Q4 2021 Ascendis Pharma A/S Earnings Call

Okay.

Operator: Good day and thank you for standing by. Welcome to the Q4 2021 Ascendis Pharma Earnings Conference Call. At this time, all participants are in a listen-only mode.

Good day, and thank you for standing by and welcome to the Q4 2021 Sunday Pharma earnings Conference call.

At this time all participants are in a listen only mode. After.

Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during that session, you will need to press Star 1 on your telephone. Please be advised that today's conference is being recorded and if you require any assistance during the call, please press star 1. I would now like to hand the conference over to your speaker today, Mr. Tim Lee, Senior Director of Investor Relations. Tim Lee, the floor is yours.

After the Speakers' presentation, there'll be a question and answer session.

Quick question joined that session, you will need to press star one on your telephone please be.

If I had that today's conference to be caught it.

And if you require any assistance during the call. Please press star.

I would now like to hand, the conference over to your speak today, Mr. Tim Lee Senior director of Investor Relations delete the floor is yours.

Tim Lee: Thank you, operator. Thank you everyone for joining our full year 2021 Financial Results Conference call today. I'm Tim Lee, Senior Director, Investor Relations, Ascendis Pharma. Joining me on today's call is Jan Mikkelsen, President and Chief Executive Officer; Scott Smith, Senior Vice President and Chief Financial Officer; and Jesper Hoyland, Global Chief Commercial Officer.

Thank you operator thank.

Thank you everyone for joining our full year 2021 financial results conference call today.

I'm, Kimberly senior director Investor Relations of the Sandoz pharma <unk>.

Joining me on today's call Jan Mikkelsen, President and Chief Executive Officer.

Scott Smith, Senior Vice President and Chief Financial Officer.

Yes, well hoyland global Chief commercial officer.

Tim Lee: Dr. Dana Pizzutti, Head of Development Operations and Chief Medical Officer. Dr. Juha Poonanen, Head of Oncology, and Dr. Stina Singel, Head of Clinical Development Oncology. Before we begin, I would like to remind you that this conference call will contain forward-looking statements that are intended to be covered under the safe harbor provided by the Private Securities Litigation Reform Act. Examples of such statements may include, but are not limited to, our U.S. commercialization and continued development of SkyTrofa for the U.S. market. Our progress on our pipeline candidates and our expectations with respect to their continued progress. Statements regarding a strategic plan.

Doctor Dana presume D head of development operations, and Chief Medical Officer.

Doctor you have pre internet head of oncology.

And Dr. Christina single head of clinical development oncology.

Tim Lee: Our goals regarding our clinical pipeline, statements regarding the U.S. market potential for SkyTrofa and our pipeline product candidates, and statements regarding our regulatory filing. These statements are based on information that is available to us today. However, actual results and events could differ materially from those in the forward-looking statements, and we may not achieve our goals, carry out our plans or intentions, or meet the expectations or projections disclosed in our forward-looking statements, and you should not place undue reliance on these statements.

Before we begin I would like to remind you that this conference call will contain forward looking statements that are intended to be covered under the safe Harbor Safe Harbor provided by the private Securities Litigation Reform Act.

Examples of such statements May include but are not limited to our U S commercialization and continued development of Sky crossed off the U S market.

Our progress on our pipeline candidates and our expectations with respect to their continued progress.

Statements regarding our strategic plans.

Our goals regarding our clinical pipeline statements regarding the U S market potential for Sky Trophy, and our pipeline product candidates and statements regarding our regulatory filings.

These statements are based on information that is available to us today.

Actual results and events could differ materially from those in the forward looking statements and we may not achieve our goals carry out our plans or intentions or meet the expectations or projections disclosed in our forward looking statements and you should not place undue reliance on these statements.

Tim Lee: Our forward-looking statements do not reflect the potential impact of any licensing agreements, acquisitions, mergers, dispositions, joint ventures, or investments that we may enter into or terminate. We assume no obligation to update these statements as circumstances change, except as required by law.

Our forward looking statements do not reflect the potential impact of any licensing agreements acquisitions mergers dispositions joint ventures or investments that we may enter into or terminate.

We assume no obligation to update these statements as circumstances change.

Except as required by law.

Tim Lee: For additional information concerning the factors that could cause actual results to differ materially, please see our Forward-Looking Statements section in today's press release and the Risk Factors section of our most recent annual report on Form 20-F. Transcon Human Growth Hormone, or Transcon HGH, is approved by the FDA in the U.S. under the brand name Skytropha for the treatment of pediatric patients one year or older who weigh at least 11.5 kilograms and have growth failure due to inadequate secretion of endogenous growth hormone. In addition, the European Commission has granted a marketing authorization for Lone Pax Somatropin Ascendis Pharma, developed under the name Transcon HGH, as a once-weekly subcutaneous injection for the treatment of children and adolescents ages 3 to 18 years with growth failure due to insufficient secretion of endogenous growth hormone. In general, we refer to this product as Transcon HGH unless we are referring to the product in the context of a particular jurisdiction such as the United States or the European Union.

Information concerning the factors that could cause actual results to differ materially. Please see our forward looking statements section in today's press release and the risk factors section of our most recent annual report on form 20-F.

Kranjcar on human growth hormone Transcon Hgh is approved by the FDA in the U S. Under the brand name <unk> for the treatment of pediatric patients one year older where at least 11, five kilograms and have growth failure due to inadequate secretion of endogenous growth hormone. In addition, the European Commission has grant.

It a marketing authorization for the Olympics Homotropic standards format developer in the transfer developed under the named Transcon Hgh as a once weekly subcutaneous injection for the treatment of children and adolescents ages three to 18 years with growth Daniel due to insufficient secretion Dodgers growth hormone.

In general we refer to this product is transcon hgh, unless we are referring to the product in the context of a particular jurisdiction such as the United States or the European Union.

Tim Lee: Sky Copa was approved by the FDA in August 2021 for the treatment of pediatric patients one year older who weigh at least 11.5 kilograms and have growth failure due to inadequate secretion of endogenous growth hormone. Otherwise, please note that our product candidates are investigational. Our product candidates are investigational product candidates. And not approved for commercial use.

Sky Copa was approved by the FDA in August 2020, 2021 .

For the treatment of pediatric patients one year older who had at least 11 five kilograms that growth failure due to inadequate secretion of growth hormone otherwise. Please note that our product candidates our investigational.

Our product candidate our investment product.

Candidates are investigational product candidates.

And not approved for commercial use as investigational products, the safety and effectiveness of the product candidates have not been reviewed or approved by any regulatory agency. None of the statements made on the conference call regarding our product candidates shall be viewed as promotional.

Tim Lee: As investigational products, the safety and effectiveness of the product candidates have not been reviewed or approved by any regulatory agency. Therefore, none of the statements made on the conference call regarding our product candidates should be viewed as promotional. On today's call, we'll discuss our full year 2021 financial results and provide further business updates. Following some prepared remarks, we will then open up the call for questions. I will now turn the call over to Jan Mikkelsen, President and Chief Executive Officer.

On today's call, we'll discuss our full year 2021 financial results and provide further business updates. Following some prepared remarks, we will then open up the call for questions.

I will now turn the call over to Jan Mikkelsen, President and Chief Executive Officer.

Thanks, Tim.

Jan Mikkelsen: Thanks, Tim, and good afternoon. 2021 was an extraordinary year for Ascendis. The regulatory approvals of transcontamine in the U.S. and Europe were a key milestone in achieving our Vision 3 by 2. The approvals of Transcon in the US and Europe were a validation of the Transcon technology platform. Validation of our Alkaloid Network Product Innovation, and Vegetation of our Infrastructure, and capabilities to achieve approvals in the US and Europe of a combination product, including biological manufacturing.

And good afternoon.

Yeah.

So in tier one Boston external humira for surgeons.

The regulatory approvals of transcon growth hormone in the U S and Europe , where a key milestone in achieving all of this should three months.

Yeah.

There are pools of transcon growth hormone.

In Europe were up.

Vegetation after transcon technology platform.

Reputation alcohol alcohol, reaching their full color innovation.

And vegetation or infrastructure.

<unk> capabilities to achieve approvals in the U S.

Europe offer combination prologue, including biologic drug manufacturing.

Jan Mikkelsen: We believe these successes confirm that we have the right strategy, and the people, and capabilities in place to achieve our Vision 3 budget, and to build a sustainable, profitable, leading global biopharma company. We didn't stop here.

Do you believe.

Such cases confirmed that <unk> has the right strategy.

Yeah.

And the people.

And capabilities in place to achieve our vision two months free.

And to build a sustainable profitable.

Global Biopharma company.

Got it.

We didn't stop here.

Jan Mikkelsen: In 2021, we also realized significant advances in other areas essential to our Vision 3.0 by, These include amazing, important studies for Transcon PGA's program in adult hyperparasites, and progressing our Transcon C&P program in Accra, Indonesia, of the programs are essential to our goal of achieving rectatory approvals for three independent endocrinology rare disease products, to achieve our goal of global market leadership for each of our products. We continue expanding our global clinical, and Label Expansion in the endocrinology where disease is discussed. In our second interview together.

In 2020 rule you also realized significant advances.

Hey, Ross is essential to our vision sweep our tree.

Does this include and based in important studies for Transcon PTH program in adult Hydrocodone started recently.

And progressing our transcon CMP program in excellent location.

Yeah.

Both.

After programs I assume some tour goal of achieving regulatory approvals.

Independent endocrinology rare disease products.

To achieve our goals.

The market you just see.

Our whole products.

Continue expanding a local clinical groups.

Lee with expansion in the endocrinology disease this year.

Our second therapeutic area.

Jan Mikkelsen: Oncology. We have two highly differentiated cancer immunotherapy programs being advanced through clinical development. We believe we can transform treatment in immuno-oncology with our products. For our third independent therapeutic year, we are conducting research, using our Transcon technology and the Ascendis Algorithm for Product Innovation to create a pipeline of independent product candidates addressing major unmet needs. That's for all our Ascendis products can do. We have the same high expectation for each of the product candidates in our third tertiary, to achieve global leadership and create a multi-billion dollar product in the world.

Oncology.

We have two highly differentiated kensal.

L P programs being advanced too.

Co development.

We believe we can transform the treatment.

Oncology.

<unk> products.

Okay.

Lastly.

For a third independent therapeutic care you are conducting grocers.

Our transcon technologies.

Our synergies as good wiechmann for product innovation to create a pipeline of independent product candidates addressing major unmet makes them.

Therefore, our expected product candidates, we have the same expectation.

Each of those product candidates.

So if you would care to achieve.

Global leadership and create and move some adult all comer opportunity.

Jan Mikkelsen: A key element in our Vision 3x3 is sustainable growth. We intend to continue developing new product candidates, using the Transcon technologies and the Ascendis Algorithm for TORC. We plan to continue to build our organization capability with the aim to bring safe, highly differentiated products to patients as quickly as possible, across multiple therapeutic areas, indication and geographic. I expect that 2022 will be another unforgettable year.

A key element in obesity III, but.

Sustainable growth.

The intent to continue developing new products or disease, using the transcon technologies.

Just echo with Mitchell Park location.

We plan to continue to build our organization capability.

The aim to bring safe highly differentiated product to patients as quickly as possible.

Of course, multiple therapeutic areas indications and geographies.

I expect that 20% you're too busy in oil unforgettable year.

Jan Mikkelsen: You can expect us to share data, and Rector Toye Milestone, across our five independent clinical programs throughout the year that demonstrate solid progress towards long-term goals. Eglin Cawthon, We plan to provide you with updates related to the commercial launch of SCARTOFA in the U.S, and the plant launched for commercialization in Europe. As we expand access to this important treatment for pediatric growth pneumonia, in the era of Grotemont. We are here to build a leading global brand. Skytrooper is only approved once we pick up on the U.S.

