Ascendis Pharma - Q4 2022
February 16, 2023
Transcript
Operator (participant)
Good day. Thank you for standing by. Welcome to the Ascendis Pharma Full Year 2022 Financial Results Conference Call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one-one on your telephone. You will hear an automated message advising your hand is raised. To withdraw your question, press star one-one again. Please be advised that today's conference call is being recorded. I would like to turn the call over to now your speaker for today, Tim Lee, Senior Director of Investor Relations. Please go ahead. The floor is yours.
Tim Lee (Senior Director of Investor Relations)
Thank you, operator, and thank you everyone for joining our Full Year 2022 Financial Results Conference Call. I'm Tim Lee, Senior Director of Investor Relations at Ascendis Pharma. Joining me on the call today is Jan Mikkelsen, President and Chief Executive Officer. Scott Smith, Executive Vice President and Chief Financial Officer. Dr. Stina Singel, Executive Vice President, Head of Clinical Development, Oncology. Joe Kelly, Senior Vice President, Head of U.S. Commercial Endocrinology. Before we begin, I'd like to remind you that this conference call will contain forward-looking statements that are intended to be covered under the Safe Harbor provided by the Private Securities Litigation Reform Act. Examples of such statements may include, but are not limited to our U.S. commercialization and continued development of SKYTROFA for the U.S. market, the commercialization of TransCon hGH for the EU market.
Statements regarding the expected timing of approval and launch of TransCon PTH in the U.S. market this year. Statements regarding the expected timing of approval of TransCon PTH in Europe. Statements regarding the potential size of the TransCon PTH the market size for TransCon PTH. 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, including the timing of clinical results. Statements regarding our pipeline product candidates. Statements regarding our planned regulatory filings, our expansion into new therapeutic areas, and statements regarding the ability to create a sustainable leading global biopharma company. These statements are based on information that is available to us today.
Actual results and events could differ materially from those in the forward-looking statements, and we may not be able to achieve our goals, carry out our plans, our intentions, our expectations or projections disclosed in our forward-looking statements. 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 our forward-looking statement section in today's press release and the Risk Factor sections of our most annual report on Form 20-F, which is being filed today, February 16th, 2023.
TransCon human growth hormone or TransCon hGH is approved by the FDA in the U.S. under the brand name SKYTROFA for the treatment of pediatric patients one year or older, weighing at least 11.5 kg and have growth failure due to inadequate secretion of endogenous growth hormone. In addition, the European Commission has granted a marketing authorization for SKYTROFA to Ascendis Pharma, developed under the name TransCon hGH. Is a once-weekly subcutaneous injection for the treatment of children and adolescents aged 3-18 for growth failure due to insufficient secretion of endogenous growth hormone. In general, we refer to this product as TransCon growth hormone unless we're referring to the product in the context of particular jurisdictions such as the United States or the European Union. Otherwise, please note that our product candidates are investigational and are not approved for commercial use.
As investigational products, the safety and effectiveness of their product candidates have not been reviewed or approved by any regulatory agency. None of the statements made on the conference call regarding our product candidates shall be viewed as promotional. On the call today, we'll discuss our full year 2022 financial results. We'll provide further business updates. Following some prepared remarks, we'll then open up the call for questions. I'll now turn the call over to Jan Mikkelsen, President and Chief Executive Officer. Jan.
Jan Mikkelsen (President and CEO)
Thank you so much, Tim. Ascendis is built on the unique TransCon technology platform, which enables development of highly differentiated product candidates across multiple therapeutic areas. Combining the TransCon technology with our algorithm for product innovation has enabled us to create and develop product candidates with a higher likelihood of success than seen with conventional drug development. One of our key product selection criteria is to fulfill best in class potential on each of the four key pillars of drug development. Safety, efficacy, tolerability, and convenience. In addition, each product candidate must have the potential to achieve $1 billion or greater revenue in a single therapeutic indication. With this approach and driven by our values of patience, science, and passion, we have demonstrated our ability to continuously build out a robust pipeline while taking product candidates from concept through approval and launch.
With expected regulatory approvals of a new product or additional indication every 1-2 years, we are fulfilling our Vision 3x3 goal of building a sustainable, profitable, leading biopharma company and creating long-term value for all stakeholders. This past year, we have advanced our pipeline as planned. Entering 2023 with an April 30 PDUFA date, an expected U.S. launch of TransCon PTH for adult patient with hypoparathyroidism by the end of Q2, along with an expected European Commission decision during Q4 as well. TransCon PTH is our second endocrinology rare disease product opportunity, representing a potential global opportunity greater than $5 billion. Turning to TransCon CNP. Last November, we reported 12 months data from the first-ever randomized double-blinded placebo-controlled phase II trial in children diagnosed with achondroplasia.
