Ascendis Pharma A/S

Ladies and gentlemen, thank you for standing by and welcome to Ascendus Pharma first quarter 2025 earnings conference call. At this time, all participants are in the 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 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to Scott Smith, Vice President and Chief Financial Officer. Please go ahead, sir.

Thank you so much, operator. And thank you, everyone, for joining our first quarter 2025 Financial Results Conference Call. I'm Scott Smith, Chief Financial Officer at Ascendus Pharma. Joining me on the call today are Yen Mickelson, President and Chief Executive Officer, Sherry Glass, Chief Business Officer, Jay Wu, Executive Vice President and President Ascendus US, and Amy Hsu, Chief Medical Officer. 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 statements regarding our commercialization and continued development of Skytrofa and Yorvapath for the U.S., European, and other 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, partnerships, and investments, our goals regarding our clinical pipeline, including the timing of clinical results and trials, our ongoing and planned regulatory filings, and our expectations regarding the timing and results of regulatory decisions, expected market developments, and our exploration of market opportunities and therapeutic areas outside of endocrinology rare disease. These statements are based on information that is available to us as of today. Actual results may differ. 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 for additional information concerning the fact that actual results to differ materially. Please see our forward-looking statement section in today's press release and the risk factor section of our most recent annual report on Form 20-F filed with the SEC on February 12, 2025. Transcon Growth Hormone, or Transcon HGH, is approved in the U.S. by the FDA and in 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 United Kingdom's Medicine 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 an investigational product, the safety and effectiveness of product candidates has 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 first quarter 2025 financial results and we'll provide further business updates. Following some prepared remarks, we'll then open up the call for questions. With that, let me turn it over to Yen.

Thanks, Scott. Good afternoon, everyone.

