Ascendis Pharma A/S (ASND) Earnings Call Transcript & Summary

Good day, and thank you for standing by. Welcome to the YORVIPATH FDA Approval Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Tim Lee, Ascendis Pharma Investor Relations. Please go ahead.

Thank you, operator, and thank you, everyone, for joining our conference call this morning. I'm Tim Lee, Senior Director, Investor Relations of Ascendis Pharma. Joining me on the call today is Jan Mikkelsen, President and Chief Executive Officer; Scott Smith, Executive Vice President and Chief Financial Officer; and Dr. Aimee Shu, Senior Vice President, Chief Medical Officer, Endocrine Medical Sciences. Before we begin, I'd 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 expected timing of U.S. commercial launch and product shipments for YORVIPATH. Our expectations were in the potential benefits of YORVIPATH, the potential market size and size of the potential patient population for YORVIPATH, our patient services for YORVIPATH, our Vision 2030, and our plans and objectives for future operations and commercialization activities. These statements are based on information that is available to us today. Actual results and events could differ materially from those in our forward-looking statements, and you should not place undue reliance on these statements. We assume no obligation to update these statements as circumstances change, except as required by law. For additional information concerning the factors that can 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 February 7, 2024. On today's call, we'll discuss the U.S. Food and Drug Administration's approval of YORVIPATH and our plans to commercially launch YORVIPATH. As part of today's webcast, we have an accompanying slide deck that you can find on the Investor Relations section of our company website. Following some prepared remarks, we'll then open up the call for questions. With that, let me pass the call over to Jan.

Thank you, Tim, and welcome, everyone, to this Ascendis Pharma call. I would like to start at the JPMorgan conference. I got asked, will there be an approval of TransCon PTH? I only said one single world, yes. And I really is extremely happy today that I couldn't live up to the promise, I have given specific all the patients also in the U.S. that we will get a treatment option. Today, we are celebrating that for first time, there is a treatment option for hypoparathyroidism also in the U.S. We have worked on this product for nearly 10 years. We are in a position, we see the benefit on a global basis, how it's helping the patient. And I'm feeling proud for all the hard work everyone at Ascendis where patient groups, their physician really have been working together to ensure there will be these treatment option also available from the U.S. We're looking forward to be in a position that we're as fast as possible can move this product opportunity out to the patients. I would now like to go to the next Slide 4. The key takeaways is basically described in Slide 4. And when we look on the labeling, we feel it representing its best-in-class potential. It's have a labeling on course treatment of hypoparathyroidism, independent of the background of -- except that it is adults and with the only limitation that it cannot be a good post-surgical. There are no REMS or black box warning. And as we did in our clinical studies, really covering patent payment. And we are obligated also to be as a post-marketing treatment to collect data. So we also can ensure that we basically can be in a situation that we can prove the benefit for this patient group too. We are now transitioning over to commercial, and we are in a position that we hope we can launch in as fast as possible for this patient, we are engaging with the health care provider and our market access team is really working already from today to ensure that we can get the commercial product out to the patients. Going to Slide 5. This is an overview of selected highlights from our U.S. prescribing information. I will not go into detail of that slide. To date, in the U.S., we have 2 products approved now. Our 2 first product we developed with the TransCon technology, SKYTROFA and YORVIPATH. At Ascendis, we develop our specific algorithm for product development. And when I see in combination with the TransCon technology to be in a position to develop 2 independent products out of 2 to the market, I feel really, very proud. We focus on huge unmet medical need in the rare disease area, we focus on making highly differentiated product, but we also have shown that the combination of the TransCon technology and our specific algorithm for product innovation are basically beating of traditional product development. But we are not compromising in any way, not to make highly differentiated products that really are addressing major unmet medical need. 2 out of 2, but we're not stopping there. Our next product is our TransCon CNP that we now focus on to getting the people the data here in the rest of the year. I will now turn it over to Aimee Shu that will talk about hypoparathyroidism and the unmet medical need.

