Ascendis Pharma A/S (ASND) Q4 2020 Earnings Call Transcript

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Ascendis Pharma A/S (ASND 0.35%)
Q4 2020 Earnings Call
Mar 10, 2021, 4:30 p.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Good morning, ladies and gentlemen, and welcome to the Q4 2020 Ascendis Pharma Earnings Conference Call. [Operator Instructions].

I would now like to turn the conference over to your host, Mr. Scott Smith, Senior Vice President and Chief Financial Officer of Ascendis Pharma. Please go ahead, sir.

Scott T. Smith -- Senior Vice President and Chief Financial Officer

Thank you, operator. Thank you everyone for joining our full year 2020 financial results conference call today.

I'm Scott Smith, Chief Financial Officer of Ascendis. Joining me on today's call are Jan Mikkelsen, President and Chief Executive Officer; Dr. Mark Bach, Head of Clinical Development and Medical Affairs for Endocrinology Rare Diseases; Jesper Hoiland, Global Chief Commercial Officer; Dr. Dana Pizzuti, Head of Development Operations; and Dr. Juha Punnonen, Head of Oncology.

Before we begin, I would like to remind you that this conference call will contain forward-looking statements that are intended to be covered under the Safe Harbor provided by the Private Securities Litigation Reform Act. Examples of such statements may include, but are not limited to, our progress on our pipeline candidates and our expectations with respect to their continued progress, statements regarding our strategic plans, our goals regarding our clinical pipeline, statements regarding the market potential of our pipeline candidates and statements regarding our regulatory filings.

These statements are based on information that is available to us today. Actual results or events could differ materially from those in the forward-looking statements and we may not achieve our goals to carry out our plans or intentions or meet the expectations or projections disclosed in our forward-looking statements. And you should not place undue reliance on these statements. Our forward-looking statements do not reflect the potential impact of any licensing agreements, acquisitions, mergers, dispositions, joint ventures or investments that we may enter into or terminate. We assume no obligation to update these statements as circumstances change, except as required by law.

For additional information concerning the factors that could cause actual results to differ materially, please see the Forward-Looking Statement section in today's press release and the Risk Factors section of our prospective supplement filed on July 9, 2020 and our Annual Report on Form 20-F being filed today.

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

On today's call, we will discuss our full year 2020 financial results and provide a business update. Following some prepared remarks, we will then open up the call to questions.

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

Jan Moller Mikkelsen -- President and Chief Executive Officer

Thanks, Scott. And good afternoon, everyone. For Ascendis, 2020 was a year to remember. We succeeded as a team and were able to meet and, in some cases, exceeded all our corporate goals in 2020. I'm proud to be able to say that the Ascendis team was adaptive, creative and focused on achieving the goals we outlined at the beginning of last year to bring our TransCon product candidates to patients as fast as possible.

For 2021, we are well positioned to continue to execute and achieve the milestones we have laid out across all of our five independent product candidates. Going back, the importance of the science, one of Ascendis core values is really at the center of what we do 365 days a year. Our understanding of the biology and the science it drives our top development process. I see it again and again. If we stick to the science, understand and respect the biology, we will be successful.

With our algorithm of product development focused on the patient and the unmet medical need, combined with the TransCon technology, we have a powerful platform that has allowed Ascendis to create not just one potential blockbuster product candidate, but a portfolio of five potential blockbuster candidates in two therapeutic areas with more to come.

Beginning with TransCon growth hormone, throughout the development, we have kept the patient needs in mind. From the beginning, we were committed to build on the last 30 years of knowledge with daily growth hormone and other long-acting growth hormone programs. We designed our TransCon growth hormone to have a similar tissue distribution pattern with receptor activation and exposure as seen for daily growth hormone once somatropin is released from the TransCon growth hormone program.

For more than 30 years, multiple companies have tried to develop a long-acting growth hormone program using several different technologies providing comparable safety, efficacy, tolerability, immunogenicity, mode of action as daily growth hormone. In spite of all this effort, to-date all patients are still being treated with daily growth hormone in the US, Europe and Japan. I am excited to be close to all potential regulatory approval of TransCon growth hormone in the US and Europe.

Last June, we submitted our PLA for TransCon growth hormone for the treatment of pediatric growth hormone deficiency and we have a PDUFA date of June 25, 2021. Later in September last year, we submitted our M&A in Europe and we expect potential approval in the fourth quarter this year. Since our regulatory submission, I can see the payoff from our design of TransCon growth hormone and the extensive preclinical and clinical programs in our interaction with FDA and EMEA.

We believe our data clearly demonstrate once-weekly TransCon growth hormone has comparable mode of action and distribution in key growth hormone responsive tissues such as brain, bone, muscle, liver and fat tissue as the growth hormone administrate for daily growth hormone and adults with growth hormone. And our discussion with FDA and EMEA give me comfort that we have developed an convincing body of non-clinic and clinical data to support our belief.

In December last year, we had a positive mid-cycle meeting with FDA where they indicated the agency has no plans for an advisory committee. We continue to have a constructive dialogue and have begun labeling discussions with the FDA. And we're looking forward to a potential regulatory approval next quarter.

In Europe, our M&A submission for TransCon growth hormone last September follow the agreement with Petco to our proposed pediatric investigation plan or called PIP covering the non-clinical and clinical development of TransCon growth hormone in children down to age of six months. To our knowledge, no overgrowth hormone or growth hormone analogs has an approved PIP. Our expectation for a potential approval of the M&A in the fourth quarter of this year is unchanged. But our innovation did not stop the design of our drug substance.

As part of our effort to address the unmet medical need, we have also developed an auto-injector for the administration of TransCon growth hormone, providing room temperature stability and a small injection volume via a 31G needle. We introduced the TransCon growth hormone alpha injector into the Phase 3 enliGHten trial where it's currently being successfully use by over 160 subjects in the US with accumulated use of more than 225 devices. We expect the TransCon growth hormone auto-injector will be available to patients at the same time as the potential commercial launch.

