Good day, and thank you for standing by. Welcome to the Q2 2025 Ascendis Pharma Earnings Conference Call. 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 on track to become a blockbuster product with durable global leadership in the treatment of hypoparathyroidism. The FDA granting us priority review for TransCon CNP recognizes 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 expansions for SKYTROFA when the FDA approved it for the 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 that of Q1, despite a strong currency headwind. In the U.S., from launch to June 30, more than 1,500 prescribers wrote prescriptions 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 have 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 markets. We currently expect further acceleration of the revenue growth when YORVIPATH reimbursement becomes available in additional Europe Direct countries. With a broad label calling for all types of chronic hypoparathyroidism supported by international guidelines and a prominent reference to YORVIPATH in a 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, we initiated the 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 three key pillars: differentiation, demand, and access. I will first speak about differentiation through mode of action. A replacement therapy for hypoparathyroidism must maintain the same mode of action as endogenous PTH throughout the body and sustain physiological levels of PTH 24 hours a day, 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. Secondly, regarding demand, we have seen strong interest and growing enrollment. In the U.S. market, in just two full quarters, we reached around 3,100 unique patients enrolled across more than 1,500 prescribers. We're seeing 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 in more than 30 countries and currently have commercial agreements covering more than 75 countries. Third is access. In the U.S., we see favorable access continuing to improve with approvals coming across all payer segments. In Europe Direct, we have a full commercial launch in Germany, Austria, and now Spain. We expect additional commercial launches later this year, both in Europe Direct and international markets. 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 has the potential to meet this efficacy and safety bar set by YORVIPATH. Our clinical trial has shown that it has been effective for all patient groups, including postsurgical HP patients, as well as genetic subtypes like DiGeorge syndrome, ADH1, and idiopathic hypoparathyroidism. Notably, YORVIPATH has received approval from the FDA, the European Commission, and other regulatory authorities for the treatment of all forms of chronic hypoparathyroidism. For all these 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 hypoparathyroidism. Moving now to TransCon CNP, we believe it is raising the bar on safety, efficacy, and tolerability while reducing treatment burden and 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 have been shown. We have demonstrated a safety and tolerability profile comparable to placebo, including no evidence of hypotensive effect and an extremely low frequency of injection site reactions. Since our announcement of monotherapy data, we have engaged with patient advocates, physicians, and regulators, all of whom have appreciated the differentiating ability of TransCon CNP to increase linear growth while also leading to stronger muscle function, improved body proportionality, and leg bowing, and reducing the overall burden of achondroplasia-related complications for the majority of treated children. Patient and caregivers appreciate the much lower burden of once-weekly injection. During the second quarter of 2025, the 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 its use 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 a 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 child, indicating they are achieving linear growth at a rate higher than 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 unprecedented in achondroplasia. Importantly, we see a clear indication of healthy growth, the linear growth accommodated by an improvement in body proportionality, and without acceleration of bone age. All patients continue in the study as of today. These results reinforce the role of TransCon CNP as a strong foundational 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 2025. 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 the treatment of growth disorders. Q2 revenue for SKYTROFA was EUR 51 million. We continue to see growth in the number of individuals treated with SKYTROFA based on new patient starts. 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 adult growth hormone deficiency. Our Phase III basket trial of SKYTROFA is planned to begin later this year and will include a range of established daily growth hormone indications including ISS, SHOX deficiency, Turner syndrome, 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 generation of innovative TransCon technology and product candidates. Additionally, our ongoing collaboration with Novo Nordisk for the development and commercialization of TransCon-based products in metabolic and cardiovascular diseases continues 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 expansions, advancing new blockbuster opportunities to drive growth for many years to come, and fulfilling our Vision 2030. 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 2025. 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 non-cash 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 translation to euro, so we are 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 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 contribute only modestly for 2025. We 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, with our focus 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. We will 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.

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 Q2. Is that the rate you mean that you see continuing?

Jess, I can start with a few overall views 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 was 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. In some ways, I actually believe that we see steady-state growth in the patient base here between Q1 and Q2 when I take into consideration the 200 patients that came from the ERP program. This aligns with our comments at the Q1 call, where we expected to see steady-state development in prescription growth. In the second half of the year, we expect acceleration in the conversion of patients that have a prescription to being on treatment. This is what we have seen. We look forward to seeing Q3 and Q4; we are extremely optimistic about this launch. I'm not just talking about the U.S.; we see the same pattern everywhere we are launching. This is really amazing. We expect to see the same stable state. Sure, there can be a seasonal factor because of summer vacations; at least we know in France, August is a closed month, and other places have similar occurrences. So Jay?

