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DATE
Thursday, August 7, 2025 at 4:30 p.m. ET
CALL PARTICIPANTS
President and Chief Executive Officer — Jan Moller Mikkelsen
Executive Vice President and Chief Financial Officer — Scott Smith
Chief Business Officer — Sherrie Glass
Executive Vice President and President, US Market — Jay Wu
Executive Vice President of Endocrine and Rare Disease Medical Science and Chief Medical Officer — Aimee Shu
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TAKEAWAYS
Total Product Revenue-- Total product revenue of €153.7 million for Q2 2025, including a negative foreign currency exchange impact of €7.6 million in Q2 2025.
Skytrofa Product Revenue-- €50.7 million in Q2 2025 with a negative currency effect of €1.8 million in Q2 2025.
TransCon PTH (Europath/Europet) Revenue-- €103 million in Q2 2025, up from €44.7 million in Q1 2025, despite a €5.8 million currency headwind in Q2 2025.
Collaboration Revenue-- €4.4 million recognized in Q2 2025.
Total Q2 Revenue Including Collaboration-- Total revenue of €158 million for Q2 2025.
Operating Expenses-- €180 million in Q2 2025, with research and development at €72 million (down from €83.5 million year-over-year) and selling, general, and administrative (SG&A) expenses of €107.6 million (up from €74.3 million year-over-year).
Net Finance Income-- Net finance income for 2025 was €22 million, driven mainly by non-cash items.
Net Cash Financial Expenses-- Net cash financial expenses totaled €5.3 million for 2025.
Cash and Cash Equivalents-- Cash and cash equivalents of €494 million at period-end Q2 2025, compared to €518 million as of March 31, 2025; The primary decline was due to currency translation (€19 million of the €24 million sequential decrease in cash in Q2 2025).
Skytrofa FDA Approval-- Received for adult growth hormone deficiency, supporting future label expansion.
TransCon Growth Hormone Approval-- Approved by FDA for adult GHD and pediatric GHD; received MAA in Europe for pediatric GHD.
TransCon PTH Regulatory Status-- Approved in the US, EU, and UK for adult hypoparathyroidism; full commercial launches in Germany, Austria, and Spain.
TransCon CNP Regulatory Progress-- NDA accepted by FDA for priority review, with a PDUFA date of November 30, 2025.
TransCon CNP Clinical Data-- Pivotal trial showed statistically significant improvement in linear growth, leg bowing, and quality of life; Interim results from the combination trial announced in June 2025 indicated linear growth rates above average for age, with gains in body proportionality and no bone age acceleration.
Europath US Launch Patients-- More than 3,100 unique US patients were prescribed by over 1,500 prescribers as of June 30, 2025; The majority of U.S. patients receiving a prescription for Europath received payer approval within three months.
Global Reach for Europath-- Recognized revenue in 30+ countries; commercial agreements cover more than 75 countries; additional launches expected later this year.
Patient Retention for Europath-- The company stated the true discontinuation rate was 'extremely low, a few percent' based on European data from the first six to nine months after launch.
Operating Cash Flow-- Statements indicate the company expects to achieve cash flow positivity on a quarterly basis in 2025.
Prescriber Reach-- US prescribers totaled over 1,500 as of June 30, 2025, which covers over 80% of high and medium priority targets in the market of 8,000-10,000 potential prescribers.
TransCon Growth Hormone (Japan)-- Partner Taizen expects approval decision later this quarter.
Planned Clinical Programs-- Initiated Pathway 60 trial to support US TransCon PTH titration up to sixty micrograms; phase III basket trial for Skytrofa in established daily GH indications; pivotal combination trial in hypochondroplasia planned.
Management Guidance on OpEx-- Management suggested ~€190 million per quarter as an appropriate ongoing estimate for operating expenses.
SUMMARY
Ascendis Pharma A/S (ASND 0.38%) reported substantial sequential revenue growth in Q2 2025, driven mainly by TransCon PTH (Europath), with new product launches and market expansions driving performance despite significant currency headwinds. Management confirmed continued growth in new and unique US patients on Europath, high payer approval conversion rates, and expanding global market presence, emphasizing durability of revenue contribution. Priority FDA review for TransCon CNP, positive clinical trial readouts for combination therapy in achondroplasia, and recent label expansions for Skytrofa and TransCon Growth Hormone during Q2 2025 were highlighted as critical future growth levers.
