Q1 2022 Ascendis Pharma A/S Earnings Call

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Today's conference is scheduled to begin shortly.

Welcome to the first quarter 2022 centers Pharma earnings conference call.

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

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I would now like to hand, the conference over to your Speaker today, Tim Lee Senior Director Investor Relations. Please go ahead.

Thank you operator.

Thank you everyone for joining our first quarter 2020 financial results Conference call today are Jim Lee Senior director of Investor Relations of percentage format.

Welcome to the first quarter 2022, Ascendance Pharma Earnings Conference Call.

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

Joining me on the call today is Jan Mikkelsen, President and Chief Executive Officer, Scott Smith, Senior Vice President and Chief Financial Officer, Dr. Dana Pizzuti head of development operations and Chief Medical Officer Dr.

After the speaker's presentation, there will be a question and answer session.

Doctor you have pre internet head of oncology and Dr. Christina single head of clinical development oncology.

To ask a question during the session, please be advised that today's conference is being recorded.

Before we begin I would like to remind you that this conference call will contain forward looking statements.

If you require any further assistance, please press star and then zero.

Tended to be covered under the safe Harbor provided by the private Securities Litigation Reform Act. Examples of steep such statements may include but are not but are not limited to our U S. Commercialization and continued development of skytrooper for the U S market.

The commercialization of Transcon hgh for the EU market.

Our progress on our pipeline candidates and our expectations with respect to their key progress statements regarding our strategic plans our goals regarding our clinical pipeline, including the timing of clinical results.

Regarding the U S market approval of Sky, Coosa, and our pipeline product candidates statements regarding our planned <unk>.

20 filings.

Our expansion into new therapeutic areas and statements regarding our ability to create a sustainable leading global Biopharma company.

These statements are based on information available to us today actual results and events could differ materially from those in the forward looking statements and we may not be able to achieve our goals carry out our plans or intentions or beat the expectations or project 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.

Additional information concerning the factors that could cause actual results to differ materially. Please see our forward looking statements section in today's press release and the risk factors section of our most recent annual report on form 20-F filed with the SEC on March <unk> 2022.

Transcon human growth hormone or transplant Hgh is approved by the FDA in the U S. Under the brand name Sky Christa the treatment of pediatric patients one year older. We at least 11, five kilograms and have growth failure due to inadequate secretion of endogenous growth hormone and.

In addition, the European Commission has granted marketing authorization for <unk> ascend is format developed under the name Transcon Hgh as a once weekly subcutaneous injection for the treatment of children and adolescents age three to 18 years with crude failure due to insufficient secretion of endogenous growth.

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

Otherwise can you just note that our product candidates, our investigational and not approved for commercial use.

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

I would now like to hand the conference over to your speaker today, Tim Lee, Senior Director, Investor Relations.

On today's call, we will discuss our first quarter 2020 financial results and will provide further business updates. Following some prepared remarks. We will then open up the call for questions I will now turn the call over to Jan Mikkelsen, President and Chief Executive Officer.

Please go ahead.

Yeah.

Okay.

Thank you, Operator.

Thanks, Tim and good afternoon.

Thank you, everyone, for joining our first quarter, 2022 Financial Results Conference Call today.

2021.

Lastly, an extraordinary year for Santos.

As we became a fully integrated commercial stage Biopharma company.

I'm Tim Lee, Senior Director, Investor Relations at Ascendance Pharma.

With the launch schedule for <unk> in the U S.

And the expansion of our clinical pipeline two five independent programs.

Joining me on the call today is Jan Mikkelsen, President and Chief Executive Officer, Scott, Smith, Senior Vice President and Chief Financial Officer, Dr. Dana Pezzuti, Head of Development, Operations and Chief Medical Officer, Dr. Yuha Poonanen, Head of Oncology, and Dr. Stina Singel, Head of Clinical Development Oncology.

The chronology rare disease and encore.

On quality.

Before we begin, I would like to remind you that this conference call will contain four, lifting statements that are intended to be covered under the safe harbor provided by the Private Securities Litigation Reform Act.

These such as comfort.

That we have the right strategy.

The people.

And capabilities in place to allow us to allows cheap or we should treat by three and to build a sustainable profitable leading global Biopharma company.

Examples of such statements may include, but are not limited to, our U.S. commercialization, and continued development of SkyTrooper for the U.S. market, the commercialization of Transcon HGH for the EU market, our progress on our pipeline candidates, and our expectations, with respect to this continued progress, statements regarding our strategic plans, our goals regarding our clinical pipeline, including the timing of clinical results, statements regarding the U.S. market approval of SkyTrooper, and our pipeline product candidates, statements regarding our planned regulatory filings, our expansion to new therapeutic areas, and statements regarding our ability to create a sustainable, leading, global biopharma company.

These statements are based on information that is available to us today. Actual results and events could differ materially from those in the four lifting statements, and we may not be able to achieve our goals, carry out our plans, or intentions, or meet the expectations or projections disclosed in our four lifting statements, and you should not place undue reliance on these statements.

Our four lifting 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.

Yeah.

In 2022.

<unk> already achieved.

We assume no obligation to update these statements as circumstances change, except as required, by law.

For additional information concerning the factors that could cause actual results to, differ materially, please see our four lifting statements section in today's press release and the risk factor section of our most recent annual report on Form 20-F filed with the, SEC on March 2, 2022.

And important milestone.

Transcon Human Growth Hormone, or Transcon HGH, is approved by the FDA in the U.S. under, the brand name SkyTrooper for the treatment of pediatric patients one year or older who weigh at least 11.5 kilograms and have growth failure due to inadequate secretion of endogenous growth hormone. In addition, the European Commission has granted a marketing authorization for lonabexomocropin, ascendansforma developed under the name Transcon HGH as a once-weekly subcutaneous injection for the treatment of children and adolescents aged 3 to 18 years with growth failure due to insufficient secretion of endogenous growth hormone.

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

In March.

We reported results.

So all the trends car PTH phase III poker.

And our pathway twice.

The primary and all key secondary endpoint.

Transcon PTH.

Okay to date.

And major unmet medical need.

For adults with chronic hydropower Tory Smith patients.

Docks rare disease population.

200000 patients in North America, Europe , and Japan, Japan alone.

Yeah.

It is rare.

For a biotech company.

You have two potential blockbuster product candidates in a row, achieving the target product profile and successfully meet the phase III trial objectives.

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

What has put <unk> in this unique position.

Yeah.

First.

Our transcon technology platform.

And I'll walk coats to product innovation.

The uniqueness of the Transcon technology platform.

Combining the benefits of two independent technology platforms like <unk>.

Tickle Pud or technology.

A predictable sustained release technology.

The transcon technology platform can be applied.

And we're supposed to talk types.

We believe this combined with a validated approach to product innovation enabled us to achieve.

Higher rate of success compared to traditional drug development.

On today's call, we will discuss our first quarter 2022 financial results and will provide, further business updates.

Segment.

Our commitment to patients and the sites.

Following some prepared remarks, we will then open up the call for questions.

Our commitment to patient and sign has guided our product development strategies.

We seek to design optimal clinical programs two different <unk> product candidates to patients as quickly as possible.

Robust clinical data.

Yeah.

So.

At this time.

That's extremely important.

We have a strong balance sheet to support long term strategic execution.

We have the capital necessary to enable both short and long term goals.

During the first quarter, we further strengthened our balance sheet through a convertible notes offering.

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

As a result with the cast on Haynesville day, we believe we are well positioned to lead to label all all of you should treat but strategy indicated.

Financing.

Thanks, Tim, and good afternoon.

What makes me so optimistic for the future.

2021 was an extraordinary year for Ascendis, as we became a fully integrated commercial, state biopharma company with the launch of SkyTropha in the US and the expansion of our clinical pipeline to five independent programs in endocrinology, rare disease and oncology. These successes confirm that we have the right strategy, the people and capabilities in place, to allow us to achieve our vision tree by tree and to build a sustainable, profitable, leading global biopharma company.

So optimistic for their patients.

In 2022, we have already achieved an important milestone. In March, we reported results for the Transcom PTA's Phase 3 program and our pathway trial, met the primary and all key secondary endpoints. Transcom PTA is a product candidate, addressing a major unmet medical need for adults with, chronic hypothyroidism patients, a large rare disease population with around 200,000 patients in North America, Europe and Japan alone.

So optimistic for this is that all of our five independent clinical programs are based on the Transcon technology duplex.

And developed using the same as what we can for product innovation.

And give us navigate.

The regulatory pathway with the sustained experienced local team.

That growth transcon growth hormone.

In the U S and Europe .

It is rare for a biotech company to have two potential blockbuster product candidates in a row, achieving their target product profile and successfully meet their Phase 3 trial objectives.

We believe we have demonstrated that we have the fundamentals for creating a continuous stream of product candidate.

With the potential to address major unmet medical need.

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Drop depend on them.

What has put Ascendis in this unique position? First, our Transcom technology platform and our approach to product innovation. The uniqueness of the Transcom technology platform, combining the benefits of two independent, technology platforms, the classical product technology and a predictive platform, The Transcom technology platform can be applied broadly to multiple drug types.

For example, we can apply the Transcom technology platform to the use of drugs, such as heroin, methadone, and methadone.

In short <unk>.

