Ascendis Pharma A/S (NASDAQ:ASND) Q1 2025 Earnings Call Transcript

Ascendis Pharma A/S (NASDAQ:ASND) Q1 2025 Earnings Call Transcript May 1, 2025

Ascendis Pharma A/S misses on earnings expectations. Reported EPS is $-1.79348 EPS, expectations were $-1.56.

Operator: Ladies and gentlemen, thank you for standing by and welcome to Ascendis Pharma First Quarter 2025 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker’s presentation, there will be a question-and-answer session. [Operator Instructions] 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.

Scott Smith: 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 Ascendis Pharma. Joining me on the call today are Jan Mikkelsen, President and Chief Executive Officer; Sherrie Glass, Chief Business Officer; Jay Wu, Executive Vice President, and President Ascendis U.S.; and Aimee Shu, Chief Medical Officer. Before we begin, I would like to remind you that this conference call will contain forward-looking statements that are intended to be covered under the Safe Harbor provided by the Private Securities Litigation Reform Act. Examples of such statements may include, but are not limited to, statements regarding our commercialization and continued development of SKYTROFA and YORVIPATH for the U.S., European, and other markets, as well as certain financial expectations, our pipeline visits, and our expectations with respect to their continued progress in 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 the 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 the information that is available to us today. Actual results may differ materially, could differ materially from those in our forward-looking statements, and you should not place undue reliance on these statements. We assume no obligation to update these statements as circumstances change, except as required by law. For additional information concerning the factors that could cause actual results to differ materially, please see our forward-looking statement 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 February 12, 2025. TransCon Growth Hormone or TransCon hGH, is approved in the U.S. by 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 investigational products, the safety and effectiveness of product candidates have not been reviewed or approved by any regulatory agency. None of the statements during this conference call regarding our product candidates shall be viewed as promotional. On the call today, we’ll discuss our first quarter 2025 financial results and we’ll provide further business updates.

Following some prepared remarks, we will then open up the call for questions. With that, let me turn it over to Jan.

Jan Mikkelsen: Thanks, Scott. Good afternoon, everyone. In the first quarter of 2025 Ascendis continued the strong start of our local YORVIPATH 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. launch of our YORVIPATH position 2025 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, YORVIPATH was prescribed in the U.S. by more than 1,000 unique prescribers for more than 1,750 patients. This represents our first full quarter for the U.S. launch. YORVIPATH, the first and only FDA approved treatment for hypoparathyroidism in adults, is addressing the underlying cause of the disease by providing active PT8 [ph] within the physiological range for 24 hours per day.

SKYTROFA, our long acting growth hormone, is firmly established as a high value brand and the preferred treatment for patients, physicians and caregivers. SKYTROFA is well positioned as daily treatment continue to exceed the U.S. market and as SKYTROFA 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 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 trial show 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 YORVIPATH, first quarter total global YORVIPATH revenue grew to €45 million compared to €40 million in the fourth quarter of last year. Following commercial availability in the U.S. in December of last year, we are seeing strong U.S. demand, reflecting both the deep unmet medical need in the market as well as the last patient population. As of March 31, more than 1,750 patients, including the 200 patients from our ERP and clinical program have been prescribed YORVIPATH in the U.S. by over 1000 unique healthcare providers.

Enrollment of patients new to YORVIPATH continued at a similar weekly rate in April. The majority of patients who have received insurance approval for their YORVIPATH 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 care plans put into place and continues to see approvals across both commercial and governments. The strong launch performance of YORVIPATH in the U.S. support our view of its excellent product profile and the major unmet medical need in the market, and we expect YORVIPATH to contribute significantly to our revenue in 2025. Outside of the U.S. we see steady YORVIPATH revenue growth in both the Europe Direct and international markets, and we expect additional acceleration of the revenue growth when YORVIPATH reimbursement becomes available in additional Europe Direct countries in the second half of the year.

The continued rapid uptake, together with high rates of patient adherence give us confidence that YORVIPATH 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 70,000 to 90,000 patients in the U.S. alone living with chronic hypoparathyroidism. Our claims analysis demonstrates that 10,000 to 15,000 of these U.S. patients are uncontrolled and 30,000 to 35,000 are partly controlled. Based on the latest clinical practice guideline, nearly all these patients are candidates for treatment with YORVIPATH. Our strong global launch give us high conviction that we can continue to build and lead this market and YORVIPATH can be a durable multibillion euro drug device product with a patent lifespan extending into the 2040s.

