Ascendis Pharma A/S Q1 FY2021 Earnings Call

Ladies and gentlemen, thank you for standing by, and welcome to the First Quarter 2021 Ascendis Pharma Earnings Conference Call. At this time, all participant lines are in the listen-only mode. After the speaker’s presentation, there will be a question-and-answer session. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your host, Scott Smith, Senior Vice President and Chief Financial Officer at Ascendis Pharma. Please go ahead.

Thank you operator. Thank you everyone for joining our first quarter 2021 financial results conference call today. I am Scott Smith, Chief Financial Officer of Ascendis. Joining me on today’s call are Jan Mikkelsen, President and Chief Executive Officer; Dr. Mark Bach, Senior Vice President of Endocrine Medical Sciences; Jesper Høiland, 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, 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 statements section in today’s press release and the Risk Factors section of our most recent Annual Report on Form 20-F. Please note that our TransCon product candidates are investigational product candidates and are not approved for marketing by the U.S. Food and Drug Administration, European Medicines Agency or other foreign regulatory authorities. As investigational products, the safety and effectiveness of the TransCon product candidates have not been reviewed or approved by any regulatory agency and no representations are made as to their safety or effectiveness for the purposes for which they are being investigated. None of the statements made on the conference call regarding our TransCon product candidates shall be viewed as promotional and/or product commercialization. On today's call, we will discuss our first quarter 2021 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.

