Ascendis Pharma A/S (ASND) Q2 2025 Earnings Report, Transcript and Summary

Good day, and thank you for standing by. Welcome to the Q2 2025 Ascendis Pharma Earnings Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Scott Smith, Ascendis Pharma's CFO. Please go ahead.

Thank you so much, operator. And thank you, everyone, for joining our second quarter 2025 financial results conference call. I'm Scott Smith, Executive Vice President and Chief Financial Officer at Ascendis Pharma. Joining me on today's call are Jan Moller Mikkelsen, President and Chief Executive Officer; Sherrie Glass, Chief Business Officer; Jay Wu, Executive Vice President and President U.S. Market; Aimee Shu, Executive Vice President of Endocrine and Rare Disease Medical Sciences and 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 as well as certain financial expectations, our pipeline candidates and our expectations with respect to their continued progress, and potential commercialization; our strategic plans, partnerships and investments; our goals regarding our clinical pipeline, including the timing of clinical results and trials; our ongoing and planned regulatory filings and our expectations regarding the timing and the results of our regulatory decisions. These statements are based on information that is available to us as of today. Actual results may differ materially from those in our forward-looking statements, and you should not place undue reliance on these statements. We assume no obligation to update these statements as circumstances change, except as required by law. For additional information concerning the factors that could cause actual results to differ materially, please see our forward-looking statements section in today's press release and the Risk Factors section of our most recent annual report on Form 20-F filed with the SEC on February 12, 2025. TransCon Growth Hormone or TransCon hGH is now approved in the United States by the FDA for the replacement of endogenous growth hormone in adults with growth hormone deficiency, in addition to the treatment of pediatric GHD and then the EU has received MAA authorization from the European Commission for the treatment of pediatric GHD. 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 Medicines and Health 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 efficacy of the 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 second quarter 2025 financial results, and we'll provide further business updates. Following some prepared remarks, we'll then open up the call for questions. With that, let me turn it over to Jan.

