EMA opinion around the middle of 2016. We will update you again once the EMA provides us with their final assessment on the potential for approval of ARIKAYCE.

I want to turn now to the broader landscape of NTM awareness, and how it is growing. Recently, the FDA hosted a patient-focused drug development day entirely devoted to NTM lung disease.

This is one of only 17 such meetings hosted by FDA across all disease states since this program was started in 2013. Other diseases previously selected include Parkinson's disease, breast cancer, pulmonary arterial hypertension, and idiopathic pulmonary fibrosis, to name just a few. The daily challenges and significant burden of living with NTM were highlighted in great detail at the session on October 15th.

The meeting was designed to explore NTM from both the patient and clinician's perspective. In the morning, patients shared the personal challenges of living with NTM with the agency. More than 75 patients, physicians, and care givers attended the meeting in person, and more than 130 participated remotely, via the Internet.

The level of attendance and dialogue was one of the most robust to date. The resounding theme throughout the day was the debilitating effects of this disease on patients, and the profound struggle doctors have in treating NTM successfully. I think it is worthwhile to spend just a few moments expressing what was shared at this meeting.

Things we take for granted are immensely challenging for patients with NTM lung disease. To give an example of what being tired means to NTM patients, one patient said she had to take a taxi to travel one city block because of her exhaustion. Another discussed how simple tasks that previously took a few minutes of time now require an entire day.

The fatigue is also exacerbated by severe, painful coughing that interrupts sleep and often triggers muscle injuries or fractured ribs. Several patients recounted how they had been receiving a broad cocktail of as many as eight different antibiotics, some for three or four decades, since being diagnosed.

Some were speaking on behalf of patients who were no longer with them, because they had succumbed to the disease.

While it is clear that there is a spectrum of severity, and who progresses, and how quickly, is hard to determine, NTM is very serious. The need for more effective therapies was universally expressed by patients and physicians alike. Perhaps most gratifying were two patients who rose to state that they had been in the ARIKAYCE 112 study and were now, for the first time since their diagnosis, culture-negative as a result of our investigational drug, ARIKAYCE.

The afternoon was spent discussing the challenges of drug development in NTM, specifically enrollment challenges, given some of the co-morbidities, like severe fatigue. Needless to say, we identified with many of these challenges, but reiterated our commitment to physicians, the FDA, and the patients, to complete our study in a timely manner.

Turning to other important activities, a particular effort is being placed on two key areas that we believe will play an important role in our eventual commercial success -- pricing and physician education.

Insmed's pricing strategy for ARIKAYCE is based on the concept of value for money, were data is the primary driver of the pricing evaluation process. Through the comprehensive and well-documented data we are collecting, we feel confident we can demonstrate the unmet need, the enormous burden of the disorder, the specific existing health system costs, and the value of the innovation we are offering, all factors that are building blocks of the therapy's value proposition for patients, physicians, and payers.

To our minds, this is what will be required in the world order of pricing an orphan drug. We have been working on collecting this information and conducting this analysis for almost two years.

In partnership with one of the nation's largest Medicare insurance providers, we recently published three pharmacoeconomic studies. At ICAC in September, claims-based data highlighted increasing incidence rates for diagnosing NTM within the Medicare population, with a 36% increase between 2008 and 2013, and an average annual incidence of roughly 15 per 100,000 members.

During Infectious Disease Week in October, we presented data demonstrating the co-morbidities and significantly greater healthcare resources associated with delays in diagnosing NTM lung infections, underscoring the importance of accurate and timely diagnoses.

And most recently, at the Academy of Managed Care Pharmacy meeting in October, we reported results from a study that showed NTM patients are far more costly to the system than a control group without NTM in the Medicare population.

Across eight healthcare service categories, emergency room visits, the average monthly utilization for a diagnosed NTM patient was anywhere from nearly twofold to more than tenfold higher than the age-matched control group. In addition, average monthly pharmacy and medical costs were nearly sevenfold higher.

