Full Year 2020 Ascendis Pharma A/S Earnings Call

Good morning, ladies and gentlemen.

Operator: Ladies and gentlemen, and welcome to the Q4 2020 Ascendis Pharma Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. If anyone should require assistance during the conference, please press star, then zero on your touchtone telephone.

Welcome to the key for 'twenty 'twenty ascend is pharma earnings conference call. At this time all participants are in a listen only mode. Later, we will conduct a question and answer session and instructions will follow at that time, if anyone should require assistance. During the conference. Please press Star then zero on your touched on.

For the film this call is being recorded I would now like to change your conference over to your host Mr. Scott Smith, Senior Vice President and Chief Financial Officer of the <unk> pharma.

Operator: I would now like to turn the conference over to your host, Mr. Scott Smith.

Operator: Senior Vice President and Chief Financial Officer of Ascendis Pharma.

Operator: of Ascendis Pharma. Please go ahead, Jay. Thank you.

Please go ahead for it.

Thank you operator, thank you everyone for joining our full year 2020 financial results conference call today, I Am Scott Smith, Chief Financial Officer of a centers join.

Scott Smith: Thank you everyone for joining our full year 2020 financial results conference call today. I'm Scott Smith, Chief Financial Officer of Ascendis. Joining me on today's call are Jan Mikkelsen, President and Chief Executive Officer, Dr. Mark Bock, Head of Clinical Development and Medical Affairs for Endocrinology Rare Diseases, Jesper Heulen, Global Chief Commercial Officer, Dr. Dana Pizzutti, Head of Development Operations, and Dr. Yuhua Punanen, Head of Oncology.

Joining me on today's call are again, Michelson, President and Chief Executive Officer.

Dr. Mark Bock head of clinical development and medical affairs for endocrinology rare diseases, yes.

Yes for Hoyland Global Chief commercial officer.

Dr. Dana <unk> head of development operations, and Doctor you Hopkinton on head of oncology.

Scott Smith: 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 progress on our pipeline candidates and our expectations with respect to their continued progress; statements regarding our strategic plans; and our goals regarding our clinical pipeline.

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 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.

Scott Smith: Statements regarding the market potential of our pipeline candidates and statements regarding our regulatory filing. These statements are based on information that is available to us today. Actual results or 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. 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 because all circumstances change, except as required by law.

Statements regarding the market potential of our pipeline candidates and statements regarding our regulatory filings.

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

Actual results or 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.

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.

Scott Smith: For additional information concerning the factors that could cause actual results to differ materially, please see the Forward-Looking Statements section in today's press release and the Risk Factors section of our Prospectus Supplement filed on July 9, 2020, and our annual report on Form 20-F being filed today. Please note that our TransCon product candidates are investigational product candidates and are not approved for commercial use. As investigational products, the safety and effectiveness of the Transcon product candidates have not been reviewed or approved by any regulatory agency. Therefore, none of the statements made on the conference call regarding our Transcon product candidates should be viewed as promotional.

For additional information concerning the factors that could cause actual results to differ materially. Please see the forward looking statements section in today's press release and the risk factors section of our prospectus supplement filed on July nine 2020, and our annual report on form 20-F being filed today.

Please note that our transcon product candidates, our investigational product candidates and are not approved for commercial use.

As investigational products, the safety and effectiveness of the transcon product candidates.

We have not been reviewed or approved by any regulatory agency. None other statements made on the conference call regarding our transcon product candidates shall be viewed as promotional.

Jan Moller Mikkelsen: On today's call, we will discuss our full year 2020 financial results and provide a business update. Following some prepared remarks, we will then open up the call to questions. I will now turn the call over to Jan Mikkelsen, our President and Chief Executive Officer.

On today's call, we will discuss our full year 2020 financial results and provide a business update.

Following some prepared remarks, we will then open up the call to questions I will now turn the call over to Jan Mikkelsen, our President and Chief Executive Officer.

Okay.

Thanks, Scott and good afternoon, everyone.

Jan Moller Mikkelsen: Thanks, Scott. And good afternoon, everyone, for Ascendis. 2020 was a year to remember.

For assemblies.

'twenty 'twenty.

To remember.

Jan Moller Mikkelsen: We succeeded as a team and were able to meet, and in some cases, exceed all our corporate goals in 2020. I am proud to be able to say that the Ascendis team was adaptive, creative, and focused on achieving the goals we outlined at the beginning of last year, to bring our Transcon product candidates to patients as fast as possible in 2021. We are well-positioned to continue to expand and achieve the milestones we have laid out across all of our five independent products.

Be succeeded as a team and we're able to meet.

And in some cases exceeded all of our cobalt goes in 2020.

I'm proud to be able to say that we're cindy's team well set that to credit to and focused on achieving that goes on at the beginning of last year.

To obtain our transcon product candidates to patients as fast as possible.

For 2021.

We are well positioned to continue to execute and achieve the milestones we have laid out across all of our five independent product candidates.

Going back.

Jan Moller Mikkelsen: The importance of science. One of Ascendis' core values. It's really at the center of what we do, 365 days. Our understanding of biology and the science it drives our top development. I see it again and again.

The importance of the signs.

One of us on this core values.

It's really at the center for what we do 365 days a year.

Our understanding of the ability on the science it was drives our drug development process.

I see it again and again.

Jan Moller Mikkelsen: If we stick to the science, understand and respect biology, we will be successful. With our algorithm for product development focused on the patient and the unmet medical need, combined with the Transcon signal. We have a powerful platform that has allowed Ascendis to create not just one potential blockbuster product but a portfolio of five potential blockbuster candidates in two therapeutic areas with more, beginning with Transcon Growth Hormone. Throughout the development, we have kept patient needs in mind from the beginning.

If you stick to the signs understand and respect for the biology, we will be successful.

We'd all agree with me for product development focused on the patients and the unmet medical need combined.

With the transcon seasonality.

We have a powerful platform.

That has allowed smbs to create not just one potential blockbuster product candidate for the portfolio of five potential blockbuster candidates into Tokyo arrows with more to come.

Beginning for transcon growth hormone.

True.

For the development.

If the patient needs in mind.

From the beginning.

Jan Moller Mikkelsen: We were committed to building on the last 30 years of knowledge with Daily Growth Hormone and other long-acting growth hormone programs. We designed our transgone growth hormone to have a similar tissue distribution pattern, receptor activation, and exposure as seen for daily growth.

We're committed to build on the last 30 years of knowledge with daily growth come on and other long acting growth hormone program.

We designed our transcon growth hormone to have a similar tissue distribution pattern.

With receptor activation and explode exposure.

For data growth tomorrow once somewhat of a peak is released from the transcon growth.

Jan Moller Mikkelsen: Once somatopene is released from the transcon-growth hormone protein, For more than 30 years, multiple companies have tried to develop a long-acting growth hormone product using several different technologies, providing comparable safety, efficacy, tolerability, immunogenicity, and mode of action as data growth. In spite of all this effort,

<unk> protocol.

For more than 30 years, which both companies have tried to develop a long excellent growth come on approach using several different technologies.

Providing comparable safety efficacy tolerability.

Dennis duty motive action as day to go to market.

In spite of all this effort to.

Jan Moller Mikkelsen: Today, all patients are still being treated with datagrowth hormone in the U.S., Europe, and Japan. I'm excited to be close to our potential regulatory approval of transcontraceptive hormone in the U.S. and Europe. Last June, we submitted our BLA for transgone growth hormone for the treatment of pediatric growth hormone deficiency, and we have a PDUFA date of June 25, 2020. Later in September last year, we submitted our M&A in Europe, and we expect potential approval in the fourth quarter.

Today, all patients are still being treated with data growth from them in the U S Europe and Japan.

I'm excited to be close to all potential regulatory approval of transcon growth hormone in the U S on Europe.

Last June we submitted our BLA for transcon growth hormone for the treatment of could add to growth come on deficiency and we have a paducah date of June 'twenty five 2021.

Later in September last year.

You submitted our MAA in Europe.

And do you expect potential approval in the fourth quarter this year.

Jan Moller Mikkelsen: Since our regulatory submission, I can see the payoff from our design of Transcon Growth and the extensive preclinical and clinical programs in our interaction with FDA and ME. We believe our data clearly demonstrate once-weekly transgone growth hormone has a comparable mode of action and Distribution in Key Growth Hormone Responsive Tissues, such as brain, bone, muscles, liver, and fat, as the growth hormone ambush for daily growth hormone and industrious growth, in our discussion with FDA and MEA.

Since our regulatory submission.

I can see the appeal from our design of transcon growth hormone.

And the extensive preclinical and clinical programs in our <unk>.

Interactions with FDA and EMEA.

Do you believe or data clearly demonstrate once weekly transcon growth hormone has comparable modal ex.

And distribution in key growth come on responses tissues, such as brain bone mass levo and fat tissue.

As the growth hormone administrated foot daily growth hormone and the doctor scope come on.

Yeah.

Hey, no discussion, but if they NBA gives me comfort.

Jan Moller Mikkelsen: Give me comfort that we have developed a convincing body of non-clinical and clinical data to support our belief. In December last year, we had a positive mid-cycle meeting with FDA, where they indicated that the agency has no plans for an advisory committee.

Debt, we have developed and convincing body of non clinique on clinical data to support our belief.

In December last year.

A positive mid cycle meeting with FDA.

Well the indicated.

The agency has no plans for an advisory committee.

Jan Moller Mikkelsen: We continue to have a constructive dialogue and have begun labeling discussions with the FDA, and we're looking forward to a potential Recto2Oil approval next quarter. In Europe, our M&A submission for transcon growth hormone last September followed the agreement with Pepco on our proposed Pediatric Investigation Plan, or called PIP, covering the non-clinical and clinical development of transcon growth hormone in children down to the age of 16. To our knowledge, no overgrowth hormone or growth hormone analose has been approved. Our expectation for potential approval of the M&A in the fourth quarter of this year is unchanged.

We continue to have a.

A constructive dialogue and have begun labeling discussions with the FDA.

And if you're looking for what to a potential regulatory approval next quarter.

In Europe our.

Our M&A submission for transcon growth hormone LASA timber follows the agreement with Pepco to our proposed could actually investigation playing for.

On covering for non clinical and clinical development of Transcon growth hormone Institute on down to eight of six months.

To our knowledge no oil growth hormone Aqua come on and of those has an approved people.

Our expectation for potential approval of the MAA in the fourth cohort of this year.

Jan Moller Mikkelsen: But our innovation did not stop with the design of our drugs. As part of our effort to address the unmet medical need, we have also developed an auto-injector for the administration of transconcrote, providing room temperature stability and a small injection volume via a 31. We introduce the transconrotamol autoinjector into the Phase III enlightenment trial, where it is currently being successfully used by over 160 subjects in the U.S. with accumulated use of more than 225 devices. We expect the transconcoctamol autoinjector will be available to patients at the same time as a potential commercial lock.

Unchanged.

But our innovation did not stop with this side of our drug substance.

As part of our effort to address the unmet medical need we have also developed and <unk> auto injector for the administration of transcon growth hormone, providing food temperature stability.

<unk> injection volume.

31 <unk>.

We introduced for Transcon growth hormone auto injector into the phase III Lachman tried.

Where is currently being so simple used by over 160 subjects in the U S. REIT accumulated use of more than 225 day of Ics.