We believe <unk> has the right approach a growing portfolio of product candidates, the right people and capabilities and the necessary funding to lever on our goal to create a sustainable global Biopharma company.

We believe this, combined with our validated approach to product innovation, enables us, to achieve a higher rate of success compared to traditional drug development.

Second, our commitment to patient and their science. Our commitment to patient and science has guided our product development strategies. We seek to design optimal clinical programs to bring differentiated product candidates, to patients as quickly as possible with robust clinical data.

Third, and in this time perhaps extremely important, we have a strong balance sheet, to support long-term strategic execution. We have the capital necessary to deliver on both short- and long-term goals. During the first quarter, we further strengthened our balance sheet through a convertible notes offering. As a result, with the cash on hand today, we believe we are well-positioned to deliver, on our Vision 3x3 strategy, independent of further financing.

What makes me so optimistic for the future?

Yeah.

Throughout the rest of the year, we look forward to sharing clinical data across our pipeline, including Oh.

Third endocrinology rare disease product candidate transparency, good fourth quarter and from.

Quality programs, which have multiple important milestones this year.

For Transcon growth hormone, which is now approved in both the U S and Europe , we continue to build awareness.

Increased adoption and coverage in the U S where its market onto that Bryan made sky Tusa.

Do you believe that Sky sofa piece, a unique important treatment option for patients.

And we are determined to build it into a D D Global brand.

So optimistic for the patient.

As a reward to ship the daily treatment paradigm.

So optimistic for Ascendis is that all our five independent clinical programs are based, on the Transcom technology platform and developed using the same algorithm for product innovation.

For precision appear.

I'm pleased to share the brand penetration continues to grow with increased prescription treated patients and cohort blocks.

And we will navigate the rectatory pathway with the same experienced global Ascendis, team that brought Transcom Growth Sumo to approval in the U.S. and Europe.

As part of our commitment.

To make transparent quotable good eating.

Treatment option in the global growth hormone market, we continue to recruit patients for our global phase III Poseidon trial of transcon growth hormone in adults with Cove tunnel deficiency.

Ask me with Salt.

The ongoing role in Ukraine.

We do not expect any patients in certain eastern European countries to be path off the pulsar trial.

And we have modified.

Our recruitment efforts to focus on other countries to compensate.

Results, you know targeting completion of enrollment of the false I tried during the fourth quarter of this year.

In addition.

To support.

For label expansion for Transcon growth hormone.

We are planning a protocol submission in the second quarter to 54 turns out to April .

Turning now to Transcon PTH.

Do you believe that's the best way to treat at home and deficient.

Is to replace the missing endogenous PTH Holden.

It's a logical levels overall.

24 hours.

For this unmet need we decided transcon PTH to pickup.

The first complete PTH hormone replacement therapy.

With addressing the underlying cause of this disease.

Okay.

The positive phase III, possibly try it for themselves for the composite primary endpoint and all key secondary endpoints confirm or could you potentially.

As a reminder, the phase III results.

<unk> 36.

The data showed that 95% off.

<unk> treated patients that is.

57 out of 60 patients, but able to eliminate Eaton you convinced them to treatment with two doses of <unk> and vitamin D.

In addition for the key secondary endpoint to Sip of arc <unk>.

Of life seems to makes sure transcon PTH is treated patient reported significant.

Decrease in disease symptoms and significant improvement in the future because the function.

Our phase two Ms Christie place III twice.

First kidney code trials able to show statistic improvement in quality of life measurement and demonstrate consistent with accruals both stocks.

I believe these improvements specific the normalization of quality of life missing why after more than two years 59 out of 50.

57 out of 50 patients <unk> two five and.

All 79 patients who competed with Green Street.

Continue treatment.

Yes.

This results from all towards a promising outcome for adults suffering from chronic pain.

Who often experience mucci, auken, cobalt pizza cheese and diminished quality of life.

We are doing that work prior to this new market and treatment paradigm.

Because these patients deserve a better life.

Understand that we are working to bring transcon PTH to go to regulatory process in the U S and Europe .

Possible.

The robust data from all phase II and phase III studies will be the foundation of our planned U S and European regulatory filings.

Remain on track with our U S and D D filing planned for Q3 and in European E pardon playing for Q4.

In Japan, we recently completed enrollment in all possibly.

<unk> phase III trial.

And we plan to report topline nickel salt data later this year.

This demonstrates our Cintas global development capabilities.

If approved we believe transcon PTH <unk> has the potential to become a wall docs just into commodity rare disease Paul.

And the only PTH replacement therapy available in an estimated.

<unk> five Bcf plus market opportunities.

So let me switch now to transform CMP at computation.

Richard's time, transcon CMP to provide sustained release of that.

Effective levels of CMP, although the Kohl's.

By avoid high SKU mix with maybe the drive off coffee back stock compensation.

Thus this simple we completed enrollment in their countries all while phase two randomized double blind placebo controlled clinical trial of Transcon CMP and children.

Echo interpretation from the age of true up to 10.

We look forward to sharing the top line was solid for this phase II study during the fourth quarter of this year.

Moving to oncology and air we have unmeet needs.

Fleet remains high.

In oncology, we are applying the same high school Wiechmann, we have used in endocrinology rare diseases to bring forward product candidates that we believe will address major unmet.

We believe we have demonstrated that we have the fundamentals for creating a continuous, stream of product candidates with the potential to address major unmet medical needs with greater success than traditional drug development.

In short, we believe Ascendis has the right approach, a growing portfolio of product candidates, the right people and capabilities, and the necessary funding to deliver on our goal to create a sustainable, leading global biopharma company.

Throughout the rest of the year, we look forward to sharing clinical data from across our pipeline, including our third endocrinology rare disease product candidate, Transcom CMP, in fourth quarter, and from our oncology programs, which have multiple important milestones this year.

For Transcom Growth Sumo, which is now approved in both the U.S. and Europe, we continue to, build awareness and increase adoption and coverage in the U.S., where it's marked under the brand name Skytrofer.

Maybe you could meet.

We believe that SkyTofa is a unique, important treatment option for patients.

With highest doses compared to traditional drop the building by building on bell onto student body.

And we are determined to build it into a leading global brand.

As we work to shift the daily treatment paradigm for physician and payer, I am pleased to share, that brand penetration continues to grow with increased prescription, treated patients, and covered lives.

As part of our commitment to make transcon-glutamone the leading treatment option in the global, glutamone market, we continue to recruit patients for our Global Phase III foresight trials of transcon-glutamone in adults with glutamone deficiency.

As a result of the ongoing war in the UK, we do not expect any patient in certain Eastern, European countries to be part of the foresight trial.

And we have modified our recruitment efforts to focus on other countries to compensate.

As a result, we are now targeting completion of enrollment of the foresight trial during, the fourth quarter of this year.

Let me switch now to TRANSCOMP CMP for a contemplation. We designed TRANSCOMP CMP to provide sustained release of effective levels of CMP over the course of a week, while avoiding a high C-max, which may be the driver of cardiovascular complications.

In addition, to support further label expansion for transcon-glutamone, we are planning a, protocol submission in the second quarter to FDA for Turner Syndrome.

Please.

Moving now to transcon-PTH, we believe that the best way to treat a hormone deficiency, is to replace the missing endogenous PTH hormone at physiological levels over 24 hours.

For this unmet need, we designed transcon-PTH to become, if approved, the first complete, PTH hormone replacement therapy, which is addressing the underlying cause of this disease. The positive Phase III pathway trial results from the composite primary endpoint and all, key secondary endpoints confirm our belief in this potential. As a reminder, the Phase III results at week 26, the data show that 95% of transcon-PTH, treated patients, that is 57 out of 60 patients, were able to eliminate convincing treatment with therapeutic doses of calcium supplement and active vitamin D. In addition, for the key secondary endpoint, two separate quality of life instruments show, transcon-PTH treated patients reported significant decrease in disease symptoms and significant improvement in their physical health.

We believe the Transcon technology, China twice some of the chatter that Hasnt statements. These immunotherapies and address additional aspect of the <unk> to reduce the patients own immune.

Our Phase 2 and Phase 3 trials are the first clinical trials able to show statistic improvement, in quality of life measurement and demonstrate consistent results across both studies.

I believe these improvements, specifically the normalization of quality of life measurement, are why, after more than two years, 57 out of 59 patients in our Phase 2 trial and all 79 patients who completed the Phase 3 trial are continuing treatment in these studies. These results from our trials are a promising outcome for adults suffering from chronic SP, who often experience multi-organ comorbidities and a diminished quality of life.

We are doing the work required to build this new market and treatment paradigm, because these patients deserve a better life.

Understanding the urgent need, we are working to bring TRANSCOMPETE 8 through the regulatory process in the U.S. and Europe as quickly as possible.

The robust data sets from our Phase 2 and Phase 3 studies will be the foundation of our planned U.S. and European retrosort findings, which remain on track with a U.S. NDA filing plan for Q3 and a European MAA filing plan for Q4.

Last December, we completed enrollment in ACCOMPIS, our Phase 2 randomized double-binded placebo-controlled clinical trials of TRANSCOMP CMP, in children with ACCOMPILATION from the age of 2 up to 10.