Thank you, Jan. I will start with Slide 9, and it is really my pleasure to be able to take us back to the fundamentals and remember the void that YORVIPATH filled. So here on Slide 9, on the right-hand side, you see the image of an intact parathyroid access. And the recognition has been for many decades that hypoparathyroidism is the last classical hormone deficiency, which has not had a hormone replacement, and it has long been recognized that an ideal replacement would accomplish the things mentioned at the bottom of the slide here, a reduction in the amounts of calcium and vitamin D requirements, a reduction in urinary calcium, an improvement in quality of life, a reduction in ectopic soft tissue calcification and an improvement in abnormal bone remodeling dynamics. And this all stems back to how the parathyroid hormone access works physiologically and when the access is intact. So what I want to show here is that parathyroid hormone, represented in the purple here, has 3 major target organs, including the bone, kidney and intestine that act in concert to handle serum and urine, calcium and phosphate, most importantly as electrolyte. And together, it is this, that maintains normal serum calcium and phosphate. So it's a little bit like saying we are -- historically, like we are treating type 1 diabetes, which results in high glucose by saying, please don't eat extra glucose, right? It's as rudimentary as trying to treat type 1 diabetes without insulin. And now we are very happy to be able to say we can bring parathyroid hormone, the missing hormone, to hypoparathyroidism of hormone deficiency that has broad-ranging effects. On Slide 10, to continue this, we show the various multi-organ manifestations of hypoparathyroidism. I know this audience knows it from before, but it is once again to highlight how systemic this condition is, including impacts on the central nervous system, renal system. And here, you also see respiratory, cardiovascular, the peripheral nervous system, neuropsychiatric, ophthalmological, dental, dermatological and musculoskeletal. So this truly a major step forward that we are able to replace the missing hormone that impacts so many systems. In fact, as shown on Slide 11, it has also been mentioned as recently as 2 years ago, when world experts convened the second international workshop on hypoparathyroidism, evaluation treatment and management. And here, they recommended to consider parathyroid hormone replacement, if it were one day available, in patients not adequately controlled on conventional therapy. To conventional therapy, as you remember, is forcing calcium and active vitamin D, which cannot be made in the absence of parathyroid hormone, just to support serum levels but doesn't impact all of those 3 organ systems, as mentioned before. And within those guidelines, these are the possibilities considering when one would -- when a prescriber should consider parathyroid hormone replacement. And those include things such as symptomatic hypocalcemia, hyperphosphatemia, renal insufficiency, hypercalciuria and poor quality of life. In general, this is quite broad and safe to say this, nearly all patients with hypoparathyroidism experience at least one of these and most all of these. In addition, individuals with poor compliance, malabsorption of food and medications, and those who are intolerant of large doses of calcium, such as limited by constipation and nausea and intolerant of active vitamin D may also benefit from direct PTH replacement therapy. And now I turn to Slide 13, where we look at the demonstrated efficacy in adults with hypoparathyroidism. This is from the pivotal pathway trial at the primary efficacy end point evaluated at week 26. And we'll go through row by row and what you can see here, the overall response at week 26 was incredibly strong with treated patients, so patients randomly allocated to TransCon PTH YORVIPATH. 69% of them reaching a multicomponent end point versus only 1%, 5% in the placebo arm. Baseline demographics for these patients very much represent who is treated in the United States and globally today. Majority were women, nearly 50 years old in age and represented a broad swath of etiologies, including postsurgical hypoparathyroidism. As the majority, idiopathic reasons, autoimmune polyglandular syndrome type 1, autosomal-dominant hypocalcemia type 1, that's a calcium sensing receptor mutation, DiGeorge syndrome and hypopara renal deafness syndrome, which is a GATA-3 mutation. So it's safe to say that this trial also included and encompass the various ways to arrive at hypoparathyroidism, both congenital, acquired and unexplained. Now I'll go line by line at the components that comprise the multicomponent endpoint. One had to be considered a responder, a trial subject, had to meet every single component on here to get that 69% above. But here, we show individually broken out how met -- with the proportion that reached each component. So as an example, 80% had achieved a normal serum calcium at week 26. 95% were independent from active vitamin D, the downstream hormone that requires PTH to be produced but now they were making it themselves, independence from therapeutic doses of calcium. No increase in study drug since week 22. So this is a 4-week period in which the dose stayed stable. And then finally, you see here, there is a fifth component that was added by FDA, and that is the study drug dose has been 30 micrograms or less per day through week 26. So that is for the duration of the blinded period of this trial. And that came from FDA an acknowledgment that they recommend a maximum dose of 30 micrograms once per day, addressing the concerns about risk of unintended changes in serum calcium due to potential variability of delivered dose. And then not shown in this particular Slide 13, but discussed in the label and text. During the extension trial through 1.5 years or week 78, there are some response rates shown. And the initial set of numbers shows a response rate for this exact end point stable dose since week 22 in YORVIPATH, and that seems to go downwards from 69%. The next part of the explanation shows that when one allows for titration, which I will add is very realistic for any hormone replacement such as insulin, thyroid hormone replacement, estrogen replacement over time, one needs to titrate. And so when allowing for the normal expected titration for failing glands or failed gland, then the efficacy rate is back up in the high 60% range. So very similar to what was seen at week 26. And this is what we would expect to see also long term in the real world. And now we'll turn to Slide 14. These are the adverse reactions as reflected in the label for YORVIPATH. These are events greater than -- that occurred in greater than 5% of subjects with hypoparathyroidism treated with YORVIPATH, and at least 2% or higher frequency when compared to those who are allocated to the placebo arm. As expected for an injectable drug, the most common adverse drug reaction were injection site reactions, followed by vasodilatory signs and symptoms, then headache, diarrhea, back pain, hypercalcemia and oropharyngeal pain or sore throat. And now, Jan, I will turn it back to you for the remainder of the presentation.