We expect the transcon coped them on auto injector would be available to patients at the same time for potential commercial launch.

Jan Moller Mikkelsen: Going forward, we are developing an integrated connective health program that links the transcon glotamone autoinjector with an app and provides information for the patient and caregivers related to adherence and dose. The pediatric growth hormone market is an established market in the U.S. and Europe with several daily growth hormone products. But we also know that drugs don't work in patients who don't take them.

Going forward, we are developing an integrated connected health program that links the transcon growth hormone auto injector weighed on.

And provides information for the patient and caregiver will lead to adherence and doses.

The pediatric growth hormone market is on <unk>.

<unk> market in the U S and Europe with 70 data growth come on products.

But we also know that drugs don't work in patients who don't take them.

Jan Moller Mikkelsen: Even modest lack of adherence leads to suboptimal outcomes and potentially drop out of therapy. In fact, we see that almost all pediatric patients in the U.S. stop therapy after three to four years. We have submitted for publication a manuscript based on claims data demonstrating that the problems of adherence and lack of treatment are potentially much worse than reported in published data. I often get asked if we think we can expand the current market with Transcon Gold.

Even modest lack of adherence leaked to soup ultimate outcomes and potentially to drop out of therapy.

In fact, we see that almost all could I took patients in the U S stopped therapy after three to four years of treatment.

We have submitted for publication Amendment based on claims data demonstrating that the problems of our hands a lack of treatment are potentially much worse than reported in pockets litho tool.

I often get asked.

If we think we can expand the current market for transcon growth hormone.

Jan Moller Mikkelsen: These new data, describing lack of adherence and lack of treatment, tell me that there is a potential big opportunity to improve patient care by improved adherence, persistence, and penetration, which will lead to better outcomes for patients and better outcomes for society. So far, I have talked about the US and Europe, but we are not stopping there.

These new data describing lack of adherence.

Lack of treatment tell me that there is a potential peak opportunity improve patient care by improved adherence for system and penetration.

Which.

<unk> will lead to better outcomes for patients and better outcome for the society.

So far I have talked about U S and Europe, but we are not stopping there.

Yeah.

Jan Moller Mikkelsen: Ascendis is a global company with a global thinking addressing unmet needs for a worldwide. In Japan, we filed a clinical trial notification last year to initiate the phase 3 right trial for pediatric growth hormone deficiency. In China, in 2018, we formed Wezen Pharmaceuticals with an investor group to develop Transcon endocrinology rare disease product in greater China. Vision continues to execute on its Phase 3 clinical trial of transcon growth hormone in children with growth hormone deficiency and will indicate clinical development for transcon PTH and transcon CMP soon. Moving to Label Expansion.

As a global company with a global thinking addressing unmet needs for our Woodbine population.

Inkjet pain, we filed a clinical trial notification last year to initiate the phase III trial for.

Pediatric Kokomo deficiency.

In China in 2018 before recent pharmaceuticals, with an Investor group to develop client con endocrinology rare disease product in greater China.

The region continues to execute on these phase III clinical trial of Transcon growth hormone and she is on the go come on with efficiency and will you take clinical development for Transcon, PTH and Transcon CMP soon.

Moving to label expansion.

Jan Moller Mikkelsen: We have the Global Phase III Foresight Trial underway for adult growth hormones. The primary objective of the FORSAIT trial from a regulatory perspective is to demonstrate efficacy compared to placebo. However, the most important comparison is to daily codeine, which is included as a third arm in the Forsythe Trust.

We have the global phase III foresight on debt.

For adult growth hormone deficiency.

The primary objective of the for type trial.

From a regulatory perspective is to demonstrate efficacy compared to placebo.

However, the most important comparison is two day to cool cool with each include third.

Force I tried.

Jan Moller Mikkelsen: We have a plan to randomize 240 subjects one to one to one. I am often asked, why is adult growth hormone deficiency so important? What do you get out of the Forsyth track?

We have a plan to randomize, two Honda and 40 subjects.

Two one to one.

I'm often asked why is adult growth hormone deficiency is so important.

What do you get out of the force Archrock.

Jan Moller Mikkelsen: Growth hormone deficiency is not just about height. However, in children, height emerges as the primary regulatory indicator. Since adults are not growing in height, the primary regulatory endpoint is to measure the metabolic consequence of growth hormone, to measure change in trunk fat. Only if a once-weekly growth hormone therapy is equivalent or better to daily growth hormone in both the pediatric and adult growth hormone deficient population will it provide all the endocrine benefits of data.

Growth hormone deficiency is not just about height in.

Children height emerged as our primary regulatory endpoint.

Since adult and outgrowing in height that price.

Regulatory endpoint is to measure the metabolic consequence of <unk> deficiency.

Two major chains and Trumpf debt.

Only if a once weekly growth hormone therapy is it.

Excellent operator to data growth for them at both the pediatric and adult growth hormone deficient populations.

Then <unk> will provide all the endocrine benefits of data growth.

Jan Moller Mikkelsen: We believe from our Phase III pediatric programs that transconclothamone can provide all these endocrine benefits, combined with a success in the adult growth hormone deficiency phase. We believe we will continue to differentiate from oil once we grow our own product. We expect to complete enrollment in the Foresight Trial by late 2021 or early 2021. Moving to TranscomPJ, I've never seen a product like this.

Do you believe for more phase III could actually programs that transcon growth hormone can provide all this endocrine benefits.

Combined with our success in adult growth hormone deficiency phase III trial.

Believe me, we continue to deepen Seth from oil once we could go come on product candidates.

We expect to complete enrollment of the force I tried by late 2021 or early 2022.

Moving to Transcon PTH.

I've never seen a product like distributor for a product that not only can a toys short term symptoms offered it to cease by with storing biochemical control and the quality of life for patients, but also potential candidates for long term complication of the disease as well.

Jan Moller Mikkelsen: A product that not only can address short-term symptoms of a disease by restoring biochemical control and the quality of life for a patient but also potentially can address the long-term complications of the disease as well. Hyperparathyroidism, HP, is a condition that affects more than 200,000 patients just in the US, Europe, and Canada. Similar to growth hormone deficiency, where the problem is an absent or insufficient amount of a respective hormone, in this case for HPPJ, in chronic post-surgical HP in around 75% of all cases.

Hydro <unk> HP is a condition with ex saved more than 200000 patients just in the U S Europe and Japan.

Similar to growth to moan deficiency.

We have the properties up soon are insufficient amount of their respective home in this case for HP <unk>.

In Chronicle post surgery HP in around 75% of all cases per tire right claims that Oregon debt produce <unk> have been damaged or destroyed and the body cannot be stimulated to produce sufficient amount of <unk>.

Jan Moller Mikkelsen: The Terateroid Claim: The organs that produce PTH have been damaged or destroyed, and the body cannot be stimulated to produce a sufficient amount of PTH. Therefore, the only way PGH can be restored to normal physiological levels is by PGH hormone replacement.

Therefore, the only way PTH can be for you.

Restored to normal physiological levels. Despite P J, it's home and for patients.

Jan Moller Mikkelsen: Transcon PGH is designed to replace the hormone at physiological levels and restore the patient to normal health. When we speak to patients suffering from HP, we hear over and over again about how poor their quality of life is, and how they had to stop going to work.

Transcon PTH is designed to replace the Holman attitudes logical livers and restore the patient to normal habits.

When we speak to patients suffering from HP.

Oh, okay.

About how pool the quality of life.

How does it have to stop going toward all worry about cash some crashes.

Jan Moller Mikkelsen: All worried about Kelsom crash and making it to an emergency room. These are the short-term symptoms driven by a lack of serum calcium control and physiological pecitation. In addition to the short-term effect, AIDS-B patients have multiple long-term complications such as insufficient kidney function, cardiovascular risk, and abnormal bone turnover. As transcontinence PTH is designed to restore PTH to physiological levels 24 hours a day, we will expect to normalize serum calcium to improve short-term outcomes. We also expect to normalize kidney function and normalize bone health to reduce long-term complications. So, what have we seen?

Making it to an emergency room.

On the short term symptom driven by lack of cm CASM control and future logical pj's slippers.

In addition to the short term effect HB patients have multiple long term complication as insufficient kidney function cardiovascular risk and op normal bone turnover.

S. Transcon PTH is designed to restore <unk> to physiological levels for us at <unk>, we would expect to normalize serum calcium to improve short term.

We also expect to normalized kidney function on normalized bone health to reduce long term complications.

So what how do we see with our six month open label extension or early data B. So all my summary, and sub domains.

Jan Moller Mikkelsen: With our six-month open-label extension, or OLAY, data, we saw all mean summary and subdomains, SF36 quality of life scores being normalized. Later this month, we will present data at an oral presentation at Indoo, where you will see results for the first time from our HP disease-specific patient-reported outcome instrument after six months in the OLL. Since then, all 58 subjects have now completed 12 months of treatment on transcon PTH without any additional dropouts, which gives me comfort that these subjects are continuing to see the quality of life benefit with a safe once-daily PGH injection.

So to seek quality of life scores being normalized.

Later this month, we will present data.

At an oral presentation that into where you will see results for the first time from our H P disease specific patient reported outcome instrument after six months in the OLED.

Since then all 58 topics have now completed 12 months of treatment on Transcon PTH.

Without any additional drop off.

It gives me confidence that these subjects are continue to see the quality of life balance sheet with a safe once daily PTH injections.

Jan Moller Mikkelsen: In addition to the great data on quality of life, Transcon PTA also demonstrates normalization of key biochemical parameters related to long-term community living. After six months in the OLE, me, 24-hour urinary calcium excretion fell on average 57% compared to baseline, almost all subjects demonstrated a normalization or improvement in urinary calcium excretion. On measures of bone health, HB patients typically have low bone turnover and, as a consequence, abnormal dense bones compared to people without HB, particularly the tropical outbreak. As expected.

In addition to the great data on quality of life Transcon PTH also demonstrate normalization of key biochemical <unk> with you too long term complications.

After six months in the OLED.

<unk> for our urinary calcium excretion fell on average.

<unk> 57 per cent compared to baseline on.

Almost all subject demonstrated a normalization or improvement in urinary calcium excretion.

On michel's on bone health HB patient, two because have low bone turnover and as a consequence.

Up normal data volume compared to people without HP.

Particularly on the tropical alcohol <unk>.

As expected.

Jan Moller Mikkelsen: As we restored physiological PTH levels, we saw bone turnover increases with the initiation of transcontinental PTH, resulting in a trend towards normalization of the abnormal dense bone, particularly the trapezoid. So what is next for TRANSCON-PT? During the second quarter of 2021, we plan to provide 12-months holiday.

<unk> is a logical pge's labor, we saw bone to novo increases with the initiation of transcon PTH treatment.

Resulting in a trend towards normalization of the ethanol boom, particularly on the trifocal uncle.

So what is next for Transcon PTH.

During the second quarter of 2021, we plan to provide 12 months for the data.

Jan Moller Mikkelsen: We expect to see continued normal quality of life, sustained reduction of HP, continue normal serum calcium, continue normal level of urinary calcium, and continue normal bone turnover. As part of extending our global reach for this potential life-changing therapy, during the second quarter, in addition to the 12-month PTAs forward. Update

We expect to see continue normal quality offline sustained reduction of symptoms.

Two new normal serum calcium continued normal level of your cash flow and continue normal turnover.