This study also highlighted the importance of aggressively treating NTM patients. Average monthly medical costs for treated NTM patients were nearly 30% lower than patients who received sub-optimal treatment. These patients also experienced 39% fewer inpatient stays, 53% fewer days per stay, and 11% fewer emergency room visits, on average, each month than those whose care was not compliant to guidelines.

These data highlight the value to healthcare plans of identifying and appropriately treating patients with NTM lung disease, as well as the potentially significant impact ARIKAYCE may be able to have, if approved for this population.

The second mission-critical component of our launch strategy is disease awareness and education. Last month in the US we launched our non-branded campaign in connection with the Chest Conference and the American Thoracic Society's NTM Week. An important component of this initiative is the website ntmfacts.com.

This dynamic website is designed to help physicians understanding the importance of an appropriate diagnosis and provides valuable information on how to recognize the signs and symptoms early, and, ultimately, how to manage NTM lung disease. The site features personal patient stories about the daily challenges of living with NTM, told by patients, as well as through the eyes of artists from around the world.

The response so far has been overwhelming. The site has had nearly 1,200 unique visitors in less than two weeks. In addition, the patient case studies have been viewed nearly 900 times. At the recent Chest Conference in Montreal, we hosted a booth that featured works of art describing how NTM patients feel.

The feedback from the pulmonologists was very positive, noting a direct alignment with their patients express to them. It is one of the innovative ways that Insmed is trying to truly build awareness and a connection between the physician community and the patients they are serving.

Our European team continues to ramp up their commercial readiness and launch planning activities. We had an expanded presence at the European Respiratory Society meeting, where we hosted a standing-room-only educational symposium led by physician thought leaders, and also had separate booths devoted to study recruitment and non-branded disease awareness.

This meeting provided an excellent forum to engage with hundreds of physicians from around the world. Getting to specifics within our broader European efforts, if approved in Europe, Germany will be the country of first commercial launch. Our disease awareness campaign in Germany continues to gain momentum in helping us educate physicians about the importance of diagnosing NTM lung disease, and assessing if, when, and how treatment should be initiated.

In September alone, nearly 200 pulmonologists visited the disease awareness website we launched in Germany in February. This represents impressive progress.

We've been able to bring the learning from these efforts back to help inform our US campaign, as well as into other areas of Europe. In fact, in the coming months, we will begin extending similar country-specific educational campaigns to our targeted launch countries, including France, the UK and Italy. We have made a number of key hires in Europe, including medical science liaisons, who are playing an important role in driving awareness and education.

Finally, we continue to support compassionate-use programs for certain NTM patients in France under the ATU, the Netherlands, and soon, Germany. It is our hope to add Italy to this list in early 2016. These efforts underscore our commitment to take a leadership role and own this disease on a global basis.

Turning to our third goal for 2015, we remain on track to have fully functioning sources of ARIKAYCE supply by the end of this calendar year, one of which has already received a certificate of GMP compliance after being inspected in connection with our European marketing application. Andy will address the status of our manufacturing in more detail.

With respect to our fourth goal, and our earlier stage pipeline, here, too, we remain on track. Last month we submitted our IND for INS 1009, and we expect to begin a Phase I study later this year. We are also advancing several other research projects, and expect to share some details in the coming months, after we further validate our initial findings with additional pre-clinical data.

And for our last goal, expanding our pipeline through corporate development, we remain attentive to opportunities, yet disciplined. We are actively evaluating assets to add to our pipeline, and we are submitting term sheets when there is a sound strategic fit.

However, we will only do a deal if it clears three key hurdles -- the strategic value is clear, the price is right, and extracting value is within our reach.

With that, I will turn the call over to Andy for this quarter's financial update.

Thanks, Will. Good morning, everyone. As Will just reviewed, we have made important progress on multiple fronts. as we evolve into a global organization, we continue to invest in manufacturing and pre-commercial preparation.

During the third quarter, we added 20 talented new people to our global team. In addition to our investment in human resources, we continue to invest in manufacturing as part of our commercial preparations. I am pleased to report that we remain on track to have Therapure, our second source of ARIKAYCE supply, online by the end of this year. We have produced multiple engineering batches, and longer-term stability testing is underway.

