Ascendis Pharma A/S Price & Performance (ASND)

Thank you so much, operator. And thank you everyone for joining our first quarter twenty twenty five financial results conference call. I'm Scott Smith, Chief Financial Officer at Ascendis Pharma. Joining me on the call today are Jen President and Chief Executive Officer Sherry Glass, Chief Business Officer Jay Woo, Executive Vice President and President Ascendis U. S. 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 Skytrof and Yorvapat for The U. S, European and other markets well as certain financial expectations, our pipeline candidates and our expectation 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 expectation regarding the timing and results of regulatory decisions, expected market developments and our exploration of market opportunities in therapeutic areas outside of endocrinology rare disease. [indiscernible] 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 and you should not place undue reliance on these statements We assume no obligation to update these statements as circumstances change except as law.

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 most recent annual report on Form 20 F filed with the SEC on 02/12/2025. TransCon Growth Hormone Or TransCon HGH Is Approved In The U. S. By the FDA and then the EU has received MAA authorization the European Commission 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 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 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 the call today, we'll discuss our first quarter twenty twenty five 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 Yun. Thanks, Scott.

Good afternoon, everyone. In the first quarter of twenty twenty one, Ascendis continued the strong start of our global U. Launch. As well as key development and regulatory progress supporting our long term growth strategy to be a leading biopharma company. The strong U. S. Lungs of our U. Pet position twenty twenty five to be an inflection point for Ascendis. With a growing revenue base, and a clear path to become cash flow positive. As of March 31, you were per 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 launch. Europad, the first and only FDA approved treatment for hypoparathyroidism in adults. Is addressing the underlying cause of the disease. By providing active PTH. Within the physiological range for twenty four hours per day. [indiscernible] our long acting growth hormone. Is firmly established as a high value brand and the preferred treatment for patients physicians, and caregivers. SKYYTOVA is well positioned as daily treatment continues to exit The US market. And as Scottovir's label, has the potential to expand beyond its single indication. Skytrofa is a key pillar in our strategy to become a global leader in the treatment of growth disorder.

TransCon CNP 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 CNP has treatment benefits in addition to linear growth. That addresses multiple aspects of the condition that are fundamental 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 trial showed that TransCon CNP has the potential to transform the lives of people with achondroplasia. In my remarks, I will discuss each of these products in detail and comment on other recent development within our business. Beginning with Europads. First quarter total global Europaths revenue grew to €45,000,000 compared to €14,000,000 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 2,750 patients including the 200 patients from our ERP clinical program have been prescribed Europet In The US. By over 1,000 unique health care providers.

Enrollment of patients new to UFS. [indiscernible] at a similar weekly rate. In April. The majority of patients who have received insurance approval for their UroLift 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 UECAD in The U. S. Support our view of its excellent product profile.