Going forward, we are developing an integrated connected health program that links the TransCon growth hormone auto-injector with an app and provides information for the patients and caregivers related to adherence and doses. The pediatric growth hormone market is an established market in the US and Europe with severally daily growth hormone products. But we also know that drugs don't work in patients who don't take them.

Even modest lack of adherence leads to suboptimal outcomes and potentially to drop out of therapy. In fact, we see that almost all pediatric patients in the US stop therapy after three to four years of treatment. We have submitted for publication a manuscript based on claims data demonstrating that the problems of adherence and lack of treatment are potentially much worse than reported in published literature.

I often get asked if we think we can expand the current market with TransCon growth hormone. These new data describing the lack of adherence and lack of treatment tell me that there is a potential big opportunity to improve patient care by improved adherence, persistence and penetration, which will lead to better outcome for patients and better outcome for the society.

So far, I've talked about US and Europe, but we're not stopping there. Ascendis is a global company with a global thinking addressing unmet needs for a worldwide population. In Japan, we filed a clinical trial notification last year to initiate the Phase 3 riGHt Trial for pediatric growth hormone deficiency. In China, in 2018, we formed VISEN Pharmaceuticals with an investor group to develop TransCon endocrinology rare disease product in greater China. VISEN continues to execute on its Phase 3 clinical trial of TransCon growth hormone in children with growth hormone deficiency and will initiate clinical development for TransCon PTH and TransCon CNP soon.

Moving to label expansion. We have the global Phase 3 foresiGHt Trial under way for adult growth hormone deficiency. The primary objective of the foresiGHt Trial from a regulatory perspective is to demonstrate efficacy compared to placebo. However, the most important comparison is to daily growth hormone, which is included as a third arm in the foresiGHt Trial. We have a plan to randomize 240 subjects one to one to one.

I'm often asked, why is adult growth hormone deficiency so important? What do you get out of the foresiGHt Trial? Growth hormone deficiency is not just about height. In children, height emerged as a primary regulatory endpoint. Since adults are not growing in height, the primary regulatory endpoint is to measure the metabolic consequence of growth hormone deficiency to measure change in truncal fat. Only if a once-weekly growth hormone therapy is equivalent or better to daily growth hormone in both for pediatric and adult growth hormone deficient population, then it will provide all the endocrine benefits of daily growth hormone.

We believe from our Phase 3 pediatric programs that TransCon growth hormone can provide all this endocrine benefits, combined with our success in adult growth hormone deficiency Phase 3 trial. We believe we will continue to differentiate from all once-weekly growth hormone product candidates. We expect to complete enrollment of the foresiGHt Trial by late 2021 or early 2022.

Moving to TransCon PTH. I never seen a product like this before, a product that not only can address short-term symptoms of a disease by restoring biochemical control and the quality of life for patients, but also potential candidates for the long-term complication of the disease as well. Hypoparathyroidism, HP, is a condition with effect more than 200,000 patients just in the US, Europe and Japan. Similar to growth hormone deficiency, where the pipeline is absent [Phonetic] or insufficient amount of the respective hormone, in this case for HP PTH.

In chronic post-surgical HP in around 75% of all cases, the parathyroid glands, the organ that produce PTH have been damaged or destroyed and the body cannot be stimulated to produce sufficient amount of PTH. Therefore, the only way PTH can be restored to normal physiological level is by PTH hormone replacement.

TransCon PTH is designed to replace the hormone at physiological levels and restore the patient to normal health. When we speak to patient suffering from HP, we hear over and over again about how poor the quality of life is, how they had to stop going to work, all worried about calcium crashes and making it to an emergency room. These are the short-term symptoms, driven by lack of serum calcium control and physiological PTH levels. In addition to the short-term effect, HP patients have multiple long-term complication as insufficient kidney function, cardiovascular risk and abnormal turnover.

As TransCon PTH is designed to restore PTH to physiological levels 24 hours a day, we will expect to normalize serum calcium to improve short-term symptoms. We also expect to normalize kidney function and normalize bone health to reduce long-term complications. So what have we seen? With our six-month open-label extension or early data, we saw all mean summary and subdomains, SF-36 quality of life scores being normalized. Later this month, we'll present data at an oral presentation at ENDO where you will see results for the first time from our HP disease-specific patient reported outcome instrument after six months in the OLE.

Since then, all 58 topics have now completed 12 months of treatment on TransCon PTH without any additional drop out, which gives me confidence that these subjects are continued to see that quality of life benefit with a safe once-daily PTH injection.

In addition to the great data on quality of life, TransCon PTH also demonstrate normalization of key biochemical parameter ready to long-term complication. After six months in the OLE, mean 24-hour urinary calcium excretion fell on average 57% compared to baseline. Almost all subject demonstrated a normalization or improvement in urinary calcium excretion.

On measures on bone health, HP patient typically have low bone turnover. And as a consequence, abnormal dense bone compared to people without HP, particularly the trabecular bone. As expected, as we restore physiological PTH level, we saw bone turnover increases with the initiation of TransCon PTH treatment, resulting in a trend toward normalization of the abnormal dense bone, particularly the trabecular bone.

So what is next for TransCon PTH? During the second quarter of 2021, we plan to buy 12 months OLE data. We expect to see continued normal quality of life through sustained reduction of HP symptoms, continue normal cerum calcium, continue normal level of urinary calcium and continue normal bone turnover. As part of extending our global reach for this potential life-changing therapy during the second quarter, in addition to the 12 months PTH forward update, we plan to submit a clinical trial notification for a trial evaluating TransCon PTH for adults HP in Japan.

Later this year in the fourth quarter, we plan to report top-line results from the PaTHway trial, a Phase 3 randomized, double-blind, placebo-controlled trial investigating the safety, tolerability and efficacy of TransCon OTH in adult with HP. The trial is expected to enroll 76 subjects at sites in North America and Europe. We are pleased by the data that we have generated so far and we believe the data support a profile for TransCon PTH to be a potential first-line therapy for HP. We are confident we can truly make a difference in the life of HP patients.