Thanks, Aimee, for your presentation. I will move fast to Slide 15 because it's giving the U.S. demographic. To our best knowledge, that's about 70 to 90 adults facing the chronic hypopara in the U.S. And we described them in 3 different boxes, the one that actually have experience with PTH about 4,000 to 5,000. And then we're also seeing an influx of new patients with we have calculated to be around 3,000 a year, where the majority of these patients is coming from the post-surgical. So you can see that hypoparathyroidism is a rare disease. There has less than 100,000 patients. But as Aimee said, all these patients really deserve to have a treatment with PTH. As you can say, if you have type 1 diabetes, you should also be treated with insulin. The largest group are the post-surgical patients, but as Aimee described, we have covered a lot of other groups of hypopara patient with a diverse background like ADH1 and other genetic but also hematological part of it. Going to Slide 15 -- 16 now. We are in a position -- we are transforming now from our pre-commercial to our commercial activities. We have, before our approval, been working with the physician on education on the disease. Now we can move to our next stage, sharing about YORVIPATH and the benefit it's providing. As YORVIPATH is our second product we are launching in the U.S., we already have an established commercial organization. We have seen the success of schedule over here in the U.S., and we were utilizing the same successful setup really to bringing YORVIPATH out to as many patients as possible -- as fast as possible. Going to Slide 18, there is about 6,000 HCPs that we someway believe is covering 80% of the patients. They will be our primary focus, and this is what we're building the sales organization to cover together with our medical affairs teams. Going to Slide 19. We will use the same way that we launch SKYTROFA. We have A.S.A.P. program where we really are helping the patients in the journey some starting the treatment through the entire journey to be a patient that really can achieve the optimal treatment to help from all different places. This is our established organization that we now have seen successful launching of SKYTROFA and really will drive the YORVIPATH too. Going to the last slide, summary and next steps. YORVIPATH is now approved, is the first and only product to treat hypoparathyroidism in adults. And when I look on the labeling, I feel that this really are reflecting everything what Aimee said about the benefit for the patient and the launch begins today. We have been extremely productive dialogue engagement with hypopara patient organization, their physicians, community, and all have been extremely engaged in having the same mutual dream to get out and treat the hypopara patients with an treatment option, and now we are here. The first thing I had was the code with the patient organization because they are the most important part. We have kicked out now our commercial launch. And I feel when I think about our product opportunities that we now are developing in rare disease endocrinology, SKYTROFA and now YORVIPATH in the U.S., the next 1 will be TransCon CNP, rebuilding an integrated pipeline of 3 independent product opportunity, and we will continue to do what we believe we are a company focused on the patient and really bringing treatment difference out to them, specific in the endocrinology rare disease. Thank you a lot, and it has been a pleasure to be part of this journey and I'm really looking forward to be in a position that we can continue the journey that we now have started. Now we're ready for questions.