Thanks, Scott. Good afternoon, everyone. The second quarter of 2025 demonstrated strong momentum towards fulfilling our Vision 2030 as we progress towards blockbuster status for multiple products, and expand our engine for future innovation. The continued strong global launch of YORVIPATH increases our confidence that YORVIPATH is underway to become a blockbuster product with durable global leadership of the treatment of hypoparathyroidism. FDA granting us priority review for TransCon CNP, recognizing its potential, if approved, to provide a significant improvement in the safety and/or effectiveness of the treatment of achondroplasia. The announcement of the interim Phase II results from the first combination therapy trial of TransCon CNP and TransCon growth hormone highlights our potential to boost healthy growth in achondroplasia. And we achieved the first of many planned label expansion for SKYTROFA, when the FDA approved it for treatment of adult growth hormone deficiency. I will review these key developments in more detail in my prepared remarks. Beginning with YORVIPATH. Revenue in the second quarter reached EUR 103 million, more than double of Q1, despite a strong currency headwind. In the U.S. from launch to June 30, more than 1,500 prescribers wrote prescription for around 3,100 unique patients, reflecting both the deep unmet medical need and compelling product profile. For U.S. patients receiving a prescription for YORVIPATH, the majority has received payer approval within 3 months. Outside of the U.S., we continue to see steady YORVIPATH revenue growth in both our Europe Direct and international market. And we currently expect further acceleration of the revenue growth when YORVIPATH reimbursement becomes available in additional Europe Direct countries. With a broad label calling all types of chronic hypopara supported by international guidelines and a prominent reference to YORVIPATH in recently published best practice consensus statement, we expect growth to continue. We have an ongoing clinical program to support label expansion. For example, in older children, an initiated PaTHway 60 trial a single-arm safety and efficacy trial to support titration up to 60 microgram doses in the U.S. The primary endpoint of this trial will be efficacy at 26 weeks, the same as our pivotal Phase III trial endpoint. We are building towards YORVIPATH's long-term global leadership based on 3 key pillars: differentiation, demand and access. I will first speak about differentiation through mode of action, a replacement therapy for hypopara must maintain the same mode of action as endogenous PTH throughout the body and sustain physiological level of PTH 24 hours, 7 days a week. Based on all the data we have seen, YORVIPATH is the only product to demonstrate it can do this. With normalization of key elements such as serum calcium phosphate, kidney function, bone turnover and quality of life. Second is domain where YORVIPATH is available, we see strong interest and growing enrollment. For the U.S. market in just 2 full quarters, we had around 3,100 unique patients enrolled across more than 1,500 prescribers. We're seeing a broad uptake across the entire country. And with our estimate of 70,000 to 90,000 patients in the U.S., we still have ample room to grow. Outside the U.S., we have recognized revenue for more than 30 countries. And currently, we have commercial agreement covering more than 75 countries. Third is access. In the U.S. we see favorable access continue to improve with approvals coming across all payer segments. In Europe Direct, we have full commercial launch in Germany, Austria and now Spain. We expect additional commercial launches later this year, both in Europe Direct and international market. In Japan, our partner, Teijin expects approval improvement for YORVIPATH later this quarter. We consistently hear about how transformative YORVIPATH has been for patients and do not believe that any publicly disclosed drug in clinical development have the potential to meet this efficacy and safety bar set by YORVIPATH. As shown in our clinical trial, it has been extended for all patient groups, postsurgical HP patients, two small genetic subtypes like DiGeorge syndrome, ADH1 and idiopathic hypopara. Notably, YORVIPATH has brought approval from the FDA, the European Commission and other regulatory authorities for the treatment of all forms of chronic hypopara. For all of the above reasons, we are confident that YORVIPATH has the potential to become a durable blockbuster over time. And we continue to expand our global leadership position in the treatment of hypopara. Moving now to TransCon CNP. We believe TransCon CNP is moving the bar on safety, efficacy and tolerability and reducing treatment burden. And we believe TransCon CNP is well positioned to become the leading monotherapy treatment for achondroplasia. In clinical trials, we have seen the desired linear growth across all ages. And to our knowledge, once-weekly TransCon CNP is the only product to show statistically significant improvement beyond linear growth compared to placebo in a pivotal trial, for example, improvements in leg bowing and quality of life. We have demonstrated a safety and tolerability profile comparable to placebo, including no evidence of hypotensive effect and extremely low frequency of injection site reaction. Since our announcement of monotherapy data, we have engaged with patient advocates, physicians and regulators. All have appreciated the differentiating ability of TransCon CNP in comparison to placebo to increase linear growth while also leading to stronger muscle function, improved body proportionality and leg bowing and reducing overall, the burden of achondroplasia-related complication for the majority of treated children. And of course, patient and caregivers appreciate the much lower burden of once- weekly injection. During the second quarter of 2025, FDA accepted our NDA submission for priority review with a PDUFA date of November 30, recognizing TransCon CNP as a therapy that could, if approved, provide a significant improvement in safety and/or effectiveness. Next, I will review our combination trial results. As we look forward to the anticipated approval of TransCon CNP as monotherapy, we are investigating it in combination with our once-weekly TransCon Growth Hormone in children with achondroplasia in our COACH trial. In June 2025, we announced week 26 interim results, which showed a clear boost in linear growth and body proportionality improvement with the safety and tolerability profile consistent with those observed for monotherapy. In the combination trial, both treatment groups exceeded the 97% factor for growth of an average state of children, meaning they are achieving linear growth at a rate higher than an average child. The week 26 data demonstrate the potential to boost growth of around 3x above that observed with monotherapies addressing the hyperactive FDR3 receptor pathway, supporting the scientific rationale for treating with TransCon CNP and TransCon Growth Hormone combined. These results are without precedent in achondroplasia. Importantly, we see a clear indication that is healthy growth, the linear growth accommodated by improvement in body proportionality and without acceleration of bone age. All patients continue in the study as of today. These results enforce the role of TransCon CNP as a strong fundamental therapy in achondroplasia. We look forward to our 12-month data release later this year and plan to start a Phase III study of the combination therapy in children with achondroplasia by the end of '25. In addition, we also expect to initiate a pivotal combination trial in hypochondroplasia. I will now turn to SKYTROFA. SKYTROFA is established as a high-value brand and a treatment choice for pediatric growth hormone deficiency. We recently received FDA approval for adult growth hormone deficiency. And with further label expansion planned, SKYTROFA remains a fundamental pillar in our strategy to become the global leader in treatment of growth disorder. Q2 revenue for SKYTROFA were EUR 51 million. We continue to see growth in the number of people treated with SKYTROFA based on new patient start. We expect the recent label expansion for adult growth hormone deficiency to further drive long-term growth. Our market research shows SKYTROFA is the treatment of choice for pediatric growth hormone deficiency among patients and physicians. And we believe we can achieve the same status for treatment of adult growth hormone deficiency. Our Phase III basket trial of SKYTROFA planned to begin later this year will include a range of established daily growth hormone indications including ISS, SHOX deficiency, Turner and SGA. I often say that at Ascendis, we're just getting started. Following closely behind this major growth opportunity, our research team is developing the next day of innovative TransCon technology and product candidates. In addition, our ongoing collaboration with Novo Nordisk for the development and commercialization of TransCon-based product in metabolic and cardiovascular diseases continue to make progress towards the clinic. Ascendis is demonstrating a significant inflection in revenue growth. We are generating important new clinical data, working towards additional key label expansion. We are advancing new blockbuster opportunity to drive growth for many years to come and fulfill our Vision 2030, and we're already preparing for our next vision. I will now turn it over to Scott.