Jan Moller Mikkelsen asserted the long-term revenue potential for TransCon PTH as "a €5 to €8 billion market segment." (No additional context can be added as no explicit GAAP/non-GAAP designation, time period, or fiscal/calendar year is provided in the source.)
Management communicated expectations for sequential revenue acceleration in Europath as new country reimbursement comes online later in the year.
Statements indicated improvements in SG&A efficiency, with sequential growth of 6% in Q2 2025, and a trend toward operating cash flow breakeven.
Combination therapy for achondroplasia demonstrated interim growth velocity "unprecedented and never been seen" with all patients remaining on study as of the call.
Jay Wu disclosed that over 80% of high and medium priority prescribers had been reached by commercial efforts as of Q2 2025.
The company is proactively initiating the Pathway 60 trial in the US and highlighted ongoing progress in label expansion and combination therapy trials for future volume growth.
Pipeline diversification and the Novo Nordisk collaboration are progressing, with expectations for new TransCon-based programs in metabolic and cardiovascular fields.
Management identified potential risks, including foreign currency exchange impacts, possible policy changes such as MFN and tariffs, and operational challenges such as the time from prescription to treatment.
INDUSTRY GLOSSARY
PDUFA date: The target date by which the US FDA must review a New Drug Application under the Prescription Drug User Fee Act framework; signals regulatory decision timing.
MAA: Marketing Authorization Application; the European Medicines Agency's process for evaluating new medicines for commercial approval in the EU.
Growth hormone deficiency (GHD): A medical condition in which the body does not produce enough growth hormone, treated by replacement therapies.
Achondroplasia: A genetic disorder causing impaired bone growth and disproportionate short stature, with dedicated therapies in development.
Hypoparathyroidism: A condition characterized by inadequate parathyroid hormone production, resulting in low calcium levels, and the target for TransCon PTH.
Pivotal trial: A statistically powered, late-stage clinical study whose results support regulatory approval decisions.
COATS trial: The company's phase II combination therapy study evaluating TransCon CNP and TransCon Growth Hormone in children with achondroplasia.
Full Conference Call Transcript
Scott Smith: Morning, everyone, 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, US market; Aimee Shu, executive vice president of endocrine and rare disease medical science 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 Skytropha and Neorvipat as well as certain financial expectations, our pipeline candidates, and our expectations with respect to their continued progress 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 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. Additional information concerning the factors that could cause actual results to differ materially, please see our forward-looking statements section in today's press release and the Risk Factors section of our most recent annual report on Form 20-F filed with the SEC on 02/12/2025. TransCon growth hormone or TransCon hGH is 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 US 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.
Jan Moller Mikkelsen: Thanks, Scott. Good afternoon, everyone. The 2025 demonstrated strong momentum towards fulfilling our Vision 02/1930 as we progress towards blockbuster status for multiple products and expand our engine for future innovation. The continued strong global launch of Eurocast increases our confidence that Europass is underway to become a blockbuster product with durable global leadership for 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 two result 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 that first of many planned label expansions for Skytopher 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 Europat. Revenues in the second quarter reached €103 million, more than double of Q1, despite a strong currency headwind. In The US, 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 Europads, the majority have received payer approval within three months.
Outside of The US, we continue to see steady Europat revenue growth in both our Europe direct and international markets. And we currently expect further acceleration of the revenue growth when Europas reimbursement becomes available in additional Europe direct countries. With a broad label covering all types of chronic hypoparathyroidism, supported by international guidelines, and a prominent reference to Europat in recently published best practice consent statements, we expect growth to continue. We have ongoing clinical programs to support label expansion, for example, in older children, and initiated the Pathway 60 trial, a single-arm safety and efficacy trial to support titration up to sixty microgram doses in The US.
