Q4 2020 Insmed Inc Earnings Call

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Good day and thank you for standing by at this time I would like to welcome everyone to the N Smith for quarter and full year 'twenty 'twenty financial Wherewithal conference call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question answer session. If you would like.

Operator: Thank you for standing by. At this time, I would like to welcome everyone to the Insmed 4th Quarter and Full Year 2020 Financial Results Conference Call. All lines have been placed on mute to prevent any background noise.

Operator: After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during that time, simply press the star, then the number one on your telephone keypad. If you would like to withdraw your question, press the pound key.

Ask the question during that time simply press Star then the number one on your telephone keypad. If you would like to draw. Your question press. The pound key. Thank you. It is on my pleasure to turn the conference over the Eleonore barrister Associate Director Investor Relations. Please go ahead.

Eleanor Barrister: Thank you. It is now my pleasure to turn the conference over to Eleanor Barrister, Associate Director, Investor Relations. Please go ahead.

Thank you Lee good morning, and welcome to today's conference call to discuss our fourth quarter and full year of financial results for 2020 and provide a business update.

Eleanor Barrister: Thank you, Lee. Good morning and welcome to today's conference call to discuss our fourth quarter and full year financial results for 2020 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.

Before we start let me remind you that today's call will include forward looking statements based on current expectations.

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.

Eleanor Barrister: Please refer to our filings with the Securities and Exchange Commission, which are available through the SEC's website at www.sec.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 is not sufficient for prescribing decisions. Joining me on today's call are members of the Insmed Executive Management Team, including Will Lewis, Chair and Chief Executive Officer, Dr. Martina Flammer, Chief Medical Officer, Roger Adsett, Chief Operating Officer, and Sara Bonstein, Chief Financial Officer.

Please refer to our filings with the Securities and Exchange Commission, which are available through the SEC's website at Www Dot SEC dot of ore 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.

Joining me on today's call are members of the Internet Executive management team, including will Lewis Chairman and Chief Executive Officer, Dr. Martina Flammer, Chief Medical Officer, Roger as debt, Chief operating officer and share of Boston Chief Financial Officer. Additionally.

Additionally, Dr. Eugene Sullivan, Chief product strategy officer will be available during the Q&A portion of today's call.

Eleanor Barrister: Additionally, Dr. Eugene Sullivan, Chief Product Strategy Officer, will be available during the Q&A portion of today's call. I will now turn the call over to Will Lewis for prepared remarks. Upon completion of those remarks, we will open the call up to your questions.

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.

William Lewis: Thank you, Eleanor. Good morning, everyone, and thank you for joining us. We hope you and your families continue to remain safe and healthy. On behalf of Insmed, I am pleased to report on what was the most transformational year in our company's history. As Insmed enters a new phase of growth in 2021, we are carrying forward the strong momentum of a successful 2020, marked by significant accomplishments across our business. In the past 12 months, we have matured from a single product company to a global organization advancing three substantial programs.

Thank you all of our good morning, everyone and thank you for joining US we hope you and your families continue to remain safe and healthy on the.

Behalf of been Smith I am pleased to report on what was the most transformational year in our company's history.

And then submit the enters a new phase of growth in 2021, we are carrying for the strong momentum of a successful 2020 marked by significant accomplishments across our business over.

Over the past 12 months, we have matured from a single product company to a global organization advancing three substantial programs.

William Lewis: These programs are TPIP, brensocatib, and erikase, and each is positioned to become potentially a cornerstone of therapy in their disease area. With that in mind, let me dive into some of the key highlights for the fourth quarter and full year 2020.

These programs are <unk> IP for Ensco, Ketchum, and Erra case, and each is positioned to become potentially a cornerstone of therapy and there are disease areas.

With that in mind, let me dive into some of the key highlights for the fourth quarter and full year of 2020.

I'll start with proportional of palm until inhalation powder for TPI P.

William Lewis: I'll start with troposinol-palmitoyl inhalation powder, or TPIP. We were very excited to provide an update on this program just last week when we announced top-line data from our Phase I study in healthy volunteers. The results demonstrated the potential for TPIP as a once-daily treatment, which may be able to unlock the full potential of the prostanoid class of therapy for pulmonary hypertension and related diseases. A detailed review is available on our website.

We were very excited to provide an update on this program just last week, when we announced topline data from our phase one study in healthy volunteers the rig.

<unk> demonstrated the potential for TPI as the.

Once daily treatment, which may be able to unlock the full potential of the process knowing the class of therapy for pulmonary hypertension and related diseases. The detailed review is available on our website.

Our second program is brands for cats, which represents a new way to harness the DPP one pathway for treating neutrophil mediated diseases.

William Lewis: Our second program is BREN Soccata, which represents a new way to harness the DPP-1 pathway for treating neutrophil-mediated diseases. In the middle of last year, we were excited to announce that the FDA had granted breakthrough therapy designation to brensocatib for the treatment of non-cystic fibrosis bronchiectasis, or NCFBE. We are also pleased to report the EMA's decision to grant brenn cacti prime designation for the treatment of NCFB. This was followed shortly thereafter by the initiation of our Phase 3 Aspen trial, which is now well underway. Additional information about brent cicatib's mechanism of action will soon be available from an investigator-initiated study of brent cicatib in patients with COVID-19.

In the middle of last year, we were excited to announce that the FDA has granted breakthrough therapy designation the brands for catch it for the treatment of non cystic fibrosis bronchiectasis or Mcf BD.

We were also pleased to report the Ema's decision to grant for instance, the prime designation for the treatment of <unk>.

This was followed shortly thereafter by the initiation of our phase III Aspen trial, which is now well underway.

Additional information about Brexit cash its mechanism of action will soon be available from an investigator initiated study of Brinci for cats in patients with COVID-19.

We anticipate that the principal investigator will obtain and share data about our drug from this study early in the second quarter.

William Lewis: We anticipate that the principal investigator will obtain and share data about our drug from this study early in the second quarter. In addition, in addition to the Aspen study, we will be advancing the clinical development of brensocazep and cystic fibrosis. We anticipate initiating our Phase 2 PK-PD multiple dose study to explore the appropriate brenn cicata dosing for cystic fibrosis patients by mid-2021. Beyond bronchiectasis and cystic fibrosis, we are continuing to explore other potential disease areas where BrenCeCat may have a therapeutic effect. As an example, a recent paper was published in the cancer research journal Cancer Cell.

In addition to the Aspen study, we will be advancing clinical development of friends from catchup in cystic fibrosis.

We anticipate initiating our phase II PK PD multiple dose study to explore the appropriate branch of cat the dosing for cystic fibrosis patients by mid 2021.

Beyond bronchiectasis cystic fibrosis, we are continuing to explore other potential disease areas, where Brent so cash it may have a therapeutic effect.

As an example of recent paper was published in the cancer Research Journal cancer cell in this article researchers who used our drug for Ensco catcher documented how it prevented lung metastases and in the animal model of breast cancer.

William Lewis: In this article, researchers who used our drug, brensucatib, documented how it prevented lung metastases in an animal model of breast cancer. As you may recall from our R&D day last September, we have begun our own exploration of the potential role of brenn succatib in oncology, among other potential diseases. This paper provides one example of Brencicatib's ability to demonstrate the potential for a positive impact across a variety of disease models.

As you May recall from our R&D day last September we have begun our own exploration of the potential role of <unk> accounts had been oncology among other potential diseases.

This paper provides one example of <unk> ability to demonstrate the potential for a positive impact across a variety of disease models will.

Look forward to keeping you updated on further advancements we expect to make across our brands to cash in program.

William Lewis: We look forward to keeping you updated on further advancements we expect to make across our Brent Ciccative Program. Now, let's turn to Eric Case, where our franchise continues to advance around the world despite the headwinds from the impact of the ongoing pandemic. We are all looking forward to the day when the COVID-19 pandemic subsides. In the meantime, our global expansion plans have continued to progress as expected, with European approval and the subsequent launch of ERACASE in Germany and the Netherlands now underway.

Let's now turn to Erra case, where our franchise continues to advance around the world. Despite the headwinds from the impact of the ongoing pandemic.

We are all looking forward to the day when the COVID-19 pandemic subsides in the meantime, our global expansion plans have continued to progress as expected with the European approval and the subsequent launch of air of case in Germany, and the Netherlands now underway.

We also remain on track for commercial launch in Japan by mid year. If there are cases approved in Japan.

William Lewis: We also remain on track for commercial launch in Japan by mid-year if EraCase is approved in Japan. Finally, in late 2020, we were pleased to initiate our Frontline Clinical Trial Program for EraCase, which is intended to support full approval of EraCase in the U.S. and potential expansion into the larger Frontline opportunity in MAC Lung Disease in the U.S., Europe, and Japan. We believe this program offers the potential to establish ArraKase as the standard of care for the frontline treatment of NTM.

Finally in late 2020, we were pleased to initiate our frontline clinical trial program for <unk>, which is intended to support full approval of air of case in the U S and potential expansion into the larger frontline opportunity and Mac lung disease in the U S Europe and Japan.

We believe this program offers the potential to establish the era case as the standard of care for the frontline treatment of MTO.

As we now turn our focus for 2021, we believe in cement as well resource within the industry, leading team and a strong capital position to execute on our goals of bringing potentially life altering treatments to patients in need will.

William Lewis: As we now turn our focus to 2021, we believe Insmed is well-resourced with an industry-leading team and a strong capital position to execute on our goals of bringing potentially life-altering treatments to patients in need. With that in mind, let me now turn the call over to Sara to run through our financial results.

That background, let me now turn the call over to Sarah to run through our financial results Sarah.

