Ascendis Pharma A/S

Good day, and thank you for standing by. Welcome to the Ascendance Farmer third quarter earnings call. At this time, all participants are in 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 1 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1 1 again. Please be advised that today's conference is being recorded. I would now like to turn the conference over to your speaker for today, Scott Smith. Chief Financial Officer, please go ahead.

Thanks so much, operator. And thank you everyone for joining our third quarter 2024 Financial Results Conference Call. I'm Scott Smith, Executive Vice President and Chief Financial Officer at Ascendus Pharma. I'm joined today by Yen Mickelson, President and Chief Executive Officer. 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 statements regarding our commercialization and continued development of Skytropha and Yorvapath for the U.S. and European markets, as well as certain financial expectations, our pipeline candidates and our expectations with respect to their continued progress and potential commercialization, our strategic plans and partnerships, our goals regarding our clinical pipeline, including the timing of clinical results in trials, our ongoing and planned regulatory filings, and our expectations regarding the timing and the results of regulatory decisions, expected market developments, and our exploration of market opportunities in the therapeutic areas of endocrinology rare disease. These statements are based on information that is available to us as of today. Actual results could differ materially from those in our forward-looking statements, and you should not place undue reliance on these statements. 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 statements section in today's press release and the risk factors section of our prospective supplement filed on September 20, 2024, and our most recent annual report on Form 20F filed with the SEC on February 7, 2024. Transcon Growth Hormone, or Transcon HGH, is approved in the U.S. by the FDA and the EU has received MAA authorization from the European Commission for the Treatment of Pediatric Growth Hormone Deficiency. Transcon PTH is approved in the U.S. by the FDA for the treatment of hypoparathyroidism in adults, and the European Commission and the U.K.' 's Medicines and Healthcare Products Regulatory Agency have granted marketing authorization for Transcon PTH as a replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism. Otherwise, please note that our product candidates are investigational and not approved for commercial use. As investigational products, the safety and effectiveness of these product candidates have not been reviewed or approved by any regulatory agency. None of the statements during this conference call regarding our product candidates shall be viewed as promotional. On the call today, we'll discuss our third quarter 2024 financial results and we'll provide further business updates. Following some prepared remarks, we'll then open it up for questions. With that, let me turn it over to Jan.