As part of extending our Billboard lease for this potentially life changing therapy. During the second quarter. In addition to the 12 months PTH forward.

Update we plan to submit a clinical trial notification for a trial evaluating transcon PTH for adult HP in Japan.

Jan Moller Mikkelsen: We plan to submit a clinical trial notification for a trial evaluating transcom PTH for adults HP in Japan. Later this year, in the fourth quarter, we plan to report top-line results from the pathway trial. At phase 3, a randomized, double-blinded, placebo-controlled trial investigating the safety, tolerability, and efficacy of transcon PTH in adults with APD. The trial is expected to enroll 76 subjects at sites in North America and Europe. We are pleased by the data that we have generated.

Later this year in the fourth quarter, we plan to report top line results for the puck weighted trial.

A phase III randomized double blinded placebo controlled trial.

In this case in mitigating the safety Tolerability and efficacy of Transcon PTH in adult with HP.

The trial.

He is expected to enroll 76 shock as sites in North America and Europe.

We are pleased by the data that we have generated so far and we believe the data support of profile for transcon PTH to be a potential first line therapy for ESP.

Jan Moller Mikkelsen: And we believe the data support a profile for transgone PTH to be a potential first-line therapy for AIDS. We are confident we can truly make a difference in the life of someone turning to Transcon CMP. We are conducting two double-bind placebo-controlled phase 2 trials in children age 2 to 10. But first, the Accomplice trial is a dose-escalation trial of 12 to 15 subjects in each cohort, conducted mainly in North American units.

We are confident we can truly make a difference.

In the life of HBV patients.

Turning to Transcon CMP via conducting two double blind placebo controlled phase II trial in children, aged two to take DSO.

The first the Companys trial is a dose escalation trial of 12 to 15 subjects in each cohort.

<unk>, mainly in North America and Europe.

Jan Moller Mikkelsen: The second is the accomplished China trial, which is a cohort expansion trial of at least 60. Subject Conducted in China, Reason received approval from the Chinese Center for Drug Evaluation to conduct the accomplished China trial with a design for dose expansion at an effective dose determined from the accomplished China trial. Combined, these two studies will enroll more than 120 subjects, aged 2-10, to be followed for 12 months in a double-blinded manner. Both Accomplice and Accomplice China will remain blinded until the 20-month follow-up is complete.

For the second East China.

China trial, which is a cohort expansion trial of at least 60.

Subject conducted in China.

<unk> received approval for the Chinese center for drop in relation to conduct the concrete China trial design.

Designed for dose expansion at an effective dose for the.

We accomplished.

Hi.

Combined these two studies will enroll more than 120 socket eight two to obtain to be followed for 12 months in adult with blinded manner.

Both our companies and countries, China will remain blinded on so the two months for the op is completed once.

Jan Moller Mikkelsen: Once completed, we will have robust clinical data from two independent, randomized, double-blind, placebo-controlled trials. We plan to provide a Transcon CMP clinical program update in the fourth quarter of 2021. Finally, in endocrinology, we announced today that Ascendis will have a student presentation at the ENDO 2021 Annual Meeting.

Once completed we will have robust clinical data from two <unk>.

Independent randomized double blinded placebo controlled trials.

We plan to provide our <unk> clinical program update in the fourth quarter of 2021.

Finally in the endocrinology be announced for data centers would have chipman presentation into 'twenty to 'twenty, one and on BC disability.

Jan Moller Mikkelsen: This will include an oral presentation of the six-month Open Label Extension from the Path Forward Trial for Transcontinental PTAs, as I mentioned. In our second therapeutic era, we hosted our first oncology R&D day back in November to share our vision of How to Use Transcon Systemic and Infotermal Technology to Establish a New Paradigm for Treatment. We think we can develop an entirely new treatment paradigm in oncology using transcon technology and address all steps of the immunity cycle.

This will include an oral presentation of the six months open label extension for.

On the path forward for Transcon PTH as I've mentioned.

In our second Tokyo Daguerre B hosted our first on quality R&D day back in November to share our vision on.

On how to use transcon systemic and <unk> technology to establish a new paradigm for treatment.

We think we can develop entirely new treatment paradigm in oncology using transcon technologies and address all states.

You move Nitty cycle.

Jan Moller Mikkelsen: We are applying the same product development algorithm in oncology as we have successfully used in endocrinology, applying transcon technology to clinically validated parent docs and biological pathways for Transcon TLR78 accounts. An R&D proposal was submitted in December 2020, to imitate the Phase 1-2 Transcend IT-101 trial during the second quarter of 2021 following monotherapy dosing. We plan to imitate those escalations in combination with a checkpoint.

We are applying the same product development accurate medium quality SP has successfully used in endocrinology.

Applying transcon technology.

Clinical validated parent docs and biological pathways.

For Transcon Chiller, seven eight equities and on deep for submitted into say 2020.

To initiate the phase one slash two trends.

One for one trial.

During the second quarter of 2021 for monotherapy dosing.

We plan to initiate dose escalation in combination with a checkpoint inhibitor.

Initial mono two mono.

Jan Moller Mikkelsen: Initial monotherapy dosing results are expected in the fourth quarter of 2021 for Transcon Alt 2 Beta Garmin. Earlier this year, we reported potential best-in-class preclinical data. Our transgonal 2-beta-gamma is designed to have best-in-class potency and receptor bias, combined with a long half-life of around 22 hours and a low Cmax. In non-human primers studies, we have observed highly biased potent activity with sustained exposure leading to best-in-class immune cell expansion, with minimal effect on eosinophils.

Monotherapy dosing results I expected in the fourth quarter of 2021.

For transcon to be day comment there.

This year for you reported potential best in class preclinical data.

Our Transcon Tupi day Karma is designed to have best in class potency receptor bias combined with a long half life of around 72 hours and at low <unk> concentrations.

In non human Primate study.

Offices are highly bias potent <unk> activity.

Sustained exposure, leading to best in class immune cell expansion.

With minimal effect of signal for us either five or IFC and VESCO lead commodity based on this data.

Jan Moller Mikkelsen: Aisle 5 or Aisle 6, and Baskerville League, March. Based on this data, we believe Transgol IL-2 beta-gamma has the potential to become a backbone agent in oncology. We expect to submit an R&D or similar application for Transconile-2-Basic Garment in the third quarter of 2020. I sincerely believe that our goals of building a fully integrated global biopharmaceutical company get one step closer. 2020 was a great year, a year to remember for Ascendis, as we advanced our endocrinology-aware disease and oncology product.

Can you believe transcon <unk> two <unk> has the potential to become effective on patent in oncology.

Treatment.

We expect to submit an R&D are similar for trying to garner two piece of government in the third quarter of 2021.

I sincerely believe that our goals of building a fully integrated global biopharmaceutical company gets one step closer each day.

2020 was echoed Ikea.

Year to remember for <unk>, SV advanced or endocrinology rare disease, and oncology product candidate in 'twenty 'twenty. One we look for to achieve additional successes SBA events oil pipe on the hit and closer to patients with unmet medical needs.

Jan Moller Mikkelsen: In 2021, we look forward to achieving additional successes as we advance our pipeline ahead and closer to patients with unmet medical needs. We are continuing to apply our algorithm to build a pipeline in oncology and are committed to entering a third therapeutic age. This is how we will achieve sustainable growth, not by advancing just one program but succeeding with multiple potential blockbuster programs in multiple therapeutic areas in multiple geographies. Now, let me turn the call over to Scott for a financial review before we open up for questions.

We are continuing to apply our equity to build a pipeline in oncology and are committed to entering a third Tokyo together.

This is how we will achieve sustainable growth.

But eventually just one column, but succeeding with multiple potential blockbuster program in multiple therapeutic areas in which both grew graphics now.

Now, let me turn the call over to Scott for a financial review before we open up for questions.

Thanks, a lot Yan.

Scott Smith: Turning to our financial results for the full year ended December 31, 2020, we reported a net loss of 419 million euros, or 8.28 euros per basic and diluted share, compared to a net loss of 218 million euros, or 4.69 euros per basic and diluted share, during 2019. Now, let me run through some components of these results.

Turning to our financial results for the full year ended December 31 2020.

We reported a net loss of 419 million euro or eight 280 per basic and diluted share compared to a net loss of 218 million euro or for six nine euro per basic and diluted share during 2019.

Now, let me run through some components of these results.

Scott Smith: Research and development costs for 2020 were 260.9 million euros compared to 191.6 million euros during 2019. R&D costs in 2020 reflect continued advancement of our pipeline, with the primary drivers of the increase including an overall increase in personnel related and R&D infrastructure costs. And for Transcon Growth Hormone or Lonopex Thaumatropin, costs were higher due to the buildup of prelaunch inventories, as well as increased clinical trial activity. As a reminder, we currently expense manufacturing costs of Lonapeg somatropin as R&D in advance of our anticipated product launch. At the time of product approval, a portion of these R&D costs may be reversed and capitalized as inventory, which will result in a one-time benefit to R&D costs.

Research and development costs for 2020 for $260 9 million compared to $191 6 million during 2019.

R&D costs in 2020 reflect continued advancement of our pipeline with the primary drivers of the increase including.

And overall increase in personnel related and R&D infrastructure cost.

And for Transcon growth hormone or <unk> costs were higher due to buildup of prelaunch inventories as well as increased clinical trial activities.

As a reminder, we currently expense manufacturing costs of <unk> summit for open as R&D in advance of our anticipated product launch at the time of product approval. A portion of these R&D costs may be reversed in capitalized as inventory.

Will result in a onetime benefit to R&D costs.

Scott Smith: For Transcon PTH, costs were higher primarily due to device development and increased clinical trial costs. For Transcon C&P, costs were higher, primarily due to increased manufacturing and clinical trial costs. And finally, for the Oncology Therapeutic Area, costs were higher due to increased manufacturing and preclinical activities primarily related to Transcon TLR78 Agonist and Transcon IL-2 Beta Gamma. Selling, general, and administrative expenses for 2020 were 76.7 million euros compared to 48.5 million euros during 2019. These higher costs primarily reflect an increase in personnel-related IT and other infrastructure costs, as well as expenses associated with the continued build-out of our commercial capabilities.

For Transcon PTH costs were higher primarily due to device development and increased clinical trial costs.

For Transcon CMP costs were higher primarily due to increased manufacturing and clinical trial costs.

And finally for oncology therapeutic area costs were higher due to increased manufacturing and preclinical activities primarily related to transcon Tls seven eight agonist and transcon IL two or beta gamma.

Selling general and administrative expenses for 2020 were $76 7 million euro compared to $48 5 million Euro during 2019.

These higher costs, primarily reflect an increase in personnel related and.

And other infrastructure costs as.

As well as expenses associated with the continued buildout of our commercial capabilities.

Scott Smith: Finance income and expenses in 2020 included a foreign exchange rate loss of 78.9 million euros compared to a gain of 7.7 million euros in 2019, primarily related to unrealized losses on translation of our U.S. dollar holdings of cash and marketable securities to euros. We ended 2020 with cash, cash equivalents, and marketable securities totaling 834.1 million euros. As of December 31, 2020, Ascendis had 53,750,386 ordinary shares outstanding. Subsequent to year end, on January 8, 2021, we invested $12.5 million in Visen Pharmaceuticals' $150 million Series B financing. Following the financing, we own approximately 44% of Visen's issued and outstanding shares.

