Ascendis Pharma A/S

Good day, and thank you for standing by. Welcome to the Q2 2025 Ascendis Pharma Earnings Conference call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising that your hand is raised. To withdraw your question, please press star 1-1 again. You may ask one question and one follow-up. 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 CFO. Please go ahead.

Manu Tak, 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 Yen Muller-Mickelson, president and chief executive officer, Sherry Glass, chief business officer, Jay Wu, executive vice president and president, US market, Amy Hsu, 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 the Orbit Path, 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 statement section in today's press release, the risk factors section of our most recent annual report on Form 20F, 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 in 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.

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 Europass increases our confidence that Europass is on the way to become a blockbuster product with doable global leadership of the treatment of hyperparatarrhism. FDA granting us priority review for TransconCMP, recognizing its potential, if approved, to provide a significant improvement in the safety and or effectiveness of the treatment of acondroplasia. The announcement of the interim phase two result from the first combination therapy trial of TransconCMP and TransconGrowthomo highlights our potential to boost healthy growth in acondroplasia. And we achieved the first of many planned label expansion for Skytofa 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 Europass, revenues in the second quarter reached 103 million euros, more than double of Q1, despite a strong currency headwind. In the US, from long to June 30, more than 1,500 prescribers wrote prescription for around 3,100 unique patients, reflecting both the deep unmet medical need and compelling product profile. For US patients receiving a prescription for Europass, the majority have received payer approval within three months. Outside of the US, we continue to see steady Europass revenue growth in both our Europe Direct and international market. And we currently expect further acceleration of the revenue growth when Europass reimbursement becomes available in additional Europe Direct countries. With a broad label calling all types of chronic hyperpare, supported by international guidelines and a prominent reference to Europass in recently published best practice consensus statement, we expect growth to continue. We have ongoing clinical programs to support label expansion. For example, in older children and initiated Partway 60 trials as single arm safety and efficacy trial to support titration up to 60 microgram doses in the US. The primary endpoint of this trial will be efficacy at 26 weeks, the same as our pupil phase three trial input. We are building towards Europass long-term global leadership based on three key pillars. Differentialization, demand and access. I will first speak about differentiation through mode of action. A replacement therapy for hyperpare must maintain the same mode of action as in DOS's PTA throughout the body and sustain physiological level of PTA 24 hours, seven days a week. Based on all the data we have seen, Europass 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 Europass is available, we see strong interest and growing enrollment. For the US market in just two full quarters, we had around 3,100 unique patients enrolled across more than 1,500 subscribers. We're seeing a broad uptake across the entire country. And with our estimate of 70 to 90,000 patients in the US, we still have ample room to grow. Outside the US, we have recognized revenue from more than 30 countries. And currently we have commercial agreement 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 Europe Direct, we have full commercial loans in Germany, Austria and now Spain. We expect additional commercial loans later this year, both in Europe Direct and international market. In Japan, our partner, Taiteng, expect approval for Europass later this quarter. We consistently hear about how transformative Europass has been for patients. And do not believe that any public disclosed drug and clinical development have the potential to meet this efficacy and safety bar set by Europass. As shown in our clinical trial, they have been extended for all patient groups, post-surgery HP patients, to small genetic subtypes like D. George's syndrome, ADS-1 and idiopathic hyperpare. Notably, Europass has brought approval from the FDA, the European Commission and other regulatory authorities for the treatment of all forms of chronic hyperpare. For all of the above reason, we are confident that Europass has the potential to become a doable blockbuster over time. And we continue to expand our global leadership position in the treatment of hyperpare. Moving now to TransconCMP. We believe TransconCMP is moving the bar on safety, efficacy and tolerability and reducing treatment burden. And we believe TransconCMP is well positioned to become the leading monotherapy treatment for end acrylplasia. In clinical trials, we have seen the desired linear growth across all ages. And to our knowledge, once weekly TransconCMP is the only product to show statistical 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-side reaction. Since our announcement of monotherapy data, we have engaged with patients, advocates, physician and regulators. All have appreciated the differentiating ability of TransconCMP 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 acrylplasia related complications for the majority of treated children. And of course, patient and caregivers appreciate the much lower burden of one-weekly injection. During the second quarter of 2025, FDA accepted our NDA submission for priority review with a perduous date of November 30, recognizing TransconCMP 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 TransconCMP as monotherapy, we are investigating it in combination with our one-weekly TransconCMP. In children with acrylplasia, in our COAS trial, in June 2025, we announced week 26 inter-rein results, which showed a clear boost in linear growth and body proportionality improvement, with a safety and tolerability profile consistent with those observed for monotherapies. In the combination trial, both treatment groups exceeded the 97% factor for growth. Of an average state of children, meaning they are achieving linear growth at a rate higher than an average child. The week 26 data demonstrate the potential to boost growth of around 3x, or three times, above that observed with monotherapies addressing the hyperactive FDR3 receptor pathway. Supporting the scientific rationale for treating the TransconCMP and Transcon growth hormone combined. These results are without precedence in acrylplasia. Importantly, we see clear indication that it's healthy growth, with linear growth accommodated by improvement in body proportionality and without acceleration of bone age. All patients continue in the study as of today. These results enforce the role of TransconCMP as a strong fundamental therapy in acrylplasia. We look forward to our 12 month laser release later this year, and plan to start a phase three study of the combination therapy in children with acrylplasia by the end of 25. In addition, we also expect to initiate a pupil combination trial in hypercantroplasia. I will now turn to Skytofa. Skytofa 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, Skytofa remains a fundamental pillar in our strategy to become the global leader in treatment of growth disorder. Q2 revenue for Skytofa were 51 million euros. We continue to see growth in the number of people treated with Skytofa based on new patients' data. We expect that recent label expansion for adult growth hormone deficiency to further drive long-term growth. Our market research shows Skytofa is the treatment and choice for pediatric growth hormone deficiency among patient and physician. And we believe we can achieve the same status for treatment of adult growth hormone deficiency. Our Phase III basket time of Skytofa planned to begin later this year will include a range of established daily growth hormone indications, including ISS, shock-deficient, TURNR, and SDA. I often say that as soon as we're just getting started. Falling closely behind this major growth opportunity, our research team is developing the next day of innovative transplant technology and product candidates. In addition, our ongoing collaboration with NOMONODIS for the development and conversation of transplant-based product in metabolic and cardiovascular diseases continue to make progress toward the clinic. Ascendis is demonstrating a significant inflection in revenue growth. We are generally importing new clinical data, working towards additional key label expansion. We are advancing new blockbuster opportunity to drive growth for many years to come and fulfill our vision 2030. And we are already preparing for our next vision. I will now turn over to Scott.