And the major unmet need in my And we expect Europest to contribute significantly to our revenue in 2025. Outside of The U. S, we see steady Europad revenue growth. In both the Europe direct and international markets. And we expect additional acceleration of the revenue growth when reimbursement becomes available in additional Europe direct countries in the second half of the year. The continued rapid uptake together with high rates [indiscernible] patient adherence give us confidence that Europan is well positioned to uniquely address the unmet medical need of this patient population. And we are regular 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 [indiscernible] thousand to 90,000 patients in The U. S. Alone. Living the chronic hypoparathyroid Our claims analysis demonstrates that ten to fifteen thousand of these U. S. Patients are uncontrolled and thirty to thirty five thousand are partly controlled. Based on the latest clinical practice guidelines, nearly all these patients are candidate for treatment with Europets. Our strong global lungs 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 life span extending into the 2040s. Turning to schedule. Q1 revenues for SKYTOVA were €51,000,000 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 US. And around 43% of the total U. S. Long acting growth hormone market. Based on third party prescription data. The pediatric growth deficient indication represents about half of the total growth hormone market. With our premium pricing and Skytofra's leading position in pediatric growth hormone, deficiency. We believe we are well positioned to expand the opportunity for Skytrofir in multiple ways. A key near term milestone is our first potential label expansion in the established growth hormone indications [indiscernible] our supplement BLA for the potential U. S. Approval in adult growth hormone deficiency. Where we have a PDUFA goal date of July 2725. We are also on track to start a basket trial for Scott Hofer in a range of indications. Including idiopathic short statute. 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 transcon growth hormone. Outside established growth hormone indication. Thus, as in a potential combination therapy with TransCon CNP for treatment of achondroplasia and other growth disorder. Which I will address in a moment. Moving to TRADCON CMP. TretCon CNP is the third key product in our endocrinology rare disease product portfolio. Genetic variant that cause achondroplasia 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 CNP provides sustained teriporelin levels of CNP, throughout the body it has been demonstrated a unique product profile. Giving it the potential to bring growth benefit and important new benefit beyond linear growth. As well as reduce risk of hypertension and injection site reactions. In our pivotal approach trial TransCon CNP demonstrated significant improvement in the primary endpoint of linear growth compared to placebo. As well as significant improvement in other clinical [indiscernible] Meaningful to the achondroplasia community. Including leg bowing muscle functionality, body proportionality and health related quality of life. Leg bowing is a common complication in achondrocases. 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 U. S. Who have confirmed the importance of addressing the complication of agonist. Roplasia beyond linear growth. Just as important to the achondroplasia community, TransCon CNP has shown a safety and durability profile compared to placebo. With low frequency of injection site reactions. 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 CNP 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 twenty twenty five, we plan to submit an IND or similar to investigate TransCon CNP or in combination with TransCon growth hormone for the treatment of hypochondriacion. Shifting to TransCon CEMP and TransCon Growth Hormone Combination Therapy We are committed to continue to drive even better outcomes 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 pathways in the growth plates and other tissue in the body We look forward to sharing top line week 26 results from the COATH TRY data this quarter.

And see great potential to further raise the bar for clinical outcomes. With TransCon CNP, as the potential future backbone therapy. We believe we can achieve even greater growth while also addressing medical complication of achondroplasia. Fundamental to the development of each of our three medicine EuropaT, Skytopher, TransCon CNP, is Ascendis 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 Ascendis, our commitment has always been been to the patient. It is one of the company's core values. I believe we have demonstrated multiple times over the history of Ascendis 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 medicine become available to patients.

Through our collaboration with Novo Nordisk for the development and commercialization of TransCon technology based products in metabolic and cardiovascular disease, and our collaboration partner Wiesen Iconis and Tagli, we continue to work to execute our Vision 02/1930 to create value in large therapeutic areas and through innovative business models. In summary, 2025 is a transformative year for Ascendis. As we grow our global revenues from Europet, Skytrover and seek to obtain key regulatory approvals deliver robust clinical data and advance drugs 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 six ks filed today. YorbaPath's first quarter revenue increased significantly to 44,700,000.0 Euro up from EUR13.6 million in the fourth quarter of twenty twenty four. Steady sequential revenue growth outside The U. S. Was augmented by the strong U. S. Launch. As Jens discussed, the trends we saw for YorbaPath in Q1 continue in Q2, both outside and inside The U. S. And we anticipate that YorbaPath will have a substantial impact on our financial profile in 2025. Turning to Skytrofa. Revenue for this quarter was €51,300,000 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 copay 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 €101,000,000 which includes non product revenue from our collaboration partners. Turning to expenses, for the first quarter, R and D costs totaled €86,600,000 compared to €70,700,000 during the first quarter of twenty twenty four.

The first quarter of twenty twenty four included a favorable €10,600,000 reversal of prior period write downs of TransCon PTH prelaunch inventories. SG and A expenses in the first quarter of twenty twenty five totaled 1 and €1,000,000 compared to €66,800,000 during the first quarter of twenty twenty four. The 34,000,000 Euro increase was primarily driven by global commercial expansion. Total operating expenses were €188,000,000 for the first quarter of twenty twenty five. As a result of the Visa IPO, we recognized a non cash gain of €33,600,000 as part of share of profit loss of associates. And we retained 39% ownership of Visa. Net finance expenses for the first quarter of twenty twenty five were €15,900,000 driven primarily by non cash items. Net cash financial income for the first quarter of twenty twenty five was €3,300,000 We ended the first quarter of twenty twenty five with cash and cash equivalents totaling €518,000,000 compared to €560,000,000 as of 12/31/2024. Turning to the remainder of 2025, we expect substantial revenue growth driven by the global launch of Yorvapath with a continued solid contribution from Skytrofo. We are not providing revenue guidance for Skytropha or YorbaPath at this time. For Skytrofa, we believe that growth in prescriptions visible in third party data track sequential revenue growth for 2025 with expected stability and mix and pricing, including normal seasonality.