These results give me confidence that this third endocrinology rare disease product candidate may have its first approval by 2025 as targeted in our Vision 3x3. Another component of Vision 3x3 is label and geographic expansion. We continue to build the value of our existing programs through additional clinical studies for label expansion and global commercial reach. Starting with our newly expanded European organization, which is preparing for launch of SKYTROFA in Germany this year, and if approved, TransCon PTH next year. With this great momentum across our pipeline, I would like to review additional details from our major programs. Turning to growth hormone. During the fourth quarter of this year, we plan to report top-line results from our global phase III foresiGHt trial in adult growth hormone deficiency, our potential second indication for TransCon Growth Hormone.
Adult growth hormone deficiency is a serious endocrine rare disease characteristic by abnormal body composition, dyslipidemia, insulin resistance, and impaired quality of life. Analysis has shown these consequences of adult growth hormone deficiency result in mean analyzed healthcare costs more than 4x that of a non-growth hormone deficient population. TransCon Growth Hormone is the only once-weekly growth hormone product releasing unmodified somatropin, we expect it to be the first adult growth hormone treatment to meet or exceed the safety, efficacy, and tolerability of daily growth hormone. Meanwhile, in the U.S., SKYTROFA is experiencing the commercial success it deserved because of its unique product strengths. As we pre-announced during JPMorgan, fourth quarter 2022, U.S. SKYTROFA revenue grew to EUR 17.1 million, providing a strong fundament for growth in 2023 and after.
With our progress towards label expansion and planned commercial launch in markets outside the U.S., we believe we are on track to build SKYTROFA into the leading growth hormone product in value by increasing the total market size. As we have predicted, we are seeing the consolidation of the daily growth hormone market as other manufacturers begin to exit the U.S. market. Turning to TransCon PTH, excitement continues to build among stakeholders around this potential treatment for adult patients with hypoparathyroidism ahead of the upcoming PDUFA date of April 13. Our expanded teams are hired, trained, and working to deepen physician and payer awareness of this serious health and quality-of-life issue that hypoparathyroidism causes.
We have already made more than 2,000 calls to physicians related to disease awareness, and we are encouraged by their interest in learning more about the multi-organ impact of this disease and its negative effect on patients' quality of life. Our commercial team, medical affairs, field reimbursement, and our manufacturing teams are ready to launch TransCon PTH in the U.S. market as soon as possible after approval. Importantly, we are launching TransCon PTH, our second endocrinology rare disease product, with the same commercial infrastructure that has proven its success with SKYTROFA. Coming back to CNP. As we did with TransCon Growth Hormone and TransCon PTH, we ran a robust phase II trial to confirm TransCon CNP's target profile on all four key pillars: safety, efficacy, tolerability, and convenience, and de-risk it at the phase II level.
This can only be done with a robust, randomized, placebo-controlled trial that will mimic the pivotal trial. We saw clear success in the COMET trial with TransCon CNP, demonstrating superiority over placebo at the 12 months primary endpoint in children aged 2-10. In addition, we saw clear dose response. All 57 patients who started this trial remain in the open-label extension today. To extend and confirm this result, including positive treatment effect observed on achondroplasia-related comorbidities, we are running our phase IIb ApproaCH trial. As investigators are aware of the phase II results, we are experienced very high insurance in our ApproaCH trial, and we expect to complete target enrollment of around 80 patients in the next quarter.
During our upcoming end of phase II meeting with FDA, we expect to collaborate on how to best achieve a broad treatment labeling rather than a linear growth labeling alone. Shifting to oncology. We are progressing with the developing of our two novel immuno-oncology programs, TransCon TLR7/8 Agonist and TransCon IL-2 β/γ. With these two clinical programs, we are positioned this year to start evaluation of clinical efficacy in seven specific tumor types, nine different indications with four different combination therapies, including by combining our two TransCon oncology product candidates with each other. Clinical proof of concept phase II top-line results are expected starting in 2024. In addition, this year we will initiate the randomized phase II trial, BelieveIT-201, using TransCon IL-2 β/γ and TLR7 Agonist combination therapy in head and neck cancer.
As we successfully demonstrated with our endocrinology programs, we are building a solid phase II clinical proof of concept for our oncology products in multiple tumor types in the next one or two years. You can see, we have and will always focus on achieving best-in-class product profiles to benefit patients on the four key pillars of safety, efficacy, tolerability, and convenience, areas in which we will not compromise. This development approach, including extremely robust clinical trial design, has positioned Ascendis to potentially launch a new product or indication every 1-2 years, building sustainability, long-term value for all stakeholders. Each successful clinical trial further confirms the power of the TransCon technology platform and our product innovation algorithm, and increases our confidence and likelihood of success for future product candidates.
With an expanded pipeline and commercial successes, Ascendis remains on track to meet or exceed our goals outlined in our Vision 3x3. I will now turn the call over to Scott for a financial review before we open up for questions.