Thank

you,

Yan.

I will touch on some key points surrounding our second quarter financial results, but for further details, please refer to our Form 6K file today. For Q2, our total product revenue was 153.7 million euros, which includes a negative sequential foreign currency exchange rate impact of 7.6 million euro. Skytofa is a non-profit, and Skytofa revenue for the quarter was 50.7 million euro, including a 1.8 million euro negative currency impact. YorubaPath delivered strong performance with revenue more than doubling to 103 million euro up from 44.7 million euro in Q1-25. This revenue growth was achieved despite a negative sequential currency headwind of 5.8 million euro. Sequential growth across global markets remained strong, with continued strong uptake in the US acting as a key growth catalyst. The YorubaPath US launch and continued performance outside the US are having a substantial impact on our financial profile, and we expect Ascendus to become cash flow positive on a quarterly basis this year. Including 4.4 million euro of revenue from our collaboration partners, total Q2 revenue was 158 million euro. Turning to expenses, R&D costs for the second quarter decreased to 72 million euro compared to 83.5 million euro in the same period last year, primarily driven by lower development cost for growth disorders. SG&A expenses in the second quarter of 2025 increased to 107.6 million euro compared to 74.3 million euro in the same period last year, primarily driven by global commercial expansion. Total Q2 2025 operating expenses were about 180 million euro. Net finance income for the second quarter of 2025 was 22 million euro, driven primarily by non-cash items. Net cash financial expenses for the second quarter of 2025 were 5.3 million euro. We ended the second quarter of 2025 with cash and cash equivalents, totaling 494 million euro compared to 518 million euro as of March 31. Of the 24 million euro 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 break even 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 YorbaPath. For SkyTrofa for modeling purposes, we continue to believe that sequential revenue growth for 2025 should track growth in prescriptions, offset somewhat by payer mix and normal seasonality. We also expect long-term growth for SkyTrofa to be driven by label expansion, with our recent adult approval expected to only contribute modestly for 2025. We also continue to watch the euro-US dollar exchange rate for any potential impact related to reported revenue. For YorbaPath, our launch is progressing exceptionally well. Globally, we see YorbaPath as a standard of care for trading 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 YorbaPath's growth trajectory, I would highlight the following. Outside the US, we currently see continued steady and sequential revenue growth. In the US, 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 YorbaPath. As Yen mentioned, the majority of US 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.

