Q4 2021 Insmed Inc Earnings Call

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Speaker 2: Thank you.

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Speaker 3: Welcome to the Insmet 4-Quarter and Full Year 2021 Financial Results. My name is Juan and I will be coordinating your call today. If you would like to ask a question during the presentation, you may do so by pressing star 1 on your telephone keypad. I will now hand over to your host, Elianor Berizer, investor relations at Insmet. To begin with, please, Elianor, go ahead.

Welcome to the Internet fourth quarter and full year 2021 Finance Agriculture. My name is one and I will be going to maintain your call. Today. If you would like to ask a question. During the presentation. You may do so by pressing the star one on your telephone keypad.

Now on the <unk>.

Your horse Atlanta batteries, there investor relation App in Smith to begin with please go.

Go ahead.

Speaker 4: Thank you, Juan. Good morning, and welcome to today's conference call to discuss our full year financial results for 2021 and to provide a business and pipeline of...

Thank you Ron Good morning, and welcome to today's conference call to discuss our full year financial results for 2021 and to provide a business and pipeline update.

Speaker 4: Before we start, let me remind you that today's call will include forward-looking statements based on current expectations.

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

Speaker 4: 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 statement.

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.

Speaker 4: 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.

Refer to our filings with the Securities and Exchange Commission, which are available through the SEC's website at Www dot.

<unk> dot Gov or from our website for information concerning the risk factors that could affect the company.

Speaker 4: The information on today's call is not intended for promotional purposes and not sufficient for prescribing.

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

Speaker 4: Joining me on today's call are members of the INSCED Executive Management team, including Will Lewis, Chair and Chief Executive Officer, Dr. Martina Flamer, Chief Medical Officer, Roger Estes, Chief Operating Officer, and Sarah Bonsdine, Chief Financial Officer.

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

Speaker 4: 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.

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.

Speaker 5: Thank you, Eleanor, and good morning, everyone. Today is a very exciting day for us at InSmed. We are going to share with you a robust set of updates that will clarify how we are thinking about our program catalyst, commercial franchise, and capital allocation over the next several years to support our mission of transforming the lives of patients with serious and rare diseases.

Thank you Eleanor and good morning, everyone. Today is a very exciting day for us.

We're going to share with you our robust set of updates that will clarify how we're thinking about our program catalysts commercial franchise and capital allocation over the next several years to support our mission of transforming the lives of patients with serious and rare diseases.

Speaker 5: At Intimid, we are building what we believe is one of the few companies in our industry capable of producing potentially multi-billion dollars of revenue by the end of this decade.

And then we're building what we believe is one of the few companies in our industry capable of producing potentially multibillion dollars of revenue by the end of this decade.

During the course of today's call. We are excited to review the path we will be following as we pursue this ambitious goal or strategy centered on developing medicines that have a significant positive impact on patients' lives.

Speaker 5: Today, InsimEd has seven ongoing mid and late stage clinical trials, commercial operations in three territories around the globe, and a research engine working behind the scenes to identify the most promising early stage candidates by harnessing innovative technology.

Today <unk> has seven ongoing mid and late stage clinical trials commercial operations in three territories around the globe and our research engine working behind the scenes to identify the most promising early stage candidates by harnessing innovative technologies.

We have segmented all of this work in the four pillars.

First of these pillars and <unk> franchise, our marketed product for the treatment of refractory Mac lung disease, where we benefited from a commercial footprint in the U S Europe and Japan.

These launches mature we intend to grow revenue globally by at least 30% this year compared to 2021.

Speaker 5: In parallel, our frontline clinical trial program is advancing to support full FDA and select international approvals of our case in newly diagnosed NTM patients.

Parallel our hotline clinical trial program is advancing to support full MTA in select international approvals of barricades and newly diagnosed MTM patients.

Speaker 5: This front line indication represents a multi-fold increase in the addressable opportunity compared to the refractory setting alone.

This frontline indication represents a multi fold increase in the addressable opportunity compared to the refractory setting alone.

Speaker 5: The ARISE study, which is the first of the two studies needed on our path to approval, is currently 50% enrolled, and we anticipate enrollment to be complete this year with top-line data in the first half of next year. We also anticipate the second study, ENCOR, will be fully enrolled next year.

The arrive study, which is the first of the two studies needed on our path to approval is currently 50% enrolled and we anticipate enrollment to be complete this year with topline data in the first half of next year.

We also anticipate the second study encore will be fully enrolled next year.

Speaker 5: For our second pillar, brenzocatib, our DPP-1 inhibitor, the Aspen trial exploring the potential of treatment of bronchiectasis is now 50% enrolled ahead of internal projections. And we anticipate it will be fully enrolled by approximately this time next year. There is real enthusiasm for this trial around the world as this rapid rate of enrollment testifies.

For our second pillar <unk>, our <unk> inhibitor, the Aspen trial exploring the potential of treatment of Bronchiectasis is now 50% enrolled ahead of internal projections and we anticipate it will be fully enrolled by approximately this time next year.

There is real enthusiasm for this trial around the world as this rapid rate of enrollment testifies.

Speaker 5: In addition to Aspen, the phase 2 PK, PD study in cystic fibrosis patients is underway, and we anticipate top line data by the end of this year or early 2023.

In addition to Aspen the phase III PK PD study in cystic fibrosis patients is underway and we anticipate topline data by the end of this year or early 2023.

Speaker 5: In line with our strategy to build a portfolio around neutrophil mediated diseases using our DBB-1 inhibitor, we are excited to report that we have identified the next two potential indications for Renzocatin, along with phase two clinical trial designs for their exploration. You will hear more about these later on today's call.

In line with our strategy to build a portfolio around neutrophil mediated diseases using our GBP. One inhibitor. We are excited to report that we have identified the next two potential indications for <unk>, along with phase II clinical trial designs for their exploration you'll hear more about these later on today's call.

Speaker 5: Our third pillar, TPIP, is a specialized proprasenal program formulation with three parallel phase two programs underway with an initial focus on potential treatments for PAH and PHILD. We will also review those trial designs later on the call.

Our third pillar TP IP is a specialized for profitable program formulation with three parallel phase III programs underway with an initial focus on potential treatments for PIH in ph ILD.

We'll also review those trial designs later on the call.

Speaker 5: Finally, translational medicine is our fourth pillar. Led by several world-class teams, our research engine is working with exciting new technologies to identify the next round of internet's early-stage pipeline candidates in the serious and rare disease space.

Finally, translational medicine is our fourth pillar led by several World class teams. Our research engine is working with exciting new technologies to identify the next round of instruments early stage pipeline candidates and the serious and rare disease space.

Speaker 5: Within this framework, we intend to generate, on average, one new IND per year. We look forward to hosting a detailed research day in the second half of this year to update you on our progress.

Within this framework, we intend to generate on average one new IND per year.

We look forward to hosting the detailed research day in the second half of this year to update you on our progress.

Speaker 5: Set against the backdrop of one of the more challenging health care markets in recent years, I believe Insimet is poised to weather the storm of these turbulent times. Our goals are ambitious, but we have been deliberate in our pursuit, and we have a track record of achieving what we set out to do.

Set against the backdrop of one of the more challenging health care markets. In recent years I believe instrument is poised to weather. The storm of these turbulent times our goals are ambitious, but we have been deliberate in our pursuit and we have a track record of achieving what we set out to do.

Speaker 5: The next stage of our growth will depend on advancing more treatments and strategically complementary indications, and from there, building additional therapeutic areas from our fourth pillar to follow the first three pillars.

The next stage of our growth will depend on advancing more treatments and strategically complementary indications and from there building additional therapeutic areas from our fourth pillar to follow in the first three pillars let.

Let's take a moment to consider what we've accomplished.

Speaker 5: Our global commercial franchise and infrastructure is already built. We benefit from revenue generation from our marketed product. We have two strategically overlapping pivotal stage programs with Brensoe Catzib and Eric Hays Frontline. We have a robust pipeline, a focused research effort to generate impactful medicines in new therapeutic areas, and a strong cash position. InsMed is on a path to realize this bright future for the benefit of our patients and our shareholders.

Our global commercial franchise and infrastructure is already built we benefit from revenue generation from our marketed product we have to strategically overlapping pivotal stage programs with Brent sarcasm and Erik as frontline, we have a robust pipeline of focused research effort to generate impactful medicines in new therapeutic areas.

And a strong cash position <unk> is on a path to realize this bright future for the benefit of our patients and our shareholders.

Speaker 5: All of this is overseen by a world-class leadership team with an impressive track record of executing commercial clinical and regulatory pathways who will now review where we stand in greater detail.

All of this is overseen by a world class leadership team with an impressive track record of executing commercial clinical and regulatory pathways, who will now review, where we stand in greater detail.

Speaker 5: Let me start that process by turning the call over to Sarah to walk through our financial results.

Let me start that process by turning the call over to Sarah to walk through our financial results.

Speaker 6: Thank you, Will. Good morning everyone. A key priority for 2021 was maintaining financial strength and we need important strides on this front.

Thank you Bill good morning, everyone.

A key priority for 2021 with maintaining financial strength and we made important strides on this front.

Speaker 4: We bolstered our balance sheet and continue to benefit from the error case revenue stream while exercising physical discipline.

We bolstered our balance sheet and continued to benefit from the <unk> revenue stream.

First I think fiscal discipline.

Speaker 6: As a result, we are in a favorable position with balance sheet stress as we evaluate the many opportunities inherent in our existing portfolio.

As a result, we are.

We're in a favorable position with balance sheet strength as we evaluate the many opportunities inherent in our existing portfolio.

Speaker 6: Earlier today, we issued our detailed fourth quarter and full year financial results in a press release. All of those results are aligned with our internal expectations.

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

All of those results are in line with our internal expectation.

Speaker 4: Let me highlight a few of our full year results for you now.

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

Speaker 4: As reported this morning, we ended the year with $766.8 million in cash and cash equivalents and marketable securities.

As reported this morning, we ended the year with $768 million in cash and cash equivalents and marketable securities.

Speaker 6: We believe this cash position will support our ongoing business into 2024.

We believe this cash position will support our ongoing business into 2024.

Speaker 4: There are three main variables that impact our cash position. First, revenue from our marketed product. Second, how fully and broadly, as well as when we choose to pursue the progress in our development pipeline. And third, how we resource launch readiness for several of these substantial programs, including inventory bills. We will carefully consider these elements as we craft our plans forward. Now.

There are three main variables that impact our cash position.

Revenue from our marketed product.

How fully and properly as well as when we choose to pursue the progress in our development pipeline.

And third how we resource launch readiness for several of the substantial programs, including inventory now we.

We will carefully consider these elements and to craft our planned power.

Now turning to the financials.

Speaker 4: Total net revenue for Eric Hase was $188.5 million for the full year 2021.

Total net revenue for aerospace was $188 5 million.

The year 2021.

Speaker 6: As we look to each of our commercial regions, net revenue for 2021 was $159.5 million in the U.S., $16 million in Japan, and $12.9 million in Europe and the rest of the world.

As we look to each of our car Salt region net revenue for 2021, but the $159 5 million and EUR $16 million in Japan at $12 $9 billion in Europe and rest of world.

Speaker 6: Notably, our U.S. revenue number for the full year 2021 demonstrates steady performance of the AirTees franchise over the prior year despite the rise and fall in infection and hospitalization rates in the shifting COVID landscape.

Notably our U S revenue number for the full year 2021 demonstrates steady performance of the <unk> franchise over the prior year, despite the rise and fall in accident hospitalization rate and the shifting content landscape.

Speaker 4: We are encouraged by the overall improvement in the way in which people have adapted to the new realities presented by COVID around the globe.

We are encouraged by the overall improvement in the way in which people have adapted to the new reality presented vehicles around the globe.

Speaker 6: Consequently, these elements give us confidence that we will return to growth this year in all of the regions we are pursuing.

These elements give us confidence that we will return to growth. This year in all of February and hence we are pursuing.

Speaker 6: On a global basis, we anticipate seeing meaningful growth in Eric's revenue this year, and are prepared to forecast at least 30% revenue growth year over year for 2022.

On a global basis, we anticipate meaningful growth in aerospace revenue. This year and are prepared to forecast at least 30% revenue growth year over year for 2022.

Speaker 4: Our growth in the US for the full year 2021 were approximately 13.2%.

Our gross to net you asked for the full year 2021 for approximately 13, 2%.

Speaker 6: Looking ahead at 2022, we anticipate growth to next in the US to be in the mid-teens consistent with our estimates from prior years.

Looking ahead at 2022, we anticipate price to act in the U S to be in the mid teens consistent with our estimates from prior years.

Speaker 4: Recall that in the U.S., the first quarter is typically the toughest due to the deductible and copay recess for our Medicare patients that occur at the beginning of the year, resulting in the donut hole effect.

Recall that in the U S. The first quarter is typically the top of the deductible and co pay resets for Medicare patients that occur at the beginning of the year, resulting in the donut hole effect.

Speaker 4: As a result, we expect to see a similar trend to what we have historically experienced from fourth quarter to first quarter revenue level.

As a result, we expect to see a similar trend to what we have historically experienced from fourth quarter to first quarter revenue levels.

Speaker 4: Cost of product revenues for the full year 2021 was $44.2 million, or 23% of revenue.

Cost of product revenues for the full year, 2021, with $44 2 million or 23% of revenue.