Turning to TransCon CMP. We are conducting two double-blind, placebo-controlled Phase 2 trials in childred aged two to 10 years old. But first, the ACcomplisH trial is a dose escalation trial of 12 to 15 subject is each cohort conducted mainly in North America and Europe. The second is the ACcomplisH China trial, which is a cohort expansion trial of at least 60 subject conducted in China. VISEN received approval for the Chinese Center for Drug Evaluation to conduct the ACcomplisH China Trial with a design for dose expansion as an effective dose determine for the ACcomplisH trial.

Combined, these two sudies will enroll more than 120 subject aged two to 10 to be followed for 12 months in a double blinded manner. Both ACcomplisH And ACcomplisH China will remain blinded until the 12 months follow-up is completed. Once completed, we will have robust clinical data from two independent randomized double blinded placebo controlled trials. We plan to provide a TransCon clinical program update in the fourth quarter of 2021.

Finally, in endocrinology, we announced today that centers will have shipment presentation at the ENDO 2021 annual meeting. This will include an oral presentation of the six months open label extension from the PaTH Forward trial for TransCon PTH as I mentioned.

In our second therapeutic area, we hosted our first oncology R&D date back in November. To share our vision on how to use TransCon systemic and inter turmoil technology to establish a new paradigm for treatment of cancer. We think we can develop entirely new treatment paradigm in oncology using TransCon technologies and address all steps of the immunity cycle.

We are applying the same product development aggregate in oncology as we have successfully used in endocrinology, applying TransCon technology to clinically validated parent drugs and biological pathways. For TransCon TLR7/8 Agonist, an IND was submitted in December 2020 to initiate the Phase 1/2 transcendIT-101 trial during the second quarter of 2021 following monotherapy dosing, we plan to initiate dose escalation in combination with a checkpoint inhibitor. Initial monotherapy dosing results are expected in the fourth quarter of 2021.

For TransCon IL-2 beta/gamma, earlier this year, we reported potential best-in-class preclinical data. Our TransCon IL-2 beta/gamma is designed to have best-in-class potency receptor bias combined with a long half-life of around 22 hours and a low Cmax concentration. In non-human primates study, we have observed a highly bias potent activity with sustained exposure leading to best-in-class remote cell expansion with minimal effect of eosinophils IL-5 or IL-6 and vascular leak gamma. Based on this data, we believe TransCon IL-2 beta/gamma has the potential to become a platform patent in oncology treatment. We expect to submit an IND or similar for TransCon IL-2 beta/gamma in the third quarter of 2021.

I sincerely believe that our goals of building a fully integrated global biopharmaceutical company gets one step closer each day. 2020 was a great year, a year to remember for Ascendis as we advanced our endocrinology rare disease and oncology product candidate. In 2021, we look forward to achieve additional successes as we advance our pipeline ahead and closer to patients with unmet medical needs. We are continuing to apply our algorithm to build a pipeline in oncology and are committed to entering a third therapeuric area.

This is how we will achieve sustainable growth, not by advancing just one program but succeeding with multiple potential blockbuster programs in multiple therapeutic areas in multiple geographics.

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

Scott T. Smith -- Senior Vice President and Chief Financial Officer

Thanks a lot, Jan. Turning to our financial results for the full year ended December 31, 2020. We reported a net loss of EUR419 million or EUR8.28 per basic and diluted share compared to a net loss of EUR218 million or EUR4.69 per basic and diluted share during 2019. Now let me run through some components of these results.

Research and development costs for 2020 were EUR260.9 million compared to EUR191.6 million during 2019. R&D costs in 2020 reflect continued advancement of our pipeline with the primary drivers of the increase, including an overall increase in personnel-related and R&D infrastructure costs. And for TransCon growth hormone, or lonapegsomatropin, costs were higher due to buildup of pre-launch inventories as well as increased clinical trial activities. As a reminder, we currently expense manufacturing costs of lonapegsomatropin as R&D in advance of our anticipated product launch. At the time of product approval, a portion of these R&D costs may be reversed and capitalized as inventory, which will result in a one-time benefit to R&D costs.

For TransCon PTH, costs were higher primarily due to device development and increased clinical trial costs. For TransCon CNP, costs were higher primarily due to increased manufacturing and clinical trial costs. And finally for oncology therapeutic area, costs were higher due to increased manufacturing and preclinical activities primarily related to TransCon TLR 7/8 Agonist and TransCon IL-2 beta/gamma.

Selling, general and administrative expenses for 2020 were EUR76.7 million compared to EUR48.5 million during 2019. These higher costs primarily reflect an increase in personnel-related IT and other infrastructure costs as well as expenses associated with the continued build out of our commercial capabilities.

Finance income and expenses in 2020 included a foreign exchange rate loss of EUR78.9 million compared to a gain of EUR7.7 million in 2019, primarily related to unrealized losses on translation of our US dollar holdings of cash and marketable securities to euros. We ended 2020 with cash, cash equivalents and marketable securities totaling EUR834.1 million.

As of December 31, 2020, Ascendis had 53,750,386 ordinary shares outstanding. Subsequent to year-end on January 8, 2021 we invested $12.5 million in VISEN Pharmaceuticals $150 million Series B financing. Following the financing, we own approximately 44% of VISEN's issued and outstanding shares. As a result of this transaction, we expect to recognize a non-cash gain in the first quarter of 2021 of EUR42.3 million.

Turning to 2021, we expect our expenses to increase as we continue to build our commercial capabilities and prepare for launch, advance our endocrinology rare disease pipeline, expand our activities in oncology and continue to invest in the TransCon technology platform, including for lonapegsomatropin, build up a commercial inventory ahead of potential launch, execution of commercial prelaunch and launch activities, investment in expanding commercial manufacturing capacity to support anticipated future demand, continued execution of the foresiGHt Trial, a global Phase 3 randomized-controlled clinical trial and adult GHD and execution of the riGHt Trial, a Phase 3 randomized-controlled clinical trial and pediatric GHD in Japan.