Thank you so much, Scott. 2024 has been another transformative year for Ascentis. 3 out of 3 of our rare endocrinology programs have delivered clinically differentiated pivotal data. Each product or program is demonstrating its potential to address major unmet medical needs and achieve blockbuster status, positioning us to be the market leader in each disease area. Our first approved product, Skytrofe, is a best-in-class once-a-weekly growth hormone and has achieved a leading position in a highly competitive US market with a single indication. Skytrofe's performance is a testament to its differentiated profile and the team's excellent execution against competition from multiple big pharma companies. We expect additional growth opportunity for Scythophora ahead. We are very excited about the upcoming launch of EUROPATH in the US. EUROPATH is the first and only product to be FDA approved for the treatment of hyperparathyroidism in adults. There are 72 90,000 adults with hypoparathyroidism in the U.S. Who would potentially benefit from this treatment? The highly positive pivotal data in AccraData that we announced in September for our third product candidate, Transcon-CMP, further strengthens our belief that it could if the crew becomes the treatment of choice in this multi-billion dollar market opportunity. Our new partnership with Novo Nordisk highlights our ability to extend the success of our transplant platform into large, high-volume therapeutic areas. By staying focused on our values of patient, science and passion, we believe we are creating extraordinary value for patients and stakeholders. I will now provide more detailed comments on each of these products and other key areas of progress. Starting with Skytofa. The fundamentals for Skytofa are strong. Demand volume in the third quarter increased more than 60 year over year. As physicians, caregivers and patients continue to recognize the benefit of Skytofa provides. We have achieved broader market assets for Skytover, but have not compromised on its value, maintaining a net value per patient of around three times that of daily growth hormone. Over time, we see an opportunity to drive Skytover growth beyond pediatric growth hormone deficiency with a number of label expansions. In September, we submitted and supplemented VLA for adult growth hormone deficiency. Next month, we expect top-line data from our phase 2 trial internal syndrome. And next year, we expect to initiate a scitrophage basket trial in established growth hormone indication, such as idiopathic short stature, small for gestational age, and the genetic condition shock, which include Turner's syndrome. Importantly, the daily growth hormone market is going to a consolidation with players such as Lilly and Genentech announcing plans to exit the market. Today, we repeatedly see that when giving the choice, Skytrover is the preferred product. The market converts to once-weekly treatment We therefore believe SCARTROFA is well positioned to compete for the 85% of prescriptions still being written for daily growth hormone. We are dedicated to make SCARTROFA into a blockbuster in the US alone. Our focus will stay on growing its market share with new patients, both treatment-naive and those switching from daily growth hormone. Increasing treatment adherence and duration and through label expansion. Supported by pricing that recognize the value of lung acting therapy. Now moving to UR-PET. We are preparing for the imminent launch of UR-PET in the US. Next month in December, we plan to begin accepting prescriptions and start the reimbursement process for the around 200 patients already being treated with UO-PATS in preparation for commercial product availability in mid-January 2025. From January 1st, we expect to begin accepting prescriptions for all adults with chronic hyperparathyroidism. To support our strong and successful U.S. loans, we have invested to expand our commercial infrastructure. including building a field organization for UiPath that is three times the number that covers Kiteofa. Since approval, our expanded UiPath field team has focused on engaging endocrinologists who treat adults, including among key opinion leaders and healthcare providers who are actively involved in the treatment of hyperparapacients. This market is driven by endocrinologists, a relatively concentrated specialty. And we estimate around 1,200 physicians have around 30,000 chronic hyperparalyzed patients in their care, or an average of about 25 patients each. We expect the initial uptake of UOPADs in the US to come from four segments. There are around 200 patients already on UOPADs, the 350 to 400 patients in the NAPA special use program that is ending soon, the last population of 4,000 to 5,000 PTH-experienced patients, and around 75,000 broader PTH treatment naive population. Outside the U.S., uptake of UroPath continues to be robust. As of today, There are now around 600 patients on commercial therapy in Germany and Austria, where the commercial launch began this year in January, and across named patient programs in multiple other countries. We believe EUROPASS is a truly unique product. We have designed it to have the same mode of action and distribution in the body as industrial speech aids, and to provide active PTA within physiological levels for 24 hours, 7 days a week. And we don't see any other compounds in the development that share these key attributes. We believe that EURAPAD will become the therapy for the majority of adults with hyperparathyroidism, which is aligned with the recently established guidelines for the treatment of hyperparathyroidism in adults. I will now provide some commentary on Transcon-CMP. Our value proposition for Transcon-CMP is simple. It is to establish a treatment for patients of all ages with achondroplasia. Our previous trial results showed that Transcon-CMP not only exceeded benchmark for growth that have been established in other randomized clinical trials, but also impacted other endpoints that are important for individuals with achondroplasia. We believe TransconCMP has a best-in-class efficacy profile with safety and tolerability similar to placebo, including an excellent injection site tolerability and once-weekly dosing. This sets the stage for its leadership in the achondroplasia market. We expect to submit an NDA to the FDA for Transcon-CMP for the treatment of children with acondyloplasia during the first quarter of 2025 and an MNA to the EMEA during the third quarter of 2025. The two once-weekly growth-promoting products in our portfolio, Skytropha and Transcon-CMP. We believe Ascendi is positioned to become the leader in treatment of growth disorder. We expect top-line week 26 data from COATS, our first combination trial of Transcon Growth Hormone and Transcon CMP in children with achondroplasia aged 2 to 11 years in the second quarter of 2025. Now moving to our recently announced Novo Nordisk collaboration. We believe this agreement is a strong validation of our ability to drive innovation, benefit patients and expand the Transcon technology platform to a larger therapeutic area as described in our vision 2030. The lead program in the collaboration is a once-monthly GPL-1 that will initially target obesity and type 2 diabetes. The global market for GPL-1s like Similutide is expected to exceed more than 50 billion this year and to double or triple in the next 10 years. And once monthly, GPL-1 could become the treatment of choice in this future market. And we are pleased to be working with NOVA Nordisk, a world leader with the manufacturing capacity and commercial infrastructure to realize the value of this opportunity. Financially, upon closing, we will receive an upfront payment of 100 million U.S. dollars and escalating tiered mid-single-digit royalties on global net sales of Transcon products, along with development, regulatory, and sales milestones. I will close with an update on our Oncology program. In September, we presented first results from the Plasm-Assisted OVM Cancer Cohort of the phase 1-2, I believe, trial of Transcon IL-2 beta gamma at ESMO, showing that anti-tumor clinical response was observed in 29 of efficacy-related patients treated with Transcon IL-2 beta in combination with chemotherapy. This was the second indication-specific cohort showing meaningful signs of anti-tumor activity in heavily pre-treated patients. Given these results, recently we closed enrollment to dose expansion cohort in the TRANSCOM IT101 and I believe trials of TRANSCOM TLR78 agonists to highly prioritize our effort on TRANSCOM IL-2 Beta Gamma. In summary, our progress and position are strong, and we believe the expected product revenue and strength of our balance sheet give us the ability to invest in global launches, label expansion, and lifecycle management for all of our three rare endocrinology programs to support each of them to reach blockbuster status. And at the same time, we will continue to invest in new product candidates created by our TransCon technology platform to build sustainable growth and profitability. I will now turn it over to Scott for a financial update.