Finally, in December, we are scheduled to produce ARIKAYCE that will be available for use in our clinical trials. As previously discussed, we are manufacturing ARIKAYCE at Therapure at a 200-liter scale, which is a fourfold increase over our current production. This will enhance not only our supply, but our projected financials by reducing the cost per batch, enabling us to achieve attractive margins. Between these two facilities, we will have adequate supply, as well as redundancy of supply, and this will be sufficient for the global launch of ARIKAYCE.

Turning now to our quarterly results, this morning we reported a net loss of $31 million or $0.50 per share, compared with a net loss of $24 million or $0.54 for the third quarter of 2014.

Research and development expenses increased to $19.2 million in the third quarter from $15.2 million in the prior year. The increase was primarily due to the advancement of our global Phase III CONVERT study of ARIKAYCE in NTM lung disease.

Third quarter G&A expenses were $11 million, versus $8.2 million in the prior year. The increase was driven primarily by our pre-commercial activities in Europe. These activities are advancing, given the important EU regulatory milestones that are on track for first half of next year.

We continue to be in a solid financial position, and ended the third quarter with $311 million of cash and investment. With regard to cash guidance, our third quarter cash-based operating expenses were $26 million, and we expect the cash operating expenses to land within our previously guided range of $50 million to $60 million for the second half of 2015.

This range reflects spending for the CONVERT study, the continued buildout of our global infrastructure, and ongoing manufacturing activities.

With that update, I will turn the call back to Will.

Thank you, Andy, for that overview, and thank you for your continued reliable stewardship of our financial and technical operations.

In closing, we have made very meaningful progress advancing our five corporate objectives. While there is still much to be done, the progress we are making, and the clear opportunity we have ahead with ARIKAYCE, reinforce my confidence in the growing intrinsic value at Insmed. I believe now, as I did when I first joined three years ago, that the best days of this Company will be realized from now through the medium term, simply by executing on the opportunities that are directly in front of us.

As a consequence, I intend to put in place a 10(b)(5)(1) stock purchase plan, as I have previously done. Under the plan, I would expect to personally acquire Insmed's share during the next four quarters regardless of price. Further information regarding my plan will be available in a future 8-K filing.

This additional investment underscores the strong belief I have that our current team, strategy, and resources position us to deliver for our shareholders. I recognize and appreciate the truth they have placed in this team. This will happen because we will deliver value by helping patients.

With that, I will turn the call back to the operator to begin Q&A. Operator?

Thank you. (Operator Instructions). Our first question will be coming from the line of Joseph Schwartz from Leerink Partners. Your line is now open.

Great. Thanks very much. Good morning. I was wondering if you could just break down for us how much of the slower enrollment is due to different factors such as a screen failure rate that's higher than expected, perhaps, maybe fewer patient at certain centers, certain aspects of the IRP that might be difficult to achieve buy-in on, tougher administrative delays, and then which of these things do you think that you can impact the most versus (inaudible) find out?

You bet, Joe, and thank you for the question. Look, I think, being very candid, if I had to rank order what really caused this delay, first and foremost, it was too aggressive a goal, and I would say that's 75% or more of what we're talking about today.

If we had to do it again, we would only change the time line. We're very pleased with what's been built. We've got more than 80 sites in more than a dozen countries around the world, and that construction was done in 10 months, while hitting all of the other goals that we have as our objectives for 2015.

Most importantly, for this study, we are getting the patients we want, which were the Phase II responders, and this study is going to produce the definitive results we need.

I will tell you that when you look at sites and the variability from one to the other, on the margin there are improvements, I think, that we can make, and we're very attuned to those.

Let me give you some examples. There are certain sites that cannot reach out to patients directly. Those sites, some of them, are really well know, require us to go in and conduct advertising around the site in order to draw patients' awareness to the trial that is ongoing, so that they will come in and ask their physician to be placed on -- as a candidate for the drug.