Thank you, Jan. I will touch on some key points surrounding our second quarter financial results, but for further details, please refer to our Form 6-K filed today. For Q2, our total product revenue was EUR 153.7 million, which includes a negative sequential foreign currency exchange rate impact of EUR 7.6 million. SKYTROFA revenue for the quarter was EUR 50.7 million, including a EUR 1.8 million negative currency impact. YORVIPATH delivered strong performance with revenue more than doubling to EUR 103 million, up from EUR 44.7 million in Q1 '25. This revenue growth was achieved despite a negative sequential currency headwind of EUR 5.8 million. Sequential growth across global markets remained strong with continued strong uptake in the U.S. acting as a key growth catalyst. The YORVIPATH U.S. launch and continued performance outside the U.S. are having a substantial impact on our financial profile, and we expect Ascendis to become cash flow positive on a quarterly basis this year including EUR 4.4 million of revenue from our collaboration partners, total Q2 revenue was EUR 158 million. Turning to expenses. R&D costs for the second quarter decreased to EUR 72 million compared to EUR 83.5 million in the same period last year, primarily driven by lower development costs for growth disorders. SG&A expenses in the second quarter of 2025 increased to EUR 107.6 million compared to EUR 74.3 million in the same period last year, primarily driven by global commercial expansion. Total Q2 2025 operating expenses were about EUR 180 million. Net finance income for the second quarter of 2025 was EUR 22 million, driven primarily by noncash items. Net cash financial expenses for the second quarter of 2025 were EUR 5.3 million. We ended the second quarter of 2025 with cash and cash equivalents totaling EUR 494 million compared to EUR 518 million as of March 31. Of the EUR 24 million sequential decrease in cash, EUR 19 million of that was due to the June 30 cash transition to -- cash translation to euro, so pretty close to overall cash breakeven for the quarter for the company. Turning to the remainder of 2025. We expect continued revenue growth driven by the strength of the global launch of the YORVIPATH. For SKYTROFA for modeling purposes, we continue to believe that sequential revenue growth for 2025 should track growth in prescriptions, offset somewhat by payer mix and normal seasonality. We also expect long-term growth for SKYTROFA to be driven by label expansion with our recent adult approval expected to only contribute modestly for 2025. We also continue to watch the euro-U.S. dollar exchange rate for any potential impact related to reported revenue. For YORVIPATH, our launch is progressing exceptionally well. Globally, we see YORVIPATH as a standard of care for treating hypoparathyroidism, and we believe it has the potential to achieve multiple billions of euros annually in peak sales over time, and our focus is on building long-term leadership. In the near term, as investors and analysts seek to model YORVIPATH's growth trajectory, I would highlight the following: Outside the U.S., we currently see continued steady sequential revenue growth. In the U.S., 7 months into launch, we are seeing strong continued demand and continuation of enrollment trends. We are seeing good conversion from enrollment to paid prescriptions with YORVIPATH. As Jan mentioned, the majority of U.S. patients are approved for reimbursement within 3 months of enrollment. Payer approvals are broad across commercial and government as well as geographies. We expect additional coverage policies and payer agreements to facilitate patient experience, access and continued long-term uptake. Based on our data so far, we expect persistence to be high because of the benefits to the patient, and we continue to monitor. And of course, we'll continue to look to help investors understand uptake and reimbursement dynamics as the year progresses. With that, operator, we're now ready to take questions.

[Operator Instructions] Our first question comes from Jessica Fye from JPMorgan.

Great quarter. You mentioned you're seeing a continuation of enrollment trends. And I think the number of unique patients enrolled grew by about 1,350 in 2Q. Is that the rate you mean that you see continuing?

Jess, I can start with a few overall view and then perhaps Jay can follow up. The number we reported was around 1,750 for the end of Q1. And here, the end of Q2, we reported 3,100. What we also said in our Q1 call that 200 patients, we will consider some kind of bolus injection because the 200 patients came from our ERP program. So when I take the numbers out from our Q1 number, the 200, it gives me about 1,550. And so in some ways, I actually believe that we see a steady state growth in the patient here between Q1 and Q2, when I take this consideration to the 200 patients that came from the [indiscernible]. And this is how we basically see the numbers, and this is very much aligned with our comments at the Q1 call, we expected to see a steady state development in the prescription and first, in the second part of the year, we expect to having an acceleration of the conversion of a patient that have a prescription be on treatment. So that is basically what we have seen. And we look forward to seeing Q3 and Q4, we are extremely optimistic about this launch. This is -- I'm not just talking about U.S., we see the same pattern everywhere where we're launching, but this really is amazing. And we expect to see the same stable state. Sure there can be a seasonal factor because of the summer vacation, at least we know in France, the August is closed and other places happening the same thing. So Jay?

Yes. Thank you, Jan. And as mentioned before, we are seeing that stabilization in enrollment. And again, we're still early in the launch. So we will need more time to observe what that steady state trend will be up as we get more months under our belt with the launch. More importantly, just as Jan mentioned earlier, we're focused beyond just the point of enrollment, right? We're looking across the entire funnel, from enrollments to approval, from approvals to patients on therapy, and we are seeing continued growth especially as it relates to the conversion of those patients on the therapy, and we're feeling good about what we are seeing.

Our next question comes from Derek Archila from Wells Fargo.