Thanks, Scott, and good afternoon, everyone. Our goal at Ascendis is to create a leading biopharma company by bringing highly differentiated product candidates, addressing major unmet medical needs as fast and safely as possible to the patients. Beginning with our TransCon technology and algorithm for product innovation, we designed our TransCon Growth Hormone product candidate and developed it from idea stage to Phase 3 pivotal trial. This year we are seeing the results of our efforts as we are approaching the due date June 25th for TransCon Growth Hormone. We held our late-cycle meeting with FDA in April, in which FDA confirmed at that time that they are planned to meet the PDUFA action date. After the late-cycle meeting, FDA conducted a BIMO inspection at our Palo Alto site over a six-day period with no 483 observation. Finally, we and our contract manufacturers have also submitted a response to FDA's information request related to our contract manufacturing sites. We feel good about a potential US approval for TransCon Growth Hormone for the treatment of pediatric growth hormone deficiency. We believe our ongoing discussions with FDA are progressing well. Based on the latest feedback, we believe we will get a label that will support the scientific basis for TransCon Growth Hormone having a comparable mode of action to daily growth hormone. The great thing about retaining the same mode of action is that patients, physicians and payers can rely on the at least 30 years of scientific and clinical data to predict expected treatment results for overall endocrine health, including growth velocity. But getting an approval is just another important step in our plan to build a market-leading product. We are all aware of our long-acting growth hormone preparations that have been approved but not launched or have been launched but then removed from the market. To have a market-leading product, we also have to provide a strong value proposition to patients, physicians and payers. For patients, our once-weekly TransCon Growth Hormone has in clinical trials shown safety, including hematologic profile comparable to daily growth hormone and superior outcomes measured by annualized height velocity in pediatric growth hormone deficiency compared to daily growth hormone. We believe our once-weekly TransCon Growth Hormone administered with an auto-injector in a room temperature-stable presentation will reduce the treatment burden for patients compared to daily growth hormone. For physicians, we believe our once-weekly TransCon Growth Hormone may improve patient compliance compared to daily growth hormone, which potentially could lead to better outcomes. And for physicians, finally, they may have a growth hormone therapy for patients and caregivers that is associated with less treatment burden compared to daily growth hormone. Largely for payers, our recent US insurance claims analysis data presented at the end of 2021 demonstrated the financial benefit of treating pediatric growth hormone-deficient patients with growth hormone therapy and the dramatic need for improved adherence. We are continuing to execute on our global clinical reach and label expansion for TransCon Growth Hormone. In Europe, we expect a decision from the European Commission on our marketing authorization for TransCon Growth Hormone in the fourth quarter of this year. In Japan, we continue to execute on the Phase III riGHt trial for pediatric growth hormone deficiency. And in China, VISEN Pharmaceuticals recently completed enrollment of its Phase III clinical trial of TransCon Growth Hormone in children with growth hormone deficiency. We also have the global Phase III foresiGHt Trial underway for adult growth hormone deficiency to support label expansion for TransCon Growth Hormone. And we continue to expect to complete enrollment of the foresiGHt Trial by late 2021 or early 2022. In summary, for TransCon Growth Hormone, we are aiming to bring a highly differentiated product to the patient that can become a global leader in the growth hormone market and provide benefits to patients, physicians and payers. Moving to TransCon PTH. We were excited about the 58-week results from the open-label extension of the Phase II PaTH Forward Trial in adult hypoparathyroidism. When we reported the 26-week data, we showed that we had a potential hormone replacement therapy that demonstrated normalization of serum calcium, normalization of phosphate, normalization of phosphate-calcium complex, and normalization of urinary calcium. We also saw the major impact TransCon PTH treatment had on quality of life on the SF-36 functional health survey. And we saw a trending toward normalization of skeletal remodeling. Coming to the 58-week results, the open-label extension trial is the first time to our knowledge that such a large group of hypoparathyroidism patients has been exposed to physiological levels of PTH for over a year and it demonstrates how this treatment might help this patient group on a long-term basis. If I just sum up the 58-week results, what we saw was as expected, the durable response and well-tolerated safety profile that we hoped for. All the elements of normalization of calcium metabolism and hemostasis that we observed at the 26 weeks continued at 58 weeks, including normalization of 24-hour urinary calcium excretion, along with the initial rise of bone turnover followed by a decline trending to the mid-normal level. All this effect was observed in the absence of active vitamin D intake and the requirement for therapeutic intake of calcium supplements. What is remarkable and rewarding to me is that these 58 patients continue to participate in the open-label extension. I believe this is a reflection of the positive impact TransCon PTH is having on this patient's short-term symptoms and quality of life. I have never been part of a trial where we started with 59 patients and have 58 patients more than one year into an open-label extension. The patient demographic in our Phase 2 trial showed a very mixed population, subjects suffering from post-surgical hypoparathyroidism, idiopathic hypoparathyroidism, and autonomous hypoparathyroidism, some with kidney stones, renal insufficiency, some just recently diagnosed with hypoparathyroidism, and some with hypoparathyroidism for more than four years. Some patients had mild disease and some had up to eight grams of calcium supplements plus active vitamin D at baseline. Despite the wide variety of severity and disease background, 58 still continued in the open-label extension. I believe the improvement in quality of life is driving that. Looking at the adherence level, it was 99.8%, strongly suggesting that TransCon PTH is providing a benefit for the short-term symptom, as the patients don't want to miss a shot. Everything I've seen with all the data suggests that patients benefit from TransCon PTH, regardless of severity and disease background. We have seen that with the data, with the adherence to the trial retention and now we're also hearing the same measures from the physicians being part of the trial. Some physicians are now saying that all patients may benefit from TransCon PTH, not just because of biochemical control, but because the patients' lives are improving. The patient can now become active again and return to work. This is exactly why I see TransCon PTH addressing a major unmet medical need for the patient, but also for society, by enabling the patient to find active employment and work again. So when I look at the data, when I hear the stories from the patient, when I hear the stories from the physician, I feel so optimistic. I'm hopeful that we really can help the more than 200,000 patients that are in the US, Europe and Japan and for the first time can potentially provide a formal replacement therapy that normalizes their lives for them, not only based upon short-term symptoms but also potentially on long-term complications. Later this year in the fourth quarter, we expect to have the 84-week top line open-label extension update from PaTH Forward. We also expect to report our top line Phase III PaTHway Trial results by the end of the year. We believe the data being generated support a profile for TransCon PTH to be a potential first-line therapy for hypoparathyroidism. At the time of regulatory submission planned for the first half of 2022, we expect to have a solid data package with both long-term 84-week data from our Phase II PaTH Forward Trial and six-month randomized controlled data from the Phase III PaTHway Trial. To achieve global clinical reach, earlier this month we submitted a clinical trial notification to initiate a Phase III clinical trial evaluating TransCon PTH for adult hypoparathyroidism in Japan. We look forward to sharing additional results later this year, as our goal is to make this important therapy available to hypoparathyroid patients worldwide as fast as possible. Turning to TransCon CNP. We are on track to provide an update on the clinical program in the fourth quarter of this year. As you know, we are conducting two randomized double-blinded placebo-controlled Phase II trials in children aged two to 10. The first ACcomplisH trial is a dose-escalating trial of 12 to 15 subjects in each cohort conducted mainly in North America, Australia, and Europe. The second one by VISEN Pharmaceuticals is a completed China trial, which is a cohort expansion trial of at least 60 subjects conducted in China. We are planning to keep the data blinded for one year for each cohort. Once completed, we will have robust clinical data from two independent randomized double-blinded placebo-controlled trials. To date, the safety is everything we have hoped for. There have been no injection site reactions and no indication of cardiovascular risk. Our top priority is the achondroplasia patients in developing a safe and differentiated treatment option that addresses the comorbidity of their disease. Turning to oncology. We hit a major milestone late last year with our first R&D for our oncology division, which is also our first IND leveraging the TransCon hydrogen technology for sustained intratumoral delivery. We expect to initiate dose escalation in combination with a checkpoint inhibitor in July and to have initial results for monotherapy dose escalation for TransCon TLR7/8 Agonist in the fourth quarter. For our second oncology program, we are on target to submit an IND for TransCon IL-2 beta/gamma in the third quarter of 2021. TransCon IL-2 beta/gamma is designed for systemic administration via IV route and leverage the TransCon systemic technology that you know from our endocrinology portfolio. As we have done in endocrinology, our understanding of the biology has guided us into signing a compound with independently optimized receptor binders, potency and pharmacokinetics to create a potential best-in-class IL-2 product. Summing up, starting with a product concept we are now less than one month away from our first PDUFA action date which is a significant achievement. But as I mentioned, when I started today's comments, we are not just trying to bring a product to market. We are driving to solve major unmet medical needs that we can meet by our TransCon technologies. We want to establish Ascendis as a fully integrated global biopharmaceutical company that has a portfolio of multiple independent products that make a difference in the life of patients. We have many important milestones to execute on in 2021. I have never been more confident that we have the fundamentals in place to successfully build a leading biopharma company with multiple market-leading products in both endocrinology, rare diseases and oncology. Now, let me turn the call over to Scott for a financial review before we open for questions.