In Japan, we recently completed enrollment in our Partway Japan Phase 3 trial, and we plan to report top-line results later this year, which demonstrates Ascenti's global development capabilities.

If approved, we believe TRANSCOMPETE 8 has the potential to become our largest endocrinology rare disease product, and the only PTE 8 replacement therapy available in an estimated more than 5 billion plus market opportunity.

We look forward to sharing the top-line results for this Phase 2 study during the fourth quarter of this year.

<unk> system to potentially be unique.

Moving to oncology, an era where unmet need remains. In Oncology, we are applying the same algorithm we have used in endocrinology rare diseases, to bring forward product candidates that we believe will address major unmet medical needs with higher success compared to traditional drug development by building on well-understood biological pathways.

To transform this treatment paradigm quality view, using transcon into tumors and sue stomach technology to an eight two in hanes anti tumor effects.

Bogs, providing sustained modulation of tumor micro environment and activating asks you to talk to you.

Transcon Telos seven need equity.

We believe that TRANSCON technology can address some of the challenges that have limited these, immunotherapies and address additional aspects of the immunity cycle to induce the patient's own immune system to potentially eliminate the tumor.

Using the transcon intra tumor technology platform and is designed to kick start the immune system inside.

Yeah.

To transform this treatment paradigm in oncology, we are using TRANSCON intratumor and systemic, technology to enhance antitumor effects by providing sustained modulation of tumor microenvironments and activating of pseudotoxins in wound cells.

Transport to Peters comment is using the transcon systemic technology platform and is designed to increase this to sustain me stimulation of the body's okay. So system.

Do you believe transcon to breach a covenant development program.

And then a.

Treatment.

So you're beginning to see promising results and we will provide additional data by the industry.

First we plan to proceed with the agencies, you're willing to do some clinical data.

TRANSCON TLR78 Agonist is using the TRANSCON intratumor technology platform and is designed, to kickstart the immune system inside the tumor.

Data from our Chiller seven eight equities program.

At the end of last year, we reported early signs of kidney because it features.

I see.

And well tolerated safety profile.

Enrollment continues in our phase one two stocking of Transcon T at all.

Peak equities mono therapy and in combination with checkpoint inhibitor in patients with advanced or metastatic solid tumors.

Later this year.

To ship, both topline monotherapy and combo therapy dose escalation data from this trial.

TRANSCON IL-2 Beta Gamma is using the TRANSCON systemic technology platform and is designed, to increase the systemic stimulation of the body's own cancer immune system.

For Transcon <unk> be Tacoma.

<unk> already moved into <unk>.

Food monotherapy cohort in all phase one two.

Believe trial.

Dosing at 80 micrograms per kilo.

With expected strong safety profile and if it just has to be decided this molecule.

We believe TRANSCON IL-2 Beta Gamma development program may yield advances over all current, treatment options.

So youre using the transcon technology to release and permanent high pool to be to comment bias IL two molecule.

We are beginning to see promising results and we will provide additional data by the, end of the year.

The results we plan to present later this year will include additional clinical data, from our TRANSCON TLR78 Agonist program. At the end of last year, we reported early signs of clinical efficacy and a well-tolerated, safety profile.

Proven transcon technology, we are flattening the PK profile and expanding that to a project we do by avoiding the high Simex I just know to drive toxicity.

Enrollment continues in our Phase I-II study of TRANSCON TLR78 Agonist monotherapy and, in combination with checkpoint inhibitor in patients with advanced or metastatic solid tumors. Later this year, we expect to share both top-line monotherapy and combo therapy dose escalation, data from this trial.

For TRANSCON IL-2 Beta Gamma, we have already moved into our third monotherapy cohort in, our Phase I-II IL-2 belief trial with dosing at 80 micrograms per kilo with the expected strong safety profile and effect just as we designed this molecule.

During this summer would you can forward to share initial data related to trying to quantify the two beta comment activation of the pixel <unk>.

We are using the TRANSCON technology to release a permanent, high-potent Beta Gamma Bios IL-2, molecule. Through the TRANSCON technology, we are flattening the PK profile and expanding the therapeutic, window by avoiding the high C-max that is known to drive cancer.

We also expect topline monotherapy data by the end of 2022.

This call quarter via targeting the first patient dose in combination to a key portion of pes want to either to pizza.

During this summer, we are looking forward to sharing initial data related to transcon, IL-2-beta-gamma activation of the vector immune cells.

I believe trial.

Transcon, either to visa card and Transcon Telos, seven eight equities X on a different path.

Assistant.

And we are developing the programs in parallel.

We believe there could be working together and so not to.

Good and you.

Boom in therapy, even move therapy.

Independent of checkpoint doses.

We also expect top-line monotherapy data by the end of 2022.

Later this quarter, we are targeting the first patient dose in a combination therapy portion, of phase 1-2 IL-2-beta, I believe, transcon IL-2-beta-gamma and transcon TLR7-8 agonist act on different parts of the immune system.

We expect <unk> to clinical trials exploring this potential <unk> to get the data this year.

Growing bill pay technology and quality.

And we are developing the programs in parallel, as we believe they could be working together, in synergy to become a new backbone in therapy, in immunotherapy, independent of checkpoint inhibitors.

We expect to initiate clinical trials exploring this potential clinical synergy together later, this year.

We are finalizing the selection of also took her together.

Going beyond endocrinology and oncology, we are finalizing the selection of our third, therapeutic area.

And I'm looking forward to sharing more information of this with you in the end of this year.

And I'm looking forward to sharing more information of this with you in the industry.

In theft issue.

Okay.

It's a busy time for us dentists, but we never forget why we're here. To make a meaningful difference in the life of patients.

Is the pace of time for Santos, but renewable forget why we here to me.

And meaningful difference in the lives of patients.

Our corporate strategy has been clearly defined in our Vision 3 by 3.

Our corporate strategy has been clearly defined and there'll be some tweaks.

And we continue to achieve consistent, impactful results as we're working across the portfolio.

And we continue to achieve constant.

<unk> with solids, SB, you've working across that portfolio.

The values that drive our organization, patient, science, and passion, combined with our strong, financial position and expanding in-house capabilities, position us to advance the rectatory, clinical, and commercial milestone that will contribute to our long-term sustainability and profitability.

The values that drive all.

Our organization.

Patient signed protection combined with our strong financial position and expanding in house capabilities position us to advance the regulatory clinical and commercial milestones that contribute to our long term stability and profitability.

I firmly believe we have the right team, culture, and capability in place to execute.

Firmly believe we have the right team culture and capabilities in place to execute.

I will now turn the call over to Scott for additional details and financial reviews before, we open for questions.

I will now turn the call over to Scott for additional details and financed.

Before we open fluctuations.

Thank you, Jens.

Yes.

As Jens eloquently laid out, 2022 is an important transition year for us dentists. We have demonstrated we have all the elements of success in place to deliver sustainable, growth, and we have a strong balance sheet to support execution of our Vision 3 by 3 strategy and long-term profitability.

As Yan eloquently laid out.

'twenty two is an important transition year for our centers.

We have demonstrated.

<unk>, we have all the elements of success in place to deliver sustainable growth and we have a strong balance sheet to support execution of our vision three by three strategy and long term profitability.

Turning now to our financial results for the quarter ended March 31, 2022, we reported a net loss of $125 5 million euro or $2. Two one euro per basic and diluted share compared to a net loss of $62 3 million euro or.

Turning now to our financial results for the quarter ended March 31, 2022, we reported, a net loss of 125.5 million euro, or 2.21 euro per basic and diluted share, compared to a net loss of 62.3 million euro, or 1.17 euro per basic and diluted share, during the first quarter of 2021, and we ended the first quarter with cash, cash equivalents, and marketable securities totaling approximately 1.1 billion euro.

One $1 seven euro per basic and diluted share during the first quarter of 2021.

And we ended the first quarter with cash cash equivalence and marketable securities totaling approximately $1 1 billion euro.

Let me now run through some key components of these results. Total revenues for the first quarter were 6.8 million Euro compared to 0.7 million Euro, during the first quarter of 2021. Revenues include U.S. Skytropha net sales as well as licensed clinical supply and services, provided to third parties, primarily these in pharmaceuticals.

Let me now run through some key components of these results.

Total revenues for the first quarter were $6 8 million euro compared to <unk> 7 million Euro during the first quarter of 2021.

Revenues include U S. <unk> net sales as well as license clinical supply and services provided to third parties, primarily being Sun pharmaceuticals.

Reported U S Sky trove of net sales for the first quarter our net.

Limited U.S. Skytropha net sales for the first quarter, which are net of provisions, to cover estimated sales deductions and product returns, were 1.9 million Euro.

Net of provisions to cover estimated sales deductions in product returns or $1 9 million world.

Now turning to operating expenses, research and development costs for the first quarter, were 83.2 million Euro compared to 88.1 million Euro during the first quarter of 2021. This reflects stabilization of our overall R&D costs due to successful progression of, early stage programs through late stage development and approval.

Now turning to operating expenses.

Research and development costs for the first quarter were $83 2 million euro compared to $88 1 million Euro during the first quarter of 2021.

This reflects stabilization of our overall R&D cost due to successful progression of early stage programs through late stage development and approval.

Selling general and administrative expenses for the first quarter were $47 4 million euro compared to $37 2 million during the first quarter of 2021.