Sara M. Bonstein: Thank you, Will, and good morning, everyone. As Will mentioned, 2020 was a year of tremendous growth for Insmed. Marked by significant progress across all of our programs, earlier today, we issued our detailed fourth quarter and full year financial results in a press release. Let me highlight just a few of our full year results for you now. As reported this morning, we ended the year with $532.8 million in cash and cash equivalents, which we believe will enable us to advance our three key strategic priorities, aircase, forensics active, and CPI.

Thank you will and good morning, everyone as the.

Will mentioned 2020 once a year of tremendous growth for Internet marked by significant progress across all of our programs.

Earlier today, we issued our detailed fourth quarter and full year financial results in the press release.

Let me highlight just a few of our full year results for you now.

As reported this morning, we entered the year with $532 $8 million from cash cash equivalents, which we believe will enable us to advance our three key strategic priorities are key for us to tap the M. P. P. I P.

Sara M. Bonstein: Total net revenue for Eric Case was $164.4 million for the full year 2020. Throughout the COVID-19 pandemic in 2020, Aircase continued to have steady performance. As we look ahead to 2021, we anticipate returning to growth when the impact of the pandemic subsides. We look forward to sharing further updates later in the year.

Total net revenue for aerospace was $164 $4 million for the full year of 2020.

Throughout the COVID-19 pandemic of 2020 aerospace continues to have steady performance.

As we look ahead for 2021, we anticipate returning to growth on the impact of the pandemic subsides.

The forward to sharing further updates later on the here.

Our gross to net for the full year 2020 were approximately 12%.

Sara M. Bonstein: Our gross net for the full year 2020 was approximately 12%. Looking ahead, while gross SINETs historically have been highest in Q1 due primarily to the coverage gap as a result of the benefit reset at the beginning of the year, we anticipate our full year growth synapse to be in the mid-teens for 2021. This modest increase year-over-year is mainly attributed to select contracting to ensure maximum patient access.

Looking ahead, while gross to net has historically have been highest from Q1 due primarily to the coverage GAAP as a result of the benefit reset at the beginning of the year.

We anticipate our full year gross to net to be in the mid teens for 2021.

This modest increase year over year is mainly attributed to select contracting to ensure backs on patient access.

Sara M. Bonstein: Cost of product revenues for the full year 2020 was $39.9 million, or 24%, which is in the range we anticipated. As a reminder, our cost of product revenues in 2019, which was 18%, benefited more from inventory expense prior to FDA approval in the United States. Turning to our GAAP operating expenses, for the full year 2020, research and development expenses were $181.2 million compared to $131.7 million for the full year 2019. We anticipate R&D expenses to continue to grow year-over-year as we support our growing development pipeline.

Cost of product revenues for the full year 2020 was $39 $9 million for 24%, which is in the range we anticipated.

As a reminder, our cost of product revenues in 2019, which was 18% benefited more from inventory expense prior to FDA approval of therapies.

Turning to our GAAP operating expenses for.

The full year 2020 research and development expenses for $181 $2 million compared to $131 $7 million for the full year 2019.

We anticipate R&D expenses will continue to grow year over here as we support our growing development pipeline.

SG&A expenses for $203 $6 million for 2020 compared to $210 $8 million for 2019, demonstrating our focus on prudent spending.

Sara M. Bonstein: SG&A expenses were $203.6 million in 2020 compared to $210.8 million in 2019, demonstrating our focus on prudent spending. Total operating expenses for the full year 2020 were $429.6 million compared to $371.7 million in 2019. Looking ahead in 2021, we will continue to invest in our core operating business, including the commercialization and clinical support of Aircase globally, the ongoing and planned development of Bredso Katib, and the continued advancement of TPI. We remain laser-focused on prioritizing appropriate development investment with responsible cost control. With that, let me turn the call over to Martina for an update on our pipeline. Thank you.

Total operating expenses for the full year 2020 for $429 $6 million compared to $377 million in 2019.

Looking ahead in 2021, we will continue to invest in our core operating business, including the commercialization and clinical support of Eric Heath globally. The on.

Ongoing and planned development of Prince of Catherine on the continued advancement of TPI P. We remain laser focused on prioritizing appropriate development investment with responsible for cost control.

With that let me turn the call over to Martina for an update on our pipeline Artina.

Martina Flammer: Thank you, Sara, and good morning, everyone. As Will mentioned, 2020 was a year of remarkable achievement for Insmed, underscored by advancements across our pipeline. Let me now address our progress and next steps for each of our programs. First, PPIP is a novel dry powder formulation of troposinopalmitoyl, which is a prodrug of troposin. We believe GPIP represents an opportunity to harness the full potential of the prosthenoid pathway. Let me start by drawing your attention to the top-line data we shared just last week from our Phase I single and multiple ascending closed-dose trial in healthy volunteers. TPIP was generally safe and well-tolerated, and it showed a substantially lower C-max and longer half-life than currently available inhaled troprostenal therapy. These findings support the continued development of TPIP with once-daily dosing in patients with PAH.

Thank you Sarah and good morning, everyone. As will mentioned 2020 was the year of remarkable achievement for Internet underscored by advancement of cross sell pipeline.

Let me now address our progress and next steps for each of our program for.

First P. P. IP is a novel dry powder formulation of Coprostanol, Palmetto, which is of pro drug of the Prost.

We believe <unk> represents an opportunity to harness the full potential off the profit the nice pathway.

Let me start by drawing your attention to the top line data when she had just last week from out of phase one single and multiple ascending.

Those trials in healthy volunteers.

Keep the IP was generally safe and well tolerated and showed substantially lower C Max and longer half life and currently available inhaled Coprostanol therapy.

These findings support the continued development of keep the IP with once daily dosing in patients with P. H.

For an in depth review of these results I encourage you to visit our website for the detailed press release and conference call webcast.

Martina Flammer: For an in-depth review of these results, I encourage you to visit our website for the detailed press release and conference call webcast. Regarding next steps, we remain on track to advance to the next stage of clinical development, which will follow two paths in parallel. First, we will gather information on the impact of TPIP on pulmonary vascular resistance, or PBR, and over a 24-hour period, in a handful of patients with PAH or in Group 1, in an open-label study.

Regarding next steps we remain on track to advance the the next stage of clinical development, which will fall of two paths in parallel.

We will gather information on the impact of cheap VIP on pulmonary vascular resistance or P. D. R and over 24 out of period in the handful of patients with a P. H one in an open label study.

As planned we anticipate sharing top line patient data from this study in the second half of this year.

Martina Flammer: As planned, we anticipate sharing top-line patient data from this study in the second half of this year. The second phase will investigate the effect of TPIP on PVR and 6-minute walk distance in patients with PAH over a 16-week treatment period.

The second path will investigate the effects of the P. P. IP on P. B R and six minute walk distance in patients with P. H over a 16 week treatment period.

We plan to initiate this trial in the fourth quarter.

Martina Flammer: We plan to initiate this trial in the fourth quarter. In addition to those two studies in PEH, we are planning to initiate a separate study for Group 3 PHILD patients in addition to our work exploring a development pathway for TPIP and idiopathic pulmonary fibrosis, or IPF. We plan to use an up-titration dosing schedule for the maximum individually tolerated dose exceeding 600 micrograms once daily.

In addition to those two studies in P. H, we are planning to initiate a separate study for group three P. H ILD patients. In addition to our work exploring the development pathway for keep the IP and idiopathic pulmonary fibrosis or IPF.

We plan to use an uptight duration of dosing schedule for the maximum individually tolerated dose exceeding 600 microgram once daily.

Let's now turn to friends of cabinet of novel oral reversible inhibitor of <unk> peptidase, one or keep you want.

Martina Flammer: Let's now turn to PrensoCathet, a novel oral reversible inhibitor of peptidyl peptidase 1, or TPP1. We view Brento-CATEP as the cornerstone of our efforts to build a program around the TPP-1 pathway with enormous potential across a range of therapeutic areas. We saw several key achievements over the course of 2020, including the publication of our final results from our Phase II Willow Study in the New England Journal of Medicine in September.

We view brands, who cast of as the cornerstone of our efforts to build the program around the TPP one pathway with the enormous potential across the range of therapeutic areas.

We saw several key achievements over the course of 2020, including the publication of our final results from a phase II study in the New England Journal of Medicine in September.

As will mentioned we were also pleased to report the Prince of Catholic was granted breakthrough therapy designation by the FDA, that's where all of this priority of medicine of Prime designation by the DNA for N P. S T.

Martina Flammer: As mentioned, we were also pleased to report that PrensoCathet was granted Breakthrough Therapy designation by the FDA as well as Priority Medicine or Prime designation by the EMA for MCF. Underscoring the Strengths of our Phase II Willow Data

Underscoring the strength of our phase II Willow data.

We were pleased to announce that late last year, the initiation of a phase III Aspen study of friends of Pat the in patients with bronchiectasis.

Martina Flammer: We were pleased to announce late last year the initiation of our Phase 3 Aspen Study of Brent Sokatep in patients with bronchiectasis. As you may recall, the Aspen study is designed to confirm the positive results we saw in our Phase II willow study. And as such, Aspen retains many key elements of willow.

As you May recall of the Aspen study is designed to confirm the positive results. We saw I know of phase two will of study and as such Aspen retains many key elements of Willow.

For a detailed overview of the trial design I encourage you to review our R&D day presentation, which remains available on our website.

Martina Flammer: For a detailed overview of the trial design, I encourage you to review our R&D day presentation, which remains available on our website. We look forward to sharing updates with you as the trial progresses. In parallel, Stop COVID-19, an investigator-initiated study of brancicaptive in approximately 400 hospitalized patients with COVID-19, is now fully enrolled. As a reminder, this study is being conducted under the direction of Professor James Chalmers at the University of Dundee and across a number of hospitals in Scotland.