You could expect us to share data.

And regulatory milestones.

Across.

Five independent clinical programs throughout the year.

Demonstrate solid progress towards long term growth.

Equally important.

Do you plan to provide you with updates related to the commercial launch of schedules in the U S.

And the plan launch become association in Europe .

As we expand access to this important treatment option for pediatric growth hormone deficient.

Yeah.

In the era of growth hormone.

We're here to build a leading global brands.

Okay.

Throughput.

Once we do go to more on the U S market.

Jan Mikkelsen: In the four short months since its launch, our commercial teams have leveraged their decades of endocrinology experience and relationships, to meet the target prescribers. Maximize awareness of CARTOPHA to multiple channels and events, and provide patient treatment and support through our Ascendis Signature Access Program, because of their industry knowledge and effort. Precision Interest and Adoption of Skyscraper, continues to grow, as of February 20. 704 skyscraper prescriptions have been written by 259 prescribers.

In the four short months since as long as our commercial teams have levers the advocates endocrinology.

And really should see to meet the target prescribers.

<unk> awareness post cutover to flexible chairman and events.

And provide patient treatment and support to all our strategies.

Sigma to assess.

<unk> program.

Because of this industry knowledge and defaults.

Physician interest and adoption of schedule, but.

Continues to grow.

As of February 27.

700, and full skytrooper prescription has been increased by 259 prescribers.

Jan Mikkelsen: 44% of prescribing physicians have written prescriptions for more than one of their patients. In November 2021, in Europe, we received a positive CHMP opinion for Transcon Group, for Pilate at Gupta. Followed quickly by the European Commission approval in mid-January 2020.

44% of prescribing physicians have written prescriptions for more than one of their patients.

In November 2021 in Europe .

Received.

Costa to see.

<unk> your opinion for transcon growth for.

For pediatric growth hormone deficiency.

Quickly by the European Commission.

January 2022.

Yeah.

Jan Mikkelsen: As a Danish company, Europe is an important market to us, and the unmet medical need for prolactin growth hormone deficient patients is just as great. But because the market opportunity for growth and timelines to secure reimbursement varies from country to country, replaying to a bit, to establish direct sales capabilities in some European countries and establish distribution partnership in all. In this way, we look forward over time to maximize value and intend to bring a broad portfolio of transcontinent-based products to European decision and, Moving to the dot go to more efficient, We expect transconcoctamol to make a meaningful difference for adults suffering from adult concoctamol. We expect by releasing unmodified.

So Daniel Company Europe is an important market to us and the unmet medical need for Codexis.

Deficient patients who suggested escalate.

But because the market opportunity for growth and timelines to secure reimbursement varies from country to country. We plan to have bids to establish direct sales capabilities.

Typically this is some European countries and the staff as to distribution partners.

In this way, we look full time to maximize value.

To bring a broad.

<unk> portfolio of Transcon based products too.

As you should and patients.

Moving to the adult growth hormone deficiency indication.

We expect transcon growth hormone to meet and meaningful difference for adults suffering for adult growth hormone deficiency.

We expect.

Releasing modified similar to.

Jan Mikkelsen: Transcontinental mode may be able to address the many different aspects of this, and Restore Overall Endocrine Health, in addition during the second quarter of 2020. We plan to submit a protocol to the FDA in turn of sitting, and Komusuma Disorder Affecting Development. We are pursuing this label expansion to help more patients and create a market-leading brand in growth hormone therapy. Turning now to Transcom PTA. Maple Leap 2023, will be a very important year for. Living with Hygopertia, who face significant challenges in both health and quality of life.

Transcon growth hormone.

To address many different aspects of the disease and restore.

Or a decline.

In addition, during the second quarter of 2022 replaying.

Our protocol.

The internal Sutent and.

In conclusion.

Disorder affecting development.

<unk>.

We are pursuing this label expansion to more patients and created a market leading brand and <unk> therapy.

Turning now to Transcon PTH.

Okay.

We believe <unk> will be important.

Pete.

But hybrid hybrid Todd.

Who faced significant China, both health and quality of life.

To date.

Jan Mikkelsen: HP remains the last large classical hormone deficiency, for which a hormone replacement therapy, is not yet available. Conventional therapy with calcium supplement and activated vitamin D is aiming at maintaining serum calcium in the normal range with the hope of reducing short-term, And not.., and is not able to address the on-the-line. In addition, these conventional therapies can lead to long-term complications, that include severe diseases, such as chronic, Riemann and Bassett-Gandhi classifications. Cardiovascular Complications and Problems, Numerous publications have reported that despite being an unconventional therapy, Patients continue to experience short-term symptoms. Often resulting in... Hospital, Space and Emergency Departments.

HP remains the Saar.

Yes.

<unk> deficiency for a.

A home with placement IOP.

Not yet.

Sure.

Convince them to therapy could cause some software and <unk> devices.

Amy at mean <unk> person in the normal range.

We do think short tubes.

And not.

And he is not able to address the underlying disease.

In addition, this convinces therapies can be too long term completion.

That includes severe diseases, such as chronic diseases.

<unk> got new types of application.

Cardiovascular complication and voting ballots.

Numerous publication has reported that despite being on conventional therapies patients continue to experience short term symptom often resulting in.

Hospital stays and emergency Department visits.

Jan Mikkelsen: Finally, patient with ATP report below normal quality of life, at the same or worse level than many other crimes, with significant impact on daily. With this in mind, we designed Transcon P-TECH to restore physiological levels of paratype hormone P-TECH. Later this month, we look forward to sharing top-line results from our Phase 3 pathway. As a reminder, this is a six-month, randomized, double-blind, placebo-controlled clinical trial in North America and Europe, investigating the safety, tolerability of N-efficacy and transcon PTAs in adults with NDE.

Finally patient with HP report could do normal quantity offline.

Of course Labor then menu for the chronic diseases.

Significant impact on daily activities with this in mind, we designed transcon PTH to restore Lockheed.

Look you Couldnt labors per tire Holman PTH.

Yeah.

Later this month.

Forward to sharing top line results from our phase III concrete trial.

As a reminder, this is a six months randomized double blind placebo controlled clinical trial, North America and Europe .

Investigating the safety Tolerability and efficacy and transcon PTH in adults.

Jan Mikkelsen: We believe that all chronic HP patients could benefit, did benefit from a resolution of physiological levels of PTSD. And we believe that Transcon PGH, if approved, could become an important treatment option. Be Authentic, How does Transcon PTH differ from other PTH therapies that have been on the market? First, Transcon PTH allows the release of predictable levels of PTH in the physiological range across a 24-hour period.

Do you believe that for chronic HBV patients.

Beneficial.

These statements from them versus oration, both crucial logical levels of <unk>.

And we believe that transcon PTH <unk> could become.

Important treatment option for these patients.

We are often asked how does transcon PTH depot from other <unk> therapies.

Sure.

First transcon PTH allows.

Release of predictable levels of <unk> industries, a lot you couldnt ratings accruals, a 24 hour period.

Jan Mikkelsen: Second, we designed Transcon PTAs to be a first-line hormone replacement therapy, potentially eliminating the requirement for conventional therapies by restoring calcium hemostasis and quality. Let me recap the phase two data that gave us the initial insight in the potential for this important problem, in the Open Label Extension, of the study, Ed Mondt, 86% of the sockets have normal serum catalysis, were all convincing therapy of activated vitamin D, and taking less than. Alexander Milibrand, the day of...

Second reduce our transcon PTH to be a cruise line.

<unk> replacement therapy.

Potentially eliminating the crime.

Conventional therapies by restoring hemostasis and quality of life.

Let me recap the phase II data that gave us the initial fee side is the potential for this important product.

In the open label extension portion of the study at.

Months six.

86% of the softer half normal serum ketchum weigh.

Yeah.

Vincent to repeat of incubated by some.

And taking this thing 600 milligram with the architecture.

Jan Mikkelsen: These are the same parameters being used as our primary endpoint interfaces. In addition, subject reported normalized quality of life scores on all summary and subdomain, Importantly, subject randomized to trans-competing, Demonstrate a statistic improvement compared to placebo after four weeks in the blinded portion of the day, and continue normalization from week 6 to March. We believe that these improvements in quality of life could be one of the main reasons why, 57, out of 59 patients, continue to be part of the organ-level extension story, even now after As you know, We remain excited by the data we have seen so far, and we think Transcon PTA could introduce A Paradigm Shift in Health HP, Among the face three. Assuming the face tree was also up.

These are the same <unk> being used as a primary endpoint in the phase III.

Hi.

Energy <unk>.

Subject reported normalized quality of life scores.

In summary, and soft demand.

Importantly, subject randomized to transcon PTH.

Demonstrate extra statistic improvement compared to placebo.

Four weeks and the client portion of the trial.

Continuing normalization performed six two months six.

We believe that these improvements in quality of life could be one of the main reason why.

57 out of 59 patients continue to be part of the Fulton Papal extension study even now after two years.

As you know.

We remain excited by the day. So if you have seen so far and transcon PTH.

Introduce Pat.

Paradigm shift.

Pete is treated.

Among the phase III.

Assuming the phase III results are positive we plan.

Jan Mikkelsen: We plan to submit an NDA for transcon PTAs to the FDA in the third quarter of 2020, followed by MNA submission to EMEA in the fourth quarter. In Japan, where the pathway Japanese Phase 3 study of transconvictia is underway, we expect top-line results in the third quarter. Because hyperparasitism can affect all ages, we also plan to imitate a study of transcompetence in children with ADHP during the fourth quarter. We can estimate it, more than 200,000 patients suffering from HP in the U.S. Europe, and Japan alone, and the lack of autism. Treat, The Underlying.

To submit an NDA for transcon PTH to the FDA in the third quarter.

'twenty two.

Followed by M&A solution to EMEA in the fourth quarter.

In Japan, where the Parkway.

Phase III study of transcript P. J you saw it that way.

Top line results in the third quarter.

Because hydro peso can affect you.

You also plan to initiate a study of transcon PTH and should that with HP during the fourth quarter of 2022.

Two.

<unk> estimated.

More than 200000 patients suffering from its peak in the U S.

Europe , and Japan alone and the lack of oxygen to treat the underlying disease do you believe transcon PT ethos.

Jan Mikkelsen: We believe TranscomPJ, if approved, could become our largest endocrine rare disease product. We think and believe Transcol-PK could potentially be the only product to fully address this, plus five people. Margaret Oppenheimer.

If approved could become ollie's army into crime rare disease product.

We think and believe Transco PT could potentially be the only product to fully get rates.

Cost 5 billion market opportunity.

Jan Mikkelsen: I would like to update you on Transcon CMP for a few... Continuous exposure of CMP has been shown to counteract the growth inhibition effect of the FDR3 mutation associated with aconitoplasia and to stimulate, We are investigating Transcon CMP's ability to provide prolonged exposure and COPD, allow for penetration into the target group at predictable levels or..., to rebalance the pathway that we're good at, in the fourth quarter of 2020.

I would like to update you on transcon CMP for Echo depletion.

Seniors exposure CMP is shown to counter.

The growth in IP should effect of FTR treat mutation ex receipt of this export to Asia and to stimulate growth.

We are investigating transcon CX.

Relative to provide prolonged exposure and <unk>, allowing for penetration into target growth rates.

Predictable levers sports alright.

We balance the coffee that quickly.

In the fourth quarter of 2022.

We expect to share top line data from the Congress.

Jan Mikkelsen: Our Phase 2, randomized, double-blinded, placebo-controlled clinical trials of Transcon C&P in North America, Europe, and, and a few other countries in New Zealand and Australia. Page from 2 to 10, which is on the account, in the Account of Accomplished, 42% of the subjects are in the age group from 2 to 5.