Thanks, Jan. In tandem with the progress we have made this year with our three endocrinology rare disease programs and the success of extending the application of our TransCon platform into obesity and type 2 diabetes, Cendes also became much stronger financially in 2024. Product revenues have grown significantly. We raised capital in the third quarter. We are securing additional non-dilutive capital through the Novo Nordisk collaboration, and we remain disciplined with our spend. We head towards next year with ample financial capability to execute on our key 2025 strategic priorities. Expand the label for Skytropa to adult growth hormone deficiency and build on its leadership position as a best-in-class growth hormone product. Successfully launch Yorvapath in the U.S. and in multiple countries in our Europe direct and international markets. And submit Transcon CMP for approval in the U.S. and E.U. and initiate preparations for launch in achondroplasia. I will touch on some key points surrounding our third quarter financial results, but for further details, please refer to our 6K filed today. Skytrofa volume increased more than 60% in the third quarter of 2024 compared to the third quarter last year, while reported revenue was 47.2 million euro compared to 47 million euro reported in the third quarter of 2023. The increase in volume was offset primarily by higher sales deductions compared to the prior year as a result of broader market access. Skytropha revenue in the third quarter of 2024 related to channel inventory was approximately €3.5 million lower compared to the third quarter last year. Skytrofa revenue in the third quarter of 2024 was also negatively impacted by adjustments related to prior period sales deductions of 2.5 million euro. Skytrofa revenue for the first nine months of 2024 totaled 138.5 million euro, a 21% increase year over year, compared to 114.4 million euro during the same period in 2023. For the first nine months of 2024, Skytrofa volume more than doubled, but was partially offset by higher sales deductions, including an accrual true-up of €9.3 million related to periods prior to January 1, 2024. Overall, despite the accrual true-ups in Q2 and Q3, with more claims in hand, we can see that realized pricing has been stable since the beginning of the year. With stable pricing, a few extra shipping days, and increasing demand, we expect Q4 revenue to increase sequentially and expect full-year 2024 Skytrofa revenue, excluding sales deductions related to prior years, to be 200 to 220 million euro. We estimate by the end of Q3 2024, based on third-party data, Skytrophia penetration in the overall treated growth hormone market was approximately 6% with our single indication for pediatric GHD. In addition, we estimate, based on third-party data, that sales of daily growth hormone products represent about 85% of total U.S. prescriptions, leaving lots of room for further growth for Skytrophia and market expansion. Shifting to Transcon PTH, third quarter YorvaPath revenue outside the U.S. increased more than 60% to 8.5 million euro, driven by growing patient and physician demand, partially offset by accruals reflecting the end of the free pricing period in the third quarter. Final pricing in Germany is expected to be completed next year. Closing out the top line, total revenue for the third quarter was 57.8 million euro, including 2.1 million euro tied to rendering of services and license revenue. Turning to expenses, R&D costs in the third quarter of 2024 totaled 73.5 million euro, compared to 111.4 million euro during the third quarter of 2023. The 34% decline was largely due to lower external development costs for Transcon HGH, Transcon PTH, and Transcon CNP, as well as the ICONIS transaction. SG&A expenses in the quarter totaled €69.8 million compared to €63.6 million during the third quarter of 2023. The €6 million increase was primarily due to higher employee costs, including the impact from global commercial expansion. Total operating expenses were 143.4 million euro for the third quarter of 2024, an 18% decrease compared to 175.1 million euro during the third quarter of 2023. Total operating expenses for the first nine months of 2024 were 439 million euro. Net finance income in the quarter was 2.9 million euro compared to finance expenses of 20.4 million euro in the third quarter of last year. As a reminder, the net finance line can fluctuate quarter to quarter, driven in part by non-cash items related to our outstanding convertible nodes. Finally, we ended the third quarter with cash, cash equivalents, and marketable securities totaling €626 million, compared to €399 million as of December 31, 2023. To be clear, Total cash does not include the expected $100 million upfront payment from Novo Nordisk, which is due following closing of the transaction. For the full year 2024, based on current plans, we expect product revenue from Skytrofa and the Over the Path XUS to continue to grow. Specifically, we expect Skytrofa revenue, excluding sales deductions related to prior years, to be 200 to 220 million euro. and total operating expenses, SG&A and R&D, to be approximately 600 million Euro, which includes expenses related to launching YorvaPath in the US. We are ready and well capitalized to deliver a successful launch of YorvaPath in the US with product availability expected in mid-January. With that, operator, we are now ready to take questions.