Scott Smith (EVP and CFO)
Many thanks, Jan. To follow on Jans comments, we are excited to see the realization of Vision 3x3 with a continued flow of new products and additional indications every 1-2 years. For example, as Jan noted, we expect to launch TransCon PTH in the U.S. and SKYTROFA in Germany this year, followed by the first European country launch of TransCon PTH in early 2024. With results for SKYTROFA in adult growth hormone deficiency and TransCon CNP and achondroplasia on the horizon, we expect this cadence of approvals and launches to continue beyond 2024. In this way, we are creating sustainable long-term value for Ascendis and our stakeholders through our proven R&D development capabilities. I will quickly touch on a few points.
For further details on our full year 2022 financial results, please refer to our Form 20-F, which is being filed today. As we previously announced in early January, SKYTROFA U.S. revenue for the fourth quarter of 2022 grew to EUR 17.1 million. These results exceeded the algorithm that Jan laid out last May, which projected EUR 60 million. For the full year 2022, total revenue was EUR 51.2 million, including SKYTROFA revenue of EUR 35.7 million, as well as licensed clinical supply and services provided to third parties, primarily VISEN Pharmaceuticals. With profitable growth of SKYTROFA, our overall operating loss grew about 2% sequentially to EUR 147.4 million for the fourth quarter from EUR 144.5 million in the third quarter of 2022.
We ended 2022 with cash equivalents, and marketable securities totaling EUR 743 million. As Jan described at the JPMorgan conference, annualizing fourth quarter SKYTROFA revenue of EUR 17.1 million provides a foundation for 2023. We expect to add at least as many reimbursed patients this year as we did in 2022, which would provide even greater growth. At this time, we believe we are on track to exceed the current Ascendis compiled consensus estimate for 2023 SKYTROFA revenue of EUR 96 million. TransCon PTH, our PDUFA date is April 30th this year. If approved, we expect to begin shipping product by the end of the second quarter. A quick reminder on selected key 2023 corporate milestones.
For TransCon growth hormone, as mentioned, we plan to launch SKYTROFA in Europe, starting with Germany in Q3. We also expect to report top-line data from the global phase III foresiGHt trial in adult growth hormone deficiency, our second indication in Q4. TransCon PTH, we are planning for FDA approval by the PDUFA date of April 30 and launch in the U.S. by the end of Q2. We expect the European Commission decision in Q4. For TransCon CNP, we are on track to complete enrollment of the phase IIb ApproaCH trial in achondroplasia in Q2. Within our oncology therapeutic area, we expect to report top-line results and declare the recommended phase II dose from monotherapy dose escalation cohorts for TransCon IL-2 β/γ later this quarter, and to declare the recommended phase II dose from TransCon IL-2 β/γ combo therapy with checkpoint inhibitor in Q3.
Finally, as you see with our reporting today, continued optimization of finance systems and processes have enabled us to accelerate our year-end reporting. With that, operator, we are now ready to take questions.
Operator (participant)
Thank you. Our first question for today will be coming from Jessica Fye of JPMorgan. One moment please while I open your line.
Jessica Fye (Managing Director and Equity Research Analyst)
Thanks for the comments on how to think about SKYTROFA sales this year. Can you comment on your comfort level with consensus estimates for TransCon PTH this year? Actually, while we're at it, where is that consensus figure based on your latest compilation of the analyst numbers?
Jan Mikkelsen (President and CEO)
Jess, are you reflecting into SKYTROFA or TransCon PTH?
Jessica Fye (Managing Director and Equity Research Analyst)
For PTH.
Jan Mikkelsen (President and CEO)
I actually have not looked on the consensus number for PTH. I don't think we have collected that information, so I don't think we can really address that. We can mainly address the places where we feel confident to give an algorithm that can reflect our expectation as we have done from SKYTROFA.
Jessica Fye (Managing Director and Equity Research Analyst)
Okay. I'm gonna ask something else then. Can you tell us how many cumulative new patient prescriptions there were for SKYTROFA as of year-end? I think you were previously giving that quarter by quarter. Can you also tell us when we should look for the next update from the phase II extension for TransCon CNP?
Jan Mikkelsen (President and CEO)
Let us just go back to how we basic are looking on the forecasting related to the revenue of SKYTROFA in the U.S. in 2023. We have seen in here in 2022, that month by month we have increased the number of new patients that got reimbursed, and we have continued to see this trend also in 2022. This is why it was important to look on the fourth quarter, because we're also seeing, at the same time, we're seeing an really, really strong retention. When you start on SKYTROFA, you stay on SKYTROFA. When we take the EUR 17.5 million and multiply that with four, Scott is calculating, it's about EUR 70 million.