Congrats on the progress here. I just wanted to confirm something. So it sounded like you noted that there's 3 months from enrollment to conversion. I guess I just wanted to know like what are you doing to kind of improve that? And I guess, how much progress can you make on improving on that 3 months?

Nothing has really changed compared to what we said on our Q1 call. There is a lot of elements that Jay and the entire integrated commercial team are working with. We can go a little bit more in specific. But in the overall view, sure the different politics from the different PBM need to be installed. There is a lot of elements that still takes time. And we're also working a lot on the procedure of how we basically can help patients to be sure and physician and back office. So that is happening for our assist program that really are helping the patients. So nothing has changed compared to what we said in Q1 where we believe that we will first see in the second part of the year when many of these activities will be implemented. We will see an improvement in the time from a prescription and to a patient is on treatment. Jay, you can give a little bit more flavor on some of the initiatives on a high level because we have so many initiatives going on.

Absolutely. And thank you for the question. From a time to approval standpoint, as we said, we're seeing the majority within 3 months. And I would divide our efforts probably in a few buckets. The first 1 is upstream, right? We're continuing our payer education, whether it's at a commercial level or a public level, just on the clinical value proposition of the product, the full expansion for label because as you can all appreciate, whenever there's a new specialty drug on market, particularly a rare disease one, it oftentimes takes a bit of time for them to consider either a category or product that they may not have previously had on formulary or plan. So we anticipate that to continue to improve, which will, of course, have downstream impacts on the speed. More downstream from that, we also have a very experienced top, right? I think we've mentioned this before, we're quite experienced with being in managed care spaces. So some of the bread and butter work as it relates to ensuring that providers and patients are continuing to follow up, fill out their paperwork correctly, to decrease cycle times to ensure that, that paperwork isn't the reason why maybe something goes back and forth 1 or 2 extra times, which will then also increase the cycle. And then lastly, I would say, as we continue to have patients within the funnel, just making sure again that our partnership with our specialty pharmacy, so on and so forth, again, streamlining those processes to continue to shave off time as we work through this initial launch phase. All that to say, we're incredibly encouraged by the speed in which we're seeing and a reflection of the experience hub that we have, and we continue to look forward to seeing how that will progress.

Our next question comes from Tazeen Ahmad from Bank of America.

I was wondering if you could give us some color on the types of patients. There's been a lot of talk about initially severe patients, the most severe patients being put on YORVIPATH first. But do you have any color on what the split is between definitionally what a severe patient is versus the type of patients that are getting on that might be on the more moderate size?

Thanks, Tazeen, for the question. First of all, there is no medical definition that defines severity of hypopara. So we cannot go in and claim database on saying this is a severity that you have in the disease because all of them is not classified related to that. When we talked about the element of being uncontrolled, partly controlled or something we call controlled, this was mainly related to one single parameter looking on the claim databases and see how often they're seeing a physician. How often they are seeing a physician, I think, has a lot of multiple aspects that some way are not only reflecting where you're living in the country, what kind of medical access you have and also how often are there an endo that really can see you. So we did it from this perspective because we wanted to be quite sure we're addressing a physician that see a high number of patients in hypopara. And that was why we addressed this physician as our priority in our, you can say, commercial strategies. And so we can certainly not define and answer your question because there is no way this is part of the reimbursement system, is no part of what we can see for the patient because it's not a medical term that ever is defined. But I think, Tazeen, to give you also the other aspect on it, when we look on the guidelines that we see being integrated many different places, they are not using this kind of term either. So the guidelines just having a broad aspect on all the different elements that really qualify to be on PTH treatment. And in general, all the guidance we have seen being issued from all different places in the world now that are indicating that 95% percent of all patient basis should be on PTH treatment. And I think that is pretty logical. Think about how many patients on type 1 diabetes. Would you ever consider that you will not take all patients that have type 1 diabetes on insulin treatment. And I think you will see the same thing happening with hypopara.

Our next question comes from Yaron Werber from TD Cowen.

Great. Congrats, again. A couple of interrelated questions. Can you give us a little bit of a sense, Scott, you mentioned last quarter to expect Europe to grow about EUR 4 million to EUR 5 million. So that puts you at around EUR 24 million. So it almost seems like you did sort of EUR 79 million to EUR 80 million in the U.S. Am I sort of in the ballpark? And I guess, secondly, it's -- when one looks at -- we shouldn't be expecting that you're going to be growing patients 1,500 quarter- over-quarter. So can you give us a little bit of a sense how to think about what a sequential normalized growth at this point in the U.S. can be so we don't get out of hand?

I think I can help, Scott, this time, which I often do because what we said in our Q1 call, if you look on Q3 to Q4 revenue increased net revenue in euro was about EUR 4 million to EUR 5 million. And in this 2 quarter, it was basic Europe or ex U.S. revenue. And we also said at that time that we expect that to continue in '25. When we see more country coming on full commercialization as we just got Spain now, and we expect a few country more perhaps increase, but it will first have a material impact 2 to 3 months after basic initiation of full commercialization. So therefore, I will say your assumption is pretty correct and also reflecting what we said in Q1 this way. Related to the question you commented, it's some way a forward-looking statement. I know it's really being covered by Scott's fast reading. But from my perspective is that we see a strong, strong launch here in the U.S. We have seen nearly the same numbers between Q1 and Q2. And we're really looking forward, as Jay said, correctly, is early in the launch, it will be too early for us to come up with any kind of prediction how we really will see the next 6, 7 quarters to go.