And I think we have an opportunity to improve some of our one-on-one dialogue with sites prior to their being opened.

But these, as I say, are more on the margin. If we look at the rank order again, number one, too aggressive a goal. The other things that I've talked about are relevant. I think it's fair to say there were some ex-US country approvals that took longer than expected. But, again, I think that shifts out a few months, not anything dramatically.

Does that answer your question?

Yes, definitely helpful. Thanks.

And then, I was just wondering, can you tell us how many patients have been enrolled through time, up until this point, and what has the screen failure rate been, relative to your comments that the enrollment is -- rate is not indicative of the market opportunity?

Yes, and I appreciate that. We're not going to provide interim updates on enrollment numbers. I will say that we have a meaningful percentage of our targeted patients enrolled.

We are adding new talent to our clinical operations team. We're applying best practices, as I mentioned, across sites.

I will just dwell for a moment to perhaps give a little more flavor on the topic of screen failure, and while this is not a number we're going to provide, I can tell you that as of now, we're on track with our expectations. There are new countries coming online, and some of these are in their earlier days.

So, it's still a good practice not to read too far into this, but there isn't anything from our internal metrics, other than this very ambitious goal that we laid out, that is off track.

Okay. Thanks for taking it.

You bet.

Thank you. Our next question comes from the line of Matt Roden from UBS. Your line is now open.

Hey, guys. This is actually Andrew Peters, in for Matt today.

Hey, Andrew.

So -- hey, guys. So, a couple of questions. I guess you talked about kind of the biggest difference here is being too aggressive a goal. I guess I just want to understand a bit more as to kind of why hasn't or why didn't, kind of the learnings from 112 kind of lead you to a more realistic goal for timeline. I guess how did that extrapolation go?

And then, getting back into the site question, if -- were these challenges that you're seeing regarding the ability of the sites to contact patients, things like that, was that new and unexpected? I guess it's really kind of why were those sites selected in the first place?

And then, just lastly, a question on the EMA filing. Can you elaborate a bit more into the thinking to focus around the decision to focus on NTM only? I just want to understand, is this driven kind of by interaction with regulators, or is it more of kind of a commercial strategy question? Thanks.

Sure. So, there are a bunch of questions there. Let me try and see if I can recollect them each in turn, and then I'll revisit with you again to make sure I've answered them all.

When we talk about the goal that we framed, there really is not good precedent out there, and that's one of the big challenges of NTM. It's also the opportunity, but it is one of the big challenges.

And we looked at 112. 112 was a study that took 18 months to enroll. We looked at the enrollment rate per patient per site, and we thought with additional resources, an a great deal of energy and planning we would be able to, I would say, significantly surpass that, and I think what we've learned is that that's not what we're going to be able to achieve.

I don't think that additional resource or additional horsepower, even more dramatically than what we have added here, would have moved the needle much. You've got a very, very challenging study in terms of going all around the globe to 16 different counties and to think that you're going to get as much as we have gotten done, I think, is a very good accomplishment, plus, there are just idiosyncrasies that are out of our control, like the logistical issue we described in Japan, that just add time.

So, 112, really, is the best framework. We thought we could do a little bit better than that. It turns out that that was incorrect.

But I think what we are building -- again, I would just emphasize -- is the study design, is the infrastructure that we want to produce the result we're after.

I think the next question you asked was on --

Just --

The outreach to patients.

Yes.

I'm sorry. Go ahead.

It's just site selection and outreach to patients is -- do you think kind of enrolling?

Yes, how do they get in? Right.

Yes.

Yes, and that's a fair question. We have qualified all of these sites. It is not uncommon that some sites cannot reach out to patients. That's true for basically all studies. It's not just unique to NTM. So, we knew that that was going to be a factor.

We had hoped that some of the practices we were bringing around some of these sites would result in the proactive outreach of patients. In some cases, that's been the case, and we've actually gotten much better response rates than we expected. In others, not as much, and so, we're spending the time now looking at the distinction between those sites to see how we can bring those that are in the less-performing category back up to the surpasses expectations category.

