Q3 2021 Insmed Inc Earnings Call

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Hello, and welcome to the in Smith third quarter 2021 financial results. My name is Katie and I'll be coordinating your call today, if you'd like to ask a question. During the presentation. You may do so by pressing star one on your telephone keypad.

Katie: Hello, and welcome to the InSmid 3 quarter 2021 financial results. My name is Katie, and I'll be coordinating your call today. If you'd like to ask a question during the presentation, you may do so by pressing Star 1 on your telephone keypad. I will now hand over to your host, Eleanor Brassier, to begin. Please go ahead. Thank you, Katie.

I'll now hand over to Joyce Olive Nebraska to begin. Please go ahead.

Eleanor Brassier: Thank you, Katie. Good morning, and welcome to today's conference call to discuss our third quarter 2021 financial results and provide a business update. Before we start, let me remind you that today's call will include forward-looking statements based on current, Such statements represent our judgment as of today and may involve risks and uncertainties that may cause actual results to differ materially from the results discussed in the forward-looking Please refer to our filings with the Securities and Exchange Commission, which are available through the SEC's website at www.s.gov, or from our website, for information concerning the risk factors that could affect the company.

Thank you Katie good morning, and welcome to today's conference call to discuss our third quarter 2021 financial results and provide a business update.

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 involve risks and uncertainties that may cause actual results to differ materially from the results discussed in the forward looking statements.

Please refer to our filings with the Securities and Exchange Commission, which are available through the SEC's website at Www Dot S. E C dot gov or from our website for information concerning the risk factors that could affect the company.

The information on today's call is not intended for promotional purposes and not sufficient for prescribing decisions.

Eleanor Brassier: The information on today's call is not intended for promotional purposes and is not sufficient for prescribing. Joining me on today's call are members of the InSmet Executive Management, including Will Lewis, Chair and Chief Executive Officer, Dr. Martina Flammer, Chief Medical Officer, Roger Asset, Chief Operating Officer, and Sarah Bonstein, Chief Financial Officer. I now turn the call over to Will Lewis for prepared remarks. Upon completion of those remarks, we will open the call up for your questions. Thank you, Eleanor. Good morning, everyone.

Joining me on today's call are members of the executive management team, including will Lewis Chair and Chief Executive Officer, Dr. Martina Flammer, Chief Medical Officer, Roger <unk>, Chief operating Chief operating Officer, and Sara <unk> Chief Financial Officer.

Let me now turn the call over to will Lewis for prepared remarks. Upon completion of those remarks, we will open the call up for your questions.

Thank you Ellen good morning, everyone. We are pleased to share our third quarter results with you today.

William Lewis: We are pleased to share our third quarter results with you today. I want to start my comments by saying that InSmed has seen remarkable growth and accomplishment during the time of the pandemic. This growth has ushered in a new framework. We are currently advancing four strategic pillars. First is Ericase, our marketed product for the treatment of refractory Ntm, which is now approved in three major territories around the world, the U.S., Europe, and Japan. Notably, the Japan launch kicked off in July.

I want to start my comments by saying the instrument has seen remarkable growth and accomplishment during the time of the pandemic.

This growth has ushered in a new framework and Smith, we are currently advancing four strategic pillars.

First as Eric case, our marketed product for the treatment of refractory MTM, which is now approved in three major territories around the world. The U S Europe, and Japan, notably the Japan launch kicked off in July we are very pleased with the progress to date and we believe there is tremendous opportunity to help patients in this region.

William Lewis: We are very pleased with the progress to date, and we believe there is tremendous opportunity to help patients in this region. When we think about the overlap of NTM and bronchi-ectis call points, our commercial operations in the U.S., Europe, and Japan are preparing us well in advance for the potential launch of Brent So Kativ, should that product candidate achieve regulatory approval. Ericase is also being explored in a frontline clinical trial program in patients with NTM lung disease, which will allow us to take advantage of our commercial footprint.

When we think about the overlap of MTM in bronchiectasis co points, our commercial operations in the U S. Europe, and Japan are preparing us well in advance for the potential launch of <unk> should that product candidate achieve regulatory approval. <unk> is also being explored in the frontline clinical trial program in patients.

MTM lung disease, which will allow us to take advantage of our commercial footprint.

The second pillar is Brent so Catherine or <unk>, one inhibitor currently in the phase III Aspen trial for the treatment of bronchiectasis.

William Lewis: The second pillar is Brenso-Catib, our DPP1 inhibitor, currently in the Phase 3 Aspen trial for the treatment of bronchiysis. In addition to Aspen, we continue to work toward advancing brinso-cadib in a phase two trial in cystic fibrosis.

In addition to Aspen, we continue to work toward advancing <unk> in a phase two trial in cystic fibrosis.

These two initial indications our team has identified additional opportunities where friends who kept it may have utility by way of the DPP, one inhibition pathway and we look forward to having more to say about the progress we're making on these potential additional indications early next year.

William Lewis: Beyond these two initial indications, our team has identified additional opportunities where Brent So Katte may have utility by way of the DPP1 innovation pathway, and we look forward to having more to say about the progress we are making in these potential additional indications early next year. Our third pillar is TPIP, a troposinol prodrug, which we are advancing through clinical development for the potential treatment of pulmonary arterial hypertension, or PAH, and pulmonary hypertension associated with interstitial lung disease, or PH, ILD.

Our third pillar is TPI P. A proportional pro drug, which we are advancing through clinical development for the potential treatment of pulmonary arterial hypertension or P. A H and pulmonary hypertension associated with interstitial lung disease or ph ILD.

William Lewis: Finally, our efforts in translational medicine. This pillar is focused on identifying the next set of clinical candidates to enter our pipeline, with a sharp focus on disruptive technologies in the rare disease landscape that could yield a high degree of impact for underserved patients. We see these investments now as a key to developing a future pipeline that we hope will quickly follow the anticipated success of the first three pillars. We believe that within each of these pillars is enormous potential that could catalyze the next phase of growth for We expect to share more on each of these pillars early next year. Finally, let me briefly address the ongoing pandemic.

Finally, our efforts in translational medicine. This pillar is focused on identifying the next set of clinical candidates to enter our pipeline with a sharp focus on disruptive technologies in the rare disease landscape that could yield a high degree of impact for underserved patients. We see these investments now as a key to developing the future pipe.

<unk> that we hope will quickly follow behind the anticipated success of the first three pillars.

We believe that within each of these pillars has enormous potential that could catalyze the next phase of growth for instance, we.

We expect to share more on each of these pillars early next year.

Finally, let me briefly address the ongoing pandemic throughout the second quarter, we saw promising signs of a return to growth early in the third quarter. These signs of growth were muted by the impact of the Delta variant around the world.

William Lewis: Throughout the second quarter, we saw promising signs of a return to growth. Early in the third quarter, these signs of growth were muted by the impact of the Delta variant around the world. We continue to see the temporary negative impact of COVID surges when they occur but believe we have the means to return to growth once they have abated, even in the endemic phase of this virus. One consequence of this persistence of the virus is that we have made the decision to require all U.S. employees of InS to

To see the temporary negative impact of Covid surge is when they occur but believe we have the means to return to growth once they have a base even in the endemic phase of this virus.

One consequence of this persistence of the virus is that we have made the decision to require all U S employees have been Smith to get vaccinated starting in mid December.

William Lewis: Med to get vaccinated starting in mid-December. No doubt this will result in some employees choosing to leave their employment within. While this is regrettable, we believe this requirement is the best way to protect physicians, patients, caregivers, and employees and to play our part to help bring this pandemic under control.

No doubt this will result in some employees choosing to leave their employment with <unk>. While this is regrettable. We believe this requirement is the best way to protect physicians patients caregivers and employees and to play our part to help bring this pandemic under control.

We are in an exciting and pivotal moment and in Smiths growth trajectory. The next 12 months will be an extremely important execution period as in Smith continues to perform across our commercial operations clinical trial work and research efforts I believe we have the patient focus collective drive infrastructure and strong capital position.

William Lewis: We are at an exciting and pivotal moment in Insomed's growth trajectory. The next 12 months will be an extremely important execution period as Insomid continues to perform across our commercial operations, clinical trial work, and research efforts. I believe we have the patient focus, collective drive, infrastructure, and strong capital position to help us recharge. With that, I'll turn the call over to Sarah to walk through our financials. Thank you, Will. Good morning, everyone.

To help us reach our goals with that I'll turn the call over to Sarah to walk through our financial results.

Thank you will good morning, everyone earlier today, we issued our detailed third quarter financial results in a press release overall, our financial results were aligned with our internal expectations.

Sara M. Bonstein: Earlier today, we issued our detailed third quarter financial results in a press report. Overall, our financial results were aligned with our internal expectations. Let me highlight just a few of those results for you now. As reported this morning, we entered the third quarter with $847 million in cash and cash equivalence. We anticipate this cash position will support data readouts from the Erichase Frontline Program, the Phase 3 trial of Brent So Captive and Barakia, as well as phase two results for TPI.

Let me highlight just a few results for you now.

As reported this morning, we entered the third quarter with $847 million in cash and cash equivalents. We anticipate this cash position will support data readouts from the Eric pipeline program. The phase III trial, Pfizer captive in bronchiectasis as well as phase II results for <unk>.

Sara M. Bonstein: For the third quarter, 2021, total net revenue for Erickase was $46.8 million, demonstrating resilience and steady performance of the franchise in the face of the Delta variant. Our growth to nets in the U.S. for the third quarter, 2021, was approximately 12%. As previously disclosed, we anticipate our growth to net for our U.S. business to be in the mid-teens for the full year 2021. Costs of product revenues for the third quarter were $10.2 million for 22% of revenues, which was in line with our cost of product revenues in the third quarter of 2020. Let me now turn to our GAAP operating expenses. For the third quarter,

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For the third quarter 2021, total net revenue for <unk> was $46 $8 million, demonstrating resilience and steady performance of the franchise in the face of the Delta variants.

Our gross to net in the U S for the third quarter 2021 or approximately 12%.

As previously disclosed we anticipate our gross to net for our U S business to be in the mid teens for the full year 2021.

Cost of product revenues for the third quarter was $10 $2 million or 22% of revenues, which was in line with our cost of product revenues in the third quarter 2020.

Let me now turn to our GAAP operating expenses.

For the third quarter 2021 research and development expenses were $73 million and SG&A expenses were $63 million as previously disclosed our research and development expenses are expected to grow as we continue to support our development pipeline and invest in our research capabilities.

Sara M. Bonstein: Research and Development expenses were $70.3 million, and SG&A expenses were $60.3 million.