In the first quarter of 2025, Ascendi has continued the strong start of our global UoS loans, as well as key development and regulatory progress supporting our long-term growth strategy to be a leading biopharma company. The strong US loans of our Europass position 2025 to be an inflection point for incentives with a growing revenue base and a clear path to become cash flow positive. As of March 31, Europass was prescribed in the US by more than 1,000 unique prescribers for more than 1,750 patients. This represents our first full quarter for the US norms. EURAPATH, the first and only FDA-approved treatment for hypoparathyroidism in adults, is addressing the underlying cause of the disease by providing active PT8 within the physiological range for 24 hours per day. Skytropha, our long-acting growth hormone, is firmly established as a high-value band and the preferred treatment for patients, physicians and caregivers. Skytropha is well positioned as daily treatments continue to exit the US market and as Skytropha's label has the potential to expand beyond its single indication. Skytofa is a key pillar in our strategy to become a global leader in the treatment of growth disorder. Transcon-CMP, the first long-acting therapy in development for the treatment of achondroplasia, is set to become the second pillar in our growth disorder strategy. We believe that Transcon-CMP has treatment benefits in addition to linear growth that addresses multiple aspects of the condition that are fundamentally important to patients. We submitted an NDA to FDA in March and expect to file an MAA with EMEA in Q3 this year. Data from three randomized double-blind, placebo-controlled clinical trials show that Transcon-CAMP has the potential to transform the life of people with achondroplasia. In my remarks, I will discuss each of these products in detail and comment on other recent developments within our business. Beginning with EUROPATS. First quarter, total global EUROPATS revenue grew to 45 million euros. compared to 14 million euros in the fourth quarter of last year. Following commercial availability in the US in December of last year, we are seeing strong US demand, reflecting both the deep unmet medical need in the market, as well as the large patient population. As of March 31, more than 1,700 and 50 patients, including the 200 patients from our ERP and clinical program have been prescribed UroPath in the US by over 1,000 unique healthcare providers. Enrollment of patients new to UroPath continue at a similar weekly rate in April. The majority of patients who have received insurance approval for their UOPAT prescription received that approval in four to eight weeks. And we are pleased with the approval rate we have seen. We are beginning to see favorable payer plans put into place and continue to see approvals across both commercial and government plans. The strong launch performance of EUROPATH in the US supports our view of its excellent product profile and the major armament needs in the market. And we expect EUROPATH to contribute significantly to our revenue in 2025. Outside of the US, we see steady EUROPATH revenue growth in both the Europe direct and international markets. And we expect additional acceleration of the revenue growth when EURAPAT's reimbursement becomes available in additional EURAPAT direct countries in the second half of the year. The continued rapid uptake together with high rates of patient adherence give us confidence that EURAPAT is well positioned to uniquely address the unmet medical needs of this patient population. And we are regularly reviewing input and data from patients to evaluate if there are additional ways to improve the treatment profile even more. We estimate there are over 400,000 patients globally and around 70,000 to 90,000 patients in the US alone. living with chronic hyperparathyroidism. Our claims analysis demonstrate that 10,000 to 15,000 of these US patients are uncontrolled, and 30,000 to 35,000 are partly controlled. Based on the latest clinical practice guidelines, nearly all these patients are candidates for treatment with UOPAT. Our strong global loans give us high conviction that we can continue to build and lead this market. And EUROPAD can be a durable multi-billion euro drug device product with a patent lifespan extending into the 2040s. Turning to Skytofa. Q1 revenues for Skytofa were 51 million euros. With continued patient growth and global expansion offset by the typical first quarter revenue dynamic in the U.S., we have around 7% market share of the total growth hormone market in the U.S. and around 43% of the total U.S. non-acting growth hormone market based on third-party prescription data. The pediatric growth division indication represents about half of the total growth hormone market. With our premium pricing and Skytrover's leading position in pediatric growth hormone deficiency, we believe we are well positioned to expand the opportunity for Skytrover in multiple ways. A key near-term milestone is our first potential label expansion in the established growth hormone indications from our supplement BLA for the potential US approval in adult growth hormone deficiency. where we have a PDUFA goal date of July 27, 25. We are also on track to start a basket trial for SCARTOFA in a range of indications, including idiopathic short stature, shock deficiencies, Turner syndrome, and SGA. We are planning to discuss this trial with the FDA in an end of phase two meeting this quarter. Importantly, We are also investigating trans-con growth hormone outside the established growth hormone hormone indication, such as in a potential combination therapy with trans-con CMP for treatment of aconthoplasia and other growth disorder, which I will address in a moment. Moving to trans-con CMP. Trans-con CMP is the third key product in our endocrine endocrinology rare disease product portfolio. The genetic variant that caused a contraplasia changed the way receptor work in multiple tissues throughout the body, not just in the growth plate and in bones, resulting in a wide range of serious medical complications in childhood and lasting throughout adulthood. Because Transcon CMP provides sustained therapeutic levels of CMP throughout the body, it has been demonstrated a unique product profile, giving it the potential to bring growth benefit and important new benefits beyond linear growth, as well as reduce risk of hypertension and injection site reaction. In our period approach trial, TransconCMP demonstrated significant improvement in the primary endpoint of linear growth compared to placebo, as well as significant improvement in other clinical endpoints meaningful to the acroendoplasia community, including leg bowing, muscle functionality, body proportionality, and health-related quality of life. Leg bowing is a common complication in acroendoplasia. that can result in chronic pain and impaired physical function, driving many to undergo complex, painful corrective surgeries. I have been in meetings with patient organizations in Europe and the US who have confirmed the importance of addressing the complications of acupuncture beyond linear blows. Just as important to the acupuncture community Transcon-CMP has shown a safety and durability profile compared to placebo with low frequency of injection site reaction, all which were mild and no evidence of symptomatic hypertension. After positive interaction with the FDA relating to the content of our NDA submission, we are pleased to have submitted Transcon-CMP for the review in March. In the EU, we plan to submit an MAA during the third quarter of this year. Additionally, during the fourth quarter of 2025, we plan to submit an IND or similar to investigate Transcon-CMP or in combination with Transcon-Glutamone for the treatment of hypochondriasis. Shifting to Transcon-CMP and Transcon-Glutamone combination therapy. We are committed to continue to drive even better outcome for people living with achondroplasia. This is why we are conducting the COAT trial, being the first phase two study combining CMP and growth hormone in achondroplasia, each of which stimulates different signaling pathway in the growth plate and other tissue in the body. We look forward to sharing top-line week 26 results from the CoachTri data this quarter and see great potential to further raise the bar for clinical outcomes. With Transcon-CMP as the potential future backbone therapy, we believe we can achieve even greater growth while also addressing medical complications of air-condorplasia. Fundamental to the development of each of our three medicines, EUROPAT, SCARTOFA, TRANSCRON-CMP, is Ascendi's proprietary Transcon technology platform. With the Transcon technology and our deep understanding of disease biology, it is possible to create medicine with highly differentiated treatment benefit, not possible with other technologies. At Ascendi, our commitment has always been to the patient. It is one of the company's core values. I believe we have demonstrated multiple times over the history of Ascentis our resilience and our ability to adapt and find solutions to attain this goal. We remain as dedicated as ever to ensure that all our medicines become available to patients. Through our collaboration with Novo Nordisk for the development and commercialization of Transcon technology-based product in metabolic and cardiovascular disease, and our collaboration partner, Visum, Iconis, and CyDyn, we continue to work to execute our vision 2030 to create value in large therapeutic areas and to innovative business models. In summary, 2025 is a transformative year for attendees. as we grow our global revenues from Europat, Skytofa, and seek to obtain key regulatory approvals, deliver robust clinical data, and advance stocks with blockbuster potential to drive growth for many years to come. I will now turn to Scott.