Turning to SKYTROFA. Q1 revenues for SKYTROFA were €51 million. 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. long acting growth hormone market based on third party prescription data. The pediatric growth deficiency indication represents about half of the total growth hormone market. With our premium pricing and SKYTROFA’s leading position in pediatric growth hormone deficiency, we believe we are well positioned to expand the opportunity for SKYTROFA 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 U.S. approval in adult growth hormone deficiency where we have a PDUFA goal date of July 27, 2025.

We are also on track to start a basket trial for SKYTROFA in a range of indications including idiopathic short stature shock deficiencies, Turner syndrome and SDA. We are planning to discuss this trial with the FDA in an end of Phase 2 meeting this quarter. Importantly, we are also investigating TransCon Growth Hormone outside the established growth hormone indication such as in a potential combination therapy with TransCon CNP for treatment of achondroplasia and other growth disorders which I will address in a moment. Moving to TransCon CNP. TransCon CNP is the third key product in our endocrinology rare disease product portfolio. The genetic variant that causes achondroplasia changes the way receptors 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 therapeutic levels of CNP throughout the body, it has been demonstrated an unique product profile given is 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 pivotal ApproaCH Trial, TransCon CNP demonstrated significant improvement in the primary impact of linear growth compared to placebo as well as significant improvement in other clinical endpoint 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 achondroplasia 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 achondroplasia 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 injectant 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 their 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 CNP or in combination with TransCon Growth Hormone for the treatment of hypoparathyroidism.

Shifting to TransCon CNP and TransCon Growth Hormone combination therapy, we are committed to continue to drive even better outcome for people living with achondroplasia. This is why we are conducting the COACH Trial, being the first Phase 2 study combining CNP 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 COACH Trial 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 complications of achondroplasia. Fundamental to the development of each of our three medicines, YORVIPATH, SKYTROFA, TransCon CNP 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 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 product in metabolic and cardiovascular disease and our collaboration partner Visen, Iconis [ph] and [indiscernible], we continue to work to execute our Vision 2030 to create value in vast therapeutic areas and through innovative business model.

In summary, 2025 is a transformative year for Ascendis as we grow our global revenues from YORVIPATH and SKYTROFA 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 it to Scott.

Scott Smith: 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. YORVIPATH first quarter revenue increased significantly to €44.7 million, up from €13.6 million in the fourth quarter of 2024. Steady sequential revenue growth outside the U.S. was augmented by the strong U.S. launch. As Jan discussed, the trends we saw for YORVIPATH in Q1 continue in Q2 both outside and inside the U.S. and we anticipate that YORVIPATH will have a substantial impact on our financial profile in 2025. Turning to SKYTROFA, revenue for this quarter was €51.3 million. 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 million, which includes non-product revenue from our collaboration partners. Turning to expenses for the first quarter, R&D costs totaled €86.6 million compared to €70.7 million during the first quarter of 2024. The first quarter of 2024 included a favorable €10.6 million reversal of prior period write downs of TransCon PTH prelaunch 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 Visen IPO we recognized a non-cash gain of €33.6 million as part of share of profit loss of associates and we retained 39% ownership of Visen. Net finance expenses for the first quarter of 2025 were €15.9 million driven primarily by non-cash items. Net cash financial income for the first quarter of 2025 was €3.3 million. We ended the first quarter of 2025 with cash and cash equivalents totaling €518 million, compared to €560 million as of December 31, 2024. Turning to the remainder of 2025, we expect substantial revenue growth driven by the global launch of YORVIPATH with a continued solid contribution from SKYTROFA. We are not providing revenue guidance for SKYTROFA or YORVIPATH at this time.

For SKYTROFA, we believe that growth in prescriptions, visible in third party data, will track sequential revenue growth for 2025 with expected stability in mix and pricing, including normal seasonality. For YORVIPATH, 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 in reimbursement dynamics as the year progresses. With that operator, we are now ready to take questions.

Q&A Session

Operator: Thank you. [Operator Instructions] And our first question today will come from Jessica Fye with JPMorgan. Your line is open.

Jessica Fye: Hey guys, good afternoon. Congrats on the strong results with YORVIPATH. 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 YORVIPATH 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.