Speaker 4: This is consistent on a percentage basis with the cost of product revenues in the full year of 2020.

This is consistent on a percentage basis.

The product revenues and our full year 2020.

Turning to our GAAP operating expenses.

Speaker 4: For the full year 2021, research and development expenses were $272.7 million and SDNA expenses were $234.3 million.

For the full year 2021 research and development expenses were $272 7 million and SG&A expenses were $234 $3 million.

Speaker 4: In closing, Intimate has entered 2022 in a very strong capital position as we support the four pillars of our business.

In closing <unk> has entered 2022 and a very strong capital position as we support our four pillars of our business.

Speaker 4: We intend to be responsible stewards of cash, with the foresight to invest now to unlock the potential for candidates that may represent real improvements in healthcare for patients.

We intend to be responsible stewards of cash with the foresight to invest now to unlock the potential for candidates that may represent real improvements in health care for patients.

Speaker 4: I'll now turn the call over to Martina for an update on our clinical development pipeline. Martina? Thank you, Sarah.

I'll now turn the call over to Martina for an update on our clinical development pipeline Martina.

Thank you Sarah and good morning, everyone Glenn too.

Speaker 4: 2021 marks another transformational year for INTIMED with respect to our clinical trial work. Today, I'm excited to be able to share important updates around several of our programs in development.

2021, Mark another transformational year for Internet with respect to our clinical trial work to do.

And excited to be able to share important updates around several of our programs in development.

Speaker 4: Let's begin with Brents or captain, our GCP1 inhibitor, targeting neutrophil mediated disease.

At the beginning of expensive cabinet GBP, one inhibitor IGT neutrophil mediated diseases.

Speaker 6: I'm pleased to report that our phase three absence study for the potential treatment of bronchiectasis is now 50% enrolled. And we anticipate enrollment to be complete at approximately this time next year.

I'm pleased to report that our phase III study for the potential treatment of Bronchiectasis is now 50% enrolled and.

And we anticipate enrollment to be complete at approximately this time next year.

Speaker 4: Let me remind you that this trial is expected to enroll more than 1,600 patients at more than 400 clinical sites around the world.

Let me remind you that this trial is expected to enroll more than 600 patients at more than 400 clinical sites around the world.

Speaker 4: If there is one takeaway I can leave you with, it is this. For Aspen to be halfway enrolled in just one year is an extraordinary achievement. And we believe this milestone demonstrates significant enthusiasm for the potential of friends of global navigating.

If there is one takeaway I can leave you with.

It is Steve.

And to be halfway enrolled in just one year is an extraordinary achievement and we believe this milestone demonstrates significant enthusiasm for the potential of <unk> per cabinet for bronchiectasis patients.

Speaker 6: We are grateful to our investigators and to patients who have dedicated their time to this program at a very challenging time in respiratory medicine.

We are grateful to our investigators and to patients who have dedicated their time to this program in a very challenging time in respiratory medicine.

Speaker 4: I'm also pleased to share that the first meeting of the Data and Safety Monitoring Board, or DSMB, took place at the end of last year, where it was recommended that the Aspen trial continue at length.

And also please to share at the first meeting of the data and safety monitoring board like SMB took place at the end of last year.

Both recommended that Yadkin trials continue and plan.

Speaker 6: Recall that bronchiectasis is a globally prevalent disease with no approved treatment and with over a million patients diagnosed worldwide. This represents an enormous opportunity.

Recall that funky emphasis is a globally prevalent disease with no approved treatment and we.

With over a million patients diagnosed worldwide.

This represents an enormous opportunity for outcome.

Speaker 6: Furthermore, we believe COPD and asthma patients who may have undiagnosed bronchiectasis present additional market opportunities given the comorbidity of these indications.

Furthermore, we believe COPD and asthma patients, who may have undiagnosed bronchiectasis prevent additional market opportunities given the comorbidity of 15.

Indications.

Speaker 6: Let's now turn to the next area of Brents-O'Catholic development in 55 Road.

Let's now turn to the next area have been surpassed the development and cystic fibrosis.

Speaker 6: We are on track to release results this year or early 2023 from the SACE2-TKPD study, which will be instructive as to the appropriate dosing strength for CF patients.

We are on track to release results this year or early 2023, and the phase III PK, PD study, which will be instructive as to the appropriate dosing strength, our CF patients.

Speaker 4: The trial is a single-blind assessment of one daily brenthocastis at 10, 25 and 40 milligrams versus placebo in 36 patients with TS.

The trial is a single brand sentiment of once daily brands surpass it.

10, 25 and 41 Glenn.

<unk> placebo and 36 patients with Fcs.

Speaker 6: Treatment duration is 28 days and we will evaluate PT and safety data as well as reduction of NSD levels in sputum and blood along with other exploratory spirometry measurements such as MPD1.

Treatment duration is 28 days, and we will evaluate PK and safety data as well as reduction of and Delever Studeman blood.

Along with other exploratory spirometry measurements, such as SD Wan.

Speaker 6: Following a review of safety and PK data, there is optionality to go to a 65 milligram dose, which may be warranted. Even CF patients often have different metabolic profiles for picking out CF patients.

Following a review of safety and PK data there is optionality to go to a 65 milligram dose.

Which may be warranted, given CF patients often have different metabolic profile.

Looking out in CF patients.

Speaker 6: All toxicology work to support higher dose levels has been completed.

Our toxicology work to support higher dose level has been completed.

Speaker 4: The tremendous success of our phase two rural study highlighted the efficacy of DPP-1 inhibition in treating bronchiectatic patients and suggest its potential role in treating CF patients.

The tremendous success of our phase II will.

Highlighting the efficacy of CPP, one condition and treating project added patient and its.

Its potential role in treating CF patients.

Speaker 6: In addition, what excites us is the pathway of DPP1 inhibition for the treatment of many neutral mediated diseases. And we have been doing significant work to explore how our compound may benefit patients and other diseases.

In addition, what excites US is the pathway LTE PD, one inhibition for the treatment of main neutrophil mediated diseases.

And we have been doing significant work to explore.

<unk> may benefit patients in other disease areas.

Speaker 6: I'm excited to share with you today that we are moving prandtl-cafes into two new potential indications, chronic rhinosinusitis without native polyps, or CRS, and hydrodynamic superotiever, or HS.

I'm excited to share with you today.

Panther captain into two new potential indications.

Chronic rhinosinusitis without nasal polyps, where CRM and hydride tinnitus severity book or agent.

Speaker 4: These indications are an exciting new chapter in brain-to-pathic development, echoed by the enthusiasm from the deep bench of experts within the Internet who have experience in these disease states.

These indications are an exciting new chapter in <unk> development.

Put by the enthusiasm from the deep bench of experts within intimate with it.

<unk> in these disease states.

Speaker 6: We see clear scientific rationale supporting the potential role of francotaphic in pursuing this indication.

We see clear scientific rationale supporting the potential role of <unk> in pursuing this indication.

Speaker 6: as we are targeting the neutrophilic activity in the inflammatory pathway of disease.

We are targeting the neutrophil like activity in the inflammatory pathway.

Speaker 6: We believe that DPP1 inhibition, leading to a reduction of NLP levels, may be able to interrupt the inflammatory components of these diseases.

We believe the DPP, one inhibition, leading to a reduction of NLP level may be able to interrupt the inflammatory component of disease.

Yeah.

Speaker 6: First, it's important to distinguish CRS without nasal polyp, which we are targeting, from CRS with nasal polyp.

Further it's important to distinguish crs without nasal polyps, which we are targeting from Crs with nasal polyps.

Speaker 6: Both can be severe diseases, but with CRS without polyps, we generally see more neutrophil recruitment in the inflammatory process, aligning with the mechanism of action demonstrated by Brent's attack.

Both can be severe diseases.

Crs this I'll call. It we generally see one or two further recruitment anti inflammatory process aligning.

Aligning with the mechanism of action demonstrated by price effect.

Speaker 4: There are currently no approved therapies for patients with CRS without natapollin, which is the most common type of rhinosymocytosis.

There are currently no approved therapies for patients with Prs without nasal polyps, which is the most common type of rhinosinusitis.

Speaker 6: TRS without natural polyps is characterized by chronic inflammation and fibrosis of the mucous membranes in cytosine.

Crs without nasal polyps is characterized by chronic inflammation and fibrosis of the mucous membrane and fact that finances.

Speaker 6: The most common symptoms include nasal obstruction, decreased sense of smell, and facial pain.

The most common symptom include a nasal obstruction decreased sense of smell and facial pain.

Speaker 6: Patients with ERS also report lower quality of life measures, impacting bodily pain, general health, physical and social functioning, and the diseases associated with increased rates of depression.

Patients with Crs also report lower quality of life measures impacting bodily pain general health physical and social functioning and the disease is associated with increased rates of depression.

Speaker 4: Currently, the only available treatment options for patients with TRS without polyps are corticosteroids, antibiotics, or endoscopic procedures.

Currently the only available treatment options for patients with Crs without polyps are corticosteroids antibiotics or endoscopic procedures.

Speaker 6: These endoscopic surgeries may have to be repeated. We are targeting patients at the severe end of the disease spectrum for whom surgery does not work.

Endoscopic surgery, he has to be repeated.

We are targeting patient at the severe end of the FCC spectrum for whom surgery does not work.

Speaker 6: all of these signals that we need an urgent need for a safe oral therapy for these patients.

All of the signals that we need an urgent need for a safe oral therapy for these patients.

Let's now turn to <unk>.

Speaker 6: HS is a chronic inflammatory skin disorder characterized by painful, inflamed, and swollen lesions affecting hair follicles, causing the armpits groin and skin folds.

<unk> is a chronic inflammatory skin disorder characterized by painful inflamed and swollen lesions affecting hair follicle.

It's growing in Skinful.

Speaker 6: The clinical course is variable, ranging from relatively mild disease, characterized by the recurrent appearance of inflamed lesions and nodules, to severe cases with deep abscesses, drained fistulas and severe scars.

The clinical course of variable ranging from relatively mild disease characterized by the recurrent appearance of inflamed lesions in module two severe cases.

Abscesses draining fistulas Entyvio scars.

Speaker 6: Patients' reported quality of life measures indicate a high psychosocial impact from the disease with increased rates of anxiety and depression.

Patient reported quality of life measures indicate a high psychosocial impact from the disease with increased rates of anxiety and depression.

Speaker 4: We are targeting the moderate to severe end of the disease spectrum. There's only one approved therapy for HS, which doesn't work for all patients. And given the complexity of the disease, patients can require multiple treatments and sometimes surgery to maintain control of the disease.

We are targeting the moderate to severe end of the disease spectrum.

There's only one approved therapy for inkjet, which does not work for all patients.

And given the complexity of the disease patients can require multiple treatment and sometimes surgery to maintain control of the disease.

Speaker 4: we have seen enthusiasm among healthcare professionals for investigational therapies to help identify new effective treatment options for both HS and CRS.

We have seen enthusiasm among health care professionals.

Vacation on therapy to help identify new effective treatment option for both HSN and TRA.

Let me take a moment to walk through the study design.

Speaker 6: Our current plan is to move CRS into the clinic in a phase two study over a 24-state treatment period, exploring Trenso-passive at 10 and 40 milligrams versus placebo.

Our current plan is to move into the clinic in a phase II study over a 24 week treatment period.

Flooring plant capacity of 10, and 40 milligram versus placebo.

Speaker 4: followed by four weeks off therapy with the primary endpoints of change in an established measure of total symptoms for

Followed by four weeks of therapy with a primary endpoint of change in an established measure of total symptom score.

Let's now turn to the trial design in <unk> we.

Speaker 6: We anticipate that our phase two trial in HS will span a 16 week treatment period exploring 10 and 40 milligram of brenzocastis versus placebo, followed by a 36 week open label extension period.

We anticipate that our phase II trial in Hs will span a 16 week treatment period, exploring 10, and 40 milligram of <unk> versus placebo.

Led by a 36 week open label extension period.

Speaker 4: The primary endpoint will be percentage of subjects achieving hydroadenitis superativa clinical response at week 16.

Primary endpoint will be percentage of subjects, achieving hydro at night is Super Akiva clinical response at week 16.

Speaker 4: All of this aligns with our broader strategy of building a portfolio around the DPP-1 inhibition pathway to target neutrophil-mediated diseases.

All of this aligns with our broader strategy of building a portfolio around the GBP one inhibition pathway.

Tiger neutrophil mediated diseases.

Speaker 6: We anticipate advancing one of these new indications into the clinic this year. And we will have more to say about our overall progress with Brents and Pat, with all indications, in the next few quarters.

We anticipate advancing one of these indications into the clinic this year.

And we will have more to see about our overall progress with Banco Cat I think all indications in the next few quarters.

Speaker 4: Let's now turn to the Arricades Frontline Program.

Let's now turn to the arcade frontline program.

Speaker 4: I am excited to report that the ARISE study is now 50% enrolled. And we anticipate reaching enrollment completion this year with top line data from ARISE in the first half of 2023. We also anticipate Encore to be fully enrolled in 2020.

I am excited to report that the arrive study is now 50% enrolled and we anticipate reaching enrollment completion. This year with top line data from a rise in the first half of 2023.

Also anticipate encore to be fully enrolled in 2023.

Speaker 4: As a reminder, data summarized will inform and allow us to finalize the PRO utilized in GYEONG for trial.

As a reminder, data from whereby we will inform and allow us to finalize the PMO utilized in Jan per trial.