Our phase two randomized double blind placebo controlled clinical trial of Transcon CMP in North America Europe and.

Q4 countries in Youll see them in Australia.

Eight from two children with achondroplasia.

In the equitable accomplished trial.

42% of this shocking.

Each group from two to five years.

Jan Mikkelsen: We are really thrilled by the blinded safety data reported last December in our R&D update, and we are looking forward to sharing the top-line results in the fall quarter. Given the serious and irreversible early impact of this, be also planned during the second quarter. Fyland, and D-Eplication.

We are really thrilled.

The blinded safety data reported last December at all.

Uptake and we are looking forward to share with top line results in the fourth quarter of this year.

Given this year's Universal.

Correct.

You also claims during the second quarter of this year to filing.

And R&D application.

Jan Mikkelsen: [inaudible] or similar for a conscious infant trial in the patient age. Zhou, Tazeen, Stretching Natural Colors, We believe our product candidates have the potential to transform cancer immunity. Initial data from, The Transcontinental.

Or similar for our concretes infinite tribes.

The patient base.

Zero to two years.

Switching now to oncology.

We believe our product categories have been particularly two storms for cancer immunotherapy.

Okay.

The initial data from.

The transcon chiller seven.

Jan Mikkelsen: 78 agonist first in human dose escalation trial has been promising and we expect to see further validation of our technology and approaches in oncology later, for Transcon TLR78. Enrollment continues in transit. IP. One. A Phase 1-2 Study of Transcon TLR-78 Aconitin, with or without checkpoint inhibitors in patients with advanced and metastatic soreness.

<unk> equities first in human dose escalation trial has been promising and we expect to see further validation of our technology approaches in oncology agencies.

For Transcon Chiller 70 equities enrollment continues in transit.

101, as Chris want to started off Transco Telos seven eight equities.

All right.

Pardon inhibitor in patients with <unk> and metastatic solid tumors.

Scott Smith: We expect top-line dose escalation data for TRANSCOM TLR78 agonist monitor, and in combination therapy with ketone inhibitor in the third quarter. For transgon IL-2, beta-gamma. We expect top-line monotherapy data from the phase 1-2. I believe, try in the fourth quarter of 2020. During the fourth quarter of 2022, we plan to submit an R&D or similar for Phase 2, cohort expansion to investigate Transcom TLR780 ECONYST and Transcom IL-2 Beta-Garmin as a combination.

We expect topline dose escalation patient for transcon, <unk> equities monotherapy and combination therapy with checkpoint inhibitor in the third quarter of 2020.

For Transcon <unk> Pizza comment, we expect topline data from the phase one two.

Belief trials in the fourth quarter of 2022.

During the fourth quarter of 2022, we plan to submit an IND or similar for stage two.

Cohort expected.

Base ticket count continued Australian equities, and try and scope to Peter come as a combination therapy.

Scott Smith: We took major steps in 2021 by progressing towards our Vision 3. We believe we are moving towards becoming a viable, sustainable and profitable biopharmaceutical company. We estimate that our first therapeutic error of endocrinology rare disease alone will represent and combine, 10 billion U.S. global dollars. We also have a highly differentiated oncology pipeline and we plan to add a third to go there. I look forward to updating you further as the year goes on.

We may just.

601 by progressing to obesity treatment treatment.

We believe we are moving towards becoming a viable sustainable and profitable biopharmaceutical company.

We estimate that our first took over the air.

Into promoted a few rare disease.

As a percent and combined.

We didn't use slope.

We also have a highly different stages oncology product and you're trying to as I took over here.

I look forward to updating you further as the year.

Yes.

Scott Smith: I will now turn the call over to Scott for a financial review before we open up for questions. Thank you, Jan. Turning to our financial results for the full year ended December 31, 2021, we reported a net loss of 383.6 million euros, or seven euros per basic and diluted share, compared to a net loss of 419 million euros, or 8.28 euros per basic and diluted share, during 2020.

I will now turn the call over to Scott for financial review before we open up for questions.

Thanks Ian.

Turning to our financial results for the for the full year ended December 31 2021, we.

We reported a net loss of $383 6 million Europe .

Or seven euro per basic and diluted share compared to a net loss of 419 million euro or 8280 per basic and diluted share during 2020.

Scott Smith: Let me now run through some components of these results. Total revenues for 2021 were 7.8 million euros compared to 7 million euros during 2020. Revenues include U.S. Skytropa sales, as well as licensed clinical supply and services provided to third parties, primarily those in pharmaceuticals. Reported US Skytropa sales for 2021, reflecting the launch in October, were 0.9 million euros.

Let me now run through some components of these results.

Total revenues for 2021 were $7 8 million euro compared to $7 million Euro during 2020.

Revenues include U S Sky Trophy sales as well as license clinical supply and services provided to third parties, primarily these in pharmaceuticals.

Reported <unk> sales for 2021, reflecting the launch in October were $1 9 million Euro.

This was reduced by provisions we made to cover estimated sales deductions in product returns determined that initial launch.

The majority of Sky drove our sales in 2021 were related to initial inventory stocking.

Scott Smith: The majority of Skytropa sales in 2021 were related to initial inventory stock. As a reminder, we recognize revenue upon receipt by our specialty pharmacy and specialty distributor customers and not upon dispense of the product to the patient. Now turning to operating expenses. Research and development costs for 2021 were 295.9 million euro compared to 260.9 million euro during 2020.

As a reminder, we recognize revenue upon receipt by our specialty pharmacy, and specialty distributor customers and not upon dispense the product to the patient.

Scott Smith: R&D costs in 2021 reflect continued advancement of our pipeline, with the primary drivers of the increase including an overall increase in personnel related, And then for Transcon HGH, R&D costs were lower, primarily due to a one-time benefit related to capitalization of inventory as a result of the FDA approval in the third quarter of Transcon HGH, known by its U.S. trade name of SkyTrophy. This was partially offset by investments to expand our future manufacturing capacity as well as increased clinical trial related activities to support increased global clinical reach and label expansion, for Transcon PTA. R&D costs were higher primarily due to increased clinical trial-related spend.

Now turning to operating expenses.

Research and development costs for 2021 were $295 9 million euro compared to $260 9 million Euro during 2020.

R&D costs in 2021 reflect continued advancement of our pipeline with the primary drivers of the increase including an overall increase in personnel related.

Okay.

And then for Transcon Hgh R&D costs were lower primarily due to a onetime benefit related to capitalization of inventory as a result of the FDA approval in the third quarter of Transcon Hgh known by its U S trade name of Sky trough.

This was partially offset by investments to expand our future manufacturing capacity as well as increased clinical trial related activities to support increased global clinical reach and label expansion.

For Transcon PTH.

R&D costs were higher primarily due to increased clinical trial related spend.

Scott Smith: Device Development Costs and Manufacturing Costs, including the successful completion of drug substance PPQ batches, as well as initial costs of building commercial inventory. For Transcon C&P, costs were higher primarily due to increased manufacturing and clinical trial related costs, and finally for our Oncology Therapeutic Area. R&D costs were higher due to increased manufacturing and clinical trial costs for Transcon TLR78 agonist, and also due to increased manufacturing for clinical and clinical trial costs for Transcon IL-2 beta gamele. Selling general and administrative expenses for 2021 were 160.2 million euro, compared to 76.7 million euro during 2020.

Device development costs and manufacturing costs, including the successful completion of drug substance <unk> batches as well as initial costs of building commercial inventory.

For Transcon CMP costs were higher primarily due to increased manufacturing and clinical trial related costs and finally for our oncology therapeutic area.

R&D costs were higher due to increased manufacturing and clinical trial costs for transcon <unk> agonist and also due to increased manufacturing preclinical and clinical trial costs for transcon <unk> beta gamma.

Selling general and administrative expenses for 2021 were $160 2 million euro compared to $76 7 million during 2020.

Scott Smith: These higher expenses primarily reflect an increase in personnel-related and commercial expenses, as well as IT systems and other infrastructure costs, as we prepared for and launched SkyTrofa in the U.S. Finance income and expenses in 2021 included a net foreign exchange rate gain of 59 million euros compared to a net loss of 78.9 million euros in 2020. Primarily related to unrealized gains on translation of our U.S. dollar holdings of cash and marketable securities to Europe. We ended 2021 with cash, cash equivalents, and marketable securities totaling 789.6 million euros.

These higher expenses, primarily reflect an increase in personnel related and commercial expenses as well as it systems and other infrastructure costs as we prepared for and launched <unk> in the U S.

Finance income and expenses in 2021 included a net foreign exchange rate gain of 59 million euro compared to a net loss of $78 9 million Euro in 2020.

Primarily related to unrealized gains on translation of our U S dollar holdings of cash and marketable securities to Europe .

We ended 2021 with cash cash equivalents and marketable securities totaling $789 6 million Euro.

Scott Smith: Turning to an update, on our U.S. launch of Skytropa for pediatric GHD. Overall, demand for Skytropa has continued to grow since launch in October 2021. Through February 28th, 708 Skytropa prescriptions have been written by 263 prescribers. Each prescription is usually written for one year.

Turning to an update.

On our U S launch of Sky trough for pediatric ghd.

Overall demand for <unk> has continued to grow since launch in October 2021.

Scott Smith: Of those 263 prescribers, 44% have prescribed Skytropa to more than one patient. And as of the end of February, 36% of lives were covered per MMIT. From a market access perspective, we continue to see more health care plans making SkyTropha available to their members over time, with an increasing percentage of prescriptions approved for reimbursement through the prior authorization or medical exception processes where needed. And we are also in active dialogue with major PBMs and other payers to broaden patient access to SkyTropha.

Through February 28, 780, <unk> prescriptions have been written by 263 prescribers.

Each prescription is usually written for one year.

Of those 263 prescribers, 44% have prescribed <unk> to more than one patient.

And as of the end of February 36% of lives were covered for MMA team.

From a market access perspective, we continued to see more health care plans, making <unk> available to their members over time with an increasing percentage of prescriptions approved for reimbursement through the prior authorization or a medical exception processes where needed.

And we are also in active dialogue with major pbms and other payers to broaden patient access to sky trough out.

Scott Smith: In summary, we continue to be excited by the strong physician and patient interest in Skytropha, and we look forward to updating you on our progress in the coming quarters. Turning to 2022, we expect our expenses to increase as we continue to build our commercial capabilities and organization in preparation for additional anticipated product launches in 2023. And as we advance our endocrinology rare disease pipeline, expand our activities in oncology, and continue to invest in the transcon technology platform, including for transcon growth hormone, continued investment and expanding commercial manufacturing capacity to support anticipated future demand.

In summary, we continue to be excited by the strong physician and patient interest in Sky profile and we look forward to updating you on our progress in the coming quarters.

Turning to 2022, we expect our expenses to increase as we continue to build our commercial capabilities and organization in preparation for additional anticipated product launches in 2023.

And as we advance our endocrinology rare disease pipeline expand our activities in oncology and continue to invest in the transcon technology platform.

Including for Transcon growth hormone continued investment in expanding commercial manufacturing capacity to support anticipated future demand.

Geographic expansion for pediatric ghd in the European Union. Following MAA approval in January 2022, and continued execution of label and geographic expansion in our ongoing clinical trials.

Scott Smith: For TRANSCON-PTH, key activities will include continued execution of the Adult Hypoparap program, including the Phase 2 Path Forward Trial and the Phase 3 Clinical Program, including the Pathway Trial and the Pathway to PAN Trial, preparation for the Initiation of a Phase 3 Pediatric Hypoparatrial, and ongoing manufacturing of PPQ batches and activities to build commercial inventories. For Transcon C&P, key activities include continued execution of our Phase II clinical program, which includes two randomized, double-blind, placebo-controlled clinical trials in achondroplasia, the ongoing ACCOMPLISH trial and the ACCOMPLISH China trial, which is being coordinated through Visa and Pharmaceuticals.