So, it's a mix. And it's probably reasonable to say that we should have anticipated that would be more prevalent, given how many different sites we're going to. But in the category of lessons learned.

And I think we intend to make it right for those sites that haven't been performing as well. And we've got the resources and the capability to do that.

I don't think that we've done a poor job of site selection. I really want to emphasize that point. We have spent a lot of time, some extra time, in hand-picking these sites to ensure that we're going to get the patients we want. And so, I feel very good about what has been built in the 10 months that we've been at this.

Does that answer your question, before I turn to your question on the EMA?

It does.

Okay. On the EMA, you asked, NTM-only, and the strategy there, and why step away from CF.

The similarity challenge is what provoked our belief that it would be wiser to return to CF at some point in the future. Again, we hit our primary end point on the Phase III study across Europe in CF.

By setting aside that opportunity for now, it enables us to focus our resources on NTM. Obviously, there's a lot going on at the Company, but I think this is also the right strategic move.

When we look at where we end up, if we can secure NTM approval in Europe, this is an appropriately unmet medical need that this drug, we think, is going to make a material difference in. Some of the best examples of the regulatory posture with regard to that, at least, on a country basis, can be seen in France where the ATU approval, which is getting reimbursed at around $60,000 US a year, shows that there is both a recognition of the need, and a support for the use of this drug.

And I think that is probably the best harbinger of what the commercial opportunity, we think, is for ARIKAYCE in the treatment of NTM, if it's approved, across Europe.

Does that answer your question? I think CF is off the table for now. There is the opportunity to return to it, but I think in a world that is genericizing, inhaled CF antibiotics, is not the area of greatest unmet medical need, and that's what's driving our decision.

Okay, great. Very helpful. Appreciate that.

You bet.

Thank you. Our next question comes from the line of Josh Schimmer from Piper Jaffray. Your line is now open.

-- for taking my questions. I'm not sure if you had mentioned, will the enhanced enrollment efforts have any impact on R&D, going forward? Or should we look at this quarter as reflective of the steady-state R&D spend over the course of the remainder of the trial?

Yes, so I think the -- it will go up a little bit, but I don't expect it to be a materially different performance, and I'll just to turn to Andy to add any color he'd like to on that.

No, I think that's right. As we get to full enrollment across all sites, it will continue to ramp a little bit.

And then -- well, maybe to put you on the spot a little bit, on the enrollment update, I guess if you recognize that your initial guidance was too aggressive, how can be confident that your new guidance is not too aggressive?

Yes, and I think that's a very fair question. I appreciate your asking it.

When we think about how are we going to be able to deliver this time, we have most of our sites up and running now. So, we have a lot more data and visibility. What we have tried to do with this guidance is provide a broad range of where we may land in terms of ultimate timing. And as time goes forward here, and we get to our next quarterly call, I think we're going to be making an effort to narrow this guidance a bit further, as more data comes in, enrollment continues, and the performance of sites becomes more steady-state.

And I hope that that's helpful. That's our ambition here. I think in the category of we've done this correction once, we want to make sure we get it right.

The most important point I would make here is that rewinding in time, what would I change, it would just be the guidance on timing. The construction that has taken place here is what we all, collectively, want.

Got it. Great. Maybe you can promise to buy everyone on the call dinner if the time slips further.

That's fair.

(Laughter).

Thanks a lot.

You're welcome.

Thank you. Our next question comes from the line of Ritu Baral from Cowen. Your line is open.

Ritu, are you there?

(Inaudible) check your mute button?

She may come back in. Why don't we go to the next question?

Hello?

Oh, there we go.

Hello? Can you hear me? Yes.

Now we're good.

I forgot.

That' all right.

I was apologizing for the background noise while I had myself muted for the background noise. Thanks for taking questions.

What is -- what's the site count going to be now, do you think? I mean, you alluded to a number right now that's 110-plus. How many do you think you might need to add, and how many more acceptable sites, from a quality perspective, are there out there that you haven't already tapped?