Speaker 6: These timelines are consistent with what we have seen in our previous NTM trial, reaffirming that enrollment of NTM trials typically proceeds at a slow pace.

These timelines are consistent with what we have seen in our previous MTN trial.

Reaffirming that enrollment of MTM trial typically proceed at a slow pace.

Speaker 6: As was the case in our previous trials, positive student cultures are not always present at the time of patient screening, and it is not surprising to see screen failure rates for past 40 percent.

As was the case in our previous trial.

The sputum culture, and not always present at the time of patient screening and it is not surprising to see screen failure rates surpassed 40%.

Speaker 4: Recall that ARISE is preferentially enrolled over ENCQOR with a randomization of 2 to 1, and once ARISE is fully enrolled, we anticipate enrollment in the ENCQOR study to accelerate.

Recall that Orion preferentially enroll over encore with a randomization of two to one and once arrived is fully enrolled we anticipate enrollment in your study to accelerate.

Speaker 4: As additional study sites come online, we also anticipate this will help drive enrollment momentum in all.

As additional study sites come online. We also anticipate this will help site enrollment momentum in Hong Kong.

Speaker 6: In addition, Oncor is a more attractive study from a patient recruitment perspective because it provides an uninterrupted treatment cycle allowing patients to stay on therapy for a full 12 months versus six months for a ride.

In addition, all creates a more attractive study from a patient recruitment perspective, because it provides an uninterrupted treatment cycle, allowing patients to stay on therapy for a full 12 months versus six months right.

Speaker 4: This is a relevant factor for patients and physicians as they evaluate their participation in these clinical trials.

This is a relevant factor for patients and physicians.

How do we get participation in these clinical trials.

Speaker 6: We look forward to maintaining our enrollment momentum in both of these studies and will update you on our progress.

We look forward to maintaining our enrollment momentum in both of these studies and we'll update you on our progress.

I'll now turn to GPA.

Speaker 4: CPIP is our troposinol prodrug and safe through development for both PAH and THILD.

<unk> is our to cross the note pro drugs in phase III development for both CAH and ph ILD.

Speaker 6: This is an exciting opportunity as we believe that our compounds could envelope the full potential of the prostonoid pathway to benefit patients with certain rare pulmonary disorders.

This is an exciting opportunity and we believe that our compounds could unlock the full potential of the <unk> pathway to benefit patients with certain rare pulmonary disorder.

Speaker 6: Let me take a moment to walk you through our phase two trial defense.

Let me take a moment to walk you through our phase II trial design.

Speaker 4: The first study to discuss is the randomized double-blind placebo-controlled phase 2B study that will assess the efficacy, safety, and PK of TPIP in patients with PAH over a 16-week treatment period.

But first I need to discuss is the randomized double blind placebo controlled phase <unk> study will assess the efficacy safety and PK of <unk> in patients with ph or a 16 week treatment period.

Speaker 6: Target enrollment in this study is approximately 100 patients.

Target enrollment in this study is approximately 100 patients.

Speaker 6: Patients will be dosed once daily, and each patient will be up-citrated to his or her individual maximum tolerated dose.

Patients will be dosed once daily and each patient will be up titrated to his or her individual maximum tolerated dose.

Speaker 6: The primary measure is the change from baseline in pulmonary vascular resistance, or PDR, at week 60. And the key secondary measure will evaluate the impact of CPIP on six-minute walk distance at various times.

The primary measure is the change from baseline in pulmonary vascular resistance or PDR.

<unk> 16, and the key secondary measure will evaluate the impact of Tpa P. M six minute walk distance.

There is time point.

Speaker 6: as planned site initiation for the Phase IIb trial in PAH patients began late last year. We will update you on enrollment progress in the coming quarter.

As planned site initiation for the phase III trial in ph patients began late last year.

We'll update you on our relevant progress in the coming quarters.

Speaker 6: The second study to discuss is the randomized double-blind placebo-controlled phase 2 trial in PHIL.

The second study to discuss is the randomized double blind placebo controlled phase II trial in ph, ILD, which will assess the safety and tolerability of <unk> IP over 16 weeks.

Speaker 4: which will assess the safety and tolerability of TTIP over 16 weeks. Target enrollment.

Enrollment is 32 patients.

Speaker 4: As with the study in PAH, patients will be dosed once daily and each patient will be up titrated to his or her maximum tolerated dose.

As with the study and ph patients will be dosed once daily and each patient will be up titrated to hit maximum tolerated dose.

Speaker 4: Other key endpoints will include TPIP's decay profile, as well as various exploratory efficacy measures, including effects on 6 minute water.

Other key endpoints will include TPI PK profile as well as the various exploratory efficacy measures, including effects on six minute walk distance.

Speaker 4: We think TPIB may be well positioned for this indication by the way of inhaled droughts of administration which delivers basic dilation to the ventilated areas of the lung.

We think <unk> may be well positioned for this indication by the way of inhaled route of administration, which delivered Peyton dilation through the ventilated areas of the month.

Speaker 4: Systemically administered therapies, on the other hand, can lead to vasodilatation in the areas of the lung that due to fibrosis are not ventilated, leading to a ventilation for fusing mismatch.

Systemically administered therapies on the other hand can lead to visit the donation in the areas of demand due to fibrosis and up until eight.

Leading to a ventilation perfusion mismatch.

Speaker 4: The TPIP route of delivery is intended to mitigate this problem with a potentially more favorable side effect profile, as well as longer lung residency time versus inhaled salivation.

The GPS route of delivery is intended to mitigate this problem with a potentially more favorable side effect profile as well as lower lung residency time versus the peso.

Speaker 4: Site initiation for the phase two trial in PHILD patients.

Thank you Ashish and for the Phase II trial in ph ILD patients.

It's $2, a 24 hour right part.

Even in <unk> patients.

Speaker 4: And we're hopeful that with Omicron receding, we will be successful in identifying volunteers and advancing enrollment.

And we're hopeful that with Amazon. This evening, we will be successful in identifying volunteered and advancing enrollment.

Speaker 4: While this study is not rate-limiting to the other Phase 2 trials we have discussed, we are excited by the potential the results could suggest for our TTIP program.

While the study is not rate limiting to the other phase II trials, we have discussed.

We are excited by the potential of the results could suggest.

The IP program.

Speaker 4: from patients in this study as we collect data over the course of the talk, we pretty much would that be it.

Results from patients in this study as we collect data over the course of select clothes are recognizing that.

Speaker 6: significant and flowing excitement behind our fourth pillar, translational medicine.

A significant and growing excitement behind our fourth pillar translational medicine.

Speaker 4: This pillar is led by multiple teams and contains several exciting technology programs running in parallel, some of which are complementary to one another and others that are standalone therapies targeting different and unrelated conditions.

This pillar is led by multiple teams and contained several exciting now I'll, let you program running in parallel some of which are complementary to one another and others that are standalone therapy targeting different an unrelated condition.

Speaker 4: We envision that some programs within these four pillars may act as a platform capability, for example, the potential de-immunization of capsids in chemotherapy.

We envision that some programs within these four pillar May act as a platform capabilities for example, the potential dehumanization of capsid and gene therapy.

Speaker 4: we anticipate that translational medicine will serve as the IMD engine for intimate future, thereby addressing the question of what may follow the anticipated success of our first three pillars.

We anticipate a transformational medicine will sort of AMB engine for Internet future yes.

Addressing the question of what May fall at the anticipated success of our first three pillars.

Speaker 4: We hope to make significant progress from this effort in 2022, culminating in the filing of an IND in a new non-pulmonary indication by the end of the year.

We hope to make significant progress from this effort in 2022, culminating in the filing of an eye AMD, new non pulmonary indication by the end of the year.

Speaker 6: In parallel to this program, there are several other components of our fourth pillar, and we envision a detailed research date in the second half of this year, at which time we anticipate sharing preclinical data.

In parallel to this program there are several other components of our fourth pillar and we envision a detailed three such date.

Half of this year at which time, we anticipate sharing preclinical data.

Speaker 4: While this represents an important pillar for our future, I continue to work closely with Sarah to ensure capital allocation for each area remains measured and is deployed only with successful data along the way.

While this represents an important pillar for our future I continue to work closely with Sarah to ensure capital allocations to east areas remains nation, and it's deployed only with successful data along the way.

Speaker 6: In summary, InSmit realized several major clinical achievements over the past year. 2022 is poised to be a critical year of execution across our clinical operations, and we look forward to delivering on the catalyst with offline today.

In summary, infamous realized several major clinical achievements over the past year.

2022 is poised to be a critical year of execution across our clinical operation and we look forward to delivering on the catalysts we've outlined today.

Speaker 6: With that, let me turn the call over to Roger to discuss some key operational updates. Roger?

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

Speaker 5: Thank you, Martina. Good morning, everyone. From an operational standpoint, there are two main areas I want to focus on today.

Thank you Martina and good morning, everyone.

From an operational standpoint, there are two main areas I would focus on today.

Speaker 5: I'll start with a commercial operation surrounding our first pillar, barricades.

Start with the commercial operations surrounding our first pillar Eric Capes.

Speaker 5: From there, I'll turn to the expansion of our second pillar, Frenzocatib, and the additional clinical indications we've decided to target.

From there I'll turn to the expansion of our second pillar <unk> and the additional clinical indications, we have decided to target.

Speaker 5: For our case franchise, Intimate's commercial operations continue to perform extremely well over the course of 2021. Last year ushered in a new era for our case, which is now long.

For aerospace franchise intimate commercial operations continued to perform extremely well over the course of 2021.

Best year ushered in a new era for aggregates, which is now launched in the U S Europe and Japan.

Speaker 5: I'd like to take a moment to walk you through our recent progress in each of these regions.

I'd like to take a moment to walk you through our recent progress in each of these regions.

Let's begin with the U S.

Speaker 5: The arcade franchise has remained resilient throughout the ongoing pandemic, underscored by a solid fourth quarter performance, despite the arrival of the Umkhran surges that rapidly swept the country.

The arcades franchise has remained resilient throughout the ongoing pandemic.

Scored by a solid fourth quarter performance. Despite the arrival of the Hong Kong.

Surges this rapidly swept the country beginning late last year.

Speaker 5: We continue to see regional variability across the U.S. in some areas more impacted by COVID than others.

We continue to see regional variability across the U S, but some areas more impacted by COVID-19 than others.

Speaker 5: In particular, we have noted the impact of Omicron on the availability of workers in the medical setting. And we are all keenly aware of the pressure on healthcare professionals, particularly pulmonologists, infectious disease doctors, and respiratory therapists.

In particular, we have noted the impact of <unk> on the availability of workers in the medical setting.

All keenly aware of the pressure on healthcare professionals, particularly pulmonologist infectious disease doctors and respiratory therapists.

Speaker 5: However, despite these challenges, we believe we have the resources to achieve growth as our therapeutic specialists continue to have positive interactions with physicians treating refractory NTM patients.

However, despite these challenges we believe we have the resources to achieve growth as our therapeutic specialists continue to have positive interactions with physicians treating refractory MTM patients.

Speaker 5: Although COVID has impacted physicians' ability to see NTM patients, we also believe that the pandemic has brought to light a larger focus on pulmonary disease, and potentially a higher index of suspicion for refractory NTM.

Although COVID-19 has impacted physician's ability to see MTM patients. We also believe that the pandemic has brought to light a larger focus on pulmonary disease and potentially a higher index of suspicion for refractory angina.

Speaker 5: These factors combined with our ability to adapt to the new circumstances of COVID create potential for growth in the US and our international markets.

These factors combined with our ability to adapt to the new circumstances of Covid create potential for growth in the U S and our international markets.

Let's drill down into our ex U S commercial efforts.

Speaker 5: beginning with Japan, where we are extremely pleased with the launch progress thus far.

Beginning with Japan.

Are extremely pleased with the launch progress thus far.

Speaker 5: As a reminder, the launch of Japan began in July of last year.

As a reminder, the largest Japan began in July of last year.

We believe that the opportunity.

Speaker 5: This market is significant, and that in terms of revenue, Japan will be the second largest market for aricase after the U.S.

This market is significant.

In terms of revenue to pay will be the second largest market for aerospace after the U S.

Speaker 5: Recall that for the first year of market availability in Japan, all drugs are restricted to a two-week dispensing limit.

Recall that for the first year bucket availability in Japan, all drugs are restricted to a two week dispensing limit.

Speaker 5: Practically, this requires the patient to return to their physician's office every two weeks to receive their prescription.

Practically this requires the patient to returns in a physician's office every two weeks to receive their prescription.

Speaker 5: This two-week restriction also impacts affordability for patients.

This two week restrictions also impacts affordability for patients.

Speaker 5: Monthly patient co-pays are capped in Japan. So under the current restriction, a patient would receive a maximum of one month's supply for their co-payment.

Must be patient co pays are capped in Japan.

So under the current restriction a patient would receive a maximum of one month supply for their copayments.

Speaker 5: Once this restriction is lifted in June , patients will be able to receive up to three months of Arachates for the same co-payment.

Once this restriction is lifted in June patients will be able to receive up to three months of <unk> for the same copayments.

Speaker 5: In addition, the Japanese Society for Tuberculosis and Non-Tuberculosis Microbacterium published guidelines on the appropriate use of our case, recommending usage for patients who do not achieve culture conversion with a multithreat regimen over six months.