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 star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 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 Fay from JPMorgan, the floor is yours.

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

Hey Jess, I can start with a few overall view and then perhaps Jake 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 that 200 patients, we will consider some kind of bolus injection because the 200 patients came from our EIP program. So when I take the numbers out from our Q1, one number, the 200, it give 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 bolus. And this is how we basically see the numbers, and this is where most aligned with our comments at the Q1 call, we expected to see a steady state development in the prescription. And first in the second part of the year, we expect to having an acceleration of the conversion of a patient that have a prescription to be on treatment. So that is basic what we have seen. And we look forward to see Q3 and Q4. We are extremely optimistic about this launch. It's a, I'm not just talking about US, we see the same pattern everywhere where we launching, but it's really is amazing. And we expect to see the same state state. Sure, there can be a seasonal factor because of the summer vacation, at least we know in France, the August is closed and other places are happening the same thing. So, Gage.

Thank

you, Yen. And as mentioned before, we are seeing that stabilization and 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 out as we get more months under our belt with the launch. More importantly, just as Yen 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.

Thanks, Jay. Thank you for your question. Our next question

comes from Derek Achilia from Wells Fargo, the floor is yours.

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 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 is a lot of elements that Jay and the entire integrated commercial team are working with. We can go a little bit more in specific, but in the overall view, sure, the different politics from the different PPM need to be installed. There is a lot of elements that still takes time. And we also working a lot on the procedure, how we basically can help patients to be sure, and physician and back office. So that is happening for our ASAP program that we are helping the patient. So nothing can change 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 initiative on a high level, because we have so many initiatives going on. Absolutely, and

thank you for the question. From a time to approval standpoint, as we said, we're seeing the majority within three months. Now we divide our efforts probably in a few buckets. The first one is upstream, right? We're continuing our payer education, whether it's at a commercial level or a public level, just on the clinical value proposition of the product, the full expansive for label, because as you can all appreciate, whenever there's a new specialty drug on market, particularly a rare disease one, it oftentimes takes a bit of time for them to consider either a category or product that they may not have previously had on formulary or plan. So we anticipate that to continue to approve, which will of course have downstream impacts on the speed. More downstream from that, we 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 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 experienced hub that we have. And we continue to look forward to seeing how that will progress.

Great,

thank you.

Thank you for your question.

Our next question comes

from Daseen Hamad from Bank of America. The floor is yours.

Hey guys, thanks for taking my question. I was wondering if you could give 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 your VPAP first, but do you have any color on what the split is between definitionally what a severe patient is versus the type of patients that are getting on that might be on the more moderate side?

Thanks for the question. First of all, there is no medical definition that defines severity of hyperparal. So we cannot go in and claim database and saying this is a severity that you have in the disease because all of them is not classified related to that. When we talked about the element of being uncontrolled, partly controlled or something we call controlled, this was mainly related to one single parameter looking on the claim databases and see how often they're sitting in physician. How often they're sitting in physician, I think has a lot of multiple aspect that somebody are not only reflecting where you're living in the country, what kind of medical access you have and also how often are there an endo that really can see you. So we did it out from this perspective because we wanted to be quite sure we addressing a physician that see the high number of patients in hyperparal. And it was why we addressed this physician as our priority in our, you can say commercial strategies. And so we can say did not define and answer your question because there is no way this is part of the reimbursement system, is no part of we can see of the patient because it's not a medical term that

ever is defined. But I think 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 PGA treatment. And in general, all the guidelines we have seen being issued from all different places in the world now, they are indicating that 95 to percent of all patients basis should be on PGA treatment. And I think that is pretty logical. Think about how many patients on type one diabetes. Would 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 hypopara.