Thank you so much, Jan. I will touch on some key points surrounding our first quarter financial results. But for further details, please refer to our 6K filed today. EuroPath first quarter revenue increased significantly to 44.7 million euro, up from 13.6 million euro in the fourth quarter of 2024. Steady sequential revenue growth outside the U.S. was augmented by the strong U.S. launch. As Yen discussed, the trends we saw for Yorvapath in Q1 continue in Q2 both outside and inside the U.S., and we anticipate that Yorvapath will have a substantial impact on our financial profile in 2025. Turning to Skytropha, revenue for this quarter was 51.3 million euro. Sequentially, pricing and market share remained stable, but revenue in the U.S. was negatively impacted by seasonal items, including reduction in channel inventory and higher co-pay assistance. Those seasonal headwinds should reverse beginning in Q2. We also continue to watch the euro-dollar exchange rate for any potential impact related to reported revenue. Total revenue for the first quarter was 101 million euro, which includes non-product revenue from our collaboration partners. Turning to expenses, for the first quarter, R&D costs totaled 86.6 million euro compared to 70.7 million euro during the first quarter of 2024. The first quarter of 2024 included a favorable 10.6 million euro reversal of prior period write-downs of Transcon PTH pre-launch inventories. SG&A expenses in the first quarter of 2025 totaled €101 million compared to €66.8 million during the first quarter of 2024. The €34 million increase was primarily driven by global commercial expansion. Total operating expenses were €188 million for the first quarter of 2025. As a result of the Visa and IPO, We recognized a non-cash gain of 33.6 million euro as part of share of profit loss of associates, and we retained 39% ownership of Visum. Net finance expenses for the first quarter of 2025 were 15.9 million euro, driven primarily by non-cash items. Net cash financial income for the first quarter of 2025 was 3.3 million euro. We ended the first quarter of 2025 with cash and cash equivalents totaling 518 million euro compared to 560 million euro as of December 31, 2024. Turning to the remainder of 2025, we expect substantial revenue growth driven by the global launch of EuroPath with a continued solid contribution from Skytrofa. We are not providing revenue guidance for Skytrofa or EuroPath at this time. For Skytropha, we believe that growth in prescriptions, visible in third-party data, will track sequential revenue growth for 2025 with expected stability and mix in pricing, including normal seasonality. For YorvaPath, outside the U.S., we continue steady revenue growth, while inside the U.S., our launch is progressing exceptionally well. We will continue to look to help investors understand uptake and reimbursement dynamics as the year progresses. With that, operator, we are now ready to take questions.

Thank you. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. And to withdraw your question, please press 11 again. We do ask that you please limit to one question and one follow-up to allow time for everyone to ask a question. And our first question today will come from Jessica Phi with JP Morgan. Your line is open.

Hey, guys. Good afternoon. Congrats on the strong results with Your RePath. It seems like the number reflects very good execution on reimbursement. Can you talk about your latest expectation for the proportion of patients with a script who you think will ultimately get reimbursed once Your RePath is, say, at steady state? And then the follow-up would just be, was there any initial channel fill reflected in the 1Q revenue number? And if so, can you quantify that? Thank you.

Thanks, Jess, for the questions. And Scott, we'll take the easy one, the last one.

Yeah, Jess, so channel inventory has averaged about one to two weeks at any one time. We ship once a week, so it's hard to get less than one week of channel.

The second one, and just why it's a little bit more complicated, because there's somebody looking in the future. What we can see, we see a very, very, very positive trend. We see the adaption of the different PPMs, the different payer forms. And if I'm somebody who should come with my own guess about it, and this is more a guess because we don't know exactly, there will never be 100% approval of all the patients. And I believe if we really are successful, and I hope we won, and I believe we're going to be successful, I believe 17 to 18% will get reimbursed. But I think, Jay, if you have another comment to it this way.