Our next question comes from Gavin Clark-Gartner from Evercore ISI.

Congrats on another great quarter. First, what do you believe the ultimate conversion rate from the enrollment forms to pay drugs will be at any point in time? And then secondly, looking ahead, do you plan to keep reporting the enrollment forms YORVIPATH?

It's really difficult for us to give you a clear number. But what we always will see in the U.S., there will be a percentage of patients that have really difficulties to get reimbursed even if we try and help them multiple times. And what we see during the launch, which we have seen before, is that, what I call, the tail is getting faster and faster cleared out. And I can guarantee we will do everything in Ascendis manner to help that all the patients can come on treatment. Can we guarantee that everyone can go on treatment? No. There will be a number of patients even after 6, 9, 12 months, really struggling we will say is really hard to be covered. So you can ask about my personal success. My personal success will be if we get in steady state launch really with a mature product can get around 90% of all patients on treatment. I will feel it as a personal success and my contribution to help patients with hypopara. Jay, you can also come with your personal success number, if you want to do that.

Appreciate the question. I would say layer on a couple of things, right? I think the enrollment to approval, again, it's not just driven by payers. Of course, that's a component of it, right? Because as we've discussed before, there are certain plans and policies for which you have to go through exception or appeals process. And I think as Jan alluded to, that right tail will take some time to clear depending on the plan and as things evolve. The other component from enrollment to approvals is entirely unrelated to payers and it may just be more driven by ensuring, again, providers are leveraging the paperwork appropriately. Patients are following up with outreach a lot of that, which we'll continue to pursue across the spectrum because we know, again, that these patients can and should benefit from the product if they're already in the funnel. And we will do everything we can to clear that long tail out, knowing that it will take some time and when you look at a lot of rare disease analogs in these types of spaces, it can take some time to get there. But this is a long haul, and we're looking at it more from that lens to making sure we're optimizing every step of the way.

And are you guys planning to report enrollment forms for YORVIPATH in the next quarter also?

I think we will give you the necessary KPIs that we're doing today, and we will continue to do that in every quarter until we feel we come into a steady state where we feel that there is enough information just out from revenue that you can basically do your modeling. Until that, we will continue to provide the necessary data that support that you can make some modeling of the launches. Just to say and repeat it me, again, this is amazing launch. Q1 was great. Q2 was also amazingly great, and we have not seen any weakness in the launch.

Our next question comes from Li Watsek from Cantor.

Congratulations on the quarter. This is Daniel [indiscernible] on for Li Watsek. We're just curious about the pull-through of the patients that get on to YORVIPATH. How should we think about compliance, especially if you're saying that 1,500 PFS number as net patients going forward?

Where we have the best long-term data is from Europe, where we basically started the longest about 6 to 9 months before. And when we look on a rate, what we call true discontinuation is extremely low, a few centers. So we really see the benefit of the therapy. People are taking the therapy, they're taking it. They're keeping doing it. And I believe that is the contribution on how we're addressing a major unmet medical need with the treatment of YORVIPATH. So everything what we see here is far away for what you see with the diabetes drug, people stay on it even much better than insulin that you see in type 1 diabetes. And I think this is mainly a contribution to the positive CMS effect that is with this product.

Okay. Cool. And just on the -- just going back to Yaron's question earlier about the 1,500-patient net enrollment per quarter. Just for me to fully understand this is the patient start forms that you're referring to?

Yes, that is what we're referring to as unique prescriptions, meaning is that is a new patient that had got a prescription. This is what we call unique prescriptions.

Our next question comes from Joseph Schwartz from Leerink Partners.

I'm Joori Park dialing in for Joe. The first one is on YORVIPATH. I believe there were 1,500 prescribing health care providers in the U.S. by the end of the quarter. Can you help us understand how much of your target physician base this represents? And secondly, on CNP, a competitor recently announced that their long-acting CNP area under the curve PK level was 3x greater than the levels of TransCon CNP. Based on your experience with TransCon CNP, how could that translate in the clinic in your view? And how does that profile differ from your combination approach?

Yes. Let me start with the easy one or potentially will have taken that over to Jay. And I will take them more, I can say, scientifically interesting question as number two.

Sure. So happy to start with the first question. From a target list standpoint, we're talking about 8,000 to 10,000. So that you could consider that as a universe, about 3,000 of which we decile as high medium and we're seeing pretty good field execution metrics across that. So over 80% reach across our high medium priority targets.