Thank you for your question. Our next question comes from Johan Werber from

TD Cowling. The floor is yours.

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 four to five million. So that puts you at around 24. So it almost seems like you did sort of 79 to 80 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 1500 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.

I can say I can help Scott this time, which I often do. Because what we said in our Q1 call, if you look on Q3 to Q4, revenue increase, net revenue in Europe, was about four to five million euro. And in this two quarter, it was basic Europe or ex US revenue. And we also said at that time that we expect that to continue in 25. When we see more country coming on food commercialization, as we just got Spain now, and we expect a few country more, perhaps it will increase, but it will first have a material impact two to three months after basic imitation of food 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 a forward looking statement. I know it's really being covered by Scott's fast reading, but from my perspective is that we see a strong, strong long here in the US. We have seen nearly the same numbers between Q1 and Q2. And we really looking forward as Jay said correctly, this is an early in the long, it will be too early for us to come up with any kind of prediction, how we really will see the next six, seven a quarter to go.

Thank you for your question. Our next question comes from Gavin

Clark Gartner from Evercore ISI, the floor is yours.

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 finally, what do you think Secondly, looking ahead, do you plan to keep reporting the enrollment forms for your Vipath?

Thank you.

It's 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 time. And what we see during the longs, 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 a sense, in this 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, 12 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 a steady state longs, really with a mature product, could get around 90% of all patients on treatment. I will feel it as a personal success and my contribution to help patients with hyperparal. Jay, you can also come with your personal success number if you want to do that. Appreciate

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

every step of the way. And are you guys planning to report enrollment forms for your path

in the next quarter also?

I think we will give you the necessary KPIs that we're doing today, and we will continue to do that in every quarter. Also, 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. Other than that, we will continue to provide the necessary data that support that you can make a solid modeling of the long tails. Just to say and repeat it, me again, this is amazing long tails. Q1 was great, Q2 was also amazing, great, and we have not seen any weakness in the long tails.

Very helpful, thanks.

Thank you for your questions.

Our next question comes from Il Watzek from Cantor. The floor is yours.

Hi, congratulations on the quarter. This is Daniel Brunder on Fordly Watzek. We're just curious about the pull-through of the patients that get onto your V-Path. How should we think about compliance, especially if you're saying that 1,500 PFS number is net patients going forward? Thank you.

Where we have the best long-term data is from Europe where we basically started by long, so about six to nine months before. And when we look at a rate, what we call true discontinuation, is extremely low, a few percenters. So we really see the benefit of the therapy. People take the therapy, 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 your V-Paths. So everything what we see here is a far away from what you see with a diabetes drug, people stay on it even much better than insulin that you see in type 1 diabetes. And I think this is a many contribution to the positive CNS effect that is with this product.

Okay, cool, thank you. And just going back to Jaron's question earlier about the 1,500 patient net enrollment per quarter, just for me to fully understand, this is the patient start form that you're referring to?

Yeah, that is what we referring to is unique prescriptions, meaning is that it's a new patient that have got a prescription. This is what we call unique prescriptions.

Great, thank you so much and congrats again.

Thanks.

Thank you for your question. Our next question comes from Joseph Schwartz from

LearLink Partners, the floor is yours.

Yeah, hi, I'm Juri Park, dialing in for Joe. Thank you for taking your questions. The first one is on your V-Path. I believe that there were 1,500 prescribing healthcare 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, how many of your patients are in the same clinic? Transcon CNP, a competitor recently announced that their long-acting CNPs 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.

Yeah, let me start with the easy one, or potentially I will take that over to Jay. And I will take the more interesting, I can say scientific interesting question as number two. Sure, so

happy to start with the first question. From a target list standpoint, we're 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.