Yes. Thank you, Jan. As mentioned before, we are seeing stabilization in enrollment. Being early in the launch, we will need more time to observe what that steady-state trend will be 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. We're looking across the entire funnel, from enrollments to approval, from approvals to patients on therapy. We are seeing continued growth, especially as it relates to the conversion of those patients on 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 three months from enrollment to conversion. I guess I just wanted to know what are you doing to kind of improve that? And I guess, how much progress can you make on improving on that three months?

Nothing has really changed compared to what we said on our Q1 call. There are many elements that Jay and the entire integrated commercial team are working on. We can go a little bit more specific. But in the overall view, sure, the different politics from the different PBMs need to be addressed. There are many elements that still take time. We're also working a lot on the procedures of how we can assist patients to ensure they and their physicians are supported in the process. This is happening through our assist program that really helps the patients. Nothing has changed compared to what we said in Q1, where we believe that we will first see improvement in the second half of the year when many of these activities will be implemented. Jay, you can give a little bit more flavor on some of the initiatives at a high level because we have many initiatives underway.

Absolutely. Thank you for the question. From a time to approval standpoint, as we said, we're seeing the majority approved within three months. I would divide our efforts into a few buckets. The first is upstream. We're continuing our payer education, whether at a commercial or public level, just on the clinical value proposition of the product and the full expansion of the label because, as you can appreciate, whenever there's a new specialty drug on the market, particularly a rare disease one, it takes some time for payers to consider a category or product that they may not have previously had on their formulary or plan. 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 team. We're quite experienced in managed care settings. Some of the routine work involves ensuring that providers and patients are continuing to follow up and fill out their paperwork correctly to decrease cycle times, preventing the paperwork from being the reason something goes back and forth multiple times. Lastly, we are continuing to work with our specialty pharmacy partners and so forth, again streamlining processes to continue to reduce time as we work through this initial launch phase. All that said, we're encouraged by the pace we're seeing and a reflection of the experience hub we have, and we look forward to 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 discussion 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 types of patients that might be on the more moderate side?

Thanks, Tazeen, for the question. First of all, there is no medical definition that defines severity of hypoparathyroidism, so we cannot claim a database on saying this is the severity that patients have. When we talk about being uncontrolled, partly controlled, or something we call controlled, this was mainly based on a single parameter looking at claim databases and how often they are seeing a physician. How often they see a physician reflects many aspects, including where you live and your access to care, as well as the availability of an endocrinologist. We approached this from this perspective to be sure we are addressing physicians who see a high number of hypopara patients, and that was why we directed our commercial strategies in this manner. It’s important to note that we cannot define patient severity as it's not a medically defined term. However, we see growing guidance that indicates around 95% of the patient base should be on PTH treatment, which seems logical. Consider how many patients with Type 1 diabetes would you ever consider not putting on insulin treatment; it highlights the need for broad treatment access in hypoparathyroidism as well.

Our next question comes from Yaron Werber from TD Cowen.

Congratulations once again. I have a couple of related questions. Can you provide some insight, Scott? Last quarter, you indicated that we should expect Europe to grow by about EUR 4 million to EUR 5 million, which would bring you to around EUR 24 million. It seems like you generated approximately EUR 79 million to EUR 80 million in the U.S. Is that correct? Additionally, we shouldn't anticipate growth in patients of 1,500 quarter-over-quarter. Can you give us an idea of what normalized sequential growth in the U.S. might look like at this point?

I can help, Scott, on this one. What we said in our Q1 call was that if you look at Q3 to Q4 revenue, the net revenue increase in EUR was about EUR 4 million to EUR 5 million. This figure related to Europe or ex-U.S. revenue. We also indicated at that time that we expect that to continue through 2025. As more countries come online with full commercialization—like we just got Spain—and we expect a few more to increase, it's likely that the material impact will be seen 2 to 3 months after the initiation of full commercialization. So I would say your assumption is pretty correct and reflects what we indicated in Q1. Regarding your second question, as it's a forward-looking statement, I know it's being covered by Scott's quick summary. However, 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 looking forward to seeing long-term growth trends informed by ongoing market analysis later in the year.

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 enrollment forms to paid drugs will be at any point in time? And then secondly, looking ahead, do you plan to keep reporting enrollment forms for YORVIPATH?