Yeah, happy to chime in on that. I think, as Jan mentioned, we are still early in the launch, right? So from that perspective, we're still seeing policies be set into place. So it is a bit early to be able to anticipate what that steady state will be. I do think a few examples that give us a lot of confidence that we are headed in the right direction is a couple. One, you're seeing policies, favorable policies, be put into place both from a commercial standpoint as well as government. So we're seeing that start to take hold. And then two, even absent of a formal policy in place, we do see patients get approved across the board, again, agnostic of whether it is a commercial plan or government plan. It just sometimes may take a few more steps, whether it is through medical exception and in some rare cases even through appeal and or peer-to-peer. But largely, we are seeing many patients get through. You will expect a long tail, just given that every payer plan is different, given the heterogeneity in the US. But overall, we have a lot to be encouraged about. And I think more importantly, it just really emphasizes the clinical value proposition of this product and the fact that payers, providers, and patients are all responding to it.

I think, but yes, I think some way when I talk about my feelings, My feeling is that I believe every patient that in some way have a desire to go on treatment should come on treatment because I have seen or heard a med patient the benefit there is on the treatment in it. But I also accept reality in this way here. But I also believe we are in a unique positioning. We are addressing a major unmet medical need. We have really a product that really are providing the benefit to the patient. We are in a position that patients are diagnosed with the disease. At the same time, there is clear guidelines that say there should be a treatment. Can you find a better case for any patient really not to get the ultimate goal? If you get and want to be on treatment, you should be on treatment.

And our next question comes from Tazeen Ahmed with Bank of America Securities. Your line's open.

Hi, good afternoon. Thanks for taking my question. Yen, can you give us a little bit of color on the splits between U.S. and ex-U.S. revenue for the quarter for Euripath? And can you give us a sense, because it seems like you do have some patients receiving drug in the U.S., What the length of time is, I know it's early, but what is the length of time that you're seeing between when a script is written to when the patient is receiving therapy? Thanks.

Yeah. Let me first address the question between Europe and U.S. And as you have seen, we are not really describing that in our numbers. but also believe that we give you good guidance how to potentially to calculate it. As we said, when we look on the ex-US, we see a steady growth, a steady acceleration. But we first expect in the second half of this year to see an acceleration of the acceleration when we get more countries basic into the situation that will be fully reimbursed. So when I look on the difference between Q3 and Q4 last year, it's something around the element an increase around 4 to 5 million euro in for one quarter to the next quarter. So when you think about that we increased our basic revenue from about 14 to 45 then you can take basic the difference and then subtract about four or five million. And then I think you would get a number around 26 million, which are some way reflecting the algorithm I would use if I should look at it.

And our next question will come from Gavin Clark Gartner with Epicor. Your line is open.

Hey guys, congrats on the very strong launch progress. First, just to follow up on the payer point and the favorable access, have you finished negotiations with the majority of commercial payers at this point? And do you respect the remaining to be published policies to look similar to the ones that are already published? And has the rebating fallen in line with your expectations with those conversations?

Yeah, it's a question. I will take the global perspective. As you heard about ex-US, we are basically fully reimbursed now in Germany. There is a final list price you can find. We also have that for Austria. In France, we have an AP2 program. We can also have a different program in Greece. So ex-U.S., we are working on really getting all country by country fully reimbursed. It takes time. It's something that some way both will happen here in 2025 and also in 2026. When we come into the end of 2026, we believe we will have the vast majority of the important country being fully reimbursed. If you come to the U.S., which there is a strong focus on, don't forget the more than 300,000 patients outside U.S. I think Jay can give you more color about his discussion with the different plans in the U.S.

Thanks, Jan, and thanks, Gavin, for the question. Yes, to answer your question, the conversations with payers have been going very well. We have multiple commercial policies in place with our national accounts. So while we don't comment on policy by policy, that gives you a sense that we are gaining a lot of good traction there. And the policies that are put in place are favorable and consistent with label. While we don't comment on the gross net arrangements that we have with each, what I will say is that it is commensurate with what we said before. This is a first and only approved product in a rare disease setting with clinical value benefit that we strongly believe in and we feel we've been able to convey with payers. And from that lens, it is commensurate with the incredible clinical value proposition that we bring, and we certainly lead with that and expect it to reflect that.

Okay, great. And then quick follow-up. For the new prescriptions that are coming in, what proportion are NatPara or PTH naive versus experienced? Thank you.

I don't think we really have the full insight exactly how many deaths coming from the NAPAR. Sherry, you can potentially correct me if we have got more insight to that. There was some question we discussed last week. We know that the vast majority of patients coming from conventional therapy, but perhaps, Sherry, you can discuss exactly how many NAPAR patients that we believe has been transferred over.