Thank you. As a reminder, if you would like to ask a question, please press star 11 on your telephone. We also ask that you limit yourself to one question and one follow-up. Please wait for your name and company to be announced before you proceed with your question. And our first question for the day comes from Jessica Faye of JP Morgan. Your line is open.

Hey, guys. Good afternoon. Thanks for taking my questions. You laid out a case for a strong initial U.S. launch for YorgyPath, and we're clearly seeing that ex-U.S. already. Can you talk about why you have confidence that you'll be able to keep the patients that you pick up in light of various competitors potentially entering the market? And my second one, or follow-up, is just in the past you've talked about an expectation to reach operating cash flow break-even by the end of 2025. Is that still your expectation?

Thanks, Jess. I will take the first question and then I will delegate it to Scott to take the second question. And I think, yes, we basically in some way reflected that in our initial remarks. Because what we described, what is really a true replacement therapy? Because we are talking about patients that do not have sufficient endogenous hormone to really have a normal, functional life. like a type 1 diabetes. And when we look at the characteristics, which have been proven in multiple, multiple publications, specifically from NIH, where they use infusion pumps, taking PTH into short-acting PTH, but they can keep up the physiological concentration 24 hours, 7 days a week. So when we think about what needs to be taken as what we call a true replacement therapy, is that you need to have the same mode of action like you have in the Dutchess hormone. And basically, you need it because there are so many multiple organs that need some way to get the right receptor activating, signal pathway activating to have the normal physiological function. The second thing is that you need also to have the right distribution. Because it needs to hit both, for example, just an organ and kidney, both in the blood and the urine side. It needs to go to the brain. It needs to go everything else too. And the last thing is basically the PK profile. You need to have the right concentration, 24 hours, 7 days a week. And whatever I do, When I look on the clinical programs that I used, I cannot find anyone that's just living up to the level of what I call a replacement therapy. That was the first question. I think Scott would take the second one.

With regard to our goal to be cash flow break-even, that still remains the goal, and we believe we can achieve that with the cash and cash equivalents that we have on hand. Thank you.

Thank you. One moment for the next question. And our next question will be coming from the line of Tazeem Ahmad of Bank of America Securities. Your line is open.

Hi, guys. Good evening. Thanks for taking my question. Mine's on CNP. Can you just give us an update on where you are in preparing for your meeting with FDA and or your application? What are the open items that need to be completed? before you can guide us to whether or not the data that you have is indeed going to be sufficient for application. And also, could there be potentially a pathway where you start your submission and provide data on a rolling basis if the agency is looking for extended data? Thanks.

Thanks a lot for the question. And to our knowledge, and that is after interaction with both regulatory agencies in Europe and U.S., we have the integrated data packet that needs to be part of the submission. So we basically have no missing data that we actually need to be generating for BASIC to finalize the application here, for example, with FDA. We're doing that and we're getting ready to refiling what will happen in Q1. It's pretty near now. And when I look on the packet, we really are providing a packet that only provides the best in class growth of the children. But we also, for the first time, can address comorbidities. And I think that's something we will continue to share with you, how we really are providing a treatment of acondoplasia instead of just providing linear growth. If you just wanted to have linear growth, I would just give them growth hormone. It's the best hormone to provide linear growth. And I think this is why we are unique position because we have the opportunity really to address the comorbidities and we will continue to give you data how really that is really coming from the data packet we are submitted to the regulatory agencies.

Thank you, one moment for the next question.

And our next question will be coming from Derek Oxilla of Wells Fargo.

Derek, your line is open.

Hi, this is Simona for Dairy. Thanks for taking our questions. So, for Skytropha's approval, have you made any progress with the payers? And do you have any updates on if it's on formulary or if there's any new blocks for market entry? And just one on your path, will this launch require a medical exception for access to the drug?