Selling general and administrative expenses for the first quarter were 47.4 million Euro, compared to 37.2 million Euro during the first quarter of 2021.

These higher expenses primarily reflect increased costs to establish our commercial organization, in the U.S. Finance income and expenses for the first quarter included a net foreign exchange rate, gain of 11.7 million Euro compared to a net gain of 34.2 million Euro during the first quarter of 2021, primarily related to unrealized gains on translation of our U.S. dollar holdings of cash and marketable securities to Euro.

These higher expenses, primarily reflect increased costs to establish our commercial organization in the U S.

Okay.

Finance income and expenses for the first quarter included a net foreign exchange rate gain of $11 7 million euro compared to a net gain of $34 2 million Euro during the first quarter of 2021, primarily related to unrealized gains on translation of our U S. Dollar holdings of cash and marketable securities to Europe .

Finance expenses for the first quarter also included $4 2 million Euro and transaction costs related to our U S $575 million convertible senior notes financing.

Finance expenses for the first quarter also included 4.2 million Euro in transaction costs, related to our U.S. $575 million convertible senior notes financing. Going forward, we may potentially report significant volatility in the finance income and expense, line as IFRS accounting rules will require us to re-measure the conversion option embedded in the convertible notes at fair value on a quarterly basis.

Going forward, we may potentially report significant volatility in the finance income and expense line as I FRS accounting rules will require us to re measure the conversion option embedded in the convertible notes at fair value on a quarterly basis.

Finally, we ended the first quarter with cash, cash equivalents, and marketable securities, totaling approximately 1.1 billion Euro.

Finally, we ended the first quarter.

With cash cash equivalents and marketable securities totaling approximately $1 1 billion euro.

Okay.

Turning to an update on our U.S. launch of SkyTrofa for pediatric GHD, demand for SkyTrofa, continues to be strong. The total number of patients receiving prescriptions enrolled through our patient hub grew from, 369 at the end of 2021 to 978 as of March 31st. The number of healthcare practitioners prescribing SkyTrofa increased from 139 at the end of, 2021 to 349 as of March 31st. In addition, through the first quarter of 2022, 46% of these healthcare practitioners, have prescribed SkyTrofa to more than one patient, compared to 41% at the end of 2021.

Turning to an update on our U S launch of Sky tougher for pediatric ghd.

<unk> continues to be strong.

The total number of patients receiving prescriptions enrolled through our patient hub grew from 369 at the end of 2021 to 978 as of March 31.

The number of health care practitioners prescribing Skype <unk> increased from 139 at the end of 2021 to 349 as of March 31.

In addition through the first quarter of 2022, 46% of these health care practitioners have prescribed sky trials led to more than one patient <unk>.

Compared to 41% at the end of 2021.

From launch through April 29th, 1,231 Skytrofa prescriptions have been written by over 400 prescribers and submitted to our patient hub for processing. Of those prescribers, nearly 50% have prescribed Skytrofa to more than one patient.

From launch through April 29.

1231, Sky 12 up prescriptions have been written by over 400, prescribers and submitted to our patient hub for processing.

Of those prescribers nearly 50% have prescribed sky trial set to more than one patient.

From a market access perspective, 45% of US lives were covered per MMIT as of the end, of April, reflecting continued adoption of Skytrofa on formulary by healthcare plans.

From a market access perspective, 45% of U S lives were covered and then 19 as at the end of April .

Reflecting continued adoption of sky trough on formulary by health care plans.

We believe Skytrofa has unique benefits for patients and payers alike, and we will continue, to work with payers, PBMs, and GPOs to maximize coverage within our premium responsible pricing strategy.

We believe Sky Trophy has unique benefits for patients and payers alike.

And we will continue to work with payers and Pbms and G. P o's to maximize coverage within our premium responsible pricing strategy.

As a reminder, once approved for reimbursement by a payer, the patient will generally finish, their current supply of daily growth hormone or Skytrofa fast start treatment before beginning reimbursed therapy with Skytrofa.

As a reminder, once approved for reimbursement by a pair that patient will generally finish their current supply of daily growth hormone or sky trough of fast start treatment.

Before beginning reimbursed therapy with Sky 12, Phil.

Yeah.

Turning to the remainder of 2022, we expect our expenses to increase modestly as our pipeline, matures and we continue to build our commercial capabilities and organization in preparation for additional anticipated product launches, and as we advance our endocrinology rare disease pipeline, expand our activities in oncology, and continue to invest in the TransCon technology platform.

Turning to the remainder of 2022, we expect our expenses to increase modestly as our pipeline matures and we continue to build our commercial capabilities in Oregon and organization in preparation for additional anticipated product launches and as we advance our endocrinology rare disease pipeline.

Expand our activities in oncology.

And continue to invest in the Transcon technology platform.

Let me now also provide an update on select corporate milestones.

Let me now also provide an update on select corporate milestones for.

For TransCon PTH, we are on track for a planned NDA submission in Q3 2022 and a planned MAA, submission in Q4 2022.

For Transcon PTH we.

We are on track for our planned NDA submission in Q3 2022.

In a planned MAA submission in Q4 2022.

And for Pathway Japan, top-line results are expected later this year.

And for pathway, Japan topline results are expected later this year.

For TransCon CNP, top-line data from the Phase 2 Accomplished Trial are expected in Q4 2022.

For Transcon CMP topline data from the phase II accomplish trial are expected in Q4 of 2022.

Yeah.

For TransCon TLR78 Agonist, top-line monotherapy and combo therapy dose escalation data from, the Phase 1-2 Transcend IT 101 clinical trial are expected in Q3 2022.

For Transcon <unk>, seven eight agonist topline monotherapy and combo therapy dose escalation data from the phase one to transcend <unk> 101 clinical trial are expected in Q3 2022.

For TransCon IL-2 Beta Gamma, we are on track to dose the first patient in the checkpoint, combination dose escalation arm of the IL-BELIEVE clinical trial in the second quarter of 2022, and monotherapy top-line results are expected from IL-BELIEVE in Q4 this year.

For Transcon IL two beta gamma we are on track to dose the first patient in the checkpoint combination dose escalation arm of the I'll believe clinical trial in the second quarter of 2022.

And monotherapy topline results are expected from I believe in Q4 this year.

Within oncology, we expect to submit an IND or equivalent for a phase II cohort expansion in order to evaluate the combination of Transcon T. L are seven eight agonist and transcon IL two beta gamma therapy in Q4 2022.

In Oncology, we expect to submit an IND or equivalent for a Phase 2 cohort expansion, in order to evaluate the combination of TransCon TLR78 Agonist and TransCon IL-2 Beta Gamma therapy in Q4 2022.

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

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

Yeah.

As you can see, it's a busy year ahead for Ascendus, with key catalysts across the pipeline, both in endocrinology-rare disease and oncology.

As you can see it's a busy year ahead for our centers with key catalysts across the pipeline both in endocrinology rare disease and oncology.

As Yen noted, we strengthened our finances earlier this year, raising capital at favorable, terms with our convertible note financing in Q1, and now, with over 1 billion euro on our balance sheet, we have the capital to fund our growth initiatives and execute on, We very much look forward to seeing many of you face-to-face at the BFA conference in Las Vegas tomorrow.

As Yan noted, we strengthened our finances earlier this year raising capital at favorable terms with our convertible note financing in Q1 and now with over 1 billion Euro on our balance sheet, we have the capital to fund our growth initiatives and execute on our vision three by three to build a sustainable global Biopharma.

Company.

We very much look forward to seeing many of you face to face at the Bofa conference in Las Vegas Tomorrow.

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

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

Thank you.

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And in the interest of time, we kindly ask that you please limit yourself to one question and one follow-up.

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And our first question comes from Jessica Fye from J.P. Morgan.

And our first question comes from Jessica Fye from Jpmorgan. Your line is open.

Your line is open.

Hey, guys. Good afternoon. Thanks.

Thanks for taking my question.

Okay Trophy number I had a couple questions there just to kind of clarify what were seeing here.

The patients who have been prescribed <unk> Sky Trophy.

What proportion where reimbursed during the first quarter.

And in light of the lag that you mentioned between plans adopting coverage in patients starting up on reimbursed product. After they finished using their free drug and can you tell us of the patients who have been prescribed <unk>.

What proportion of those patients are on plans that now covers petrofac.

Uh huh.

Hey, guys.

Thanks Jess for the.

Two creation.

Good afternoon.

Thanks for taking my question.

Let us start with the.

The last question you have about the time. So this is actually at a time that's still.

Getting develop when you come to a more steady state situation. So if we start to discuss spend number now than you would be basically keep you a completely different number.

In light of the Skytropha number, I had a couple questions there just to kind of clarify what we're seeing here.

Tusa tweet from now in two to three months from now because its basic appalling of general principally because we have both fast start program in the <unk> program, you're coming which offer a majority of the patient comes so we basically have in position that we also have.

From the day, you said that they're stuck with east the majority of that patient is still coming from switch patients. So we still have many of them will have daily quota much supply and first of all it would take some time before that have used off the data go to multiple times before overstock Skytrooper and also the reimbursement system and that it is a wide eyes.

Delay in this number.

We will come up as we said before in a situation when we come up with our Q2 financings. We would give you an updated perspective, both on what we expect to have be or revenue basis.