For TransCon PTH continued execution of the Phase 2 PaTH Forward trial, which continues to retain 58 subjects in the open-label extension and execution of the PaTHway trial, a North American and European Phase 3 randomized-controlled clinical trial and adult HP. For TransCon CNP execution of the clinical program, which includes two randomized placebo-controlled Phase 2 clinical trials and achondroplasia, the ongoing ACcomplisH Trial and the ACcomplisH China Trial, which is being conducted through our strategic investments in VISEN Pharmaceuticals. And lastly, in our oncology therapeutic area, execution of the transcendIT-101 clinical trial for our TransCon TLR 7/8 Agonist and advancing the TransCon IL-2 beta/gamma program into clinical development.

We expect other SG&A expenses in addition to lonapegsomatropin commercial prelaunch and launch activities will include continued investments in personnel, systems and infrastructure to support our rapidly progressing portfolio and growing organization. For 2021, we remain on track for hitting our corporate milestones. For lonapegsomatropin, these include with a PDUFA date of June 25, 2021, we anticipate approval for pediatric GHD in the second quarter followed by commercial launch in the third quarter and we anticipate European Commission approval for pediatric GHD in the fourth quarter.

For TransCon PTH, we plan to file a clinical trial notification for a Japanese Phase 3 trial in adult HP in the second quarter followed by reporting top line results for the phase 3 pathway trials in North America and Europe for adult HP. For TransCon CNP, we expect to provide a clinical program update in the fourth quarter. For Transcon TLR7/8 Agonist after dosing in the monotherapy part of the transcendIT-101, we plan to initiate the dose escalation part in combination with a checkpoint inhibitor in the second quarter and plan to present initial transcendIT-101 results in the fourth quarter. And finally, for IL-2 beta/gamma, we've planned to submit an IND or similar findings in the third quarter.

Before we open up the call for questions, I want to make some points about our anticipated commercial activities for lonapegsomatropin in 2021. During Q2 this year, we anticipate approval for pediatric GHD on the PDUFA date of June 25. Then during Q3, we expect to have product available in the US for pediatric GHD. During Q3, once product is available, we anticipate beginning to provide access to lonapegsomatropin for pediatric GHD patients by onboarding patients through our dedicated patient hub and we do not expect to have placement on commercial formularies at that time. Finally, during Q4, we anticipate European Commission marketing approval for pediatric GHD. We plan to provide guidance on the timing of launch in Europe later this year.

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

Questions and Answers:

Operator

[Operator Instructions] Your first question comes from Michelle Gilson from Canaccord Genuity. Your line is open.

Michelle Gilson -- Canaccord Genuity -- Analyst

Hi. Thank you for taking my questions. I guess, the first one, can you maybe discuss the cadence for TransCon GH of getting on to the formularies? How did that happen over the course of a year? And then, my second question for TransCon PTH from a safety perspective, is there a difference between replacing PTH at physiological levels in hypopara patients, I guess, at the dosage you're evaluating versus adding pulses of PTH to stimulate an anabolic effect? And then, I guess, at the doses that you're evaluating for TransCon PTH, would you expect there to eventually be a black box warning or limitation duration therapy like there is for Forteo, given these different effects on the bone?

Jan Moller Mikkelsen -- President and Chief Executive Officer

Thanks, Michelle. So, before our potential, we'll turn it over Jesper. I couldn't potentially take a little off the PTH, a question that you take up. And let me just repeat what we're doing with TransCon PTH related to bone structure. If you have an untreated HP patient that have a higher bone density because you basically have an unnatural low bone turnover because you have not the physiological PTH level of PTH. And if you look on the CM level of PTH is well documented in the literature that you basically see and basic curve that have a peak to trough about 30% during the entire 24-hours cycle. And what we saw in the six months open label extension data? What we saw that when we restored physiological PTH levels? We basically activated the normal bone turnover that you see in a normal human being that have no issue related to potential lower level of PTH. We saw that by accelerating at a higher level of both the anabolic and catabolic bone markers, but still being placed in what we call the higher level of normal levels.

And what we saw was the associated consequence of that. We also saw that this bone density that is abnormal dense because it actually have a structure that basic are not like a normal bone because it has no bone turnover, start to be normalizing. So therefore, we saw that trend to approaching the normal level with our SAT score is defined as zero. That is what we observed in the six months data. This is a continuous process where we saw the main effect on trabecular bone. If we basically looked on cortical bone, that was not the same kind of decline in SAT score. It was basically stable because they don't have that elevated high density that you basically specific for trabecular bone structure. What we saw with our bone markers what we saw in our bone density is just following exactly as what we have expected from the physiology of restoring a normal PTH level.

In our interaction with FDA and EMEA, our first discussion related to PTH and effect as an anabolic compound was when we discuss the basic conduct a COG study. A COG study is basically a study that has been done for all other PTH product to my knowledge. We got a clear answer back from justification and scientific justification that there was no need to do it, because what you are applying in the TransCon PTH product is just a normalization of PTH level and not generating and what I'd call a superficial logical PTH level that you do with the classical compound of PTH that are being used as a [Indecipherable] in osteoporosis.

Therefore, I believe there is a fair chance that we can avoid any kind of REMS program, because what we continue to see with our clinical data and remember at the date of filing, we will have 18 months. So we basically follow this for one month more. We expect to have such a strong data package, that we can provide what we see is just a normalization of this. So I'm hopeful that the signs will continue to play in, so we can be in a position that we can do a scientific justification saying there is no need for a REMS program.

And also, we are also seeing now that if you look on the osteoporosis compound, that black box warning has been removed for Forteo. And also, that is a basic in U.S. situation, because in Europe, they're not believing that the pre-clinical finding you take with osteoporosis or osteosarcoma for short-acting PTH is relevant for humans. So from that perspective, I think we have a strong scientific justification, to avoid both a black box warning and a REMS program.