Sara M. Bonstein: and SG&A expenses were $60.3 million. As previously disclosed, our research and development expenses are expected to grow as we continue to support our development pipeline and invests in our research capabilities. In closing, InSment ended the third quarter in a strong capital position, underscored by an ongoing commitment to a responsible use

In closing instrument ended the third quarter in a strong capital position underscored <unk> ongoing commitment to the responsible use of cash with that I'll now turn the call over to Martina for an update on our pipeline on Tina.

Sara M. Bonstein: With that, I'll now turn the call over to Martina for an update on our pipeline.

Martina Flammer: Thank you, Sarah, and good morning, everyone. InSmit made important progress across our clinical development programs in the third quarter. In addition to our ongoing clinical research, our medical affairs efforts continue to serve a key purpose at INC. I'd like to highlight a few examples of the range of data In Smith presented at Medical Congresses during the third quarter and at ID Week 2021. We shared data demonstrating that in Japan, hospitalization rates were higher for COPD patients with NTM lung disease compared to COPD

Thank you Sarah and good morning, everyone.

<unk> made important progress across our clinical development programs in the third quarter.

In addition to our ongoing clinical research Medical affairs effort continued to serve a key purpose it isn't it.

I'd like to highlight a few examples of the range of data Internet presented at medical Congresses during the third quarter.

And <unk> 2021 we should have data demonstrating that in Japan hospitalization rates were higher for COPD patients with <unk> lung disease compared to COPD patients, who do not have MTN.

Martina Flammer: to see UPD patients who do

Martina Flammer: underscoring the importance of appropriate management of patients who present with dyscomorbidity These results, built on similar data we have previously presented regarding increased hospitalizations and mortality among COPD patients who also had NTM in the U.S., highlight the global need to treat NTM patients with this comorbid condition. At the test annual meeting,

Scoring the importance of appropriate management of patients who presented this comorbidity.

These results build on similar data we have previously presented regarding increased hospitalizations and mortality among COPD patients, who also had N T M D U S hi.

Highlighting the global need to treat MTM patients. This is comorbid condition.

At the chest annual meeting we were pleased to share data from the COPD Foundation U S Bronchiectasis and MTN research registry demonstrating that approximately one third of patients who were treated for MTM and were later identified as refractory had differences in clinical characteristics.

Martina Flammer: We were pleased to share data from the CUPD Foundation.

Martina Flammer: Foundation, U.S. Brankyectasis and NTM Research Regist, demonstrating that approximately one-third of patients who were treated for NTM and were later identified as refractory had differences in clinical characteristics, such as lower body mass index and reduced lung function, compared to patients who are not refractive. These findings suggest that an understanding of the differences in clinical characteristics of patients may help identify and treat refractory MTM patients at earlier time points.

Such as lower body mass index, and reduced lung function compared to patients who are not refractory.

These findings suggest that understanding of the differences in clinical characteristics in patients may help identify and treat refractory MTM patients at earlier time points.

Finally, we were pleased to share pharmacokinetics and pharmacodynamics data from our phase II Willow study of friends or Pat at the European Respiratory Society International Congress.

Martina Flammer: Finally, we were pleased to share pharmacokinetic and pharmacodynamic data from our phase-to-will study of

Martina Flammer: from our face-to-will study of Pranthropathet at the European Respiratory Society International Congress. These results demonstrated that patients treated with prancocatid were more likely to have sputum-nutritive levels below the limit of quantification at the end of treatment compared to patients treated with placebo. In addition, higher systemic exposure to pransocath was associated with achieving sputum-neutrophalysis levels below the limit of quantification.

These results demonstrated that patients treated with friends with cat, one more likely to have sputum neutrophil elastase levels below the limit of quantification at the end of treatment compared to patients treated with placebo.

In addition, higher systemic exposure to brands for cat that was associated with achieving sputum neutrophil elastase levels below the limit of quantification.

Martina Flammer: In our Aspen trial, we hope to establish a correlation between reduction in neutrophil LFD levels and the occurrence of pulmonary exacity. Let's now turn to our clinical development. Phase 3 Aspen trial of bronchranocative in patients with bronchiaxst, and our results in encore studies for Erycase as a frontline treatment for patients with neck lung disease. Patient enrollment continues to track in line with our expectations. Let me expand on our progress with Brenta.

As been trial, we hope to establish a correlation between reduction in neutrophil elastase level and your current pulmonary exacerbation.

Let's now turn to our clinical development program.

Phase III, Aspen trial upfront and surpassed it in patients with bronchiectasis and horizon Encore studies for Aric taste as a frontline treatment for patients with Mac lung disease patients.

Patient enrollment continues to track in line with our expectations.

We expanded our progress with brand for pet.

We're pleased to convey that the European medicines agency's pediatric committee has approved the French who had the pediatric investigational plan for the treatment of patients with non cystic fibrosis bronchiectasis.

Martina Flammer: We're pleased to convey that the European Medicines Agency's Pediatric Committee has approved the Brancocataph pediatric investigational plan for the treatment of patients with non-cystic fibrosis bronchial asthma, which means that we now have alignment for our pediatric study plan across the FDA, EMA, and P&B. Importantly, our Aspen trial will now include 40 adolescent patients between 12 to less than 18 years of age, which will fulfill the pediatric study requirements to support marketing applications in this patient population in the U.S., Europe, and Japan. We look forward to providing updates on our progress. Our Prenzocatth clinical development work also continues for the Phase 2 Pharmacodinetics and Pharmacodynamic study in cystic fibrosis.

Which means that we now have alignment for our pediatric study plan across the F. E M. A N P M D.

Importantly, our ASP and trial will now include for the adolescent patients between 12 to less than 18 years of age, which will fulfill the pediatric study requirements to support marketing applications. In this patient population in the U S Europe, and Japan, we look forward to providing updates on our progress.

Our printer cat the clinical development work also continues for the phase two pharmacokinetic and Pharmacodynamic study in cystic fibrosis, and we are on track to release results next year.

Martina Flammer: And we are on track to release results next year. In parallel, we have identified opportunities that we believe will support Prince of Tatsy's expansion to additional neutrophil-mediated indications where there is a clear and strong scientific rationale to support the mechanism of X. In line with our mission, we believe we can deliver the greatest value by focusing on serious diseases that affect smaller patient populations, where there is a clear gap in the current treatment lens.

In parallel we have identified opportunities that we believe will support brands surpass its expansion to additional neutrophil mediated indications, where there is a clear and strong scientific rationale to support the mechanism of action.

In line with our mission, we believe we can deliver the greatest value by focusing on the serious diseases that affect smaller patient population, where there is a clear gap in the current treatment landscape.

We anticipate updating you on our work in additional indications early next year.

Martina Flammer: We anticipate updating you on our work in additional indications early next year. Now, let's turn to TTIP, which we believe may be able to harness the full potential of the prosanoid pathway. Starting with our phase 2A study in patients with PA, recall that this study is designed to measure the impact of single doses of TPP on pulmonary vascular resistance or PVR over 24 hours. We hope to see PBR reduction that is extended well beyond that, which is currently available with Tropros. As a reminder, we're using a low dose for this.

Let's now turn to TP, IP, which we believe may be able to harness the full potential off the <unk> pathway.

Starting with our phase Iia study in patients with ph recall that this study is designed to measure the impact of single doses of TP IP on pulmonary vascular resistance or P. D. R over 24 hours.

We hope to see <unk> reduction that is extended well beyond that which is currently available to us to prosper in U S.

As a reminder, we are using a low dose for the study.

Our phase <unk> study, we would expect the duration of PBR reduction to be longer given that we're using an up titration approach, which we anticipate will translate to clinical benefit.

Martina Flammer: For our phase 2B study, we would expect the duration of PVR reduction to be even longer, given that we're using an up titration approach, which we anticipate will translate to clinical benefits. COVID-19 has presented enrollment challenges for the phase 2A trial, as we are looking for patients to volunteer in the ICU setting at a time when there are surges in the Delta variant. Nonetheless, we have multiple studies open and have identified several patients, and we remain hopeful that we will have data from a small number of patients from this study by the end of the year.

COVID-19 has presented enrollment challenges for the phase Iia trial as we are looking for patients to volunteer in the ICU setting at a time when their searches in the delta the variance.

Nonetheless, we have multiple study sites open and have identified several patients and we remain hopeful to have data from a small number of patients from this study by the end of the year.

In parallel with the phase III as we're working to initiate a phase <unk> study, which will measure the impact of <unk> on P. B R and six minute walk distance over a 16 week period in patients with ph.

Martina Flammer: In parallel to the phase 2A study, we're working to initiate a phase 2B study, which will measure the impact of TPI on PBR and 6-minute walk distance over a 16-week period in patients with PAH. The phase-to-B study will also utilize an up-titration approach to each patient's maximum-tolerated dose.

The phase <unk> study will also utilize an up titration approach to each patients maximum tolerated dose.

Martina Flammer: Consistent with our expectations, we remain on track to initiate sites by the end of the year. We also anticipate initiating early next year a phase two study evaluating TPIPIP for the treatment of pulmonary hypertension associated with interstitial lung disease or pH ILD. Let me close out my remarks by addressing the importance of our fourth pillar, translational medicine. We have identified promising clinical candidates from our internal research efforts, as well as business development activities, to expand our pipeline of clinical programs aimed at treating serious and rare diseases. As our late-stage product candidates advance to potential commercialization, our approach is to identify at an early stage the next set of candidates to enter our pipeline.

Insistent with our expectations, we remain on track to initiate sites by the end of the year.

We also anticipate initiating early next year, a phase II study evaluating TP IP for the treatment of pulmonary hypertension associated with interstitial lung disease or ph ILD.

Let me close out my remarks by addressing the importance of our fourth pillar translational medicine.

We have identified promising clinical candidate from our internal research effort as well as business development activities to expand our pipeline of clinical programs aimed at treating serious and rare diseases.

As our late stage product candidates advancing to potential commercialization. Our approach is to identify at an early stage. The next set of candidates to enter our pipeline. We adhere to important criterion is search starting with the patient experience, which is of the utmost important and internet.

Martina Flammer: We adhere to important criteria in this, starting with the patient experience, which is of the utmost importance on the Internet, with a line of sight to a potential high degree of impact on the course of disease. Of note, our translational medicine capabilities are not limited to pulmonary therapeutic areas. We look forward to sharing updates from our translational medicine efforts early next. With that, let me turn the call over to Roger to discuss some key operational updates. Roger,

With a line of sight to a port.

Central high degree of impact on the course of disease.

Of note, our translational medicine capabilities are not limited to pulmonary therapeutic areas.

We look forward to sharing updates from our translational medicine efforts early next year.

With that let me turn the call over to Roger to discuss some key operational update Raj.

Joe.