The primary endpoint of this trial will be efficacy at twenty-six weeks, the same as our pivotal phase three trial endpoint. We are building towards UFS 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 twenty-four hours, seven days a week. Based on all the data we have seen, Europet 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 demand.
Where Europet is available, we see strong interest and growing enrollment. For The U.S. market, in just two 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 US, we still have ample room to grow. Outside The US, we have recognized revenue for more than 30 countries. And currently, we have commercial agreements covering more than 75 countries. Third is access. In The US, we see favorable access continue to improve, with approvals coming across all payer segments. In your direct, we have full commercial launch in Germany, Austria, and now Spain.
We expect additional commercial launches later this year both in your direct and international markets. In Japan, our partner, Taizen, expects approval for Europad later this quarter. We consistently hear about how transformative Europet 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 Europads. As shown in our clinical trial, this has been extended for all patient groups, post-surgery HP patients, to small genetic subtypes like Dijkor's syndrome, ADS one, and idiopathic hypoparathyroidism. Notably, Europet has broad approval from the FDA, the European Commission, and other regulatory authorities for the treatment of all forms of chronic hypoparathyroidism.
For all of the above reasons, we are confident that Europet 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 TransCon CNP is moving the bar on safety, efficacy, 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 mild injection site reactions. Since our announcement of monotherapy data, we have engaged with patients, 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 complications for the majority of treated children. And, of course, patients and caregivers appreciate the much lower burden of once-weekly injection.
During 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 it in combination with our once-weekly TransCon growth hormone in children with achondroplasia in our COATS 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 of children, meaning they are achieving linear growth at a rate higher than an average child. The week twenty-six data demonstrated potential to boost growth of around three times above that observed with monotherapy, addressing the hyperactive FDR3 receptor pathway, supporting the scientific rationale for treating with TransCon CNP and TransCon growth hormone combined. These results await our procedures in achondroplasia. Importantly, we see clear indication that it is healthy growth with linear growth accompanied 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 twelve-month 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 Truiniti, a pivotal combination trial in hypochondroplasia. I will now turn to Skytrofe. So Skytrofe 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, Skytrofe remains a fundamental pillar in our strategy to become the global leader in the treatment of growth disorders.
Q2 revenue for Skytrofe was €51 million. We continue to see growth in the number of people treated with Skytrofe, based on new patient starts. The expected recent label expansion for adult growth hormone deficiency is expected to further drive long-term growth. Our market research shows Skytrofe is the treatment choice for pediatric growth hormone deficiency among patients and physicians, and we believe we can achieve the same status for the treatment of adult growth hormone deficiency. Our phase three basket trial of Skytrofe planned to begin later this year will include a range of established daily growth hormone indications, including ISS, shock deficient, Turner, and SDA. I often say that Ascendis is just getting started.
Falling closely behind this major growth opportunity, our research team is developing the next stage of innovative TransCon technology and product candidates. In addition, 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. We are advancing new blockbuster opportunities to drive growth for many years to come and fulfill our Vision 02/1930. And we're already preparing for our next vision. I will now turn it over to Scott.
Scott Smith: 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-Ks filed today. For Q2, our total product revenue was €153.7 million, which includes a negative sequential foreign currency exchange rate impact of €7.6 million. Skytropha revenue for the quarter was €50.7 million, including a €1.8 million negative currency impact. Europap delivered strong performance with revenue more than doubling to €103 million, up from €44.7 million in Q1 2025. This revenue growth was achieved despite a negative sequential currency headwind of €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 Europap 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 €4.4 million of revenue from our collaboration partners, total Q2 revenue was €158 million. Turning to expenses, R&D costs for the second quarter decreased to €72 million compared to €83.5 million in the same period last year, primarily driven by lower development costs for growth disorders. SG&A expenses in 2025 increased to €107.6 million compared to €74.3 million in the same period last year, primarily driven by global commercial expansion. Total Q2 2025 operating expenses were about €180 million.
Net finance income for 2025 was €22 million, driven primarily by noncash items. Net cash financial expenses for 2025 were €5.3 million. We ended 2025 with cash and cash equivalents totaling €494 million compared to €518 million as of March 31. Of the €24 million sequential decrease in cash, 19 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 Europap.