For Transcon PTH key activities will include continued execution of the adult Hypo <unk> program, including the phase III path forward trial, and the phase III clinical program, including the pathway trial and the pathway to Pan trial.

Preparation for the initiation of our phase III pediatric HEICO para trial.

And ongoing manufacturing at <unk> batches and activities to build commercial inventory.

For Transcon CMP key activities include continued execution of our phase III clinical program, which includes which includes two randomized double blind placebo controlled clinical trials in achondroplasia, the ongoing accomplished trial and the accomplished China trial, which is being coordinated through visa pharmacy.

<unk>.

Scott Smith: And lastly, in our Oncology Therapeutic Area, key activities include continued execution of the Transcend IT-101 clinical trial, for our Transcon TLR78 agonist, in the I'll Believe trial for transconile 2-beta gamma. In addition to Skytropa commercial launch activities in the U.S., we expect other SG&A activities will include Transcon PTH pre-launch activities, and continued investments in personnel, systems and infrastructure to support our rapidly progressing portfolio and growing organization.

And lastly in our oncology therapeutic area key activities include continued execution of the transcend.

<unk> hundred one clinical trial.

For our Transcon Tls seven eight agonists.

And the I'll believe trial for Transcon <unk> to Gamble.

In addition to Sky <unk> commercial launch activities in the U S. We expect other SG&A activities will include Transcon PTH prelaunch activities and continued investments in personnel systems and infrastructure to support our rapidly progressing portfolio and growing organization.

Scott Smith: As Jan noted, we have a lot happening at Ascendis, so let me now provide also an update on our remaining corporate milestones and other key events. For Transcon Growth Hormone, we plan to submit a protocol to FDA to initiate a trial in Turner syndrome, in Q2 2022. Related to the Foresight Trial, our Phase 3 trial in adult growth hormone deficiency. The invasion of Ukraine has impacted our ability to continue clinical trial activities in Ukraine, Russia, and Belarus.

As Yan noted we have a lot happening at ascend is so let me now provide also an update on our remaining corporate milestones and other key events.

For Transcon growth hormone, we plan to submit a protocol to FDA to initiate a trial in Turner syndrome.

In Q2 2022.

Related to the <unk> trial, our phase III trial in adult growth hormone deficiency.

The invasion of Ukraine has impacted our ability to continue clinical trial activities in Ukraine, Russia, and Belarus, while this may affect our timelines. There is currently no material impact to our business from the situation.

Scott Smith: While this may affect our timelines, there is currently no material impact to our business from the situation. For Transcon PTH, we expect to report top-line results from our Phase 3 pathway trial in North America and Europe this month, followed by an expected NDA submission to FDA in Q3 2022, and an expected MAA submission to EMA in Q4 2022. Pathway Japan top-line results are expected in Q3 this year, and finally, we plan to submit an IND or equivalent for pediatric hypoparathyroidism in Q4 2022, for Transcon C&P. Top line data from the Phase 2 Accomplished Trial are expected in Q4, this year. And we plan to file an IND or equivalent for the accomplished infants trial in Q2. 2022.

For Transcon PTH, we expect to report topline results from our phase III pathway trial in North America and Europe . This month, followed by an expected NDA submission to FDA in Q3, 2022, and an expected MAA submission to EMA in Q4 2022.

Pathway, Japan topline results are expected in Q3 this year and finally, we plan to submit an IND or equivalent for pediatric hyperparathyroidism in Q4 2022.

For Transcon CMP.

Topline data from the phase II accomplished trial are expected in Q4 this.

This year.

And we plan to file an IND or equivalent for the accomplish infants trial in Q2.

2022.

Operator: Within our Oncology Therapeutic Area for transconile to beta-gamma, monotherapy top-line results are expected in Q4 this year, for Transcon TLR78 Agonist. Top-line monotherapy and combo therapy dose escalation data in the Transcend IT-101 clinical trial are expected in Q3 this year. And lastly, for oncology, we expect to submit an INDR equivalent for a phase two cohort expansion for evaluating the combination of transcon TLR78 agonist and transcon IL-2 beta gamma therapy in the fourth quarter.

Within our oncology therapeutic area for Transcon IL, two beta gamma monotherapy topline results are expected in Q4 this year.

For Transcon <unk> are 708 agonist.

Top line monotherapy and combo therapy dose escalation data in the transcend <unk> 100 <unk>.

One clinical trial are expected in Q3 this year.

And lastly for oncology, we expect we expect to submit an IND or equivalent for a phase II cohort expansion for evaluating the combination of transcon Tls seven eight agonist and transcon <unk> beta gamma therapy in the fourth quarter.

Operator: Finally, we plan to announce our third therapeutic area in the fourth quarter this year. And with that, operator, we are now ready to take questions. Thank you. As a reminder, to ask a question, you'll need to press star 1 on your telephone. To withdraw your question, please press the pound key.

Finally, we plan to announce our third therapeutic area in the fourth quarter this year.

And with that operator, we are now ready to take questions.

Thank you.

As a reminder to ask a question you will need to press star one on your telephone to withdraw your question. Please press the pound key.

Please limit yourself to one question and one follow up.

Standby tayo the Q&A roster.

Operator: We ask that you limit yourself to one question and to one follow-up. Standby to compile the Q&A roster. Our first question, Jessica Fye of J.P. Morgan, your line is open. Hey guys, good afternoon.

Our first question Jessica Fye of Jpmorgan Your line.

Hey, guys. Good afternoon, thanks for taking my questions.

Jessica Fye: Thanks for taking my questions. Does the 708 prescriptions of the February 28th equate to 708 patients, given what you said about each script usually being written for a year, or are any of those scripts refills? And to make sure, when you say a script is written for a year, Are you saying that's like a script for, you know, the first month of therapy and it has 11 refills or is it the single script really written for like a full year's worth of product?

708 prescriptions as of February 28th equate to 708 patients given what you said about each script, usually being written for a year or are any of the scripts refills.

And to make sure when you say a script is written for a year.

Are you seeing thats like a script for the first month of therapy. It has 11 rebuilds or is it a single script really written for like a full years worth of product.

Jessica Fye: and I have a follow-up. I think, thanks, yes. I think it's a good clarification that we are building is that because we wanted to get a clear winner. Description is being written to because it was covering for one, and Shu. There is a lot of refills, but it's still covering under the same prescription. So when we talk about the number 704, we basically, believe that all of them are independent patients. Scott is correcting me, 7 or 8.

And then I have a follow up.

I think thanks Jess.

<unk>.

I think it's a good.

Good clarification that we build.

Is that because we wanted to get it clear when a prescription is being region should because people covering full one year and Shaw.

So a lot of greenfield, but it's covering onto the same prescription so when we talk about but not booked seven over for the basin.

Believe that is all of them it dependent patients.

Scott is correcting me seven elite.

[laughter].

Jan Mikkelsen: Okay, great. Next one is, does the CRL for Simatrigon affect your discussions with payers at all? I guess, were any of the payers waiting to see how that FDA decision and potential contracting with that product played out prior to finalizing contracts with Ascendis? First of all... We are the only approved, once we give product opportunity in the U.S. We have seen how oil, long-acting has not been approved. We have no explanation and knowledge about it.

Okay great.

Next one is does the TRL for snap <unk> affect your discussions with payers at all I guess, where any of the payers waiting to see how that FDA decision and potential contracting with that product played out prior to finalizing contracts with offenders.

First of all.

Okay.

We are the.

The only approved once we do product opportunity in the U S market.

We have seen how oil.

Oil.

Long acting has not been approved we have no explanation.

About it what we are.

Jan Mikkelsen: What we are Moving forward is our planned commercial launch strategy, and we're following it, and we really believe that we're executing as we only had, So when we saw there was a CRL for this product opportunity, we also believed that it was part of our expectations. We had different scenarios and it was definitely one of the scenarios we were working into our launch strategy. I believe Jesper's team and Margaret's team.

Moving forward is our planned commercial launch strategy and be following it and we really believe that to be executing as we only had to postpone.

So when we sold that Walter.

For this product opportunity we all.

Also believes that it was part of our expectations, we have different scenarios and there was definitely one of the scenarios, we can into our overall strategy.

I believe yes, both tea and the marketing team.

Jan Mikkelsen: Under Jesper is doing an amazing job to get this market assessed and I also think the numbers we've seen and how we're getting covers is living up to exactly the plan that we expected to be at the time where we are now. So when I shoot someone, I might read about the lungs. We believe we will have been the leading brand in the U.S. market independent on all our product options. We only see if there will be one more or two more long-acting in the U.S. market.

<unk> is doing an amazing job to get this market emphasis and I also think the non box, we see and how we are getting cohorts is living up to exact EBIT claim that we expect it to be at the time were beyond now so we're not huge somewhere like my read about the launch.

We believe we would have been the leading brand in the U S market independent on all protocol opportunity, we only see if that would be one more or two more long acting bill.

But in the U S market is only about what is the total conversion of the entire market segment over too long acting and how fast it's growing we have no down when we look at our product profile, we see what we have seen from our label. We believe we have everything.

Jan Mikkelsen: It's only about what is the total conversion of the entire market segment over to long-acting and how fast it's going. We have no doubt when we look at our product profile, we see what we have seen from our label. We believe we have everything built in to build up a leading brand here in the U.S. and be doing it day by day.

Pillar two.

<unk> brand here in the U S and be doing it day by day.

Thank you.

Operator: Thank you. Our next question comes from Tazeen Ahmad of Bank of America, your line is open. Hi, good afternoon.

Our next question comes from <unk> Ahmad of Bank of America. Your line is open.

Tazeen Ahmad: Thanks for taking my question. Maybe a point of clarification around growth to net. Can you give us a sense, it's very early days, of where you're starting out and where you might think it will flatten out as the year progresses?

Hi, good afternoon, thanks for taking my questions.

Maybe a point of clarification around gross to net can you give us a sense. It's very early days of where you're starting out and where you might think.

Flattened out of senior progressive.

Scott Smith: And then, as far as the quarter goes, did you see any kind of heightened impact from Omicron, particularly in December? We just want to get a sense of any kind of additional variability to expect from COVID going forward. Thank you. I think Scott will take the first question, and yes, we can, explain how the commercial infrastructure has adapted to all different kinds of scenarios and how they're adapting to the changes in the COVID and Tazeen, on your question about gross to net, So, products sold through at this point is, I would say, with minimal discount, and we're not specifically disclosing where we expect it to go. We did take a provision, as you can see in the financial statements, to reduce reported net sales.

And then as far as the quarter goes did you see any kind of heightened impact from omicron, particularly in December .

We just wanted to get a sense of any kind of additional variability to expect from Covid going forward. Thank you.

I think.

Scott will take the first question and guess what Karen.

Explain how the commercial infrastructure has adapted to all different kinds of scenarios and how they're adapting to the change so did the COVID-19 .

And <unk> on your question about gross to net.

The.

So products sold through at this point is I would say with nimble discount and we're not specifically disclosing where we expect it to go we did take a provision that you can see in the financial statements to reduce reported net sales that accounts for the initial launch phase.

Jesper Hoyland: That accounts for the initial launch phase that we're in now, and the fact you might have product returns, you might have other prompt pay discounts and chargeback and rebates, I would say I wouldn't necessarily look at that as any forward-looking guidance. Yeah, if I can add, we're very pleased with where we are right now. When we were sitting doing the launch, we did anticipate COVID to be in place. And of course, we have seen pediatric centers being locked from the point of view that our representatives have not been able to do face-to-face calls. That has then transformed into virtual calls with them.