The other part which also is a scientific justification, is that patient have been on pump, where they're using either Forteo or Natpara for multiple, multiple years. And just recall if you use a pump system, with either Forteo or PTH-31, your basic half and IV injection for eight to 12 times in a subcutaneous tissue in one hour. This will provide a flat, flat, flat continuous exposure inside the plasma compartment. And when you look on long term case studies, even in children pediatric, you see normal growth there. So I don't believe there is any kind of scientific justification, that is possibility, that there is a lot of discussion basic have and meaningful impact on the bone structure.

Jesper, will you talk about how we are addressing and ensuring we have the optimal place for our market assess?

Jesper Hoiland -- Senior Vice President, Global Chief Commercial Officer

Absolutely. And Michelle thank you very much. Basically for lonapegsomatropin, our key focus is market access for the commercial markets. The commercial market represents roughly 180 million Americans, and is represented also mainly -- 75% of the market is via the three big PBMs, and that's -- the way that you negotiate with the PBMs for market access, is basically they send out their requests during the summer months, and then the final call you could say for addressing the market access for 2022, basically comes in the last week of August beginning of September. So we have a golden opportunity to be first on the market with lonapegsomatropin, as we are anticipating the PDUFA date on 25th of June, and therefore, we will be negotiating with the three big PBMs market access for 2022, and we do believe that we will have a good market access for 2022 on the basis of, that we would be the first in the long-acting segment potentially, the lonapegsomatropin. I hope that answered your question?

Jan Moller Mikkelsen -- President and Chief Executive Officer

Thanks Jesper.

Michelle Gilson -- Canaccord Genuity -- Analyst

Yes thank you very much and congrats on the [Speech Overlap].

Jan Moller Mikkelsen -- President and Chief Executive Officer

Thanks a lot.

Operator

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

Jessica Fye -- J.P. Morgan -- Analyst

Hey guys, good afternoon and thanks for taking my questions. This one might be for Dana, can you tell us whether the necessary pre-approval inspections have taken place yet for TransCon Growth Hormone and your expectations for those being completed prior to the PDUFA, given any COVID travel issues? I know you said multiple times on the call, that you guys expect approval in 2Q. So it sounds like maybe things are on track there. That's the first question. And then second, kind of building on the last question, thinking ahead to the 12 month open label extension data for the PTH phase 2 trial coming up in 2Q, can you talk about what you would expect to see on BMD at the 12-month time point, and what that means for the product? I guess more specifically, at what point do you expect to have clinical data that will demonstrate, that the normalization that you're seeing in BMD early on does not overshoot and lead to below normal BMD. Thank you.

Jan Moller Mikkelsen -- President and Chief Executive Officer

So Dana, would you take the first question?

Dana Pizzuti -- Senior Vice President, Development Operations

Yes, as far as the inspections go, we're finally starting to see a bit of movement from the FDA in terms of their activity. In fact, we've recently had a GCP inspection at a site for our number one enroller of growth hormone. So that was completed last week. As far as the manufacturing inspection goes, we are still in communication with the FDA, about when that would be scheduled, and there are a couple of opportunities in terms of alternate approaches that are available. So we still feel that we sort of can address these issues, before it has any impact on the PDUFA date. But we're also noticing that FDA is doing more manufacturing inspections outside the U.S., as COVID is somewhat subsiding in certain places. Okay?

Jan Moller Mikkelsen -- President and Chief Executive Officer

I think just going back to your second question, and I think we need to take it into this perspective as my initial comments to Michelle, because there will be basic layouts, that what we are seeing now is just a normalization of bone structure that you expect to do, when you actually are coming into a replacement therapy and observing that you are providing PTH and physiological level. And you can also see the differentiation between trabecular and cortical bone. If you look in the data, you can see where we expect to see the biggest remodeling is on trabecular bone, and we also seeing that right structure coming in of the bone. So my perspective is that, I cannot see any worry about that, because that is not normal biology, and we have children that have been 10 years on infusion pump, growing up with normal bone structure on an infusion pump. We have adults that are sitting five to six years on infusion pump, and observing all the same things.

And I think everyone to just have a clear understanding about an infusion pump and insulin and other things like that, would acknowledge, there is a total flat curve you provide with infusion pump. So I am really lost in the logic of where it is coming in, because what we are just seeing is normal biology, which we see on lot of other elements. We see the same thing with urinary calcium. We see the loss of soft tissue calcification. We see expected normal physiology. I cannot change physiology. If you want to have a hormone-replacement therapy, then you need to expect to see the outcome of being a normal human being.

Jessica Fye -- J.P. Morgan -- Analyst

Great, thank you.

Jan Moller Mikkelsen -- President and Chief Executive Officer

We just follow the science, and that is what we're doing. I cannot change science. I can follow and adapt to science.

Operator

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

Alethia Young -- Cantor Fitzgerald -- Analyst

Yes, thanks for taking my question and congrats on all the progress. I just wanted to flow -- maybe two questions. One just clarifying on the formulary, maybe I missed it, do you think that you'll have kind of a broad the formulary that could include adults and some of the other growth hormones? And then the second one is just, in oncology, as you continue to kind of do work there, do you feel like there is one target between IL-2 or TLR 7 that has kind of a, in a greater target risk or do you kind of feel like it's somewhat equal and you have a fair amount of confidence in both? Thank you.

Jan Moller Mikkelsen -- President and Chief Executive Officer

Jesper, I actually think, that what you are now addressing is part of our important long strategy. And you know for every product, one step is to getting approved and we have seen long-acting product being approved now in the U.S. without being launched, because that is not what I call an associated launch strategy, where the product access is meaningful to launch. So what we are addressing is the key element in our entire long strategy, and this is where we have a huge comfort in what we're doing, because we're not only feeling that we are providing a best-in-class product opportunity, but we are also providing into the first-in-class growth hormone deficiency market for pediatric children. So Jesper, do you have anything further to add?

Jesper Hoiland -- Senior Vice President, Global Chief Commercial Officer

Yeah, of course, just to add that in the initial phase, we anticipate to get the pediatric indication, which is the vast majority of the market, whereas the adult indication only represents 10% to 12% of the market. So we will enter into the lion's share of the market, and with the pediatric indication.