For Skytropha, 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 Skytropha 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-US dollar exchange rate for any potential impact related to reported revenue. For Europap, our launch is progressing exceptionally well. Globally, we see Europap 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 Europap's growth trajectory, I would highlight the following. Outside The U.S., we currently see continued steady sequential revenue growth. In The U.S., seven 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 Europap, as Jan mentioned, the majority of U.S. patients are approved for reimbursement within three 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: Thank you. At this time, we will conduct a question and answer session. As a reminder, to ask a question, you will need to press 11 on your telephone and wait for your name to be announced. To withdraw your question, please press 11 again. You're allowed one question and one follow-up question. Please stand by while we compile the roster. Our first question comes from Jessica Fye from JPMorgan. The floor is yours.
Jessica Fye: Great. Thanks, guys. Great quarter. You mentioned you're seeing a continuation of enrollment trends. I think the number of unique patients enrolled grew by about 1,350 in February. Is that the rate you mean that you see continuing? Thank you.
Jan Moller Mikkelsen: Hey, 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, at 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. And so in some way, 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 ERP program. 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 have an acceleration of the conversion of a patient that has a prescription to 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 now just talking about the U.S.
We see the same pattern everywhere we're launching, but it's really it's amazing. And we expect to see the same steady state. Sure. That can be a seasonal factor because of the summer vacation, at least we know in France, August is closed and other places happening the same thing. So Katie, for your comment. Yeah. Thank you, Jan.
Jay Wu: 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 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 onto therapy, and we're feeling good about what we are seeing.
Operator: Thanks, Jay. Thank you for your question. Our next question comes from Derek Achillia from Wells Fargo. The floor is yours.
Derek Archila: Hey, thanks for taking the question and congrats on the progress here. I just wanted to confirm something. So it sounded like you noted that there's three months, you know, 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 three months? Thanks.
Jan Moller Mikkelsen: There's a lot of elements that nothing has really changed compared to what we said on our Q1 call. 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 a different PPM need to be installed. There is a lot of elements that still takes time. And we're also working a lot on the procedure, how we basically can help patients to be sure and physician and back office. So this is happening for our asset program that we are helping the patient. So Nordic 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 on a high level because we have so many initiatives going on.
Jay Wu: Absolutely. And thank you for the question. From a time to approval standpoint, as we said, we're seeing the majority within three months. Now divide our efforts probably in a few buckets. The first one is upstream. Right? We're continuing our payer education, whether it's at commercial level or a public level, just on the clinical value proposition of the product. The full expanse of the label, because as you can all appreciate, whenever there is 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.
We anticipate that to continue to improve, which will of course, have downstream impacts on the speed. More downstream from that, we're also have a very experienced hub. 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 paperwork isn't the reason why maybe something goes back and forth one or two 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 pharmacies, so on and so forth, again, streamlining those processes to continue 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.
Operator: Great. Thank you. Thank you for your question. Our next question comes from Tazeen Ahmad from Bank of America. The floor is yours.
Tazeen Ahmad: Hey, guys. Thanks for taking my question. I was wondering if you could give us some color on the type of patients. There's been a lot of talk about initially severe patients, the most severe patients, being put on Europath first. But do you have any color on what the split is between definitionally what a severe patient is versus the type of patient that are getting on that might be on the more moderate side? Thanks.
Jan Moller Mikkelsen: Thanks, Tazeen, for the question. First of all, there is no medical definition that defines severity of hypoparathyroidism. So we cannot go in and claim database and say 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 sitting and physician.
How often they're sitting in physician, I think, have 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 and into that really can see you. So, we did it out from this perspective because we wanted to be quite sure we're addressing a physician that see you with a high number of patients in hypoparathyroidism. And it 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.
It's no part of can see of the patient because it's not a medical term that error is defined. I think me, 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 guidelines we have seen being issued from all different places in the world now, they are indicating that ninety-five percent of all patient bases should be on PTH treatment. And I think that is pretty logical.