Roger: Thank you, Martina, and good morning, everyone. From an operational perspective, its med made important progress during the third, Our case now has a commercial presence in three major territories U.S., Europe, and while the COVID-19 pandemic continues to shift, regional differences among and within each of these territories, I believe there is untapped opportunity to be found in each of these markets over the long term. Let me begin with our U.S. case, which has shown steady performance in the dynamic COVID

Thank you Martina and good morning, everyone.

From an operational perspective, it's made made important progress during the third quarter.

Our cases now has a commercial presence in three major territories, the U S Europe and Japan.

While the COVID-19 pandemic continues to shift and we see regional differences among and within each of these territories. We believe there is untapped opportunity to be found in each of these markets over the long term.

Let me begin with our U S business, which has shown steady performance in the dynamic COVID-19 environment.

Roger: While we did see some effect of delta surges throughout the third quarter, primarily in parts of the country that have the highest NTM patient concentration, we believe we have passed the peak of the Delta variant and anticipate growth will return once COVID stabilizes.

While we did see some effect of delta searches throughout the third quarter, primarily in parts of the country that have the highest MTM patient concentrations. We believe we are past the peak of the Delta Varian and anticipate growth will return once COVID-19 stabilizes.

While it is difficult to predict with any precision when COVID-19 will subside. We believe we have the right tools to drive growth when it does as we continue to see opportunities around the country in regions, where there is less of a COVID-19 impact.

Roger: While it is difficult to predict with any precision when COVID will occur, we believe we have the right tools to drive growth when it does, to see opportunities around the country, regions where there is less of a COVID presence. We believe the keys to growth include NTM patients feeling comfortable returning to their in-person doctor, of our targeted pulmonologist and infectious disease specialist turn their attention away from managing the COVID pandemic, opening up their practices for Beginning with Europe, where we continue to pursue our case reimbursement on a country-by-country basis, Recall that we previously achieved list price parity and reimbursement in Germany and the Netherlands.

We believe the keys to growth include MTM patients feeling comfortable returning to in person Doctor visits.

Ability about targeted pulmonologists and infectious disease specialists to turn their attention away from managing the COVID-19 pandemic and opening up their practices for in person visits to facilitate diagnoses of refractory N T M lung disease.

Let's now turn to our international commercial efforts, which we expect will continue to add to the global aerospace revenue profile.

Beginning with Europe, where we continued to pursue our case reimbursement on a country by country basis.

Recall that we previously achieved list price parity and reimbursement with the U S and Germany the Netherlands.

In the U K, we have previously achieve list price parity with the U S. And we are pleased to report that in September we achieved reimbursement in Wales, which is now the first UK nation to reimburse Erra case.

Roger: In the UK, we have previously achieved list price parity with the U.S., and we are pleased to report that, in September, we achieved reimbursement in Wales, the first UK nation to reimburse Eric. This is a very encouraging milestone as it followed a rigorous assessment of our case's place and value in this market. As a reminder, in addition to our reimbursement, the ATU program in France has been recalled that Europe follows a central approval process, followed by country-level reimbursement and subsequent law. We anticipate the reimbursement environment will become more favorable as the impact of COVID subsides. As a reminder, we anticipate Europe will represent the smallest revenue contribution of the three regions where our case is commercially available.

This is a very encouraging milestone as it followed a rigorous assessment of Ara cases place and value in this market.

As a reminder, in addition to our reimbursed markets. The HEU program in France has been extended.

Recall that Europe follows a central approval process, followed by country level reimbursement and subsequent launch.

We anticipate the reimbursement environment will become more favorable as the impact from Covid subsides.

As a reminder, we anticipate Europe will represent the smallest revenue contribution of the three regions, where our cases commercially available.

Near term, we are turning our efforts to secure reimbursement in Ireland additional countries in the U K, Italy, Belgium and France.

Roger: Near-term, we are turning our efforts to securing reimbursement in Ireland and additional countries in the UK, Italy, Belgium, and France. We look forward to keeping you updated on our progress. I'll now turn to our efforts in Japan. We launched in late July, so it's early in the launch, but we are extremely excited about our initial progress and the market opportunity in Japan, which, according to available literature, represents the largest diagnosed refractory NTM population of the markets that ends met in. Let me now expand on a few early positive signs we're seeing. First, initial uptake of new patient starts has been strong, even in the face of COVID.

We look forward to keeping you updated on our progress.

I'll now turn to our efforts in Japan.

We launched in late July so it's early in the launch, but we are extremely excited about our initial progress and the market opportunity in Japan, which according to available literature represents the largest diagnosed refractory MTM population of the markets that <unk> is pursuing.

Let me now expand on a few early positive signs we're seeing in Japan.

<unk> initial uptake of new patient starts has been strong even in the face of Covid.

Through the first couple of months of launch the number of patients initiated on irrigation is lower in Japan to what we saw in the U S. At the same time point, but the ramp is similar which is encouraging early trend.

Roger: Through the first couple of months of launch, the number of patients initiated on Ericase in Japan was lower than what we saw in the U.S. at the same time. However, the ramp is similar, and is encouraging early trends.

We have also received positive anecdotal feedback from physicians with respect to the Tolerability and the safety profile of Ara case for their patients.

Roger: We have also received positive anecdotal feedback from physicians with respect to the tolerability and the safety profile of our case for their patients. Let me clarify a few nuances of the Japanese market. First, we are currently seeing the majority of patients in the hospital setting during the first week of therapy for the purpose of starting our case. This is not unusual for this market and something we've also experienced in the TAH market in Japan. We anticipate that the hospital setting will yield beneficial patient management and retention by allowing doctors to give patients the best attention, fully understand the side effects, and educate patients on what to expect from their therapy.

It's important to clarify a few nuances of the Japanese market.

First we are currently seeing the majority of patients in the hospital setting during the first week of therapy for the purpose of starting in our case treatment, which is not unusual for this market and something we've also seen in the P H market in Japan.

We anticipate that the hospital setting will yield beneficial patient management and retention results by allowing doctors to give patients the best attention and care fully understand the side effect profile and educate patients of what to expect from their therapy.

Roger: Patients will also be thoroughly trained on how to successfully administer Aracase using the nebubon, An important note, as a consequence of initiating therapy in hospital, the initial revenue for a Japanese patient starting on Aero case is for a seven-day pack rather than a which a patient would receive when initiating therapy in the U.S. or, For the first year after approval in Japan, doctors are restricted to prescribing no more than two weeks of therapy at a time, standard for all new drugs in Japan.

Patients will also be thoroughly trained on how to successfully administer advocates using the nebulizer.

An important note as a consequence of initiating therapy in hospital. The initial revenue for Japanese patients starting on in our case is for a seven day pack rather than a 28 day pack, which a patient would receive with initiating therapy in the U S or Europe.

For the first year after approval in Japan doctors are restricted to prescribing no more than two weeks of therapy at the time, which is standard for all new drugs in Japan.

We are extremely proud of the ongoing work of our therapeutic specialists in this market.

Roger: We are extremely proud of the ongoing work of our therapeutic specialty. We are tracking well ahead of our internal expectations in the number of Tier 1 targeted hospitals, and total hospitals that have adopted the Lamarra. While less than one-third of our therapeutic specialist visits were in-person during the third trimester, Pam lifted the state of emergency at the beginning of October. Currently, about 70% of the Japanese population is fully vaccinated, which bodes well for COVID becoming endemic, opening up more beds in the hospital for the initiation of our case NTM patients visiting them, and our sales team having more in-person access to physicians.

We are tracking well ahead of our internal expectations in the number of tier one targeted hospitals and total hospitals that have adopted the luminary device.

While less the one third of our therapeutic specialists visits were in person during the third quarter.

Japan lifted the state of emergency at the beginning of October.

Currently about 70% of the Japanese population of fully vaccinated, which we think bodes well for Covid, becoming endemic opening up more beds in the hospital for initiation of our case treatment.

N T M patients visiting their doctors and our sales team having more in person access to physicians.

We are very excited about the progress in this important market early indications are that we have a very strong launch and expect Japanese revenues to build over time.

Roger: We are very excited about the progress in this important market. Early indications are that we have a very strong launch and expect Japanese revenues to build over time. I look forward to updating you on future developments as we work to deliver our case. Let me close out my remarks by acknowledging the strength of our technical operations remains on solid footing as it relates to production and inventory of our commercial products. With respect to our pipeline, we continue to manufacture adequate amounts of clinical supply product to support our ongoing summary. Insmet continues to make important advancements in the third first quarter of the Japanese launch under our belts, in our case now launched We will continue to benefit from a strong commercial position.

I look forward to updating you on future developments as we work to deliver our case to patients.

Let me close out my remarks by acknowledging the strength of our technical operations at in Smith with <unk>.

Pain on solid footing as it relates to production and inventory of our commercial product.

With respect to our pipeline, we continue to manufacture adequate amounts of clinical supply product to support our ongoing trials.

In summary is may continue to make important advancements in the third quarter.

For the first quarter of the Japanese launch under our belts in our case now launching our three strategic markets on three continents, we will continue to benefit from a strong commercial position.

Looking ahead, our existing commercial operations are laying the groundwork for potential brands catch up commercialization given.

Roger: Looking ahead, our existing commercial operations are laying the groundwork for potential brenzocative commercialization, given the overlap of NTM and Bronchi-Exys. I'm extremely proud of the team's hard work that helped us achieve these milestones. I look forward to keeping you updated on our future progress, and I'd now like to turn the call back. Thank you, Roger. In closing, I believe InSmed is approaching the next wave of transformation as we work to become a leading biotechnology company.

Given the overlap of MTM in bronchiectasis call points.

I'm extremely proud of the team's hard work that helped us achieve these milestones I look forward to keeping you updated on our future progress.

Now I'd like to turn the call back to will.

Thank you Roger in closing I believe in some it is approaching the next wave of transformation as we work to become a leading biotechnology company. The entire instrument team is unified around our collective goal to deliver life changing medicines for traditionally underserved patients I think the entire instrument team for their continued.

Roger: The entire Insomid team is unified around a collective goal to deliver life-changing medicines for traditionally underserved patients. I thank the entire Insomid team for their continued dedication, passion, focus, and commitment to this unwavering goal. I would also like to thank the patients and caregivers who participate in our studies. On behalf of the Insomid team, we extend our gratitude to you for driving us in everything we do. With that, I'd like to open the call to questions, operator. Can we take the first question, please?

Dedication passion focus and commitment to this unwavering goal.

I would also like to thank the patients and caregivers who participated in our studies on behalf of the instrument team. We extend our gratitude to you for driving us in everything we do with that I'd like to open the call to questions. Operator can we take the first question. Please.

Of course, if you'd like to ask a question. Please press star followed by one on no telephone keypad now.