Finance income and expenses in 2020 included a foreign exchange rate loss of $78 9 million euro compared to a gain of $7 7 million Euro in 2019, primarily related to unrealized losses on translation of our U S. Dollar holdings of cash and marketable securities to euros.

We ended 2020 with cash cash equivalents and marketable securities totaling $834 1 million Euro.

As of December 31, 2020.

Ascend has had 53.750 million 386 ordinary shares outstanding.

To year end on January eight 2021, we invested $12 $5 million in visa <unk> pharmaceuticals, $150 million series B financing.

Following the financing we own approximately 44% of <unk> issued and outstanding shares.

Scott Smith: As a result of this transaction, we expect to recognize a non-cash gain in the first quarter of 2021 of 42.3 million euros. Turning to 2021, we expect our expenses to increase as we continue to build our commercial capabilities and prepare for launch. Advanced Endocrinology Rare Disease Pipeline, Expand Our Activities in Oncology, and Continue Investing Transcon Technology Platform, including for Lanopec Somatropin, buildup of commercial inventory ahead of potential launch, and execution of commercial pre-launch and launch activities.

As a result of this transaction, we expect to recognize a noncash gain in the first quarter of 2021 or $42 3 million Euro.

Yeah.

Turning to 2021, we expect our expenses to increase as we continue to build our commercial capabilities and prepare for launch.

Advance our endocrinology rare disease pipeline.

Expand our activities in oncology and continue to invest in the transcon technology platform, including.

For a lot of pay so much open bill.

Buildup of commercial inventory ahead of potential launch execution.

On a commercial prelaunch and launch activities.

Scott Smith: Investment in expanding commercial manufacturing capacity to support anticipated future demand. Continued execution of the Foresight Trial, a global phase 3 randomized controlled clinical trial in adult GHD, and execution of the RITE Trial, a phase 3 randomized controlled clinical trial in pediatric GHD in Japan. For Transcon PTH, continued execution of the Phase 2 Path Forward Trial, which continues to retain 58 subjects in the Open Label Extension, and execution of the Pathway Trial, a North American and European Phase 3 randomized controlled clinical trial in adult HP.

Investment in expanded commercial manufacturing capacity to support anticipated future demand.

Continued execution of the foresight trial, a global phase III randomized controlled clinical trial in adult ghd and.

And execution of the right trial, a phase III randomized controlled clinical trial in pediatric ghd in Japan.

For Transcon PTH continued execution of the phase II path forward trial, which continues to retain 58 subjects in the open label extension.

And execution of the pathway trial in North American and European Phase III randomized controlled clinical trial in adult HP.

Scott Smith: For TRANSCON's PNP, execution of the clinical program, which includes two randomized placebo-controlled phase II clinical trials in achondroplasia, the ongoing ACCOMPLISH trial and the ACCOMPLISH China trial, which is being conducted through our strategic investment in Visa and Pharmaceuticals. And lastly, in our Oncology Therapeutic Area, execution of the Transcended 101 clinical trial for our Transcon TLR78 agonist and advancing the Transcon We expect other SG&A expenses, in addition to Lanipeg somatropin commercial pre-launch and launch activities, will include continued investments in personnel, systems, and infrastructure to support our rapidly progressing portfolio and growing organization. For 2021, we remain on track to hit our corporate milestones.

For Transcon CMP execution of the clinical program, which includes two randomized placebo controlled phase II clinical trials in a contemplation the ongoing accomplished trial and the accomplished China trial, which is being conducted through our strategic investments and based on pharmaceuticals.

And lastly in our oncology therapeutic area execution of the transcended one on one clinical trial for our Transcon <unk> <unk> agonist and advancing the transcon IFC, a beta gamma program into clinical development.

We expect other SG&A expenses. In addition to a lot of peg Somatropin commercial prelaunch and launch activities will include continued investments in personnel systems and infrastructure to support our rapidly progressing portfolio and growing organization.

Okay.

For 2021, we remain on track for hitting on corporate milestones for launch for <unk>. So much open. These include with a <unk> date of June 25, 2021, we anticipate approval for pediatric ghd in the second quarter, followed by commercial launch in the third quarter and we anticipate European Commission approval for pediatric Ghd.

Scott Smith: For Lonapeg somatropin, these include: with a PDUFA date of June 25th, 2021, we anticipate approval for pediatric GHD in the second quarter, followed by commercial launch in the third quarter, and we anticipate European Commission approval for pediatric GHD in the fourth quarter. For Transcon PTH, we plan to file a clinical trial notification for a Japanese Phase III trial in adult HP in the second quarter, followed by reporting top-line results for the Phase III pathway trials in North America and Europe for adult HP.

In the fourth quarter.

For Transcon PTH, we plan to file a clinical trial notification for our Japanese phase III trial in adult HP in the second quarter, followed by a reporting top line results for the phase III pathway trials in North America, and Europe for adult HP.

For Transcon CMP, we expect to provide a clinical program update in the fourth quarter.

Scott Smith: For Transcon C&P, we expect to provide a clinical program update in the fourth quarter. For Transcon TLR78 agonist, after dosing in the monotherapy part of the Transcend IT-101, we plan to initiate the dose escalation part in combination with a checkpoint inhibitor in the second quarter, and plan to present initial Transcend IT-101 results in the fourth quarter. And finally, for IL-2 Beta Gamma, we plan to submit an IND or similar filing in the third quarter. Before we open up the call for questions, I want to make some points about our anticipated commercial activities for Lonapeg Somatropa in 2021.

For Transcon <unk> agonist after dosing in the monotherapy part of the transcend at 101, we plan to initiate the dose escalation part in combination with a checkpoint inhibitor in the second quarter.

And plan to present initial transcend it one on one results in the fourth quarter.

Finally for IL, two beta gamma we plan to submit an IND or similar filing for the third quarter.

Before we open up the call for questions I want to make some points about our anticipated commercial activities for <unk> in 2021.

During Q2 this year, we anticipate approval for pediatric ghd on the <unk> date of June 25.

And during Q3, we expect to have product available in the U S for pediatric ghd.

During Q3 once product is available we anticipate beginning to provide access to a lot of <unk> for pediatric ghd patients by Onboarding patients through our dedicated patient hub and we do not expect to have placement on commercial formularies at that time.

Finally during Q4, we anticipate European Commission marketing approval for pediatric Ghd, we plan to provide guidance on the timing of launch in Europe later this year.

Scott Smith: During Q2 this year, we anticipate approval for pediatric GHD on the PDUFA date of June 25th. Then, during Q3, we expect to have product available in the U.S. for pediatric GHD. During Q3, once the product is available, we anticipate beginning to provide access to Lonopec's Fomotropin for pediatric GHD patients by onboarding patients through our dedicated patient hub, and we do not expect to have placement on commercial formularies at that time. Finally, during Q4, we anticipate European Commission marketing approval for pediatric GHD. We plan to provide guidance on the timing of launch in Europe later this year. With that, operator, we're ready to take questions.

With that operator, we're ready to take questions.

Ladies and gentlemen, if you have a question at this time. Please press the star and then the number one our net.

Jones on the phone.

For your question has been answered or you wish to remove yourself from the queue. Please press the pound key.

Your first question comes from Michelle Gilson from Canaccord Genuity. Your line is open.

Let me. Thanks. Thank you for taking my questions I guess the first one can you.

Maybe discuss the cadence for.

For Transcon GH of getting on to the formularies.

How does that happen over the course of the year.

And then my second question.

Operator: Ladies and gentlemen, if you have a question at this time...

For Transcon PTH from a safety perspective is there a difference between replacing PTH.

Operator: Please press the star and the number 1 key on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. Your first question comes from Michelle Gilson from Canaccord Genuity; your line is open.

PTH and physiological levels in hyper care patients.

I guess at the doses, you're evaluating versus adding pulses of PTH to stimulate an anabolic effects.

Michelle Gilson: Thank you for taking my questions. I guess the first one: can you maybe discuss the cadence for transcon-GH of getting on to the formularies? How does that happen over the course of a year? And then my second question for transcon-PTH, from a safety perspective, is there a difference between replacing PTH at physiological levels in hypoperipatients, I guess at the doses you're evaluating, versus adding pulses of PTH to stimulate an anabolic effect? And then, I guess, at the doses that you're evaluating for transcon-PTH, would you expect there to eventually be a black box warning or limitation on duration therapy, like there is for 4-KO?

Then.

I guess.

Is that you are evaluating for Transcon PTH would you expect there to eventually be a black box warning or limitation on duration therapy like their spend for a tail.

On these different effects on the zone.

Yes.

Thanks, Michele so before potentially but tune it over two years, but I couldnt potentially take a little of the Peach H. So the accretion that you take off and.

Let me just repeat.

What are we doing with transcon PTH related to bone structure.

If youll have in untreated patients.

That had a higher bone density because your basic half and.

Nashville, low turnover because you are have not for future logical PTH level of peak PTH.

Jan Moller Mikkelsen: Thanks, Michelle. So before I potentially turn it over to Jesper, I could potentially take a little of the PTH question that you're taking up and let me just repeat what we're doing with transcompetase related to bone structure. If you have an untreated HPV, you basically have an unnaturally low bone turnover because you basically have an unnaturally low PTH level. And if you look at the serum level of PTAs, it is well documented in the literature that you basically see a curve that has a peak to trough of about 30%, doing the entire 24 hours cycle.

And if you look on the see them.

Level <unk> is well documented inbuilt at tier two debt you basically see.

And basic a curve that have a peak to trough of about 30%.

Doing the entire 24 hours.

Cycle.

And.

What we sold in the six months open label extension data what.

What we sold that wouldn't be restored Fisher logical PTH levels.

We basic activated been normal palm to know what that you would see in a normal tuman b debt.

Jan Moller Mikkelsen: What we saw in the six months' open label extension data, we saw that when we restored physiological PTH levels, we basically activated the normal bone turnover that you see in a normal human being who has no issue related to potential lower levels of PTSD. We saw that by accelerating a higher level of both the anabolic and catabolic bone markers but still being placed in what we call a higher level of the normal level. And what we saw was the associated consequence of that.

That had no issue related to potentially the overall level of PTA.

We saw that by accelerating and on higher level of the both the antibody and catabolic for Marcus but still being placed in what we call the higher level of Gordon on maintenance.

And what we saw was the associated consequence of debt. We also saw that this bone density debt is up normal guidance because it ex will have a structure that basic on.

Jan Moller Mikkelsen: We also saw that this bone density that is abnormally dense because it actually has a structure that is not like a normal bone because it has no bone turnover start to be normalizing. So therefore, we saw that and a trend to approaching the normal level, which is defined as zero. That is what we observed in the six months' data. This is a continued process where we saw the main effect on trabecular bone if we basically looked at cortical bone. There was not the same kind of decline in Z-score. It was basically stable because they didn't have the elevated high density that you basically see specific for the trapezoidal bone structure.

Not like a normal bone because it has no bones renewable start to be normalizing. So therefore, we sold debt and train two are promising the.

Normal levels, which instead score is defined SCO digest, what we've observed in the six months data.

This is a continuous process, where we sold the main effect on track with Codelco.

Basic looped on cortical bone.

That was not for us.

Same kind of decline in surgical it was basically stable because but don't have the elevated high density that your basic seat specific for tropical iPhone structure.