Think about how many patients on type one diabetes. Will you ever consider that you will not take all patients that have type one diabetes on insulin treatment? And I think you will see the same thing happening with hypoparathyroidism.
Operator: Thank you for your question. Our next question comes from Yaron Werber from TD Cowen. The floor is yours.
Yaron Werber: Great. Thanks for my question and 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 €4 million to €5 million, so that puts you at around €24 million. So it almost seems like you did sort of €79 million to €80 million in The US. 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 gonna be growing patients 100 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 US can be so we don't get out of hand? Thank you.
Jan Moller Mikkelsen: I can think I can help Scott this time, which I often do. Because what we said in our Q1 call, and if you look on Q3 to Q4, revenue increase net revenue in euro was about €4 to €5 million. And in this two quarters, it was basically your euro or ex-US revenue. And we also say that time that we expect that to continue in 2025, when we see more countries coming on full commercialization as we just got Spain now, and we expect a few countries more. Perhaps it will increase, but it will first have a material impact two to three months after basic mediation or 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 comment, it's some way 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 US. We have seen nearly the same numbers between Q1 and Q2. And we're really looking forward, as Jay said correctly, this is an 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 six, seven quarters to go.
Operator: Thank you for your question. Our next question comes from Gavin Clark Gartner from Evercore ISI. The floor is yours.
Gavin Clark Gartner: Hey, guys. Congrats on another great quarter. First, what do you believe the ultimate conversion rate from the enrollment forms to paid drugs will be at any point in time? And then secondly, looking ahead, do you plan to keep reporting the enrollment forms for Europath? Thank you.
Jan Moller Mikkelsen: Really difficult for us to give you a clear number. But what we always will see in The US, 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, what 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 six, nine, twelve months, really struggling we will say it 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, could get around ninety percent of all patients on treatment. I will feel it as a personal success and my contribution to help with hypoparathyroidism. Jay, you can also come with your personal success number. It's you want to do that.
Jay Wu: Appreciate the question. You know, I would say layer on a couple 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 you know, as we discussed before, there are certain plans and policies for which you know, 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.
Gavin Clark Gartner: And are you guys planning to report enrollment forms for Europath in the next quarter also?
Jan Moller Mikkelsen: 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're coming to a steady state where we feel that there is enough information just out from revenue that you can basically do your modeling. Once in that, we will continue to provide the necessary data that support that you can make a sudden modeling of the launches. Just to say and repeat it me again, this is an amazing launch. Q1 was great. Q2 was also amazingly great, and we have not seen any weakness in the launch.
Gavin Clark Gartner: Very helpful. Thanks.
Operator: Thank you for your question. Our next question comes from Li Watsek from Cantor. The floor is yours.
Daniel Brundra: Hi. Congratulations on the quarter. This is Daniel Brundra on for Li Watsek. We're just curious about the pull-through of the patients that get onto 1,500 PFS number is net patients going forward. Thank you.
Jan Moller Mikkelsen: Where we have the best long-term data is from Europe where we basically started their launch about six to nine months before. And when we look on a rate, what we call true discontinuation, is extremely low, a few percenters. So we really see the benefit of the therapy. People taking the therapy are taking it. They're keeping doing it. And I believe that is the contribution on how we are addressing a major unmet medical need with the treatment of Europaths. So everything what we see here is far away from what you see with a diabetes drug. People stay on it even much better on than insulin that you see in type one diabetes.
And I think this is the main contribution to the positive CNS effect that is with this product.
Daniel Brundra: Okay. Cool. Thank you. 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?
Jan Moller Mikkelsen: Yeah. That is what we're referring to is unique prescriptions. Meaning is that it's a new patient that has got a prescription. Is what we call unique prescriptions.
Daniel Brundra: Great. Thank you so much, and congrats again.
Jan Moller Mikkelsen: Thanks.
Operator: Thank you for your question. Our next question comes from Joseph Schwartz from Leerink Partners. The floor is yours.
Drew Reed Park: Yeah. Hi. I'm Drew Reed Park dialing in for Joe. Thank you for taking our questions. The first one is on Europath. I believe that there were 1,500 prescribing health care providers in The US 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's 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? Thank you.