The rest of the year and we will also give you more solid data why do we believe we can pull out you must more solid data because we will have all the fundamental for.

For two full quarters and when we have that we feel much more comfort for basic bean position can give you information data that can give you and way to make them realize that forecast of the sales for the first question I think Scott has some cushion.

Related to that.

Of the patients who have been prescribed Skytropha, what proportion were reimbursed during the first quarter?

And in light of the lag that you mentioned between plans adopting coverage and patients starting up on reimbursed product after they finish using their free drug, can you tell us, of the patients who have been prescribed Skytropha, what proportion of those patients are on plans that now cover Skytropha?

Just your question.

Related to how many patients are.

Reimbursed now that came on to therapy I think is the one.

I'm addressing once the patient.

And I have a follow-up.

Thanks, Jess, for the two questions.

Let us start with the last question you have about the time.

This is actually a time that's still getting developed when you come to a more steady-state situation.

<unk> their first claim reimbursed I would say we have limited information after they start being dispensed via the specialty pharmacy, However from a financial perspective as I mentioned, we take a net provision for a variety of different discounts and rebates and product returns and we've tried to be as conservative as possible and 12 as Jan mentioned.

So if we start to discuss the number now, then we will basically give you a completely different number in two to three weeks from now, in two to three months from now.

Because it's basically applying a general principle because we have the Fast Start program.

In the Fast Start program, you come in with the majority of the patient comes.

So we basically will have in position that, as we also have seen from the data that Scott released, the majority of the patient is still coming from Swiss patients.

So many of them will have daily growth hormone supply.

And first of all, it will take some time before they have used up their daily growth hormone supply before they start with Skytropha, and also the reimbursement system in that.

That is why there is a delay in this number.

Our experience around how the patient evolves over time.

We will come up, as we said before, in a situation when we come up with our Q2 finances. We will give you an updated perspective both on what we expect to be our revenue basis for the rest of the year.

So basically that's what we're doing here when we talk about net revenue your basic as some of what I call basically the worst case scenario.

And we will also give you much more solid data.

Why do we believe we can provide you much more solid data?

Because we will have all the fundamental analytics for two full quarters.

Incorporate already at that stage, if that's a product recall and other things like that because we don't want to be in a position that we suddenly.

Are in a position that we need to redo a lot of expected revenue basis on a net base because someone's incomes up into the end of the year I know, it's a pretty conservative way to do it but we believe it's a right way to do it because it gives you a great fundamentals for having what we call a real mix.

And when we have that, we feel much more in comfort for basically being in a position that can give you information, data that can give you a way to make a reliable forecasting of the sales.

Revenue basis, instead of what we call a potent net revenue basis.

Okay. Thanks, and a follow up question is just do you expect priority review in the U S for Transcon PTH.

I think Dana achieve high power Hain south into here, So I do not know what that means.

[laughter] plus I think we're going to make a strong case for it and.

I think it's always up to the agency to sort of make their ultimate decisions, but we will be talking with them about indefinitely.

Thanks.

Okay.

Thank you. Our next question comes from Josh Shanker from Evercore ISI. Your line is now open.

For the first question, I think Scott has a question related to that.

Jeff, your question related to how many patients are reimbursed now that came on to therapy I think is the one that I'm addressing.

Once the patient receives their first claim reimbursed, I would say we have limited information after they start being dispensed via the specialty pharmacy.

However, from a financial perspective, as I mentioned, we take a net provision for a variety of different discounts and rebates and product returns.

Thanks, So much for taking my question for Transcon, PTH put a lot of interest and enthusiasm for the product to have.

Therefore, our protective and potentially cardio protective properties, but do you think you'll be in a position to generate clinical data to really support that go beyond the theoretical until tomorrow.

Tangible proven advantage. Thanks.

Okay.

So.

When we look on the potential of Transcon PTH.

And we try to be as conservative as possible until, as Yen mentions, we get our experience around how the patient evolves over time.

So, basically, that's what we're doing here when we talk about net revenue.

We believe so.

We are providing <unk> to the patients, giving the right molecule in the future logical levels 24 hours a day.

It's providing S youll say.

Total Rai.

We are getting to a pace will be normalization of all.

Biochemical through cycle.

We're seeing both be amazed it including quality of life parameters wouldn't be specific go to element cardiovascular risk.

We basically, have some, what I call, basically worst case scenario.

We incorporate already at that stage if there's a product recall and other things like that because we don't want to be in a position that we suddenly are in a position that we need to redo a lot of expected revenue basis on a net base because something comes up in the end of the year.

Exiting we already have what are called surrogate markers that.

I know it's a pretty conservative way to do it, but we believe it's a right way to do it because it gives you a great fundamental for having what we call a real net revenue basis instead of what we call a percent net revenue basis.

Okay, thanks.

My best way.

Our strong scientific clinical correlation for example phosphate.

Had some phosphate complex I think is a strong scientific conviction that also are providing if you have been elevated up to a hollywood, providing what we call a cardiovascular risk.

For example to go to the kidney, which saw a huge issue for the patient group because that basic I'm positions, you're dumping all of the cuts into the quickness system and pacing power going to be.

Diamonds and one of the element we can do Josh is that when we now have patients already in treatment for 234 years. We can go back and look in <unk> for example.

Retracement nuc underway that basic outperform and sure we cannot have what we called Gulf of guiding placebo controlled because we cannot really being in a position that we can just spin to have patient going on treatment. So long time quit all keeping the assets to all medications, but what we can do.

Our belief is that there are strong.

Strong benchmark is compared to all the data that is built on the patient population.

Patients with high school territories.

That would be a strong comparison to it but I believe also in this case stays strong surrogate markers like urinary 24 hour catch them with basic on the proceeds should be really can give a strong scientific rationale why it should be.

Giving.

Constitute impact on Dana also has a few comments to it.

And the follow-up question was just, do you expect priority review in the U.S. for Transcon PTH?

I think Dana, she had her hands up in the air, so I do not know what they mean.

Josh as we've looked at the data and some of the correlation between the PTH levels that we have and the urinary calcium levels you know what.

Well, I think we're going to make a strong case for it, and I think it's always up to the agency to sort of make their ultimate decisions, but we'll be talking with them about it definitely.

Thanks.

We're seeing is that it doesn't take much PTH to restore the resort this ability in the kidney. So I don't know how long, it's going to take to see clear.

Clinical benefits or the lack of progression.

Like particularly renal complications related to the calcium but the longer.

We hope to better.

Does that or it should be or more stable these patients should be.

So that's.

That's one way that we're looking at it.

Okay are there ways to quantify the amount of calcium in the kidney like there from the heart.

The way, we actually quantifying what we call the how to look on.

What we called the short term is to look on 24 hour urinary calcium because.

Just Luke.

Yeah.

Different documentation from 58 days, a clear correlation between what we called in.

<unk>.

Impairment compared to other effect that you see with having it delivered a 24 hour urinary retention.

But as Dana said, it's really interesting from a scientific perspective, what we're seeing now because we basically can track because we have so many patient different doses at both we see different part of the path because it's a mood cheap or Pcs and we see the Tristful, which we believe is the.

Most important the staples lucky cause PTH levels.

But different organ have basic differently to respond to it.

I missed it before the kidney is actually one of the issues often to so many to normalize with the Pea takes NBC that really be an easy and low dose <unk> Islam is a constant.

The low level of the official logical level than we see the improvement.

Thank you.

Thank you.

Our next question comes from, Josh Schimmer from Evercore ISI.

Our next question comes from David Leibowitz from Citi. Your line is open.

Your line is open.

Thanks so much for taking the question.

Thank you very much for taking my question.

For Transcon PTH, I've heard a lot of interest and enthusiasm for the product to have nephro, protective and potentially cardioprotective properties.

Could you understanding that at this point in time, you're not comfortable giving us timing and certain specifics on reimbursement could you run us through the typical process.

When do you think you'll be in a position to generate clinical data to really support that and go beyond the theoretical into the more tangible proven advantage?

Thanks.

So when we look on the potential of Transcon PTH, we believe the way we are providing PTH to the patient, giving the right molecule in the physiological level 24 hours a day, is providing, as you said, total right.

We are getting to a place where we do normalization of all biochemical, physical, everything what we have measured, including quality of life parameters.

For a patient coming to a doctor to.

When we specifically go to elements like cardiovascular risk, I actually think we already have what I call surrogate markers that, in my best way, have a strong scientific clinical correlation.

For example, phosphate, calcium phosphate complex, I think there is a strong scientific connection that they also are providing.

If you have them elevated up to a higher level, they are providing what we call cardiovascular risk.

If we, for example, go to the kidney, which is a huge issue for the patient group, because the basic iron positions, you are dumping all the calcium to the kidney system, and basic are going to do no damage.

Prescribed for.

Growth hormone.

What it takes to get the prescription how the prescription gets submitted to the insurer how long can they be looking at depending on.

What's the nature of their insurer is and where their status of coverages.

Just to get us some sort of idea of what the process is facing these patients right now.

Yes. It is.

Christian with so many many many scenarios for answering the question.

First of all it's fair must dependent are you on.

Patient or you already have big step of treatment on data.