In addition, the Japanese society for tuberculosis, and non superb dulosis micro bacterium published guidelines on the appropriate use of our case.

<unk> usage for patients, who do not achieve culture conversion with a multi drug regimen over six months.

Speaker 5: The guidelines also offer advice on managing adverse events.

The guidelines also offer advice on managing adverse events.

Speaker 5: We see this as a positive development that may help physicians better understand the key considerations as they think about prescribing Arachate to their patients and managing the side effect profile.

We see this as a positive development as it may help physicians better understand the key considerations as they think about prescribing <unk> to their patients and managing the side effect profile.

Speaker 5: We are extremely excited about the opportunity in Japan and look forward to updating you on our progress.

We are extremely excited about the opportunity in Japan and look forward to updating you on our progress.

I'll now turn to Europe .

Speaker 5: We anticipate the addressable market is smaller than those in the U.S. and Japan. However, we have made excellent progress with positions. As reimbursement occurs in additional countries, we anticipate Europe will be a meaningful revenue contributor to the overall franchise.

We anticipate the addressable market is smaller than those in the U S and Japan.

However, we have made excellent progress with physicians as reimbursement occurs in additional countries, we anticipate Europe will be a meaningful revenue contributor to the overall franchise.

Speaker 5: As we work to drive growth in this market, we continue to believe that the literature estimation of 1,400 diagnosed refractory MAC patients in Europe may be understated.

As we work to drive growth in this market. We continue to believe that the literature estimation of 1400 diagnosed refractory Mac patients in Europe may be understated.

Speaker 5: Our case is currently available under a free pricing program in Germany, and the price is renegotiated after the first year on the market.

Our cases currently available under our free pricing program in Germany, and the prices renegotiated after the first year on the market.

Speaker 5: We await a final pricing decision in Germany in the first half of this year.

We await a final question decision in Germany in the first half of this year.

Speaker 5: With the product also available and reimbursed in the Netherlands, Wales and Scotland, we now turn our attention to England, France and Italy, as we await reimbursement decisions from those territories throughout this year.

For the product is also available and reimbursed in the Netherlands Wales, Scotland.

We now turn our attention to England, France and Italy.

As we await reimbursement decisions from those territories throughout this year.

Speaker 5: We have confidence in the future growth from each of our three regions where our case is available.

We have confidence in the future growth from each of our three regions, where <unk> is available.

Speaker 5: As we continue to learn about and adapt to the realities of COVID, we believe we have the resources for our commercial operations to succeed in this challenging environment.

As we continue to learn about and adapt to the realities of Covid. We believe we have the resources for our commercial operations to succeed in this challenging environment.

Speaker 5: I'd like to now turn to our second pillar, Friends of Gazip, and the market opportunity in our newly announced indications, CRS and HS.

I'd like to bounce her to our second pillar Pretzel catchup.

Our market opportunity and our newly announced indications Crs NHS.

Speaker 5: CRS without nasopalps represents a significant opportunity.

Crs without nasal polyps represents a significant opportunity.

Speaker 5: There are approximately 33 million patients diagnosed with CRS in the U.S.

There are approximately 33 million patients diagnosed with Crs in the U S.

Speaker 5: Of those patients, approximately 26 million patients have CRS without nasal polyp.

Of those patients approximately 26 million patients have crs without nasal polyps.

Speaker 5: We are targeting the severe end of the disease spectrum, which represents a smaller, though still substantial portion of the overall CRS without nasal pumps marked.

We are targeting the severe end of the disease spectrum.

Which represents a smaller though still substantial portion of the overall crs without nasal polyps market.

Speaker 5: We believe a good proxy for severe disease are those patients who require surgical intervention.

We believe a good proxy for severe disease are those patients who require surgical intervention.

Speaker 5: Each year in the US, approximately 155,000 patients undergo surgery for CRS without nystoplasty.

Each year in the U S. Approximately 155000 patients undergo surgery for Crs without nasal polyps.

Speaker 5: Of those, approximately 15% or 23,000 patients require revision or repeat surgery.

Those approximately 15% or 23000 patients require a revision or repeat surgery.

Speaker 5: We consider those patients undergoing repeat surgical intervention to be most severe.

We consider those patients undergoing repeat surgical intervention to be most severe.

Speaker 5: To be clear, these are annual incidence numbers, and pending supported clinical data, we expect these patients to take brenzocatib chronically.

To be clear these are annual incidence numbers and pending supportive clinical data. We expect these patients to take Bristow Curt it chronically.

Speaker 5: As Martina mentioned, there are currently no approved treatments for this indication.

As Martina mentioned there are currently no approved treatments for this indication.

Speaker 5: If we are able to demonstrate clinically meaningful impact on this disease, we believe physicians may be inclined to try a well-tolerated effective therapy prior to recommending either initial or repeat surgery.

If we are able to demonstrate clinically meaningful impact on this disease. We believe physicians may be inclined to try a well tolerated effective therapy prior to recommending either initial or repeat surgery.

Speaker 5: We believe patients may also prefer a well-tolerated effective oral medication to a surgical intervention.

We believe patients. They also prefer a well tolerated effective oral medication to surgical intervention.

Speaker 5: With HS, we estimate there are approximately 300,000 patients in the U.S.

With Hs, we estimate there are approximately 300000 patients in the U S.

Speaker 5: Approximately one third of these patients, or about 100,000, have moderate to severe disease. We will be targeting the more severe patient group.

Approximately one third of these patients or about 100000.

<unk> to severe disease.

We will be targeting the more severe patient group with pretzel catch it.

Speaker 5: Chimera is currently the only approved treatment for HHS patients, and we believe that Brento-Cativ, a well-tolerated oral therapy with an attractive safety profile, will be a welcome addition to the treatment armamentary. We anticipate Brento-Cativ

<unk> is currently the only approved treatment for Hs patients. We believe the pretzel catches a well tolerated oral therapy with an attractive safety profile will be a welcome addition to the treatment armamentarium.

We anticipate rental catheter launching bronchiectasis first.

Speaker 5: We believe this indication may support attractive pricing if we are able to show clinically meaningful impact on this disease.

We believe this indication based support attractive pricing, if we are able to show clinically meaningful impact on this disease.

Speaker 5: As we selected additional diseases to target, we wanted to ensure that the pricing was sustainable, assuming we are also able to show clinically meaningful results.

As we collected an additional diseases to target we wanted to ensure that our pricing was sustainable.

Assuming we are also able to show clinically meaningful results.

Speaker 5: We believe the presence of improved biologics in both severe CRS with nasal polyps and HS validates the potential of these disease states to support strong pricing as well.

We believe the presence of approved biologics in both severe crs with nasal polyps and Hs.

The potential of these disease states to support strong pricing as well.

Speaker 5: When we take a step back and look at the overall picture of our Brenzocat targeted indications, both the ectasis, cystic fibrosis, CRS, and HS, we see a pathway to what we believe is a very sizable market opportunity.

When we take a step back and look at the overall picture of our friends look at its targeted indications, but the emphasis cystic fibrosis Crs NHS, we see a pathway to what we believe is a very sizable market opportunity.

Speaker 5: In summary, the operational outlook at InSmed is strong, and I'm proud of the team that has helped us execute on our milestones during a productive 2021.

In summary, the operational outlook and it's been strong I am proud of the team that has helped us execute on our milestones during a productive 2021.

Speaker 5: I look forward to what I believe will be another transformational year for the company.

I look forward to what I believe will be another transformational year for the company.

Speaker 5: I'll now turn the call back to Will. Thank you, Roger. I'd like to close out my remarks by emphasizing Instamed's position of strength, backed by a seasoned leadership team, a reliable and growing commercial franchise, a diverse pipeline of early- to late-stage assets, and a solid cash position. We have the elements we need to advance this company to the next level of growth.

Now I'll turn the call back to will thank.

Thank you Roger.

I'd like to close out my remarks by.

By emphasizing instruments position of strength backed by a seasoned leadership team a reliable and growing commercial franchise a diverse pipeline of early to late stage assets and a solid cash position. We have the elements we need to advance this company to the next level of growth.

Speaker 5: I believe Incemed can reach our goal of becoming one of the next great biotechnology companies. We will work to execute against the objectives we have laid out for you today for the benefit of our patients and our shareholders.

We've implemented to reach our goal of becoming more the next great biotechnology companies, we will work to execute against the objectives. We have laid out for you today for the benefit of our patients and our shareholders.

Speaker 5: I'd like to acknowledge the hard work from the entire INSMED team. And I would like to extend my gratitude to the patients and caregivers who participate in our clinical studies. And with that, I'd like to open the call to questions. Operator, can we take the first question, please?

I'd like to acknowledge the hard work from the entire inspect team and I would like to extend my gratitude to the patients and caregivers who participated in our clinical studies and with that I'd like to open the call to questions. Operator can we take the first question. Please.

Speaker 3: Of course, if you would like to ask a question, please press star followed by 1 on your telephone keypad now. If you change your mind, please press star followed by number 2. Please limit yourself to questions per person so we have a chance to get around everyone. If you have any follow-up questions, you can join the queue again. When preparing to ask a question, please ensure your phone is unmuted locally.

Of course, if you would like to ask a question. Please press the star followed by one on your telephone keypad now if you turn your mind. Please press the star followed by number two please.

Please limit yourself to questions per person. So we have a chance to get everyone. If you any follow up questions. You can join the queue again when preparing to ask a question. Please ensure your phone is on mute locally.

Speaker 3: And the first question comes from Jessica Fai from GP Morgan. Please Jessica, your line is now open.

And the first question comes from Jessica Fye from Jpmorgan. Please Jessica your line is now open.

Speaker 7: Hey, guys. Good morning. Thanks for all the updates and for taking my question. For the 22 revenue guidance pointing to sales of at least $245 million for error case this year, I know you talked about growth in all regions, but can you help us think about the contribution from each geography that underpins that floor and maybe talk about the extent to which this might be conservative or how much conservatism you kind of reflect in that number? Thank you.

Hey, guys. Good morning, Thanks for all the updates and for taking my question.

Or the 22 revenue guidance pointing to sales of at least $245 million for Hurricane. This year I know you talked about growth in all regions, but can you help us think about the contribution from each geography that underpins that floor.

And maybe talk about the extent to which this might be conservative or how much conservatism you kind of reflecting that number. Thank you.

Speaker 5: Yeah, sure, appreciate that question. Look, I think we've all experienced the uncertainty that surround the pandemic's ebb and flow. What we tried to do with this forecast was to put out there a number that we feel very good about in terms of its defensibility, despite whatever may happen in the pandemic market. So I think there are some things that we can do to help the economy. And I think that's a really important part of the process.

Yeah sure I appreciate that.

Look I think we've all experienced.

<unk> the uncertainties that surround the pandemics ebb and flow what we've tried to do with this forecast was to put out there a number that we feel very good about in terms of its defensibility, despite whatever may happen in the.

Pandemic market so.

I think they are.

Speaker 5: Certainly the first quarter, as you know, is always the most challenging for.

Certainly the first quarter as you know is always the most challenging for.

The rare disease products, but.

Speaker 5: a positive year across the board? I don't know, Sarah, if you want to add anything to that. Yeah, no, thanks, Josh, for the question. Maybe just a couple other things to add. We're obviously very encouraged and excited to be able to share at least a 30% growth. That's obviously a meaningful growth year over year from 21 to 22. As Will mentioned, Q1 is always sort of the most challenging quarter in the U.S. due to the donut hole reset and all those good things that we see across high-priced rare disease products. And as the year progresses, Japan, we expect to be a meaningful contributor. As Roger mentioned, you know, the second-largest contributor in our three regions with that June time point as the length of the two-week prescription, which, you know, really helps patients from a copay perspective. So, hopefully, that gives you a little more color. Great, thanks.

We see a positive year across the across the board I'm not sure. If you want to add anything to that yeah. No. Thanks Jess for the question, maybe just a couple of other things to add.

Yes.

Obviously, very encouraged and excited to be able to share at least a 30% growth is obviously a meaningful growth year over year from 'twenty, one to 'twenty two as well mentioned Q1 is only sort of the.

The most challenging quarter in the U S. Due to the donut hole reset at all of those good things that we see across high price rare disease products and as the year progresses on Japan, we expect to be a meaningful contributor as Roger mentioned the second.

Just contributor in our three regions with that June time points as the lift of the two week prescription.

Really helps patients from a copay perspective, so hopefully that gives you a little more color.

Speaker 7: Great, thanks. If I could have a second question on PPIP. For that phase 2b in PAH, what background therapies are allowed and what do you expect the mix of single and dual agent background meds to be? And I know you're expecting better sort of coverage with PPIP relative to Tyvaso, but do you expect the PBR data in the phase 2b to compare well to Tyvaso?

Great. Thanks, and if I could have a second question on the IP for that phase to be in ph what background therapies are allowed and what do you expect the mix.

Single and dual background meant to be.

I know youre expecting better sort of coverage with tpi's relative to play VSO, but do you expect the PDR data in the phase II b to compare well to <unk>. So.

Speaker 5: So I'll ask Martina maybe to take that question. Yeah, so, you know, we expect that the TPI, what we've seen from TPIP in the Healthy Volunteers study is that we don't go up to such a high CMEG. We have a larger and a prolonged exposure along the AOC perspective.

So I'll ask Martina maybe to take that question, yes. So.