Jan Moller Mikkelsen: What we saw with our bone markers, what we saw in our bone density, is just following exactly what we have expected from the physiology of restoring a normal PTH level in our interaction with FDA and EMEA. Our first discussion related to PTH and its effect as an anabolic compound was when we discussed whether we should basically conduct a CARC study. A CARC study is basically a study that has been done for all other PTH products, to my knowledge. We got a clear answer back from

What we saw with our Beaumont goes what we so bone density is.

Just following exactly what we have expected upfront.

Future oddity of restoring enormous P chase level.

In section with.

<unk> in EMEA.

Our first discussion related to P. J, it's an effect.

<unk> compound was wouldn't be discuss cheville basic conduct a <unk> study of <unk> studies basic study that has been done for <unk> PTH product to mind on that.

We got a clear and so back from.

Jan Moller Mikkelsen: Justification and Scientific Justification that there was no need to do it because what you are applying in the Transcon PTH product is just a normalization of the PTH level and not generating what I call a super physiological PTH level that you do with a classical compound of PTH that is being used as a therapeutic agent in osteoporosis. Therefore, I believe there is a fair chance that we can avoid any kind of REMS program.

Justification and scientific justification that there was no need to do it because what you're applying in the transcon PTH product is just a normalization of <unk> living and not generating.

One on coal and superficial logical PTH levels that you do predict cash compound of pega's debt being used as it to a per 80 after approvals.

Therefore, I believe there is a fair chance that we can evolve and.

Any kind of Rems program, because what we continue to see if we dealt with clinical data and remember at the day to a filing we will have 18 months to be basically follow this for one.

Jan Moller Mikkelsen: Because what we continue to see with our clinical data, and remember that the data are filing, we will have 18 months. So we basically can follow this for one month. We expect to have such a strong data packet that we can provide what we see is just a normalization of this.

We expect to have such a strong data package that we can provide what we see is just a normalization of this.

Jan Moller Mikkelsen: So I'm hopeful that the science will continue to play out. So we could be in a position that we can do a scientific justification saying there is no need for a REM. And also, we're also seeing now that if you look at the after process compound, the block fat box rule has been removed for Teo. And also, that is a basic and U.S. situation because in Europe, they are not believing that the preclinical finding you take with osteoporosis or osteosarcoma for a short-acting PTH is relevant for humans.

So I'm.

Hopefully the signs will continue to play in so we can be in a position that we can do.

Our scientific justification St is no need for airframes.

Program and also we're also seeing now debt if you look on the osteoporosis compound debt.

Block Black box has been removed for for to you and also debt is a basic and U S consideration because in Europe the knot.

Believing debt.

Clinical findings you take with the process.

After sarcoma for.

Short acting <unk> is relevant for humans, so often debt perspective, I think we have a strong scientific justification to avoid both a black box warning and a rems program.

Jan Moller Mikkelsen: So from that perspective, I think we have a strong scientific justification to avoid both a black box warming and a REMS program. The other part with the ulcer is that patients have been on pump therapy where they are using either Foteo or Napal for multiple, multiple years. And just recall, if you use a POP system with either Forteo or PTH-30W, your basic... have an IV injection for 8 to 12 times in subcutaneous tissue in one hour.

The other part which also is scientific justification is that patients have been on pump, where they're using either for two or net par for multiple multiple years and just recall if you use a pump system either for <unk> or pjs searching for your basic.

Yeah.

Half an IV injection for eight to 12 times in a subcutaneous tissue in one hour.

Jan Moller Mikkelsen: This will provide a flat, flat, flat continuous exposure inside the plasma compartment. And when you look at long-term... Case Studies, Even in pediatrics, you see normal growth there. So I don't believe there is any kind of scientific justification that it's possible to, that there's a lot of discussion, and basic have a meaningful impact on botox. Jesper, will you talk about how we are addressing and ensuring we have the optimal place for our market assessment?

This will provide a flat flat flat continues exposure inside for personal and compartment and when you look on long terms case studies.

Even in children pediatric you'll see normal growth there. So I don't believe there is any kind of scientific justification that is parts of those two that day. So a lot of discussion basic half and meaningful impact on the bulk structure.

Yes, Bob will you talk about how we are addressing and ensuring behalf for optimal place for off market assets.

Yes.

Absolutely and Michelle Thank you very much basically for alumina. Thanks, so much for peak.

Jesper Heulen: Absolutely. And Michelle, thank you very much.

Our key focus is market access for the commercial market.

Jesper Heulen: [inaudible]

Jesper Heulen: The commercial market represents roughly 180 million Americans, and it represented also mainly 75%

<unk> market represent roughly $180 million and merit.

And then the rent percentage also mainly <unk> 75 per cent of the market is via the free Big Pbms.

Jesper Heulen: , , , ,

Jesper Heulen: The three big PBMs, and that's the way that you negotiate with the PBMs for market access is basically what they send out.

And that's the way that you negotiated with the Pbms for market access is basically they send out their requests.

Jesper Heulen: And the final call, you could say, for addressing market access for 2022 basically comes in the last week of August or beginning of September. So we have a golden opportunity to be first on the market with Lonapex somatopene, as we are anticipating the PDUFA date on the 25th of June. And therefore, we will be negotiating with the three big premiums for market access for 2022. And we do believe that we will have good market access for 2022, and on the basis of that, we would be the first in the long-acting segment, potentially, with Lonapex somatopene. I hope that answers your question.

During the summer months and then the final call you could say for addressing the market access for 'twenty 'twenty to basically come in in the last week on.

August beginning of September so we had a golden opportunity to be first on the market with a donor pig so much for Pete.

As we are anticipating the Paducah date on the 26th of June and therefore, we will be negotiating the free big Pbms market access for 2022, and we do believe that we will have a good market access for <unk>.

1022 on the basis for all of that we would be the first in the long acting segment potentially.

I don't want to pay so much for Pete.

I hope that answered your question.

Jesper Heulen: Thanks, Jesper.

Thanks, Yes for rates.

Operator: And congrats on the new year.

And congrats on this.

This year.

Thanks, Paul.

Operator: And your next question comes from the line at Jessica Fye from JP Morgan. Your line is open.

And your next question comes from the line of Jessica Fye from JP Morgan Your line is open.

Jessica Macomber Fye: Hey guys, good afternoon. Thanks for taking my questions. This one might be for Dana. Can you tell us whether the necessary pre-approval inspections have taken place yet for transcon growth hormone and your expectations for those being completed prior to the PDUFA, if there are any.

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

Maybe this one might be for Dana can you tell us whether the necessary preapproval inspections.

Have taken place yet for transcon growth hormone and your expectations for those being completed tired so to do that.

Then any COVID-19 travel issues I know you said multiple times on the call that you guys expect approval on <unk>. So it sounds like maybe things are on track there, but that's that's the first question and then second kind of building on the last question thinking ahead to the 12 month open label extension data for the PTH phase two trial coming up in Q can you talk about what you would have.

Jessica Macomber Fye: , , , , , , , , , , , , ,

Jessica Macomber Fye: Multiple times on the call, you guys said that you expected approval in 2Q. So it sounds like maybe things are on track there. But that's the first question.

Jessica Macomber Fye: And then second, kind of building on the last question, thinking ahead to the next 12 months.

Jessica Macomber Fye: Label Extension Data for the PTH Phase 2 trial coming up in 2Q. Can you talk about what you would expect to see on BMD at the 12-month time point and what that means for the product?

Expect to see on BMD at the 12 month time point and what that means for the product.

Jessica Macomber Fye: I guess...

And I guess more specifically at what point do you expect to have clinical data that will demonstrate that the normalization that you're seeing in BMD early on is not over yet.

Jessica Macomber Fye: Specifically, at what point do you expect to have clinical data that will demonstrate that the normalization that you're seeing in BMD early on does not overshoot and lead to below-normal BMD? Thank you.

To below normal PMT. Thank you.

Dana Pizzutti: So, Dana, would you like to take the first crack? Yes, as far as the inspections are concerned.

So Dana would do first.

As far as the inspections go we're finally, starting to see a bit of movement from the FDA in terms of.

Dana Pizzutti: Yes, as far as the inspections go, we're finally starting to see a bit of movement from the FDA in terms of their activity. In fact, we recently had a GCP inspection at a site for our number one enroller of growth hormone.

Their activity is in fact, we've recently had a GCB inspection at our site.

For our number one and roller of growth hormone.

Dana Pizzutti: So, that was completed last week. As far as the manufacturing inspection goes, we are still in communication with the FDA about when that will be scheduled. And there are a couple of opportunities in terms of alternate approaches that are available. So we still feel that we can address these issues before it has any impact on the PDUFA date. But we're also noticing that FDA is doing more manufacturing inspections outside the U.S., as COVID is somewhat subsiding in certain places.

So that was completed last week as.

As far as the manufacturing inspection goes we are still in communication with the FDA about when that would be scheduled.

And there are a couple of opportunities in terms of alternate approaches.

Approaches that are available.

No.

We still.

Field that we sort of Canada.

Can address these issues.

Before it has any impact on the Peru for date.

But we're also noticing that FDA is doing more manufacturing inspections outside the U S.

As Covid is.

Somewhat subsided in certain places.

Jan Moller Mikkelsen: I think they're going back to your second question, and I think we need to take it in this perspective as my initial comments to Michel. Because there, we basically lay out that what we are seeing now is just a normalization of the bone structure that you expect to do when you actually are coming into replacement therapy and observing that you are providing PTH and physiological levels. And you can also see the differentiation between trapezoidal and cortical bone.

Right.

Okay.

I think just going back to your segmentation.

And I think we need to take it into this perspective as my initial comments to michelle's.

Because there'll be basic layout that wont be seeing now is just a normalization of the bone structure that you expect to do when you ex coming into replacement therapy, and absorbing debt, you, providing ptas and physiological levels.

And you can also see the differentiation between tropical though on cortical bone. If you look on the data you can see where we expect to see EBIT because the remodeling.

Jan Moller Mikkelsen: If you look at the data, you can see where we expect to see the biggest remodeling is in the trapezoidal bone, and we are also seeing the right structure coming out of the bone. So from my perspective, I cannot see any worry about that because that is not normal biology, and we have children that have been 10 years on the infusion pump growing up with normal bone structure on the infusion pump. We have adults that have been sitting for 5 to 6 years on an infusion pump and observing all the same things.

On tropical of books, and we're also seeing debt structure coming in off the bone.

For my perspective is that I cannot see any worry about that because that is not normal by on a T. And we have children that have been 10 years on infusion pump growing up with normal bone structure on infusion pumps, we have a dollar debt sitting five to six years on the infusion pump and observed.

And all of the same thing and I think everyone that just have a clear understanding about an infusion pump and insulin and other things that debt was acknowledged as a total flat curve you provide for you to infusion pump.

Jan Moller Mikkelsen: And I think everyone that just has a clear understanding about an infusion pump and insulin and other things like that will acknowledge that it is a total flat curve you provide with an infusion pump. So I really am lost in the logic of where it is coming from because what we are just seeing is normal biology, which we see in a lot of other things. We see the same thing with urinary calcium. We see the loss of soft tissue calcification.

I really lost in the law, where it coming in because what we just seen as the normal biology, which we see on lot of element. We see the same thing with Q&A, our cash and we see the loss of soft tissue calcification, we see expected and all the normal seasonal loyalty.