We look forward to sharing updates with you as the trial progresses.

In parallel stop the COVID-19, an investigator initiated study of friends of captive in approximately 400 hospitalized patients with COVID-19 is now fully enrolled.

As a reminder of this study is being conducted under the direction of the Professor James Thomas at the University of Dundee.

And across a number of hospitals in Scotland.

Yes.

Recall the professor Thomas was also the principal investigator of all of his tastes to Willow study.

Martina Flammer: Recall that Professor Thomas was also the principal investigator of our Phase II Willow study. It is our expectation that Professor Thomas will share data from the STOP COVID-19 study early in the second quarter of this year, and we hope it will provide further validation of the TPP1 inhibition pathway, as well as important data regarding neutrophil functioning that could provide future clinical utility. As ASPEN and STOP COVID-19 advance, we're working to expand our focus for brain sarcophagus to additional potential indications as we continue to build our program based on the TPP-1 pathway beyond Frontier.

It is our expectation that professor Thomas will share data from the start of COVID-19 study early in the second quarter of this year and we hope it will provide further validation of the P. P people on inhibition pathway as well as important data regarding neutrophil functioning that could provide future clinical utility.

S Aspen and stop COVID-19 advance we're working to extend our focus for brands for cat the two additional potential indications.

We continue to build out program based on the TPP one pathway.

Beyond Bronchiectasis, we remain on track to initiate in mid 2021 of phase two pharmacokinetics pharmacodynamics multiple dose study to explore the appropriate bench of cat the dosing for cystic fibrosis patients.

Martina Flammer: We remain on track to initiate a Phase II pharmacokinetics-pharmacodynamics multiple-dose study to explore the appropriate benzocatib doses for cystic fibrosis patients. At the same time, we continue to advance our research efforts to support extension to other neutrophil-mediated indications across a range of therapeutic areas. I would like to take a moment to touch upon another exciting development opportunity for PrancerCat. In January, the publication Cancer Cell highlighted the role of frantzocaptive in inhibiting lung metastases of breast cancer in a mouse model.

At the same time, we continue to advance our research efforts to support expansion to other neutrophil mediated indications across the range of therapeutic areas.

I would like to take a moment to touch upon another exciting development opportunity for a range of pet.

In January the publication of cancer cell highlighted the role of French of captive in inhibiting lung metastases of breast cancer in a mouse model.

Martina Flammer: Cancer Cell is internationally regarded as one of the top cancer research and oncology journals and publishes articles on all aspects of cancer cell biology. The paper builds upon earlier suggestions that neutrophil extracellular traps, or NETs, may be important in cancer metastasis. Nets are highly damaging web structures studded with DNA and proteases that trap microbes but are also involved in autoimmune disease and cancer. Activated neutrophils can release nets into their surroundings. Previous preclinical studies have shown that catapsin C and NETs play an important role in metastasis. Forensic HACCP directly inhibits catapsin C, or TPP1, and interferes with net production.

Cancer cell is internationally regarded as one of the top cancer research and oncology Journal and publishes the articles on all aspects of cancer cell biology.

The pay per builds up on earliest suggestion of the neutrophil extra salary of traps on net maybe important in cancer metastases.

Net of highly damaging web structures started with DNA and proteins.

The trap of microbes.

Also involved in autoimmune disease and cancer.

Activated neutrophils can release net into their surroundings previous preclinical studies have shown the <unk> C and net play an important role in the past disease.

Rents of Pat the directly inhibits the taps and see what TPP, one and in 50 years with net production.

In this cancer cell paper do you also showed that the administration of our drug branch of a captive was able to suppress the lung metastases in the mouse model.

Martina Flammer: In this Cancer Cell paper, the authors showed that the administration of our drug, brenzotacid, was able to suppress lung metastases in a mouse model. We believe this represents an exciting potential opportunity for parental catheters in oncology, which is just one area where we think our compound can have potential clinical benefits. We are encouraged by these early results that suggest validation of the importance of the TPP-1 pathway, and we will continue to advance our research efforts for brain sarcophagia in oncology.

We believe this represents an exciting potential opportunity for Prince of cap in oncology, which is just one area, where we think our compounds can have potential clinical benefits.

We are encouraged by these early results that suggest validation of the importance of the TPP one past week and we will continue to advance our research efforts for Brent will catch up in oncology.

Let's now move onto our post marketing frontline clinical trial program for air of case.

Martina Flammer: Let's now move on to our Post-Marketing Frontline Clinical Trial Program for Eric. This program is designed to both support the full approval of Eric Case in the U.S. as well as potential expansion into the larger front-line opportunity in MAC lung disease in the U.S., Europe, and Japan. These efforts support our overarching goal of shifting the treatment paradigm for patients suffering from NTM lung disease. The program involves two separate but interrelated clinical trials, ARISE and ENCORE.

This program is designed to both support the full approval of Erra case in the U S as well as potential expansion into the larger from plant opportunity in Mac lung disease in the U S Europe and Japan.

These efforts support our overarching goal of shifting the treatment paradigm for patients suffering from ATM lung disease.

The program involves two separate but the interrelated the clinical trials of rice and encore.

Earlier this year, we were excited to announce the deal Ryzen Encore trials were initiated and began dosing patients in December of 'twenty 'twenty.

Martina Flammer: Earlier this year, we were excited to announce that the ARISE and ENCORE trials were initiated and began dosing patients in December 2020. As a reminder, a more detailed look into the study schematics and designs can be found in the investor presentation available on our website. As sites open worldwide, we expect to provide an update on this program later this year. In summary, we made important progress across our clinical programs in 2020. We remain excited and optimistic about the potential underlying our pipeline and look forward to sharing developments with you in the future. I will now turn the call over to Roger to discuss some key operational updates.

As a reminder, the more detailed look into the study schematics and design can be found in the investor presentation available on our website.

S sites opened worldwide, we expect to provide an update on this program later this year.

In summary, we made important advancements across our clinical programs in 2020.

We remain excited and optimistic about the potential underlying our pipeline and look forward to sharing developments with you in the future.

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

Roger: Raja

Roger Adsett: Thanks, Martina, and good morning, everyone. I'm pleased to report a strong fourth quarter and full year from an operational perspective. Let me begin with our case in the U.S., where our commercial business remains steady despite the challenges presented by COVID-19. Once the pandemic subsides, we anticipate a return to growth.

Thanks, Martina and good morning, everyone.

I'm pleased to report a strong fourth quarter and full year from an operational perspective.

Let me begin with the allocation of the U S for our commercial business remained steady despite the challenges presented by COVID-19.

Once the pandemic subsides, we anticipate of returned to growth.

This will be driven in part by on leveraging important tools, including the strong recommendation for the use of bear case and the international treatment guidelines for MTM lung disease, which includes the recommendation for allocation as part of a multi drug regimen for certain patients.

Roger Adsett: This will be driven in part by our leveraging important tools, including the strong recommendation for the use of ARACASE and the International Treatment Guidelines for NTM Lung Disease, which includes the recommendation for ARACASE as part of a multi-drug regimen for certain patients. This is in addition to the FDA approval of our supplementary new drug application in October 2020, which added important efficacy data regarding durability and sustainability of culture conversion to the Aracease label.

This is in the addition to the FDA approval of a supplementary new drug application in October 2020.

The important efficacy data regarding the durability and sustainability of culture conversion to the allocation of label.

Roger Adsett: While we have seen the impact COVID-19 has had on reducing the volume of patient visits to physician's offices and, therefore, new patient diagnoses, our team remains confident in the long-term potential of our experience. We continue to believe that the pandemic has increased attention on the importance of respiratory health, further supporting the long-term opportunity for our case once patients are comfortable returning to visiting their physicians.

While we have seen the impact of COVID-19 has had on reducing the volume of patient visits to physicians offices, and therefore, new patient diagnoses are T remains confident in the long term potential Americas we.

We continue to believe that the pandemic is increased attention on the importance of respiratory health for.

For the supporting the long term opportunity for error of case once patients are comfortable returning to visiting their physicians.

I will focus of the balance of my comments on our international commercial expansion that is currently underway and the we anticipate will accelerate in 2021 for.

Roger Adsett: I will focus the balance of my comments on our international commercial expansion that is currently underway and that we anticipate will accelerate in 2021, further supported by important learnings from our successful U.S. commercial law. Let's start with Europe, where our case was granted marketing authorization last October for the treatment of MAC lung infection in adults with limited treatment options who do not have cystic fibrosis. We launched in Germany first, with initial sales occurring in Q4 2020 and the full launch commencing in January, with a list price that is in line with the U.S. list price for Arica.

Further supported by important learnings from our successful U S commercial launch.

Let's start with Europe for Air cases granted marketing authorization last October for the treatment of Mac lung infection in adults with limited treatment options, who do not have cystic fibrosis.

We launched the Germany first with initial sales occurring in Q4, 'twenty and full launch commencing in January with the list price of it is in line with the U S list price for air of case.

We will once again, the time of COVID-19, lockdowns in parts of the country, which like the U S has an impact on in person access for intimate sales representatives as well as in person patient visits to the clinic.

Roger Adsett: We are launching at a time of COVID-19 lockdowns in parts of the country, which, like the U.S., has an impact on in-person access for Insmed sales representatives, as well as in-person patient visits to the clinic. The German team has adapted with virtual interactions and events that have been well received. Initial feedback from physicians is very positive, both on Arracase as a product and on the patient support program that is available to patients initiating treatment with Arracase.

The German team has adapted with virtual interactions and events that have been well received.

Initial feedback from physicians is very positive both on air of cases of product as well as the patient support program that is available to patients initiating treatment with air of case.