We expect TPS, but we've seen some PP&E in the healthy volunteer study is that we don't go up to such a high <unk>, but we have a larger and a prolonged exposure along the A&P perspective, we've seen that you have licenses that is pulling out.

Speaker 4: We've seen the T half-life in the studies going out, even with our lowest dose, to 24, 36, and even to 48 hours. So we expect that we will have a good impact on the PBR.

Even with our lowest dose to <unk> 2436 to.

Eight hours. So we expected we will have a good impact on the PDR.

Speaker 4: And from the PK profile, as what we saw in the healthy volunteer study, there's no reason to believe that that would be significantly different in the PH patient.

And from the PK profile as what we saw in the in the healthy Volunteer study. There's no reason to believe that that will be significantly different in the ph patients.

Speaker 3: Thank you. Our next question comes from Jeff Hahn from Morgan Stanley . Please, yes, your line is now open.

Thank you our next question comes from.

<unk> from Morgan Stanley <unk>. Your line is now open.

Speaker 8: Hi, this is Melina on for Jeff. Thanks for taking our questions. Can you talk a little bit more about for Brent so captive, the CRS and HS indications? What are the determining factors to advance those indications into the clinic this year? Is there any specific data that you're waiting on for each indication? Yep. Thank you.

Hi, This is mohit on for Jeff Thanks for taking our questions.

Can you talk a little bit more about.

Four branches Catherine the Crs in Hs indication what are the determining factor to advance those indications into the clinic next year.

Is there any specific data that youre waiting on for each indication.

Yes. Thank you.

Speaker 5: Yeah, no, appreciate that. I would say that we went through a pretty significant process and maybe Roger you want to talk a little bit about that. Then Martino ask you to comment on the on the logic scientifically. Yeah, sure. Thanks will. So we actually did a pretty exhaustive process where I'm working with some external partners. We screened diseases and we actually ended up screening about 150 neutrophil mediated diseases.

Yes, no appreciate that I would say that we went through a pretty significant process and maybe Roger you wanted to talk a little bit about that Martine I'll ask you to comment on the on the logic scientifically yes sure. Thanks will so we actually did a pretty exhaustive process, we're working with some external partners we screened.

And we actually ended up screening about 150 neutrophil mediated diseases.

Speaker 5: Our next step as we sort of narrowed that down was to look at those the disease states that were primarily driven by neutrophil involvement and we've skidded that list down to about a little more than 60 diseases.

Step as we sort of narrowed that down was to look at those the disease states that were primarily driven by baidu fulfill involvement.

You need that list down to about little more than 60 diseases.

Speaker 5: From there, we then looked at the FE. We wanted to understand the size of the opportunity. We looked at the burden of the disease and narrowed that final list down. And then, as we selected CRS and HS,

From there. We then looked at the FTE, we wanted to understand the size of the opportunity with.

So the burden of the disease and know that final is down to down and then as we selected Crs in Hs.

Speaker 5: We really focused on, number one, the science. So obviously, through and by neutrophil involvement, the unmet need of the patients, and importantly, the competitive intensity, which is somewhat related to the unmet need of the patients. But in HS, there's only one approved therapy, as we mentioned, which is Chimera.

Really focused on number one the science, so obviously driven by neutrophil involvement.

Unmet need of the patients.

And importantly, the competitive intensity, which is somewhat related to the to the to the unmet needs of patients but in Asia. There is only one approved therapy as we as we mentioned which Samir.

Speaker 5: In CRS without nasal polyps, which is the neutrophilic phenotype of the disease, there are no approved therapies, and that's counter to the CRS with nasal polyps where there's a number of biologics depiction, Nucala for example, that are targeting that portion of the population.

Sure.

Without nasal polyps, which is the neutrophils.

The type of the disease.

There are no approved therapies and that's counter to the Crs with nasal polyps, where there is a number of biologics fiction.

Mccallum for example that are targeting that portion of the population. So the competitive intensity is really is really attractive to us and then finally as I mentioned in my prepared comments as we looked at pricing, we expect that <unk> will be supported in bronchiectasis with some attractive pricing.

Speaker 5: So the competitive intensity is really attractive to us. And then finally, as I mentioned in our preparer comments, as we looked at pricing, we expect that the Brents & Katz will be supported in bronchiectasis with some attractive pricing. And we wanted to make sure that across our indications that we felt that payers would reimburse us at that same sustainable, attractive pricing. And we think across our disease states with bronchiectasis, CF.

And we wanted to make sure that across our indications that we felt that payers would reimburse us add that same sustainable attractive pricing and we think cross our disease states rebroadcast assist GFS.

Speaker 5: CRS and NHS that we will be able to achieve that. So we feel very good about these disease states we're targeting now and the impact that we're going to bring to patients.

Crs and NHS that we will be able to achieve that so.

We feel very good about the about these disease states, where we're targeting now with the impact of what they bring to patients.

Speaker 4: Yeah, and about scientific rationale. So there are no really good preclinical models for both of these diseases, but they are both associated with neutrophil inflammation. And if you look at TRS without nasal polyps, neutrophils play a key role in the cyborotic remodeling of the mucous membrane inside the sciences.

And above scientific rationale. So there are no really good preclinical model for both of these diseases.

Associated is neutrophil and inflammation.

Look at Crs without nasal polyps neutrophils are playing a key role in the fibrotic remodeling of the mucus membrane inside to finance it.

Speaker 4: This remodeling leads, over time, to tissue damage and worsening and worsening of that disease.

This remodeling meets overtime to tissue damage and worsening and worsening of that disease.

Speaker 4: So from both in TRS and in HS, the neutrophil component is an important driver. And in HS, the neutrophils are prominent, and you see them in the affected skin region. What you also see in this affected skin region is that an uncontrolled release of these NSPs leads to a high contribution and a presence of NETs.

So from from both in Trs <unk> and Hs the neutrophil component is an important driver.

HSE the neutrophils are prominent and do you see the need be effected skin lesion with you all.

Also see aided effected skin lesions.

Our controlled release.

Leads to a high contribution and the president of neck.

Speaker 4: And there is a correlation between this net formation and the severity of the disease. So for both of them, parental captive attracts what is the effect of cells. And that is the neutrophilic activity through the TPP1 incubation.

And there is a correlation between this net formation and the severity of the disease. So for both of them pretzel captive attract what is the extra sale and that is the neutral selling activity through the TPP one inhibition.

Speaker 5: And I would just say, you know, we are moving forward with all speed in both of these indications. You saw a draft designs of clinical trials in the slides today and the discussion that Martina provided.

And I would just say we are moving forward with all speed and both of these indications you saw drafts.

The designs of clinical trials.

In the slides today and the discussion that Martina provided.

Speaker 5: Those are going to continue to be refined. We've had very good KOL interactions, but very strongly supportive of pursuing these.

Those are going to continue to be refined we've had very good KOL interactions.

Strongly supportive of pursuing these.

Speaker 5: The only thing that holds us back from doing perhaps even more of what Roger was indicating is resource and thinking carefully about balancing how many eggs to put in this particular basket. We have excellent data in bronchiectasis. We have a very strong scientific rationale for these next three indications, as you've just seen.

The only thing that holds us back from doing perhaps even more of what Roger was indicating is resource and thinking carefully about balancing how many eggs to put it in this particular basket we have excellent data in bronchiectasis, we have a very strong scientific rationale for these next three indications.

Speaker 5: And I think what this really represents is the tip of the iceberg for DPP1 inhibition in neutrophil-mediated diseases.

As you've just heard.

Think what this really represents is the tip of the iceberg DPP one inhibition in neutrophil mediated diseases, we've really unlocked a pathway here and I think the potential for <unk> to get even bigger than it already is is very real and that puts this into a.

Speaker 5: We have really unlocked a pathway here. And I think the potential for Brents O'Kathib to get even bigger than it already is, is very real. And that puts this into a...

Speaker 5: pretty enticing blockbuster category. So lots of work to be done and validation to be provided behind that ambition, but I think the more we look at this and the more science we study, the more excited we get.

But pretty enticing blockbuster category, so lots of work to be done and validation to be provided behind that ambition, but I think the more we look at this and the more science. We study the more excited we get.

Speaker 8: Great, thank you for all that detail. And if I could just ask one more quick one on the TTIP program. I think the phase 2a data was pushed back originally from the first half this year to just 2022. Have you gotten any sense from prospective participants what they need to see in order to be willing to go into the ICU, particularly during these winter months when COVID rates might be higher?

Great. Thank you for all that detail and if I could just ask one more quick one on the <unk> program I think the phase Iia data with pushed backwards first half this year.

2022 have you gotten any sense from prospective participants what they need to see in order to be willing to go into the ICU, particularly during these winter months when Kodak rates may be higher.

Speaker 5: Yeah, this is a frustrating one for all of us. Um, look, the faith to a study has been, um, in design and out there for some time. The big challenge here is that

Yes. This is a frustrating one for all of us.

The phase Iia study has been in design and out there for some time the big challenge here is that.

Speaker 5: As far as we know, there is no precedent for this study. Doing the right heart catheterization on somebody that lasts more than about four hours, we're not aware of studies that have ever done that. We're proposing to do it for 24 hours. And what's interesting about that is that the key opinion leaders who have opened their centers to pursue this are enthusiastic about doing so. They really think this data is going to de-risk this program's potential very substantially.

As far as we know there is no precedent for this study during the right heart catheterization on somebody that lasts more than about four hours, but we're not aware of studies that have ever done that we're proposing to do it for 24 hours and.

What's interesting about that is the key opinion leaders who have opened their centers to pursue this are enthusiastic about doing so they really think the state is going to de risk this program's potential.

Turning to substantially so we are excited to get the data finding someone to volunteer who has an.

Speaker 5: So we are excited to get the data. Finding someone to volunteer who has PAH in an advanced state and is willing to have a right heart catheterization for 24 hours while they sit in an ICU surrounded by COVID infected patients, that's a very high bar. I think we probably underestimated how severe and asked that was.

In advanced stage and is willing to have a right heart catheterization for 24 hours, while they sit in an ICU surrounded by COVID-19 infected patients. So that's a very high bar I think we probably underestimated how severe and ask that it was but we're pursuing it we have identified some patients by name.

Speaker 5: But we're pursuing it. We have identified some patients by name. They will indicate at times that they want to come in, and then they get a little bit nervous. So we're trying to work as productively as we can.

We will indicate at times that they want to come in and then they get a little bit nervous. So we're trying to work as productively as we can and as Omicron received I think we have a very good chance of getting those patients. That's why we sort of said well.

Speaker 5: And as Omicron received, I think we have a very good chance of getting those patients. That's why we sort of said, look, to get all the data, it may take a little bit longer. But importantly, we plan to get the data. And once we get it, we will share it. And that could be at any time across the year.

You get all the data it may take a little bit longer, but importantly, we plan to get the data and once we get it we will share it and that could be at any time across the year.

Great. Thanks very much.

Speaker 3: Thank you. Our next question comes from Ritu Baral from Cohen. Please, Ritu, your line is now open.

Thank you. Our next question comes from Ritu <unk> from Cowen. Please wait to your line is now open.

Speaker 7: Good morning, guys. Thanks for taking the question. I wanted to ask about Aspen and what you're seeing so far. Have you been looking at event rates?

Good morning, guys. Thanks for thanks for taking the question I wanted to ask about Aspen and what Youre seeing so far have you been booking at event rates.

Speaker 8: in a blended event rate for exacerbations in Aspen, how are they comparing to expectations? And, frankly, should we be thinking about any COVID impacts on exacerbation rates in this population, you know, up, down, with rates, and whether this seems to be happening more with COVID in this population, if you could just help frame that.

London's event rates.

For Exacerbations and ask then how high those comparing to expectations.

Frankly should we be thinking about any COVID-19 impact on exacerbation rate in this population.

Yes.

Down with Wayne.

And whether this seems to be happening more with COVID-19 . In this population if you could just help frame that.

Speaker 6: Yes, so what we're doing is we're applying this passion.

Yes, so what we're doing is we're in a blinded fashion.

Speaker 4: looking at the events rate on a weekly basis and is what we're seeing matching our assumption.

Looking at the advance rate, although weekly basis.

It's what we're seeing that's in our assumption.

Speaker 6: So from that perspective, what we're seeing is matching our assumptions at this time.

So from that perspective, what we're seeing is matching our assumption at this time.

When it comes to Covid.

Speaker 4: There is an additional aspect in every respiratory study right now. So we also know which patients, how many patients have COVID. So remember, all of this is in a blinded mesh, in a blinded way. We're not, we don't see the individual arms. But we have a clear view of what is the patient population? Do we see anything that deviates right now from our assumptions? And at this point in time, we see what we would, what we had at.

So that is an additional aspect in everybody's territory study right now so we also know which patients how many patients have COVID-19 . So remember all of this is in applying that mesh in a blinded way we're not.

We don't think individual arm that we have.

Have a clear view of what is the patient population do we see anything that deviates right now from our assumption and at this point in time, we see what we would what we had estimated and similar to what we saw at Willow and similar to what we saw in wealth. So we're in a great spot right now.

Speaker 5: And similar to what we saw at Willow. And similar to what we saw in Willow. So we're in a great spot right now, Ritu. I mean, this trial is not only enrolling quickly, but the monitoring that Martina is describing has gone.

This trial is not only enrolling quickly, but the monitoring that Martina is describing is gone.