Yes. Thanks for the question, Gavin. Yes, Yen's right. The data is not entirely definitive on this point, but we know that we have the vast majority of our patients overall are coming from conventional therapy. So that's very clear. And we do have, you know, something like 10 to 15% of patients that have been on some sort of PTH in the past. And then you know, a subset of those were more recently on NAPARA. But the bottom line is, you know, overwhelmingly coming from conventional therapy.

Yeah, from that perspective, we believe that in Q2 and Q3, we will see the majority of the rest of the NAPARA patient coming over because Amy, you're sitting with the patients, you can explain that there is an later coming out explaining that you're in a position that they're stopping.

Right. There's still, as far as we know, there's still some supply, so they still may be on it, but we know it will exhaust soon.

Yeah. So the basic, when we look at the patient that's coming over, the 1,750 This is not a power patient. This is basically a patient that's coming from conventional therapy. There's 35,000 patients we are addressing now. So there is a lot of deepness to go in in this way.

Great.

Congrats on the progress.

And our next question comes from Derek Archila with Wells Fargo. Your line is open.

Yeah, congrats on the quarter and thanks for taking the question. So maybe just first on Can you comment on the depth of prescribing and the number of docs that are really prescribing, you know, maybe two, three, four patients with your VPath? And then just to follow up to the last set of questions, just, you know, are you seeing patients that are newly diagnosed or well-controlled on conventional therapies move over to your VPath? Thanks.

Yeah. If I just could answer all your questions, I will be a happy person. I'm still a happy person. But... When I summary and share, you can also add in. We cannot really know if they are well controlled, partly controlled, or not controlled. that is not really anything we can see. We don't believe that it's really part of the reimbursement system. I actually think why we call them uncontrolled, we likely will see more of them because we have an algorithm that basically are saying that 10 to 15,000 of the patients we define as uncontrolled is because we are seeing an endo in a very, very, very high frequency. And that was why we know that we just went to this physician that will automatically have all these patients coming in. So when they're coming and control patients that see the endo on much, much less frequent, are they getting on napalm? I hope so, but I cannot really know. But we know we really addressed the patients that see the endo in high frequency. And I believe that it's basically I would call the genius part of our commercial organization really working on not getting patients into the endos. It takes too long time. If I want to go into Amy's practice and Stanford, I need to wait three months to get an appointment with her. And I think we cannot wait for patients for that. And it was why I think they made a really, really genius move in the commercial organization. go to the places where we know patient comes in very, very, very far. So my expectation is that I believe we have a high percent of uncontrolled, partly controlled, but it's mainly only built on the algorithm because they are seeing the endo much more often than the other ones. So Sherry, do you have anything to add?

I think you covered it well, Yen. I would maybe just say one of the things we're really excited about is we know there are quite a good healthy number of those uncontrolled and partially controlled patients. So something like 10,000 to 15,000 uncontrolled and another 30,000 or so partially controlled. And as Yen said, the uncontrolled patients are seeing their endos four times or more a year. So we know, to Yen's point, that they're getting in and therefore that we expect to see a steady flow of patients coming in and having the option to get on drug over the course of the year.

Yeah, and one of the reasons why we don't know it is because it's not part of being reimbursed or not. So if it was a part of the reimbursement system to have this uncontrolled party control or control, we would know much more on it, but it's not a decision in the reimbursement system.

And the next question comes from Yaron Werber with TD Cohen. Your line is open. Yaron, your line is now open. Our next question will be from Joe Schwartz with Learing Partners. Your line is open.

Thank you and congrats on the very strong quarter. I was wondering if you have a sense of how many of your target endos in the US have adequate resources at their center in order to be able to go back and forth with payers who might not approve reimbursement of URV right away? Just given there's so many patients in the US and a finite number of physician offices who treat them, could their ability to navigate this process represent a cap on URV path revenue growth at some point?

Joe, it's something that Jay and the commercial organization have really a lot of thoughtful thinking about it. How can we ensure the journey for the patient, the physician, the office that's dealing with it is really going to be the most soft journey we ever could think about. And I think we have so much experience in this area, mainly out from our Skytropha. The 10,000 patients we took big portion of them to medical exceptions. And I think there was the learning we got, there was the system we're building on. And I think this is why we are potentially one of the best equipped companies really to deal with medical exception from all the elements we learn from the Skype profile. Jay, you can go much more into how we are helping them.