We will also very pleased to secure early reimbursement in the Netherlands also other price of is in line with the U S price.

Roger Adsett: We were also very pleased to secure early reimbursement in the Netherlands, also at a price that is in line with the US price. In our case, this is only the second drug selected to undergo a process piloted by the Dutch government that aims to speed up access to innovative new medicines for Dutch patients. Our case was selected to participate in this program, and as a result, reimbursement for our case was accelerated by approximately three months compared to our expectations. This allowed Insmed to launch in the Netherlands as of February 1st.

In other cases, only the second drug selected to undergo a process of piloted by the Dutch government. The names to speed up access of innovative new medicines for Dutch patients.

Eric cases for elected to participate in this program and as a result reimbursement for advocates was accelerated by approximately three months compared to our expectations. This will.

A lot of insight at the launch of the Netherlands as of February one.

As previously communicated we expect for reimbursement decisions across Europe to continue throughout 2021 and into 2022.

Roger Adsett: As previously communicated, we expect reimbursement decisions across Europe to continue throughout 2021 and into 2022. In the UK, we have a list price for our case that is in line with the US price, and we expect a decision on central reimbursement in England later this year, with the other countries within the UK initiating their own review processes as early as next month. As we've shared previously, the rollout of our European launch is supported by a solid infrastructure. Our model combines building our own commercial entities and field force in major markets while utilizing distributor models where appropriate.

In the U K, we have a list price for air case of this in line with the U S price and we expect the decision on central reimbursement in England. Later this year with the other countries within the UK initiating their own review processes as early as next month.

As we've shared previously the rollout of our European launch is supported by a solid infrastructure.

The model combines building our own commercial entities and field force and major markets, while utilizing distributed of models where appropriate.

As we secure reimbursement in additional countries, we anticipate having approximately 40 field base customer facing personnel across Europe by the end of this year.

Roger Adsett: As we secure reimbursement in additional countries, we anticipate having approximately 40 field-based, customer-facing personnel across Europe by the end of this year. Looking further ahead, we anticipate growing to a team of 50 by 2022. We are pleased with the feedback and progress made so far and look forward to providing further updates on our European launch efforts. We're equally excited about the opportunity we have in Japan. As a reminder, Insmed decided to register and commercialize our case, if approved, in Japan by itself.

Looking further ahead, we anticipate growing to a team of 50 by 2022.

We are pleased with the feedback of progress made so far and look forward to providing further updates on the European launch efforts.

We're equally excited about the opportunity we have of Japan.

As a reminder, intimate decided to register and commercialize Ara case, if approved in Japan by ourselves.

We have assembled an extremely strong experienced and talented team of Japan.

Roger Adsett: We have assembled an extremely strong, experienced, and talented team in Japan. We submitted our application to Japan's Ministry of Health, Labor, and Welfare in March of 2020 and remain on track for a 12-month review. If our case is approved, pricing discussions will commence, and we anticipate these discussions could take up to three months.

We've submitted our application to the to Japan's Ministry of Health Labor and welfare in March of 2020 and remain on track for 12 months of review.

The fabrication is approved pricing discussions will commence and we anticipate these discussions could take up to three months.

We are therefore planning for reimburse launch mid year, if Eric has approved.

Roger Adsett: We are therefore planning for a reimbursed launch mid-year if our case is approved. Japanese key opinion leader interest in ARACASE remains very strong, and we are gratified from the early support they have offered to Insmed in bringing ARACASE to Japanese patients. We've already had appropriate medical engagement with major medical associations in Japan, including the Japanese Association for Infectious Diseases, the Japanese Respiratory Society, and the Japanese Society of Tuber

Japanese key opinion leader of interest in our case remains very strong.

We are gratified from the early support they are offered to his bedroom Brigade Erra case, the Japanese patients.

We've already had appropriate medical engage with major medical associations in Japan, including the Japanese Association for infectious diseases, the Jefferies respiratory Society, and the Japanese society of tuberculosis and N T M.

Is perhaps noteworthy the Japanese society of tuberculosis added MTM to the societies day in January of 2020, indicating strong interest in MTM lung disease.

Roger Adsett: It's perhaps noteworthy that the Japanese Society of Tuberculosis added NTM to the society's name in January of 2020, indicating strong interest in NTM lung disease. In preparation for the launch of our case in Japan, if approved, we have deployed a team of 15 therapeutic specialists in Japan, as well as a small team of medical scientific liaisons, have been in place since the fourth quarter of 2020. As part of a co-promotion agreement, we have been promoting a generic macrolide to Japanese physicians and educating them on the appropriate NTM-MAG treatment guidelines, which include the use of a macrolide.

The preparation for the launch of our case of Japan. If approved we have deployed a team of 50 therapeutic specialists in Japan as well as a small team of medical scientific liaisons will.

Being in place since the fourth quarter of 2020.

As part of our co promotion agreement, we have been promoting of generic macrolide to the Japanese physicians and educating on the appropriate N T M bad treatment guidelines, which includes the use of a macrolide.

This has allowed us to engage with physicians and understand where the NTN back patients are being treated.

Roger Adsett: This has allowed us to engage with physicians and understand where the NTMBAC patients are being treated. While COVID has limited some interactions, we are pleased with the response from targeted physicians. Based on the opportunity we see in Japan, we plan on adding an additional five therapeutic specialists this year, bringing the total to $20,000. We anticipate this team will call on over 550 physicians across more than 200 hospitals across Japan. We estimate this covers approximately 80% of the refractory patient population.

While Covid has limited some interactions we are pleased with the response of targeted physicians.

Based on the opportunity we see in Japan, we plan on adding an additional five therapeutic specialist this year.

Speaking of the total to 20.

We anticipate this team will call on over 550 physicians across more than 200 hospitals across Japan.

We estimate this covers approximately 80% of the refractory patient population.

In closing we are extremely excited about the opportunities ahead as we expand the global footprint of our case the pursuit of the long term potential of the franchise for the U S Europe and Japan.

Roger Adsett: In closing, we're extremely excited about the opportunities ahead as we expand the global footprint of Arrakis and pursue the long-term potential of the franchise in the U.S., Europe, and Japan. I'd like to thank the Insmed team for their continued commitment to the NCM community as we work to achieve these milestones. And with that, I'll turn the call back to Will.

I'd like to thank the ins by the team for their continued commitment to the NTN community as we work to achieve these milestones.

Let me turn the call back to will.

Thank you Roger.

I'd like to close our prepared remarks by reiterating how proud I am of the instrument team for achieving this remarkable progress in such a challenging year for.

William Lewis: Thank you, Roger. I'd like to close our prepared remarks by reiterating how proud I am of the Insmed team for achieving this remarkable progress in such a challenging year. By virtue of our evolution over the past 12 months, we now enjoy the opportunity to pursue three major clinical programs built on a strong foundation of research. 2020 was by far the most transformational year in our company's history, and I would draw your attention in particular to the strength and performance of our executive team, which is an indication of the broad array of talent that makes up the global team at Insmed.

Virtue of of our evolution over the past 12 months, we now enjoy the opportunity to pursue three major clinical programs built on a strong foundation of research.

<unk> thousand 20 was by far the most transformational year on our company's history and I would draw your attention in particular to the strength and performance of our executive team, which is an indication of the broad array of talent that makes up the global team of instrument books.

Looking ahead I truly believe we are well positioned for an even more exciting year in 2021.

We are focused on delivering exciting new data as it emerges from our pipeline in support of our ambitious vision.

This vision is built upon the deep and sincere commitment to help patients and I am extremely proud of the portfolio. We have developed in its pursuit.

I would like to thank the entire instrument team for its commitment to deliver as we add even more ambitious goals with that I'd like to open the call for questions. Operator can we take the first question. Please.

William Lewis: Looking ahead, I truly believe we are well positioned for an even more exciting year in 2021. We are focused on delivering exciting new data as it emerges from our pipeline in support of our ambitious vision. This vision is built upon a deep and sincere commitment to help patients, and I am extremely proud of the portfolio we have developed in its pursuit. I would like to thank the entire Insmed team for its commitment to delivering as we set even more ambitious goals. With that, I'd like to open the call to questions. Operator, can we take the first question, please?

Certainly your first question comes from the line of Marty Auster from Credit Suisse. Your line is now open.

And will.

All of our army of merchant I was I was curious if you could kind of expand more of them are too.

It's really interesting comments about the potential for brinci kind of going forward and just sort of the diversity of indications that might be available to you. How are you thinking about kind of realistically ex sort of how many kind of how many phase two proof of concept you can really kick off for a kick off over the next year or two and then kind of what's the constraint. There is it just wanted to be really key.

Operator: Certainly. Your first question comes from the line of Marty Oster from Credit Suisse. Your line is now open.

William Lewis: Will, or maybe Martina, I was curious if you could kind of expand on that. I thought Martina made some really interesting comments about the potential for Brent Swicata going forward and just sort of the diversity of indications that might be available to you.

For for them the science before you launch programs as the personnel Workforces of capital.

Then finally will I'm sorry for central on the multi partner if you could maybe update us on where the discussions are with astrazeneca around their kind of potential of the opt in to conduct work in C. O P D N or asthma, and whether or not that that option. They have is there any sort of time kind of constraints around that for them to make a decision.

William Lewis: How are you thinking about, kind of, realistically, sort of how many, kind of, how many phase two proof of concepts you can really kick off over the next year or two? And then, kind of, what's the constraint there? Is it just wanting to be really careful with the science before you launch programs? Is it the personnel workforce? And then, finally, Will, sorry for such a long multi-parter, if you could maybe update us on where the discussions are with AstraZeneca around their, kind of, potential to opt in to conduct work in COPD and or asthma and whether or not that option they have.