Jay Wu: So happy to start with the first question. From a target list standpoint, we're talking about eight to 10,000, so that you can consider that as our 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.
Jan Moller Mikkelsen: So the second question is interesting. Because, for many, many years, there was a lot of skepticism about our sustained profile. And then suddenly, there was a big change where the summary says, there is some benefit by having a sustained profile that does not give a high Cmax that basically can indicate risk of hypertension. And, also, you need to have continuous exposure over one week. And so we started and designed our TransCon CNP in 2015. And now we are in 2025. They're starting now to go after that concept.
From my perspective is that when you look on how we designed it, that also all our associated pattern filing we have with it or the IP we have of the optimal prodrome the medical treatment benefit it is, 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 that was AOC I really don't care about AOC. I want to know key element. What is really the half-life? How is this exposure really happening?
Is it something that picks up to a very, 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 an 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 brake because it's really the hill is rolling down. That really decides the speed. If you have taken the brake off, the brake is off. That is where I really don't get the biological and scientific concept. That is related to linear growth.
When we look at some of the other effects 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 is that downfall. Can you get more out on having a higher AOC? First of all, it needs to have the right AOC. This must be a higher exposure. Completely over the once-weekly profile. And no one disclosed that because then they need to have a longer half-life than ours that is about two and a half to three days. And I have not got any kind of disclosure than they are there.
When I go out to our combination therapy, it's basically a 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 balancing different pathways. And that is what we do in the combination team trying to come to CNP, and the growth hormone effect, which are 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 up on that.
So I feel really, really confident with our code state our combination therapy, that is really is a unique way where you really can totally provide for patients, for physicians, a complete new treatment standard.
Drew Reed Park: Got it. Thank you.
Operator: Thank you for your question. Our next question comes from Ilana Merle from UBS. The floor is yours.
Ilana Merle: Hey, guys. Thanks for taking my question, and congrats on the strong quarter. Curious for achondroplasia, what's your base case for the indication statement for TransCon CNP, whether it'd be for the treatment of achondroplasia or for the increase in linear growth in achondroplasia, like VoxoGo has? And I guess any expectations for differentiation in the label relative to Voxago, 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 CNPs? Specifically any thoughts on CMM three thirty-three and where that might stand relative to the TransCon CNP IP estate? Thanks.
Jan Moller Mikkelsen: We are progressing to the regulatory review with our TransCon CNP exactly as we hope for in an accelerated priority review. Everything is happening on the right time. So labeling discussion is one of the last parts in the review cycle. So it's really, really difficult for me to come up with any kind of elements. What are Morwell 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 have seen 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 during a normal development of a child also to an achondroplasia child. So how can you discriminate? Is it really the treatment benefit or just a normal development? And this is why it's so extremely important to be in a position that you are referring to data that's 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, parents really love their once-weekly profile. It's such 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 interested in 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 when we developed that in 2015, we basically filed a lot of IP. There was how to make an optimal prodrug. There was the benefit of having a prodrug that gave sustained things. As there is no clear for me exactly what is the primary structure that they have in the BMN, three. It's impossible for me to say exactly what they are. But if you can see me, at least you can see I have a great smile on my lip. Face because we are pretty good in what we're doing when we file IP.
Ilana Merle: Understood. Thank you.
Operator: Thank you for your question. Our next question comes from Kelly Shi from Jefferies. The floor is yours.
Kelly Shi: Congrats on another strong quarter, and thank you for taking my questions. For Europath, what is the typical type titration period that you are seeing right now across the broader patient spectrum in the real world? And once the patient completed titration period, should we expect a higher monthly cost?
Jan Moller Mikkelsen: So at least I got the first question related to the titration period. And I think Aimee, our chief medical officer, knows a lot about what we have seen in our clinical trial. I think we are much more uncertain about what is exactly happening in what we call in real-life clinical elements. But what the key element for me, and I take it from that perspective, do we see a lot of patients on set extraction at that stage? Do we see a lot of patient drop out because there's a problem with it? And we don't see that.