Phase that we're in now and the fact that you might have product returns you might have other prompt pay discounts and charge backs and rebates, but I would say I wouldn't necessarily look at that as any forward looking guidance.

Yes.

Yeah, if I can add we are very pleased with where we are right now wouldn't be receding. During the launch we did anticipate COVID-19 to be in place and of course, we have seen pediatric centers.

Being locked from the point of view that our representatives have not been able to do face to face calls.

That has been transformed into virtual calls with them.

Jesper Hoyland: However, as we're speaking, we are certainly seeing the markets, i.e. the hospitals opening up and giving us access on a face-to-face call, which is, of course, a preference to us. So in short, we have baked it into our expectations. And certainly, we anticipate to see the market opening up now as spring is coming. And also, hopefully, COVID is going to be behind us.

We are speaking we are certainly seeing the market I E. The hospitals opening up and giving us access on a face to face coal, which is of course, our preference to us. So in short we had baked it into our expectations and certainly we anticipate to see the market opening up now as spring is coming and also hopefully.

Covid is going to be behind us.

Scott Smith: Just to jump back to Scott for a second, can you just clarify on gross to net? Are you saying that you did not discount this first quarter? I just want to understand that a little bit better.

Okay. Thanks, Jesper just to jump back to Scott for a second can you just clarify on gross to net are you, saying that you did not.

Count this first quarter I, just want to understand that a little bit better.

Scott Smith: So, we have a specialty pharmacy and specialty distributor network that's set up. There's on-invoice discounts that are, I would say, fairly minimal, single digits in the aggregate. And we also, on top of that, booked a provision that you can see in the financials to reflect the startup phase that reduced our net sales down from the on-invoice price. That provision was about 1.2 million euro.

So we have.

Especially pharmacy and specialty distributor network that setup.

There's an invoice discounts that are I would say fairly minimal single digits in the aggregate.

And we also on top of that booked a provision that you can see in the financials to reflect the startup phase that reduced our net sales down from the on invoice price that provision was about $1 2 million thereof.

Thank you.

Operator: Thank you. Our next question comes from Michelle Gilson of Kennecott Genuity. Your line is open.

Our next question comes from Michelle Gilson of Canaccord Genuity. Your line is open.

Michelle Gilson: Hi. Thank you for taking my question. I guess to start, one for Scott.

Hi, Thank you for taking my question.

I guess just one for Scott.

Scott Smith: You know, you mentioned that revenue recognition is to the specialty distributor. Can you maybe help us understand how much is in the channel? And then one on PTH from me too.

You mentioned that the revenue recognition is to the specialty distributor.

Can you maybe help us understand how much is in the channel.

And then one on PTH from me too can you remind us what kind of regulatory discussion discussions you've had around PTH and <unk>.

Scott Smith: Can you remind us what kind of regulatory discussions you've had around PTH and, you know, to what extent the FDA has some input in the phase three trial design and the primary endpoint? And then, you know, what really needs to be shown within the phase three data set to get a label as a PTH replacement therapy versus an adjunct to therapy in that, you know, differentiation from that PARA in the labeling in terms of what regulators want to see to differentiate, I guess, the two programs? Michel, that was many questions. But I think Dana and I can combine take the second part, but I think we should let Scott get some speaking time. So he will be first.

To what extent the FTAA had some employed in the phase III trial design and the primary endpoint.

And then what really needs to be shown within the phase III dataset to get a label as a PTH replacement therapy versus an adjunct therapy in that.

<unk> from that part in the labeling.

In terms of what regulators want to see to differentiate I guess the two programs.

Hi, Michelle.

Many questions but.

I think Dana and I can combine takes a second talk about I've seen visualized Scott get some speaking time, so <unk> first.

Scott Smith: So the question, I believe, was what inventory is in the channel versus what's sold through. As of December 31, as I think we just said on the prepared remarks, the initial sales were largely stocking as of that period, but separately, of course, we reported the same launch metrics that we gave you at J.P. Morgan through the end of February. So you can see how patient demand overall has grown. Michelle, going back to you, and I will start and then I will turn it over to Dana and she will explain how the interaction is on.

Michelle.

The question I believe was what inventories in the channel versus what's sold through as of December 31, as I think we just.

I said on the prepared remarks that the initial sales were largely stocking as of that period, but separately of course, we reported the same launch metrics that we gave you a J P Morgan and through the end of through the end of February .

So you can see how patient demand overall has grown.

Yeah.

Michelle going back to you and I will start and then I'll turn it over to Dana and she will explain how the interaction is on but let US just go back and look about white of your teeth.

Jan Mikkelsen: But let us just go back and look about why are we taking a hormone replacement therapy, and what do it really mean for this? composite endpoint we have. First of all, We have some of the same parameters in our primary endpoint that you basically have seen in an adjunct labeling. Normalization of serum calcium, taking away vitamin D, taking away calcium supplements.

Got home replacement therapy, and what do we really need for this.

Composite endpoint behalf first of all.

We have some of the same Pam just in our primary endpoints that your basic Hep C.

And a chunk leaping normalization of <unk>.

Taking away vitamin D taking away some supplement but then.

Jan Mikkelsen: But then everything comes back to what is really the definition of success for each single parameter. And just taking something like serum cancer, we need to be higher than 8.3. Because we believe that it's what we call normal serum cancer. If you go into an adjunct lately, then you say, I'm highly successful if I just take 50% away. What we did, for example, doing with activated vitamin D, it needs to be down to zero because no normal person, to my knowledge, takes activated vitamin D. If you go to the junk label, you need to reduce 50% of the calcium supplement.

Come back to what is really but the condition of success for each single pad, where you go and just taken something like <unk>, we need to be higher than $8 tweak because we believe that is a north Dakota normalcy.

If you go into an adjunct late did you say.

Highly successful if I, just take 50% of women.

What we did for example doing with activate devices.

It needs to be down to zero, because no normal person to speak.

To my knowledge sake activated vitamin D.

If you go to the adjunct leaving you need to reduce 50% of the <unk> supplement.

Jan Mikkelsen: So, if you take 8 grams of calcium supplement, which is not national for an ASB patient, then if you take 3.9... Grant per day, you are successful in an adjunct labeling. We need to take it down to the level that you take with a multivitamin class. Because we cannot demand people take a certain multivitamin type.

If you take eight gram of catch some supplement which are not.

So far in HD patients then if you take three nine Gram per day to assist with benign and adjunct lately.

To take it down to the label what you take to the boutique tabs.

Tablet because I'll be conducting my people should take them, which are expected to be.

Jan Mikkelsen: So you can see, even if we have the same parameter, what our primary endpoint is really reflecting is a hormone replacement therapy, where you go in and you basically take our transcom PTAs on a daily treatment, and then you basically get a normal serum capsule, don't take activated vitamin D, and just take the same amount of a normal vitamin, multivitamin. That is a hormone replacement therapy, and that is why we're discussing that with the Reptotoy agency. Dana, you can comment about our interaction, how we progressing, how we have discussed it, how we have basically agreed to everything after phase three endpoint. Yes, sure, Michelle, thanks for the question.

So you can see even if we have the same pattern.

Primary endpoint is really with predicting is homelink replacement therapy, where you go in and you basically take our transcon PTH online.

<unk> and you basically get enormous catch them don't take activated vitamin D and the.

C amount often normal vitamin mewtwo, vitamin, Texas Eastern home replacement therapy, and that is widely discussion with the regulatory agencies.

And then you can comment about all interaction how we are progressing well we have discussed with how we have.

Equity two of everything of the phase III endpoints.

Dana Pizzutti: We've had numerous interactions with FDA and actually before, you know, we even started the Phase 3 and even sent them the protocol, we talked with them about our Phase 2 data and the fact that we wanted to be a replacement therapy. Okay, so we designed a fairly rigorous trial. So as soon as the protocol was done before we started to enroll, you know, people, we sent the agency, you know, the protocol, they sent back comments, and we've had, you know, sort of a few interactions as we enrolled patients and then as patients progressed through the trial.

Yes.

Sure Michel Thanks for the question, we've had numerous interactions with FDA and actually before we even started the phase III and even sent them. The protocol, we've talked with them about our phase two data and the fact that we wanted to be a replacement therapy.

So we designed a fairly rigorous trial so as soon as the protocol was done before we started to enroll people we sent the agency.

The protocol they sent back comments and we've had sort of a few interactions as we enroll patients in that as patients progress through the trial and right up until.

Dana Pizzutti: And, you know, right up until the last few months, we talked with them about our analysis plan, you know, before we hit the sort of end of the double blind period, we had to finalize that, send that to the FDA before we do anything. And so, you know, we think we're in a pretty good place.

The last few months, we've talked with them about our analysis plan before we hit the sort of the end of the double blind period, we had to finalize that and that to the FDA before we do anything.

Dana Pizzutti: And we've, you know, acknowledged the FDA input and are planning to analyze the data, you know, consistent with what their, you know, advice has been. So, so it's been, you know, an ongoing collaboration with them. So we're really thrilled to have the data coming out in the next week. Thank you. Our next question comes from Josh Schimmer of Evercore. Your line is open.

So.

We think we're in a pretty good place and we've.

Its knowledge the FDA input and are planning to analyze the data you know.

Consistent with what they are.

It has been.

So it's been an ongoing collaboration with them.

So related to holidays are coming up in the next weeks.

Thank you.

Our next question comes from Josh Shimmer of Evercore.

Your line is open.

Josh Schimmer: Great. Thanks so much for taking the questions. I guess the first question is, thank you for joining us for this SkyTrophy launch. Why are you already noting provisions for product returns? Seems a little bit early.

Great. Thanks, so much for taking the questions I guess first on the <unk>.

Scott Smith: Have you been seeing any product returns thus far, and why? And then, for the PTH program, what do you see as the primary barriers to broader adoption of PTH replacement? It looks like Takeda was trying to promote some of the quality of life benefits of Natpara and the cardio-renal benefits of Natpara. They did have some supportive data, but it didn't seem like they were gaining much traction with a broader hypoparathyroidism audience.

On the schedule for lunch why are you already noting provisions for product returns seems a little bit early have you been seeing any product returns, thus far and wide.

And then for the for the PTH program.

Do you see as the primary barriers to broader adoption of PTH replacement. It looks like Takeda was trying to point out some.

The quality of life benefits of that power in the cardio renal benefits of that perhaps they did have some supportive data, but didn't seem like they were getting much traction too.

To a broader hyperparathyroidism audience last question as we think about the decision tree.

Scott Smith: And then the last question, as we think about the decision tree for transcon CMP at the end of the year, are there certain phase two outcomes that you think could support filing for accelerated approval? And if so, what might they be?

For Transcon CMP at the end of the year.

Phase two outcomes that you think could support filing for accelerated approval and if so what might they be thank you.

Thanks, Jos who will say.

Jan Mikkelsen: Thank you. Thanks. Yes, more questions so but I think I will let Scott start first. Josh, related to the question, are you seeing product returns, to my knowledge, no, although it is early, so the end is fall.

More question, so, but I think I'm gonna data Scott stopped first.

Josh related to the question are you seeing product returns.

To my knowledge no. Although it is it is early.

And this fall the reason we take a provision is for.

Scott Smith: The reason we take a provision is from an accounting perspective, based on the experience we have commercializing, we take a conservative position and just account for the fact that there'll be a number of chargebacks, returns, rebates, write-offs, things like that. Over time, of course, we would expect the provision to bleed off, if none of those things are realized. Thanks, Scott.

From an accounting perspective based on the experience we have commercially commercializing we take a conservative position and just account for the fact that there'll be a number of charge backs returns rebase write off costs things like that over time of course, we would expect that provision to go.

Laid off with if none of those things are realized.

Okay.

Thanks, Scott related to the P. J, it's Christian.