Sure. So let me start really quickly with the second one first on EPS.

Obviously, we remain in contact with them and Theres nothing really the update there. They are clearly interested in the drug on its potential and I think each day as we discover more and more about the validity of not just this particular compound, but the pathway itself. It makes this area all of the more attract.

So we will see where that takes us I think right now, we feel very well positioned and capitalized and resource.

William Lewis: Sure, so let me start really quickly with the second one first. On AZ, obviously, we remain in contact with them, and there's really nothing really to update there. They're clearly interested in the drug and its potential, and I think each day as we discover more and more about the validity of not just this particular compound but the pathway itself, it makes this area all the more attractive. So we'll see where that takes us.

To be able to pursue all of the opportunities that this drug may provide to us.

I will use that to segue to your first question I think the first thing I would frame out for everyone's understanding is that from the moment. We saw the Willow data we have been at work on the <unk> pathway. So this is not something we're turning our attention to now it's something we're sharing more and more as we move forward with the community there've been a number of.

Preclinical disease models that we've looked at we've shared some of that data and I'd encourage folks to revisit our research and development day, we're very deliberate in what we called out on that day in terms of disease models, where we had already seen progress.

William Lewis: I think right now that we feel very well positioned and capitalized and resourced to be able to pursue all of the opportunities that this drug may provide us. And I'll use that to segue to your first question.

I think when we look at something like this cancer cell paper, it wasn't particularly surprising to US we indicated that the research day last year. The oncology was an area, where we thought this could have applicability of this data obviously validates that two of much greater degree and I think it's exciting that it is coming from of third party because of that.

William Lewis: I think the first thing I would point out for everyone's understanding is that from the moment we saw the Willow data, we have been at work on the DPP1 pathway, so this is not something we're turning our attention to now. It's something we're sharing more and more as we move forward with the community. There have been a number of preclinical disease models that we've looked at. We've shared some of that data, and I encourage folks to revisit our research and development day. We were very deliberate in what we called out on that day in terms of disease models where we had already seen progress.

<unk> provides I think an extra layer of validation and support for.

For the the mechanism.

Where do we go from here I think what we have in hand is a very high probability of success for non CF bronchiectasis and that alone creates an enormous opportunity for this company that I would describe as disruptive we positive.

We think about where to go from there cystic fibrosis, we have validated internally with our own reflection of an examination is worthy of additional investment in clinical development beyond that oncology is clearly one area. We're looking at but it is not alone there are several others and I guess, what I would say is.

William Lewis: I think when we look at something like this cancer cell paper, it wasn't particularly surprising to us. We indicated at research day last year that oncology was an area where we thought this could have applicability. This data obviously validates that to a much greater degree, and I think it's exciting that it is coming from a third party because that provides, I think, an extra layer of validation and support for the mechanism. Where do we go from here?

We do see constraints on how much can be done all at once but having said that I don't think that's the rate limiter right now it's of.

Throw examination of the science is an exploration of the prudent use of capital to create high probability and impactful outcomes.

And as we go through the year. It is our intention to be able to reveal other areas, where we think development is warranted with this compound I hope that's responsive.

Yeah, I think you will appreciate it.

Your next question comes from the line of Matthew Harrison from Morgan Stanley. Your line is now open.

William Lewis: I think what we have in hand is a very high probability of success for non-cf-bronchiectasis, and that alone creates an enormous opportunity for this company that I would describe as disruptively positive. As we think about where to go from there, cystic fibrosis is one area we have validated internally through our own reflection and examination as worthy of additional investment and clinical development. Beyond that, oncology is clearly one area we are looking at, but it is not alone.

Hi, Thanks for taking the question. This is connor on for Matthew.

A couple from us.

So you mentioned the the work going on in the U K.

But we were just wondering if you could comment more broadly on on how you see the ramp going I guess.

In terms of what countries are you targeting next and then how quickly you expect the uptake given the the digital efforts and Covid and.

William Lewis: There are several others, and I guess what I would say is we do see constraints on how much can be done all at once. But, having said that, I don't think that's the rate limiter right now. It's a thorough examination of the science. It's an exploration of the prudent use of capital to create high probability and impactful outcomes. And as we go through the year, it is our intention to be able to reveal other areas where we think development is warranted with this compound. I hope that's responsible. Yeah, thank you.

William Lewis: Yeah, thank you all. I appreciate it.

Operator: Your next question comes from the line of Matthew Harrison from Morgan Stanley. Your line is now open.

Operator: Hi, all. Thanks for taking the question. This is Connor on behalf of Matthew.

William Lewis: So, a couple of questions from us. You mentioned the work going on in the UK, but we're just wondering if you could comment more broadly on how you see the ramp going, I guess, in terms of what countries you're targeting next, and then how quickly you expect updates given the digital efforts and COVID. Sara may have mentioned this as well, but can you also just comment on your expectations for the growth profile in the US given COVID, and do you see that being as inversely related to the vaccine rate? And then, just quickly, can you just speak to 2021 expenses? Sorry, that was kind of a lot.

Guidance for when the vaccination program will be completed so we're hopeful that all of that is positive, but perhaps for more color I will ask Roger to comment.

Yeah. Thanks will so I think as we look at the European launch certainly, which we mentioned that the lockdown in parts of Germany.

William Lewis: Yeah, I just want to make sure I'm responsive to that. The first question that referenced COVID in the UK, you mean in regards to the..., of the launch. I see. Okay. Yeah.

Have hindered some access for our sales reps and for for patients actually visiting the clinic, having said that I think we're pleased with the progress that we've made so far the <unk>.

William Lewis: So for the launch, I'll ask Roger to address how that's going generally on the, and then we'll take your question on the impact on the US and the vaccines. I think, just to put a finer point on this, because it's really a global comment, our patients are at the front line of receiving vaccinations. And we think that that's obviously going to afford a lot of opportunities for us in 2021, both with the existing efforts that are being made across the US and in the countries where we're approved and reimbursed in Europe, but also those that will be added.

Team has been working for for several years with the with Kols.

And we know that they've been eagerly anticipating the launch of allocation that we believe that as we get on the other side as you mentioned of the vaccinations that we will we will be able to to to see that debt launch ramp.

I think in general in Europe, you see more of a center of excellence model than you do in the U S, where we met where we called for quite a quite heavily on the community physicians, both Ids and Pulmonologists. So there's a natural rate limiter, there, but we still expect that Europe will be we will have a meaningful launch for us will.

William Lewis: And perhaps most interestingly, the timing of the Japanese launch, if approved, once again, should fall on the far side, just on the far side of the anticipated government guidance for when the vaccination program will be completed. So we're hopeful that all of that is positive, but perhaps for more color, I'll ask Roger to comment.

In the U K as we mentioned the central reimbursement, we are anticipating that England will review that.

William Lewis: Yeah, thanks, Will. So I think that as we look at the European launch, certainly, as we mentioned, the lockdown in parts of Germany has hindered some access for our sales reps and for patients actually visiting the clinic. Having said that, I think we're pleased with the progress that we've made so far. The team has been working for several years with KOLs, and we know that they've been eagerly anticipating the launch of our case.

Roger Adsett: And we believe that as we get on the other side, as you mentioned, the vaccinations, we will be able to see that launch ramp. I think, in general, in Europe, you see more of a center of excellence model than you do in the U.S., where we call quite heavily on community physicians, both IDs, and pulmonologists. So there's a natural rate limiter there, but we still expect that Europe will have a meaningful launch for us.

Roger Adsett: Within the U.K., as we mentioned, central reimbursement. We're anticipating that England will review that and will be the first to provide central reimbursement, with the other countries within the United Kingdom following thereafter. And we expect reimbursement to continue throughout 2021 into 2022 with those European markets. So we're pleased with the progress we've made so far. Certainly, COVID is an issue as it has been in the U.S., but we believe that the long-term opportunity within Europe is fundamentally intact, and we look forward to getting on the other side of this and seeing that growth.

Think of the questions.

I guess with respect to some of the interest around for.

For instance, cat I've been on College, you have you guys contemplated I guess any.

Any earliest stage work to look at novel D. P. A.

D V P. One inhibitors, maybe in an effort to try to establish some level of of differential pricing, which presumably is is is fairly wide between.

Roger Adsett: And just in response to your question on expenses, I'll ask Sara to address that.

Sara M. Bonstein: Sure. Thanks, Connor, for the question. So on expenses, while we're not providing specific guidance, what I can share is that for research and development, we do expect expenses to increase year over year, and that's primarily to support our ASPEN program, ARISE, ENCQOR, as well as TPIP. So what I can say is we're laser-focused on resourcing these programs to be successful, and we have done just

Something like Ah bronchiectasis, and where most oncology drugs the price.

Yeah. So I appreciate the question I think we're while we're at the early days of our exploration in the oncology arena. It certainly is something that we're going to be the.

Sara M. Bonstein: understood. Thank you.

Issue you raised will be mindful of I think the first we want to file the science and see where it can be most impactful and I have to say this is one of those compounds that is somewhat recently observed if you're really lucky you come across them once in a lifetime.

Operator: Your next question comes from the line of Stephen Wiley from Stifel. Your line is now open.

Operator: Yeah, good morning. Thanks for taking the questions.

William Lewis: I guess with respect to some of this interest around Brent's Academy on ecology, have you guys contemplated, I guess, any earlier stage work to look at novel DPP1 inhibitors, maybe in an effort to try to establish some level of differential pricing, which presumably is fairly wide, something like bronchiectasis. How Are Most Oncology Drugs Priced

This pathway is really the discovery of the Willow study, it's not simply that it is potentially affected the bronchiectasis is that we think we of unrest Ah subject of study of professor Chalmers and many other key opinion leaders and that this DPP one inhibited inhibition.