You know, we basic will expect an acceleration of the number of new patients because of lot of good reason, and I can come back to that, Jess, if you want that. We actually expect to see more patients per month of new reimbursed patients than we actually saw in 2022. We feeling really, really confident that we will exceed the consensus number that is out on the street today related to SKYTROFA. The element that basic are providing our increase in number of monthly new reimbursed patient is that the physician is starting really to get the knowledge about the product strength of SKYTROFA. It's not something you experience in one month. You need to see six months, 12 months growth data, and this is what we are starting to see.
We're really seeing how we really have a highly differentiated product compared to daily growth hormone. The other point is that we see the consolidation of the daily growth hormone market that started for about three years ago, where we saw after our phase II data that the consolidation of the daily growth hormone market is really kicking in now. There is a major switch away from some of the six daily growth hormone player, which all have the same product. This is why we feel very confident about how we really will grow SKYTROFA into the most valued product in the growth hormone market in the near future. Related to CNP, you had a question related to CNP. Just perhaps you can specify exactly what you wanted to know there.
Jessica Fye (Managing Director and Equity Research Analyst)
Well, I think in the past you had talked about the high velocity for a proportion of patients that had been on out to a certain time point, and I think we're gonna maybe update that when all of the patients got out to that time point. Is there-
Jan Mikkelsen (President and CEO)
Exactly.
Jessica Fye (Managing Director and Equity Research Analyst)
plan to update that data, when should we expect it?
Jan Mikkelsen (President and CEO)
Yes, we are planning to give you this data. We think it's extremely important to give you this data where we see the continuous effect of Ascendis Pharma's TransCon CNP, because I'm still in this extremely struggling manner, and this is what we really have got a lot out of analyzing all the data for our ACcomplisH trial to find out why they're staying 100% on this treatment. We're starting to get a much, much better understanding of that. This is why we will now are discussing with regulatory agencies, how we can have other secondary endpoint that really are reflecting how we are addressing really the comorbidities and not just linear growth. Linear growth is not really the biggest issue for this patient group. Basic, the comorbidity and other effect of disease.
This is where we believe TransCon CNP is a unique product because you have continuous exposure of the CNP molecule and therefore changing things that is not only related to linear growth.
Operator (participant)
Thank you. Our next question will be coming from Tazeen Ahmad of Bank of America. As a reminder, please limit yourself to one question and one follow-up and get back in the queue if you have additional questions. Thank you.
Tazeen Ahmad (Managing Director)
Thanks for taking my question. As it relates to PTH, can you just give us an update, if you haven't already, on how many patients you've enrolled in the early access program so far? Do you have a sense of how many patients will be enrolled in that program by the time of the PDUFA and then following with the launch? Thanks.
Jan Mikkelsen (President and CEO)
I think that is an extreme. First of all, we are extremely pleased with how the program is progressing and our regulatory interaction, and also that we got the approval to start an EIP program, which basically can give the opportunity to get patients under the treatment before we get the expected approval. We are executing on that, really starting the entire system, and we will explain when we come to the approval process, what is the number of patient we will have in this trial and also how we continue with these patients.
Tazeen Ahmad (Managing Director)
Maybe just to follow up then. Would you expect that to be an early source of patients to convert to commercial?
Jan Mikkelsen (President and CEO)
I just think we are addressing a key element in the EIP program. We are addressing the patient group that already were experienced with a PGH treatment regime, a short-acting PGH treatment. It could be Natpara, it could be Forteo, it could be Tymlos or someone else, but that was exactly what we're addressing. The last population where we basically recruited patients to our phase 2 program and our phase 3 program, they're coming from what we call patients that never really have been exposed to PGH treatment. I don't see that is really a differentiation between these two patient group. I think both patient group have the same high unmet medical need. They have the same benefit of the PGH treatment. I don't see any kind of difference between these two group related to be fast starter in our programs.
Operator (participant)
Thank you. Our next question will be coming from Tazeen Ahmad of Bank of America. Your line is open. Tazeen Ahmad of Bank of America, your line is open.
Scott Smith (EVP and CFO)
I think she just asked the question, so I'd go to the next one.
Operator (participant)
Thank you. One moment. The next question is coming from David Lebowitz of Citi. Your line is open.
David Lebowitz (Senior Research Analyst)
Thank you so much for taking my question. As the PDUFA date is approaching, could you give us any insight into what the label might ultimately look like? I know that Natpara was considered an adjunct. You seek to be going more as a hormone replacement, and Natpara has the presence of a black box for osteosarcoma, but you didn't really have an osteosarcoma experience. Could that black box be removed? Just be curious to hear your thoughts.