[Operator Instructions] And our first question will come from Jessica Fye from JPMorgan Chase.

Congrats on the approval with the hypopara treatment indication. Two questions. Can you talk about the degree to which data on urinary calcium is captured on the label? I know the EPAR talks about the product normalizing urinary calcium. And then second, given you were previously ready to launch in the U.S. last year, can you talk about the launch time lines as it relates to product you're currently completing manufacturing of? And when we might hear if you get clearance to commercialize the existing manufactured product?

The first question, I will transfer over to Aimee, but I believe we have presented the positive data that is also on withdrawing the PTH level on the kidney function. But Aimee, you can basically reflect how it's integrated -- in the basic.

Yes. So Jess, in the label, it's under Section 14, where we described the baseline demographics of the clinical trial patients and how at baseline they start out with a high abnormal urine calcium level.

And does it speak to where that goes?

It does not.

The urinary calcium was one of the elements that we not got included inside the labeling on it. We feel that the way we are communicating on that will be through our publications, which are proving how we also have a benefit on that. There's a lot of good reason and a lot of good discussion we have with the regulatory agencies on taking this into our labeling. And I feel that it's a way where as well, we have seen the benefit of this and is recognized. I feel that it's not really what's the most important thing for us to bring on. Going back to your second question, yes, from a commercial perspective, we are ready. We have established infrastructure for being ready to move into the market. What we're waiting for is being ensuring we have the drug product ready for the U.S. commercial launch. You know we are in many different countries today from Austria and Germany, we have our direct commercial loans and then we are providing for name patent program different places in the world. From the U.S., as you will see later on, and we have and from initial part -- and shelf life or we can say, an expiration date that are starting in 12 months, meaning is that we are producing batches. So we're quite sure we can get them into the U.S. market as fast as possible. This is one of the thing that we basically will improve very fast after launch, so we can move up to the normal level of expiration days that we would like to have.

Our next question will come from Li Watsek from Cantor.

Congrats on the approval. I wonder if you can maybe give us some guidance on pricing and how your conversations with payers go with respect to pre-authorization and if there is any [ steps added ]? And then we also noticed that the maximum dose in the U.S. label is 30 mg versus 16 mg for the European label. So maybe just clarify if there is a difference in terms of the maximum dose and what's the implication?

Yes. Let me take the first question related to the pricing. Our vision for such a product is the same as every other product. We want to come out to as many patients as possible. We feel that every hypopara patients deserve to have a treatment with PTH basic also, as Aimee told, is reflecting in the guidelines. We are now integrating all different aspects, so we can have a holistic view about how we are optimal addressing this unique goal in the U.S. And in this regard, we have not decided on basic the price yet. We are initiating discussions with reimbursement company now, and that is the integrated part of that discussion, too. So when we come to the next event we have, I think it will be our Q2 call. I will expect that we can come with much more clarity related to how our U.S. prices will be. The second question was related to labeling between 6 to 30 and 6 to 60. And Aimee can talk about how the patient's basic [ world ] in a position that in our primary end point at the time, the last 4 weeks, there was only very few patients that basic were over 30 micrograms. So we always have their few patients being over 30 micrograms. And we feel that there is a 2 different agencies, FDA and EMA. Sometimes they look on the same data by different views. But what we're feeling here is that we basically have a product that really in the U.S. also be seen 6 to 30, really give for the majority of the patients really and treatment that really are a treatment of hypoparathyroidism. Aimee, do you have further comments?