Operator: Of course, if you'd like to ask a question, please press star, followed by one on your telephone keypad now. We take our first question from Jennifer Kim from Cantil Fitzgerald. Jennifer, please go ahead.

We take our first question from Jennifer came from Cantor Fitzgerald, Jennifer. Please go ahead.

Jennifer M. Kim: Hey, thanks guys. Congratulations on the Quarter, and thanks so much for taking the question.

Yeah.

Hey, Thanks, guys congrats on the quarter and thanks, so much for taking the questions I have a few here maybe to start with just commercial color on aerospace.

Jennifer M. Kim: I have a few here. Maybe to start with just commercial color and Eric Case. Could you elaborate more on the positive trends in Japan? I think you mentioned that the ramp is somewhat similar.

Elaborate more on the positive trends in Japan, I think you mentioned that the ramp is somewhat similar to the U S. I'm wondering you know if you can give some updated color around around the timing of that.

Jennifer M. Kim: to the U.S. I'm wondering, you know, if you can give some updated color around the timing of that, you know, when we should see that ramp up more. And then

We should see that ramp up more.

Jennifer M. Kim: That ramp up more. And then second, related to commercial performance, in the U.S., you said that the peak of the Delta impact has passed. So to what extent has Delta muted U.S. growth in this quarter? Just trying to get an idea of what we could see in the future. And then going into.. your pipeline

And then second related to the commercial performance in the U S. You said that the peak of the Delta impact has passed so to what extent do you think delta muted U S growth in this quarter I'm, just trying to get an idea of what we can see in the future.

And then going into your your pipeline you mentioned your next clinical candidate will be in the pulmonary therapeutic areas and I apologize if I missed this but was this an internal or external candidates and then also it is the idea here to be somewhat complementary to two I guess TPI Pierre how are you thinking about how that fit.

Jennifer M. Kim: You mentioned your next clinical candidate will be in the pulmonary therapeutic areas. I apologize if I missed this, but was this an internal or external candidate? And then also, is the idea here to be somewhat complementary to, I guess, TIP, or how are you thinking about how that fits into the pipeline? Thanks so much.

And to the pipeline. Thanks, so much.

William Lewis: Sure, thank you for the question, Jennifer, and I'll ask Roger to comment on Japan and U.S. Great, thanks, Will. So from a Japanese perspective, you did hear correctly. So we're really encouraged by the early trends that we're seeing, Just to reiterate, we launched at the end of July, so it's still early days. But what we're seeing is initiation of our case patients in the hospital. We think that that's going to be very beneficial as far as training the patients on the device, on the tolerability, and managing the side effects, which we know can be in the first week and having the best medical care to help coach the patient through that I think is going to be beneficial for the long And while the uptake has been incredibly strong, the number of patients that we have in Japan, U.S. is a little lower, but the ramp is following the same trajectory as was highly correlated, saw in the U.

Sure. Thank you for the question, Jennifer and I'll ask Roger to comment on Japan and U S.

Great. Thanks will so from a Japanese perspective, you did hear correctly. So we're really encouraged by the early trends that we're seeing in Japan and just to reiterate we launched at the end of July So it's still early days.

But what we're seeing is initiation of Eric as patients in the hospital, we think that that's going to be very beneficial as far as training the patients on the device on the tolerability and managing the side effects, which we know can be a.

In the first week and and having the best medical care to help the coach the patient through that I think is going to be beneficial for the long term.

And while.

The uptake has been incredibly strong the number of patients that we have in Japan versus the U S is a little lower but the ramp is following the same trajectory as we've seen it was highly correlated with the trajectory we saw in the U S will.

William Lewis: We'll continue to monitor it because it is still early, but we think it's very, With regard to the U.S. And the impact that we saw COVID have in the third quarter. As we had mentioned, I think in the second quarter, we had really seen some encouraging signs.

We will continue to monitor it because it is still it's still early but we think it's very encouraging sign.

With regards to the U S and the impact that we saw of Covid.

And in the third quarter as.

As we had mentioned I think in the second quarter, we had really seen some some encouraging signs we had seen our prescriptions ramp up month over month, and we were really pleased heading into the summer and then Delta Varian came out of nowhere and really impacted primarily in the in the states, where we had high N T. M concentration so think about the Gulf States.

Roger: We had seen our perspective, up month over month, and we were really in the summer, and then the Delta variant came out of nowhere and really impacted primarily in the states where we had high NTM concentrations. So think about the Gulf states, warmer weather, close to the water, and so that really impacted the ability for physicians to treat NTM patients for NTM patients seek care. On the other hand, we did see some really strong performance in areas where we didn't have such an impact from COVID, where we had potentially higher vaccination, and we still saw some growth in those regions. So we still see that regional variability.

<unk> warmer weather or close to the water and so that really impacted the.

The ability for physicians to treat MTM patients for MTM patients to seek care on the other hand, we did see some really strong performance in in in areas, where we didn't have such an impact from Covid, where we had potentially higher vaccination rates for example.

And we saw some growth in those regions. So it does we still see that regional variability, we really believe that once we get on the other side of Covid and nobody can predict when another another very it's going to hit or whether we might see that spike but at some point. We believe we will hit that endemic phase and we think that we're really poised for growth based on some of the refinements, we've been making to our messaging.

Roger: We really believe that once we get on the other side of COVID, nobody can predict when another variant is going to hit or when we might see that spike. But at some point, we believe we'll hit that endemic, and we think that we're really poised for growth based on some of the refinements we've been making to our messaging, our targeting, and patients returning to seek care and physicians turning their attention away from COVID and to some of these more chronic diseases.

Our targeting and Ah patients returning to seek care and physicians turning their attention away from Covid and just some of these more chronic diseases, we know Ncos progressive and and as patients returned to seeking care for a lot of these of these chronic diseases I think we'll we're well positioned to return to growth in the U S.

Roger: We know NTS is progressive, and patients return to seeking care for a lot of these chronic conditions. We're in well, and I'll just add to that, you know, if you want a snapshot of how bad Delta was, just take a look at the CDC infection rate over the last year or two, quite striking the rapidity of the surge caused by Delta, and if you then go further to understand that that was concentrated in areas with heavy But it was certainly something that came on abruptly and severely, and I'm glad we're past the peak, and I just have to give a shout-out to our therapeutic specialists and our outward-facing components of our commercial team.

Yeah.

And I'll just add to that you know if you want is a snapshot of how bad Delta was just take a look at the CDC infection rate over the last year or two.

It's.

Quite striking the rapidity of the surge caused by Delta and if you then go further to understand that that was concentrated in areas with heavy MTM patient populations.

I hope I can say that that's about as bad as it can get.

But it was certainly something that came on in Brooklyn, and severely and I'm glad we're past the peak and I just have to give a shout out to our therapeutic specialists and R. R.

Outward facing.

Components of our commercial team everything from the folks that are helping patients.

Roger: Everything from the folks that are helping patients understand how to use the medicine effectively to the education efforts that are helping these physicians deal with these patient populations at a time when they are absolutely called away to deal with the ICU being overwhelmed by COVID patients. It is really bad and tough on the front lines.

William Lewis: We all hear about it. But, you know, we heard a startling statistic the other day that there are a number of these cutting-edge hospitals that are really short-staffed in the midst of all this. So not only is the physician distracted, is COVID causing them to work and focus in the ICU, but their ability to lean on their own staff is limited. And so I think it's really been an extraordinary accomplishment to have the steady performance that we've seen, particularly during this difficult Delta variant. Your third question was about our next clinical candidate, and I want to be clear, I think you said that it was pulmonary.

William Lewis: It's actually not, and that was one of the points of distinction we wanted to make for our translational medicine efforts. Our translational medicine effort is really made up of a collection of personnel and technologies that are really quite exciting. They're cutting-edge. I think we're going to be really excited to share more detail about that early next year. And one of the reasons we're sharing this with you now is so that you can be mindful of those products not just coming forward in the form of one or two, but this really represents an engine.

We feel about that early next year and one of the reasons. We're socializing. It with you now is so that you can be mindful of.

Those products not just coming forward in the form of a one or two but this really represents an engine. This is the future of instrument. This is the next generation of programs that will follow behind the first three pillars, where we have a tremendous amount of enthusiasm and I think the commercial potential that flows from being so impactful on patients is self evident.

William Lewis: This is the future of insomet. This is the next generation of programs that will follow behind the first three pillars, where we have a tremendous amount of enthusiasm, and I think the commercial potential that flows from being so impactful on patience is self-evident. But we also note that companies that have been wildly successful with their early products sometimes hit a rut where they don't have the answer to the question of what's next. We now have that answer, too, and we're extremely excited about it, and we'll have more to say about that in detail early next year. Great

But we also note that companies that have been wildly successful with their early products.

Sometimes hit air pockets, where they don't have the answer to the question of what's next we now have that answer too and so we're extremely excited about it and we'll have more to say about that in detail early next year.

Okay.

Great that's super helpful and thanks for that clarification around your pipeline congrats everyone.

Jennifer M. Kim: Great, that's super helpful, and thanks for the clarification around your pipeline. Congress, everyone.

We take our next question from Anita Chen from burn, but capital markets. Please go ahead.

Operator: We take our next question from Anita De Shamp from Beringberg Capital Markets. Anita, please go ahead.

Hi, good morning.

Anita De Shamp: Hi, good morning. I just have a couple of questions around the study with TPP, the 24-R study with a 30-day follow-up. Just wanted to know how you were coming up with the enrollment for those, considering the small patient population. And also, if you could talk about the opportunity and timeline for Brenzo-Kative in the pediatric population.

I have a couple of questions.

Debbie with TP IP 24 hour study.

Just wanted to know.

How youre coming up with <unk> and gentlemen for the small patient population.

And also if you could talk about the opportunity and timeline.

For the <unk> PDF.

Pediatric population.

I'll ask Martinez to address that yeah. So for phase III. This is our our study where we're monitoring.

Martina Flammer: I'll ask Martina to address that. Yeah, so for Phase 2A, this is our study where we're monitoring patients for 24 hours. This is a single-dose, low-dose study with several sites open and who have identified patients already for this study. Also, for context, if you have a right-heart capacity, that is usually a procedure that would take an hour and a half, maybe two hours. We are doing this over a 24-hour period, and that's why we talk to you about the ICU necessity for such a study, and that is where it is right now challenging. Nevertheless, we do believe that we will have data from a handful of patients by the end of this year.

Patients about 24 hours, we call this as a.

Single single dose low dose study and with several sites open and who identified patients already for this study also for context if you.

If you have a right hard cut that cost that is usually a procedure that would take an hour and a half maybe two hours. We are doing this over a 24 hour period and that's why I mean, we talk to you about the ICU necessity for such a study and that is where it is right now challenging Nevertheless, we do believe that.