Thank you, Jan. Turning to our financial results for the quarter ended March 31, 2021, we reported a net loss of €62.8 million or €1.17 per basic and diluted share compared to a net loss of €63.3 million or €1.32 per basic and diluted share during the first quarter of 2020. Now, let me run through some key components of these results. Research and development costs for the first quarter were €88.1 million compared to €57.5 million during the first quarter of 2020. R&D costs in the quarter 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 the buildup of prelaunch inventories, investments to expand our future manufacturing capacity as well as increased clinical trial-related activities. As a reminder, we currently record all manufacturing related to lonapegsomatropin as R&D costs including manufacturing of prelaunch inventories which are immediately written down as R&D costs until we can demonstrate these values are recoverable. Since lonapegsomatropin is our first commercial product, we first deem these recoverable upon obtaining regulatory approval. Therefore, upon regulatory approval, we will reverse prior period write-downs of prelaunch inventories as a reduction to our R&D costs and recognize the cost of such material in our inventory. For TransCon PTH, costs were higher primarily due to increased clinical trial-related activities and manufacturing-related device-related development costs including production of PPQ batches. And for TransCon CNP, costs were higher primarily due to increased manufacturing-related and clinical trial-related costs. And finally, for our oncology therapeutic area, costs were higher due to increased manufacturing-related preclinical and clinical costs primarily related to TransCon TLR7/8 agonist and TransCon IL-2 beta/gamma. Selling, general, and administrative expenses for the first quarter were €37.2 million compared to €17.9 million during the first quarter of 2020. These higher costs primarily reflect an increase in personnel-related, IT, and other infrastructure costs as well as increased expenses in our commercial organization as we prepare for the launch of lonapegsomatropin. Related to our investment in VISEN Pharmaceuticals, as previously disclosed, first quarter results included a one-time non-cash gain of €42.3 million as a result of VISEN Series B financing in January. Finance income and expenses in the first quarter included a foreign exchange rate gain of €34.2 million compared to a foreign exchange rate gain of €10.3 million in the first quarter of 2020, primarily related to the translation of our US dollar holdings of cash and marketable securities to euros. We ended the first quarter of 2021 with cash, cash equivalents, and marketable securities totaling €771.1 million. And as of March 31, 2021, the company had 53.829379 million ordinary shares outstanding. Turning to the remainder of 2021, key items impacting expenses include the anticipated launch of lonapegsomatropin, advancing our endocrinology rare disease pipeline, expanding our activities in oncology, and investing in the TransCon technology platform including for lonapegsomatropin, buildup of commercial inventory ahead of a potential launch; execution of commercial prelaunch and launch activities; investments in expanding commercial manufacturing capacity to support anticipated future demand; continued execution of the foresiGHT Trial, a global Phase 3 randomized controlled clinical trial in adult GHD and continued execution of the riGHt Trial, a Phase III randomized controlled clinical trial in pediatric GHD in Japan. For TransCon PTH, continued execution of the Phase II PaTH Forward Trial, execution of the PaTHway Trial a North American and European Phase III randomized controlled clinical trial in adult hypoparathyroidism, and an increase in manufacturing costs related to the production of PPQ batches for anticipated regulatory filings in the first half of 2022. For TransCon CNP, execution of the clinical program which includes two randomized controlled Phase II clinical trials in achondroplasia, the ongoing ACcomplisH Trial and the ACcomplisH China Trial which is being conducted through our strategic investment in VISEN Pharmaceuticals. And lastly, in our oncology therapeutic area, execution of the transcendIT-101 clinical trial of TransCon TLR7/8 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 continue to remain on track for hitting our corporate milestones for lonapegsomatropin with a PDUFA date of June 25, 2021. We anticipate approval for pediatric GHD in the US in the second quarter, followed by a commercial launch in the third quarter and we anticipate European Commission approval for pediatric GHD in the fourth quarter. For TransCon PTH, we expect to report in the fourth quarter top line results for the Phase III PaTHway Trial in North America and Europe for adult hypoparathyroidism and 84-week results from the open-label extension portion of the PaTH Forward Trial. TransCon CNP, we expect to provide a clinical program update in the fourth quarter. For TransCon TLR7/8 Agonist, we anticipate initiating dose escalation in combination with a checkpoint inhibitor in July for transcendIT-101 and we plan to present initial monotherapy dose escalation results for transcendIT in the fourth quarter. And finally for TransCon IL-2 beta/gamma, we plan to submit an IND or similar filing in the third quarter. Before we open up the call for questions, I want to reiterate a few points about our anticipated commercial activities for lonapegsomatropin in 2021. We anticipate approval for pediatric GHD on the PDUFA date of June 25. During the third quarter we expect to have product available in the US for pediatric GHD. During the third quarter 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 finally, during the fourth quarter we anticipate European Commission marketing approval for pediatric GHD. We plan to provide guidance on the timing of the launch in Europe later this year. With that operator, we are now ready to take questions.