Just to add on and to reinforce what Yan said, our hub is a well-oiled machine at this point, right? Incredibly experienced. As we all know, the growth hormone deficiency space is a heavily managed space. So not only is our hub infrastructure equipped both from a volume and speed perspective, we also have a strong field reimbursement manager footprint that is constantly supporting these offices along the way as well. We feel good about our ability to resource and support our customer needs as needed. To your question directly, of course, there's going to be some offices, particularly the ones where perhaps it's lower volume, they may see fewer cases. That's not, I would say, unique to many other specialties that experience the same type of office burden. But again, going back to what Yan was sharing earlier, we're well equipped. and have the capabilities to ensure that we are allowing that to not be the bottleneck as to why patients will get on therapy.

Thanks for the color. To follow up, could I just ask what you hope to see in terms of clinical benefit from the combination of Transcon, CNP, and HGH in the COACH trial?

Yeah, thank you. Now you're asking about the future again, and this is good. I'm covered by... Scott's statement, even if it went a little bit fast for me to understand what he said. But I actually saw an interesting research. And why it was interesting for me, because they tried to take, which it was actually something I never thought about myself, and this is potentially why I thought it was really interesting. They looked on achondroplasia and hypochondroplasia. Adcontraplasia, as you can see, the more severe form for adcontraplasia, hypercontraplasia, a little bit more, you can say, easy form for adcontraplasia, less severe, less break, because what FTR3 superactivation is, is really putting a break on the system. So when you took on adcontraplasia, you have the break full down, hypercontraplasia partly down. And then they look, what is the difference between growth hormone treatment over years with the two different therapeutic areas, achondroplasia and hydrochondroplasia. And I have to think that it was very well done. And you can basically, I can give you the numbers. So when you go to achondroplasia, you basically get at 5, 6 centimeters, which are typical what we have seen. But when you go up to hypochondriplasia, you are up on the 8 centimeters. And I actually think that it was really smart research, because in some way, what we're doing with CMP, we take an acondriplasia patient and remove the break. So I don't know the results, Joe, but I thought that it gave me some strong belief that we're going to make a new standard for treatment. not only for height, but also other places in the body where we really want to see a benefit in it.

Thanks for the insight.

And the next question will come from Paul Choi with Goldman Sachs. Your line is open.

Hi. Thanks. Good afternoon, and congratulations on the commercial progress. On your path, I wanted to ask if you have any color from the field as to what patient types it might be being utilized in. Is it almost primarily post-surgical patients or are you seeing other causes of disease like genetic or other patients utilizing it too? And my second question on Transcon CMP is just Any updated thoughts or plans for development in the youngest patient population, those shortly after birth through, let's say, three years old, just kind of what you're thinking is there in terms of potentially expanding into that population?

Yeah. Let's keep first up in the demographic on the U.S., because if you look on the demographic in the U.S., is that we have about 20% coming from, we could call the genetic, immunological, everything else, and then about 80% coming from the post-surgical. And there was very much reflected in our clinical trials. So in our clinical trials, we even have ADH1 patients. We actually had two. Even they are extremely hard to find because there are so few of them that have hypochondriasis. We actually managed to get them in. So from that perspective is our clinical trial. This is basically reflected the numbers. I do not know, Amy, if you have any comments. You can come with all the different genetic variants we have there.

Yeah, we had GATA3 mutations. We had autoimmune polyglandular syndrome type 1 and DeGeorge syndrome. These were all seen in the trial. We know that we were seeing them in the expanded access program. We don't always get that information on the commercial. From what we hear from our clinicians with whom we speak, they're applying this to everybody. Yes.

So basically, a hyperparapation is a hyperparapation. And this is how they define it. And I don't think there is any kind of selection from the background demographic, because in our clinical trial, we have all the broad background demographic. And if you look on the labeling, independent of background. It's not restricted for not treating any kind of background. So we believe what we see in our commercial patient population really just reflect the mirror what we see in the US.

And the next question comes from Lee Watzik with Cantor Fitzgerald. Your line is open.

Hi, hey guys. Wanted to add our congrats as well on the strong launch. Maybe just first on your B-PAD, you know, in terms of, you know, contracting in the future. I know you're still in the process. But any guidance that you can provide on sort of the trend for growth to net for the rest of the year relative to Q1? And I have a follow-up.

Scott or Jay, who will take that?

I'll just say some preliminary comments. So on gross to net, you can't get out of the mandatory government rebates. So the biggest driver is likely to be mandatory government rebates that you see in the Medicare and Medicaid channel, which probably average very low, 20%. And commercial will depend on contracting, of which Jay can comment.

Yeah.

Yep. Just as I echoed before, the contracting should be fairly minimal, again, reflecting the clinical value proposition that we have. So, you know, if there's a change, it won't be materially different just relative to the other markets we've been in.

Okay. And then just follow up on the phase two coach trial. I know you have a starting dose for Sky Chofa. So is there a sort of a titration scheme here that we should think about with a top dose that you can go to?