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 say there is some benefit by having a sustained profile that not give a high C max 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 CMP 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 and also all our associated pattern filing we have with it, all the IP we have of the optimal product, 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 big up to a very, very high value there shortly and then you basically are going up to, as they call it, the dangling 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 the way 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 strength and other things like that, quite sure having continuous exposure, but we do not know exactly if that is maxed out or not. So, often that perspective is very doubtful. Can you get more out on the having an higher AOC? First of all, it needs to have the right AOC. It must be an higher exposure completely over the once weekly profile, and no one deserves 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 exposure 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 balance different pathways. And that is what we do in the combination between transconcerned CMP and the growth hormone effect, which are basic at the same time in a more simplified manner. Remove the break with what we do with the CMP and then having a speed up on that. So I feel really, really confident with our code state, our combination therapy, that really is a unique way where you really can totally provide for patients, for physicians, a complete new treatment standard.

Got it, thank you.

Thank you for your question. Next. Our next question comes from Ilana Murrell from UBS. The floor is yours.

Hey guys, thanks for taking the question and congrats on this round quarter. Curious for achondroplasia, what's your base case for the indication statement for transconcerned CMP, whether it be for the treatment of achondroplasia or for the increase in linear growth in achon like Voxogo has? And I guess any expectations for differentiation in the label relative to Voxogo, 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 BMN 333 and where that might stand relative to the transconcerned CMP IP estate, thanks.

Yeah, we are progressing to the rectus or review with our transconcerned CMP 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 part or in the review cycle. So it's really, really difficult for me to come up with any kind of elements. What I'm more referring to you is the data we have that is really backing up transconcerned CMP. And I believe this is why we got the priority review, because we have data that gives 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 doing a normal development of a child also to an accountant pleasure child. So how can you discriminate is it really is a treatment benefit or just a normal development? And this is why it's so extremely important to be in a position that you're referring to data that's done in a placebo controlled manner in a pivotal tribe. I'm not referring to the other benefit we have, no risk of hypertension, low injection type. This is why the, and sure obvious, patient parents, parents, parents, parents really love the 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 Transcom GMP is providing, which I basically have never seen in any other well controlled people of tribe. 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 product. There was the benefit of having a product that gave sustained things. As there is no clear for me exactly what is the bimaring structure that they have in the BMN 333, 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 face because we are pretty good in what we're doing when we file IP.

Understood, thank you.

Thank you for your question. Our next question comes from Kelly Shi from Jeffreys. The floor is yours.

Congrats on another strong quarter and thank you for taking my questions. For your repass, what is the typical titration period that you are seeing right now across now broader patient spectrum in real world? And once a patient completed a titration period, should we expect a higher monthly cost? Thank you.

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

So once the patient completed titration, should we expect a higher monthly cost because they stay on higher dose rates?

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

Thank

you.

Thank you for your question. Our next question comes from Paul Chow from Goldman Sachs. The line is yours.

Hi, good afternoon and congratulations on the strong quarter result. Yen, just to follow up on your last comment about potentially harmonizing the US label with the EU label and the 60 microgram dose, when might you be in a position to submit that data to the FDA and then commercially, what portion of the patient population would that potentially allow you to address as not being currently suited by the available presentations in the US market? Thank you for taking our questions.

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

Thank you for your question. Our next question comes from Alex Thompson from Stifle. The floor is yours.

Great. Thanks for taking my questions. I guess on your way past 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.

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.

Thank you for your question.

Our next question comes from Luca Isley from RBC. The floor is yours.

Oh, great. Thanks so much for taking my question and congrats on the quarter. Maybe Scott, lots of questions. I was in the top line, right? At least so, but how about SG&A? I mean, up 44% year over year and 6% quarter over quarter. I 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? And then maybe secondarily, can you just remind us about ascendance exposures around tariffs and MSN? Again, appreciate the situation is still fluid and we don't have all the details, but any high level commentary, much appreciated. Thanks again.

Okay, great. On SG&A and expenses overall, so remember last quarter, we did 190 million euro of OPAX and we said that wasn't a bad run rate, maybe plus or minus each quarter. So this quarter we're minus about 10 from that. So we're about 180 of OPAX this quarter. And as you point out, it's probably not best to look year over year because we had a lot of growth in the last year. It's really the sequential build. So I would look at the 6% sequential growth for SG&A as potentially not a bad number to think about, but in the overall context of, I would still say about 190 OPAX 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 euro of cash delta. So overall, everything across the company, it was about five euro 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 we do believe that we're, as a flexible company, we're pretty well positioned to mitigate impact of any policy should it emerge.