Jan Moller Mikkelsen: We see expected all the normal physiology. I cannot change physiology. If you want to have hormone replacement therapy, then you need to expect to see the outcome of being a normal human being. Great, thank you. I'll be just part of the science. And that is what we're doing. I cannot change science. I can only follow and adapt to science.

Cannot change piece of allergy.

If you want to have a home replacement therapy, then you need to expect to see the outcome of being a normal human b.

Great. Thank you.

I'd be just followed besides.

And that is what we're doing I cannot change signs I can follow and adapt to science.

Operator: And your next question comes from the line of Alicia Young from Canter. Your line is open.

And your next question comes from the line of Alethia Young from Cantor. Your line is open.

Alicia Young: Thanks for taking my question and congrats on all the progress. One question, just clarify on the formulary. Maybe I missed it. Do you think that you'll have like kind of a broad formulary that could include adults and some of the other growth hormones?

Thanks for taking my question and congrats on all the progress.

I just wanted to maybe two.

Two questions one just clarifying on the formulary and maybe I missed it.

Do you think that Youll have a kind of a broad formulary that could include adult for some of the other growth hormones and and then the second one is just in oncology.

Is it contained to kind of do work there do you feel like Theres, one target between IL, two or DLR seven that has kind of a no go.

Operator: Your line is open.

Your target risk or do you kind of feel like it's somewhat equal on E M.

Jan Moller Mikkelsen: Jesper, I actually think that what you are now addressing is part of our important launch strategy. And you know, for every product, one step is getting approved. And we have seen actually a long-acting product being approved now in the U.S. without being launched because that is not what I call an associated launch strategy where the product is meaningful to launch. So what you are addressing is the key element in our entire launch strategy.

On a fair amount of confidence on both thank you.

Yes, Paul.

Exiting debt what you are now addressing as part of our important long strategy and you know for every product a one step is to getting approved and we have seen ex those being long acting product being approved now in the U S without being launched because that is not what I call an associated launch strategy with the prop.

Access is meaningful to launch so what we you are addressing is for key element in our entire long strategy and this is where we have a huge comfort in what we're doing because we're not only feeling that we are providing a best in class product opportunity, but we are also providing into the first in class growth hormone deficiency.

Jan Moller Mikkelsen: And this is where we have a huge comfort in what we are doing because we are not only feeling that we are providing a best-in-class product opportunity, but we are also entering the first-in-class growth hormone deficiency market for pediatric patients. So Jesper, do you have anything further to add?

The market for that Peter.

Children.

So, yes, but do you have anything for them to it.

Jesper Heulen: Yeah, of course, just to add that in the initial phase, we anticipate to get the pediatric indication, which is a vast

Yeah of course, just to add that in the initial phase we anticipate to get the pediatric indication, which is the vast vast majority of the market.

Operator: Transcribed by https://otter.ai

Adult indication only represent 10 to 12 per cent of the market. So we will enter into the lion's share of the market and with a pediatric indication.

Jan Moller Mikkelsen: and going back to oncology. You saw we built up a pipeline of three independent product opportunities into Canology Red. We will continue to build up our pipeline in oncology, as we have with our two Hopeful Clinical Programs now in three to four months from now. We really have a paradigm shift in how we treat tumors. And what we really want to do with a tumor is give it a kickstart. We want to kickstart the...

And going back to oncology.

You saw we build up a pipeline of three independent product opportunity endocrinology rare disease, we would continue to build up our pipeline in oncology.

What we have with our too.

Yeah.

Hopeful clinical programs now in the three to four months for now we really have a paradigm shift how to treat tumor and what we really want to do for the tumor is make a kick start we want to kick start the.

Jan Moller Mikkelsen: The Homogenic Response into a Solid Tomb, This is how we think. And at the same time, we come up with what we believe could be a negative, generation of how to do immunological stimulation. We have seen the success of checkpoint inhibitors, but we have also seen the limitations. When we see how potent our transcon I2 is, it is a really unique compound. And this is why we see and build on the entire immunological understanding from Juha and his entire group to build more product opportunities.

The emergency response into a solid tumor.

This is how we think and at the same time become with.

What we believe could be and next generation of how to do it more logical stimulation.

We have seen the success of checkpoint inhibitors, but we're also seeing the limitation.

When we see how potent our transcon <unk>.

Peter Gummies.

It's really a unique component.

And this is why we see and built on the entire immunological understanding from you and his entire group is to build more product.

Jan Moller Mikkelsen: So we basically are a fully integrated oncology company with all the aspects of the immunological immune cycle where we've addressed all pathways. And this is our vision; we want to be a major player in that sector. Yohan, do you have other comments?

So we basically are fully integrated oncology company with all the aspect of the <unk> immune.

Cycle wherever you've addressed all partly and this is our vision, how we want to be a major player in that segment too you have to have other comments.

And I think access to add debt I think we believe that they both have very unique GAAP properties and we will have a unique opportunity in the treatment of cancer.

Jan Moller Mikkelsen: And I just want to add that we believe that they both have very unique properties and will have a unique opportunity in the treatment of cancer. Obviously, our very different product profiles, one being intratumoral administration, and one being systemic, we expect them to also work very effectively together. They're hard to compare with each other, but I think our point really is that they both have their unique spots in the treatment of cancer and will also work additively when treating these patients. So I think of the vision and thinking behind it.

Day Avi.

A very different product profiles on being entered Tumoral administration, one being systemic we expect them to also work very effectively together.

Yeah hard to compare with each other but I think our point really is that they both have their unique spot.

Spot in the treatment of cancer and we will also work additive Lee when treating these patients.

So I think the visionary thinking behalf and why we believe we wanted to be a player in oncology. Even if we would think debt is so different environment compare to rare disease endocrinology.

Jan Moller Mikkelsen: So I think the visionary thinking we have and why we believe we wanted to be a player in oncology, even if we would think that it's such a different environment compared to rare disease endocrinology. We believe in the power of the transcon technology that gives us such a major advancement to make highly differentiated product opportunities basic no one else can make. And by doing that, and built on our algorithm on the basic validated target, and the validated parent drug, we also believe we can be in the same, successful way in our development.

We believe of the power for Transcon technology that gives us a major advancement to make highly differentiated product opportunities basic no. One is can make and.

But doing debt and built on our algorithm on basic validated target validated parent drug. We also believe we can be in the same.

Successful way in our development.

Jan Moller Mikkelsen: And when we go to the third product opportunity, we basically build on what we have done in Transcon IL-2 Beta Gamma and Transcon TLR-78; there will be a strong synergy between what we're doing in the third one. This is how we want to think, how we want to make a paradigm shift.

And when we go to the third product opportunity, we basically per build on what we have done in transcon Iot piece of gum Transcon Telos seven eight that will be a strong synergy what we're doing in the search one. This is on how we want to think how we want to make a paradigm shift.

Great. Thank you.

Operator: And your next question comes from the line of Joseph Schwartz from SVB Learing. Your line is open.

And your next question comes from the line of Joseph Schwartz from SBB Leerink. Your line is open.

Joseph Patrick Schwartz: Transcon C&P in your opening remarks, but I was just wondering if you could just elaborate a little bit more on the program. How did you choose your accomplished study doses and how have you designed your accomplished China study in order to leverage your findings in the accomplished study in the U.S. and EU trial and how should we interpret these two results when they emerge later in 4Q?

Okay.

But I was just wondering if you could just elaborate a little bit more on the program.

How do you how did you choose your accomplish studied doses on how have you designed your China study in order to leverage your final day he accomplished.

Accomplish title on the U S.

Ooh trial, and how should we interpret force to resolve one day launch later on platform.

Joseph Patrick Schwartz: I, we just lost the beginning of it, but I believe that what you're referring to is our Transcom CNP program.

We just losses beginning of it but I believe that what youre, referring to is our transcon CMP program.

Oh, yes, yes.

Jan Moller Mikkelsen: I think that is what you are referring to, and I actually believe that we are making a major effort now to understand this.

I think that is what you're referring to and I exited leaf that we having a major effort now to understand.

This.

Jan Moller Mikkelsen: I think it is important to see. We know how C&P has functioned. We have known that for 50, 20 years. We know the biology and the science behind it, and that is what has directed our two programs with Transcon CMP. We are now in a position that we have a unique product opportunity with Transcon CMP, which can provide a continuous exposure for up to one week with a one-finger dose, and we know we can do it in an extremely safe manner. And we do it now in two independent products, or what you can say, two independent clinical trials. But what we really want to do is not only look at one single pair of me.

I think important disease.

We know how CMP has function we have no debt for 15 20 years, we note that the quality and the science behind it and Digest what have directed our.

Two program Retrenchment CMP.

We are now in a position that we have a unique product opportunity with transcon, CMP, which can provide a continuous exposure for up to one week.

One single dose and we know we can do it in extremely safe manner.

And we do it now into independent product.

You can see two independent clinical trials, but what we really want to do is not only look.

One single per meter.

Jan Moller Mikkelsen: We are aiming to go down to newborn children as fast as possible. We were, because of our unique safety profile, able to start already at age 2. And we are dedicated to moving it down as early as possible, as fast as possible, down to newborns because we know...

We are aiming to go down to the newborn children as fast as possible because of our unique safety profile minus two start already.

Two and we are dedicated to move it down as early as possible as fast as possible down to newborn children, because we know.

Jan Moller Mikkelsen: If we want to address comorbidity, some of them are irreversible, happening at a very, very early stage, and that is really what we want. Mark is leading a major effort in Ascendis to really expand the program involving a lot of different comorbidities. And I do not know, Mark, if you can say a few words how you also use our huge national history study now and try to integrate the development comorbidities and try to develop them in a unique clinical development plan so we can potentially address not only the high but also the other Kuma people.

If we want to address comorbidity some of them.

Suppose happening in our Bev out early states and that is really what we want to do.

Mark is leading an effort in ethane how really to expand the program involving a lot of different court more pizza twos and I do not know Mark if you could say a few words. How you also use a huge national history study now and try to integrate the development co Morbidities and.

Try to develop that in an unique clinical development claim so we potentially can address not only height.

But also the other comorbidities.

Sure I can say a few words thanks Ian.

Mark Bock: This website is providing us with very valuable information. And, you know, one of the things we find when we talk with individuals with achondroplasia is that height is not the biggest issue that they want us to look at, but rather, a lot of the comorbidities, issues with the foramen magnum, issues with otitis media, issues with the airway. And so, for us, it's been very important not just to be prepared to look at height, but to really understand the comorbidities better, and we are using the natural history study to try to gain information about the comorbidities, frequency, time of occurrence, and to give us enough information to, you know, successfully study them in a clinical trial. So, I think that's what Jan is alluding to, and it's actually providing us with, even early on, what we think will be useful.

So we have an ongoing natural history study, which is providing us very valuable information and.

One of the things we find when we talk with.

Individuals with achondroplasia is there the height is not the biggest issue that they want us to look at but rather a lot of the comorbidities.

Issues with foramen magnum issues with otitis media.

With airway.

And so for US it's been a very important not just to be prepared to look at night, but to really understand the co morbidities banner and we are.

Using the using the natural history study to try to gain information about the comorbidities frequency time of occurrence and to give us enough information to successfully studied them in a clinical trial. So I think that's what you're alluding to and it's actually providing us even early on what we think will be useful information.

Jan Moller Mikkelsen: So, what is Mark? The hope is that we can integrate that knowledge into our clinical development.