Jan Moller Mikkelsen -- President and Chief Executive Officer

And going back to oncology, you saw we built up a pipeline of three independent product opportunity, endocrinology rare disease. We will continue to build up our pipeline in oncology. What we have with our two hopeful clinical programs, now in three to four months from now, we really have a paradigm shift, how to treat tumor. And what we really want to do with the tumor, is make a kick-start. We want to kick start the immunogenic response into a solid tumor. This is how we think and at the same time, we come with, what we believe can be a next-generation of how to do immunological stimulation. We have seen the success of checkpoint inhibitor, but we're also seeing the limitation. When we see how potent our TransCon 2 beta gamma is a really unique compound. And this is why we see and build on the entire immunological understanding from Juha and his entire group, is to build more product opportunity, so we basically are a fully integrated oncology company, with all the aspect of the immunological -- immune cycle, where we have addressed all pathway, and this is our vision, how we want to be a major player in that segment, too. Juha, do you have other comments?

Juha Punnonen -- Senior Vice President, Head of Oncology

Yeah, I think just to add that I think, we believe that they both have very unique properties and we will have a unique opportunity in the treatment of cancer. They obviously are very different product profiles, one being intra-tumoral administration, one being systemic. We expect them to also work very effectively together, hard to compare with each other, but I think our point really is that they both have their unique spot in the treatment of cancer, and will also work additively while treating these patients.

Jan Moller Mikkelsen -- President and Chief Executive Officer

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

And when we go to the third product opportunity, we basically build on what we have done in TransCon IL-2 beta gamma, TransCon TLR 7-8, that will be a strong synergy what we're doing in the third one. This is how we want to think, how we want to make a paradigm shift.

Alethia Young -- Cantor Fitzgerald -- Analyst

Great, thank you.

Unidentified Participant

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

Unidentified Participant

[Technical Issues] TransCon CNP in your opening remarks, but I was just wondering if you could just elaborate a little bit more on the program. How do you choose your ACcomplisH study doses and how have you designed your ACcomplisH China study in order to leverage your findings in the ACcomplisH study in the U.S. and EU trial, and how should we interpret these two results when they emerge later in 4Q?

Jan Moller Mikkelsen -- President and Chief Executive Officer

We just lost the beginning of it, but I believe that what you're referring to is our TransCon CNP program?

Unidentified Participant

Oh yeah, that's correct. TransCon CNP.

Scott T. Smith -- Senior Vice President and Chief Financial Officer

I think that is what you were referring to. And I actually believe that we are having a major effort now to understand this -- I think important disease. We know how CNP has functioned, we have known that for 15-20 years. We know that biology and the science behind it, and that is what has directed our two program with TransCon CNP. We are now in a position that we have a unique product opportunity with TransCon CNP, which can provide a continuous exposure for up to one week with one single dose, and we know we can do it in an extremely safe manner. And we do it now in two independent product, you can say, two independent clinical trials. But what we really want to do, is not only to look at one single parameter. We are aiming to go down to the newborn children as fast as possible. We will, because of our unique safety profile, manage to start already an NH-II. And we are dedicated to move it down as early as possible, as fast as possible, down to newborn children, because we know if we want to address comorbidity, some of them are irreversible happening in their early stage, and that is really what we want to do.

Mark is leading a major effort in Ascendis, how really to expand the program, involving a lot of different comorbidities. And I do not know Mark, if you could say a few words, how you also use our huge natural history study now, and try to integrate the development and comorbidities and try to develop them in a unique clinical development plan, so we potentially can address not only heiGHt, but also the other comorbidities?

Mark A. Bach -- Senior Vice President, Clinical Development and Medical Affairs for Endocrine Medical Sciences

Sure, I can say a few words. Thanks Jan. So we have an ongoing natural history study, which is providing us very valuable information and one of the things we find when we talk with individuals with achondroplasia, is there -- the heiGHt is not the biggest issue that they want us to look at, but rather a lot of the comorbidities, issues with foramen magnum, issues with otitis media, issues with airway. And so for us, it has been a very important, not just to be prepared to look at heiGHt, but to really understand the comorbidities better, and we are using the natural history study, to try to gain information about the comorbidities' frequency time of occurrence, and to give us enough information to successfully study them in a clinical trial. So I think that's what Jan is alluding to, and it's actually providing us even early on, what we think will be useful information. Thanks Jan.

Jan Moller Mikkelsen -- President and Chief Executive Officer

So what is Mark...

Unidentified Participant

Thanks for that.

Jan Moller Mikkelsen -- President and Chief Executive Officer

This finding is that, we could integrate that knowledge into our clinical development now.

Mark A. Bach -- Senior Vice President, Clinical Development and Medical Affairs for Endocrine Medical Sciences

Right.

Unidentified Participant

Okay, great. Thank you. And then my next question is on TransCon PTH. Based on our conversations with endocrinologists, some docs prefer to see T scores over Z scores in adults, and our question is do you have plans to present this and how does that compare to T scores?

Jan Moller Mikkelsen -- President and Chief Executive Officer

T score and Z score are complete different independent benchmark in measuring. Z score is to a normal population, and this is also what we are using in growth hormone deficiency when we talk about heiGHt. You typically use a set score, because that is the most relevant one. When you talk about osteoporosis compound, you often use a T score, because this is the way you basically are trying to compare what was optimal for the person. But I think that is not really the aim of this year. We also can look on the T score, it's basically providing the same guidance and the same thing that we see as the S score, But as we have a hormone-replacement therapy, it is typical what you want to, you want to do a normalization of all different element of the body to be as a normal human being, this is the definition of hormone-replacement.