Just to clarify and also add in Scott's comments, we're not importing finished product 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.

Thank you

so much. Thank you for your question. Our next question comes from Lina Garshel from Oppenheimer. The floor is yours.

Hey, good afternoon and thanks for taking our questions. Yeah, I'm just curious, you know, 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 you had started to think about hypochondroplasia and now we're seeing a formal announcement of intention to go in that direction. So I'm just wondering what may have changed that affected your decision process here and if you could also maybe just share briefly what you think is the opportunity for us to send this in hypochondro. Thank you.

Yeah, hypochondroplasia is what I will call and perhaps it's wrong way to define it, but I call it a milder form of hypochondroplasia. They don't have many of them the same, what we call body disproportionality, but you can say some in old days, many of these patients basically come in the ISS, your panic short status. And now because of much more influence of genetic testing, you basically have a development large group that more is well-defined from genetic testing to be hypochondroplasia. This is one point that basic are saying, patient that was in one therapeutic group is now being moved over in a different therapeutic 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 transconcMP and transcon-Growthamone, then even if you have a very much heterogenic patient population, then by having a combination product, you basically can ensure all of them will do extremely well. So you can say that is what really are bringing up my attention, 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 in re-changes of the therapeutic groups where the hypochondroplasia is growing because of 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 extremely positive data we got for our close trial where when you have such a heterogenic, some of the key element will be the CMP, growth hormone will help, one CMP is the key element, CMP will help. And this is why when you have such a heterogenic group, having the combination therapy will be the most realistic way to treat them in a way where you really will have a fundamental good treatment regime.

Great, thank you for that Adetala.

Thank you for your question. Our next question comes from the line of David Lebowitz from Citi, the floor is yours.

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 your past?

Curious to

know.

You know, I've always been bullish

and said that it's going to be a five to eight billion market segment. I had no doubt that it would be that.

Thank you for taking my question. Thank you for your question.

Our next question comes from Yong Zong from Wedbush, the floor is yours. Hi,

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

The first one is we actually made some kind of preseason with chytrophin. We will wait until we get the approval and the likely cost will force me to wake up in the morning very, very, very early so there will be a press release or some kind of call at five o'clock in the morning. And I think at that time we will explain exactly when we have seen the labeling, got all the CMC information back from FDA and other places when we will launch the product. And Jay will also be forced to be up in the morning and he will explain how we're going to do our launch strategy in this way. So you need to wait a little bit to this early morning call and we will try not to do it on Sunday, but we will try to take it every other day. So the second part is a little bit about what we talked about before. This hypercontroplasia in my view is extremely heterogenic population now with a lot of what are called treatment burden in different way and also now with the reallocation of patients from the ISS group into the hypercontroplasia. It will someway 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 someway eliminate the discussion if we will have in the clinical trial a single and arm also reflecting trans-concerned CMP as a monotherapy, but it's our belief that the combination therapy will be what is best for the patients in this way. So this is aware after the time being, we believe that the combination is the most robust treatment on it, but obvious there will be some patients that also just with benefit of having trans-concerned CMP as

a monotherapy.

Thank you.

Thank you for your question. Our final question comes from Maxwell Scar from Morgan Stanley. The floor is yours.

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 COACHE 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.

Hey, yeah. I had a lot of discussion with Amy Shue 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 our counterplecture. There are basic growing faster than a normal child. I have four children and I remember when they have growth spurs. It was not really good. We're pretty tall, we're Scandinavian. So you really grow a lot. So you basically will be in a position that 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 transconcerned CMP as a monotherapy and then you will boost again. If there is desire from the parents, for the child and other things related to that. And if it's really unneeded at that time. So in some way, when I think about the overall way, how we will do the best for the patient in the aconder patients, is basically to give them the option that they 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 and that get and then they can continue with our transconcerned CMP. And if they have a desire to

move

into and other one yearly or two yearly treatment, they will can do that again. That is more or less our thinking in this way.

Great, thank you very much. 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 conference. This does conclude the program. You may now disconnect.

Thanks so much. Thank you.