Jan Mikkelsen: Thanks Jess for the questions and Scott will take the easy one, the last one.

Scott Smith: Yes, 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.

Jan Mikkelsen: The second one and Jess why it’s a little bit more complicated because there’s some way looking in the future. What we can see, we see a positive trend. We see the adaption of the different PPMs, the different payer forms. And if I’m somewhere to 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.

Jay Wu: Yes, 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 of it in the U.S., but overall we have a lot to be encouraged about and I think more importantly it just really emphasizes the clinical value proposition of these products and the fact that payers, providers and patients are all responding to it.

Jan Mikkelsen: I think, but Jess, I think some way when I talk about my feeling, my feeling is that I believe every patient that some way have a desire to go on treatment should come on treatment because I have seen, I have heard med patient the 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 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 guideline they 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 on treatment, you should be on treatment.

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

Tazeen Ahmad: Hi, good afternoon. Thanks for taking my question. Jan, can you give us a little bit of color on the split between U.S. and ex-U.S. revenue for the quarter for YORVIPATH? 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.

Jan Mikkelsen: Yes. Let me first address the question, the split between Europe and U.S. and as you have seen, Tazeen 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-U.S. we see a steady growth, a steady acceleration. What 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 of an increase around €4 million to €5 million from one quarter to the next quarter. So when you think about that we increased our basic revenue from about €40 million to €45 million, then you can take basic the difference and then subtract about €4 million to €5 million and then I think you would get a number around €26 million which are somewhere reflecting the algorithm I would use if I should look at it.

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

Gavin Clark Gartner: 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 expect 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?

Jan Mikkelsen: Yes, it’s a question, I will take the global perspective. As you heard about ex-U.S. we are basic 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 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 but also in 2026. When we come into 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.

Jay Wu: 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.

Gavin Clark Gartner: Okay, great. And then quick follow-up for the new prescriptions that are coming in. What proportion are NATPARA or PTH naïve versus experienced? Thank you.

Jan Mikkelsen: I don’t think we really have the full insight exactly how many deaths coming from the NATPARA. Sherrie, 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, Sherrie, you can discuss exactly how many NATPARA patients that we believe has been transferred over?

Sherrie Glass: Yes, thanks for the question, Gavin. And yes, Jan’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 10% to 15% of patients that have been on some sort of PTH in the past and then a subset of those were more recently on NATPARA. The bottom line is overwhelmingly coming from conventional therapy.

Jan Mikkelsen: Yes. From that perspective, we believe that in Q2 and Q3, we will see the majority of the rest of the NATPARA patient coming over, because Aimee, you’re sitting with the patients, you can explain that there is a letter coming out explaining that you are physician, that they’re stopping.

Aimee Shu: 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.

Jan Mikkelsen: Yes. So the basic, when we look at the patient that’s coming over the 1,750, this is not NATPARA patients. This is basically patient that’s coming from conventional therapy. The 35,000 patients we are addressing now. So there is a lot of deepness to go in this way.

Gavin Clark Gartner: Great. Congrats on the progress.

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

Derek Archila: Yes, congrats on the quarter and thanks for taking the questions. 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 the YORVIPATH. And then just to 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 YORVIPATH? Thanks.

Jan Mikkelsen: Yes, if I just could answer all your questions, I will be unhappy person. I’m still a happy person. But when I, some way and share, you can also some way 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 assessment. I actually think why we call them uncontrolled, we likely will see more of them because we had an algorithm that basically are saying that 10,000 to 15,000 of the patient we define as uncontrolled is because we are seeing and endo in a very, very, very high frequency. And this is 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 NATPARA? I hope so, but I cannot really know. But we know we really addressed the patient that sees 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 Aimee’s practice at Stanford. I need to wait three months to get an appointment with her. And I think we cannot wait for patient for that. And that 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 we are seeing the indo much more often than the other ones.

So, Sherrie, do you have anything to add?

Sherrie Glass: I think you covered it well. Again, 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 arm and partially controlled patients. So something like 10,000 to 15,000 uncontrolled and another 30,000 or so partially controlled. And as Jan said, the uncontrolled patients are seeing their endos four times or more a year. So we know to Jan’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.