The first part of Skytropha, I think we have been pretty clear how we are improving our market assessed situation, which has happening a lot in this year, was really impacting our Q1 results in this way. We are still in a situation where we are getting medical exception in the errors, but we definitely are in a complete different market assessed situation this one. But I believe what we see here, and I think you need to go back and see how we really want to balance Skytropha into the growth hormone market. We believe Skytropha, because of its best-in-class nature, can be positioned as a high-value product opportunity. We believe this is responsible to have a price that on net value is 3x higher than daily growth hormone because of all the benefit we're providing. And I think this is the key element in our commercial strategy on how to make Kartoffel to a bockblossom just in the US alone is to keep value. And what is also helping us is the consolidation. We saw first that one of the big pharma left it And now we see another big farmer leaving it. And I believe if you're sitting with a daily growth hormone and you don't have any kind of once-weekly product in one way or the other way, you actually are going to leave this market. So the consolidation is happening, which is a little bit slower than we have predicted, but it's happening. And we will be there to really, really to utilize this opportunity every time they come. We also have a strong reputation. We are a company that never have been on a short list. We are a company that have the most supply chain that really have not been disrupted by any kind of delivery. Related to UiPath, it's an interesting comment out from the thing because when you look on a product being launched specific in the rare diseases and to the group of product we belong to, there's two things that is a key element for uptake. One is that you're basic on label for the majority of the patients, and I can guarantee we are that. Second point, do you really have guidelines that basically promote that you are inside the guidelines for the majority of patients? And please read the guidelines that just got issued for a few years ago around Hypopare patients here in the US for adult treatment. And I think we are in such a unique position. We're both unlabeled. We are also in a position, we are inside the guidelines, so we feel that we basically are providing the benefit to the patient. And just don't forget, we are the only product out there. No other products there. So when you see the three elements, your single product, no one else's choices, you are on label, and you're inside the guidelines, I actually believe you have a very, very, very, very strong position to get the journey from a prescription out to be fully reimbursed in the US. in the most easy way.

Thank you. One moment for the next question.

And the next question will be coming from the line of Yaron Verber of TD Cowen. Your line is open.

Yeah, hi. Great. Thanks for taking my question. Yaron, maybe just a couple on your v-pass um i think in the past we were sort of expecting and that the pair will get pulled off the market by takeda by the end of this year can you give us a little bit of a sense how is this going to work is it driven by like a hard date like december 31 or is it just driven by when they run out of supply and then also in europe um I know you're waiting for the NatPAR inventory to run out before your VPath really takes off. Can you give us a little bit of an update on timing, your expectations? Thank you.

Yes. You know, you're asking me a question that is outside my control because I cannot control when NatPAR is running out of stock. We know they're staying everywhere. There are CAs that are in production and they're running out batches. We know now we are in a position in the U.S., I believe they will try to get out of the US market as fast as possible because they are basically providing free drug out to each single patient in the US. In Europe we have seen an interesting pattern for them where they are trying to come out with every inventory they are doing as fast as possible in using all different means to do that. And to our best estimate In some way it will be in next year you will see the big transition happening. But at the same time we saw in the two different patterns in two different countries. In Germany, the Swiss, the Nepal patients because they said there was an improved treatment. Now in Germany they are over and taking new patients now because the pool of Nepal patients is running out. Austria, different. Just keep the net power patient under power as long as possible, and then take new patients. So what is going to happen in the US when I see these two countries, two different patterns? We believe from the four groups we talked about, all of them will be switched.

Thank you. One moment for the next question. And our next question will be coming from the line of Gavin Clark Gardner of Evercore. Your line is open.

Hey, guys. Congrats on all the progress. So I just wanted to ask about the 4,000 to 5,000 PTH experience patients in the U.S. that you've noted. Are all these patients actively managed in the healthcare system? And I guess more specifically, how long do you believe it could take to get the majority of these patients onto your path? Could it be within the first year, two years? Any estimate would be helpful. Thank you. Thanks for the question.