Jan Mikkelsen (President and CEO)
Thanks, David. I think when we look on the biology and the product design of TransCon PTH, we are providing a stable physiological level of PTH 24 hours, seven days a week. We are not providing any hyper physiological concentration of PTH that can provide to the anabolic effect that in animal model have been associated with osteosarcoma, specific the rat model. How from that perspective is that, and also why we got a waiver to make a carcinogenic trial or animal trial, we will not expect, and we have not seen any indication in our labeling discussion that we will be coming in the same, you can say, group of short-acting PTHs that basically got the same class labeling, because we are providing a complete different product profile than the short-acting PTHs.
To our best knowledge today and in our discussions, we don't expect any REMS program, and we don't expect any black box warning. That was your first question, and you're quite right. How we designed TransCon PTH was really to prove a product profile that was reflecting hormone replacement instead of an adjunct, thus why to be successful in the clinical trial, you need to stop 100% from active vitamin D. You also need only to take calcium supplement that really are just reflecting a normal multivitamin from Costco. We are really addressing a complete different product profile.
David Lebowitz (Senior Research Analyst)
Thanks for taking my question.
Operator (participant)
Thank you. One moment while we prepare for the next question. Our next question is coming from Li Watsek of Cantor. Your line is open.
Li Watsek (Research Analyst)
Hey, thank you for taking my questions. I guess for TransCon PTH, just wondering if you can share some of the latest feedback that your sales team maybe received from, you know, payers and physicians. Then maybe talk about your latest thoughts on how you might approach pricing, and market access. Thank you.
Jan Mikkelsen (President and CEO)
When I think about the patients, when I think about the physicians, the message has not been different for the latest year. Everyone recognize that hypoparathyroidism is a serious disease, everyone understand the benefit of replacing a missing hormone with a physiological level 24 hours, seven days a week. How it both address short-term symptoms like quality of life, urinary calcium, but also long-term risk. What we're seeing is that the awareness of that is being building up much, much more about the awareness of the disease. I believe this is where we come in with our education first telling about the awareness of the disease, which are really a big part of what is happening today with all our established infrastructure here in the U.S.
After an approval, we can go out and explain how we can benefit this kind of disease, both short-term and long-term. I really feeling that we are right. What we did with SKYTROFA is the guidelines we do with always our product. We develop best-in-class products addressing real unmet medical needs. We take a premier responsible pricing situation where we believe if you really develop a product that really address a real unmet medical need with a real product, that is enough for both the patient, the physician, the society, and the payer for us to share that cake. Then everyone is winner, no one is loser. This is where we want to be with each of our products. We need to have them so highly differentiated, addressing a real unmet medical need, and everyone believe it's a win for everyone.
We can see that with TransCon PTH.
Li Watsek (Research Analyst)
Great. Thank you.
Operator (participant)
Thank you. One moment while we prepare for the next question. Our next question is coming from Paul Choi of Goldman. Your line is open.
Paul Choi (Executive Director)
Thank you. Good afternoon, and thanks for taking our questions. I want to ask, given that you're using the same infrastructure to market PTH in the U.S. that you're currently using for SKYTROFA, I guess, are there any learnings that you might, you know, share from the launch of SKYTROFA that you would think be applicable? Or what changes would you make, I guess, in terms of either your thoughts on approaching, you know, payer access, and/or contracting compared to SKYTROFA? Then I had a pipeline question as a follow-up.
Jan Mikkelsen (President and CEO)
Great. Let me start on that. We are utilizing the same infrastructure. Sure, we have dedicated sales force. We will have dedicated people for the two different product. You know, there's a huge difference to be the first product to go out and launch, where you establish all the infrastructure, IT systems, all the different necessary teams that is necessary to really to launch a commercial product. We have de-risked that now. We're coming from a stage where we launch in form an already successful established commercial infrastructure built from Joe and the other people in Princeton here in the U.S. What we're doing is that we basically are placing what I call TransCon PTH into an infrastructure that already has proven its capability with a product, I believe, really addressing a huge unmet medical need, where there's no alternative treatment.
I think this is a fundament for a huge success.
Paul Choi (Executive Director)
Okay. Thank you. As a follow-up, just on terms of the pipeline, do you plan to publish the baseline patient characteristics for the 80 children that are being enrolled in the ApproaCH trial? Could you also specify, in terms of your oncology program, the head and neck population that you're planning to pursue? Is it just HPV-positive or is it post PD-1 and post Erbitux? If you could maybe add a little color on that would be great. Thank you for taking our questions.
Jan Mikkelsen (President and CEO)
I think, Stina will take number two, or you can take one, and I can take the other one. Let me take, number 1. It's a very, very interesting question because I do not know if the question the, where it's really are addressing, because I actually think we have published all the demographic from our patient population and demographic that have been into the ACcomplisH trial, the 57 that's still in it. I actually are somewhere a little bit puzzling with that question because all data is out. You can say, hey, why did you not, come in with the analyzed height velocity pre-screening. Because it's totally irrelevant for the clinical efficacy of it.