William Lewis: Yeah, so I appreciate the question. I think while we're at the early days of our exploration in the oncology arena, it certainly is something that we're going to be mindful of the issues you raise. I think first we want to follow the science and see where it can be most impactful. And I have to say, this is one of those compounds that, as someone recently observed, you know, if you're really lucky, you come across them once in a lifetime.

May have an.

And impactful clinical.

Consequence, and many different disease areas oncology as one will obviously are drawn to because there is a clear on the medical need the scientist was theoretically pretty strong and now we have validation. So it's sort of demands our attention and with that in mind I think we're going to be looking at a lot of different directions, we may travel, including some of the ones you.

Suggest.

Okay, and then and.

And then just the quick question on television.

William Lewis: This pathway is really the discovery of the Willow study, and not simply that it is potentially effective in bronchiectasis. It's that we think we have unearthed a subject of study for Professor Chalmers and many other key opinion leaders in that this DPP-1 inhibition may have... Impactful clinical consequences in many different disease areas. Oncology is one we obviously are drawn to because there's a clear medical need. The science was theoretically pretty strong, and now we have validation. So it sort of demands our attention. And with that in mind, I think we're going to be looking at a lot of different directions we could travel, including some of the ones you suggest.

I know you're going to be initiating the fees to later this year.

I know that the functional class of patients that have been in the world into the prior Prost. The noise studies has been a little bit different I think the.

The type of ASO Registrational study was functional class three I think of the price of the noise of dog the kind of two through for and.

I know, there's some literature, suggesting that the variability of of six minute walk test is is correlated to function of the class. So is that something that you care about at all in terms of how you're gonna set your eligibility criteria for for the face to it.

So I will ask regarding the development plan Martina to address that question and then.

William Lewis: Okay, and then, and then just a quick question on TPIP. I know you're going to be initiating phase two later this year.

Yeah. So yeah of functional class on if you look at the Beach. This is the class of what you really touch patients based on the severity of the disease that class of one when you don't have a lot of symptoms of cats.

Operator: I know that the functional class of patients that have been enrolled into prior prostanoid studies has been a little bit different. For example, the Taibaso Registrational Study was Functional Class 3. I think other prostenoids have done kind of 2 through 4. There is some literature suggesting that the variability of a six minute walk test is, is, is correlated to functional class. So is that something that you care about at all in terms of how you're going to set your eligibility criteria?

And the last two and three is the way the most impacted but there is also you opportunity to really improve for this patient and that will be the class that we will be looking at.

From an eligibility criteria of but also can improve when you go on to the class for for example, the the patients who from of six minute walk distant perspective would not be able to do that much anymore. Because both of the patients actually are probably not the mobile. So this is the area of severity in class for example, too and the <unk>.

<unk> that we will be looking at.

One of the most interesting things about this compound is it the potential not only NPH, but also it's potential in P. H I L D and even possibly in idiopathic pulmonary fibrosis patients.

Martina Flammer: So, I'll ask you, in regard to the development plan, Martina, to address that question and then...

Martina Flammer: Yeah, so functional classes, if you look at this, this is the class where you really judge patients based on the severity of the disease, and like class one, where they don't have a lot of symptoms yet, but class two and three is where they're most impacted, but there is also the opportunity to really improve for this patient, and that will be the class that we will be looking at from an eligibility perspective, but also to improve. When you go on through classes like class four, for example, those are patients who, from a six minute walk distance perspective, would not be able to do that much anymore because most of those patients are probably not mobile.

It's quite extraordinary to be joining.

This group of.

Programs pursuing these diseases. This late in the game right. There are a lot of approved drugs in this therapeutic area. However, it's really the dawn of the birth of the full of utilization of the price annoyed class and this compound is specifically designed over the last half a decade too.

To.

Extract the full value of the price Noyd class and so I think people should understand the TPI P. As purpose designed to really make a clinical impact that is very different from what has been seen with regular wait for cross millions of various forms of delivery.

Great. Thanks for taking the questions and congrats on the the execution in what was obviously of pretty difficult here.

William Lewis: One of the most interesting things about this compound is its potential not only in PAH but also in its potential

Thank you.

[noise] hearing nekton comes from the line of the <unk> from Goldman Sachs Killin Snow open.

William Lewis: Fibrosis patients, it's quite extraordinary to be joining this group of programs pursuing these diseases this late in the game, right? There are a lot of approved drugs in this therapeutic area. However, it's really the dawn of the birth of the full utilization of the prostanoid class, and this compound has been specifically designed over the last, you know, half a decade to extract the full value of the prostanoid class. And so I think people should understand that TPIP is purpose-designed to really make a clinical impact that is very different from what has been seen with regular prostanoil and its various forms of delivery.

Have you on this is Jack on for Greg Uhm, Congrats on the quarter.

Maybe first off if you could talk a little bit more about sort of the the quarterly cadence of how you see both hurricane sales for covering and the you asking of teaching comment and then maybe you know ads companies come on line in Europe, you know what kind of of contribution that can be then as we think about the international opportunity and kind of.

You know, maybe five years out or sort of you know at peak, how do you envision kind of the the breakdown in potential peak revenues between the U S here of Japan or U S. Ex you ask just kind of of you know for our longer term modeling considerations.

William Lewis: Thanks for taking the questions and congrats on the execution of what was obviously a pretty difficult year. Thank you.

Operator: Thank you.

Operator: Your next tune comes from the line of Craig Suvannavejh from Goldman Sachs. Your line is now open. Hi everyone, this is Jack on for Greg.

So I will just it's gonna be a little disappointed I'm not I'm not going to give you a five year forecast for right now, but I will give you some color on where I think we're going the first is that the last year saw really steady performance in the face of incredibly challenging circumstances, and I mentioned that only as a way to share the learnings from that experience.

William Lewis: Congratulations on the quarter. Maybe first off, if you could talk a little bit more about sort of the quarterly cadence of how you see, you know, both our cases sales recovering in the US, to the extent you can comment, and then maybe, you know, as countries come online in Europe, you know, what kind of a contribution that could be. Then as we think about the international opportunity kind of, You know, maybe five years out or sort of, you know, at peak, how do you envision kind of the breakdown of potential peak revenues between the US, Europe, Japan, or US, ex-US just kind of, you know, for our longer-term modeling considerations?

And the point of insight that I think is the most profound that when COVID-19 subsides, we saw a very rapid return of patients and of the physician's offices and consequently of returned of growth. So we think that is the harbinger of what's the come in 2021, and obviously as we mentioned before the vaccination is hitting our patients first and all of <unk>.

<unk> Hood in all areas around the world and so that should be.

Helpful. I think what we think about the international launch in the immediate term, it's very exciting to be getting Europe, and if approved also Japan and to remind everyone. There is a higher diagnosed prevalence of refractory Mac patients in Japan than there is in the U S. So these are really exciting market opportunities for us and things of that we've been working on for.

Several years up to this moment.

William Lewis: It's going to be a little disappointing. I'm not going to give you a five-year forecast right now, but I will give you some color on where I think we're going. The first thing is that the last year saw a really steady performance in the face of incredibly challenging circumstances. And I mentioned that only as a way to share the learnings from that experience.

As we think about the free for the future beyond this first year of launch. We're also focused on the frontline approval of the drug in the full approval in the United States and that's what it arrives in on court will enable so that study starting at the end of last year. It really puts us in a position to nominally create the momentum this year build upon it next year in the.

Different areas, but then add to it the possibility of label expansion and just to remind everybody frontline MTM Mac is about five times the size of refractory Mack.

William Lewis: And the point of insight that I think is the most profound is that when COVID subsides, we saw a very rapid return of patients into their physicians' offices and, consequently, a return to growth. So we think that is the harbinger of what's to come in 2021. And obviously, as we mentioned before, the vaccination is hitting our patients first, in all likelihood, in all areas around the world. And so that should be helpful.

So this is a really interesting franchise on its own right. It's been very steady through an incredibly challenging circumstance and we think will returning to growth in 2021, both on the U S and with our international launches an expansion.

And if I can mitigate of quick follow up to that how.

How do you think about.

The extent to which are case can kind of offset some of your cash burn in the near term.

First of all of these clinical programs and you know how do you kind of look at your your funding requirements on like maybe a two year forward.

William Lewis: I think when we think about the international launch in the immediate term, it's very exciting to be adding Europe and, if approved, also Japan. And to remind everyone, there's a higher diagnosed prevalence of refractory MAC patients in Japan than there is in the U.S.

Yeah, So I'll ask Sarah to address the sure thing Zac Uhm. So Eric cases has been and will continue to be.

Great contribution as we think about our burn and sort of thing all setting of heartburn Uhm. We have on provided specific guidance on the runway and those types of things May continue Eric case instead of.

William Lewis: So these are really exciting market opportunities for us and things that we've been working on for several years up to this moment. As we think about the future beyond this first year of launch, we're also focused on frontline approval of the drug and full approval in the United States, and that's what Arise and Encore will enable. So that study, starting at the end of last year, really puts us in a position to not only create momentum this year, build upon it next year in these different areas, but then add to it the possibility of label expansion.

On one of the tools, we had to help fund our ongoing business and just reiterate we ended the year with very strong cash position $533 million in cash sounds very strong cash position.

Alright, thank you.

Your next question comes from <unk> from calm in your line of Snow open.

Hi. This is one of the Hunter to thank you for taking the question and congrats on the I think maybe just really quickly on the.

William Lewis: So this is a really interesting franchise in its own right, it's been very steady through an incredibly challenging circumstance, and we think we're returning to growth in 2021 both in the U.S. and with our international launches.