We'll have the data from a handful of patients by the end of this year.

Martina Flammer: So I think your second question was about the pediatric program for Brentocative. Pediatric programs are of high interest to regulatory authorities, and that is true across the globe. And what is really important is that we have achieved aligned programs. In many cases, different regulators require different study designs, sometimes causing you to have actually two or three different studies. So the importance for us to be able to have 40 patients that are included in Aspen is, first of all, important from an operationalization point of view, but it also gives us the opportunity to have this data available early when, in many cases, you have pediatric reports that are coming out quite later than your initial pivotal program.

So I think taking the second question was about the pediatric program.

For both brands for captive pediatric programs are of high interest to regulatory authorities and that is true across the globe and what is really important is that we haven't achieved.

Aligned program in many cases, the different regulators require different study design sometimes.

Causing you to have actually two or three different studies. So the importance for us to be able to have 40 patients that are included in Aspen is first of all important from an effective operationalization, but it also gives us the opportunity to have this data available early when in many cases you have pediatric.

Reports that are coming out quite later than your initial pivotal program.

Okay. Thank you Mike.

Anita De Shamp: Okay, thank you, Marina. And just one more question on Eric Hay's adoption, now that you're able to sort of see its pattern in Japan and also, you know, with several countries in Europe coming on board. When are you likely to resume giving guidance?

Just one more question on the.

One on <unk>.

Every case the adoption.

Now that you are able to sort of see a pattern in Japan and also with several countries in Europe coming on board.

Roger: Sure, Anita, thanks for the question. So we rescinded guidance, you know, in the beginning of the pandemic, as you saw many companies do. We understand and appreciate that the investment community would look for us to provide guidance at this point, at some point in 2020.

When are you likely to resume giving guidance.

Sure Nathan Thanks for the question, so we rescinded guidance.

In the beginning of the pandemic as you saw many companies do.

Understand and appreciate that the investment community would look for us to provide guidance.

At this point at some point in 2022, and we will look to provide a level of forward looking guidance.

Roger: At some point in 2022, we will look to provide a level of forward-looking guidance.

Okay. Thank you.

Yep.

Our next question comes from Joseph Schwartz from S. P. B Leerink. Please go ahead.

Operator: Our next question comes from Joseph Schwartz of SVB Lerink. Please go ahead.

Hi, I'm Jerry dialing in for Joe. Thank you for taking our question.

Joseph Patrick Schwartz: Hi, I'm Drew Rely in for Joe. Thank you for taking our questions. First question, I guess, are you satisfied that you pulled out all the stops in terms of employing creative initiatives to diagnose onboard patients remotely in a world where COVID seems like it's going to be endemic for the foreseeable future?

First question I guess are you satisfied that you've called out all the stops in terms of employing creative initiatives to diagnose.

And onboard patients remotely in a world, where COVID-19 seems like it's going to be and then that for the foreseeable.

The foreseeable future.

Roger: Tos, Roger, to address that. Yeah, thanks.

So I'll ask Roger to address that.

Yes. Thanks.

We continue to look for innovative ways to help.

Roger: We continue to look for innovative ways to help patients be diagnosed and treated in a remote setting. We see sort of the ebbs and flows of patients taking telemedicine. One of the unique challenges is to actually collect sputum remotely from a patient and have them then be diagnosed with a refractory MAC based on a positive We are implementing several initiatives, including sponsoring a program to facilitate remote, um, capturing and sending it off to central labs for testing to facilitate that diagnosis, and we can deploy that regionally as bikes go up and down.

Patients will be diagnosed and treated in a remote setting we see sort of the ebbs and flows of of patients taking tele medicine. One of the unique challenges is is to.

To be able to actually collect dispute them remotely from a patient and and have them then.

And be diagnosed with refractory Mac based on a positive culture, we are implementing several several initiatives, including sponsoring a.

Our program to.

Facilitate remote.

Capturing of sputum, and sending it off to central labs for testing to facilitate that diagnosis and we can deploy that regionally as we see these spikes go up and down for.

For for Covid. So I think we'll continue to innovate will continue to look for new ways to facilitate that and <unk> and.

Roger: So I think we'll continue to innovate, and we'll continue to look for new ways to facilitate that and encourage patients to seek care for their NTM and to talk to their doctor Generally, we see across the universe of chronic diseases that a lot of patients are delaying cancers and hypertension. And so it's important that we work with our patient groups and with our patients to encourage them to continue to seek care. You know, the only thing I would add to that is, and this is a really important point, the patients are there, the physicians are there. We know that there are pools that we have not yet reached.

And encourage patients to to continue to seek seek care for for further N T M and to talk to their doctors I think generally we see across the across the universe of chronic diseases.

Patients are delaying delaying care.

For for even things such as such as cancers, and hypertension et cetera and.

And so it's important that we work with or without patient groups and and with or without patients to encourage them to continue to seek care and we look for innovative ways to continue to do that.

William Lewis: And again, a shout out to the creativity that's been brought to bear by the commercial team out of necessity in this very, very difficult environment, the most difficult period of which is this recent Delta variant that we've seen play out. And as you heard in Rogers' earlier comments, one of the most exciting things, and I've seen in this last quarter, is that the impact of some of these creative approaches has been evident.

Yeah. The only thing I would add to that is I want you to understand and this is a really important point. The patients are there. The physicians are there. We know that there are pools that we have not yet reached and again a shout out to the creativity, that's been brought to bear by the commercial team.

Out of necessity in this very very difficult environment. The most difficult period of which is this recent delta variant that we've seen play out and as you heard in Roger's earlier comments one of the most exciting things that I've seen it in this last quarter is that the impact of some of these creative approaches has been evident in those areas where delta was not.

William Lewis: In those areas where Delta was not as prevalent, we did see responses to these creative approaches, and I think that that deserves a lot of recognition and credit for our commercial team, and it bodes well for the future when the collective, you know, United States is beyond this Delta, this Delta variant. Then I think all those efforts and creativity can be brought to bear, and the evidence from that will be clear, and that's why we have conviction today that even during the endemic phase going forward, we will see growth.

As prevalent we did see in response to these creative approaches and I think that that deserves a lot of recognition in credit for our for our commercial team and it bodes well for the future when the.

Collective.

You know United States as is.

Beyond this delta this filter variant than I think all of those efforts and creativity can be can be brought to bear and the evidence from that will will.

It will be clear and that's why we have conviction today, but even during the pandemic phase going forward, we will see growth.

Yeah.

Okay, great. Thank you for that.

Joseph Patrick Schwartz: Okay, great, thank you for that. And then, I guess, what are your latest thoughts on the size of the European and Japanese markets? So, for example, if you have a better estimate on the number of addressable patients in Germany and the Netherlands, now that you're in those countries, are there reasons to believe that there could be more addressable patients than originally anticipated?

And then I guess what are your latest thoughts on the size of the European and Japanese markets. So for example, do you have a better estimate on the number of addressable patients in Germany, and Netherlands now that you're in those countries are there reasons to believe that there could be more addressable patients than originally anticipated.

Roger: Yeah, sure, thanks. Thanks.

Roger you want to take that.

Yeah sure. Thanks, Thanks, I think as we've previously commented we see Europe as probably the smallest opportunity from a diagnosed refractory Mac.

Roger: I think as we've previously commented, we see Europe as probably the smallest opportunity from a diagnosed refractory MAC patient population. Having said that, we do believe that there's probably a significant amount of undiagnosed MAC patients, and that's one of the efforts that we'll be pursuing as we get able to launch across Europe. We do think that, as we do think that, as we're pursuing, as we do think that, as we're pursuing, as we do think that, as we're pursuing, as we get able to, as we're as patients will be returning to their physician's offices in Europe as the same dynamic as plays out there as it has in the U.S. with impacts of patients postponing care and not being able to enter the clinics to interact with their physicians.

Patient population.

Having said that we do believe that there's probably a significant amount of diagnosed Mac patients and that's one of the efforts that we'll be pursuing them.

As we get them.

222 to launch across across Europe.

We do think that as.

Patients will be returning to to their physicians offices in Europe as the same dynamic as plays plays out there as it has in the U S with impacts of patients are postponing care and not being able to enter the clinic.

Interact with their physicians, but over time, we do think that we'll be able to increase the diagnosis in in in Europe, and we believe that.

Roger: But over time, we do think that we'll be able to increase the diagnosis in Europe and we believe that There's probably a higher number of refractory MAC patients in Europe than what the medical literature indicates, In Japan, we think that it is the largest diagnosed refractory mac population, larger than the U.S. There's a few reasons for that. We think that the medical screening, the annual physical that Japanese patients undergo includes a lung scan, and so they are able to pick this up, pick up NTM a little earlier than they do in the U.S. And we think that the early signs of the launch and the interest we've had from KOLs, the interest we've had from patients, uh... in our case and the launch uh... validate the assumption uh... that we have in the medical literature that we've seen uh... that this is a is a substantial market uh... and the uptake we've seen so far is uh... it's very promising and we look forward to updating further on that as we go

There's probably a higher number of refractory Mac patients in.

In Europe, and what the medical literature indicates in Japan, we think that it is the largest diagnosed refractory Mac population larger than the U S. There's a few reasons for that are we think that the medical screening.

Annual physicals that Japanese patients undergo includes a lung scan and so they are able to pick this up.

N T M a little earlier than they do in the U S and we think that the early signs of the launch and the interest we've had from Kols. The interest we've had from patients in allocation and the launch validates the assumption that we have in the medical literature that we've seen that this is a substantial market.

And the uptake we've seen so far is very promising and we look forward to updating you further on that as we go.

Okay, Great and then if I could just squeeze one more in how close are you to wrapping up arise given that you started in late 2027 month study just wondering if you have any line of sight.

Joseph Patrick Schwartz: Okay, great. And then if I could just squeeze one more in,

Joseph Patrick Schwartz: How close are you to wrapping up a rise, given that you started it in late, you know, 2020, and this is a seven-month study? Just wondering if you, you know, have any line of sight.

William Lewis: Yeah, so we haven't given specific guidance on enrollment timelines for any of our trials, just out of respect for the unknowns surrounding COVID. And I have to say, the Delta variant probably showed us that that was a wise instinct to follow. We will provide some direction once we get to a place where we see steady performance that we think allows us to interpolate and do so reliably for the benefit of our shareholders.

Yes, so we haven't given specific guidance on enrollment timelines for any of our trials.

Out of respect for the unknown surrounding Covid and I have to say the Delta Vernon I think probably showed us that was a wise instinct to follow.

We will provide some direction once we get to a place where we see steady.

Our performance that we think allows us to interpolate and do so reliably for the benefit of our shareholders.

And we would expect that that'll be some time.