So the second question is interesting because for many, many years, there was a lot of skeptics about our sustained profile. And then suddenly, there was a big change where the some may say, there is some benefit by having sustained profile does not give a high Cmax that basically can indicate risk of hypertension. And also, you need to have continuous exposure over 1 week. And so we started and designed our TransCon CNP in 2015 and now we are in 2025, we are starting now to go after that concept. From my perspective is that when you look on how we designed it and also all our associated patent filings we have with it or the IP we have on the optimal product, the medical treatment benefit and other things like that, people are now trying to copy with other concepts. And when I think about the concept I think there was some kind of making success of a product without disclosing the key element. The key element was AUC. I really don't care about AUC, I want to know key element, what is really the half-life? How is this exposure really happening? Is this something that beat up to a very, very high value there shortly and then you basically are going up to, as I call it, the danger zone of hypertension. That is not really a optimal product in this way. I believe what we saw in all our clinical data, it's really hard to do a lot when you remove a break because it's really the hill is rolling down that really designed the speed. If you have taken the brake off, the break is off. That is why I really don't get the biologic and scientific concept. That is related to linear growth. When we look at some of the other effect where we see muscle strengthening and other things like that, quite sure having continuous exposure, but we do not know exactly if that is maxed out or not. So out from that perspective, it's very doubtful, can you get more out on having a higher AUC. First of all, it needs to have the right AUC. This must be a higher exposure completely over the once-weekly profile. And no one discloses that because then they need to have a longer half-life than ours, that is about 2.5 to 3 days and I have not got any kind of disclosure that they are there. When I go out to our combination therapy, it's basically completely different concept because the concept of that is between synergies, between different biological pathways, which are well-known from so many other therapeutic areas to have the optimal treatment, you cannot overcompensate just by one pathway, but you're basically providing the benefit in a holistic manner in a much more normal manner by balanced different pathway. And that is what we do in the combination between TransCon CNP and the growth hormone effect. With that basic at the same time in a more simplified manner remove the brake with what we do with the CNP and then having a speed on that. So I feel really, really confident with our current state, our combination therapy that is really is a unique way where you really can totally provide for patients for physician at completely new treatment standard.

Our next question comes from Eliana Merle from UBS.

Congrats on the strong quarter. Curious for achondroplasia, what's your base case for the indication statement for TransCon CNP whether it be for the treatment of achondroplasia or for the increase in linear growth in achon like Voxzogo has? And I guess, any expectations for differentiation in the label relative to Voxzogo such as in terms of the indication statement or, say, other secondary endpoints? And then second, a follow-up question, just -- what's your perspective on the IP landscape for weekly CNP specifically, any thoughts on BMN 333 and where that might stand relative to the TransCon CNP IP estate?

Yes. We are progressing to the regulatory review with our TransCon CNP exactly as we hoped for in an accelerated priority review. Everything is happening on the right time. So labeling discussion is one of the last part in the group cycle. So it's really, really difficult for me to come up with any kind of elements. What I'm more referring to you is the data we have that is really backing up TransCon CNP. And I believe this is why we got the priority review because we have data that give a strong evidence that we can provide treatment benefit beyond linear growth. And now we're talking about everything what we have seen related to leg bowing, everything what we are seeing to muscle strength because people saying that they have also seen it. But you're not seeing it in a real manner. You need to see it in a placebo-controlled manner because either body proportionality is actually improving doing and normal development of a child also to an achondroplasia child. So how can you discriminate this really is a treatment benefit or just enormous development. And this is why it's so extremely important to be in a position that you're referring to data that is done in a placebo-controlled manner in a pivotal trial. I'm not referring to the other benefit we have, no risk of hypertension, low injection site. This is why the -- and sure obvious patient parents, parents, parents really love the once-weekly profile. It's just a little burden for them to give it in. So I think what I see here I'm not so much really concerned about exactly what is coming into the labeling. I'm more interesting is the benefit that we can go out and explain that TransCon CNP is providing, which I basically have never seen in any other well-controlled pivotal trial. I think that is the key element for me, and I think this is what we see everywhere. And the second question was about the IP. I believe that when we developed that in 2015, we basically filed a lot of IP. There was how to make an optimal product. There was a benefit of having a product that gives sustained things. As there is no clear for me exactly what is the primary structure that they have in the BMN 333, it's impossible for me to say exactly what we are. But if you can see me, at least, you can see I have a great smile on my lip and face because we are pretty good in what we're doing when we file IP.

Our next question comes from Kelly Shi from Jefferies.

Congrats on another strong quarter. For YORVIPATH, what is the typical titration period that you're seeing right now across now broader patient spectrum in real world? And once the patient completed titration period, should we expect a higher monthly cost?

So at least I got the first question related to the titration period. And I think, Aimee, our Chief Medical Officer knows a lot what we have seen in our clinical trials. I think we are much more uncertain about what is effectively happening in what we call real life clinical element. But what's a key element for me and I take it from that perspective, do we see a lot of patient unsatisfaction at that stage? Do we see a lot of patients drop out because there's a problem with it, and we don't see that. So I cannot really comment about what is exactly happening in the titration in -- for that patient in real world, but at least we can see that is happening successful. And your second question was?