Then you just take the Big group of these two into the knee patients with basic needs to go through all the different kind of test that involves stem test actually pulse.

We have opened growth play a lot of different tests that take a period of time, we need to get a status that you have the diamond moves off growth hormone deficiency. If you take the patient that's coming from already status on data classroom. It's from that perspective is must must must easier before.

You already have been to all the different diagnosis and therefore expected. This is why could change should we see a majority of the patient coming for suites patient because but don't need to go to the entire system to be established with diagnosis of having co promote deficiency.

That was too Big Group then you go into each of the two there.

They're much depends just coming full system, where we already have market assists or knock modernization and then there is a different place to have market. This.

Is not a simple way to have Marc. This is you will have different what are called co op marketing assets I E.

Basic.

Acquire.

A lot of different elements to fulfill it and you would take different times and different.

System, you'll have dependent on the market access do you have in your insurance, but what we see of Otis groups because all the groups now.

And we get them both.

We call that already have the organization.

It keeps them from the system, where you go to me because extension. This is we need to where there is no market to state we are still getting medical acceptance because if you'll have a choice of data growth.

And you have got Hulu from an optimal treatment option.

It's actually possible to get medical exception and this is where we see them come full circle.

No I cannot answer you Christian data because this is describing about.

200 different pathway is the complexity of the U S system related to basic getting boost and aesthetics U S commercial treated patients.

Thank you for that and then one follow up here.

And one of the elements we can do, Josh, is that when we now have patients already in treatment for two, three, four years, we can go back and look and look on their, for example, the filtration, look at the way the basic are performing.

And sure, we cannot have what we call double-guided placebo control, because we cannot really be in a position that we can defend to have patients going out on treatment for a long time without giving them access to our medication.

But what we can do, which I believe is a very, very strong benchmark, is compare to all the data that is built on the patient population of patients with hyperthyroidism.

And I think there will be a strong comparison to it.

Dana also have a few comments to add in.

Could you, possibly outline for us what the revenues might have been before provisions.

But I believe also in this case, there are strong surrogate markers, like urinary 24-hour calcium, with basic iron in a position that we really can give a strong scientific rationale why it should be given, positive impact on that.

Well, yeah, Josh, as we've looked at the data, and some of the correlation between the PTH levels that we have and the urinary calcium levels, you know, what we're seeing is that it doesn't take much PTH to restore the resorptive ability in the kidney.

So I don't know how long it's gonna take, to see, you know, clinical benefits or the lack of progression of like particularly renal, you know, complications related to the calcium.

But the longer that we look, the better, you know, the better it should be or more stable these patients should be.

So, you know, that's one way that we're looking at it.

Are there ways to quantify the amount of calcium, in the kidney like there are for the heart?

Give us just perspective on the level of impact at this point.

The way we actually are qualifying what we call the, how to look on what we call the short-term weight is to look on 24-hour urinary calcium.

Because just look on different documentation from FDA, there is a clear correlation between what we call renal impact impairment compared to other effect that you see with having an elevated 24-hour urinary calcium.

But as Dana said, it's really interesting, from a scientific perspective what we're seeing now because we basically can track because we have so many patients on different doses and what we see different part of the body because it's a multi-organ disease.

And we see the threshold, which we believe is the most important, the stable physiological PGH level.

But different organs have basic different way to respond to it.

And as Dana said before, the kidney is actually one of the easiest organ to some way to normalize with the PGH.

I think this is something to be to become near what's disclosed in our numbers because as I said, what Scott said.

And we see that really, really easy in low-dose PGH.

As long as it's a constant in the low level, of the physiological level, then we see the improvement.

We have a conservative manner, where the book's subtracting.

Elements like.

Rebate, but you also.

They seek.

Taking away if there is any.

Any kind of material, but not getting sold and other things like that so I think we have four or five ways, whether it'd be subtracting four blocks the cold, but gross margin and then you'll have growth mark in one year and close to your gross margin three of those Martin for before we go back to the final won't be called net net revenue and that is.

We give to you.

And that is not realized revenue.

Revenue. This is where you could leave that in the future if there's any kind of discounting coming.

We will take it away so it's not what we call <unk>.

This is where we'll be in a position where do you expect.

For future with WP any kind of elements that we need to discount it is already being taken into consideration.

Yeah.

Thank you.

Thank you.

Our next question comes from Vikram <unk> from Morgan Stanley . Your line is open.

Our next question comes from David Leibowitz from Citi.

Great. Thanks for taking my question.

So first could you just give us an update on where transcon hgh.

Stand in Europe and what.

What are the next steps there for securing reimbursement across some of the key geographies that you would need to start commercializing it to really start.

Initially ramping that launch.

Your line is open.

Yes.

Christian and what we were really waiting for.

<unk> basic transcon PTH toolkit.

The path to two phase III data that can be achieved and you can see why.

Because the complexity of Europe is that it's not a single market.

<unk>.

Different safest market.

And one of the element we are focused on is to be profitable.

Having.

P&L played and this is why.

To have the optimal way to penetrate the different European market, we will be in a position that we could build on the synergy the economy of scale of lungs, two extremely important product just after each one of them.

Thank you very much for taking my question.

Now we have the phase III data.

Could you, understanding that at this point in time, you're not comfortable giving us the timing and certain specifics on reimbursement, could you run us through the typical process for a patient coming to a doctor to get prescribed for a growth hormone, what it takes to get the prescription, how the prescription gets submitted to the insurer, how long, you know, can they be looking at, depending on what the nature of their insurer is and where their status of coverage is, just to get us some sort of idea of what the process is facing these patients right now?

We have the approval in Europe , we basically executing on our European strategy and this is a strategy that is built on not spending 120 <unk>.

And generate $5 million.

Revenue is building and piano play because.

<unk> company.

Yeah, this is a question where there is so many, many, many scenarios for answering.

First of all, it's very much dependent, are you a new patient or you already have been, established a treatment on daily growth hormone.

Lastly enough know what to do because.

Then you just take the big group of these two into the new patient, you basically need, to go through all the different kind of tests that involve stem test, x-ray, you still have open growth plate, a lot of different tests that take a period of time really to get established that you have the diagnosis of growth hormone deficiency.

If you take the patient that's coming from already established on daily growth hormone, from that perspective it's much, much, much easier because you already have been through all the different diagnoses and therefore have established.

This is why potentially we see a majority of the patients coming from switch patients, because they don't need to go through the entire system to be established the diagnosis of having growth hormone deficiency.

Because it seems certainly enough a lot of color.

That was two big, big groups.

Company coming into Europe , and belief that is a place where you basically could execute and make a highly profitable business.

And what are called rapid global expansion you don't do that you go country by country build it up and take high volume high marks in country. That's the first state and then you've got the expansion from there.

Okay.

Got it thank you and.

A follow up on a separate topic so for the pillar seven eight and IL two readouts that we're looking forward to in <unk> and <unk>, what could we expect to learn in terms of number of patients the amount of follow up.

And what do you hope to see from each of these readouts to feel like each program has.

A viable path forward.

Then you go into each of the two big groups.

You know other stocks with a few remarks, and then Steve will take over.

Very much depends, are you coming from a system where we already have market assessed or not, market assessed.

Would be moved into oncology icon ask what type of time why do you do that again.

And then there is different places to have market assessed.

This is not a simple way to have market assessed.

You will have different what I call power of market assessed.

And each of them will basically require a lot of different elements to fulfill it.

And it will take different times in different system you have dependent on the market assessed, you have in your insurance.

But what we see of all these groups, we get all the groups now.

Q have rare disease and new content, you can tell me Nate.

And we get them both on what we call that already have the pre-autization.

We also get them from the system where you go to medical exemption.

This is meaning typically where there is no market assessed, they are still getting medical, exemption.

Because if you have a child on daily growth that's not grown and you have some optimal, treatment option, then it's actually possible to get medical exemption.

Perhaps it's easier to dominate rare disease, endocrinology and going into oncology, but why.

Actual <unk> in the same way because we have the transcon technology and then we have all as cooley's muscle in which where we can really make highly differentiated product opportunities that no. One does it will have to meet.

And when I think the sooner TV building up you know Python approached the kickstart the Kickstarter in solid tumor there'll be placed inside the tumor inside the tumor.

Crop that get sustained released over weeks one single injection and then you activate the immune system in fact, the tumor and then be calling out and saying you have today is that with checkpoint inhibitor. What you also see the limitation and we are not here to develop something and submit to you that the checkpoint inhibitors.

We are here to develop something that is improvement next generation compared to checkpoint inhibitors and this is our vision and that is what we are building up with clinical data.

And this is where we see them come from.

Sadly enough, I cannot answer your question better because this is describing about 200, different pathways in the complexity of the U.S. system related to basic getting reimbursed and establish you as a commercial treated patient.

Data that really can support debt issue so.

Thank you for that.

Steven can give little bit more perspective, what we have seen no initial readouts, we have seen with all the data.

And one follow-up here.

Could you possibly outline for us what the revenues might have been before provisions, to give us a perspective on the level of impact at this point?

I think this is something we typically never disclose in our numbers.

Thank you Yang forget Chiao are seven eight program, we expect to have about 18 patients at a time that we disclose to allocate it ended the year.