You cannot use an analyzed height velocity that have been collected before they go into the trial because we have `40% of the children between two and five. When you look and achondroplasia child is nearly built the normal analyzed height velocity, and the first four years you have a heavily deceleration of analyzed height velocity. If you take an analyzed height velocity just collected up to 12 months before they go into a trial, it's not reflecting any meaningful value that go in and compare to the analyzed height velocity you compare in this patient group because they start on the age already two. This is why you do what is obvious in drug development. You're making a placebo group. This is why you have a placebo group. I think that is the key element to do.
Look at our dosing from 6-100, then you can take six like, nearly like also a placebo group. Then you can take the six and/or the placebo, move them into the achondroplasia specific height assays and see are they matching. They're matching 100%. Compare this is my basic scientific nonsense and only are misleading and have not reflecting any kind of solid scientific value in interpolating the data. Stina?
Stina Singel (EVP and Head of Clinical Development and Oncology)
In oncology, we are evaluating for proof of concept efficacy in seven different tumor types. You're right, we do have one of our priority areas is head and neck cancer. We are evaluating in first or second line metastatic head and neck cancer as a dose expansion cohort single arm in the IL-Believe study. Those patients will be will have had no more than one line of chemotherapy-containing regimen in the advanced metastatic setting. The randomized phase II study, BelieveIT-201 study, will be in the neoadjuvant setting. These are patients in a non-metastatic setting. Before they get surgery, they will get systemic treatment before surgery. We're looking at pathologic response as our primary endpoint to look for evidence of proof of concept efficacy.
Jan Mikkelsen (President and CEO)
Thanks, Stina.
Operator (participant)
One moment while we prepare for our next question. Our next question is coming from Derek Archila of Wells Fargo. Your line is open.
Derek Archila (Managing Director and Biotechnology Equity Research Analyst)
Great. Thanks, and thanks for taking the question. Just two really quick ones from us. Jan, I just wanted to confirm, I thought I caught you saying that you were in labeling discussions for TransCon PTH. So I just wanted to confirm that. Also, I guess when should we expect additional updates from ACcomplisH? Is that something we should see, you know, again, first half of this year, second half of this year? Thanks.
Jan Mikkelsen (President and CEO)
When you go through an approval process, I think for me it's such a planned process. Four months before an expected approval date, this need to happen. Three months before an expected approval, this need to happen. Two months before that. If anyone somewhere have been to an approval process, I think we have 10 weeks before the PDUFA date now. You know, if you're not started a label discussion, the risk of not getting approval is high. Therefore, I believe this is where I'm tracking how we are progressing to the approval process. Are we really on track of what everything needs to happen for the expected time? If that's not happening, I will be extremely worried and find out what is going on.
Yes, we are in a label discussion because you should be that at least three months before an expected approval. This is why I feel that I'm confident that I have not seen anything that not give me a belief that TransCon PTH is a product that is approved. I believe, I cannot really remember all our corporate milestones now. Sorry for that, because that's a little bit too many of them. I believe that is in Q4, we will give you an update again related to the 57 patients that will come out from the ACcomplisH trial. It will be in the second half of this year.
Derek Archila (Managing Director and Biotechnology Equity Research Analyst)
Excellent. Thank you very much.
Operator (participant)
Thank you. One moment while we prepare for the next question. The next question is coming from Josh Schimmer of Evercore. Your line is open.
Josh Schimmer (Managing Director and Senior Biotechnology Equity Research Analyst)
Good. Thanks so much for taking the questions. First on SKYTROFA. Could you elaborate a little further on what you're seeing in terms of daily growth hormone options withdrawing from the market? I know there have been some reported shortages, but I didn't realize that reflected the full withdrawal. Who have you seen withdrawing and do you expect others to follow? How do you anticipate the impact of Novo Nordisk potentially launching a once a week growth hormone option as well in the market later this year? Thanks.
Jan Mikkelsen (President and CEO)
Thank you. Let me start first on the daily growth hormone, because I actually believe that it's a textbook really, and if I had taken an MBA, potentially I would have done that in my study and my final project. It's really what I call a textbook example. Growth hormone or the daily growth hormone market was the first that got biosimilar, where Sandoz and Teva entered there with their bioequivalent version on it. There somebody had six players in this daily market segment, all of them providing exactly the same entity, the same treatment. You can change this back and forward between the product dependent on rebate and other things like that. That was different in formulation. That was a little bit different in devices and other things like that.
What we saw for about three, four years when we came out with our phase II data, we saw already that some of the big player and many started some way to reconsider how do we really play it when that's coming and superior treatment into this segment, which will be highly differentiated compared to what we call the daily market segment. At that time, we already saw three of the companies basic removing their sales force. This is step one, as I call, you remove sales force. The second one is that you go to the next state, you remove the hub, then you stop up manufacturing, which, I think three or four of them have done it now.