Once the patient a complete titration, should we expect a higher monthly cost, because they are on higher dose, right?

I think in the U.S., we have an approval up to -- from 6 to 30 micrograms. So basically, we are in a position that we're only using 1/10 at the time. Outside U.S., there is a possibility to use up to 60 microgram. We have just initiated in what we call our 60- microgram trial, which will facilitate this is our aim. This is a 26-week trial to facilitate that we can get on labeling that can use up to 60 micrograms in the U.S. And I think when Jay has seen all the data and the coming near commercial, what I call commercial launch of up to the 60 micrograms, there will be a discussion from Jay's side exactly how we are handling the reimbursement for that situation. I think it's too early for us to comment on that.

Our next question comes from Paul Choi from Goldman Sachs.

Congratulations on the strong quarter results. Jan, just to follow-up on your last comment about potentially harmonizing the U.S. label with the EU label and the 60-microgram dose. When might you be in a position to submit that data to the FDA? And then commercially, what portion of the patient population would that potentially allow you to address that not being currently suited by the available presentations in the U.S. market?

Thanks a lot for the question. I actually think this is a lot of questions in the question because what is happening in the U.S. today, and I think there is a lot of different places where different elements on how to solve the issue if a patient needs more than surgical. There is some patients because of the label restriction to 30-microgram that will stay in a position that they're taking 30 microgram. And if needed, there will potentially take additional calcium supplement or an additional active vitamin D. There is other places where the basic patients on a physician's off-label will potentially get access to a higher dose, which we obviously have no any involvement and no recommendation. So from my perspective is that there is a need for a dose higher than 30. And we will do everything we can do to get it as fast as possible out to the patients. We're starting the trial now. It's a small trial. It's less than 20 patients. We are target enrollment of 18. It's only 26 week and we are utilizing the same pen devices that we basically have been already in the market. So there is no CMC component in this way. It's just for Aimee Shu and all her people to basically get the clinical trials done and get to the regulatory team to get it filed and approved. And we will do that as fast as possible. But it looks pretty, pretty promising to get it in.

Our next question comes from Alex Thompson from Stifel.

I guess on YORVIPATH as well, you've talked about the breadth of prescribers. So I wonder if you could comment on proportion of prescribers that you've seen with multiple prescriptions, multiple patients on therapy and how you see that trend changing over time?

We cannot really address that question. We don't have sufficient data that we really will feel confident to come with data that really support and strong trend analysis currently.

Our next question comes from Luca Issi from RBC.

Great. Congrats on the quarter. Maybe, Scott, lots of questions. Obviously, on the top line, rightly so, but how about SG&A, I mean, up 44% year-over-year and 6% quarter-over-quarter, appreciate how you're launching a drug, but how should we think about modeling SG&A for the rest of the year? I guess what I'm trying to ask here is how should we think about potential to achieve profitability in Q3 versus Q4? And then maybe secondarily, can you just remind us about Ascendis exposures around tariffs and MFN. Appreciate the situation is still fluid, and we don't have all the details, but any high-level commentary, much appreciated.

Okay. Great. On SG&A and expenses overall. So remember, last quarter, we did EUR 190 million of OpEx, and we said that wasn't a bad run rate, maybe plus or minus each quarter. So this quarter, we're minus about 10 from that. So we're about EUR 180 million of OpEx this quarter. And as you point out, it's probably not best to look year-over-year because we had a lot of growth in the last year. It's really the sequential build. So I would look at the 6% sequential growth for SG&A as potentially not a bad number to think about. But in the overall context of -- I would still say about EUR 190 million OpEx per quarter is not a bad number to think about. With respect to profitability, yes, we expect that this year. I mean, if you look at our financials and back out June 30 currency, thanks to our whatever it was called Liberation Day, that cost about EUR 20 million of cash delta. So overall, everything across the company, it was about EUR 5 of burn in Q2. And actually, on an operating basis, we're just slightly positive on cash. So that should be relatively doable this year. With respect to MFN and tariffs, I think you said it pretty well. there's really too much in development right now to make any comment, specifically on it. But we do believe that we're as a flexible company, we're pretty well positioned to mitigate impact of any policy should it emerge.

Just to clarify and also adding to Scott's comments, we're not importing finished product to the U.S., we import them in different states and finalize them inside the U.S. So in whatever way we look at it, we cannot see how it really should provide a major material impact on our business and how we operate.

Our next question comes from Leland Gershell from Oppenheimer.

Jan, just curious, in the past, you had not expressed much interest in hypochondroplasia as a development program and maybe you have started to lean a bit toward that earlier this year, and now we're seeing a formal announcement of intention to go in that direction. So I'm just wondering what may have changed that affected your decision process here? And if you could also maybe just share briefly what do you think is the opportunity for Ascendis in hypochondro?