Jan Mikkelsen: Yes. And one of the reason why we don’t know it is because it’s not part of being reimbursed or not. So if we’re part of the reimbursement system to have this uncontrolled, partly control or control, we will know much more on it, but it’s not a decision in the reimbursement system.

Operator: And the next question comes from Yaron Werber with TD Cowen. Your line is open. Yaron, your line is now open. Our next question will be from Joseph Schwartz with Leerink Partners. Your line is open.

Joseph Schwartz: 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 U.S. 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 offices who treat them, could their ability to navigate this process represent a cap on YORVIPATH revenue growth at some point?

Jan Mikkelsen: 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 SKYTROFA that 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 SKYTROFA. Jay, you can go much more anything than that.

Jay Wu: Yes. Just 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 type of office burden. But again, going back to what Jan 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.

Joseph Schwartz: 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 and the COACH Trial?

Jan Mikkelsen: Yes, Joe, now you’re asking about the 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 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. Well 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 braked. Because what FTR3 super activation is really putting a brake on the system. So when you took on achondroplasia you have the break full down, hypochondroplasia partially down.

And then they look what is the difference between growth hormone treatment over years with the two different therapeutic error achondroplasia and hypochondroplasia. And I actually think that it was very well done and you could basically, I can give you the numbers. So when you go to achondroplasia you get 5 cm, 6 cm which are typical what we have seen. But when you go up to hypochondroplasia you up on the 8 cm. And I actually think that it was really smart research because in some way what we’re doing with CNP we take an achondroplasia patient and remove the brake. 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.

Joseph Schwartz: Thanks for the insights.

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

Paul Choi: Hi, thanks. Good afternoon and congratulations on the commercial progress. On YORVIPATH, 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 postsurgical patients? Or are you seeing other causes of disease like genetic and 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?

Jan Mikkelsen: Yes. 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 postsurgical. And that was very much reflected in our clinical trial. 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 hypochondroplasia. We actually managed to get them in. So out from that perspective is our clinical trial. This is basic reflected the numbers. I do not. Aimee, if you have any comments, you can come with all the different genetic variants we have there.

Aimee Shu: Yes, we had GATA3 mutation. We had autoimmune polyglandular syndrome type 1 and DiGeorge syndrome. These are 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 who are with whom we speak, they’re applying this to everybody.

Jan Mikkelsen: Yes. So basically a hypopara patient is a hypopara patient and this is how I 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 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 U.S.

Operator: And the next question comes from Li Watsek with Cantor Fitzgerald. Your line is open.

Li Watsek: Hey guys, wanted to add our congrats as well on a strong launch. Maybe just first on YORVIPATH in terms of 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.

Jan Mikkelsen: Scott or Jay, who will take that?

Scott Smith: 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.

Jan Mikkelsen: Yes, Jay.

Jay Wu: Yes, just as I echoed before, the contracting should be fairly minimal, again reflecting the clinical value proposition that we have. So, if there’s a change, it won’t be materially different just relative to the other markets we’ve been in.

Li Watsek: Okay. And then just follow-up on the Phase 2 COACH trial. I know you have a starting dose for SKYTROFA. So is there sort of a titration scheme here that we should think about and what a top dose that you can go to?

Jan Mikkelsen: No, it’s basic is that we have a starting dose for the TransCon Growth Hormone in the combination with CNP and they’re also measuring IGF-1 as they do in all trial. 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 Aimee, the protocol better than I do.

Aimee Shu: And may I hear from Li which condition was she asking?

Jan Mikkelsen: As a combination.

Aimee Shu: Combination? Yes, so there will be a starting dose that is informed both based on the Phase 2 trial that we’re currently doing in the combination trial and also from the many the conditions we’re studying where they’re short stature but a sufficient Growth Hormone access. Right? So this will give us, based on what we’re seeing so far, there can be a very good and safe universal starting dose typically.

Li Watsek: Great, thank you.

Operator: And our next question will come from Ellie Merle with UBS. Your line is open.

Ellie Merle: Hey guys, thanks for taking the question. And curious, just the feedback from the early patient starts how the titration process has gone on YORVIPATH 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.

Jan Mikkelsen: 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 out. 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 is exactly as high as we saw it in the clinical trials, which was really unique and drop out. We have given you the German numbers under 1% and we see the same thing everywhere. If you start on YORVIPATH, you stay on YORVIPATH and that is a chronic treatment rest of your life.

Ellie Merle: Thank you.