Because as I said and what Scott said, we do it in a very, very conservative manner, where we both subtracting element like rebate, but we also basic taking away if there is any kind of material that's not getting sold and other things like that.

So I think we have four or five ways where we're subtracting for what we call the gross, market.

And then you have gross market one, you have gross market two, you have gross market three, you have gross market four.

Before we go back to the final one, we call net net revenue.

And that is what we get.

And depending on how many patients make it to the first tumor assessment at week nine we do expect to have approximately 10 patients with efficacy evaluable data.

And for the Iot Beta Gamma program.

Our actively in dose escalation. So it really depends on when we may or may not hit a maximum tolerated dose.

We'll have more patient, but as Ian has mentioned before we are already are dose escalating in dose level, three which is a microgram per kilogram.

And we're doing it with the standard three plus three dose escalation can you just take the patients so called quake in monotherapy and in combination with <unk>.

So we're not sitting above the two rates that's about 20 companies.

Two rigs when I see how fast the appropriate and why of the progressing so far.

Because we just signed it in an optimal way to see the rise of secrecy without.

Safety concern and what we see today is really everything I said around how we designed it.

So.

Really really looking forward to cheer this data with you later this year.

Okay.

And that is not realized net net revenue.

Thank you.

This is where we believe that in the future, if there's any kind of discounting coming, then we will take it away.

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

So it's not what we call net net revenue of today.

This is where we will be in a position where we expect for future, which there will be any kind of element that we need to discounting is already being taken into consideration.

Hi, good afternoon, thanks for taking my questions.

Just one or two for me first maybe for Scott just looking at the Opex. So SG&A was maybe a little bit down this quarter versus four two clearly you're in a launch and you guided to a modest increase the rest of this year just wondering.

What was behind.

Perhaps not spending as much this past quarter, given the spectrum for lunch.

Thank you.

Thanks for your question Leland I think that as we alluded to with regard to R&D to some extent in SG&A. There have been one time cost to build the infrastructure. So I think a combination of some costs rolling off.

Our next question comes from Vikram Purohit from Morgan Stanley.

Set by increased personnel basically flattish.

Flattish expenses.

Okay, and then also wanted to ask in terms of.

The China trial, given all the Covid impact in that geography wanted to ask if there's any particular impact too.

Your line is, open.

To accomplish with respect to COVID-19 things.

Great.

Yes, and just a quick follow up on I should have added that we also are basically in steady state with the SG&A infrastructure.

Thanks for taking my question.

So first, could you just give us an update on where, Transcon HGH stands in Europe and what what are the next steps there for securing reimbursement across some of the key geographies that you need to start commercializing in to really start initially ramping that launch?

As well as the R&D infrastructure.

And then your question about the status.

The status of accomplish in China.

No.

East European part of.

That's how I understood your question.

It sounds like Youre addressing what used to appear.

Elements.

Shanghai and so forth just wondering if there's been any impact on the accomplish China trials.

We've been conducting with.

Hmm.

Yeah, it's a question and what we were really waiting for was basic Transcon PTAs to get, the positive phase three data that we achieved.

Thanks.

Yes, the accomplish the child trial is actually pretty interesting because we managed to get a lot of enrolment done. So we actually got the Coty as we wanted to do we Axel.

And you can say why.

Because the complexity of Europe is that it's not a single market. It's a multiple, multiple differentiated market.

And one of the elements we are focused on is to be profitable and having a PML play.

Following up a lot of debt, but we also realize that China is such a big country that basic data element I just as they have affected on the Cobra deterioration and those are the comps thats not effective with it so from that perspective, we feel that we are doing that but as we said before we also claiming to basically do the same.

<unk> in the European and the U S. Because we feel that and we are getting so much response from the patient groups that really won't like to see the same core the expansion. So we will do the same thing in what we call in U S and EU focused trial, where we do expect that the same thing what we teach and.

China to have adopted and it's mainly being driven out from their perspective is that we.

We have so many children in our sheet trials. This is our nascent phase two trial and the basic asking us why can be not coming to a treatment and we don't patient for which we will do what we can do for legislation and this is why we explained the SS two basic having transcon CMP.

And this is why to have the optimal way to penetrate the different European markets, we will be in a position that we can build on the synergy, the economy of scale of launching two extremely important products just after Israel.

This patient group too.

One thing just to add to it.

Scott comes about that soon.

<unk> pharma is now mature.

Now we have the phase three data.

We have the approval in Europe.

<unk> mature to a states when we take new product <unk>.

We basically are executing, on our European strategy.

<unk>, when we see new product coming to them quantity basic nearly with the same speed are taking out.

The opposite.

Like Scott children.

Finalized our <unk>.

Commercial manufacturing now out of with some development. We do the same thing now with P takes.

Finalizing the validation fashion all the P. P. Q activities next year, we move them out to commercial manufacturing.

We do that in nearly the same speed as we exit generated the pipeline. So this is why we coming to a steady state and messages from feeling on wheat and machine developed to develop drugs such as food and.

And this is a strategy that is built on not spending 120 million and generate 5 million in revenue.

It's building and PML play because we are a European company.

We sadly enough know what to do because I've seen sadly enough a lot of company coming, into Europe and believe that is a place where you basically can execute and make a highly profitable business on what I call rapid global expansion.

You don't do that.

You go country by country, build it up and take high volume, high marketing country as the first date.

And then you build the expansion from there.

Got it.

As we continue to do with the speed and dedication we have so our or plant is a new product be approved every year Bill. It was taken here and we've looked at it we really can fulfill that ambition.

Thank you.

And a follow up on a separate topic.

Thank you. Our next question comes from Joseph Schwartz from SBB Securities. Your line is open.

So for the TLR78 and IL2 readouts that, we're looking forward to in 3Q and 4Q, what could we expect to learn in terms of number of patients and on a follow up?

Thank you.

Just a question on Sky trough and then one on th.

And what do you hope to see from each of these readouts to feel like each program has a viable path forward?

Thanks.

First I was wondering if you could describe for US your free drug policy in terms of the duration of therapy that patients are entitled to receive.

You know, I will start with a few remarks and then Stine will take over.

When we moved into oncology, I got asked multiple times, why do you do that?

You have rare disease endocrinology.

They need their insurance to cover the Bill and do you have any data at all that you can share with us that illustrates the success rate for patients being able to receive insurance coverage once theyre free drug supply runs out.

You can dominate that.

Perhaps it's easier to dominate, rare disease endocrinology in going into oncology.

But why, actually, are Buddhists in the same way?

Because we have the transform technology and the way we have our algorithm for innovation, where we can really make highly differentiated product opportunities that no one else ever, ever has made.

And when I think the synergy we're building up in our pipeline approach, the kickstarter, the kickstarter in solid tumors, where we place inside a tumor, inside a tumor, a drug that gets sustained release over weeks, one single injection.

And then you activate the immune system inside the tumor.

Good question from the perspective is that just something be analyzing looking on the data a lot 18 months and we see the expected development, we see but.

Development is that when we start a patient to have the opportunity to come into our program, but it's not all of them done.

And we accuracy to path to suit the risks go directly into so to suit ops into this opportunity to code early efforts to date and what we know are following this as were really really love to see more and more mobile more data because you have different patient groups.

One week now you patient, one which switch station, but what is really dependent it's also how we pulled off the market.

Of course.

Normal market size and how we get market assist is also changed to a ratio when they're moving so.

So what we're seeing is not a steady state.

But what we expect we expect that the majority of patients that Destocking is cross dock program basically.

As commercial patients.

But what we do not know is the effect of the timing and how long time. It takes we have some time, but it's not meaningful for us to give you a every time, because there's extra changing amongst timeline getting faster and faster.

And then we're going out and saying, you have today established checkpoint inhibitors, but we also see the limitation.

Okay. Thank you and then on PTH to what extent do patients feel better when they are on transcon PTH therapy, I'm asking because it seems like many of the day to day symptoms you'd capture in a clinical trial or cognitive.

And we are not here to develop something in synergy with checkpoint inhibitors.

We are here to develop something that is improvement for the next generation compared to checkpoint inhibitors.

And this is our vision.

And that is what we're building up with clinical data that really, can support that vision.

But there seems to be a bigger impact on physical function, England cognitive and your data. So I'm wondering why that is and what it might mean in the real world.

So Stephen can give a little bit more perspective, what we have seen and our initial readout we have seen with all the data.

Thanks, Jan. For the TLR78 program, we expect to have about 18 patients dosed by the time, that we disclose our data end of the year.

And depending on how many patients make it to the first tumor assessment at week nine, we do expect to have approximately 10 patients with efficacy-evaluable data.

For the IL-2 Beta Gamma program, we are actively in dose escalation.

Yeah, It's a good question Dana become with Christian.

Christian about it but what we did is basic in phase two.

So it really depends on when we may or may not hit a maximum tolerated dose, we will have more patients.

<unk> deep into phase III.

Good.

Because in phase two basic have the entire I do not know how many years different sub domains. We analyzed it will strengthen costco or something like that and we saw improvement in all of them after Dana and she can explain it is that.

She had intense discussion with regulatory agents and what they believe will stay most important one and what that did leave its potential is the ones that are like for us to move forward with the <unk>.

Liquid this opt in rates mainly in.

Looking in a strong.

Discussion with 50, which one vessel.