Our first question comes from Jessica Fye with JPMorgan. Your line is now open.

Hey guys, good afternoon. Thanks for taking my questions. I feel like you just said multiple times in this call that you're still expecting approval on the PDUFA date for TransCon Growth Hormone, but we're still getting a bunch of questions related to this being a drug device application. So on that note, I was wondering if you could talk about what interactions, if any, you're having with the device division of the FDA on TransCon Growth Hormone? And maybe is it possible to have a finalized drug label, but still have outstanding issues that need to be resolved around the device?

Thank you for the question. What we are doing is consistent with our usual practice in endocrinology, which is to develop a combination product. This approach has always allowed us to bring a unique differentiated product to market. Regarding your inquiry about the device and related matters, this is simply part of our standard product development process. Based on the questions we've received and our interactions with the FDA, especially the device division, which we've been working with for the last six to seven years during the design of all the factors study, I feel confident about our position. Currently, we are in a favorable place. We've completed all essential inspections and still have interactions with the FDA, primarily for clarification on manufacturing size. These questions, which typically would be addressed during an on-site inspection, are now being handled through standard email correspondence. Overall, it's reassuring to be where we are now because the discussions regarding labeling have advanced as we anticipated. Everything we have observed and our current status align with our expectations for our PDUFA date since we filed. Dana, do you have any additional comments?

No, I think you've really sort of laid it out nicely. And Jess, it's really just because it is a combination product, so you can't sort of get approval on one part of it without the other, right? So they go hand-in-hand. And as Jan said, we've been responding to all of the requests and so have our manufacturers including drug substance and drug product manufacturers, as well as the device manufacturers. So they've received what they asked for.

And don't forget we are less than one month now. I think it's the 25th or 26th.

Great. Thank you.

Thanks, Jess.