Yes, it's a great question, actually. We continue to look at and evaluate sites, and there's a process that we use. We begin with those areas where we already have country approval. So, for example, we're continuing to look, even within the United States, for sites.

And I think as awareness continues, and as people become aware that the ability to enroll patients will extend beyond the end of the year, that will change the appetite for some of these sites that have become aware through many of the congresses that we mentioned, to enroll some of their patients.

So, that process is underway. The specific number -- I wouldn't put a final circle around it. What I would tell is that we've identified, to date, at least 130 that we could go, and I think we'll continue to pursue sites, as we mentioned at the very outset of the year, north of 100, for sure.

Okay. And do you think will change the patient balance across geographies?

No, and I -- again, to be clear, this is not exclusively a broad -- we are not adding half a dozen new countries we weren't previously going to go to. We're still not in Russia, not in the Ukraine, those kinds of decisions that are really shaped and a view that the medium and long-term needs of the study must be met from a quality point of view.

So, I feel good about the countries we have. I feel good about the sites that have been and are under consideration. Each one undergoes a screening process, and then gets a visit before we open it for patient screening and enrollment. I think the balance of patients will continue to be what it has been.

I don't see that being upset in any way. Really, this site construction, this trial construction is going as it should. What has happened is that we can now look upon it, and make an intelligent judgment about how long it will take to get it completed.

Before, we really lacked the information to make that assessment, and that's why the goal is inconsistent and incongruent with where we are.

You may have muted again.

Operator, let's go to the next question, if there is one. She usually comes back into the queue.

Certainly, our next question will be coming from the line of Liisa Bayko from JMP Securities. Your line is now open.

Hi, there. Can you maybe tell us are you getting the most traction at sites in North America, or are you getting the most traction at sites on a more global basis?

Yes. So, it's actually a mix.

Okay.

We get good traction at the sites that were involved in 112, all of which, or almost all of which were in the US. I think we've been surprised by some of the sites. And I'll give you an example. In Australia, we had a site at a TIV that had suggested they might have 3 patients that has already screened 8 and thinks they may have another half dozen to 10 patients in the near term that they'll want to screen.

So, I think two things happen. When they start to look, and they understand the operation of the trial, once they've got their first patient screened, they tend to find several more, and so that is something we're trying to communicate around to the sites.

And it's not surprising. There's effort required to screen patients, and once they've committed to doing so, it tends to be in their interest do more than just the one.

Okay. And then, just to clarify, or just to make sure we're on the same page, you're not planning any changes to the inclusion and exclusion criteria? You don't anticipate making any?

No.

Okay. All right, thanks.

You're welcome.

Thank you. Our next question comes from the line of Ritu Baral from Cowen. Your line is now open.

Hi, guys. Sorry about dropping off. I had one more follow-up question, unless Liisa asked it ahead of me.

It seems like the responses to the 100-day questions are taking a bit longer than we sort of expected. Are there any surprises in those questions around the NTM opportunity? Is there any more color you can give as to why this is taking a bit longer than we're used to.

Yes. No, and that is by design. So, I appreciate the question.

To refresh everyone's recollection, the 112 study which forms the basis for the evaluation of our application, had a one-year patient follow-up, which finished up in sort of the third quarter of this year, give or take.

And the CSR that is written for the -- at the tail end of the completion of the study, had to be done. Now that we have that one-year data, and it so compelling, it's really critical that we get that final data included in the CSR.

So, we originally went back to the EMA, we requested the six months to be able to submit by the end of the calendar year, so that we could include that CSR from the 112 study. That's a really important point. It is -- everything else is ready to go. That particular CSR has got to be in the dataset.

Got it. Thanks.

Thank you. (Operator Instructions). I am not showing any questions at this time. I would now like to turn the call back over to Will Lewis for any closing remarks.

Thank you for your questions and participation on today's call. We appreciate your continued interest and support and look forward to updating you again on our future quarterly calls. Have a great day.

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program, and you may all disconnect. Everyone have a great day.