Operator: The next question comes from Kelly Shi with Jefferies. Your line is open.

Unidentified Analyst: Hi, good afternoon. This is Joseph [ph] for Kelly. Congrats on the strong 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 YORVIPATH, would you consider running a clinical utility trial to facilitate uptake in milder [ph] patients? Thank you.

Jan Mikkelsen: Related to your first question, as the part we discussed before, being uncontrolled, partly controlled 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, we believe many of them, the majority is coming for 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 what you wanted us to address?

Unidentified Analyst: On the value proposition of YORVIPATH, 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?

Jan Mikkelsen: I don’t think really this is the key element for going on a treatment. I have to say 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 YORVIPATH treatment not only for the patient, but not only for this physician, but basic for the entire society.

Unidentified Analyst: All right, thank you.

Aimee Shu: 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 and that when that is able to be lowered in whatever way that the kidney function gets better. So there may not, we’ll see what the need is for demonstrating this yet again.

Unidentified Analyst: Very helpful, thank you so much.

Operator: And the next question comes from Luca Issi with RBC. Your line is open.

Luca Issi: Oh, 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 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 YORVIPATH? 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? I much appreciate it. Thanks so much.

Jan Mikkelsen: Yes, you Mentioned two compounds. One is the calcilytics [ph] which are being positioned into a Phase 3 trial of ADH1. Currently ADH1 is being treated with YORVIPATH and they’re coming on treatment today. It has been hard for us to find ADH1 patient. And Sherrie you went into the claim database and how many patients did you find with ADH1?

Sherrie Glass: Yes, there were something like 350 patients who’d had a claim associated with ADH1 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.

Jan Mikkelsen: So it’s not going to change anything for us because we addressing the position of calcilytics into the era of for example what we call chronic hypopara patient that is not eight years one. 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 not have endogenous PTHs. How can you increase the level of industrious PTH when they’re not producing it? They’re already producing on MAX and there is actually very nice poster. They’re basically showing that they are taking calcilytic 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. There are five patients that is one thing the MPX this is the once weekly one. And we have the possibility to develop once weekly product for a long time. And now I’m talking of the content of once weekly first, we some ways stalled it a little bit because we couldn’t see the unmet Medicare needs 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 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 the asset baseline like basal insulin and then we still will 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. I cannot remember what is that bike, but I always get it wrong. But the element of that is basic a technology which are basic as an active entity is an isolated PTH that stays 99.9% associated to basic the element of albumin. I do not know how that ever can activate the phosphate receptor, how they can get into the brain and really restore normal [indiscernible] PTH level in the normal distribution you have out through the body. I’m also lost in the science there.

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

David Lebowitz: Thank you very much for taking my question. First of all, if you look at the NATPARA patients that were left from this withdrawal, how long do you think it takes until that whole population gets worked through? And then further looking back at NATPARA and looking what you’ve seen during your first quarter of punch, 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?

Jan Mikkelsen: First of all, you cannot compare the clinical benefit between NATPARA and YORVIPATH. NATPARA 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 NATPARA 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 are getting their last shipment now. So and I think as to our knowledge, the shipment is three months. So we expect that the last series of NATPARA patients will become over in either end of Q2 or Q3. That is our expectations.

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

Leland Gershell: Thanks. Great to see the strong execution on [indiscernible] YORVIPATH. A couple questions from us. Just apologies if this had been asked before, but with respect to potential benefits on renal, I know Jan, you had said that you don’t see that as a key driver for YORVIPATH 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 whatever needs they have in terms of conventional therapy? And that is second question. Thank you.

Jan Mikkelsen: It’s not a part of the reimbursement process. We don’t see that it’s the element that decide offers 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 is not defined anyway or that that is first one correction, Aimee 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 4.

Aimee Shu: That’s right. CFR lower than 15 or 30…

Jan Mikkelsen: Which are a very, very low number, which are Stage 4 where we never started the drop.

Leland Gershell: Got it. Okay, that’s helpful. And then just looking forward to the COACH data. 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 your combination? Thank you.

Jan Mikkelsen: When we think about achondroplasia, the key element for us to address complications but we cannot avoid also to address linear growth. 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 they will be part of the data we basically will report when we come up with the analyzed high velocity height, as there is 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.

Leland Gershell: Great, thanks very much.

Operator: 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.