I believe this PCH experience group, they're used to do the daily administration. If you're coming from, for example, for Tero, some patients are doing injection four times a day. But you know the Forteo and other short acting, many of them have a limited time frame for only two years because of the super physiological PTH level they're providing. So when I look on the 4,000 to 5,000, the majority is NADPAR patients that couldn't come into the program, that basically got started when they have the recall. So when the PAR special use program, to our best estimate, only can take one out of 10 patients. So they were certainly sitting without any kind of PTH treatment option. I believe this patient group will try to be coming into an endocrinologist as fast as possible. This is why we're talking with the patient organization. We're talking now that here in the middle of January, UBASIC will have product availability here in the US and really go in and start to get the prescription. We have our hub, the ASSOC program, really a unique element that will help the patient in the journey from the prescription to basically to be in a position where they are fully reimbursed and be on drugs. We have the infrastructure to it. We know how to get it done. We believe there are so many patients that are just waiting for this opportunity to get a treatment.

Thank you. One moment for the next question.

And the next question is coming from the line of Lee Wasack of Cantor. Your line is open.

Hey, guys. Thank you for taking my questions. I guess relative to the pediatric growth hormone market, how should we think about the revenue contribution from the adult market as well as the Turner syndrome? And it sounds like you're initiating a basket trial. Maybe just comment on the market opportunity there relative to the growth hormone market. Thanks.

Yeah. When we look on the growth hormone market, the On label, we only have access to the market segment that is covered by pediatric growth hormone deficiency. We have now filed the adult growth hormone deficiency, which opened up for a complete interesting segment. Currently, it's only established at 10% of the growth hormone market, but it's a highly, highly under-penetrated treatment population in the U.S. Best estimate we have is about five to eight percent is being treated with adult growth hormone deficiency. So it's really to develop a market that can be nearly the same size as the pediatric market. We focus on being quite sure we are, Skytover should be the choice in all indication where we have the growth hormone market. And this is why we're making the basket trial where we are taking the ISS, SCA and shock, which include Turner. By having this label expansion, we will be in a position that we are nearly covering the entire growth hormone market. And this is our vision to build Skytropha to the blockbuster it should be. Going to PTH, going to Hypopara is quite different because The adult segment is basically the majority of the market. Patients are coming with pediatric, what we call hyperpara. The majority were not coming from post-surgery, but more coming from immunological genetic diseases. So it's a quite different segment in this way, and it's much, much smaller than the adult segment. We are initiating a trial in the pediatric segment. It will be just in the planning now. And it's a part of also our obligation to the European authorities also make it available in the pediatric segment.

Thank you. One moment for the next question.

And our next question will be coming from the line of Joe Schwartz of Lee Reap Partners. Your line is open.

Great. Thanks so much. First question is on YorviPath. I was just wondering, how do you expect the launch of Yorvi in the U.S. to compare to Europe in general? And then is the monthly serum calcium monitoring requirement in the U.S. likely to be a significant deterrent for patients which impacts the launch curve at all in your view?

Let me start on the last question, Joe. What I've seen, I've seen the UM criteria for some of the places, and I have never seen that being installed as any kind of criteria. So I don't think this is really the case. I know the patient often will have this kind of measurement. so it's not like it will be a burden to have it but i'm not seeing it in the um criteria from anyone related to the u.s market is quite different than the german austrian market penetration curves from germany austria compared to us have quite different slopes so from that perspective is that it's such a unified market segment in the u.s it thinks goes faster in the U.S. There is much more open-minded sets to try new treatment. What we're seeing now in Germany, everyone tried with one or two patients. Now it's going up. So the average patient per physician was between one and two. Now we're first coming to the states where they're going to be in two and three for the physician. And this is some kind of what I call You first penetrate, then you broaden it. But what we expect to see in the U.S. is a much, much larger and faster uptake.

Okay. Thank you very much. And then on Skytropha, is today's adjustment to the 2024 revenue guidance due to lower volume, price, or both? Can you help us understand why the additional adjustment is necessary? beyond what we saw previously, and whether these dynamics have any potential to carry over into 2025?

I think Scott will take that.

I think, Joe, in Q3, volume was a little bit lower than expected, but we also had fewer selling days. We're off to a pretty good start here in Q4, but we want to be a little bit more cautious until we see more data. So given we had the call today, we came in with the number that you saw. Some dependencies that could, you know, increase the number for Q4 would be things like channel buying that we haven't seen in previous periods or higher refill rates with prescriptions, but we just don't have enough experience to say that that's something to expect in Q4 yet. Okay.

Thank you. Thank you. One moment for the next question. And the next question will be coming from the line of Vikram Parrot of Morgan Stanley. Your line is open.