So I cannot really comment about what exactly is happening in the titration for the patient in the real world, but at least we can see that it's happening very successfully.
Kelly Shi: And your second question was?
Kelly Shi: So once the patient completes titration, should we expect a higher monthly cost? Because they stay on a higher dose. Right?
Jan Moller Mikkelsen: I think in The US, we have an approval up to from six to thirty micrograms. So, basically, we are in a position that we're only using one pen at a time. Outside the US, there is a possibility to use up to sixteen micrograms. We have just initiated what we call our sixty microgram trial, which will facilitate this is our aim. This is a twenty-six-week trial to facilitate that we can get on labeling that we can use up to sixty micrograms in The US.
And I think when Jay has seen all the data and becoming near commercial, what I call commercial launch of up to the sixty 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.
Kelly Shi: Thank you.
Operator: Thank you for your question. Our next question comes from Paul Choi from Goldman Sachs. The line is yours.
Paul Choi: Hi, good afternoon, and 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 sixty 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 as not being currently suited by the available presentations in The US market? Thank you for taking our questions.
Jan Moller Mikkelsen: Thanks a lot for the question. I actually think this is a lot of questions in the question because what is happening in The US today and I think there are a lot of different places where different elements on how to solve the issue if a patient needs more than thirty micrograms. There are some patients because of the label restriction to thirty micrograms, that will stay in a position that they're taking thirty micrograms. And if needed, that will potentially take additional calcium supplements or additional active vitamin D.
There are other places where the basic the patient on an physician off-label will potentially get access to a higher dose, which we obviously have no involvement in and no recommendation. So from my perspective is that there is a need for a dose higher than thirty. And we would 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 targeting enrollment of 18. It's only twenty-six weeks. And we are utilizing the same pen devices that the basic have been already in the market. So there is no CMC component in this way.
It's just for Aimee Shu and her team to basically get the clinical trial done and get through 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.
Operator: Thank you for your question. Our next question comes from Alex Thompson from Stifel. The floor is yours.
Alex Thompson: Great. Thanks for taking my questions. I guess on Europath as well, you've talked about the breadth of prescribers. 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? Thanks.
Jan Moller Mikkelsen: 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.
Operator: Thank you for your question. Our next question comes from Luca Issi from RBC. The floor is yours.
Luca Issi: Great. Thanks so much for taking my question. Congrats on the quarter. Maybe, Scott, lots of questions, obviously, the top line, rightly so. But how about SG&A? I mean, up 44% year over year and 6% quarter over quarter. Appreciate, obviously, 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? Then maybe secondarily, can you just remind us about Ascendis exposures around tariffs and MFN? Again, appreciate the situation is still fluid, and we don't have all the details. But any high-level commentary, much appreciated. Thanks again.
Scott Smith: Okay. Great. SG&A and expenses overall, so remember last quarter, we did €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, you know, minus about 10 from that. So we're about a 180 of OpEx this quarter. And as you point out, you know, 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, you know, potentially not a bad number to think about.
But in the overall context of, you know, I would still say about a 190 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 €20 of cash delta. So overall, everything across the company, it was about €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 tariff, I think you said it pretty well.
There's really too much in development right now to make any comments specifically on it. But you know, we do believe that we're as a flexible company, we're pretty well positioned to mitigate the impact of any policy should it emerge.
Jan Moller Mikkelsen: Just to clarify and also add in Scott's comments, we're not importing finished products to The US. We import them in different states and finalize them inside The US. 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.
Luca Issi: Thank you so much.
Operator: Thank you for your question. Our next question comes from Leland Gershell from Oppenheimer. The floor is yours.
Leland Gershell: Hey. Good afternoon, and thanks for taking our questions. Yeah, I'm just curious, you know, it's in the past, you had not expressed much interest in hypochondroplasia as a development program, and maybe you had 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, may have changed that affected your decision process here, and if you could also maybe just share briefly what you think is the opportunity for Ascendis in hypochondroplasia. Thank you.