And that's what I understood you right.

Just is that youre asking the.

Basic why some of those shoulder.

<unk> has not really got the right penetration.

But it goes back to how you use those best optimal weight with short Act.

Jan Mikkelsen: Related to the PTH question. And as I understood, you're right. Just that you're asking the basic why some of those shorter acting PGHs have not really got the right penetration. But it goes back to how you use the best optimal way, the short act. You open the cartridge.

You opened the cartridges.

Jan Mikkelsen: Check the content, take it into an infusion pump. So you can give it at the physiological level 24 hours, 7 days a week. That is what is happening with us. If you give a short acting, the best case you can see is that you can get an, Partly Normalization of Serum Calcium, Partly Reduction of Activated Vitamin D, Partly Reduction of Serum Calcium.

Take our content.

Ticketing to an infusion pump.

You can keep it into the future logical level 24 hour seven day, a week that is what is happening with a lot of that.

A short acting but best case, you can see is take you can get.

Policy normalization of Trillium Ketchum talking of adoption of activated vitamin D popular adoption on.

Jan Mikkelsen: Kate and Sophomore, You're not seeing the expected 24-hour urinary calcium benefit. You're not seeing any kind of statistics, effects related to quality of life. So when you compare this short-acting PTH product with the target product profile, or what we aiming to show in our phase three clinical trial, that's coming up in the coming days. It's a true hormone replacement therapy. And this is how Ben just explained how she has built up, in interaction with recruitment agencies, what is the meaning of a hormone replacement therapy.

Cut some supplement.

Youre not seeing the expected 24 hour urinary catch up benefit youre, not seeing any kind of statistic.

It's a perfect related to quality of life.

So when you compare this short acting PTH products with the target product profile of what we're aiming to show in our phase III clinical trial, that's coming up and becoming this week.

A true hormone replacement therapy.

This is Jeff.

Just explain how.

She has been stopped.

Action with Victor toy agencies, what is the meaning often holding replacement therapy.

Jan Mikkelsen: This is the same thing to think about other hormone replacement therapies, would it not be. Unbelievable to think any diabetes, type 1 diabetes patient should have insulin. Why is it so difficult to believe that when you can have physiological level of PTH, maybe... P.J.

So you tend to think about auto home replacement therapy.

Would it not be.

Unbelievable to take any debt.

That would be just patient and not shoot happening soon.

Why it's so difficult to believe that when you can have some logic to the level of <unk> Baby P. J.

Jan Mikkelsen: 's Patient at Lack, Sufician and Dosh's, P.J. 's, not to have that and this is what the benefit we want to show in all our clinical trials everything from the primary endpoint we discussed urinary calcium continuum quality of life etc etc change in bone remodeling everything what we want really showing what is really how to normalize the life of this patient by having restoring the normal physiological. The CMP question you're addressing is a really, really good one. And it's also one of the interactions I have on... All this with Dana and her team from Brekker Toys.

Patient that lack sufficient industrious P chase.

Not sure have that and this is what the benefit we want to show it all clinical trials averaging.

Everything from the primary endpoint we discussed.

So continue on quality of life is safe to say top change in bone remodeling. It we're taking what we want to see.

Really showing what is really how to normalize the lives of these patients by having restoring the enormous histological P T.

But good CMP question you addressed is a really really good one.

And it also that one of the interaction might have thought.

August with Dana and her team from breakfast tourism.

Jan Mikkelsen: What is basically the strategy to get this important product out to the patient as fast as possible? And I can guarantee you, Josh, we're working dedicated to get that done. And I think Dana and her team together, the rest of the clinical development team and everyone is trying to do that. So what we believe is a proportional part of that is to look and see the data we're getting out in the future, because this is data that's coming from a really robust tree, data that's coming from, 57 patients. And remember. More than 40% of the patients are in the age group from 2 to 5. This is not all children.

What is basic the strategy to get this important call it out to the patients as fast as possible.

And I can guarantee you Josh we would continue to cater to get that done.

I think Dan on how cheap to get the right of the clinical development team and everyone is trying to do that.

So what we believe is important part of that is to look and see the data, indicating up end of this year.

Because this is state of us coming from our beauty with post treatment data that's coming from.

57 patients.

And remember.

More than 40% of the patients in the <unk>.

Scoop from two to five.

Jan Mikkelsen: More than 40% are in base groups 2 to 5, and we will look at that on a double-blinded placebo-controlled efficacy and safety after one year with all the different codes. At the same time, we're also doing cohort expansion, really enrolling on what we believe could be a recommended dose. And we also want to imitate in newborns or in studies between zero and two years this year.

It is not.

Children more than 40% in base grew to two funds.

And we will look on that on the total blinded placebo controlled efficacy and safety after one year with all the different cohort at the same time, we also doing cohort expansion really in voting on what we believe could be a recommendation.

<unk>.

And we also want to imitate.

Newborn all.

<unk> started to achieve zero in two years. This year. So actually believed the package we building off now.

Vikram Purohit: So, I actually believe the package we're building now related to our transcon CMP is unique, not only for aconoplasia but perhaps for many other growth disorders because where we believe C&P could be an important component. Thank you. And again, we ask that you please limit yourself to one question and one follow-up. Our next question comes from Vikram Purohit of Morgan Stanley. Your line is open. Great, thanks for taking my question. So I had two on Sky Tropha.

Ladies around our transcon CMP is unique not only for our compensation.

As for menu oil.

Growth two sold because wherever you believe CMP.

Important component.

Thank you.

Again, we ask that you please limit yourself to one question and one follow up.

Our next question comes from Vikram Rohit.

Morgan Stanley Your line is open.

Great. Thanks for taking my question.

I had two on Sky Trophy first of the prescriptions that you've seen written so far could you comment on how many have been for treatment naive patients versus for patients that are being switched over from a previous daily growth hormone and then secondly from any conversations you may have had with doctors prescribing the therapy since launch. However, they described the authorization process, where that's been applicable.

Jan Mikkelsen: First, of the prescriptions that you've seen written so far, could you comment on how many have been for treatment naive patients versus for patients that are being switched over from a previous daily growth hormone? And then secondly, from any conversations you may have had with doctors prescribing the therapy since launch, how have they described the authorization process where that's been applicable in terms of how long it took to get their patients approved and how much of an administrative burden the discussions with insurers have posed to their staff? Thank you. Thanks a lot.

In terms of how long it took to get their patients approved and how much of an administrative burden to discussions with insurers have posted their staff. Thank.

Thank you.

Jesper Hoyland: I think I will start and then both Jesper and Scott can help me in adding in some facts if I forget it. What we see, we see a development in the ratio between what I call the new patient compared to the switched patient. What we saw from the beginning was that the vast majority of patients were switched patients because they didn't need to wait for the establishing of the right diagnosis which involved multiple tests including a stem test of growth hormone stimulation.

Thanks, a lot I think I will start and then both of you.

Yes, Paul and Scott can help me.

Adding in some factories.

Forget it.

What we see we see development in the ratio between what I call the patient compared to switch patients. What we saw from the beginning was to have wished majority of patients were switched patients because that didn't need to wait for the stepping off the right diagnosis, which involve multiple.

Including estimates of growth hormone stimulation. So what we saw from the initial.

Jesper Hoyland: So what we saw from the initial... Part of this is mainly switching patients. We see now that it's switching more and more over to naive patients from that. And one of the things I was most surprised about was just after one week, we got our first commercial patient. But I think, but in a general perspective, can explain what our effort is really about to be quite sure we are converting as fast as possible, as many as possible, over to commercial patients, and we have a unique setup to our hub that really is the foundation in getting this done.

Part of this is may be switch patients, we see now it's switching more and more over to patients.

Patients.

And one other thing I was most surprised about was just after one week of offers promotions patient, but I think yes booked in a journal perspective kind of explain what our effort is really to be quite sure you'll be converting as fast as possible.

As many as possible to commercial patient and we have a unique set of <unk> that really August fundament in getting this done yes, Bob.

Jesper Hoyland: Absolutely. And basically, what we're having is we have the ASAP program that I'm sure that you're seeing, Vikram. And that is very common to have also normally called the FASTA program. And you will anticipate that it takes anywhere between, Two weeks to six weeks for the normal, prior off, which is the typical routine that all growth hormone patients are going through.

Absolutely.

Basically what we're having is we have the.

The program that I'm sure that you have <unk> and that is very common to have also normally called fast start program.

And you will anticipate that it takes anywhere between.

Two weeks to six weeks for the normal prior offs, which is the typical routine that all.

Jesper Hoyland: Prior approval is a common standard for drugs that cost more than a thousand dollars a month, which is, of course, what we are talking about here. And then, in case of rejection, we are going for what's called medical exceptions, and there is paperwork involved in it, but doctors see it as an opportunity to help their patients go from, you could say, the hard work of once daily treatment to once weekly and thereby getting much better compliance from the patients in terms of remembering to take the injections.

Hormone patients not going through.

Oh I see.

Common standout for drugs that cost more than $1000 a month, which is of course when we are talking about here and then in case of a reduction.

Going forward, what called medical exceptions and Darius at.

Paperwork involved in it but the doctor to see as an opportunity to help their patients going from <unk>.

You could see hot-work up once daily treatment and transferring that patients on to once weekly, thereby getting much better compliance from the patients in terms of remembering to take the injection. So all in all that's the scheme that the patients go through and we are certainly focusing in.

Jesper Hoyland: So all in all, that's the scheme that the patients go through. And we are certainly focusing in as Yantas in the first place on the switch patients because they were in the queue to get transferred. And then of course, as time goes by, we will also see new patients coming on board. Thank you as well.

<unk> in the first place on the on the switch patients because they were in the queue to get transferred and then of course as time goes by we will see nave patients and new patients coming on bolt.

Thanks, Yes, great.

Thank you.

Operator: Great. Thank you. Our next question comes from Joseph Schwartz of SVB Lear Inc. Your line is open.

Our next question comes from Joseph Schwartz of SVP Leerink. Your line is open.

Joseph Schwartz: Hi, I'm Jermaine Dialing in for Joe. Thank you for taking our questions. I know it's early days, but you know, when can we expect to see sales guidance for SkyTrooper? When we feeling confident in giving you numbers that we believe in, it was going to be reflecting how, the sales is progressing during the first period of time and one of the guidance at least for myself and this is something we discussion because we have different gut feelings everyone at least i would like to see at least two full courses, And then when we have seen at least two full quarters, we can look at it and then think about it and saying, is that really?

Hi underneath dialing in for Joe. Thank you for taking our question.

It's early days, but when can we expect to fulfill guidance with ghansham.

When we feeling confident in giving you numbers that we believed in it.

To be reflecting hull.

<unk> is progressing during the first period of time and one of the guidance at least for muscle and this is something to be discussion because we have different cost feelings everyone at least I would like to see at least two full quarters.

And then when we have seen at least two full quarter. We can look at it and then think about it I am saying is that really.

Joseph Schwartz: Sushila Hernandez, Yaron Werber, Derek Archila, Jan Mikkelsen, Ascendis Pharma, Aimee Shuh, And this is what I'm saying to Jesper: we are here to build up the leading brand. We want to have a plan that we execute not only the most prescribed growth hormone product but also the most high-value product.

Sufficient good enough to give you guidance into a range that is not really meaningless for you, but really you wanted recall finance modeling guidance.

I really don't really care, so most advanced with first.

Quarter, what I really want to know and this is what I am saying two years ago, we are here to build up.

Leading brands.

We want to have a plan that we execute during on not only be the most prescribed growth hormone product, but also the most high value protein.

Jan Mikkelsen: And that is what we're building our strategy on. And that is evolving yes from a commercial side, but also then a clinical development, even Scott, where we want to go in and be sure that we're building up the right label expansion so we can address the entire growth hormone market. And this is how we built up a leading brand, not only in the U.S., but on a global basis. Okay, great.