Hi, good afternoon. Thank you for taking our questions. So we had one on the recently announced NOVA Nordisk collaboration. We were just curious, as that moves forward, what the next public disclosures there could be, what we can expect to learn from yourself and or NOVA Nordisk, and then secondly, for the oncology pipeline. We were curious what the next milestones there might be and how you're thinking about progressing the oncology efforts you have in place with potential partnerships and what partnership economics or a good partner for those efforts might look like in the future.

Thank you. Thanks for the questions. Related to the first question, we have seen extremely powerful transcom technology making three out of three endocrinology products from idea stage until basic people with data, and two of them are approved now. And this is the Transcon technology with our algorithm for product innovation. And Numanortis took that up too. So we basically are in a position when I see what we can provide with our Transcon technology in obesity, metabolic diseases like diabetes, is we can take a peptide with well-known properties, already proven safety, proven efficacy, and do exactly the same thing. And at the same time, we can make it to once monthly, but potentially also improve tolerability to potential efficacy in the same time. We're really proud to have a partner like NOA Nordisk. There's only two companies in the world, in my view, that have the manufacturability capacity really to make, and commercial infrastructure, to really to make this in a billion, billion, billion dollar product. And these two companies, we actually have a unique, great collaboration with, and they're not only using it for one, of the product that will continue to apply multiple, multiple products on it. Related to specific progress, related to specific update about progress on how they're utilizing the Transcon technology, I believe the best one to answer that will be Novo Nordisk in this case. Going back to oncology, we have been extremely encouraged by the effect we have seen in platinum resistant ovarian cancer in late stage patients that basically have no hope. We actually see meaningful clinical benefit in this and this is what we are really trying to focus on and really pursuing in the fastest and best possible manner to really help these patients. As we said, we are open in the way we will create value out of oncology pipeline in all different structures. And we will pursue the structure that focus on getting out to as many patients as possible, as fast as possible, but also creating most value for stakeholders.

Thank you. One moment for the next question. And our next question will be coming from the line of Kelly Shai of Jafri's. Your line is open. Kelly, your line is open.

Thank you. Thank you for taking my questions. I just want to confirm several numbers in the press release. It was mentioned that the first three quarters of 2024 totaled at 138.5 million euro, and the full year guidance at 200 to 220. So that gives Q4 sales need to be 61.5 million to reach the lower bond. And is this the sales result adjustment? And secondly, for the Transcom CMT NDA submission, just curious, have you talked to regulatory agencies that a 12-month data is enough for the submission? Thank you.

I think I would delegate the first part of the question to Scott. And he just wrote down all your numbers and double-checking them now.

Yes. The updated guidance of 200 to 220 million of revenue excludes the impact of prior period sales deductions or sales deductions related to periods prior to January 1, 2024.

Related to your second question, it's clear we have not got any requests that deliver more than the 12 months data related to efficacy. During filing, you always have what we call safety date update, and you have cut of different safety that always be given during the period where you have the regulatory evaluation.

Thank you. And one more moment for the next question. Our next question will be coming from the line of David Lobinowitz. City, your line is open.

Thank you very much for taking my question. I got two for you. First, on a long-acting GLP-1 agonist, given that GLP-1s are titrated as part of normal treatment, what type of challenges does a long-acting present in this regard? And the second question will be, as on Skytropa, Could you, I guess, give us perspective on how the net or average price has evolved as you've added new payers and to give us perspective just for modeling purpose and how we should view this going forward?

Okay, thanks a lot. When you talk about length, the long-acting GPL-1, I would like to refer back to the basic biology of the DPL-1, because what is really driving the tolerability issue? And to our knowledge is that it's basically when you go from the trough level, this is called the lowest level, or up the peak level, and how fast you really are doing that. This is where you see the tolerability issue in it, so therefore you see when patients stopping treatment have problems with the treatment is because they're going fast up from a trough to a peak. This is why you have titration, where you start on a lower dose, go up to the next dose, just to be sure you're accommodating that you deal with this toolability. When you take a look at our profile that you saw in our JPMorgan deck or also other places, you can see one of the uniqueness with our transcom technology is that we have an extremely long Tmax. And what does that mean? It means that it takes an extremely long time for being in a position that you go from a trough to a peak level. And therefore, which we also have seen in our own data in animal studies, that you basically have a much better tolerability profile than you have in more short acting, where you go very, very, very fast up to the element of the max dose. It's pretty clear. We had a clear statement in our preferred remark. that if you take the legal level of daily growth hormone and take it to 1x, Skytropha has the 3x value.

Thank you. One moment for the next question. And our next question will be coming from the line of Paul Cho of Goldman Sachs. Your line is open.