Thank you, Li. So as you know, the dosing of up to 60 micrograms was used in our clinical trials and is what is approved in Europe. And the U.S. label reflects up to 30 micrograms. And as Jan was mentioning, a lot of the data that is summarized in the publications and also in the label includes safety and efficacy up to 60 micrograms. Safety up to 60 micrograms and then efficacy up to 30 micrograms. But given that there were very few patients who at any one point require doses above 30 micrograms, the efficacy is by and large very similar between when we have used the -- up to 60-microgram data set and the 30-microgram data set.

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

Maybe I just wanted to follow up on the question around the dose. As you've launched in Europe, do you have a sense of what the average dose is being used for the adult since the launch in, maybe, let's say, Germany? And in the past, Jan, I think you've talked about -- not to think about the dynamics of the launch in Europe necessarily as reflective of what to expect to the U.S. Now that you have the final label in hand, can you give us your updated thoughts on what you think the trajectory of pickup will be for PTH in the U.S. relative to what you've seen in Europe?

Yes. I actually expected this question. So I actually went back to U.S. or the Germany [ and her team ] and asked them this question. Now we have patients more than 200 -- I think, more than 250 patients now. How many are basic, are taking a double dose. And to their knowledge, I could not get a confirmation of any patient yet that basic, we are in a position to take adopted dose. So from that perspective, you can say that -- you can see that the vast majority are all patients basically are having an optimal treatment in less than 30. The question which are potentially the most relevant is that if you potentially need -- an addition to your 30-microgram daily dose, you will potentially still benefit dramatically for having 30-microgram dose and then potential at either attach some supplement or potentially some active vitamin D for that. The physicians are the ones that described what is the best for the patient. So the physician will always be in a position to do the optimal for the patients. Related to your second question, related to when I look on the penetration we see in Germany, when I look on the labeling we have here in the U.S., I believe based both labels are really best-in-class labeling for really treatment optimal for the patients. There is -- when you look on the broadness of the patient group, you need to be adult. In Europe, you need to have chronic hypopara. In Europe, you don't need -- in U.S., you cannot be coming for the acute. There is no limitation in the background where you got the hypopara. So you basically can treat every patient with hypopara. There is no limitation in [ rents ]. There is no limitation in other things. So I feel both labeling are optimal for really coming out and treating the patients. So Tazeen, when I think about it, are more and more positive after I saw the U.S. labeling that I ever thought I will be.

Our next question will come from Kelly Shi from Jefferies.

Congrats on achieving a great milestone. So regarding the first wave of patients for the U.S. launch, except for the patients who had experience with NATPARA, how do you see PTH therapy awareness improve over time? And what would be the size by our estimate of the new patient group could be immediately prescribed?

When I look on the patient group, and either you come in as a new diagnosed hypopara patients or you come with the definition of having chronic hypopara for perhaps 1 year, 2 years, 5 years, 10 years, all of them deserve a treatment. And I also believe when I see the guidelines that Aimee reflected on them and talked about the patients that it basically is reflected in that -- that should be treated. So I believe I cannot guess where the patient would come from because I do believe that will come from everywhere. We saw the same thing in Germany where I expected that seeing more, much more in hypopara patients, but we saw more and more naive patients. For example, in Austria, where we also had commercial loans, I think half of the patient basics are naive patients. And I think it illustrates the unmet medical need this naive patient has exactly. And so therefore, when I look on the patient group in the U.S., sure, we have a huge responsibility for the hypopara patients that potential will have a limited time of treatment on hypopara because of it record, and we need to be quite sure we will do everything we can do for this patient group so they don't need to move over to conventional therapy. But I also believe that the unmet medical need with the naive patient is as high. And this is why I'm not really describing where I believe the patient will come from a specific place, I believe they will come from everywhere.

Our next question will come from David Lebowitz from Citi.

With respect to the NATPARA experience patients, how many of those patients are still in the system, given they haven't had a drug for quite some time to -- do these patients still see their doctors regularly? Or is there going to be more of an active effort to actually get in touch with them to bring them back?