It's really difficult for us to give you a precise number. However, we always see that there will be a percentage of patients who face significant difficulties getting reimbursed even after multiple attempts to assist them. During the launch, we've noted that the clearing process for those candidates is becoming faster and faster. I can guarantee we will do everything in Ascendis's power to help all patients come on treatment. However, we can't promise that everyone will manage to start treatment; even after 6, 9, or 12 months, there will be patients struggling with coverage. I believe my personal success metric is getting 90% of all patients onto treatment; that would be my aim. Jay, do you want to add your perspective?

Thank you for the question. I would add that not just the payers drive enrollment to approval; there are other factors too. As we stated before, certain plans have policies where exceptions or appeals must be processed. As Jan pointed out, this right tail will take some time to clear, depending on the plan and how things evolve. Additionally, the conversion from enrollment to approvals may depend on ensuring that providers are handling the paperwork appropriately and that patients are following up effectively. We continue to pursue every avenue because we know these patients can and should benefit from the product. It’s a long road ahead, and we're focused on optimizing each step.

And are you planning to report enrollment forms for YORVIPATH in the next quarter as well?

We will provide the necessary KPIs as we do today and will continue to do so in every quarter until we think we come into a steady state where sufficient information will come from revenue that allows for modeling based on revenue alone. Until then, we will keep providing the necessary data to assist with your models. I want to emphasize again: this is an extraordinary launch. Q1 was great, Q2 was also outstanding, and we haven’t seen any negative trends.

Our next question comes from Li Watsek from Cantor.

Congratulations on the quarter. This is Daniel dialing in 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 is net patients going forward?

The best long-term data we have is from Europe, where we started about 6 to 9 months earlier. When we look at the rate of true discontinuation, it's extremely low in a few centers. We are seeing the benefits of the therapy, and people are continuing their treatment. I believe this is attributed to addressing a major unmet medical need with YORVIPATH. Everything we've observed suggests higher compliance than you would see with diabetes drugs; patients are engaging with the therapy at a greater rate than seen previously with type 1 diabetes.

Okay. Cool. And 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 correct; we are referring to unique prescriptions, meaning this is a new patient that had received a prescription. This is what we call unique prescriptions.

Our next question comes from Joseph Schwartz from Leerink Partners.

The first one is on YORVIPATH. I believe there were 1,500 prescribing healthcare 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 three times 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?

Let me start with the easy question, and I can hand over the more scientific question to Jay. We are talking about 8,000 to 10,000 as a total target list. About 3,000 doctors we focus on in our decile priority. We're seeing good field execution metrics across that—over 80% reach across our high-medium priority targets.

So regarding the second question, the interest comes from the discussions we've had for many years. Some skeptics had concerns about the sustained profile. Recently, there was recognition that a sustained profile might be beneficial while not having a high Cmax, which could indicate a risk of hypertension. We designed TransCon CNP with an emphasis on continuous exposure over a week. We feel confident that our clinical data supports this design. While other companies have announced higher AUC, it remains essential to establish the half-life and exposure levels to truly evaluate the clinical relevance. In terms of our combination therapy, the strengths lie in the synergies of various biological pathways known in several therapeutic areas to produce optimal treatment. This approach differs from simply increasing one pathway. TransCon CNP and TransCon Growth Hormone combined will allow for a holistic 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 for the treatment of achondroplasia or for the increase in linear growth in achons like Voxzogo has? Any expectations for differentiation in the label relative to Voxzogo, such as in terms of the indication statement or other secondary endpoints? And then secondly, 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?

We are progressing with our TransCon CNP through the regulatory review as we hoped for in an accelerated priority review. Everything is happening on time. Labeling discussions are one of the last parts of the review cycle, so it’s tough for me to provide specific details. What I can emphasize is the data we have backing TransCon CNP. I believe this is why we received priority review since we have substantial evidence of treatment benefits extending beyond linear growth. We can see improvements in areas such as leg bowing and muscle strength. Some comparison trials lack a placebo-controlled structure. Therefore, it is vital we advocate the benefits we can provide through well-controlled pivotal trials. So while I can’t comment on the specifics, I am confident in the therapeutic value of TransCon CNP. Regarding the second question, when we developed our product in 2015, we filed numerous IPs for optimal products and treatment benefits. Without clear disclosures regarding BMN 333, I can’t provide comments on comparisons, but I am optimistic about our filings and protections.

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 the broader patient spectrum in the real world? And once a patient completes the titration period, should we expect a higher monthly cost?