William Lewis: And we would expect that that will be sometime in the earlier part of next year. But at this time, we don't have any further guidance other than to say that these trials are all tracking our internal expectations. And so we feel good about where we are.

In the earlier part of next year.

But at this time, we don't have any further guidance other than to say that these trials are all tracking our internal expectations.

And so we feel good about where we are.

Okay, great. Thank you very much.

Joseph Patrick Schwartz: Okay, great. Thank you very much.

Yeah.

We take our next question from Jeff Hung from Morgan Stanley. Please go ahead, Jeff.

Operator: We take our next question from Jeff Hung from Morgan Stanley. Please go ahead, Jeff. Thanks for asking the question.

Thanks for taking the questions for Eric as you indicated we're past the peak of Delta variant can you talk about any changes you're seeing or hearing on physician offices reopening Ah patients returning to in office visits and then customer engagement by your therapeutic specialists in person in the field and how did these dynamics impact your confidence in growth for the remainder of the year.

Jeff Hung: Thanks for taking the questions. For Eric Case, you indicated we're past the peak of Delta Bariant. Can you talk about any changes you're seeing or hearing about physician offices reopening, patients returning to in-office visits, and then customer engagement by your therapeutic specialist in person in the field? And how do these dynamics impact your confidence in growth for the remainder of the year? And then I'll follow up. Roger, do you want to take that one?

And then I have a follow up.

Roger you want to take that one.

Yeah sure I think so as we as we think about the Delta Varian and we're tracking the CDC data, we certainly see the cases are going down.

Roger: Yeah, sure. I think, as we think about the Delta variant and as we're tracking the CDC data, we certainly see the cases are going down. And what we hear anecdotally from our field force is that patients are, or physicians are able to turn their attention back to their private practices, take patient visits. And so we do see more inpatient interactions, and in-person interactions from our sales force with physicians. we think that that's really important as we're able to get back to growth. And in addition, as we've said previously, where we had not had the impact of COVID, we actually saw growth in those regions where the impact was lessened.

And what we hear anecdotally from our field forces that Ah patients or are or physicians are able to turn their attention back into their their private practices takes it take patient visits and so we do see more inpatient interactions in person interactions from our Salesforce with physicians, we think that that's a really important as.

As we're able to get to a return to growth.

And and in addition, as we've as we've said previously where we had not had the impact of Covid, we actually saw growth in those regions, where the impact was lessened. So as we see those returns those dynamic returns, particularly in those high N. T. M concentration markets, we think that bodes well for our for a return as a return to growth.

Roger: So as we see those returns, those dynamic returns, particularly in those high NTM concentration markets, we think that bodes well for our return to growth and getting those patients back into the office and treated. You know, as Will mentioned, these patients are out there. We know that they're there, and it's a matter of them returning to the office, the physician having time and capacity to treat them, and we believe that that bodes well for our case in the long run.

And getting those patients back it back into the onto the office and treated them as.

As will mentioned these patients there are out there we know that they're that they're out there and it's a matter of them returning to the office to physician, having time and capacity to treat them and we believe that that bodes well for fabrication of the long term.

Great and then in Japan, how has the two week limitation of prescriptions and patients returning to physicians to get refills now how has that been relative to your prelaunch expectations and or the proportion of patients getting refills above below or in line with your expectations.

Roger: And then in Japan, how has the two-week limitation of prescriptions and patients returning to physicians to get refills been relative to your pre-launch expectations, and is the proportion of patients getting refills above, below, or in line with your expectations? Thanks. Roger, go ahead.

Yeah.

So would you go ahead, yeah. Thank you so so.

Roger: Yeah, thank you. So we actually don't have specific refill information on Japan at this point, but I will say that this is the common, the common rule across Japan is that you're restricted to the two-week limitation within the first year. So Japanese patients and physicians are very attuned and accustomed to this. As we mentioned, the majority of patients are starting in a hospital setting, so they go for between four and seven days in the hospital to initiate therapy.

So we actually don't have a specific refill information on Japan at this point, but I will say that this is the common the common.

Rule across Japan is that restricted to the two week limitation within the first year. So Japanese patients that physicians are very attuned and accustomed to this as we had mentioned the majority of patients are starting in a hospital setting. So they go in for between four and seven days in the hospital to initiate there.

And so what they start off with is a seven day pack rather than than a two seven days 14 days once they're discharged from the hospital. The they will receive from the pharmacy, another pack and in the equipment to take home with them.

Roger: And so what they start off with is a seven-day pack rather than two seven-day packs or 14 days. Once they're discharged from the hospital, they will then receive from the pharmacy another pack and the equipment to take home with them. We haven't seen, based on the results we're seeing, it appears that these patients are continuing therapy. The anecdotal response from reports from physicians is that patients are actually tolerating the product really well.

We haven't seen a.

Based on the results we're seeing it appears that these patients are continuing therapy. The anecdotal response from our reports from physicians or the patients are actually tolerating the product really well and we think that bodes really well for continuation of therapy are longer term.

Roger: And we think that bodes really well for continuation of therapy longer term as, as, as, as, as the treatment progresses and and we don't anticipate that the two-week limitation is going to be is going to be an issue for these patients or for the physicians and just a reminder is the first year since approval so approximately so we were approved in June and so we'll we'll see that limitation lifted at that point assuming that there's no untoward side effects and to date we haven't seen anything there to be of concern

As a as is the treatment progresses, and and we don't anticipate that the two week limitation is going to be it's going to be an issue for these patients for the physicians.

And just a reminder is the first year since approval. So approximately so we were approved in June.

And so we will we will see that limitation lifted at that point, assuming that there's no untoward.

Side effects and to date, we haven't seen anything there to be a concern.

Thank you.

Operator: Our next question comes from Stephen Wiley from Stifle. Stephen, please go ahead.

Yeah.

Yeah.

Our next question comes from Stephen Willey from Stifel Stephens. Please go ahead.

Stephen Douglas Willey: Yeah, good morning. Thanks for taking the time to ask the question.

Yeah. Good morning, Thanks for taking the questions.

Stephen Douglas Willey: Um, So maybe just to follow up on that last point, I know in the phase three air case relapse refractory trial, you guys characterized the early discontinuation of patients within the first 30 days to be somewhere around 30 percent. Based upon your comments regarding Japan, I'm just wondering.

So maybe just to follow up on that last point I know in the I think it was in the phase three air case relapsed refractory trial, you guys characterize the early discontinuation of patients within the first 30 days I guess to be somewhere around 30%.

Based upon your comments regarding Japan I'm, just wondering if you can kind of frame what that early attrition rate might look like relative to the U S trials statistic for the phase III trials.

Stephen Douglas Willey: I was wondering if you could kind of frame what that early attrition rate might look like relative to that U.S. trial statistic.

Stephen Douglas Willey: or the phase three trials statistics. And then also just wondering, just given the reduced number of patient or, I guess, in-office visits in the U.S. that have happened here over the course of the last 12 to 18 months. Have you seen that?

Statistics and then also just wondering just given the reduced number of.

Inpatient or I guess.

In office visits in the U S that have happened here over the course of the last 12 to 18 months have you seen that number.

Stephen Douglas Willey: over the course of the last 12 to 18 months. Have you seen that number? trends up just given that there's, I guess, less patient handholding during the initiation of therapy.

Trend up just given that there's a I guess less Ah patient handholding, Jeremy during the initiation of therapy.

Roger: Yeah, sure. We actually haven't broken down the discontinuation rates from Japan at this point. It's still pretty early, as I said, we've got about two months of launch under our belt, so we don't have adequate samples breaking down the discontinuation other than the anecdotal reports, which are from the physicians and from our team in Japan, that the hospitalization, which is designed to help patients get through that first week and to manage the side effects and ensure they continue treatment, has been well received, and physicians and patients are happy there

Roger you want to take those.

Yeah sure, we actually haven't broken down it just continuation rates from Japan at this point, it's still pretty early as I said, we're we've got about two months of launch under our belt. So we don't have adequate sample breaking down the discontinuation other than the anecdotal reports.

Which are that the the from the physicians and from our team in Japan.

That the hospitalization is which is designed to help patients get through that that first week and to manage the side effects and ensure they continue on therapy.

As has been has been well received and physicians and patients are happy there. So we can update I'm going forward you know what with what we're seeing there but at this point, it's too early to just to share any specific statistics on discontinuation rate as you mentioned in the clinical trial, we saw about a 30% discontinuation rate and we'll see what.

Stephen Douglas Willey: So we can update going forward, you know, what we're seeing there, but at this point, it's too early to share any specific statistics on discontinuation rates. As you mentioned in the clinical trial, we saw about a 30% discontinuation rate, and we'll see what kind of impact the specific care that these patients are receiving in the hospital setting will have on their continuation rates. Regarding patient visits, so the data we have on patient visits is a lagging indicator, so it takes a while for that to get reported.

Kind of impact the specific care that these patients are receiving in the hospital setting, we'll we'll will have on on on their continuation rates.

Regarding the patient visits so the data that we have and collecting on patient visits.

<unk> is a lagging indicator so it takes a while for that to get reported so we don't have good information at this point as to what.

Stephen Douglas Willey: So we don't have good information at this point as to, you know, what patient visits to the pulmonologists and IDs are looking like. So I can't share any sort of forward-looking data there. We did see an impact clearly during the COVID pandemic. We did see patient visits decline, and we're anticipating that as the COVID pandemic becomes more endemic, and patients are able to return to offices, and physicians are able to open their offices again, we'll see those trends up. But we don't have an immediate data source that gives us that real-time sort of information. So you don't have any information that suggests a correlation between

Patient visits for her to the Pulmonologists and Ids are looking like so I can't share any sort of forward looking data there we.

We did see an impact on.

Clearly joined the drill co, but we did see a patient a patient visits decline.

And we're anticipating that as as the Covid pandemic becomes more endemic and patients are able to return to offices and physicians are able to open their offices again that we'll see those those those trend up but we don't have a.

Immediate data source that gives us that real time sort of information.

So you don't have any information that suggests a correlation between them.

Stephen Douglas Willey: inpatient visits and then what that early discontinuation statistic looks like.

Inpatient visits and then what that really discontinuation statistic looks like.

Stephen Douglas Willey: I'm sorry, the question is the correlation between inpatient visits and discontinuation. Yes, I'm just wondering if there are fewer in-office visits from patients, specifically during those first 30 days of initiating therapy.

I'm sorry. The question is what is the correlation between inpatient visits and discontinuation.

Yeah. So I'm just wondering if theres fewer in office visits from patients specifically during that first 30 days of initiating therapy, whether or not that that that reduce time in a physician's office.

Roger: therapy, whether or not that reduced time in a physician's office, which we've seen from COVID here over the last 12 to 18 months, has impacted that discontinuation statistic during the first 30 days of therapy. Okay.