Speaker 5: remarkably well. And that is something, as she said, we're tracking on a weekly basis. So we are all over this.

Remarkably well and that is something as you said, we're tracking on a weekly basis. So we are all over this.

Speaker 7: Got it. And then, of course, a question for Roger, just on the new Brembo indications. As you think about that severe PRS population, you think about HS, who are the treating physicians that you think will ultimately be commercially targeted? Are they like ENTs and then specific derms, or are they sort of more broad than how I might be thinking about it?

Got it and then a quick question for Roger just on the new trends or indications as you think about that severe.

Crs.

Population, you think about who are the who are the treating physician.

Be commercially targeted.

Yes.

And then.

Specific terms or are they sort of more more broad than how I might be thinking about it.

Speaker 9: Yeah, thanks for two. So so you're right. It's the for the for the CRS. It's the entities. So these would be the folks that will primarily be performing the surgery. So we will be targeting the entities. And to be honest, we'll need to figure out, you know, there's about 10 to 12,000 entities in the US.

Yes. Thanks, Ritu. So so you are right.

For the Crs, it's <unk>. So these would be the folks that will primarily be performing the surgery. So we will be targeting eog's and to be honest, we will lead to figure out there is about 10 to 12000 <unk> in the U S.

Speaker 5: approximately the same number for derms, you know, we'll need to segment that population and do the work to figure out who we're going to be reaching out to address these diseases and see who are the experts in that field.

So the same number for <unk>, we will need to segment the population and do the work to figure out who we're going to be reaching out to to address the address these diseases and see who are the experts in that field.

Speaker 5: But yes, ENTs and then with the derms, we'll do the same process, right? About 10 to 12,000, we'll take a look at probably a really good indicator is you see a dermatologist who's using Humira, that's going to give you a really good lead as to who you need to be talking about to bring Brenzo to them. So, we'll update you later with more specifics about that, but those are the specialists that we're focusing on.

And then with the terms will do the same process right about 10 to 12000, we'll take a look at probably a really good indicator as you see a dermatologist is using <unk>, that's going to give you a really good lead us to believe.

Need to be talking about <unk> to debt. So we'll update you later with more specifics about that but that's those are the specialist that we're focusing on.

Speaker 3: Thank you. Our next question comes from Judah Froma from Credit Suisse. Please, Judah, your line is now open.

Thank you. Our next question will come from Judah Frommer from Credit Suisse. Please do that your line is now open.

Speaker 10: Hi guys, thanks for taking the question. First, just a quick follow up on on asking. You mentioned kind of the 50 enrollment versus internal projections. Did those change at any time tied to COVID or is that kind of, you know, an initial projection that stuck? And then you did talk about

Hi, guys. Thanks for taking the question first just a quick follow up on you mentioned kind of the 50% enrollment versus internal projections.

Change at any time tied to COVID-19 or is that kind of.

And the initial projections that stock and then you did talk about.

Speaker 10: enrollment timelines, does that kind of foretell a lead out in kind of the mid-2024 range?

Enrollment timelines does that kind of foretell, a readout and kind of the mid 2024 range.

Speaker 5: Well, these are consistent. The internal projections were set after COVID was underway, as you might recall. So they certainly contemplated that. I would say...

Well.

These are consistently in the interim.

All projections were set after cohort was underway, but recall so.

It's certainly contemplated that I would say.

Speaker 5: We took a pretty aggressive line on what we were trying to accomplish here, as we described early on. We were going to really resource this trial and give it our best efforts. And I would say, even in the context of those ambitions, this has outperformed. And I think what we were trying to put our finger on today is that.

We took a pretty aggressive line on what we were trying to accomplish here as we described early on we were going to really resource this trial and given our best efforts and I would say even in the context of those ambitions. This has outperformed.

And I think what we've.

We're trying to put our finger on today is that.

Speaker 5: You know, a part of that is coming from the enthusiasm that surrounds the arrival of this potential medicine described by someone at the American Thoracic Society as potentially the holy grail of pulmonary medicine. So there's real palpable enthusiasm for this program out there and that's affecting enrollment.

Part of that is coming from the enthusiasm that surrounds the arrival of this potential medicine described by somewhat.

American Thoracic society is potentially the Holy Grail of pulmonary medicine.

So theres real palpable enthusiasm for this program out there and thats affecting enrollment.

Speaker 5: I think the other question was timing for data. So this is a 13-month study, 12 months on drug, and then one month off drug. So you can run the math off of whenever we're finally fully enrolled, it'll be roughly 13 months plus the time to lock the database and release it in top-line form. So we say approximately this time next year we should be fully enrolled.

I think the other question was timing for that.

For data. So this is a 13 months study 12 months on drug and then one month off drug. So you can run the math off of whatever.

We are finally fully enrolled it'll be roughly 13 months plus the time to lock the database and releases and topline form.

So we say approximately this time next year, we should be fully enrolled.

Speaker 10: Okay, that's helpful. And then there were a couple comments just around.

Okay. That's helpful. And then there were a couple of comments just around kind of <unk>.

Speaker 10: kind of cash allocation priorities, you know, up funding the presentation and then kind of toward the end and not over allocating to pillar four. Can you give us a little bit more color around priorities for cash allocation? Are there specific areas you're thinking about that you may need more, whether it's accelerating on-call enrollment or maybe the allocated sales force or pushing these new-brenzo indications, just any cost?

Cash allocation priorities.

Upfront in the presentation, and then kind of towards the end did not allocating over allocating to pillar four can you give us a little bit more color around priorities for cash allocation are.

Are there specific areas, you're thinking about that you may need more whether it's accelerating on core enrollment or you know maybe the oracle salesforce or pushing these these new brands.

Indications or just any color would be helpful.

Speaker 5: Well, the first thing I would say is, as we think about the four pillars, obviously the largest spend is on the first two at the moment, where we have pivotal trials that are global in reach and large in scope.

Well the first thing I would say is as we think about the four pillars. Obviously the largest spend is on the first two at the moment, where we have pivotal trials that are global in reach and large in scope.

Speaker 5: TPIB probably follows behind that and then the fourth pillar punches way above its weight with very little resource because it's an earlier stage and importantly the medicines that are being produced there.

<unk> probably follows behind that and then the fourth pillar.

Punches way above its weight with very little resource because it's an earlier stage and importantly, the medicines that are being produced there.

Speaker 5: they proved to be effective, have a potentially shorter pathway through the regulatory maze.

They proved to be effective have a potentially shorter pathway through the regulatory matters.

Speaker 5: because they can be highly impactful to very severe patients.

They can be highly impactful to very severe ah patients. So we have a long way to go to accomplish that but but.

Speaker 5: So, you know, we have a long way to go to accomplish that, but I'm excited about the prospects of that. And we'll have more to say about the fourth pillar in detail in the second half of this year when we do our R&D day. Hopefully, you noticed on the slide where we've enumerated nine different programs, you get some sense for how productive this engine already is.

Cited about the prospects of that and we'll have more to say about the fourth pillar in detail in the second half of this year. When you at R&D day, hopefully you noticed on the slide where we've enumerated nine different programs to get some sense for how productive. This engine already is and where it could lead us as a company is very exciting.

Speaker 5: and where it could lead us as a company is very exciting.

Speaker 5: I don't know, Sarah, if you want to talk about guidance for any of those different spends and how we're thinking about it. Yeah, sure. You know, as Will mentioned...

But I don't know, Sir if you want to talk about guidance for those different spends and toward thinking about it yes sure.

Will mentioned.

Speaker 6: Our largest, you know, focus from a capital prioritization perspective is around the Eric Case and Brentso programs. And so as we think about

Since our largest focus from a capital prioritization perspective is around the <unk> program.

Speaker 6: ARISE, ASPEN, ENCOR, we are resourcing those programs and ensuring those programs are as successful as they can be. And so as you see the success that we've had with ASPEN, you know, over 50% involved, just the degree of that study, just as a reminder, that means it's over 800 patients that we've enrolled in about a year. That's pretty remarkable as you think about comparator.

Think about.

Arise Aspen encore.

We are resourcing those programs and ensuring those programs are as successful as they can be.

And so I do see the success that we've had with Asps.

50 over 50% involved just to grant that study just as a reminder that means it's over 800 patients that we think.

About a year, that's pretty remarkable if you think about comparator.

Speaker 6: trial so you know we are resourcing these programs appropriately and Martina and I stay in close contact around prioritizations around all four pillars translational medicine

I'll trial. So we are resourcing these programs appropriately.

And Martina and I stay in close contact around prioritization around all four pillars translational medicine.

Okay.

Speaker 6: It's an immaterial spend for the amount of answers and questions we're going to be able to get out of that pillar.

It's immaterial spends for the amount.

Out of answers of questions, we're going to be able to.

To get out of that color.

Great. Thank you.

Speaker 3: Thank you. Our next question comes from Joseph Schwartz from SVB Leadering. Please, Joseph, your line is now open.

Thank you. Our next question will come from Joseph Schwartz from SVP Leerink. Please go ahead. Your line is now open.

Speaker 8: Hi, I'm Drury Valium for Drove, and thank you for taking our questions. First is on pricing in Japan. Does AirQs get renegotiated after the first year in Japan?

Hi, I'm here with Joe Thank you for taking our question.

Okay first of all on pricing in Japan.

We negotiated after the first year in Japan.

Speaker 9: Yeah, thanks for the question. There will be pricing adjustments for barricades in Japan. We're not anticipating it for the first year, but there are, I think it's every two years that we're anticipating that there will be pricing adjustments potentially in Japan. It's not a given, but we're anticipating that there may be those renegotiations every couple

Yes. Thanks for the question there will be pricing adjustments for Eric H in Japan, we're not anticipating it for the first year, but there are I think it's every two years simply anticipating that there will be pricing adjustments potentially in Japan, it's not it just sounds like it's not a given but we anticipate that maybe.

Maybe those renegotiations every couple of years.

Speaker 8: Okay, great. Thank you. And then if we could just squeeze one in, for ARISE, I believe the first patient was dosed last, late December , late December , and it's like about 14 months to get 50% enrollment, you know, curious, what gives you confidence that the ramp up of enrollment could happen in the next 10 months or so of the year that's remaining? You know, are you planning to have more sites? Or are you detecting more interest? Any color of that would be helpful. Thank you very much.

Okay, great. Thank you you have enough data.

<unk> I believe the first patient was dosed last may.

In late December .

December and just think about what key months that 50% enrollment and I'm curious what gives you confidence that.

Ramp up of enrollment could happen in the next 10 months or so.

Yes, that's remaining and are you planning on my side.

Just any color on that would be helpful. Thank you very much.

Speaker 5: Yeah, I mean, if you heard in Martina's comments, one of the challenges of NDM studies is just that these patients are very...

Yes, I mean, if you heard in <unk> comments, one of the challenges of MTS.

MGM studies is just that these patients are very <unk>.

Speaker 5: skittish, particularly in the global pandemic. We've been through this before with two other studies in the refractory population, both phase two and phase three, so we're accustomed to it. If you look across this disease state, this is sort of the typical.

Particularly in the global pandemic, we've been through this before with two other studies in a refractory population both phase II and phase III. So we're accustomed to it if you look across this disease state.

Speaker 5: approach. What's interesting is that notwithstanding getting them in the clinical setting, the commercial opportunity that gets represented by this.

Sort of a typical.

Approach, what's interesting is that notwithstanding.

Getting them in the clinical setting the commercial opportunity that gets represented by this.

Speaker 5: um the uptake is quite substantial so we're excited to get to the other side of Arise and Encore because of what we think it's going to represent. um there are a lot of patients out there that are going to benefit from this.

The uptake is quite substantial so we're excited to get to the other side of a rise in oncor because of what we think it is going to represent.

There are a lot of patients out there that are going to benefit from this.

Speaker 5: It is also important to remember that we're asking in the ARISE study for patients to take the drug for six months and then one month off.

It is also important to remember that we're asking in the arise study for patients to take the drug for six months and then one month off and that is not what guidelines call for so it's a little bit of a higher hurdle to.

Speaker 5: And that is not what guidelines call for. So it's a little bit of a higher hurdle to get them to step into a rise. It's one of the reasons why we think Encore is going to enroll faster. There are several countries that are not participating in a rise that are participating in Encore.

Get them to step into arise. It's one of the reasons why we think encore is going to enroll faster. There are several countries that are not participating in arise that are participating in encore.

Speaker 5: And so that will also add additional sites and enrollment horsepower to on-floor once ARISE is completed.

And so that will also add additional sites and enrollment horsepower to oncor, what's arise is completed but we.

Speaker 5: But we know what the screening is, we know what the front end of the funnel is, if you will, and that's where our confidence comes from that we think we'll be able to complete this.

We know what the screening is we know what the.

Under the funnel is if you will and Thats, where our confidence comes from that we think will we'll be able to.

<unk> and <unk>.

In due time.

Speaker 3: Thank you. Our next question comes from Stephen Wiley from Stifel. Please, Stephen, your line is now open.

Thank you. Our next question comes from Stephen Wiley from Stifel. Please ask Steven Your line is now open.

Speaker 10: Yeah, good morning. Thanks for taking the questions. Maybe just to follow up on the last on the last question. I think there was a comment that Martina made around.

Yes, good morning, thanks for taking the questions.

Maybe just to follow up on the west on the last question I think there was a comment that Martina made around.