For the titration period, we rely more on Aimee, our Chief Medical Officer, who knows about what we've seen in our clinical trials. We are less certain about what happens in the real world, but so far we are not seeing significant patient dissatisfaction at that stage. Nothing has indicated patients are dropping out due to issues. So, while I cannot offer specific insights on in-world titration timings, we see it happening successfully. Regarding your second question, once patients complete titration, we have approval in the U.S. for doses from 6 to 30 micrograms. Therefore, we could see patients on higher doses. Outside the U.S., there is potential for using up to 60 micrograms. We initiated our 60-microgram trial, targeting this increase. Jay will assess data considering the near commercial launch of 60 micrograms and how reimbursement will be addressed for that situation.

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 allow you to address that is not currently addressed by the available presentations in the U.S. market?

Thank you for the question. I think there are many elements in your inquiry. In the U.S. today, there are various strategies available to address patients requiring doses higher than 30 micrograms due to current label restrictions. Some patients may take 30 micrograms from physicians off-label, while others may require calcium supplements or active vitamin D. It’s clear there is a need for higher doses. We'll work diligently to get this approval expedited. The trial is a small one, with less than 20 patients, lasting only 26 weeks. We’re using existing pen devices, meaning no complications from CMC. We’re mainly focused on clinical trial execution and regulatory filing. We want to ensure this is delivered to patients as quickly as possible.

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 the 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 would feel confident to support a 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. I 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 the potential to achieve profitability in Q3 versus Q4? And then maybe secondarily, can you just remind us about Ascendis's exposures around tariffs and MFN? I appreciate the situation is still fluid, and we don't have all the details, but any high-level commentary would be much appreciated.

Great. On SG&A and expenses overall, remember that last quarter we reported EUR 190 million of OpEx, which isn’t a bad run rate, possibly plus or minus each quarter. This quarter, we clocked in at about EUR 180 million of OpEx. As you point out, looking year-over-year isn’t the best consideration because we had significant growth last year. It’s more about the sequential build. I'd consider 6% sequential growth for SG&A to be a reasonable number. Overall, sticking to about EUR 190 million OpEx per quarter isn't a bad estimate. Regarding profitability, yes, we are expecting that this year. If you analyze our financials and adjust for the currency translation on June 30, because of what we call Liberation Day, that led to about a EUR 20 million cash delta. Overall company collection was about EUR 5 million of burn in Q2. On an operating basis, we’re slightly positive on cash, so achieving positive cash flow this year seems doable. With respect to MFN and tariffs, as you rightly said, it’s fluid, so I prefer not to get into specifics here. However, given how flexible we are as a company, I believe we can mitigate any potential impacts from evolving policies.

To clarify and add to Scott's comments, we're not importing finished products to the U.S. Rather, we bring in components and finalize them domestically. So, ultimately, we cannot see how any possible changes would have a significant impact on our business or operations.

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 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 briefly share what you think is the opportunity for Ascendis in hypochondroplasia?

Yes, I refer to hypochondroplasia as a milder form of achondroplasia. Patients don’t have much of the disproportionality issues. You can say some older patients were previously classified under ISS status. Now, due to better genetic testing, there's a better understanding of this group. When I noted the potential of combination therapy with TransCon CNP and TransCon Growth Hormone, I felt that even the very heterogeneous population can benefit from targeted management. I derived clarity from engaging with patients and their organizations. It has broadened my understanding of the unmet medical need. There are three main pillars that have shifted my perspective towards hypochondroplasia. The initial reallocation of patients from ISS to this category, along with the benefits seen in our combination therapy, rallied my interest.

Our next question comes from 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 it is a EUR 5 billion to EUR 8 billion market segment. No doubt that it will be that.

Our next question comes from Yun Zhong from Wedbush.

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

We established a precedent with SKYTROFA. We’ll wait until we get the approval, and I will probably be woken up extremely early to take press release or call at 5:00 AM my time. At that point, we will provide insights into the labeling and our launch strategy. I cannot predict what path we'll take for hypochondroplasia, but I do believe that due to the heterogeneous patient population, combination therapy may provide the best option for patients. However, this doesn't rule out a consideration for monotherapy, depending on regulatory feedback. We see the combination therapy as potentially the most robust treatment option at this time.

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 discussion with Aimee Shu regarding this. She is close to the details because when we initiated this trial, we discussed expectations. We are now observing an unprecedented growth velocity in achondroplasia; children are growing faster than the average child. I have four children myself, and I remember their growth spurts. That being said, we see robust data across studies, raising the potential of accelerating growth in the combination therapy. Thus, if there is demand from parents for their child, we might allow them to switch to monotherapy after achieving a desired growth outcome. Our goal is to provide flexible options based on individual patient needs and the ongoing study results.

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.