No.

It's basic is that we have a starting dose for the transcon rotamone in the combination with CMP. And they're also measuring idea one, as they do in all trials. If there is any possibility that the physician desires to go up in dose or down in dose, they have the opportunity to do it. But Amy, you know the protocol better than I do.

And may I hear from Lee which condition was she asking for?

The combination.

Yes, so there will be a starting dose that is informed both based on the phase two trial that we're currently doing in the combination trial and also from the conditions we're studying where there's short stature but a sufficient growth hormone access. So this will give us information. Based on what we're seeing so far, there can be a very good and safe universal starting dose typically.

Thank you.

And our next question will come from Eliana Merle with UBS. Your line is open.

Okay, guys. Thanks for taking the question. I'm curious just the feedback from the early patient starts, how the titration process has gone on your path, just logistically, you know, kind of any color anecdotes on how that's been going for physicians and patients and any color so far on what you're seeing from the, uh, refill rate? I know it's early on, but I'm curious any trends that you're seeing there. Thank you.

What I'm typically looking on is numbers. And one of the numbers I look a lot is two things, adherence. Second number I'm looking on is how many patients are dropping off. I think it's two good numbers to look if you have a successful, meaningful treatment of the patient with really addressing a major unmet medical need and really do that. And when I look on the adherence, it's exactly as high as we saw it in the clinical trials, which was really unique. And dropout, we have given you the German numbers on the 1%, and we see the same thing everywhere. If you start on your pants, you stay on your pants.

And that is a chronic treatment, rest of your life.

The next question comes from Kelly Shee with Jefferies. Your line is open.

Hi, good afternoon. This is Jose for Kelly. Congrats on this wrong quarter, and thanks for taking our question. I have a question in terms of payer dynamics. What are the major reimbursement pushbacks And based on these dynamics, what percent do you estimate you can capture in the mild, moderate, and severe segments? And also, on the clinical value proposition of the orbit path, would you consider running a clinical utility trial to facilitate uptake in milder patients? Thank you.

Related to your first question, as the part we discussed before, being uncontrolled, particle-controlled, or control is not part of the reimbursement system. So we cannot really see that. We don't know exactly where they're coming from a different group. We believe many of them, the majority, is coming from the uncontrolled because they see the physician much more often. So that is not any part of the reimbursing discussion. The second question, I need to understand a little bit more about what exactly it was you wanted us to address.

On the value proposition of your VPATH, the potential for preventing renal damage, would you consider running a clinical utility trial to perhaps facilitate uptake in milder patients who are controlled on SOC standard of care?

I don't think really this is the key element for going on the treatment. I actually think the key element to go on the treatment is the benefit you get as a person you're getting normal again. The long term risk It's basically what we call a health economic discussion when we talk about the benefit of the treatment for the society. And we are evaluating exactly how we can do that in the best possible manner to really show the financial benefit it is really to be on a UROPAD treatment, not only for the patient, not only for the physician, but basically for the entire society. All right. Thank you.

literature data already out there that we may be able to leverage showing that some of the conventional therapy itself is toxic to the kidney, right? And that when that is able to be lowered in whatever way, right, that the kidney function gets better. So there may not, you know, we'll see what the need is for demonstrating this yet again.

Very helpful. Thank you so much.

And the next question comes from Luca Izay with RBC. Your line is open.

Oh, great. Thanks so much for taking my question, and congrats on the launch here. Maybe a quick one on competition. BridgeBio presented their data for their molecule earlier this week, and I believe MBX will do the same next quarter. So wondering what's the latest thinking on both molecules and how competitive you think they can be versus your VPAT. And then maybe Scott, super quickly, how should we think about the SG&A for the remainder of the year, given the meaningful jump this quarter versus last quarter? Any thoughts there? Much appreciated. Thanks so much.

Yeah, you mentioned two compounds. One is the catalytic, which are being positioned into a phase III tribe of ADH1. ADS-1 is being treated with UroPax and they're coming on treatment today. It has been hard for us to find ADS-1 patients and Sherry, you went into the claim database and how many patients did you find with ADS-1?

Yeah, there were something like 350 patients who'd had a claim associated with ADH1 in the past four or five years, and even fewer than that within the last year. So it was a very tiny number. This was from a large national claims database with hundreds of millions of lives.