Speaker 10: screen failure rate that you guys were seeing and I believe it was a riser on core being I think somewhere north of 40% and was just wondering if you could maybe kind of provide some commentary around what seems to be driving that specifically and whether or not that's in line with prior studies that you've done in this disease setting I guess specifically Congress yeah

Screen failure rate that you guys were seeing and I believe will summarize our encore being I think somewhere north of 40% and.

I was just wondering if you could maybe provide some commentary around what seems to be driving that specifically.

Whether or not that's in line with prior studies that you've done in this disease setting I guess specifically come.

Yeah.

Speaker 6: The first thing to remember is that prior studies that we've done, a convert study, was in a refractory population. So those are already patients that are diagnosed and they haven't responded to treatment. So you get this positive sputum culture already when patients come to physicians and they are at the site. In the frontline indications, so these are naive patients and very often for these patients to produce sputum is already hard.

That's the first thing to remember is that prior studies that we've done in a combat spending within a refractory population. So those are already patients that are diagnosed and they haven't responded to treatment. So you get this positive sputum cultures.

We are ready when patients come to physicians MTR to site in the frontline indications. So this is a naive patient and very often for these patients to produce them it's already hard.

Speaker 4: Then, to actually get a positive view on culture is the next hurdle. And in addition, today...

And to actually get a positive culture, it's the next hurdle.

In addition today.

Speaker 4: What you often have to do with this patient, you actually help them to induce sputum production. So there is an element of that that sites don't do this today that's related to the COVID.

You also have to deal with this patient to actually help too.

And to induce sputum production. So there is an element of basket size don't do this debate that's related to the Covid.

Speaker 4: that they often have and then it takes a significant amount of time until you really get to a culture that is positive. And we want to ensure that we have a high quality culture and we have the right patients.

Guidance is that they had intended.

It takes a significant amount of time until you really get to a culture that is positive and we want to ensure that we have a high quality culture.

Speaker 4: You don't want patients in the study who just have colonizations but they don't really have a good public culture. So that's just part of that. Now, it's a different environment when you're in a study situation than what you would be having in the normal clinical practice setting. There is a higher level on that.

It's the right patient.

One patient in the study who just tactical organization I think don't really Hasnt been published.

So that type.

Part of that now it's a different environment when you're in a static situation than what you would be having in a normal in the normal clinical practice setting there is the highest.

Speaker 4: And that part of it, we've seen this higher screen failure rates often because it's very hard for them to produce it. They just can't come up with it. Then you have to wait until you get that positive culture to make sure we have the right patient in this study.

And that basically we've seen this at screen failure rates, often because it's very hard for them to produce it they can come up with it and you have to wait until you get that positive.

Just to make sure we have the right patients in this study.

Speaker 4: Those are very big drivers for the screen failure rates as well.

Those are very big drivers.

For the screen failure rates as well.

Speaker 10: Okay, that's helpful. And then, I guess, just with respect to the Phase 2a study for brent's catabin CF, I think prior guidance maybe suggested that was going to be a 22 disclosure. I think you're now maybe talking really 23. Maybe it's just semantics. But is there anything rate limiting there in terms of enrollment? Is that COVID related? Is that you pushing those escalation a little bit higher than you perhaps were before?

Okay. That's helpful and then.

Just with respect to the phase Iia study for <unk> kind of Mcs.

I think prior guidance, maybe suggest that that was going to be 22 disclosure I think youre not maybe talking really 'twenty three maybe it's just semantics, but is there anything rate limiting there in terms of enrollment is that is that COVID-19 related is that you're pushing dose escalation a little bit higher than you perhaps were before.

Speaker 5: No, that doesn't really, that hasn't really changed. All we're really trying to indicate is that.

No.

That doesn't believe that hasn't really changed all we're really trying to indicate is that.

Speaker 5: At this stage, it's hard to predict exactly what the enrollment path will be. There's no new information that would redirect the timing of that. We'll update you throughout the year as we see what the progress is. I think if we've added that extra little bit of space, it's in the event that we were to go up to 65 milligrams, for example. Martina talked about the three doses we're currently targeting. Depending on how patients respond, we may need to go to 65.

At this stage, it's hard to predict exactly what the enrollment path will be.

There is no new information that would redirect the timing of that we'll update you throughout the year as we see what the progress is I think if we've added that extra.

Little bit of space in the event that we were to go up to 65 milligrams. For example, Martina talked about the three doses were currently targeting depending on how patients respond we may need to go to 65.

Speaker 5: And so to do that might take a little bit longer, but that's all that's really playing out there.

And so to do that might take a little bit longer, but that's all that's really playing out there.

Alright, thanks for taking questions.

Speaker 3: Thank you. Our next question comes from Lisa Baker from Everscore. Please Lisa, your line is now open. Hi, thanks for the question and you have some updates.

Thank you. Our next question comes from Lisa Baker from Evercore. Please <unk>. Your line is now open.

Hi, Thanks for taking my question and that's another update.

Speaker 6: I'd love to understand a little bit more about the dynamics of how you're thinking about era case. You're kind of well into the quarter already for the first quarter. Any updates on sort of trends you're seeing? And then as you think about guidance for next year, can you give us any color on what is the growth coming? Primarily ex-US, US, maybe you can give us some breakdown of how you're thinking about the 30 percent growth across the different regions.

I understand a little bit more about the dynamics of how youre thinking about Eric Hayes.

Kind of well into the quarter already for the first quarter any updates on sort of trends you're seeing and then as you think about guidance for next year can you give us any color on what is the growth coming.

Primarily ex U S. U S. Maybe you can give us a breakdown of how you are thinking about.

30% growth across the different regions.

Speaker 11: Sure, happy to. Thanks, Lisa, for the question. So we're excited and encouraged to be able to.

Sure happy to.

Thanks, Lisa for the question so.

And encouraged to be able to reinstate our revenue guidance first time in two years that we've been coming out with revenue guidance with a 30% year over year growth.

Speaker 11: Reinstate revenue guidance first time, you know, in two years that we've been, you know, coming out with revenue guidance with a 30% year-over-year growth is, you know, a substantial growth. We anticipate that we will see growth from all three of our regions. As I mentioned earlier in the prepared remarks, Q1 is at least the toughest in the U.S. due to the donut hole reset and all of those good things, as you've historically seen throughout our Q1s. And as Roger mentioned in his remarks around sort of the nuances.

Substantial growth, we anticipate that we will see growth from all three of our regions.

As I mentioned earlier in the prepared remarks Q1 is at least the toughest in the U S. Due to the donut hole reset at all of those good things that as you've historically seen throughout our coupons.

And as Roger mentioned in his remarks around sort of the nuances.

Speaker 11: in the Japan market on the two-week restriction being lifted in the June time frame. So some, you know, nuances as you think about the different regions, but we do expect to see growth in all three of our regions and we have as a global society.

In Japan market on the two week restrictions being lifted in the June timeframe. So some.

And as you think about the different regions, but we do expect to see growth in all three of our regions and we have as a global society.

Speaker 11: gotten to a place where we understand COVID and folks are, you know.

Got it to a place where we understand coed and <unk>.

Speaker 11: learning how to live in this in this new in this new environment. So hopefully that gives you a little more color. Yeah maybe I'll just add in a couple of comments because I think what we're seeing uh and and as Sarah had said you know it first quarter is always a tough quarter uh for the U.S. with the with their the uh co-pays and and the deductible restats and so forth.

<unk> sorry.

Learning headwinds.

And this new in this new environment. So hopefully that gives you a little more color there and maybe I'll just add in a couple of comments because I think what we're seeing.

As Sarah said first quarter is always a tough quarter for the U S with the weather.

Sure.

Co pays and the deductible resets and so forth.

Speaker 9: But what we're really encouraged if we look at Omicron and look what's happened with COVID, we got, you know, the whole country got hit with that at various times. And we're seeing, you know, it's still a regional impact.

But we're really encouraged if we look at <unk> and look what's happened with Covid, we got.

The whole country got hit with that.

<unk> times.

And we're seeing still a regional impact, but we're seeing trends in the northeast where hospitalizations just plummeting in the U S.

Speaker 9: But we're seeing trends in the Northeast where hospitalization is just plummeting in the US.

Speaker 9: And we're seeing some specific areas where our sales reps are able to get back in front of customers and have more in-person calls, and we think that that's really important.

And we're seeing some specific areas that we.

Our sales reps are able to get back in front of customers and have more in person calls and we think that that's really important.

Speaker 9: You know, we know the pulmonologists have been particularly hit hard in IDs with the whole COVID situation. And as we see that start to subside and, you know, knock on wood, we're all hoping we're getting to the other side of this. We think we'll see patients coming back in. We think, you know, a lot of these pulmonologists are going to be really focused on respiratory health. Everybody's focused on long COVID, understanding the impact of that disease. I think that's going to drive index of suspicion for NTM and for other comorbidities and focusing on long term.

We know with the Pulmonologists have been particularly hit hard in Ids.

The whole COVID-19 situation.

And as we see that start to subside knock on wood. We're all hoping we are getting to the other side of this we think most of the patients coming back in we think a lot of these pulmonologists are going to be really focus on respiratory health everybody's focused on lung colon COVID-19 understanding the impact of that disease, and I think that's going to drive index of suspicion for MTM.

Further other comorbidities and focusing on lung health.

Speaker 9: So we're really optimistic for growth across our regions. We've got a number of catalysts in Europe where they reimburse the decisions.

So we're really optimistic for growth across our regions. We've got a number of catalysts in Europe with the reimbursement decisions in Japan, we're really thrilled with how the launch has progressed in Japan will watch watching what's happening with lower corn, there as well.

Speaker 9: In Japan, we're really thrilled with how the launch has progressed in Japan. We'll watch what's happening with Omicron there as well. I would say that it's interesting, the data I had just seen showed that actually...

I would say that it's interesting the data I'd just seen showed that actually does seem to be hitting their population harder than it should the U S and Europe .

Speaker 9: It seems to be hitting their population harder than it's hit the US and Europe .

So they've actually recorded in Japan.

We're higher than what we saw in the summer, which was the delta variance. So it's had a really pretty profound impacts.

Some theories floating around I think the boosted population in Japan is about 9%.

Was the data that I heard which is significantly less than what we've seen in western countries. So, but if we see the same pattern, there where you see it, peaking and then receding dramatically.

Think that will continue that launch of pace.

We had the catalyst of the Japanese society, providing that.

Speaker 9: input and recommendation for our case.

Input and.

A recommendation for air case.

Speaker 9: The copay dynamic that will come with the two-week restriction being lifted in June , we're really optimistic that we'll drive that growth in Japan as well. So across our regions, we're really optimistic, and that's reflected in what we try to play out there as our fight.

The copay.

The dynamic that will come with in two weeks.

Restrictions being lifted in June we're really optimistic that will drive that growth in Japan as well so across our regions, we're really optimistic and thats reflected in what we've tried to lay out there.

Speaker 6: guidance. Okay, great. And then just on the for Japan and in Europe , does this reflect, you know, the kind of 2021 numbers you provide? Is that mostly end-user demand or is there any kind of channel fill there, anything about that? I know you kind of, at least in Japan, launched fairly recently and I'm just trying to understand if there's this channel fill dynamic or if that's really reflecting end-user demand. And then for Europe , how do you get to a point where you have a better sense of, you know, what the patient number is?

As our guidance.

Speaker 6: Okay great and then just on the um for um Japan and in Europe do does this reflect you know the the um the kind of

Okay, Great and then just on the.

For.

Japan and in Europe .

Does this reflect the.

Yes.

The kind of 2021 numbers you provided is that.

Speaker 6: mostly end user demand or is there any kind of channel fill there or anything like that? I know you kind of, at least in Japan, launched fairly recently and I'm just trying to understand if there's this channel fill dynamic or if that's really reflecting end user demand. And then for Europe , how do you get to a point where you have a better sense of...

Mostly end user demand or is there any kind of channel fill there or anything about that I know you're kind of at least in Japan launched fairly recently and I'm just trying to understand if there is there is this channel sell dynamic or if thats really reflecting end user demand.

And then for Europe , how can you get to a point, where you have a better sense of.

Speaker 6: you know what the patient number is, just like our, sorry, just because where you're at already in terms of, you know, the share you seem to be getting, it's already pretty substantial. And just wondering when you might have a better handle on actually how many patients there are available out there.

If the patient number is it just like ours, right, just because where youre out already in terms of.

Sheri you seem to be getting already pretty substantial and just wondering when you might have a better handle on actually how many patients are not available elsewhere.

Speaker 9: Yeah, so we don't see that. I think your first question was really are we seeing stocking, right? So are we putting products into the channel? And we work with wholesalers in Japan, and this is reflecting user demand. So we sell the devices directly into the hospitals. And in our case, it goes to the wholesalers and to the hospitals. But because it's a fairly expensive product, you don't see a lot of stocking and carrying of that inventory. And in Europe , it's the same phenomenon, right? So we don't have that kind of phenomenon occurring.

Yes. So so we don't see that I think your first question was really are we seeing stocking right. So why are we putting putting products into the channel.

And we work with wholesalers wholesalers in Japan, and this is reflecting.

It reflecting user demand so we feel that the devices directly into into the hospitals.

Eric case goes to the wholesalers into the hospitals, but because it's a fairly expensive product you don't see a lot of stocking and carrying that inventory.

In Europe , it's the same phenomenon right. So we don't have that kind of that kind of phenomenon occurring.