Pro forma product and what we are building a whole strategy on and that is one thing useful from a commercial side, but also in the clinical development, even Scott wherever you want to go in and be sure that the building after a bright leave of expansion. So if you can address the entire growth come on market and this is how we built up a deal.

Being Frank not only in the U S, but on a global basis.

Operator: Thank you. And then I have a question relating to Transcon C&P. So a competitor recently announced that in children less than five, they saw trends favoring their agent compared to placebo on an annualized growth velocity. We haven't seen the data, but it appears that there could be some differences based on age.

Okay, great. Thank you and then I have a question relating to your Transcon <unk>.

A competitor recently announced that ensure.

They saw a trend favoring our agent compared to placebo on an annualized growth velocity, we haven't seen that data, but you know it appears that there could be some differences based on each.

Now that you're studying transcon <unk> children as young as two an accomplishment even younger and accomplish okay.

Leland Gershell: I know that you're studying transcon C&P in children as young as two and accomplished and even younger and accomplished infants. So I'm curious what you make of that and if you're anticipating any differences in younger children. Thank you very much. Thanks a lot.

So I'm curious what you make of that and if you're anticipating any definite cool. That's helpful. Thank you very much.

Jan Mikkelsen: I think I can comment about some of the facts, and Dana and her team are really always looking into the safety, and also we provide a safety update in our R&D date, but the facts are we have 42% of our children in the accomplished trials is actually in the age between two and five. And we have, for many of them, we have more than one year safety database. So, Dana, perhaps you can in some way sum up some of what we have seen from a safety perspective. And the easiest way for you, just take it on a blinded basis.

So look I think I can comment about some of the effect.

Good day and her team are really oldest looking into but safety and also be providing a safety update in the R&D day, but the facts Avi you have 42% of our children in the accomplished triumph is exited in the ace between two and five and we have for many of them we have more.

Then one year safety database, so Dana perhaps you can somebody some up some of what we have seen from a safety perspective, and the easiest way for you've just taken on a blinded basis.

Dana Pizzutti: Yes, well, so far, the compound has been extremely safe, and we haven't seen any problems related to cardiovascular side effects or things like that. So, you know, we're very pleased with that. And we also feel that the sort of continuous release of CMP, you know, is an advantage. I think, you know, to your other point, though, we do notice that, you know, the younger kids grow faster, right?

Yes, well so far.

The compound its been an extremely safe and we haven't seen any.

Problems related to.

Cardiovascular side effects or things like that so.

We're very pleased with that.

We also feel that the sort of continuous release of CMP.

It is an advantage.

I think.

To your other point, though we do notice that.

Dana Pizzutti: And so there, you know, is an opportunity to potentially have a greater impact on that group once we, you know, can unblind the data. But, but, you know, again, even sort of our natural history shows that, you know, that's, you know, sort of the some of the biggest, you know, changes that they have in their growth. So, you know, we're very excited about, you know, finally being able to tease it out and break it down, right, by age group so that we can, you know, get a better idea of, you know, whether the effects are even more magnified in the younger age group. Thanks a lot.

The younger kids grow faster right and so there.

It is an opportunity to potentially have a greater impact on that group once we can on blind the data but.

Again, even sort of our natural history shows that.

That's sort of the some of the biggest changes that they have in their growth. So.

We're very excited about.

Finally, being able to tease it out and break it down by age group. So that we can get a better idea of whether the effects are even more magnified in the younger age group.

Scott Smith: But I think Scott can someday also provide you with our link or the slide related to our research and development day that we had in December last year, where we provided an extensive safety update about the patient in the accomplished trial on a blinded basis. There you can see all the complete elements we have. Thank you. Our next question comes from David Lebowitz of Citi. Your line is open. Well, thank you very much for taking my question. I've got two for you here.

Thanks, a lot.

But I think Scott can somebody also provide you with all the all the slides related to our research and development day that we had in December of last year, where we provided and distinctive safety update about the patient.

These trials on a blinded basis. There you can see all the complete elements we have.

Thank you.

Our next question comes from David Lebowitz.

<unk>.

Your line is open.

Well. Thank you very much for taking my question.

Two for you here a quick one on Skype profile.

David Lebowitz: A quick one on Cytrofa. Given the uptick from earlier in January on prescriptions, how can we think in that in terms of cadence going forward on sales for the drug throughout the year? and flipping over to Transcon PTH, on what basis do, Physicians typically prescribe for these patients. Is it based on things such as reduction of vitamin D, active vitamin D and calcium?

Given the uptick from earlier in January prescriptions, how can we think of that in terms of cadence going forward on sales for the drugs throughout the year.

And flipping over to Transcon PTH.

On what basis do.

Physicians typically prescribe.

For these patients is it based on things such as reduction of vitamin D. Activate even D and calcium is it more an intangible quality of life type items and with that in mind do you have two different quality of life type items as secondary endpoints could you compare each of those end.

Jan Mikkelsen: Is it more on intangible quality of life type items? And with that in mind, you have two different quality of life type items as secondary endpoints. Could you compare each of those endpoints and what they mean? And how would these actual endpoints?

Points and what they mean and.

How would these actual endpoints.

Jan Mikkelsen: be meaningful to prescribers. Okay, there was a lot of pressure related to PTAs, but let us start with the Skytober first and think about what is a whole read about this year. And you know, we share in three different KPIs with you. But yes, he has about 20-40 KPIs he's looking on week by week to be sure we are matching and really going in the right direction. So the KPIs we are using in, because we don't, believe at our current stage of our initial launch, we basically have what we call revenue basis that really are predicting how this product opportunity really are pulled.

The minutes meaningful to prescribers.

Okay. What's a lot of question related to P J, but let us start with the sky.

And think about what is how about this year and we have shown three different kpis with you.

But guess what he has about 2014 kpis. He is looking at one week.

Weak two species.

Matching and really going into the right direction.

The Kpis, we are using in because we don't.

The lease at our current states of our initial loans be basic have what we call revenue basis that really are predicting how this product opportunity really full.

Jan Mikkelsen: Proformed inside the US market. And this is why we follow the different KPI and one of the numbers, the Feminine O.A. This is a pretty good number in prescription. 708 patients now under treatment with sclerotrophic in the US.

Performance inside the U S market and this is why we follow the different <unk> and one of the numbers sort of the same annoyed.

This is a pretty good number and.

<unk>.

708 patients now onto treatment, which is cultural fit in the U S.

Jan Mikkelsen: I actually am pretty proud of that and I'm proud of the organization that has managed to get this to happen. And I'm quite sure we will be marching to this number and increase it month by month. So when we look at all the different integrated KPIs we're using to follow the launch, we are in a position that we feel pretty, We know we're okay because we always want to do it better. And the day we stopped actually not to believe that we can do it better, I think we're doing a major mistake.

Pretty proud of that proud of the organization that have managed to get this to happen and.

And I'm quite sure view, both be marching to this number and increase it months by months. So when we look on all of our different integrated Kpis. We used to follow the law. We are in a position that we feel pretty.

We know what okay, because you always wanted to it Dave and David stop absolutely not to believe that we can do it better.

Doing well.

Mistake, but what we have seen also known as <unk> is living up to favorite thing what we have expected.

Jan Mikkelsen: But what we have seen until now in this long, is just living up to everything what we have expected. And we will see that continue to continue, and I believe the more and more we get a market assessment, the faster and faster we can penetrate, also to get not only the prescription done, but we also can get it over to commercial patients faster and faster. And that is the trend we see. I do not know if you have anything to add, Jesper, to this, before I go to PJ. No, I think it's bang on.

And we will see that continue to.

And I believe the.

More won't be gateway market assessment with fossil faster, we can penetrate also to get them not only the prescriptions on book, we also concluded or to commercial patients Fox and fastball and <unk> received I do not know if youre admitting to Ed you spoke to this before I go to <unk>.

Yes.

Jesper Hoyland: We are following it very closely, and we are very pleased with where we are right now. So week by week, we are looking at it and making judgments. And also, as you're saying, we have very positive feedback. So that's, of course, giving us momentum and confidence for the future. We will be the market leader in the long-acting sector. Yeah, going back to PTAs.

No I think it Bang on we are following it very closely and we are very pleased with where we are right now so a week by week, we're looking at it.

Making judgment I'd also ask you are seeing and we have very positive feedback. So thats of course, giving us momentum and trust for the future we will be the leader in the long acting segment.

Yeah going back to <unk> and I think this is Tim.

Jan Mikkelsen: And I think this is a question that somebody will come back to me when I look at what I have seen in the open label extension trial. Because what we have seen in the open label extension trial is that the science is really. And too, because when we see something that's not expected to happen, it's because we don't understand the science.

A Christian suddenly going back to me when I look and what we have seen in the open label extension trial, because what we have seen in the open label extension trial is that the signs it's really true.

And two because when we see something does not expect to have news because we don't understand the signs, but the science, where you have lots of <unk> and what the impact of that is actually being prudent to some menu population, where there had been using a short acting PTH and infusion pumps and we're seeing the same.

Jan Mikkelsen: But the science where you have physiological PTH and what the impact of that is actually been proven to so many publications where they have using a short-acting PTH and infusion. And we've seen the same thing in our Phase 2 open-label extension project. But think about the fact... We have this patient now for two years in an open-label study, two years. We have.

<unk>.

Phase two.

But think about the effects.

We have these patients for two years.

April started.

Two years.

Hi.

Jan Mikkelsen: 57 out of 50, taking it daily. But it's only happening because they see a major, major benefit. And this is not a long-term complication they are seeing there. Because in my experience, people don't really comply with any open-label extension just for long-term factors. They do it because it goes back to your question about quality of life. They feel they are getting their life back.

57 out of $50 million.

Taking a date Egypt.

It's only happening because the C. A major of nature of business and this is not long term computation best in there because.

The experiences that <unk>.

People don't really come.

<unk> in your open label extension just for long term factors that do it because it go back to your question about quality of life, they're feeling they're getting their license bank.

Jan Mikkelsen: Do we measure that with our SS36, where some of the subdomains are specific to some of the benefits we expect to see? We saw the benefit both on the summary and all the subdomains. Or we go to the patient-reported outcome with a more disease-specific one? I think we will see it on some of the subdomains for each of them.

Julian Mitchell.

Our <unk> 36.

Some of the soft domains are specific to some of the benefits. We expect to see we saw the benefit both on the summary, and all this off domains will be go to the patient reported outcome with a more specific one I think we received some of the <unk>.

Sure.

And that is what we expect to see bottom when we come through this year.

Jan Mikkelsen: And that is what we expect to see also when we come to this year. But what was impressive for me was that, just after four weeks, we could see it from a specific perspective. None of the other PJ's products have ever proven that, from a statistical perspective, just a few weeks in, there was an improvement in the quality of life. But I think you need to take it into the science of you stabilizing serum calcium, but you're also stabilizing a physiological PTH level.

Most impressive to me was to see just after four weeks, we could see from a strategic perspective.

None of the <unk> product has proven that could do that.

From a strategic perspective, just few weeks.

Douglas and improvement in the quality of life.

But I think you need to take it into the science about you stabilize lithium but you also stabilizing future logical PTH level and B note is a lot of P. G receptor in fact bring.

Jan Mikkelsen: And we know there's a lot of PTH receptors inside the brain. It's really accessible for the PTHs, and this is my personal view about the science behind it, is that it's the combination of a stable serum calcium and a stable stabilisation of the physiological PTHs level that provide all the benefits. But at the same time, you also see the other benefit on urinary traction, on bone.

Really assistant.

For the PT.

This is my personal view about the science behind it is that is.

The combination of a stable <unk>.