Jan Moller Mikkelsen: Yeah. Hypochondroplasia is what I will call and perhaps it's the wrong way to define it, but I call it a milder form of achondroplasia. If they don't have many of them per se, what we call body disproportionality, but you can say some in old days, many of these patients basically come in the ISS neuropathic short status. And now because of much more influenza genetic testing, you basically have a development large group that more is well defined from genetic testing to be hypochondroplasia. That's one point. That basically is saying, patients that were in one group are now being moved over in a different group and meaning 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 is bringing up my attention why I believe we need to do it. And also because I went out and talked with a lot of patients. And I had to think I 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 three pillars I have changed. And I say and we change of the therapeutic groups. Where the hypochondroplasia is growing because allocation of patient from ISS over to hypochondroplasia. And their heterogenic group that really I feel when I talk to the patients, when I talk to the patient organization, need a treatment. And the very extremely positive data we got for was post trial. Where when you have such a histogenic, some of the key element would be the CNP. Growth hormone will help. But one CNP is the key element. CNP will help.
And this is why when you have such a histogenic group, having the combination therapy will be the most realistic way to treat them in a way where you really will have a fundamental good treatment regime.
Leland Gershell: Great. Thank you for that, Jan.
Operator: Thank you for your question. Our next question comes from the line of David Lebowitz from Citi. The floor is yours.
David Lebowitz: Thank you very much for taking my question. Curious, has there been any evolution in your thinking on the ultimate size of the market for Europath? Curious to know.
Jan Moller Mikkelsen: You know, I always been bullish and said that it's going to be a €5 to €8 billion market segment. I have no doubt that it will be that.
David Lebowitz: Thank you for taking my question.
Operator: Thank you for your question. Our next question comes from Yun Zhong from Wedbush. The floor is yours.
Yun Zhong: Hi. Thanks very much for taking the questions. And the first question on TransCon CNP for achondroplasia. Assume that you receive FDA approval by the PDUFA date, 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 the 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 the COATS study?
Jan Moller Mikkelsen: The first one is we actually made some kind of with Skytropha. We will wait until we get the approval and likely discuss with force me to wake up in the morning, very, very, very early, that would be press release or some kind of call at 05:00 in my time in the morning. And 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. 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 is, in my view, is an extremely heterogenic population now with a lot of what I call burden and different ways. And also now with the reallocation of patients from the ISS group into the hypochondroplasia. It will some way from my perspective, OPTIMAL will be to use the combination.
And we will continue our dialogue with our regulatory agencies around the world to be sure that they also have the aligned view. I cannot, in 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. This way. So this is where we need to after the time being, we believe that the combination is the most robust treatment on it. But, obvious, there would be some patients that also just would benefit of having TransCon CNP as a monotherapy.
Yun Zhong: Thank you.
Operator: Thank you for your question. Our final question comes from Maxwell Scar from Morgan Stanley. The floor is yours.
Maxwell Scar: Great. Thank you for squeezing me in, and forgive me if this question has been asked. But given the magnitude of growth velocity improvement in the COATS 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? Thank you very much.
Jan Moller Mikkelsen: Hey. Yeah. I had a lot of discussion with Aimee Shu about that. She's sitting in my side. 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 and never been seen in achondroplasia. There are basic growing faster than a normal child. I have four children, and I remember when they have growth spurts. It was not really good. We're pretty tall with Scandinavian. So you 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 we some way go back and forward in that discussion. Will you take a treatment of one year? Will you take a treatment of two years? In the combination? You will get major growth and other positive development. Will you then go back for one or two years just have TransCon CNP as a monotherapy then you would boost again if there is desire from the parents for the child and birthings related to death and if it's really unneeded at that time.
So in some way, when I think about the overall way how we will do the best for the patient in the achondroplasia is basic to give them that option that we really can be in a position where they can take combination therapy likely for one year, potentially two years, and other things like that. And get all the benefit in that gate, and then we can continue with our TransCon CNP. And if they have a desire to move into another one yearly or two yearly treatment, they will can do that again. That is more or less our thinking in this way.
Maxwell Scar: Great. Thank you very much.
Operator: Thank you for your question. 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. This does conclude the program. You may now disconnect.
Jan Moller Mikkelsen: Thanks so much. Thank you.