If you go to osteoporosis, you want to redo and reset, what you call a national decline in some of the bone structure, and this is why you in some way referring into a T score. But this is coming from a demographic that is not building on the patient population, that has a complete different dense bone structure than what you see in other places, because there is a dense structure that is happening, to what we call a non-natural process, where you are basically just building up a dense bone structure, because you are now turnover. That is not the same thing to have a healthy bone structure. No one is ever claiming that's the bone structure you have in HP patient is healthy, even is more dense, because it's an old bone structure. So I think it's not meaningful to compare to a T score. Sure, we have the data if you have looked at it, what is meaningful for a hormone-replacement therapy is compared to a Z score.

Unidentified Participant

Okay, great, thank you for that.

Operator

And your next question comes from the line of Anita Dushayanth from Berenberg Capital. Your line is open.

Anita Dushyanth -- Berenberg Capital -- Analyst

Hi, good afternoon. Thanks for taking my questions. Just a couple here. Could you please remind us a sort of timeline in terms of the pediatric Phase-III trial that would commence in Japan. And sort of, I know you have applied for the CTN. So when is it sort of likely to -- sort of, we are going to get the green signal to go ahead. And then in terms of the HP Phase-III trial, would there be any change to the trial design itself in terms of inclusion or exclusion criteria of patients, based on your six-month data?

Jan Moller Mikkelsen -- President and Chief Executive Officer

I think the first question is reflecting on pediatric growth hormone deficiency trial or riGHt trial. Mark, can you give us the status of our riGHt trials that you have intensive experience in Japan?

Mark A. Bach -- Senior Vice President, Clinical Development and Medical Affairs for Endocrine Medical Sciences

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

Jan Moller Mikkelsen -- President and Chief Executive Officer

I think from a company perspective, we will be in a unique position, because it looked like all our product opportunity in three different indications, pediatric growth hormone deficiency, adult growth hormone deficiency, and HP will nearly be aligned for approval, nearly in the same time of the year. Plus I think, it is a unique situation for us to find an optimal way to make a commercial effort in this region, was typical to involve Japan South Korea and other major country outside Greater China in that region.

Anita Dushyanth -- Berenberg Capital -- Analyst

Okay. And then as far as the Phase-III HP trial, will there be any changes in the trial design based on the six month data?

Jan Moller Mikkelsen -- President and Chief Executive Officer

Related to the six month data, we have disclosed in our open-label extension. We will basically have the same patient population coming into the trial as we saw in our Phase II trial. That will not be -- I have to think this, Mark you can correct me, I think it's a little bit broader this time, because there is a patient population as HD H1 patients, that we also have included it because they will hugely benefit to have a normal physiological level of PTH like a post surgical one. So this kind of patient population also being opened up in the Phase-III trial and we also believe that it is important, that they have an opportunity to get an optimal PTH treatment, with physiological PTH level 24 hours. And from that perspective is, we actually are having the other change in basic in the -- where we looked at, what was really difficult in the Phase II trial and what the -- why we, you always took on screening failures. Why do we have screenings failure, what is the driver of the screening failure. And we actually realized, it was really, really difficult for an HP patient, just to have a normal serum calcium of 8.3. It was hot just by standard of care, taking activated vitamin D, taking calcium supplement to meet them up to 8.3. You know, the normal calcium is typically in the 9. In trials here, we have between 8.3 and 10.3. But we are in a position that we basically lower the entry criteria, so you can go down to 7.8 to be part of the trial. And it was basically to ensure, that all this patient group, which were impossible, basic to be in a position to titrate up to date.

Mark, do you have other element or anything I have forgotten?

Mark A. Bach -- Senior Vice President, Clinical Development and Medical Affairs for Endocrine Medical Sciences

Yeah, I mean, there's a few other subtle differences between phases. We are basically relying on what we learned in Phase II and going to Phase III. So in Phase II, again for the first efficacy trial, the dose is fixed or the first four weeks, and then allowed to titrate, in Phase III we are allowed to titrate from the beginning, which makes thanks clinical sense. And in phase II, the upper dose limit was lower than what we're allowing in Phase III, based on what we've learned in Phase II. So there is a few small things, and then the other is that in Phase II, we validated the disease specific quality of life instrument, that will then be used in Phase III -- so -- as an outcome measure. So I think those are the primary differences between the two trials.

Jan Moller Mikkelsen -- President and Chief Executive Officer

Thanks Mark.

Anita Dushyanth -- Berenberg Capital -- Analyst

Great. Thank you.

Operator

And your next question comes from the line of Rene Wouters from Kempen. Your line is open.

Rene Wouters -- Kempen -- Analyst

Hi guys. Thanks for taking my questions. I guess two from my side. So first one on TransCon Growth Hormone. Now that you have the two years data, can you remind us how long you are planning to continue following up these patients, and what will you do with this data and do you anticipate to submit these data to the regulators as well? And second question is on TransCon PTH; great to see that still almost all patients are on therapy in the open label extension part. Maybe moving, jumping a few steps ahead toward commercialization, what are the lessons you've learned from Natpara, and why do you think TransCon PTH will be commercially more successful? Thanks.

Jan Moller Mikkelsen -- President and Chief Executive Officer

Yes, thanks a lot. Thanks a lot for the questions. The first one is basic as addressing what do we do in the flight -- in the trial that we continue on -- in our Phase III, where we have an open label extension for both from the fliGHt and the heiGHt trial, which continue on it. And currently we see patient coming to a situation, that they basic are reaching final heiGHt. We are in a position, we will continue this open label extension trial. So we basically can continue to collect unique information about how we basic are providing a treatment, where every child have an opportunity to achieve their expected height, not only height, but also all elements like body composition and other things like that, that we mentioned. And we think that is a really important thing.

We are running our trial in multiple countries, and we hope and expect still to continue in most of this country. But Mark, you're sitting with all the cost of commitment now here, and perhaps you can give a short update about what we expect to continue to execute -- what the summary would be like to continue to give you data for this important trial?

Mark A. Bach -- Senior Vice President, Clinical Development and Medical Affairs for Endocrine Medical Sciences

Sure. Do you want me to add a couple of comments Jan?

Jan Moller Mikkelsen -- President and Chief Executive Officer

Yeah.