<unk> to try on you're planning on.

Can you speak a little bit into how you're thinking about it okay on the way it might have.

Initially into that treatment landscape and and also how you considering what kind of <unk> eligible for some type of person patients for that Uhm, China any reason to think of of do my front of your in combination you. Thank you.

Sara M. Bonstein: And if I can maybe get a quick follow-up to that, um, you know, how do you think about, you know, the extent to which our case can kind of offset some of your cash burn in the near term as you pursue all these clinical programs? And, you know, how do you kind of look at your funding requirements over, like, maybe, two years?

Yeah. So when we think about cystic fibrosis, one of the things that drew our attention of this category of initially is the notion that if you look at sort of of levels of neutrophil of the last day as in these patients cystic fibrosis sits above bronchiectasis in terms of your average patient profile and we think this mechanism speaks directly to the.

Sara M. Bonstein: Yeah, so I'll ask Sara to address that.

Operator: Sure, thanks, Jack. So error cases have been and will continue to be a great contribution as we think about our burn and sort of the offsetting of our burn. We haven't provided specific guidance on runway and those types of things, but you can view error cases as one of the tools we have to help fund our ongoing business. And just reiterate, we ended the year with a very strong cash position, $533 million in cash, so very strong cash Your next question comes from Ritu Baral from Common. Your line is now open.

The opportunity if you think about the impact of the per.

Per tech strokes in this population it's been a major advance. However, these patients still suffer from pulmonary exacerbations and as you recall from the Willow study, we saw roughly of 40% reduction in pulmonary exacerbation of.

And as a consequence, we think the Strug is sort of purpose built to cover.

Cover that last mile of need and the cystic fibrosis fibrosis patient population. So we are moving forward expeditiously to try to bring this drug two of those patients because effectively once you have eradicated the baseline.

Operator: Hi, this is Lila. I'm for Ritu.

William Lewis: Thank you for taking the question, and congrats on the update. Maybe just really quickly on the Phase 2 trial you're planning for cystic fibrosis. Can you speak a little bit about the program and where it might fit, at least initially, into that treatment landscape, and then also how you're considering potential eligible cystic fibrosis patients for that trial? Is there any reason to think it would be more refractory or in combination use?

Cause of cystic fibrosis from these patients for those that have had it for a long time of the damage is really already done and so they're going to be effectively bronchia caddick patients. So the logic is very very strong there I think as you know the metabolism of these patients is a little bit different and so the PK P. D study.

Is necessary to understand do we need to go up in dose to treat them, but it would be our expectation and hope that if this is proven out and validated that these patients who are taking those of our techs drugs will also get our drug as a way of addressing this last on that medical need which is the.

William Lewis: Thank you.

William Lewis: Yeah, so when we think about cystic fibrosis, one of the things that, um, you know, drew our attention to this category initially is the notion that if you look at sort of levels of neutrophil elastase in these patients, cystic fibrosis sits above bronchiectasis in terms of your average patient profile, and we think this mechanism speaks directly to that opportunity. And if you It's been a major advance.

The reduction of of pulmonary exacerbations.

Gotcha, Okay helpful. Thank you.

[noise] again to ask the question. Please pray for one on your telephone keypad. If you have any questions can please press dark and the number one on your telephone.

William Lewis: However, these patients still suffer from pulmonary exacerbations. And as you recall from the Willow study, we saw roughly a 40% reduction in pulmonary exacerbations. And as a consequence, we think this drug is sort of purpose-built to fill that last mile of need in the cystic fibrosis patient population. So we are moving forward expeditiously to try to bring this drug to those patients. Because effectively, once you have eradicated the baseline pulmonary exacerbation, you're going to be able to cover that last mile of need. The cause of cystic fibrosis in these patients, you know, for those that have had it for a long time, the damage is really already done. And so they're going to be effectively bronchiectatic patients. So the logic is very strong there.

Your next question comes from the line of Joseph Schwartz from S. B B Leerink your line of Snow open.

Yeah, Hi on June dialing on for child, Thanks for taking care of questions Uhm.

I was wondering for the lines prep work goes for Japan, you mentioned that you added five additional sales that I was just wondering you know what the motivation with that one of the motivation with that one but that was for you are you the checking no like soccer demand foundations and usually anticipate on you know or anything on like my lunch.

I need that taken care of that.

Sure I appreciate the question so that I will actually ask Roger to address that.

Yeah sure. Thanks will thanks for the question. So as we mentioned we've actually had 15 sales reps out uhm in the Japanese market since the the fourth quarter and that was in an effort in touch of leopard as we promoted at Macrolide to understand where these patients will be treated understand the dynamic I think the response that we've seen so far has been.

William Lewis: I think, as you know, the metabolism in these patients is a little bit different. And so the PKPD study is necessary to understand whether we need to go up in dose to treat them. But it would be our expectation and hope that if this is proven out and validated, that these patients who are taking those Vertex drugs would also get our drug as a way of addressing this last unmet medical need, which is the reduction of pulmonary exacerbations. It's very helpful.

<unk> very strong from the Kols and so as we get a greater understanding of the of the of where the patient's mind. The landscape, we felt that adding an additional five reps to to make sure. We have adequate coverage. There was the prudent thing to do so we anticipate uhm any of those five reps on the fourth quarter excuse me in the first quarter of this year.

William Lewis: Got you. That's very helpful. Thank you.

Operator: Again, to ask a question, please press star 1 on your telephone keypad. If you have any questions, simply press star, then the number 1 on your telephone keypad. Your next question comes from the line of Joseph Schwartz from SBB Luranc. Your line is now open.

Roger Adsett: Hi, I'm Julie Dialingham on behalf of Joe. Thanks for taking our questions. I was wondering, as far as the launch prep work goes for Japan, you mentioned that you added five additional sales reps, and I was just wondering, what the motivation was for that, what the motivation was that was, what that was for. Are you detecting, you know, like stronger demand from patients than initially anticipated or, you know, or is there more launch prep?

And and to support the launch assuming the approval.

Okay. Thank you and then could you just remind us the number of <unk> that you plan to study and arrive on what the helmet hold on for anything on.

That the ninth at two X box for it I put you know later in the for but I was just wondering hold on the account.

So for the specifics of the study I'll ask marketed to address it in the second but as far as pace goes I think for arise encore for Aspen, what we're trying to do is really focus on opening the different sites getting them.

Roger Adsett: Launch Presswork faster than you thought; could you provide some color on that?

Roger Adsett: Sure, I appreciate the question. I'll actually ask Roger to address that.

Roger Adsett: Yeah, sure. Thanks, Will.

Able to enroll patients that process is well underway, we'd like to see that play out all of these studies are getting fully resource from the company or investing a lot of money and and human effort into making sure that we can move the studies for to expeditiously and so once we have a better understanding of what the Pacers.

Roger Adsett: Thanks for the question. As we mentioned, we've actually had our 15 sales reps out in the Japanese market since the fourth quarter. And that was an effort, an intentional effort, as we promoted at Macrolide, to understand where these patients were being treated and understand the dynamics. I think the response that we've seen so far has been very strong from the KOLs. And so as we get a greater understanding of where the patients lie in the landscape, we felt that adding an additional five reps to make sure we have adequate coverage there was the prudent thing to do. So we anticipate adding those five reps in the fourth quarter, excuse me, in the first quarter of this year and to support the launch, assuming approval.

And the current environment right now, we don't really see any impact, but we'd like to play out over several months before we sort of give forecast some predictions on timing. So I just want to address the timing question first and then ask of Martina to talk about the design of the study.

Professor in arrive at we're looking at newly diagnosed snack lung disease patient and looking for 100 patients in the arrive 30 and 250 patient in the Encore study and yes, we started dosing at the station and does that global studies again across the U S. Europe.

Roger Adsett: Okay, great. Thanks. And then could you just remind me?

Martina Flammer: The number of patients that you plan to study and arise and what the enrollment cadence is. I know that you said to expect an update later this year, but I was just wondering how that was going.

<unk> and Latin America. So we've started initiating sites are across the globe.

William Lewis: So, for the specifics of the study, I'll ask Martina to address that in a second, but as far as PACE goes, I think, you know, for ARISE, Encore, for Aspen, what we're trying to do is really focus on opening the different sites, getting them able to enroll patients. That process is well underway. We'd like to see that play out.

Okay, great. Thanks, so much.

Your next question comes from the line of Lisa Michael from Evercore I S. I. Your line is now open.

Hi, Thanks for taking the question could you tell us that U S sales for versus the rest of the world.

Martina Flammer: All of these studies are getting fully resourced from the company. We're investing a lot of money and human effort into making sure that we can move these studies forward expeditiously. And so once we have a better understanding of what PACE is like in the current environment, right now, we don't really see any impact, but we'd like that to play out over several months before we sort of give forecasts and predictions.

Uhm So Sir you wanted the dresser sure. Thanks. Thanks for for the question. So we will be providing all will sales we are not going to be providing a breakdown of uhm regional sales and sort of some of the rationale behind that is related to just kicked off the the the launch in Europe. The.

Sales or not on material amount until we will not look to break out at uhm.

For the here.

Martina Flammer: We're looking at newly diagnosed MAC lung disease patients; we're looking for 100 patients in the ARISE study and 250 patients in the ENCORE study. And yes, we started dosing with this patient, and these are global studies, again, across the U.S., Europe, Asia, and Latin America. We've started initiating sites there across the country.

Okay, and then can you let me just talk about a little bit more in detail about the kind of work you've done to understand sort of let the patient dynamics for this year.

Where patients you know I guess.

You know you said for your office visit <unk> was it mainly driven by new patient adds it was there any change in.