Which we've seen from Covid here over the last 12 to 18 months has impacted that discontinuation statistic during the first 30 days of therapy.

I get it okay. So so I think what's more important than the physician then the visits to the physician offices is actually Ah patient Ara Erik Hirsch trainers.

Roger: Okay, so I think what's more important than this office is actually the patient, our Air Care's trainers that device to train them on the device on how to successfully initiate therapy. And so we do see that, as the in-person training varies. So we do remote, have the in-person, but the virtual training is also effective in introducing the patient. We just see as we're able to get to know them in person and spend a significant amount of time Okay, and then just lastly, I think Martina had mentioned that she was hopeful regarding the availability of face 2A TPP data before the end of the year.

That visit the patients to introduce them to the device to train them on the device on how to successfully initiate therapy.

Therapy, with Ara case, and what to expect from therapy, and so we do see that as the in person training.

A very so we do remote and we do it in person in the patient is absolutely entitled to choose and which manner. They want to receive that training I think we see slightly better results. When we have the in person training.

Roger: Is there a minimal threshold of patient numbers that we should be thinking about in terms of, "You need to enroll in order for us to get that data before you." So I want to just highlight that it's not particularly critical to me that it be done by date X versus Y. Our guidance has been that we would hope to produce it by the end of the year. We absolutely intend to follow through on that.

But their virtual training is also is also effective in introducing the patient we just see as we're able to get to in person spend a significant amount of time with patients in their homes and talking and introducing the therapy that has a beneficial impact on the patients.

William Lewis: But the one caveat there is the Delta variant, the ICU bed occupancy. What we're asking somebody to do is to go into an ICU room that is filled with COVID patients and stay there for 24 hours with a right heart calf. And as Martina said, that's a procedure that normally lasts an hour and a half.

Patients tolerating and continue on therapy.

Okay and then.

Just lastly, I think Martina had mentioned that she was hopeful regarding the availability of a phase two a T. P. I P data before the end of the year is there a minimal threshold of patient numbers that we should be thinking about in terms of.

You need to enroll in order for us to get that data before year end.

William Lewis: So it's an enormous ask, and these volunteers are hard to come by. Having said that, the centers and the KOLs that are around this are very excited about this medicine's potential and are looking very actively to try to identify such patients, and they have. We are aware of several patients that are available. They need to meet the screening criteria. They need to find

So.

To just highlight that it's not particularly critical to me that it would be done by Dave X versus Y. Our guidance has been that we would hope to produce by the end of the year.

We absolutely intend to follow through on that but the one caveat there is the delta or in the ICU bed occupancy what were.

We're asking somebody to do is to go into an ICU room that is filled with COVID-19 patients and stay there for 24 hours worth of right heart catheter as Martina said, that's a procedure that normally last an hour and a half. So it's an enormous ask and these volunteers.

William Lewis: comfort in coming into the ICU, and if that happens, then we should be able to produce data very quickly because this is, after all, 24 hours of exposure, after which we'll have the data effectively immediately. So I think it's not logistically challenging to produce the data once the patients are past the volunteer point and have qualified, and for that reason, we have conviction that we'll be able to produce data. I think the only other thing I would introduce here is that we want to make sure that the data is consistent and that we don't see any variability that would cause us to want to see more data to further validate.

<unk> are hard to come by having said that the centers and the Kols that are around this are very excited about this medicine potential and are looking very actively to try to identify as such patients and they have we are aware of several patients that are available they need to meet the screening criteria they need to find comfort in coming in.

The ICU and if that happens then we should be able to produce data very quickly. Because this is after all 24 hours of exposure after which we'll have the data effectively immediately so I think.

It's not logistically challenging to produce the data once the patients are past the volunteer point and have qualified and for that reason, we have conviction that we'll be able to produce data I think the only other thing I would introduce here is we want to make sure that the data is consistent and then we don't see any variability that when.

When causes.

Want to see more data to further validate let's be clear that the preclinical animal models around TP IP, we're very definitive.

William Lewis: Let's be clear that the preclinical animal models around TPI were very definitive. And this drug, the actual moiety, is very well known, and there's excellent human experience with it. So there aren't a lot of variables here in my mind that would introduce a delay that would be meaningful, and we think we can get the data. We think it's going to be really important, and we're looking forward to sharing it with you as soon as we get it in its imperfect form. Great

And this drug the actual moiety is very well known and there's excellent human experience with it. So there aren't a lot of variables here in my mind that would introduce a delay that that would be a meaningful and we think we can get the data and we think it's going to be really important and we're looking forward to.

When you as soon as we get it in proper form.

Stephen Douglas Willey: Great, that's helpful. Thanks for taking care of the questions.

Great. That's helpful. Thanks, taking my questions.

We have a question from <unk> from Evercore ISI Lisa. Please go ahead.

Operator: We have a question from Lisa Bako from Evercore ISI. Lisa, please go ahead.

Lisa Bako: Hi, a couple questions from me. First of all, I missed the gross to net for the quarter. Did you say exactly what that was?

Hi, a couple of questions from me first of all I missed the gross to net for the quarter did you say exactly what that was.

Yes, it was 12% Lisa.

Lisa Bako: I missed the gross to net for the quarter. Did you say exactly what it was?

Thank you okay.

Any update on Covid.

Lisa Bako: Thank you. Okay. Any update on COVID?

Meaning your effort there.

No Eric He's insulins.

Lisa Bako: Meaning your effort there, not Eric's case and influence.

So so.

The information from the trial that Professor Chalmers ran was obviously the topline was released last.

William Lewis: So the information from the trial that Professor Chalmers ran was, obviously, the top line was released last, August, July? July. So that's been out. There hasn't been anything further that has come since then. I'm just looking at Martina to see if there's any more information. I don't think so. No.

August July July.

So that's that's been out there hasnt been anything further that has come since then I'm just looking to Martina to see if there's any additional information I don't think so no.

Okay.

M T.

William Lewis: T-PIP, can you just maybe further explain, like, what are you looking for in this data? You know, I know you're only going to have a couple of patients. Are you going to continue to enroll in the full amount, and what really is the actual underlying purpose, and is it gating for kind of the next steps? What are you going to glean from this that would be in format? Yeah, so first of all, it's not gating in any way for the other phase two programs. The purpose of this trial

T P I P.

Maybe further explain like what what are you looking for in this data.

You know.

I know you are only going to have a couple of patients are you going to continue to enroll the full amount.

What what really is the actual underlying purpose and is gaining for kind of the next steps what are you going to glean from that that would be informative.

Yeah. So first of all it's not getting in any way for the other phase III programs. The purpose of this trial is to identify.

William Lewis: Yeah, so first of all, it's not gating in any way for the other phase two programs. The purpose of this trial is to identify what happens to pulmonary vascular resistance when patients are given a starting dose of our TPIP. What do we think is going to happen here?

What happens to pulmonary vascular resistance when patients are given a starting dose of <unk> TP IP.

What do we think is going to happen here well, if we look at <unk> and what they do our previous studies have demonstrated about an hour and a half of PBR reduction.

William Lewis: Well, if we look at Proposinol and Taveso and what they do, previous studies have demonstrated about an hour and a half of PVR reduction in those studies, although the duration of that PVR reduction extends a little bit as doses go up. And so one of the important distinctions here is that in our TPI study, we're going to start at a fairly low dose, perhaps somewhere around 100 micrograms, just to put that into context.

And in those in.

And those studies the duration of that PBR reduction extends a little bit as doses go up and so one of the important distinctions here is in our <unk> study, we're going to start in a fairly low dose, perhaps somewhere around 100 micrograms.

Just to put that into context, the VISO after titration in its label is.

William Lewis: So, Tivezo, after titration in its label, is guided to a maximal dose of 54 micrograms. So even though we're starting at what we consider to be a low dose, it's actually higher than the maximal dose you can reach through titration on Tivezo's label.

As guided to a maximal dose of 54 micrograms, so even though we're starting at what we consider to be a low dose actually higher than the maximal dose you can reach through titration in time as those label.

William Lewis: What do we think that's going to show? We think it's going to show a PBR reduction that we hope will last significantly longer than the hour and a half that you see with Tivezo. How much longer? We don't know. That's really what the study is going to reveal. But you can just continue.

What do we think that's going to show, we think it's going to show a P. B R. A reduction that we hope will last significantly longer than the hour and a half that you see what type of Enzo how much longer we don't know that's really what the study is going to reveal but if you can just conceptually follow.

William Lewis: It conceptually follows that if we are able to extend the duration of pulmonary vascular resistance reduction for multiple hours beyond the hour and a half, then you're effectively creating a steady state of vasodilation, and all of the downstream benefits that flow from that would be realized. And in animal models, that resulted in disease modification. And that's the histologic change that was so profound. And it's why we say we think this formulation will be able to unlock the full potential of prosanoid therapy. Okay, and is there a certain, like, duration?

Follow that if we are able to extend the duration of pulmonary vascular resistance reduction.

For multiple hours beyond the hour and a half then you're effectively creating a steady state.

Basal dilation and all of the downstream benefits that flow from that.

It would be realized in the animal models that resulted in disease modification and that's the histologic change that was so profound and it's why we say we think with this formulation will be able to unlock the full potential of Proxenoi therapy.

Okay and is there a certain like duration.

Lisa Bako: that you want to see, you know, kind of that Nader to really inform yourself that you have

That you want to see like you know.

Kind of that Nader.

Lisa Bako: Have, you know, once a day or twice a day or whatever, you know; I know you're targeting once a day.

So to really inform that have you know a once a day.

Or twice a day or whenever you know I know you're targeting once a day.

Lisa Bako: getting one today. Is that... Yeah, so one of the interesting... Yeah,

Product is that yeah, so one of the interesting or what.

Yeah.

Yeah. So remember that you see clinical benefit demonstrated with 10 days with four times to seven times, a day administration with that short one and a half hour.

William Lewis: Yeah, so remember that you see clinical benefit demonstrated with Taizzo with four times to seven times a day administration and that short one and a half hour BBR reduction. So we don't think we need to cover 24 hours uninterrupted, but if we were to get anything approaching that, we can assume that we will be able to show at least the clinical benefit that was seen with Taizzo, and our imagination is that it could be more.

<unk> reduction so we don't think we need to cover 24 hours of uninterrupted, but if we were to get anything approaching that we can.

Assume that we will be able to show at least the clinical benefit that was seen with type of Enzo and our imagination that it could be more and that's what the animal models suggest that in fact, they demonstrated because we compared our drug to type of Enzo and two oral and other formulations of Coprostanol and saw that we were.

William Lewis: And that's what the animal model suggested. In fact, they demonstrated it because we compared our drug to Taveso and to oral and other formulations of tropostinol and saw that we were, in fact, superior. So I think that's what's got us very excited about the potential here.