For YorvitaPath, outside The U. S, we continued steady revenue growth, while inside The US, our launch is progressing exceptionally well. We will continue to look to help investors understand uptake in reimbursement dynamics as the year progresses. With that, operator, we are now ready to take questions.

Thank you. 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 Fye with JPMorgan. Your line is open. Hey, guys. Good afternoon. Congrats on the strong results of your VPATH. 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 will 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 the 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, positive trend. We see the adaption of the different PPMs the different [indiscernible] [indiscernible] [indiscernible] if I'm someway to come with my own [indiscernible] 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 seven 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 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 commercial plan or government plan. It just sometimes may take a few more steps. Whether it's 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 of it 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 feeling. 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 med patients that benefit that 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're 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 are saying 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 of treatment you should be on treatment.

And our next question comes from Tazeen Ahmad with Bank of America Securities. Your line is open.

Hi, good afternoon. Thanks for taking my Yen, can you give us a little bit of color on the [indiscernible] between US and ex U. S. Revenue for the quarter? For Eurvy Path? And can you give us a sense because it's 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 the split between Europe and U. S. And as you have seen, Sachin, 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 basically into the situation that will be fully reimbursed. So when I look on the difference between Q3 and Q4, last year is something around the element of an increase, around 4 to €5,000,000 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 4 or 5,000,000 And then I think you would get a number around 26,000,000, 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 Evercore. 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, [indiscernible] fully reimbursed now Germany. There is a final list price you can find. We also have that for Austria. In France, we have an AP two program We can also have a different program in groups. So ex US, 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 '25 but also in '26 when we come to end of twenty twenty six, we believe we will have the waste majority of the important country being fully reimbursed. If you come to The US, which there is a strong focus on, Don't forget the more than 300,000 patients outside The U. S. I think Jay can give you more color about his discussion with the different plans in The US.

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 to 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 NATPARA. Sherry, you can potentially correct me if we have got more insight of 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 NaPiRp that we believe has been transferred over.

Yes, thanks for the question Gavin. And yes, Jen'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 something like ten percent to fifteen percent of patients that have been on some sort of PTH in the past and then a subset of those were more on that para. But the bottom line is overwhelmingly coming from conventional therapy.

Yeah, from that perspective, we believe that in Q2 and Q3, will see the majority of the rest of the NATPARA patients coming over because Amy, you're sitting with the patients, you can explain that there's an letter coming out explaining that you are in a position that are stopping. Right.

As far as we know, there's still some supply, so they still may be on it. But Yeah. The week we know it will exhaust soon. Yeah.

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

Great, congrats on the progress.

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

Yes, 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 maybe two, three, four patients with your VPATH. And then just a follow-up to the last set of questions, just are you seeing patients that are newly diagnosed or well controlled on conventional therapies move over to your vPASS? Thanks.

Yeah, I just could answer all your questions, will be a happy person. I'm still a happy person. But when I survey and share, you can also [indiscernible] We cannot really know if there are well controlled, costly controlled or non 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 had an algorithm that basically are saying the 10,000 to fifteen thousand of the patients we did find as uncontrolled is because they're seeing endo in a very, very, very high [indiscernible] And that was why we know that we just went to this physician that will automatically have all this patient coming in. So when they're coming and control patients that [indiscernible] that getting on NATPARA. I hope so. But I cannot really know but we know we really addressed patients that see the endo and high frequency And I believe that is basically I would call the genius part of our commercial organization. Really working on not getting patient into the endos It takes too long time as if I want to go into [indiscernible] practice in Stanford, I need to wait three months to get an appointment with her.