You basically are in a position where you are providing mainly patients that already are established on your product because you have no hub where you can change and take new patient in and you're providing them. What happened, sadly enough, for the patient now that it looked like Novo Nordisk went into a shortage of multiple product, multiple presentation of their growth hormone. Because that consolidation of the data growth hormone had happened and really is in the final place, I believe none of the other one could take over. You have to see a shortage of growth hormone treatment in the U.S.
Sure, I need to accept that the benefit of that is a great thing for us because it's very both accelerating at the same time where people really see the benefit, get the clinical experience, how we differentiate it, be having patients for one year or something on treatment. We really see this benefit. I think this is a great thing for sure for us, and we are really hopeful we can help as many patients to avoid that going into a shortage of the treatment effect.
Josh Schimmer (Managing Director and Senior Biotechnology Equity Research Analyst)
Very helpful. Thank you.
Jan Mikkelsen (President and CEO)
Your second question, Josh.
Josh Schimmer (Managing Director and Senior Biotechnology Equity Research Analyst)
Actually, I was gonna ask whether given your view of the differentiation of TransCon CNP, if you'd considered filing for breakthrough designation.
Jan Mikkelsen (President and CEO)
Yeah. First of all, Josh, you also have the question reflecting about potential the intent of Novo Nordisk long-acting product. Look on the paradigm shift. I call it paradigm shift because it come from the time where all the daily growth hormone were identical, the same treatment, the same mode of action. You go over to the long-acting, all of them are providing complete different clinical profile. They're the only one that really match an improved version of the daily growth hormone, where you get all the benefit, endocrine benefit, both related to changing not only linear growth in the pediatric symptom, but also the other associated endocrine benefit like body composition, metabolic profile, lipid, muscle, cognitive effect, and everything that you see, because we have the same unmodified somatropin molecule.
This is why it's also important for us to look in our phase III in adult growth hormone deficiency. The two other potential long-acting where we believe there's potential one less now, but the OPKO Health showed basic, not any improvement on body composition in the phase III trial. Novo Nordisk showed that can only get the half of effect basic to daily growth hormone. This is where we believe with our unmodified somatropin, potentially we will be at least as good as daily growth hormone. We believe that our product profile is always so highly differentiated to both daily growth hormone and other long-acting growth hormone that we always will provide us the clinical benefit compared to all other treatment regimens.
Operator (participant)
Thank you. Our next question will be coming from Leland Gershell of Oppenheimer.
Leland Gershell (Managing Director and Senior Biopharma Analyst)
My questions. Two from me. Jan, I know you had responded earlier that you don't expect a REMS or a black box warning on the PTH label, but could you comment on any potential for monitoring requirements with patients on the product? Thanks.
Jan Mikkelsen (President and CEO)
Could you clarify your question? What do you mean exactly?
Leland Gershell (Managing Director and Senior Biopharma Analyst)
Well, in other words, if patients need to be monitored for, you know, serum calcium, bone biomarkers, whatnot.
Jan Mikkelsen (President and CEO)
That is a question where you will say, will we provide a better stability for this patient group than they have in their current setup, where they basically are being monitored for calcium really often. I believe you will see it in different stages. I believe when you transition over from what we call the conventional part of therapy over to TransCon PTH, I think there will be at least the same kind of monitoring, because you want to be quite sure you stabilize the patient in the right manner.
When they are stable, which we see after 1-2 year on a PTH dose, where we see more and more stability coming in because the calcium metabolic system gets, or calcium hemostasis starting to be stabilized, I will potentially see from a patient perspective that you will potentially need less, what we call monitoring of it. I think this is where I believe that element like bone marker, it's not typical something you typically will analyze for any patient group in this way. What we have seen in our clinical study where we now patient up for over three, four years, you're basically seeing that we do normalization more and more and more of every parameter. That is include both bone density and it's also including bone markers. I will not expect that it will be part of a standard monitoring.
Leland Gershell (Managing Director and Senior Biopharma Analyst)
Okay. Second question for me is, with respect to achondroplasia, obviously the primary endpoint and for regulatory purposes, it's about height velocity. As you had mentioned earlier, there are many other benefits that a replacement CNP could provide. Could you just sort of inform us as to which of the other benefits that may be not captured by primary endpoint type data, but would be very important, seen as most important by the achondro community? Thanks.
Jan Mikkelsen (President and CEO)
Yeah. I think this is why we're developing TransCon CNP. We really are developing it to provide a treatment that sure is addressing linear growth. We can combine it with SKYTROFA, I can from a clinical concept, I will expect nearly you can decide what kind of linear growth you will have. What we really want to ensuring that we are addressing the underlying comorbidities of the patient. How we measure them is to have specific achondroplasia, specific comorbidities. This is comorbidities that is coming and being reported on high frequent from the achondroplasia from when you see them on team. We also are developing a patient-specific reported outcome measuring, where we're trying to capture all the benefit they are feeling because they are really seeing a huge benefit.