Thank you. Our next question comes from the line of Michelle Gilson with Canaccord Genuity. Your line is now open.

Hi. Thank you for taking my question. In your prepared remarks Jan, you mentioned that the labeling discussions are going well and you anticipate a label – the label will support the scientific basis of TransCon Growth Hormone and its comparable mode of action to daily growth hormone. And I was just curious I guess two questions sort of around these discussions. Do you anticipate that that comparable mode of action to daily growth hormone offers any, I guess, benefit in terms of your positioning in a formulary or I guess the ease of – sort of interchangeability with daily growth hormone? And then are there ways in the language of the label that can highlight the differentiating aspects of TransCon Growth Hormone, compared to maybe some of the other acting growth hormone in development perhaps in – you mentioned immunogenicity and injection tolerability?

Thanks, Michelle. When I go to the mode of action, what I actually believe and what I feel most for is the patient. I feel that when I look directly on to the labeling text from the TransCon Growth Hormone product you released so much OP would be expected to have the same distribution as daily growth hormone, which we know it's the same industrious growth hormone, the same mode of action. I felt great for the patients because it gives me strong confidence that we are in a position that we can provide all the endocrine benefits that you have achieved with daily growth hormone. We can provide a treatment that basically is providing the same safety and what we have seen in our riGHt Trial in children with pediatric growth hormone deficiency, we also saw basically a better outcome. And the mode of action is basically the way you really decide the future of each single product opportunity because it's impossible later on to basically compensate away from the mode of action in the clinical data. And the specific question where we see it and the only way we basically can compare to for example, if we look on labeling for example on other long-acting products that got approved not far away, there was a clear discussion about also elements which are important related to the mode of action how well it distributes in the body. And there is a completely different labeling text that indicates how it's restricted compared to what you see in daily growth hormone. And I think from a scientific basis also providing a good explanation when you look on the clinical outcome you get the SOS product opportunity. So, that was why we designed from the beginning our TransCon Growth Hormone really to build on the last 25, 30 years knowledge about safety and efficacy that you give by releasing an unmodified somatropin, the same entity that you basically are having in daily growth hormone and also as an industrious product. And I see this is the benefit for the patient and I think that it also goes to the physicians. They also go to the payer because the payer will understand that we are providing a benefit for all the important endocrine health benefits that you expect to always to achieve by having daily growth hormone.

Thank you. Our next question comes from the line of Joseph Schwartz with SVB Leerink. Your line is now open.

Hi, I'm Joori dialing in for Joe. Thanks for taking our question. I was wondering how you feel about consensus sales estimates for TransCon hGH? What is the best way for us to model the trajectory of the launch ramp? And are there any good analogs or factors that could influence adoption in this market that hasn't seen much new treatment advancements in a while?

Yes, that's an intriguing question that I view from a different angle. As I mentioned in my prepared remarks, our goal is to establish a globally leading brand with TransCon Growth Hormone. Are the fundamentals in place for that? Can we become the leading brand in the US? Everything I've observed regarding this product opportunity and the competitive landscape strengthens my confidence that TransCon Growth Hormone will emerge as the leading brand in the growth hormone market. This is crucial for me. We aim to be the top brand not just in the US, but also in Europe, Japan, China, and everywhere we can reach. Our path to achieving this involves optimizing value creation and market penetration. I see a product opportunity where there's a rush for rapid penetration at the expense of creating value. We have a pipeline concept in place with multiple products set to be launched sequentially, including label expansions. My primary focus is not solely on projected sales for 2022, but rather on how quickly and effectively we can maximize the value from TransCon Growth Hormone. This is our main concentration moving forward. We will enhance value and improve penetration as we build our strategy.

Thank you. Our next question comes from the line of Josh Schimmer with Evercore. Your line is now open.

Thanks for taking the questions. I have two. One is on TransCon PTH. We've talked in the past about the need to shift the treatment paradigm to broaden the patients that physicians deem suitable for PTH replacement and not just calcium and vitamin D supplementation. So, maybe you can give us a sense as to how you feel that's evolving and progressing now that you have more of the TransCon PTH data in hand? And then second, and I'm sorry if I missed this, but I think on the last update, you had indicated that you're working on a new franchise for the TransCon platform, a new target? When might we hear more about what that franchise might look like? Thanks.