Mark A. Bach -- Senior Vice President, Clinical Development and Medical Affairs for Endocrine Medical Sciences

Yeah. Okay. So if you know the enliGHten trial, which is the combined ongoing study from fliGHt in heiGHt is continuing and as Jan said, we're getting very nice data on it, some of the patients are indeed getting toward their near adult height, others have some room to go. I think at least for the time being, the study is continuing. And I would expect both clinicians and regulators may have some interest in having some longer-term data, and so at this point, I think its premature to make a commitment and how long it will continue, but it is certainly continuing for now, and delivering valuable data. I think over the next months, we'll have a better idea about what longer-term data we want or would need to collect. But, certainly its ongoing now and really still giving very useful information.

Jan Moller Mikkelsen -- President and Chief Executive Officer

So I think addressing your question. What is the learning from Natpara? Even if you develop a product like adjunct to standard per care, there is still a huge need for such a product, and then you can nearly imagine what is the need would be when you have a hormone replacement therapy and not just an adjunct therapy. That is the differentiation. We are competing in two different segments, one is an adjunct therapy, we have positioned TransCon PTH as a hormone replacement therapy, addressing all aspects of the disease, both short-term symptoms, long-term complications. That is the main difference between the two product, this is like an apple and an orange in my view.

Rene Wouters -- Kempen -- Analyst

Okay. Thank you very much.

Operator

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

Yanan Zhu -- Wells Fargo -- Analyst

Hi, thanks for taking my question. So a couple on the CNP program and a couple on the PTH program. So for the CNP program, to identify a dose to move forward into the ACcomplisH China trial, do you need to wait until all four blinded dose cohorts in the US/EU ACcomplisH trial to be completed, or could you unblind each dose cohort as you go? And then any plan to open a US/EU dose expansion trial for the CNP program? Thanks.

Jan Moller Mikkelsen -- President and Chief Executive Officer

Great question. I think we are in a position, that we are aiming not to unblind it. We think it's really, really, really important not to unblind it. But we also believe that it's possible on a blinded basis, to be in a position to have some good guidance that would be a potential are in acceleration that we have an active dose. We have a lot of primary outcome to be looking in. We also have a series of biomarkers that we are addressing and other element that could give us a guidance about where we are. And this is where Mark and his team is really developing how really to look on all this data and be convinced that we have something that is meaningful to move forward in a dose escalation and dose expansion on it. And that is the task of Mark and his people to be quite sure, but are confident that we see something on a blinded basis. So we don't want to unblind the trial before everything is done.

The second one, this is up to the situation. Yes potentially, we will do that depending on that. We are in a unique position to VISEN Pharmaceuticals and the experience for the team in China [Phonetic] to conduct this trial, that we have so fast access to patients in Greater China. But we're also seeing that is -- we're also seeing the same thing in Europe and U.S., in Australia and other places. So huge interest for our trial, that will not be limited to any kind of limitation in how many patients we want to take in. So I do not know, Mark, about our plans to potentially open up a European/U.S. arm in the dose expansion? I don't think it's something we really have decided on yet.

Mark A. Bach -- Senior Vice President, Clinical Development and Medical Affairs for Endocrine Medical Sciences

No, we had not discussed it for now. Things are going well, both in the global trial and the China trial. So it's not something we talked about so far. But certainly, should it be necessary, we could talk about it, but not on the agenda right now.

Yanan Zhu -- Wells Fargo -- Analyst

Got it. And on the PTH program, what kind of interest are you seeing in the PaTHway Phase-III trial? Is there enthusiasm due to the data you reported from the Phase-II open label extension? And then is the safety database from 76 patients considered sufficient for the regulators? Thank you.

Jan Moller Mikkelsen -- President and Chief Executive Officer

That's two questions. The first question is how high is the understanding about what we can provide with TransCon PTH throughout the HP patient society and physicians. I have never seen anything like that before. When we see the [Indecipherable] assessment, how people get their life back again. And sure, it is helping us to go out and make a broader indication about it, like in the conference, but we already see a huge enthusiasm everywhere, so to be part of this trial. So I believe that when I see how TransCon PTH is a game changer. We are addressing the life of more than 200,000 patients just in Europe, U.S. and Japan. And what we have seen basic by having 58 out of 58 basic continue on it, everyone has a huge, huge benefit of this treatment. And related to the safety database, I think, Dana, you can explain how we're building our combined safety database both from our Phase 2 trial and also what we will see in our Phase 3 trial.

Dana Pizzuti -- Senior Vice President, Development Operations

Yes. For the sort of approval, as we discussed with the agency, too, in our -- and the Phase-II meeting, the combination of the information from the Phase-II and the Phase-III will satisfy the criteria for the safety thresholds for the applications. So did that answer your question?

Yanan Zhu -- Wells Fargo -- Analyst

Got it. Thank you. Yes, very helpful. Thank you.

Operator

[Operator Closing Remarks].

Jan Moller Mikkelsen -- President and Chief Executive Officer

Thanks a lot.

Scott T. Smith -- Senior Vice President and Chief Financial Officer

Thanks.

Duration: 75 minutes

Call participants:

Scott T. Smith -- Senior Vice President and Chief Financial Officer

Jan Moller Mikkelsen -- President and Chief Executive Officer

Jesper Hoiland -- Senior Vice President, Global Chief Commercial Officer

Dana Pizzuti -- Senior Vice President, Development Operations

Juha Punnonen -- Senior Vice President, Head of Oncology

Mark A. Bach -- Senior Vice President, Clinical Development and Medical Affairs for Endocrine Medical Sciences

Michelle Gilson -- Canaccord Genuity -- Analyst

Jessica Fye -- J.P. Morgan -- Analyst

Alethia Young -- Cantor Fitzgerald -- Analyst

Unidentified Participant

Anita Dushyanth -- Berenberg Capital -- Analyst

Rene Wouters -- Kempen -- Analyst

Yanan Zhu -- Wells Fargo -- Analyst

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