One of the thing is clear for us, we see lot of other effects that's not just related to bone. We see muscle change, we see how they function better in the physical way to balance, do normal work, do normal operation, and other things like that. This is all this element we will try to capture. At the same time, we will capture the achondroplasia specific element like a number of injection and other things like that, which are.
Leland Gershell (Managing Director and Senior Biopharma Analyst)
Thanks. That's very helpful.
Operator (participant)
Thank you. One moment while we prepare for the next question. Our next question is coming from Andreas Argyrides, from Wedbush. Your line is open.
Andreas Argyrides (Research Analyst)
Hey, guys. Thanks for taking our question. When you're thinking about this is for PTH. When you're thinking about the launching opportunity in PTH, how are you thinking about it compared to the Natpara launch? Maybe you can, you know, give us some insights on how Natpara coming off the market, you know, at the end of 2023 is informing your expectations, you know, for the launch. I have a follow-up. Thanks.
Jan Mikkelsen (President and CEO)
I'm not comparing TransCon PTH in any way to Natpara. It will have complete different labeling, have complete different clinical outcome, have complete different clinical benefit. Just complete different impact on quality of life. I'm not using that as a benchmark on anything. I'm not comparing that. There was a product that came out with a labeling as an adjunct. This is not what we are addressing. There was a product that came out not seeing benefit on quality of life. It was a product that came out not showing any benefit of 24-hour urinary calcium, not really addressing the underlying disease. I don't use that at all to any benchmark. It's completely meaningless for me.
Andreas Argyrides (Research Analyst)
Okay, great. That's helpful. Maybe I guess maybe the opportunity that there is no approved product on the market. There were some patients, you know, mostly in Europe as well, who are still, you know, on it or that had access to it no longer. Are those gonna be early adopters or? Yeah, thanks. Then I have a follow-up.
Jan Mikkelsen (President and CEO)
I think actually this is exactly as somebody addressed before. Yes, there is patient that has been exposed to short-acting PTH treatment. They are used to daily injection and other elements like that. Where we see the huge benefit is independent of the background, if they have been exposed to short-acting PTH or not. I don't believe there is a less need for a patient to get on TransCon PTH treatment if you come from the group that has been on short-acting PTH or have never seen a short-acting PTH. The patient that have been on short-acting PTH have perhaps a more common understanding of a daily injection, have more common understanding about what they need to do as procedure to get that to happen. I don't believe that is a big barrier for any of the groups.
Andreas Argyrides (Research Analyst)
Okay, great. Just a quick one on SKYTROFA, and maybe you can elaborate, and I don't know if you covered this already. Sorry if you did and I missed it. If you can elaborate on the launch dynamics that are driving growth. Are you seeing higher switch rates from daily growth hormone? That's it for me. Thanks, guys.
Jan Mikkelsen (President and CEO)
We always see a higher switch rate from daily growth hormone, but we're also seeing an increased number of new patient coming on the treatment. The overall number goes up everywhere, so it's not like one getting less. Both of them are improving up to a really new height all the time.
Operator (participant)
Thank you. One moment while we go to the next question. Our next question is coming from Yaron Werber, excuse me, of Cowen. Your line is open.
Yaron Werber (Managing Director and Senior Biotechnology Analyst)
Great. Jan, I have two interrelated questions on more coverage. With PTH coming soon, there isn't really a competitor. Do you need to contract or will you contract with PBMs to get on formulary? Maybe kind of talk about your thoughts there. Obviously, the discounting shouldn't be very high at that point. Secondly, now that you'll have a second program, second product approved sort of within the endocrine bag, does it give you more leverage to negotiate better for a placement for SKYTROFA? Thank you.
Jan Mikkelsen (President and CEO)
Yeah. Us, we never really comment about how our market access strategy is and will be, and how we are really addressing the reimbursement system in the U.S. For your information, when we always look at other product, because you can do the same thing, I can give you name of products in the U.S. that basic are in a position to generate multiple billion in revenue in the U.S. without basic being provided high rebate. I think we will follow this pathway because we are providing such a benefit to the patient, the physician, and the society that we feel this is a way we will continue our market access strategy. Compared to SKYTROFA, we are actually pretty satisfied with our coverage. We believe the strength of the product, the differentiation, don't really lead us to provide into a highly rebated product.
I think that is the strength of having a highly differentiated product.
Operator (participant)
Thank you. That's all the time that we have for today. Thank you for joining the conference call. You all have a good evening.
Jan Mikkelsen (President and CEO)
Thank you.
Scott Smith (EVP and CFO)
Thank you so much. See you.