Yes. hypochondroplasia is what I will call and perhaps the wrong way to define it, but I call it a milder form of achondroplasia. They don't have many of them the same, what we call body disproportionality. But you can say some in earlier days with many of these patients basically come in the ISS neuropathic short status. And now because of much more influence genetic testing, you basically have a development of a large group that more is well defined out from genetic testing to be hypochondroplasia. It's one point that basically are saying patient that was in one therapeutic group is now being moved over in a different therapeutic group and means they are moved from ISS over to hypochondroplasia, one thing. The second thing that is that when I saw the element of combination therapy, the TransCon CNP and TransCon Growth Hormone, then even if you have a very much heterogenic patient population. Then by having a combination product, you basically can ensure all of them will do extremely well. So you can say that is what really are bringing up my attention, while I believe we need to do it and also because I went out and talked with a lot of patients. And I think I'd like to talk with the patient and the patient organization because talking with them, I get much more idea about the unmet medical need we need to address. So basically, this is the 3 pillars that have changed. And I'd say the recent change of the therapeutic groups where the hypochondroplasia is growing because of allocation of patients from ISS over to hypochondroplasia and their heterogenic group that really I feel when I talk to patients, when I talk to the patient organization, you need a treatment and they are extremely positive data we got for a trial, where when you have such a heterogenic, some of the key element would be the CNP growth hormone will help but when CNP is the key element, CNP will help. And this is why when you have such a heterogenic group having the combination therapy will be the most realistic way to treat in a way where you really will have a fundamentally good treatment regime.

Our next question comes from the line of David Lebowitz from Citi.

Curious, has there been any evolution in your thinking on the ultimate size of the market for YORVIPATH, curious to know?

You know I've always been bullish and said that is going to be EUR 5 billion to EUR 8 billion market segment. And no doubt that it would be that.

Our next question comes from Yun Zhong from Wedbush.

The first question on TransCon CNP for achondroplasia. I assume that you receive FDA approval by the PDUFA day, how quickly will you be able to launch the product? And second question on hypochondroplasia and based on your comments just now, but the press release seems to be saying that either -- still either monotherapy or combination therapy. So is it still a possibility that you might end up going with a monotherapy for hypochondroplasia? And if that's the case, then what would be the reason why you don't go with combo therapy given the obvious benefit from COACH study?

The first one is we actually made some kind of precedent with SKYTROFA. We will wait until we get the approval. And likely, Scott will forced me to wake up in the morning, very, very, very early. So there will be a press release or some kind of call at 5:00 my time in the morning. And I think at that time, we will explain exactly when we have seen the labeling, got all the CMC information back from FDA and other places. When we will launch the product. And Jay will also be forced to be up in the morning, and he will explain how we're going to do our launch strategy in this way. So you need to wait a little bit to this early morning call and we will try not to do it on Sunday, but we will try to take it every other day. So the second part is a little bit about what we talked about before. This hypochondroplasia, in my view, is extremely heterogenic population now with a lot of what I call burden in a different way and also now with the reallocation of patients from the ISS Group into the hypochondroplasia, in some way, from my perspective, optimal will be to use the combination. And we we'll continue our dialogue with our regulatory agencies around the world to be sure that they also have the aligned view. I cannot some way eliminate the discussion if we will have in the clinical trial, a single arm also reflecting TransCon CNP as a monotherapy. But it's our belief that the combination therapy will be what is best for the patients in this way. So this is where we're for the time being, we believe that the combination is the most robust treatment on it. But obviously, there will be some patients that also just the benefit of having TransCon CNP as a monotherapy.

Our final question comes from Maxwell Skor from Morgan Stanley.

Forgive me if this question has been asked. But given the magnitude of growth velocity improvement in the COACH trial, do you believe a single pivotal trial could be sufficient for approval of the combination? Have you received any preliminary feedback from the FDA or EMA?

Yes. I have a lot of discussion with Aimee Shu about that. She is sitting in my sight because when we started this trial, we talked about our own expectations. And now we're sitting with a growth velocity that is so unprecedented as has been seen in achondroplasia. They are basically growing faster than a normal child. I have 4 children, and I remember when they have growth spur, it was not really good. We pretty tall, being Scandinavian. So you've really grow a lot. So you basically will be in a position that is -- this is really a big change in that. And some way I see it in -- and some may go back and forward in that discussion. Will you take a treatment of 1 year? Will you take a treatment of 2 years in the combination, you will get major growth and other positive development. Will you then go back for 1 or 2 years, just have TransCon CNP as a monotherapy and then you will boost again. If there is desire from the parents for the child and other things related to that. And if it's really unneeded at that time. So in some ways, when I think about the overall way how we will do the best for the patient -- in the achondroplasia patients is basically to give them an option that they really can be in a position where they can take combination therapy likely for 1 year, potentially 2 years and other things like that and get all the benefit and then we can continue with our TransCon CNP. And if they have a desire to move into other 1 yearly or 2- yearly treatment, they can do that again. That is more or less our thinking in this way.

That does conclude the question-and-answer session portion of this meeting. This also concludes the meeting itself. I'd like to thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

Thanks so much.

Thank you.