Hi. Good afternoon, and thank you for taking our questions. I also want to ask on your recent Novo licensing deal. And given that GLP-1s are validated, it would seem like the 505 development pathway is open to a potential monthly GLP-1 agonist. And so development times might be shorter than a full clinical development program for a monthly GLP-1. Do you agree with this? And if that's the case, do you have any sense of what timelines might be for development here when you might start to recognize royalty revenue from your partners. Any comment there would be super helpful. Thank you.

Thank you. And I can only agree 100% with your comments. It's exactly how many cases you would take a development pathway, and it would be shorter than a normal development pathway. And also, you have the potential opportunity to get a broad labeling for the beginning with only one indication. That is the benefit of using a 545B2 Related to specific timeline, we need to refer to normal notice for this discussion.

Okay, great. Thank you. Thank you. One moment for the next question. And our next question will be coming from the line of Leland Gershel of Oppenheimer. Your line is open.

Oh, hey. Thanks for squeezing me in and for taking the questions. Just one from us. I think, Yen, you had mentioned that commercialization in France might be starting by the end of this year. I'm not sure if I missed in your prepared comments. Is that on track? And I was also wondering, as you further pursue European commercialization, if you have any further clarity on the cadence of rollout in various countries through 2025. Thanks.

Yeah. You are right. What we have established as what we call Full commercial air is only Germany and Austria. In France, we got elected to a special program called AP2. This is a program that is basically non-promotional, but we can give them commercial reimbursed drugs. And it got established for about three, four weeks since in France. And the number we have seen coming in where physicians really say, I believe, I believe, because it needs to be physician driven. We cannot commercialize. It's really unique. Going forward, we will have fully commercial countries where we call in Europe direct. where there will be full commercial countries and it will be the majority of the countries in Europe, EU, there will be basic full commercial next year in different quarters, a lot of them coming into Q2, Q3 next year. So what you saw of our success in Austria and Germany, we basically are repeating that in about 8-10 other EU direct countries. In our international market we see a lot of named patient program but we also will in the national market where we now have countries covered by distribution agreement about 30 to 35 countries and there are currently giving patient through named patient program and also next year we will start to see more and more of this country also going into full-blown commercialization. It's dependent on what we are spending a lot of resources on now. It's basically getting filing, which we have done in many, many countries, but also getting approval in all of these countries. And we're getting approval already beginning this year, and the meaning is that we know we will be full commercial this year, next year's

Great. Thanks so much for the clarity.

Thank you. And one moment for the next question. Our next question will be coming from the line of Alex Thompson of Stiefel. Your line is open.

Yeah, great. Thanks for taking our questions. I guess for your V path, can you talk a little bit about your your supply commercial supply readiness for the mid January launch? I think you mentioned that you're going to take scripts from current your V path patients in December. Could you open that up to all or are there supply constraints or some other constraints? And then on CNP, do you still have an appetite for running a broader basket study of additional indications or are you now focused on Skytropha there? Thanks.

PJs, we have unlimited supply. We can take all patient in that we want. There is no limitation in manufacturing. We already have laid out the entire year's manufacturing batches, locked every time point we want to have to be sure that we are building up the same robust supply chains that we have done with Skytropha, which has been unique even if we suddenly got major more demand. So the same thing is happening for EUROPAX and we are really on top to be sure no patient ever should go in and not can get the prescription fulfilled of Uropax. Going to CMP, you're right. We think some indication is best treated with Skytropa, but definitely there is also indication that it's best treated with CMP. And some of them are best treated with the combination of both of them, either a constant based or only on a short duration. So we are planning to go into what we call CMP related diseases, meaning is that this is diseases where the growth disorder or what we call other element of missing CMP only can be functional back to what we will see in a normal physiology by providing CMP back. So besides planning a trial in hyperchondoplasia, which will be initiated next year, we are also planning for a basket trial. We think that is an easy way where we can take multiple indications of CMP-related diseases into one single trial that we also is in the planning for doing now. So we are not restricting us just to sclerotrophic label expansion. We dedicate it to be leader in growth disorder. We have plus 20 diseases to go through and some of them we will take sclerotrophic, some of them we will take Transcon-CMP and some of them we will see the optimal treatment happening with a combination of both of them either on a constant base or on shorter duration one of the

Thank you so much for your questions and answers today. That is all the time that we have for the session. We thank you so much for joining the conference call today. You all may disconnect and have a great rest of your day.