Thanks, Ken.

So what is it mark.

The signing is that we could integrate that knowledge into our clinical development zone.

Right. Okay, great. Thanks, and then my next question is on Transcon PTH.

Operator: Okay, great. Thank you.

Joseph Patrick Schwartz: And then my next question is on TransCon PTH. Based on our conversations with endocrinologists, some doctors prefer to see T-scores over Z-scores in adults. And our question is, you know, do you have plans to present this?

Based on our conversations with endocrinologists, some docs per parcel for Keith scores.

These scores in adults.

Our question is do you have plans to present that on how does that compare to take place.

Joseph Patrick Schwartz: And how does that compare to a T-score?

Jan Moller Mikkelsen: A T-score and a Z-score are completely different depending on the benchmark measuring. A Z-score is to a normal population, and this is also what we use in growth hormone deficiency when we talk about height. You typically use a Z-score because that is the most relevant one. When you talk about osteoporosis compounds, you often use a T-score because this is where you basically are trying to compare what was optimal for the person. And but I think that is not really the aim of this here. We can also look at the T-score. It's basically providing the same guidance and the same thing that we see with the S-score.

T score on Cisco, a complete different independent benchmark, Michigan Cisco is to a normal population and this is also what we are using in growth hormone deficiency. When we talk about height. You typically use a set goal because that is the most relevant one when you talk about us.

For purposes compound you often use a T score because this is the way you basic or trying to compare what was optimal for the post.

And but I think that is not really the aim of this year. We also can look on the T score. It's basic on providing the same guidance and at the same <unk> as the ESCO, but as we have a hormone replacement therapy is typical what you want to do you want to do a normalization of all different element of the body.

Jan Moller Mikkelsen: But as we have hormone replacement therapy, it's typical what you want to do. You want to do a normalization of all different elements of the body to be as a normal human being. This is the definition of hormone replacement. If you go to osteoporosis, you want to redo, reset what you call a national decline in some of the bone structure. And this is why you're in some way referring to a T-score

<unk> B S in normal human being this is the definition of hormone replacement.

If you go to <unk>, you want to redo reset.

What we call a national decline in some of the bone structure and this is why you're some way referring into a T score, but this is coming from a demographic that is not building on a patient population that has a complete different dense bone structure than what you see in other places because there is a day.

Jan Moller Mikkelsen: But this is coming from a demographic that is not building on a patient population that has a completely different dense bone structure than what you see in other places, because it's a dense structure that is happening through what we call a non-national process where you're basically just building up a dense bone structure because you have no turnover. That is not the same thing as having a healthy bone structure. No one is ever claiming that the bone structure you have in an ASB patient is healthy, even if it's more dense, because it's an old bone structure. So I think it's not meaningful to compare it to a T-score. Sure, we have the data, and we have looked at it. What is meaningful for hormone replacement therapy is compared to a SET score.

Structured debt, it's happening to won't be coal and non natural process, where you basically just building up day.

Bone structure, because you have no turnover.

That is not the same thing to have a healthy bump structure no. One is claiming that the bone structure you have in the <unk> patient is healthy even as more times because these are all strong bone structure.

I think he is not meaningful to compare to a T score sure. We have the data have you looked at what is meaningful for hormone replacement therapy as compared to a cyclical.

Operator: Okay, great. Thank you for that.

Okay, great. Thank you for that.

Operator: And your next question comes from the line of Anita Dushan from Barron Bay.

And your next question comes from the line of IDB that day, Sean from Burton Brean Capital. Your line is open.

Anita Dushan: from Berenberg Capital, Yelani. Hi, good afternoon. Thank you for taking my questions. Just a couple here.

Hi, good afternoon. Thanks for taking my questions just a couple here.

Could you please remind us the sort of timeline.

Anita Dushan: Could you please remind us the sort of timeline in terms of the pediatric phase 3 trial that would commence in Japan? I know you have applied for the CTN, so when is it sort of likely to, you know, so you're going to get the green signal to go ahead. And then, in terms of the HP phase 3 trial, would there be any change to the trial design itself in terms of inclusion or exclusion criteria for patients based on your six-month data?

In terms of me.

Pediatric wholesale debt.

<unk> sorry.

I know you have applied for the arm.

Hey, Tim So Glenn sorry.

Sort of like <unk>.

Yeah.

Yes.

Please go ahead and then in terms of the.

HP.

Yeah.

Will there be any change to the trial design paraffin.

Tens of inclusion on this question taking patients based on your on six months data.

Anita Dushan: I think the first question concerns our Pediatric Growth Hormone Deficiency Trial or RITE Trial. Mark, could you give us the status of our RITE Trial in which you have extensive experience in Japan?

I think the first question is reflecting our pediatric growth hormone deficiency trial, all right trial market.

That gave us per stages of a REIT trials debt.

As Tim says experience in Japan.

Mark Bock: Yes, absolutely. I actually spent 10 years of my career living, working, and doing clinical research in Japan. And similar to the U.S., once you file a CTN, unless they object, then two to four weeks later, you can start your study. And so that's usually not rate-limiting. The approval is usually not rate-limiting. But in any case, that study is actually going ahead and is in the screening phase. So I think there are no roadblocks to continuing the development.

Yes, absolutely I actually spent I've spent 10 years of my career living and working on doing clinical research in Japan.

And a similar similar to the U S. When you find out once you file a TTM unless the object.

Then two to four weeks later you can start your study.

So that's usually not rate limiting the approval is usually not rate limiting but in any case.

That study is actually going ahead, and it's in the screening phase so.

So I think it's you know theres no roadblocks to continuing development in Japan.

Jan Moller Mikkelsen: I think, from a

Jan Moller Mikkelsen: I think from a company perspective, we will be in a unique position because it looks like all our product opportunities in three different indications, pediatric growth hormone deficiency, adult growth hormone deficiency, and HPE will be nearly aligned for approval in the same time period. What I think is a unique situation for us to find an optimal way to make a commercial effort in this region, which typically involves Japan, South Korea, and other major countries outside greater China in that region.

I think from a company perspective, we will be in a unique position because it looked like all of our product opportunity in three different indications pediatric growth hormone deficiency adult growth hormone deficiency, and HPE will nearly be aligned for approval nearly at the same time period with our exiting is a unique situation for.

For us to find an optimum way to make a commercial effort in this.

This region was too because it involves a Japan, South Korea, and other major country outside greater China in that region.

Jan Moller Mikkelsen: And then, as far as the Phase 3 HP trial is concerned, would there be any changes in the trial design based on the six-month data?

Okay.

Okay.

And then as far as the.

For the H B Tran.

Would there be any changes in the trial design based on the six month data.

Jan Moller Mikkelsen: Related to the six-month data we have disclosed in the open-label extension, we will basically have the same patient population coming into the trial as we saw in our Phase 2 trial. There will not be, I think, Mark, you can correct me. I think it's a little bit broader this time because there is a patient population of HDH1 patients that we also have included because they will hugely benefit from having a normal physiological level of PTH like a post-surgical one.

Related to the six months data we have disclosed in the open label extension, we will basically have the same patient population coming into the trial as we saw in our phase II trial that will not be I actually think this is Marc you can correct me I think just a little bit broad at this.

Because <unk> is a patient population as HC 801 patients. We also have included it because they have a hugely benefit to have a normal physiological level PTH like Pos. So June one. So this kind of patient population also being open at all in the face.

Jan Moller Mikkelsen: So this kind of patient population is also being opened up in the Phase 3 trial, and we also believe that it's important that they have an opportunity to get an optimal PTH treatment with a physiological PTH level for 24 hours, where we looked at what was really difficult in the phase 2 trial and why we... You always look at screening failure. Why do we have screening failure? What is the driver of the screening failure?

<unk> tried and we also believe it is important that they have an opportunity to get on optimal PGA treatment with official logical ptas.

They were 24 hours and from that perspective is we actually are.

Having the.

Other changes is basic in the well.

<unk> looked at what was really difficult in the phase II trial, and what why you orders took on screening failure why do we have the screening failure on what is a driver of the screening failure and we actually realized there was really really difficult for him. Please be patient just to have a normal <unk>.

Jan Moller Mikkelsen: And we actually realized it was really, really difficult for an HP patient just to have a normal serum calcium of 8.3. It was hard, just by standard of care, taking activated vitamin D, and taking calcium supplements to make them up to 8.3. You know the normal calcium level is typically in the 9. In a trial here, we have between 8.3 and 10.3. But we are in a position that we basically lower the entry criteria so you can go down to 7.8 to be part of the trial. And it was basically to ensure that all this patient group, which was impossibly basic,

Catch some on $8 three it.

It was hot just by standard of care, taking activated vitamin D. Taking <unk> supplement to meet them up to eight countries. You'll know that normal calcium is typically in benign in trial here be happy team eight three and 10.3, but we are in a position that we basically lowered the entry criteria.

So you can go down to seven 8% to be part of the trial and it was basically to ensure that all of this patient group, which was impossible to basic to be in a position to titrate up to debt.

Mark Bock: Yeah, I mean, there's a few other subtle differences between phase, you know, basically relying on what we learned in phase two and going to phase three. So in phase two, again, for the first, first efficacy trial, the dose was fixed for the first four weeks and then allowed to titrate. In phase three, we're allowed to titrate from the beginning, which makes clinical sense. And in phase two, the upper dose limit was lower than what we're allowing in phase three based on what we learned in phase two.

Mark do you have oil element or thing that I have forgotten.

Yeah, I mean, there's been a few other subtle differences between phase basically relying on what we learned in phase III and going to phase III, So and free.

Phase two again for the for the first first efficacy trial. The dose was fixed for the first four weeks and then allowed to titrate in phase III, we're allowed to titrate from the beginning which makes it makes clinical sense.

And.

In phase two the upper dose limit was was lower than what we're allowing phase III based on what we've learned in phase II.

Mark Bock: So there are a few small things. And then the other is that in phase two, we validated the specific quality of life instrument that will then be used in phase three as an outcome measure. So, I think those are the primary differences between the two trials.

So there's a few small things and then the other is that in phase two we validated that need specific quality of life instrument that will then be used in phase III. So that's an outcome measure. So so I think those are the primary differences between the two trials.

Mark Bock: Thanks, Mark. Great, thank you.

Thanks, Mark great. Thank you.

Operator: And your next question comes from the line of Renee Wooders from Camden. Your line is open.

And your next question comes from the lineup for any <unk> from Kempen. Your line is open.

Renee Wooders: Hi guys, thanks for taking my questions. I guess I have two from my side.

Hi, guys. Thanks for taking my questions.

I guess two for my side, So first one on Transco non growth hormone.

Renee Wooders: So, first one on transcom growth hormone. Now that you have the two years' data, can you remind us how long you are planning to continue following up these patients? And what will you do with this data? And do you anticipate submitting this data to the regulators as well? And the second question is on transcom PTH. Great to see that almost all patients are still on therapy in the open label extension part. Maybe moving, jumping a few steps ahead to commercialization. What are the lessons you learned from NetPara? Why do you think transcom PTH will be commercially more successful? Thanks.

Now that you have for two years data can you remind us how long you're planning to continue following up these stations.

Ultimately you do with this data and do you anticipate to submit these data to the regulators as well and the second question is on the Transcon PTH.

See debt, there's still almost all patients are on therapy in the open label extension part.

Maybe moving jumping a few steps ahead too towards commercialization and what are the lessons you've learned from net net farah.