And I think we cannot wait for patient for that. And it was why we 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, partially 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 again. I would maybe say one of the things we're really excited about is we know they're quite a good healthy number of those uncontrolled and partially controlled patients. So, something like ten thousand to fifteen thousand uncontrolled and another thirty thousand or so partially controlled. And as Jens said, the uncontrolled patients are seeing their endos four times or more a year. So we know, to Yan'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 we have the part of the reimbursement system to have this uncontrolled partly controlled or controlled, we will know much more on it, but it's not a decision in the reimbursement And the next question comes from Yaron Werber with TD Cowen. Your line is open. Your line is now open.

Our next will be from Joe Schwartz with Leerink Partners. Your line is open.

Thank you and congrats on the very strong quarter.

Was wondering if you have a sense of how many of your target endos in The U. Have adequate resources at their center in order to be able to go back and forth with payers who might not approve reimbursement of Yorvi right away. Just given there's so many patients in The U. S. And a finite number of physician who treat them.

Could their ability to navigate this process represent a cap on your Pass revenue growth at some point?

Joe, it's something that [indiscernible] n the commercial organization have really a lot of thoughtful thinking about it How can we ensure the journey for the patient, 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 Skytrofur, the 10,000 patient we took big portion of that to medical exceptions. And I think there was the learning we got 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 SCALTOFA. [indiscernible] Yeah, to add on and to reinforce what Jan 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 top of office burden. But again going back to what Yan was sharing earlier, 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?

Yes, Hugh. Now you're asking about future again, and this is good. I'm covered by Scott's statement even 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 it was actually something I never thought about myself and there's a potentially why I thought it was really into Then I looked on achondroplasia and hypochondroplasia. Achondroplasia, as you can see, the more severe form for achondroplasia, hypochondroplasia, little bit more you can say easy form for achondroplasia less severe less bright because what FGR3 super activation is, is really putting a break on the system. So when you took on achondroplasia, you have the brake pulled down, hypochondroplasia, partially down. And then we'll look what is the difference between growth hormone treatment Over years with the two different [indiscernible] Achondroplasia and hydrocomfortplasia. And I have to think that it was very well done and you could basic I can give you the numbers. So [indiscernible] when you go to achondroplasia, you get a five six centimeters, which are typical what we have seen. But when you go up to hypochondroplasia, you are up on the eight centimeters.

And I actually think that it was really smart results because in some way what we're doing with CMP, we take an achondroplasia 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 insights.

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

Hi, thanks. Good afternoon and congratulations on commercial progress. Yorvapat, I wanted to ask if you have any color from the field as to what patient types it might be utilized 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 CNP 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?

Yes, let's keep first up in the demographic on The US, because if you look on the demographic in US, is that we have about 20% coming from we can call the genetic immunological everything else and then about 80% coming from the post surgical And that was very much reflected in our clinical trials So in our clinical trials, we even have an ADA patients. We actually have two, even though they are extremely hard to find because there are so few of them that have hypochondriacalasia. We actually managed to get them in. So, out from that perspective, is our clinical trial This is basically reflected the numbers I do not, Amy, if you have any comments. You can come with all the different genetic variants we have there. [indiscernible] We had autoimmune polyglandular syndrome type one. And DeGeorge syndrome. These were all seen in the trial. We know that we were seeing them in the expanded access program. And we don't always get that information on the commercial From what we hear from our clinicians who are with whom we speak, they're applying this to everybody. Yes. [indiscernible] a hypoperitoneal patient is a hypoperitoneal patient. 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 reflects the mirror of what we see in The U. S. And the next question comes from Lee Watsick with Cantor Fitzgerald. Your line is open.

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

Scott or Jake, who will take that?

I'll just say some preliminary comments. So, 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, you know, probably average very low 20% And commercial will depend on contracting of which Jay can comment. [indiscernible] Yep. Just as I echoed before, the contracting should be fairly minimal, again reflecting the clinical value proposition that we have. 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, SKYYTOVA So is there sort of a titration scheme here that we should think about and what the top dose that you can go to?

No, it's basic is that we have a starting dose in for the TransCon growth hormone in the combination with CMP, and they're also measuring IGF-one.

As they do in all trials. And if there is any possibility that the physician desire 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. [indiscernible] may I hear from Lee, which condition was she asking? As a combination.