Staples, so compensation also should see logical P. G. SIB that provides all the benefits.

But at the same time, you also see volume benefit from Juno Texan unfold I can continue to talk about what it means for a person to have normal fuselage acquisitive, but sure in our phase III trial. When you come out to you we will be in a position what we call. The number of starts also conflict.

Jan Mikkelsen: We will continue to talk about what it means for a person to have normal physiological development. But sure, in our first retrial, when we come out here, we will be in a position that we will give you what we call the numbers that are also reflecting how we see the quality of life. Thank you. Our next question comes from Yaron Werber of Cohen. Your line is open. Hey, this is Gabon for your own.

How do you see the quality of life.

Okay.

Thank you.

Our next question comes from Yaron Werber Cowen Your line is open.

Hey, This is gave on for your own thanks for taking my questions.

Yaron Werber: Thanks for taking my questions. So first, you've shared that about 369 prescriptions had been written as of December 31st, and so all of those would be at least two months ago. Can you give us a sense of how many of these patients are now on therapy, which would also help provide some insight into the success rate of the prior authorization process?

Jan Mikkelsen: that I believe was asked about previously, and then I have a follow-up. I think the guestbook indicated that what we have, we have a fast start program, so I believe the majority of all patients are, what we call coming into our fast start program. So the basic will be on, and then during this period they will be converted into commercial patients. Decision-making, Okay, yeah, that makes sense. So how many of those patients have been converted among among the first 369 as of December 31? Those would be you know, more than eight weeks ago?

First you've shared that about 369 prescriptions have been written as of December 31.

And so all of those would be at least two months ago.

Can you give us a sense of how many of these patients are now on therapy, which would also help provide some insight into the success rate of the prior authorization process.

We've had asked about previously and then I have a follow up.

I think the.

As Tony just indicated what we have we have a fast start program. So I believe the majority of all patients.

Because coming into our fast start program, so that basic will be on treatment.

And during this period that will be converted into commercial patients dependent on the speed, yes, but talk about some where do you expect two weeks some could take up to eight week or something like that would lead to the process of getting the move from walking over to commercial.

Patients.

Okay, Yes that makes sense of how many of those patients have been converted among among the first 369 as of December 31st and those would be more than eight weeks ago or can you provide any any insight there just to give us a sense of how the conversion is going.

Jan Mikkelsen: Or, you know, can you provide any, any insight there just to give us a sense of how the conversion is going? The conversion is going exactly as what we have expected and Maxwell, as we said, which I indicated, I saw the first commercial patient coming after one week. So the commercial patients are coming exactly at the expected speed compared to what we expected to see from our knowledge of the growth hormone market function, how growth hormone treatment. We are not there different compared to that. Our next question comes from Leland Gershell of Oppenheimer, your line is open. Hey, good afternoon. Thanks for the update and taking my questions. Just a couple on Skytropa.

The conversion is going exactly as we.

Expected IMAX OSB site.

Which I indicated silver first commercial patient coming after one week. So the commercial patients are coming exactly as we would expect to speed compared to what we expected to see from our hope with go to market function how quarter among treatment, we're not that different compared to that.

Thank you.

Our next question comes from Leland <unk> of Oppenheimer. Your line is open.

Hey, good afternoon, thanks for the update and taking my questions just a couple on spectrum.

Thanks for the update on the 36% of all.

Leland Gershell: Thanks for the update on the 36% of covered lives. Could you comment maybe on how that process is going in negotiating with players relative to what your expectations have been? Are there any sources of pushback or challenges that you're encountering?

Covered lives could.

Could you comment maybe on how that process is going and negotiating with payers relative to what your expectations had been are there any sources of pushback or challenges that you're encountering or is it simply taking the time that it takes and they have a follow up thank you.

Jan Mikkelsen: Or is it simply taking the time that it takes? And then we'll follow up. That's a very interesting question because I believe we are in a situation and yes, well, he has the entire, Margalis' team at his show, and what we're doing to the market. Assets team is building on the strategy we have explained multiple times. The strategy is to build up not only the most prescribed, growth among product, but also the most high value product.

So.

However, interest in nutrition because.

I believe we are in a situation.

He has the entire.

Market assess team.

So show them and what are you doing to the market.

<unk> team is building on the strategy, we have explained which for the time.

<unk> strategy is to build up not only the most prescribed.

Growth hormone product, but also the most highest value product opportunities. So for us it's basic optimizing the value of.

Jan Mikkelsen: So for us, it's about optimizing the value of, and others benefits to the patient, and getting the market access we wanted at the speed we expected to have but, more importantly, right. Because this is how you build up a high-value product opportunity. Not just go in and get it as fast as possible; you do it in the right manner.

Structural but he in the U S. We know it is the best in class product opportunity we provided.

The benefit to the pension which.

Providing not only once weekly treatment, but also an improvement in treatment outcome in Michigan five height velocity, we saw that in our phase III study, so we providing beauty benefit to the patient and getting the market to assess as we wanted to have into speak we expect it to have.

But more important on the right.

Because this is the how your pitiful a high value product opportunity not just cooking and gives it as fast as possible.

Right.

Jesper Hoyland: And I think this is what Jesper and his team is doing. Do you have any comments more, Jesper? No, I mean, we're coming in at the point of time where we're negotiating and these things are, of course, ongoing, as we're also indicating and so far. The access that we're having, we're quite peaceful and also the approval rates that we're getting. So, all in all, it develops according to our plan, which we are, of course, peaceful. And if you go to the numbers, because that is a Scottish... And I think what he said was that we now have 36% of life covered. I feel pretty good with that number.

And I think this is the most useful and his team's doing do you have any comments <unk>.

No I mean.

We are coming in at the point of time, where we are negotiating and these things have caused ongoing as we also indicating in so far.

Access that we're having there quite piece, but then also the approval rates of vacating. So all in all it develops according to our plan, which we are of course a pizza.

And if you go to the numbers because that gives us cautious.

And I think what he said well start loss, we now have 36% of lives covered now.

Scott Smith: Perhaps you can correct me if you're right or if I'm wrong. Yeah, 36% of lives covered. Yeah, okay. I heard you're right, Scott. Yeah. Three things.

Critical to the desktop or perhaps if you can correct me if you will right.

Yes.

6% of lives covered.

Yes.

I hope Youre right.

<unk> has recently.

Scott Smith: Thanks. And just a question on PGH. Just with respect to the regulatory process, will the FDA be taking the phase two and the phase two open label extension data into account? And to what extent did they presumptively review your application, you know, pending the results from PAPA? Yeah, you are correct. We are building up, for example, the safety database from both tribes. Dana, do you have some comments about that?

Thanks.

Question on PTH.

Just with respect to the regulatory process will the FDA b.

Taking into phase two and phase two open label extension data into account and to what extent as they.

For example, we've reviewed your application.

Pending the results from painful.

Yeah.

Correct, we are building off of some of the safety database.

For both price and the Dana do you have some further comments about that.

Dana Pizzutti: Well, yeah, I think, you know, the phase three pathway trial will be the sort of flagship, you know, you know, registrational trial. I think that the long term, you know, results from path forward, though, will be extremely helpful, not only just to show the durability of the response, right, as Yen said, 57 out of 59 are still, you know, in the trial. And, you know, that'll also give us a lot more information about what happens to the bone, right, and, you know, sort of help us to validate the sort of disease specific quality of life instrument that we've been working on as well.

Well, yes, I think the phase III pathway trial will be the sort of the flagship.

Registrational trial, I think that the long term.

Results from path forward, though will be extremely helpful. Not only just to show the durability of the response rate as Yan said 57 out of 59.

Bill.

In the trial.

That will also give us a lot more information about what happens to the bone right and sort of help.

Help us to validate the a sort of a disease specific quality of life instrument that <unk> been working on as well so.

Dana Pizzutti: So, you know, I think, you know, the, the two trials would be, you know, sort of going, you know, sort of hand in hand, I mean, one is the pivotal registrational trial, you could call it, and then the other one would be, you know, strongly supportive. Before we even, you know, sort of started the phase three trial, we explained to the FDA what we would have in terms of long term safety, you know, from, you know, path forward, I think we, didn't even expect we would have such great adherence in that trial, but they were satisfied that the totality of the safety database would be sufficient for them to do their review. So I think both trials are extremely important. I think the pathway trial, though, is sort of the linchpin for the replacement concept as well.

I think.

The two trials would be you know sort of going you know sort of hand in hand, I mean, one is the <unk>.

Pivotal Registrational trial.

And then the other one would be strongly supported before we even.

Sort of.

Started the phase III trial, we explained to the FDA a what we would have in terms of long term safety.

From.

Path forward I think we do.

Didn't even expect we would have such great adherence and that trial, but.

They were satisfied that the totality of the safety database would.

Sufficient for them to do their review.

So.

So I think both trials are extremely important and I think the path way trial, though is sort of the linchpin for the replacement concept as well.

Thanks Diana.

Thank you.

Operator: Thanks, Dana. Thank you. Our next question comes from Anita Deschamps of Berenberg Capital Markets. Your line is open.

Our next question comes from Anita Dushyanth.

Bear Amber capital markets. Your line is open.

Anita Deschamps: Good afternoon, thanks for taking my question. Just regarding the number of prescribers for Skytropa, I think in the commentary you mentioned 263. Could you talk about maybe when internally the team, sales team would be able to cover the 1,400 prescribers? I think what we are doing already now and how our long strategy has been is to do targeting. So we are covering, correct me, I think it's more 80% of the prescription being done in the GoFundMe market by only targeting 20% of the prescriber. So typically in the states we indicated our lungs, we actually covered 80% of all the prescription being written in the GoFundMe market. Yes, I was wrong in understanding this right.

Good afternoon. Thanks for taking my question just regarding the number of prescribers.

Profile.

I know you mentioned Turkey.

<unk>.

Could you talk about maybe.

Okay.

<unk> be able to cover.

Thanks Robert.

I think what were you doing already now in Hull Dong strategy has been is to do targeting so we are covering just to correct me.

It's more 80% of the prescribed prescription being done in the glaucoma market, but only talking 20% of the prescriber. So typical in the states we initiated our launch with excellent cohort, 80% of all the prescriptions being written.

In the coastal market.

Yes.

Got it wrong in understanding this right.

Jan Mikkelsen: No, what we're basically doing is we're breaking the 1400 into deciles. And then of course, we keep targeting on the highest prescribers. And that's where we have, you could say the best sort of penetration.

No. What we are basically doing is we are breaking the 1400 into <unk> and then of course, we had key packaging.

High prescribers and that's why we have you could see the best sort of penetration. So we will.

Jesper Hoyland: So we will continue to work on it and expanding it. And in particular, now that the market opens up that we can do face to face calls, we can do it, we have a match in terms of competitive forces with our size force, with the competition of both Novo and Pfizer. So we certainly believe that we can maintain and focus on the market leadership that of course, we're having right now is we're the only one on the market, but then we're also going to continue to have when we see competition coming onto the market.

Continue to work on it and expanding it in particular now that the market opens up that we can do face to face calls.

We can do it we have a match in terms of competitive forces with our size false.

The competition of both novel and FIFO. So we certainly believe that we can maintain and focus on the market leadership that of course, we are having right. Now is we are the only one on the market. But then you're also going to continue to have when we see competition coming onto the market.

Operator: Thank you, everyone. Thank you. I see no further questions in the queue. I want to thank everyone. This concludes today's conference call. Thank you all for participating. You may now disconnect and have a pleasant day.

Thank you guys.

Yes.

Okay.

Thank you.

I see no further questions in the queue I want to thank everyone. This concludes.

Thank you all for participating you may now disconnect and have a pleasant day.

Excellent.

Sure.

Okay.

<unk>.

Okay.

[music].

Yes.

[music].

Okay.