Thank you, Josh. I have always believed that TransCon PTH will be a significant advantage for patients. What truly matters, however, is whether physicians and patients themselves recognize these benefits. When examining all facets of the data, including biochemical results and quality of life, we observe substantial advantages. The stories we hear from patients about returning to normal lives and experiencing major transformations are compelling. Moreover, key physicians treating patients with TransCon PTH are also acknowledging these benefits. Our objective is to provide treatment for the entire diverse group of hypoparathyroidism patients included in our Phase 2 trial, regardless of disease spectrum or severity, and all of them are experiencing positive outcomes recognized by their physicians. Interestingly, about six months ago, many physicians noted they would accept only a subset of patients, whereas now they are willing to accept all patients. This communication is essential as we continue to treat more patients with TransCon PTH, and it relates to our goal of achieving hormonal replacement for this larger patient group. In our Vision 3x3 framework, we have established three supporting layers. We have progressed with our late-stage pipeline in rare disease endocrinology and are starting clinical development this year, with two oncology clinical programs underway for multiple indications. Our Vision 3x3 serves as our strategic pathway to build a leading sustainable biopharma company, which includes pursuing a third indication that we are currently defining with lead candidates. We believe that late 2022 or early 2023 will be an appropriate time for us to share more about our pipeline and reveal details regarding this third supporting layer.

Great. Thank you.

Thank you. Our next question comes from the line of David Lebovitz with Morgan Stanley. Your line is now open.

Thank you very much for taking my question. Once TransCon HGH gets approved, how do you expect payers to come online as the year progresses going into next year? And what do you expect the landscape ultimately to look like? Do you expect to go for broad coverage with a wide array of payers, or do you expect to be more selective in how you work with payers?

I can start with the initial answer and then Jesper can follow up. But what we're doing is that, as I have some way communicated before, we are on a pathway to develop a leading brand with our TransCon Growth Hormone. In building that, we also are building in such a manner that we are creating value in a way where we're feeling we're optimizing the entire brand because we need to invest in the brand. We need to invest in global reach, in label expansion, and that is what we're doing both in adult growth hormone deficiency and we will also have other indications, other trials we will do to really invest in building up this leading brand. What we're doing is that we have a state progress to make a global commercial reach, meaning is that the first place we rollout is in the U.S. Then we have Europe, and then we have China, we have Japan, and then you can take the rest of the world. So from that perspective, we also believe in a global price structure, globalization much, much, much more. So from our perspective, we integrate all this. And this is only a small step what we do initially. But what we are basically building as a model that basically says how can we build out the leading, global brand specifically in the U.S. if you only talk about that, a leading brand in the U.S. and create the most value. So we will optimize it in the best possible way and then we will be starting to ensure that the value of TransCon Growth Hormone will basically take in and sell you more and more patients with more and more physicians that see the real value we provide to TransCon Growth Hormone. Jesper, specific for U.S. will you further comments on it?

We have an excellent product, and we expect that to be reflected in our market pricing. Our primary focus will be on the commercial market, as it presents the largest business opportunity for us. We are determined to establish our market leadership based on the value we provide. While we won't pursue every single account for broad availability, we will certainly concentrate on the valuable opportunities in front of us.

I think this is a great way to answer it is actually describe what we would do with each of our pipeline product opportunities.

Thank you for taking my question.

Thank you. Our next question comes from the line of Alethia Young with Cantor Fitzgerald. Your line is now open.

Hey guys, thanks for taking my question, and looking forward to the next month. I guess, I just wanted to talk a little bit about on the growth hormone side on the socioeconomic claims and the benefits to having your product versus others, and how you think about balancing that as you think the price of the drug? Thanks.

So mainly the pharmacoeconomic calculation we have done is basic not looking at different brands, but mainly focused on the benefit of being on growth hormone treatment compared to not having the growth hormone treatment available or potential stopping earlier in a growth hormone treatment because of the high burden of a daily injection. And I think this is where we basically have done most of our claim analysis. When you compare different brands, I actually think that you should for me at least when I'm looking from thinking about the patient, the physician and the payer, you need to look at what you're providing of integrated benefit related to endocrine health, because this is where the social economic calculation takes in because it's not only hype, this is the entire way to having the right way to do remodeling on the body, meaning growth hormone so much of we need to distribute everywhere in the body. Cognitive effect, which are impossible to measure in children but we know growth hormone has a cognitive impact because there are also a lot of growth hormone receptors in the brain. All that is the part of why we believe it was so important for us that everyone could understand our mode of action is building on what we know that daily treatment can give because we have the same active ingredients out there. And I think this is where we strongly believe in the benefit we can provide in endocrine health is really being correlated out to the same way and I believe much, much better than you actually receive with daily growth hormone because we don't have the high treatment burden. And therefore, we will both get better adherence and then potentially lead to better outcome.