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

Thank you.

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

Hey, guys. Thanks for taking the question. Curious just the feedback from the early patient starts, the titration process has gone on YorbaPath. Just logistically, 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 refill rate? I know it's early on, but 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 [indiscernible] [indiscernible] we have given you the German numbers under one percent and we see the same thing everywhere. If you start on Europeans you stay on Europanz. And that is a chronic treatment rest of your life.

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

Hi, good afternoon. Is Jose for Kelly. Congrats on the strong quarter. Thanks for taking our question. 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 your 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 [indiscernible] or controlled 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. 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 reimbursement discussion. The second question I need to understand a little bit more about what is exactly was you wanted us to address.

On the value proposition of the Orbit Pass, the the potential for preventing renal damage Would you consider running a clinical utility trial to perhaps facilitate uptake in milder patients who are control on SOC. Standard of care. I don't think really this is the key element going on a treatment. I have to say the key element to go on with treatment the benefit you get as a person. You're getting normal again. The long term risk is 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 Europad treatment not only for the patient, not only for the physician, but basically for the entire society.

All right. Thank you.

Some 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, [indiscernible] that the kidney function gets better. So may not 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 Izzi with RBC. Your line is open.

Great. Thanks so much for taking my question and congrats on the launch here. Maybe quick one on competition.

BridgeBio presented their data for their molecule early 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 Yorvipat? And then maybe Scott, super quickly, how should we think about the SG and A 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 to compound One is the catalytic which are being positioned into a phase three trial of ADX-one. Currently, ADH1 is being treated with Europax. And they're coming on treatment today. It has been hard for us to find a GS1 patient And Sherry, you went into the claim database how many [indiscernible] Yeah. There were something like three hundred and fifty patients who'd had a claim associated with ADH-one in the past like, 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 hypoparra patient that is not AES-one. You know, I'll read a lot of science I don't understand the science there. You're trying to position into a place of a patient that not have [indiscernible] [indiscernible] How can you increase the level of endogenous PTH when we're not producing it? They're already producing on max and there is actual a very nice poster basically showing that they are taking 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've seen is also indicating exactly the same thing. Scott was saying the other side, please. Okay. That is one thing. The MBX this is a once weekly one. [indiscernible] [indiscernible] possibility to develop once weekly products for a long time. And now I'm talking of the context of once weekly. First.

We in some ways, stalled a little bit because we couldn't see the unmet medical need and also because of the desire on different way of living with an hyperthera 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 patient 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 have a 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 MPX or BMX cannot remember what is that bike, but I always get it wrong. But the element of that is basic technology, which are basic asset active entity is an isolated [indiscernible] 99.9% associated to basically the element of albumin. I do not know how that ever can activate the phosphate receptor, how that 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. If, first of all, if you look at the NATPARA patients that were left from its withdrawal, how long do you think it takes until that whole population gets worked through? And then further looking back at NetParra and looking 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 in this therapy.

First of all, you cannot compare. The clinical benefit between Lapar and Europan. Lepam 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 NATPARA. 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. So and I think as to our knowledge, the shipping is a three month So we expect that the last series of NaPar patients will become 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 RiverPath. USU couple of questions from us. Just apologies if this had been asked before, but with respect to potential benefits on renal I know Jen, you had said that you don't see that as a key 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 for Diraccess to the drug for those patients who may have less or more renal impairment along with 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 decide of reimbursement or not reimbursement. So it's like the same thing as we discussed on control, party control. Controls is not part of the reimbursement process either. It's basic when you look on the labeling most plans have adapted the weight that we basically have in our labeling. [indiscernible] first one correction. Amy, we didn't study in 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. Yeah.

TFR lower than 16 or 30.

Yeah.

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

Got it. Okay, that's helpful.

And then, just looking forward to the Coach data, Are are you is there sort of a bar that you have in mind for linear growth or is this something that you could 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 air convalescent, the key element for us is to address complications. But we cannot avoid also to address linear 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 it's 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 height velocity, height status, 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 achondroplasia treatment and it's not only related to linear growth but also the associated complications.

Great. Thanks very much.

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