In fact superior so I think that's what's got us very excited about the potential here and the other the only other point I'd make is that in our phase. One study we were able to go with a single dose administration without titration north of 600 micrograms. So again, referring to 10 days ago at 54, and I understand it's dosed four times.

William Lewis: And the only point I'd make is that in our phase one study, we were able to go with single dose administration, without titration, north of 600 micrograms. So again, referring to Taveso at 54, and I understand it's dose four times to seven times a day, so it's a little bit of apples to oranges in terms of dose levels. But it's clear we can get to much more significant dosing levels, and we believe that will be extended through titration so that we will be dosing more, which should extend the duration of the PBR reduction.

Two seven times a day, so it's a little bit of apples to oranges in terms of.

Dose levels, but it's clear we can get to much more significant dosing levels and we believe that will be extended through titration.

So that we will be dosing more that should extend the duration of the P. B our reduction and if we're able to show just a baseline extension at a low dose of say 100 micrograms, one can imagine what that might possibly achieve through a dose titration and that I think is what this study is really going to unlock is the earliest look at the.

William Lewis: And if we're able to show just the baseline extension at a low dose of, say, 100 micrograms, one can imagine what that might possibly achieve through dose titration. And that, I think, is what this study is really going to unlock, the earliest look at the potential for all of those accomplishments, PBR reduction, duration of PBR reduction, and the imputed potential to go even further with dose titration.

<unk> for all of those accomplishments P. B our reduction in duration of P. B R. A reduction and the imputed potential to go even further with dose titration.

Lisa Bako: Okay, great, thank you.

Okay, great. Thank you and then just can you give us a sense of like of.

Lisa Bako: And then just can you give us a sense of your like, of your, you know?

Your $47 million of revenue how much of that was ex U S.

Lisa Bako: Of your, you know, $47 million in revenue, you know, how much of that was XUF?

Roger: Thanks, Lisa, for the question. We are currently not breaking out our revenue by region. I anticipate that next year we will break it out based on sort of materiality thresholds, but today we only provide a global number.

Thanks, Lisa for the question.

We are currently not breaking out our revenue by region am I am.

And that next year, we would break it out based on sort of materiality thresholds, but today, we are only political number.

Okay, and then for Japan, I was looking at the numbers. It looks like you kind of reported in the first quarter of launch you know over 500 patients and then the next quarter the second quarter of the launch was.

Lisa Bako: Okay. And then for Japan, I was looking at the numbers. It looks like you kind of reported in the first quarter of launch, you know, over 500 patients, and then the next quarter, the second quarter of the launch was in the U.S.

In the U S. You know I'm more than 600 or approximately 650, new patients. So it's like almost looks like kind of like a double so in terms of your comments you were saying it looks like the trajectory is for like a double quarter over quarter.

Lisa Bako: than 600 or approximately 650 new patients. So it's like, it almost looks like kind of like a double. So in terms of your comments, you're saying it looks like it's for like a double quarter of a quarter. It was something less than 500 patients for the first quarter in Japan. Is that the right way to think about it?

It was something less than 500 patients from the first quarter for Japan.

The right way to think about it.

Roger do you want to talk about trends in Japan, I guess I don't know what data.

Roger: Roger, do you want to talk about trends in Japan? I guess? I don't know what data, this may be apples and oranges in terms of comparison. Yeah, thanks, and Lisa, so without thinking about these specific patient numbers, because we didn't comment on those specific patient numbers other than the absolute number.

This may be apples and oranges in terms of comparison.

Yeah. Thanks, Lisa so so without thinking about this specific patient numbers, because we didn't comment on those specific patient numbers other than the ads.

The absolute number of patients in Japan is lower than what we've seen in the U S. But at least two months into the launch just remember this is still early but two months into the launch the trajectory. So that build is highly correlated to the U S build as we see the patients patients initiating therapy.

Roger: And Lisa, those numbers that you were quoting are:

Lisa Bako: When quoting, are you referencing U.S. patient numbers in those 500?

Lisa Bako: Yeah, I was looking back at how you guys framed it up in the first two quarters of the U.S. understood. Yeah, we have not provided that level of detail for Japan.

Okay, Okay, and Lisa those numbers that you were quoting are those are you referencing U S patient numbers and the those 500.

Yeah, but I think I'm.

Looking back at how you guys framed it up in the first two quarters of the U S launch.

Roger: Yeah, I know you just said that kind of the trajectory was the same though the

Understood Yeah, we have not provided that level of detail for Japan.

Yeah, I know you just said the kind of the trajectory it seems like the trajectory we're on the same though.

Lisa Bako: The initial number of patients was lower than in the US, so I was just kind of trying to triangulate those things. Thank you, yeah.

The initial and a number of patients was lower than the U S. So I was just kind of.

Trying to triangulate those things thank you.

Lisa Bako: Yeah, understood. Thank you so much. We have a question now from Judah Framer from Credit Suisse. Please go ahead, Judah.

Yeah understood. Thank you so much.

We take a question now from Judah Frommer from Credit Suisse. Please go ahead.

Operator: Yeah, hi, thanks for squeezing me. And most of my questions have been answered. But just a question on whether you have any color from pulmonologists, as they may head back to the office. It seems like they will be one of the busier specialties as COVID does become endemic. It seems like that could cut both ways. They could be more focused on long-term respiratory symptoms tied to COVID, but you will still have patients in your office. So perhaps there's an opportunity for increasing the diagnosis of refractory NPMAC. Do you have any sense for how that might play out? Yeah, I think what we can do is comment

Yeah, Hi, Thanks for squeezing me in most of my questions have been answered, but just a question on whether you have any color from Pulmonologist says as they may be do head back to the office. It it seems like they will be one of the busier specialties as Covid does become endemic it seems like that could place both ways there.

Could be more focused on long term respiratory symptoms tied to COVID-19, but you will have patients in your office. So perhaps there's an opportunity for increased diagnosis of refractory angina Mac do you have any sense for how that might play out.

William Lewis: Yeah, I think what we can comment on is that we have seen things snap back quickly when the phases of the pandemic have been more endemic-like, even regionally across the U.S. And we know from our marketing work that the index of suspicion of physicians is much higher now than it was pre-pandemic, and their instinct to want to treat patients is also higher. I think it is fair to characterize a higher sensitivity to respiratory disease generally, and I do think that that will result.

Yeah, I think what we can comment on is that we have seen things snap back quickly when the phases of the pandemic have been more endemic like even regionally across the U S and we know from our marketing work that the index of suspicion of physicians is much higher now than it was pre pandemic.

And their instincts you want to treat patients who is also higher I think it is fair to characterize a higher sensitivity to respiratory disease generally and I do think that that will result in more attention very.

William Lewis: in more attention, and very likely more diagnosis as people are looking for what these conditions that they're suffering from are. People want to name what they're feeling if they have nonspecific symptoms. And that is the initial experience with NT.m.

Very likely more diagnosis as people are looking for what are these conditions that they're suffering from people want a name for what they're feeling if they have non specific symptoms and that is the initial experience with MTM lung disease and.

William Lewis: lung disease, and it's not dissimilar in its early stages in terms of how the patient experiences some of the symptoms than COVID. So you can imagine people starting to get some of those nonspecific symptoms and wanting to get in to see their pulmonologist to understand what is going on, knowing that there is a condition that they have and that there's a treatment available. And as Martina mentioned during her medical review, in terms of the literature we've been producing and the data we've been examining, there's increasing literature that is suggesting that it's important to intervene and intervene.

And it's not dissimilar in its early stages in terms of how the patient experience and some of the symptoms. Then COVID-19. So you can imagine people starting to get some of those non specific symptoms and wanting to get into their pulmonologist to understand what is going on knowing that there is a condition that they have and then there's a treatment available and as Martina mentioned during her medical.

<unk>.

Review in terms of the literature, we've been producing and the data we've been examining there's increasing literature that is suggesting that it is important to intervene and intervene early in order to gain the maximum benefit from treatment of MTM lung disease. All of those things I think will coalesce and paint a picture that is bright for the future of identifying and treating these patients.

William Lewis: early in order to gain the maximum benefit from treatment for NTM lung disease. All of those things, I think, will coalesce and paint a picture that is bright for the future of identifying and treating these patients appropriately. But I think we really do need to get past the pandemic stage of this before that starts to play out.

Lately.

But I think we really do need to get past the pandemic stay.

Stage of this before that starts to play out.

Great great.

Our final question comes from Rich Valera from Kevin Ritchie. Please go ahead.

William Lewis: Our final question comes from Routu Barel from Cohen. Ritu, please go ahead.

Operator: Flyla on, and just made a quick follow-up on TV, intense there. Statesway did it coming.

Oh cool.

Oh Wow.

Oh God.

All right.

That's really cool.

Okay.

Ritu Subhalaksmi Baral: I mentioned that, the low-dor cohort, is there any potential that we could see a higher dose included? And then on the ILD study that's planning to initiate, that's also going to be an uptight study, Sure, so I think I heard your questions right, although you're

Oh.

I'm sorry.

Okay.

Okay.

Hum.

Right.

Yeah.

Oh, that's awesome.

Okay.

Martina Flammer: Sure, so I think I heard your questions right, although your line was a little muted. The ILD question about uptitration: yes, that will be an uptitration study. And your first question.

Uh huh.

Sure. So I think I heard your question right, Although Europe is a little muted.

The ILD question about is this is going to be up titration, yes that will be an up titration study and your first question.

Martina Flammer: I think the first question was about whether we would have a higher dose included in the phase-to-A studies. Now, it will be the low dose for this phase-to-a study. In the phase-2B study, it will be the up titration, and so we will see a maximum tolerability of the patient up to potentially 640 much.

But I think the first question was about whether we would have a high end dose included in the phase III study will be the low dose for the phase Iia study in the phase <unk> study will be up titration and so that will see your maximum toleration of the patient up to potentially 640 my friend.

Martina Flammer: Got it, thank you. Sorry about that idea.

Oh, sorry about that.

Yeah.

Operator: Thank you. We now hand the call back over to Will Lewis for his closing remarks. Thanks for joining us.

Thank you, we now hand, the call back over to will Lewis for closing remarks.

William Lewis: Thanks for joining us today. I hope everyone has a good day.

Thanks for joining us today and hope everyone has a good day.

Yeah.

Thank you for joining this now concludes today's call. Please disconnect your lines.

Operator: Thank you all for joining us. This now concludes today's call. Please disconnect your lines.

Yeah.

Okay.

Yeah.

Yeah.

Okay.

Yeah.

Yeah.

Yeah.

Okay.

Yeah.

Yeah.

Okay.

Uh huh.

Hum.