Our next question comes from Anita Dushyanth with Berenberg Capital. Your line is now open.

Hi, good afternoon. Thanks for taking my question. Jan, you mentioned the preliminary 58-week results related to TransCon PTH. Could you share what we might expect from the 84-week data? Specifically, what insights do you anticipate beyond just the safety data? Thank you.

Yes. That is always a great question regarding our expectations. If we look back at the 26-week, 54-week, and then 84-week periods, it’s going to be interesting because between 26 and 54 weeks, we observed the durable response we had hoped for. What we anticipated during this time was pretty predictable. The unknown factor for us was when we would see the normal remodeling of the bone structure kick in, particularly since we are running a trial with 58 patients receiving physiological PTH treatment for the first time in history. If you look at non-surgical hypoparathyroidism patients, you can see that their high-density bone structure is unhealthy and leads to larger fractures. Our goal was to integrate our hypoparathyroidism treatment with TransCon PTH to restore normal bone remodeling and, consequently, improve their health. We actually started to see this happening potentially a bit faster than expected. By the 84-week mark, we observed the bone markers declining and trending closer to normal levels. I believe this trend will continue, and we will see similar improvements in bone density, moving towards a normal bone structure and reduced fracture risk. That will be the main difference, and from a safety perspective, there were no issues between the 26 and 54-week marks; the safety remained excellent. We also noticed some patients had improvements in their kidney filtration rates early on, which turned out to be quite positive. Overall, I believe that the progress we observed at 26 weeks and now at 50 weeks is consistently heading in the right direction, indicating that we are effectively restoring normal function through novel physiological PTH levels.

That’s very helpful. Thank you.

Thank you. Our next question comes from the line of Tiago Fauth with Credit Suisse. Your line is now open.

Hey, thanks for taking the questions. Just a quick follow-up on CNP. So, you alluded that you want to keep the data blinded so what exactly could constitute the clinical program update in Q4? And what is currently your regulatory strategy or view to the best of your knowledge on what that could look like for that program? Thank you.

Thank you, Tiago. We frequently discuss this topic, especially during our dose escalation phase. A key focus is on safety, which can be evaluated in a blinded manner. If we notice any issues, we may consider unblinding to identify their source. In this trial, we have observed everything we anticipated in terms of safety, with no injection site reactions or cardiovascular risks detected. Therefore, we can confidently say this treatment is very safe. Currently, we are continuing the dose escalation while keeping each cohort blinded for one year. Our objective is to determine one or two doses for cohort expansion, and we aim to achieve this within the year. By year-end, we plan to provide an update on our progress across various trials, including the two independent Phase II trials. We are carefully considering how to share information without compromising the blinded nature of the study. I'm optimistic that we will have an interesting update to present at the end of the year.

Perfect. Thank you.

Thank you. Our last question comes from the line of Yanan Zhu with Wells Fargo. Your line is now open.

Hi. Thanks for taking my question. In terms of pricing of TransCon GH, I know you touched upon it from a strategy perspective. Just wondering, would we be looking at a price that is at a significant premium to daily, and if you can clarify on that? And also, do you plan to access the other pediatric indications for the growth hormone market like Turner syndrome and idiopathic short stature, which collectively could account for as much sales as the growth hormone deficiency indication? Thanks.

Relating to your first question, Jesper came with a clear statement. We have a superior product, we will expect superior pricing. I think there was a clear statement from Jesper, which I'd say everything. To the second question, we are dedicated to global reach label expansion. Global reach is to go everywhere in the world. The label expansion, we already started on. We have our foresiGHT Trial, which our adult growth hormone deficiency. And currently now we're discussing, what extra indication is we want to pursue in. And there's a series of interesting at this you can say indication we can pursue. And I think we have a great clinical team that basic are coming up with a very, very smart clinical design perspective, so we really can do what we want to do, ensuring there is a label expansion of our TransCon Growth Hormone to build it up to the leading brand and we will also go for the necessary indication to achieve that.

Got it. Great to know. Thank you.

Thank you. There are no further questions. Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.