Speaker 9: Um, and what was the second question? All the 1400 patients. Yes. Sorry. Thanks. Uh, look, I think

And what was the second question.

1400 basis, yes, sorry. Thanks.

Look I think.

Speaker 9: We're loathe to put out estimates that aren't supported by the literature, right? So I think everything we've looked at and all the literature that's available points to those 1,400 refractory patients.

Low to put out estimates that aren't supported by the by the literature rates. So I think everything we've looked at and as we.

And all the literature is available points of those 1400 refractory patients.

Speaker 9: We're really skeptical about that. We think it is a larger number for a number of reasons. The KOLs see these patients.

We're really skeptical about that we think it is a larger number for a number of reasons.

Speaker 9: They are anxious for the therapy, as you mentioned. We're actually seeing some substantial revenue already from Europe without reimbursement. And we have the name patient program in place there. And so we think over time, if you think about the risk factors for NTM, it's an elderly population. If you've got a history of smoking, it's proximity to the water. All of those things are true in Europe as they are in the US and Japan. So we think that the population may be understated in the literature. We don't have anything hard that we can point to around that. So we're conservative as we think about what we represent as the market might look like.

Kols see these patients.

Are anxious for the therapy as you mentioned.

We're actually seeing some substantial revenue already from Europe without reimbursement and.

We had the named patient program in place there.

And so we think over time, if you think about the risk factors for MTM, it's an elderly population.

<unk> got a history of smoking its proximity to the water all of those things are true in Europe .

In the U S and Japan.

So we think that the population may be understated as literature deal.

We don't have anything to hard that we can point to around that so we were conservative as we think about what we.

What we represent as the market might look like.

Speaker 9: But over time we'll see that and we'll validate that. It'll take longer for us to grow that market. There is a sort of a more of a medical center of excellence, kind of an approach in Europe .

But over time, we'll see that and we will validate that it'll take longer for us to two.

<unk> grown our market there is a sort of a more of a medical center of excellence.

<unk> in Europe .

Speaker 9: But we think with an improved therapy that's reimbursed, you'll see these patients be treated, you'll see them identified, and we'll see that opportunity grow over time.

But we think with an approved therapy, that's reimbursed you'll see these patients be treated you'll see them identified and we will see that.

Opportunity to grow over time.

Speaker 3: Thank you. As a reminder, to ask any further questions, please press the star followed by one on your telephone keypad now.

Thank you as a reminder to ask any further question. Please press the star followed by one on your telephone keep us now.

Speaker 3: Our next question comes from Jennifer Kim from Cantor. Please, Jennifer, your line is now open.

Our next question comes from Daniel Kim from Cantor Fitzgerald. Your line is now open.

Speaker 6: Hey everyone, thanks for taking my questions. Maybe starting with TPIP, in terms of timing for the Phase 2B trial, clinical trials have an estimated primary completion date of February 2024, and I know that's not the most reliable indicator, but I'm wondering, based on how enrollment has moved for that asset in the Phase 2A, and then enrollment we've seen with other assets as well, is it fair to call that an aggressive timeline, or is it too early to say for now?

Hey, everyone. Thanks for taking my questions, maybe starting with TP IP in terms of timing for the phase two B trial clinical trial has an estimated primary completion date of February 24, and I know thats not the most reliable indicator, but I'm wondering based on how enrollment has been for that asset.

In the phase Iia.

And then enrollment we see with other assets as well is it fair to call that an aggressive timeline or is it too early to say for now.

Speaker 5: I think it's too early to say what the timeline will be for that, that's why we didn't provide it in the written, in the spoken comments.

I think it's too early to say what the timeline will be for that is why we didn't provide it in the risked in the spoken comments.

Speaker 5: What I would draw your attention to is that I think it's very different to be enrolling for this phase 2b trial and the phase.

What I would draw your attention to is that I think it's very different to be enrolling for this phase <unk> trial and the phase two ph ILD trial. Then it is the <unk> trial with <unk> is really blocked by the onerous nature of the protocol, where a patient has to have the right heart cath for 24 hours and so.

Speaker 5: to PHIL-D trial than it is the 2A trial. The 2A is really blocked by the onerous nature of the protocol, where a patient has to have the right hard cap for 24 hours.

Speaker 5: And so getting volunteers to go into that is challenging. Both of these phase two trials, the phase 2B and PAH, and the phase 2 and PAH-ILD are following a fairly standard protocol approach. And so there's good precedent out there for enrolling patients in this kind of trial. The patients are accustomed to it. It's just a question of executing it. And I think the team has proven its worth in that regard. So I'm confident that they will deliver the enrollment in as rapid a time as quality will allow. We think this is just a fraction of the year that bathing pool in a spindle% graduates

<unk> getting volunteers to go into that as challenging both of these phase II trials the phase <unk> phase II in ph ILD are following a fairly standard protocol approach and so there's good precedent out there for enrolling patients in this kind of trial. The patients are accustomed to it. It's just a question of executing it.

The team at <unk>.

His proven its worth in that regard so I'm confident that they will deliver the enrollment in this rapid time as quality will allow.

Speaker 6: Okay, great. And maybe one quick second question. For Arikase in Japan, you've talked about the two-week prescription limit and the COVID impact as, I guess, the two things sort of restricting growth in 2022. And I'm wondering broadly what level of impact did each of these things have in 2022 in your mind? I'm just thinking about how we should start to think about 2023 as those factors go away. Thanks.

Okay, Great and maybe one quick.

Second question for Eric Keys in Japan, you've talked about the two week prescription limit and the Covid impact I.

I guess, the two things sort of restricting growth in 2020, Q and Im wondering broadly.

Level of impact in each of these things have in 2022 in your mind I'm just thinking about how we should start to think about 2023 of those factors go away. Thanks.

Speaker 9: Yeah, thanks. So first of all I just want to say I think the Japanese team has done an amazing job in launching our case and you've seen the sales that we reported from last year in just a little bit more than six months, a little bit less than six months of sales.

Yes. Thanks.

So first of all I just wanted to say I think the Japanese team has done an amazing job in launching allocation have you seen the sales of your reported from last year.

Just a little bit more than six months less than six months of sales.

Speaker 9: And so, you know, we expect this trajectory to continue apace. I think the impact of COVID and Omicron is real. You know, we are having trouble accessing physicians in person because they're being pulled to their hospital duties to take care of these patients. And the government is restricting hospital beds, so even if they're unused, which if you look at the numbers, they're probably not a lot of unused right now.

And so we expect this trajectory to continue.

I think the impact of Covid and Omicron Israel.

We are having trouble accessing physicians in person because they're being pulled to their hospital duties to take care of these patients.

Government is restricting hospital beds, so even if their unused which if you look at the numbers that probably not a lot of unused right now but.

Speaker 9: they're restricting hospital beds and reserving them for COVID patients. And recall, we had talked about earlier, there's a predication in...

Are they restricting.

Hospital beds, and reserving them for Covid patients and recall, we had talked about earlier, there's a predication.

Speaker 9: in Japan for physicians to start our case patients in the hospital for at least a couple of days so they can monitor them, make sure they're tolerating the product. Okay. Um, so we think that, uh, that it's

In.

And in Japan for physicians to start our case patients in the hospital for at least a couple of days. So they can monitor them make sure they're tolerating the product okay.

So we think that.

Speaker 9: hopefully a first quarter phenomenon, right? So we're seeing that Omicron will peak.

Sure.

Hopefully a first quarter phenomenon right, so where we're seeing that.

Speaker 9: we're getting on the side of this and be able to return to some sense of normalcy. The two week prescription I think is a real issue. I think what we've seen is the early adoption has been for those patients who have been waiting for our case have more severe patients.

Chrome will peak.

The other side of this and be able to return to some sense of normalcy.

The two week prescription I think is a real is a real issue I think what we've seen is the the early adoption has been for those patients who've been waiting for our case.

Speaker 9: and are willing to look past that co-pay burden for them to start. I think once that's lifted, we'll see a pretty strong reaction, both from the physicians in prescribing for their patients, because of course they're sensitive to the economic burden of the patient, as it's mostly elderly, and also from the patient, they'll be able to receive up to three months of medicine for the same co-pay that they currently receive up to one month right now. I think we're really excited about and have confidence in the Japanese launch. I think we've got a couple of catalysts, and the second half I think will be a stronger uptake because of those factors.

<unk> is a more severe patients.

And we're willing to look past that co pay burden for them to start I think once that's.

<unk> lifted we'll see.

Pretty strong.

Reaction both from the physicians in prescribing for their patients because they of course, they are sensitive to the economic burden.

The patient is this.

Most of the elderly.

And also for the patient there'll be able to receive up to three months.

A medicine for the same co pay that Theyre currently receive up to one month right. Now. So I think we're really excited about and have confidence in the Japanese launch I think we've got a couple of.

Catalysts in the second half I think it will be a stronger stronger uptake because of those factors.

Speaker 3: Thank you. As a final reminder, to ask any further questions, please press star followed by 1 on your telephone keypad now. The next question comes from Anita Dusla from Berenbeck. Please, Anita, your line is now open.

Thank you as a final reminder to ask any further question. Please press the star followed by one on your telephone keypad now.

Question comes from Amit Shah from <unk>. Please send me your line is now open.

Speaker 8: Hi, good morning. Thank you for the update and guidance and also congrats on the results. I had a question, sorry if I missed this in your commentary, for the application of Brembo-Cative and CRS and HS.

Hi, good morning.

Thank you for the update and guidance.

Congrats on.

Okay.

Hum.

Multiple feel more comfortable.

All right.

The closing of Guangdong Province.

Speaker 8: Would you be investigating both of those indications this year, or is there a preference one over the other, and if so, maybe talk about a rationale as to why?

Yes.

Would you be taking bold.

No the falls into wholesale.

Yes.

Deborah.

Wow.

Yes so.

Yes.

Okay.

Speaker 5: So in response to the first question, I would say we are moving both forward. We have thought in our minds that we would bring one into the clinic by the end of this year. It's not final yet, but that is certainly our current inclination.

Okay.

So in response the first question I would say we are moving both.

Sure.

Thought in our minds that we would bring one into the clinic by the end of this year, it's not final yet but that is certainly our current an inclination.

Speaker 5: Both are equally compelling. It's hard to choose between them to be very candid. I think our preference, because of the potential in these diseases, is to bring them both forward as quickly as possible. But we're trying to work a balance between resource deployment and the opportunity that they need.

Both are equally compelling it gets hard to choose between them to be very candid.

I think our preference because of the potential in these diseases is to bring them both forward as quickly as possible, but we're trying to work a balance between resource deployment and.

And the opportunities they represent.

Speaker 8: Okay, thank you. And then I know you mentioned that there's about 115 years of remediating diseases that, you know, you were looking at, and from the screening, these indications are kind of for a given curfew. So I just wanted to know, like, potentially, would grant educators find applications in some percentage of that number that you had mentioned?

Okay. Thanks.

And then.

Thank you ma'am.

About the.

Thank you Nancy.

Keybanc.

Looking now.

Clean diesel.

All right.

So I just wanted to know.

Randy.

Hey, good morning application.

Sam.

That number that you had.

Speaker 9: Yeah, to be clear, we think that what we've unlocked here is, you know, the DPP-1 inhibition pathway.

Yeah to be clear, we think that.

What we've unlocked here is.

The DPP one inhibition.

<unk> way that.

Speaker 5: interference with the inflammatory cascade is really quite profound in its potential application.

Interference with the inflammatory Cascade is really quite profound and its potential application. So we start with these four indications which rises to the top as the most probable for impact but to remind you we have already done preclinical work in other indications as well.

Speaker 5: So we start with these four indications, which rise to the top at the most probable for impact.

Speaker 5: But to remind you, we've already done preclinical work and other indications as well, like rheumatoid arthritis and lupus nephritis.

Rheumatoid arthritis, and lupus nephritis, and some other very substantial indications for a variety of reasons. It doesn't make sense for us to pursue those clinically, but we certainly are protecting them from an intellectual property standpoint, and so we're that preclinical work gets done and validates its potential application.

Speaker 5: and some other very substantial indications. For a variety of reasons, it doesn't make sense for us to pursue those clinically, but we certainly are protecting them from an intellectual property standpoint.

Speaker 5: And so where that preclinical work gets done and validates its potential application.

Speaker 5: we have pursued the IP around that. Would we go into diseases beyond this? If we had the resources down the road, yes, we would. I think this pathway presents.

We have pursued the IP around that when we go into diseases beyond this if we had the resources down the road, yes, we would I think this pathway presents a very substantial and broad opportunity I can't emphasize that enough and I think as we learn more and the scientific rationale is clear.

Speaker 5: a very substantial and broad opportunity. I can't emphasize that enough.

Speaker 5: And I think as we learn more and the scientific rationale is clear and the patient need is clear, those are things we will continue to evaluate and seriously consider pursuing.

And the patient need is clear.

Those are things, we will continue to evaluate that and seriously consider pursuing.

Speaker 3: Thank you. We currently have no further questions, so we'll hand over back to Will Lewis for any final remarks.

Thank you with that when you have no further questions.

Okay back to win their waste for any final remarks.

Thank you all for joining us this morning.

Speaker 3: This concludes today's call. Thank you so much for joining. You may now disconnect your lines.

This concludes today's call. Thank you so much for joining you may now disconnect your lines.

Speaker 1: ? ? ? ? ?

Okay.

Sure.