For these patient groups, but then you can explain some of the discussion as you know from.

But as Jan has mentioned before, we are already dose escalating in dose level three, which is a microgram per kilogram.

And we're doing it with the standard three plus three dose escalation, three to six patients per dose level cohort in monotherapy and in combination with pembrolizumab.

So when I think about the IL-2 race, that's about 20 companies in the IL-2 race.

Prior sort of.

Releases that we've had.

With the phase two we looked at.

Sort of are you know the asset 36 scale, we saw normalization essentially across all of the domains again, it's not a disease specific and then we were continuing to develop our <unk>, which is a specific.

Yeah.

Sort of instrument now.

Still used both of them in the phase III right and what the FDA asked us to do for phase III, what to focus on while we felt weird.

Some of the most important domains, okay, and I think that you know in particular.

They are particularly interested in.

Symptoms right.

And then the functioning right. So we did sort of focus on those particular areas.

We did.

Disclosed back in March we were highly statistically significant firm for pretty much every single one so.

And then even if we drill down into some of the smaller ones that we still saw very sort of favorable results for patients.

But but you know the FDA asked us to focus on the things that they felt were probably the most important.

I think another way to look at it this <unk>.

<unk> patient retention.

Because of exiting patient retention is the short term benefit you get on treatment.

Don't stay in the clinical trial open label extension, because you believe long term complication.

Ah get installed we do it because you feel.

That you see the immediately bring to people.

When, I see how fast we are progressing, and why are we progressing so fast?

We do not see we still have 57 out of $59.

Because we designed it in an optimal manner to see the right efficacy without any safety concern.

And what we see today is really everything has allowed out how we designed it.

So I'm really, really looking forward to share this data with you later this year.

Thank you.

Our next question comes from Leland Gershel from Oppenheimer.

Your line is open.

After more than two and half year in the olden days, we saw all the patients from all phase III is now onto treatment.

Hi, Justin.

Thanks for taking my questions.

Just one or two for me.

First, maybe for Scott, just looking at the op-ex, your FPNA was maybe a little bit down this quarter versus 4Q earlier in a launch and you guided to a modest increase.

The rest of us here are just wondering what was behind perhaps not spending as much this past quarter given the spectroflux?

Thanks for your question Leland.

I think that as we alluded to with regard to R&D, to some, extent in SG&A there have been one-time costs to build the infrastructure.

So I think a combination of some costs rolling off, you know, offset by increased personnel basically led to flat-ish expenses.

I think this is the best.

Okay.

And then also want to ask in terms of the China trial, given all the COVID impact in that geography, wanted to ask if there's any particular impact to accomplish with respect to COVID-19.

Wait for me to Michelle she.

Thanks.

Yeah.

And just a quick follow-up on, you know, I should have added that, you know, we also are basically in steady state with the SG&A, infrastructure as well as the R&D infrastructure.

Sure we can quantify it in all the different things.

And then your question about the status, it was the status of accomplish in China, was it?

No, the East European part of, as I understood your question, it's not like you're addressing the East European elements.

You know, Shanghai and so forth.

Just wondering if there's been any impact on the accomplished, China trial that you've been conducting with, you know, in that region.

Keep in our key so you can do eliminate fixed to patients.

Thanks.

Yeah.

The accomplished trial is actually pretty interesting because we managed to get a lot of, enrollment done. So we actually got the cohort in as we wanted to do.

But what, we did basic in phase 2 and what we did in phase 3 is a little bit different.

We actually are following up a lot of that, but we also realized that China is such a big country that basically there is element that is very, very affected on the COVID situation and there is other part that's not affected with it.

Because in phase 2, we basically have the entire, I do not know how many different subdomains we analyzed. It was 20 plus or something like that.

Patient retention for me is the key element because this is a white patients take the Cherokee why is the key.

So from that perspective, we feel that we are doing that.

And we saw basic improvement in all of them.

But as we said before, we also planning to basically do the same parallel in the European and the U.S. set, because we feel that and we're getting so much response from the patient groups that they really would like to see the same cohort expansion.

After Dana, and she can explain it, is that she had an intense discussion with the rectatory agents and what their belief was the most important one and what their belief potential is the one they would like for us to move forward with.

So we will do the same thing in what we call an U.S. and EU focused trial, where we do exactly the same thing what we did in China to have it double.

We actually selected this subdomain mainly in.., working in a strong discussion with FDA which one they saw was most important for this patient group.

And it's mainly been driven out from the perspective is that we have so many children in our chief trial.

But Dana, you can explain some of the discussion.

This is our national history trial.

As you know from, you know, prior sort of releases that we've had with the Phase 2, we looked at, you know, sort of our, you know, the SF-36 scale.

And the basic are asking us why can we not come into a treatment.

And we saw normalization essentially across all the domains.

And with our patient focus, we will do what we can do for the patient.

Again, it's not disease-specific.

And this is why we expand the access to basic having transcon CMP in this patient group too.

And then we're continuing to develop our HPES, which is disease-specific, you know, sort of instrument.

One thing just to add in with Scott's comments about it.

Now, we still use both of them in the Phase 3, right?

EBITDA with a daily injection.

Ascentis Pharma is not now matured.

And what the FDA asked us to do for Phase 3 was to focus on what we felt were some of the most important domains, okay?

We are mature to a stage when we take new product up, as we will do in our third, therapeutic area, when we see new product coming to oncology.

And I think that, you know, in particular, you know, they are, you know, particularly interested in the symptoms, right?

We basically nearly with the same speed are taking out in the opposite end, like Skytropha finalized out in commercial manufacturing.

Okay.

Adherence sweetman about 98% to 19, 9% debt.

Out of research and development.

And then the functioning, right?

We do the same thing now with PJ, finalizing the validation batch and all the PPQ activities.

So we did, you know, sort of focus on those particular areas.

Next year, we move them out to commercial manufacturing.

And as we, you know, disclosed back in March, you know, we were highly statistically significant for pretty much every single one.

You don't stay in a clinical trial or an open-label extension because you believe long-term complications mainly are getting solved. You do it because you feel normal again, that you see the immediate benefit of the drug.

We do that in nearly the same speed as we actually generate the pipeline.

So, you know, and then, you know, even if we drilled down into some of the smaller ones, we still, you know, saw very, you know, sort of favorable results for the patients.

When I see we still have 57 out of 59 after more than two and a half years in an open-label extension.

That do it because look at the short term.

So this is why we're coming to a steady state in Ascendis Pharma.

But, you know, the FDA asked us to focus on the things that they felt were probably the most important.

We saw all the patients from our Phase 3 is now under treatment.

Being Lingon, we are a machine developed to develop drugs successfully.

I think another way to look at it, Joe, is look about patient retention. Because I actually think patient retention is the short-term benefit you get on treatment.

And that is we will continue, to do with the speed and dedication we have.

So our overall plan is that new product be approved every year or every second year. And it looks like we really can fulfill that ambition.

They're feeding north Medicaid.

Thank you.

I think this is the best way for me to measure.

Our next question comes from Joseph Schwartz from SVB Securities.

Sure, we can quantify it in all the different things we did in our key secondary element in our Phase 2.

This is one of the best Michelin for me.

Your line is open.

But patient retention for me is the key element because this is why patients take the therapy, why they keep going every day with a daily injection with an adherence frequency of about 98 to 99. They do it because they get the short-term relief, they are feeling normal again.

Thank you.

This is one of the best measurements for me.

Just a question on Skytropa, and then one on PTH.

Okay.

First, I was wondering if you could describe for us your free drug policy in terms of the duration of therapy that patients are entitled to receive before they need their insurance to cover the bill.

And do you have any data at all that you can share with us that illustrates the success rate for patients being able to receive insurance coverage once their free drug supply runs out?

Good question.

Thank you.

Thank you.

From the perspective is that it's something we're analyzing a lot, looking on the data a lot every month.

This concludes today's conference call.

And we see the expected development.

This concludes today's conference call. Thank you for your participation and you may now disconnect everyone have a wonderful day.

We see the expected development is that when we start a patient, they have the opportunity to come into our start program.

But it's not actually all of them that are doing that.

Thank you for your participation.

And we actually see there's perhaps two-thirds that do it.

And the rest go directly into it.

You may now disconnect.

So two-thirds opt in for this opportunity to get early, access to that.

Everyone, have a wonderful day.

And what we now are following, and this is where I really, really love to see more, more, more, more, more data.

Because it has different patient groups, one with naive patients, one with switch patients.

But what is really dependent is also how we build up the market access.

[music].

Because you have more and more market access and how we get market access, it also changes the ratio when they're moving over.

So what we're seeing is not a steady state.

But what we expect, we expect that the majority of patients that are starting on this fast start program basically will end up as commercial patients. But what we do not know is exactly the timing and how long time it takes.

We have some average time, but it's not meaningful for us to give you average time because it's actually changing once by month, getting faster and faster.

Okay.

Thank you.

And then on PTH, to what extent do patients feel better when they're on transcon PTH therapy?

I'm asking because it seems like many of the day-to-day symptoms you'd capture in a clinical trial are cognitive.

But there seems to be a bigger impact on physical functioning than cognitive in your data.

So, I'm wondering why that is and what it might mean in the real world.

Yeah, it's a good question and Dana will come with a further question about it.