So it's not going to change anything for us because we are addressing. The position of catalytic into the era of, for example, what we call chronic hyperpara patient that is not ADS1. You know, I really love science. I don't understand the science there. You're trying to position into a place of a patient that does not have industrious PDAs. How can you increase the level of industrious PDAs when they're not producing it? They're already producing on max, and there is actual a very nice poster that's basically showing that they are taking calcium lutein into four patients for three days or six or something like that. And it's really showing that you cannot increase the secretion of PTH. So it's not something I don't understand from a scientific perspective, rational, but all the data I have seen is also indicating exactly the same thing. Scott was saying you have five patients. That is one thing. The MBX, this is the once-weekly one. And we have the possibility to develop once-weekly products for a long time. And now I'm talking of the concept of once-weekly first. We, in some ways, stalled it a little bit because we couldn't see the unmet medical need, and also because of the desire on different way of living with a hypopara patient where you sometimes need more or less and it can be done on exercise seasonal activities other things that change in your life and out from that we looked on patients how stable are them how often do they titrate up and down And we see only a small part of the patient being stable. So if we wanted to develop a once-weekly product, we would develop it as a baseline, like basal insulin, and then we still will have our daily product to really be sure they can adjust them up and down. The technology platform they're utilizing in the I always get it wrong. MBX or BMX. I cannot remember what is that bike. But I always get it wrong. But the element of that is basic technology, which are basic as an active entity. It's an isolated PTH that's 99.9% associated to basic, the element of albumin. I do not know how they ever can activate the phosphate receptor, how they can get into the brain and really restore normal industrious PTH level in the normal distribution you have out through the body. I'm also lost in the science there.

And our next question comes from David Lebowitz with Citi. Your line is open.

Thank you very much for taking my question. First of all, if you look at the Natpara patients that were left from mixed withdrawal, how long do you think it takes until that whole population gets worked through? And then further, looking back at Natpara and looking at what you've seen during your first quarter of launch, How would you, aside from the fact that the data is just superior, how would you characterize the difference in what patients are showing interest in this therapy?

First of all, you cannot compare the clinical benefit between Lepar and Uropax. NEPAR had a labeling as an adjunct therapy. Take a little bit of your daily calcium supplement away. Take a little bit of your active vitamin away, and then you take NEPAR. You have no positive impact on kidney function. You have no positive quantitative manner on quality of life. I see this as two different products, and we can never compare these two together. First question related to when the NAPA patient will be switched. We addressed it a little bit in the beginning of here, the discussion here, where we know that there was a letter from Takeda indicating that they're getting their last shipment now. And I think, as to our notice, the shipping is three months. So we expect that the last series of NAPA patient will be come over in either end of Q2 or Q3.

That is our expectations.

And our next question comes from Leland Gershell with Oppenheimer. Your line is open.

Thanks. Great to see the strong execution on USU as a path. A couple questions from us. Just apologies if this has been asked before, but with respect to potential benefits on renal I know, Jan, you had said that, you know, you don't see that as a key kind of driver for your overpath uptake. But nonetheless, are you able to comment in the early days of the U.S. launch? Are you seeing a more difficult or easier time to gain reimbursement or access to the drug for those patients who may have less or more renal impairment along with, you know, whatever needs they have in terms of conventional therapy? And then a second question. Thank you.

It's not a part of the reimbursement process. We don't see that it's the element that decides if it's reimbursement or not reimbursement. So it's like the same thing as we discussed on control, party control. Control is not part of the reimbursement process either. It's basic. When you look on the labeling, most plans have adapted the way that we basically have in our labeling, and it's not defined any way like that. One correction, Amy, we didn't study what we call severe renal impairment patients, and that is not part of our labeling, and I think it's stage four.

That's right. CFR lower than 16 or 13.

Yeah, which are a very, very low number, which are stage four, where we never started the drop.

Got it. Okay, that's helpful. And then just looking forward to the coach data, are you... Is there sort of a bar that you have in mind for linear growth, or is this something that you can see being driven forward principally on secondary benefits, say body composition or other? How are you thinking about kind of the mix of efficacy with the combination? Thank you.

When we think about acromioplasia, the key element for us is to address complications, but we cannot avoid also to address linears. so when we measure linear growth which got established from another company that is established as the primary endpoint i will personally have selected another endpoint if i could ever select that but we will because we are forced to do it because if the established clinical endpoint is that we will look on linear growth and it will be part of the data we basically will report when we come up with the analyzed high velocity, high SDS, and other things for that. And as I said before, I have great expectation. I have a strong belief that we can reset the bar for what you see in a counterplacer treatment. And it's not only related to linear growth, but also the associated complications.

All right, thanks very much.

This is all the time that we do have for questions. This concludes today's conference call and thank you for participating and you may now disconnect.