Why do you think grasp on transcon PTH will be will be commercially more successful. Thanks.

Jan Moller Mikkelsen: Yes, thanks a lot. Thanks a lot for the question. The first one is basically addressing what do we do during the flight?

Okay.

Yes, Thanks, a lot. Thanks, a lot for the question. The first one is basic us.

Addressing what do we do in the flight.

Jan Moller Mikkelsen: in the trial that we continue on in our phase three where we have the open label extension for both the flight and the height trial, which we are continuing on it, and currently, we see patients coming to a situation that their baseline is reaching final height. We are in a position, and we will continue this Open Label Extension Trial, so we basically can continue to collect unique information about how we basically are providing a treatment where every child has an opportunity to Achievement Unlocked. They are the expected height, not only height but also other elements like body composition and other things like that that we are measuring.

And the trials that we continue on.

In our phase III, where we have for open label extension for both from the flight and the height trial with continue on it and currently we see patient coming to a situation that they are basic.

Reaching final height, we on a position Vv continue this open label extension trial. So the basic can continue to collect unique information about how we basic.

Providing a treatment where every child have an opportunity to.

Ashish.

The expected height, not only high but also.

Element like body composition, and other things like that that would be Michigan, and we think that is a really important thing.

Jan Moller Mikkelsen: And we think that is a really important thing. We are running our trial in multiple countries, and we hope and expect it to continue in most of this country. But Mark, you're sitting with all the post commitments now here, and perhaps you can give a short update about what we expect to continue to do. In the summary, we'd like to continue to give you data for this important trial.

We are running our trial in multiple countries and we hope and expect sales to continue in most of this country.

And Mark you are sitting with the older post commitment now here.

And perhaps you can give a short update about what we expect to continue to execute.

But we summary, we'd like to continue to keep your data for this important trial.

Mark Bock: Sure. Do you want me to add a couple of comments? Yeah. Yeah, okay.

Yeah.

Sure do you want me to add a couple of comments in yeah.

Yes, okay. So so.

Mark Bock: So, as you know, the enlightened trial, which is the combined ongoing study from flight and height, is continuing. And, you know, and as Jan said, we're getting very nice data on it. Some of the patients are indeed, you know, getting towards their near adult height; others have some room to go.

As you know the enlightened trial, which is the combined ongoing study from from flight in height is continuing.

And as Ken said, we're getting very nice data on at some of the patients are indeed.

<unk> towards their near adult paint others have some room to go.

Mark Bock: I think, you know, at least for the time being, the study is continuing, and I would expect both clinicians and regulators may have some interest in having some longer-term data. And so at this point, I think it's premature to make a commitment on how long we'll continue. But it is certainly continuing for now and delivering valuable data. I think over the next month, we'll have a better idea about what longer-term data we want or would need to collect. But certainly, it's ongoing now and is really still giving very useful information.

At least for the time being the city's continuing and.

I would expect both both clinicians and regulators may have some interest in having some longer term data and so at this point I think it's premature to make a commitment on how long will continue but it is certainly continuing for now and delivering valuable data I think over the next.

Next month, we'll have a better idea about what what.

Longer term data, we want or would need to collect but that's certainly its ongoing now and really still giving very useful information.

Jan Moller Mikkelsen: So I think, addressing your question, what is the learning from that part?

So I think addressing your question what is the learning.

From that path.

Jan Moller Mikkelsen: Even if you develop a product like Adjunct to stand up for care, there is still a huge need for such a product. And then you can almost imagine what the need would be when you have a hormone replacement therapy and not just an adjunct therapy. That is the differentiation.

Even if you develop a protein like adjunct to standup a clear day is still a huge need for social product.

And then you can really imagine what.

What is the need would be when you have a hormone replacement therapy and not just an adjunct.

Therapy.

Adjusted for differentiation, we are competing in two different segments.

Jan Moller Mikkelsen: We are competing in two different segments. One is an adjunct therapy. We are positioning transcon PTAs as a hormone replacement therapy, addressing all aspects of the disease, both short-term symptoms and long-term complications.

One is an adjunct therapy, we are position transcon PTH as a hormone replacement therapy.

Addressing all aspect of the disease, both short term symptoms long term complications.

Jan Moller Mikkelsen: That is the main difference between the two products. This is like an apple and an orange, in my view.

That is the main difference between the two product is is like.

And Apple on an orange in my view.

Operator: Okay, thank you very much.

Okay. Thank you very much.

Operator: And your last question comes from the line of Yehen Zhu from Wells Fargo Securities. Your line is open.

And then last question comes from the line of Yanan Zhu from Wells Fargo Securities. Your line is open.

Unknown Executive: Hi. Thanks for taking my questions.

Hi, Thanks for taking my questions.

Unknown Executive: So a couple on a CNP program and a couple on a PTH program. So for the CNP program, to identify a dose to move forward into the Accomplished China trial, do you need to wait until all four blinded dose cohorts in the U.S.-EU Accomplished China trial are completed, or could you unblind each dose cohort as you go? And then any plan to open a U.S.-EU dose expansion trial for the CNP program?

A couple on the CMP program and a couple on <unk> PTH program for the for the CMP program.

To identify a dose to move forward into the accomplished China trial do you need to wait until off.

For blinded dose cohorts in the U S. EU accomplished trial can be completed or could you on blind.

Each dose cohort as you go.

And then any plans to open.

You dose expansion trial.

For the CMP program.

Jan Moller Mikkelsen: Great question. I think we are in a position that we are aiming not to unblind it. We think it's really, really, really important not to unblind the patients. But we also believe that it's possible on a blinded basis to be in a position to have some good guidance that we potentially are in a situation where we have an active dose. We have a lot of primary outcomes we're looking at. We also have a series of biomarkers that we are addressing and other elements that could give us guidance about where we are.

Thanks.

Great Christian zinc, we are in a position debt.

We are aiming not to on blinded, we think it's really really really important to on.

Not to on blinded.

But we also believe that as possible on a blinded basis to be in a position to.

We will have some good guidance that would be potential.

In a situation that we have an active dose we have a lot of.

Primary outcome be looking in we also have a series of Biomarkers that we are addressing in our.

Element that could give us and guidance above where we are and this is aware mark and his team is really developing how we need to look on all of this data and be convinced that we have something that is meaningful to move forward in a dose escalation and dose expansion.

Jan Moller Mikkelsen: And this is where Mark and his team are really developing how to really look at all this data and be convinced that we have something that is meaningful to move forward in dose escalation and dose expansion. And that is the task of Mark and his people, to be quite sure that they're confident that we see something on a blinded basis. So we don't want to unblind the trial before everything is clear.

On it.

And that is the task of Mark and his people to be quite sure that the confidence that we see something on a blinded basis. So we don't want to online for trials before everything is done.

Jan Moller Mikkelsen: The second one, this is up to the situation; yes, potentially, we will do that, depending on that. We are in a unique position because of our recent pharmaceuticals and the experience of the team in the effort to conduct this trial that we have such fast access to patients in Greater China, but we have also seen that is we have also seen the same thing in Europe and the US, in Australia and other places. So, huge interest in our trial that we should not be limited to any kind of limitation and how many patients we want to take. So I do not know, Mark, about our plans to potentially open up and... European US arm in the dose expansion. I don't think it's something we really have decided on yet.

The second one this was up to the situation, yes, potentially be redo debt depending on debt. We are on a unique position to a recent pharmaceuticals and the experience for the team index to conduct this trial that we have so fast access to patients.

In greater China, but we're also seeing debt is we're also seeing the same thing in Europe and U S in Australia and other places.

So she was interest for our trial that would be not to be limit to any kind of day.

Limitation on how many patients we want to take it.

I do not on Mark a about our plans to potentially open up.

European and U S in the.

The dose expansion I don't think it's something we really have decided on yet.

Mark Bock: No, we have not discussed it for now. You know, things are going well, both in the global trial and in the Chinese trial. So, you know, it's not something we've talked about so far, but certainly, should it be necessary, we could talk about it, but it's not on the agenda right now.

No we have not discussed it for now things are going well both on the both in the.

Global trial on the China trials so it's.

Not something we talked about so far but certainly.

Should it be necessary, we could talk about it but not on the agenda right now.

Unknown Executive: Got it. And on the PTH program, what kind of interest are you seeing in the pathway phase three trial? Is there enthusiasm due to the data you reported from the phase two open-label extension? And then is the safety database from 76 patients considered sufficient for the regulators? Thank you.

Got it and on the PTH program, what kind of interest are you seeing in the past.

On a pathway phase III trial on their answer was yes due to.

The data reported from the Phase II open label extension and then.

The safety database from 76 patients.

There is sufficient for the regulators. Thank you.

Jan Moller Mikkelsen: There are two questions. The first question is, how high is the understanding about what we can provide with transcon PJs throughout the HCP, Patient Society, and Physics? I've never seen anything like that before.

That's two question.

For the first question is.

How high is the.

Understanding about what we can provide with transcon PTH.

<unk> of the ESP.

Patient Society.

And for patients.

I've never seen anything like that before.

Jan Moller Mikkelsen: When we see anxiety asthma, how people get their life back again, and sure, it's helping us to go out and get a broader education about it, like at the endo-conference. But we already see huge enthusiasm everywhere. So to be part of this trial is really exciting.

We see.

The anxious estimate.

People get their life back again.

And sure it is helping us to go out and make a broader education about it like in the into conference well be.

You already see a shoes anxious estimate.

Everywhere so to be part of this trial.

So I believe that we now see how transcon PTH is a game changer, we are addressing the life of more than 200000 patients dosed in Europe U S and Japan.

Dana Pizzutti: So I believe that when I see how Transcom PTAs is a game changer. We are improving the lives of more than 200,000 patients just in Europe, the US, and Japan. And what we have seen, BASIC, by having 58 out of 58 BASIC programs continue on it. Everyone has a huge, huge benefit from this tree. And related to the safety database, I think Dana, you can explain how we're building up a combined safety database both from our phase two trial and also what we will see in our phase three trial.

And what we will see basic by having 58 out of 58 basic continue on it.

Everyone has a huge huge benefit of discrete.

And related to the safety database I think Damian you can explain how were building up cash.

<unk> safety database, both from our Phase II trial, and also what we will see a phase III trial.

Dana Pizzutti: Yes, for the sort of approval, as we discussed with the Agency, too, in our end of phase 2 meeting, the, you know, combination of the information from phase 2 and phase 3 will satisfy the criteria for the, you know, safety thresholds for the application.

Yes for the.

Sort of approval.

We discussed with the agency to and are in.

End of Phase II meeting.

Yes.

The combination of the information from the phase two and the phase III will.

Satisfy.

The criteria for the.

Safety for.

Operator: Got it. Thank you. Yep. Yep. Very helpful. Thank you.

<unk> for the the applications so.

Okay got it thanks for that.

Yes, yes, yes very helpful. Thank you.

Operator: And ladies and gentlemen, this concludes today's conference call. Thank you all for your participation and have a wonderful day. You may all disconnect.

Okay.

And ladies and gentlemen. This concludes today's conference call. Thank you all for your participation and have a wonderful day you may all disconnect.

Thanks, a lot.

Thanks.

Operator: Thank you for your attention, and have a wonderful day. You may all disconnect.

[music].

Yes.

Yes.

[music] zone.

Operator: ??