Martina Flammer: Okay, great. Thanks so much.

Like duration of therapy or any of those other factors I'm just curious on kind of of the flow of patient. This year and then I guess the key things are like when do you expect that to lift. This year you know as we kind of come out of the pandemic of <unk> what are the key lepers there yeah.

Operator: Your next question comes from the line of Liisa Bayko from Evercore ISI. Your line is now open. Hi, thanks for taking the question. Could you tell us what U.S. sales were versus the rest of the world?

Sara M. Bonstein: So Sara, do you want to address that?

Sara M. Bonstein: Sure. Thanks, Liisa, for the question. So we will be providing global sales. We are not going to be providing a breakdown of regional sales. And sort of some of the rationale behind that is related to the fact that we just kicked off the launch in Europe.

Yeah, I mean really simply I think we look at a broad range of metrics. Obviously of is we're tracking error of case performance and they have been remarkably steady on almost every front. The one thing we've been very clear about is that the new patient starts is the the one metric that has been hit the hardest in those areas in particular work Covid has searched.

Sara M. Bonstein: The sales are not material amounts, and so we will not look to break out that for the Okay, and then can you maybe just talk a little bit more in detail about the kind of work you've done to understand sort of what the patient dynamic for this year was, you know, I guess. You know, you said fewer office visits. So was it mainly driven by new patient ads? Was there any change in, you know, like the duration of therapy or any of those other factors?

And we've seen that consistently throughout the year as the regional variability is played out as I mentioned earlier, though I think the most important point from this in the learning is that the.

On one of the franchise is very resilient.

And the the steady performance along a lot of the metrics speaks to that I think as we look at new patient starts we have seen that return rapidly and those areas where of COVID-19 restrictions and and searches have abated. So our expectation is that as that plays out we will see that.

Sara M. Bonstein: Just curious about kind of the flow of patients this year. And then I guess the key things are like, when do you expect that to lift this year? You know, as we kind of come out of the pandemic, and what are the key levers there?

The writ large for the U S market and indeed, Europe's launches each country, the security's reimbursement of <unk>.

Specific timing, it's hard to say I do think the key drivers here our number one the vaccinations. Once those are completed people, obviously feel a lot more comfortable going to their physician many of them have a strong desire to do so and importantly, many of the physicians are very keen to reach out proactively to their patients and bring them in to their practices.

William Lewis: Yeah, I mean, really simply, I think we look at a broad range of metrics, obviously, as we're tracking error case performance, and they have been remarkably steady on almost every front. The one thing we've been very clear about is that new patient starts is the one metric that has been hit the hardest in those areas, in particular, where COVID has surged. And we've seen that consistently throughout the year as the regional variability has played out.

I think there's both Ah need there because of the challenges of the last year, but also an opportunity is Roger mentioned earlier as awareness about respiratory health is has grown substantially so.

We don't know exactly when it's going to take place, but I do see us returning to growth of as soon as that patient returns to the office visit.

William Lewis: As I mentioned earlier, though, I think the most important point from this and the learning is that, number one, the franchise is very resilient, and the steady performance along a lot of the metrics speaks to that. I think as we look at new patient starts, we have seen that return rapidly in those areas where COVID restrictions and surges have abated. So our expectation is that as that plays out, we will see that play out for the U.S. market and indeed Europe's launch as each country secures reimbursement. As to specific timing, it's hard to say.

Thank you.

Your next question.

Comes from Anita the Sean from Bahrenburg capital Your line of Snow open.

Hi, good morning, Congrats on the card on it and thanks for for taking my question. Yeah. I know you had you know sort of the address.

But I just wanted to get some of clarity on it considering the you know launch in Europe, and the different regions well. It sounds known that you know you know me and you cash saga that'd be come on board pretty quickly come back on and some other Megan can I give you credit or something that you take.

William Lewis: I do think the key drivers here are number one, the vaccinations. Once those are completed, people obviously feel a lot more comfortable going to their physicians. Many of them have a strong desire to do so, and importantly, many of the physicians are very keen to reach out proactively to their patients and involve them in their practices. I think there's both a need there because of the challenges of the last year, but also an opportunity, as Roger mentioned earlier, as awareness about respiratory health has grown substantially.

Take time to set up the reimbursement before lines and get on to mention that email will go with a study in Netherlands, the kind of help accidentally.

Getting reimbursement of <unk> almost a month. So the question is M. I mean do you expect like majority of the regions of in Europe kind of come on boy for the launch by the end of this year or are there any specific <unk> that you think my Kennedy take more time on.

William Lewis: We don't know exactly when it's going to take place, but I do see us returning to growth as soon as that patient returns to the office.

William Lewis: Your next question comes from Anita Deschamps from Berenberg, Capital, Urlanis, now open.

You know if I can connect the studies to establish the lean basement for that and then the Helen.

William Lewis: Hi, good morning, congratulations on the quarter, and thank you for taking my questions. Bill, I know you had, you know, sort of addressed this early on, but I just wanted to get some more clarity on it.

The Roger do you want to address that.

Yeah sure happy too so as we think about the the European launch sequences. You said the these countries. Some countries may take longer so we're actually it it on D day, we had a presentation that we put up of we mapped out what what we think might be the sequence of the launches. So we do thinking of markets, where we're focused on our core markets will have.

Roger Adsett: Considering the, you know, launch in Europe and the different regions, well, it's sort of known that, you know, Germany and the UK are sort of, they come on board pretty quickly compared to some other regions, like maybe France or something, which take time to set up reimbursement. And you also mentioned that, you know, there was a study in the Netherlands that kind of helped accelerate getting reimbursements in place by almost three months.

A lot of.

The majority of we're anticipating reimbursement in 2021 as you pointed out of the the cramps could take it a little bit longer will see how that plays out in the meantime, we do have the H U program in France, which allows access to those patients of need at the results of reimbursed.

Roger Adsett: So, my question is, do you expect, like, most of the regions in Europe to sort of come on board for the launch by the end of this year, or are there any specific regions that you think might generally take more time or, you know, sort of conduct these studies to establish the reimbursement for that?

So we're very pleased by if you've mentioned the Netherlands. The pilot program, we participated in and that did allow us to the to accelerate the reimbursement and so we're we're hopeful the to as we move forward will will have successful interactions with the governments of these markets, but as I said most of the the most of the market. So we're targeting will come on the 2021.

Roger Adsett: And then I have one more.

Roger Adsett: Roger, do you want to address that?

Roger Adsett: Yeah, sure, happy to. So as we think about the European launch sequence, as you said, these countries, some countries may take longer. So actually, at R&D Day, we had a presentation that we put up, and we mapped out, you know, what we think might be the sequence of launches. So we do think in our markets, where we're focused on our core markets, we'll have the majority, and we're anticipating reimbursement in 2021.

Uhm, but France will is likely to take longer but this is all of our best estimates based on the rest of the.

Yes that Tesla and thank you and then maybe some color on.

The expenses I know I know kind of talked about the R&D going up here on the yeah based on all of the development appropriate thing with the candidates, but as for it I spend on S. N E for the Yeah. I know you said you had plans for setting up commercialization of the advocate in the U S. So are the.

Roger Adsett: As you pointed out, I think France could take a little bit longer. We'll see how that plays out. In the meantime, we do have the ATU program in France, which allows access to those patients in need. And it's also reimbursed.

Roger Adsett: So we're very pleased with, as you mentioned, the Netherlands, the pilot program we participated in, and that did allow us to accelerate the reimbursement. And so we're hopeful that as we move forward, we'll have successful interactions with the governments in these markets. But as I said, most of the markets that we're targeting will come online in 2021, but France is likely to take longer. But these are all our best estimates based on precedent.

Sort of.

So for what to expect that being increasing over the cool all day. So I thought of maybe back in debt to the considering you know vaccines might be.

The more more of availability of that things might be bad for like the second half of the year.

So I'll ask of Certeau address that sure. Thanks Anita several.

Sara M. Bonstein: Yes, that's helpful. And thank you.

Some of them are not providing specific items, what I can share on SG&A, what I can share.

As we've had the infrastructure in place in both of Europe, and Japan throughout 2020, as Roger mentioned, there will be some modest growth in some of the sales of customer facing organizations of that infrastructure has been of place and we have key count on the ground and for Europe, and Japan helped drive each these launches.

Sara M. Bonstein: And then maybe some color on, you know, the expenses. I know, I know, Sara talked about the R&D going up year over year based on all the development progressing with the candidates. But as far as spend on SG&A for the year, I know you said you have plans for setting up commercialization of air cases in the US. So are we sort of supposed to expect that to be increasing over the quarters or maybe back-ended to the year considering, you know, vaccines might be more available, more availability of vaccines might be there towards the second half of the year?

Thank you Sir that'd be all for me.

Ladies and gentlemen that concludes our call for today I will had it back over to will Lewis for any closing remarks.

Sara M. Bonstein: So I'll ask Sara to address that.

Thank you all for joining us today.

Sara M. Bonstein: So while we're not providing specific guidance on SG&A, what I can share is we have the infrastructure in place in both Europe and Japan throughout 2020. As Roger mentioned, there will be some modest growth in some of the sales and customer-facing organizations, but that infrastructure has been in place, and we have key talent on the ground in both Europe and Japan to help drive these launches.

Ladies and gentlemen, this concludes your call for today. Thank you for your participation you may now disconnect.

[music].

Sara M. Bonstein: Thank you, Sara. That'll be all for me.

William Lewis: Ladies and gentlemen, that concludes our call for today. I will hand it back over to Will Lewis for any questions.

Operator: Thank you all for joining us today.

Operator: Ladies and gentlemen, this concludes your call for today. Thank you for your participation. I'm inaoudis. Good night.

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