I think, David, you're referring to our best knowledge, that was about 4,000 patients on NATPARA, I think that is our best estimate. And when the -- have the recall of NATPARA, they only managed to give treatment to about 400 patients. It means that 90% of the patient basically didn't have any treatment option except to go down to conventional therapy, basically taking care of some [ softer brand ] or active vitamin D. All these patients will be in contact with physicians because they need to get a prescription of active vitamin D, potential also to help them to the hurdle of the daily day how to manage with the disease. So to our best knowledge, and this is where we see potential limitation will be, how fast can many of this hypopara patient basically get admin appointment by the physician that -- and to -- that basic facility that can be starting the treatment.

David, I can add that -- the short answer is that hypopara -- patients with hypoparathyroidism generally would continue to see their physicians. So I think even had they been previously exposed, and now without, they are still in close touch with their endocrinologists.

Our next question will come from Joseph Schwartz from Leerink Partners.

Congratulations on the approval. It seems like this is an indication that payers have been motivated to manage access to more than others. And so I was just wondering why do you think that is? And how are you prepared to help patients get access? One thing we've heard of potentially occurring from a couple of physicians was perhaps having access limited to those patients that have had acute episodes of hypo PTH in the past, and -- like last year. So I was just wondering if you've heard that, if that's a possibility, and how you're prepared to help patients get access?

Aimee, you must near the patient that I am, and I do not know. You have heard or reflected about that comes from...

So Joseph, do you mean acute hypopara has in post-surgical and before 6 months as an example? Or do you mean those who are having hypocalcemic crises from time to time? So that means they've had long-standing established hypopara and then our hospitalized every so often because they cannot manage.

Yes, I think it was that latter point.

Sure. So whether those would be the -- your question is whether those would be the ones that would be more convincing to payers to key upfront?

Yes.

Yes, it's all speculation, and we are working through -- you could certainly think that they cost the hospital system a lot of money. But I think that will be one compelling way and has historically been a compelling way to get access to the -- for instance, NATPARA is to say that one has been hospitalized many times, that's certainly the way that the patients have, the 400 patients out of the 4,000 have had been able to assess the potential use program.

But I think the simple answer is, Joe, and it's basically going back to Aimee's slide. How I often see is that the prioritization of the approval of the prioritization is in -- are your insight exactly that lately, and also the contracts. And when I see the labeling, when I look at the guidelines, I actually believe that the vast majority of all hypopara patients are exactly qualified to and positive pre-prioritization. Scott, do you have any other comments to that point?

Sure. Yes. So I would say, Joe, all of our experience and research would indicate that the prior authorizations, which you expect a standard for the specialty category would be to label.

Our next question will come from Gavin Clark-Gartner from Evercore ISI.

I first just wanted to ask on your ability to supply the market in 2025. So first off, for the existing manufactured product, how many patients do you believe you could supply in '25? And additionally, for the commercial manufacturing that's coming online, how many patients do you believe you could supply with that? And then I have a follow-up.

So one of the things we have been extremely proud about is our robustness in our supply chains. We have now been in the market with SKYTROFA for multiple years. Never been in a position that we never, never could not support supply to a patient if the patient wanted to be untreated. We would do the same thing with YORVIPATH. We're scaling up for that. We will be in a position that we can be and hope we can trade as many as possible. We should not be the limitation and we hope we never will beat that. So from that perspective is that we are doing everything, so we always will have the same acknowledge from the patient, from the physician that we are a reliable company.

Got it. And do you have an estimate how many patients in the U.S. are on PTH today, whether that's your expanded access program for YORVIPATH? Any ongoing extension studies for YORVIPATH or any patients that may be on teriparatide?

There was a lot of questions. So I really do not know -- we know how many patients that, for example, are on FORTEO or [ Tyvaso ] or anyone else who we know how many patients we are on our ERP program, and we will convert them as possible to this. So that is what we intend to do, get them over as commercial patients as fast as possible.

Our next question will come from Derek Archila from Wells Fargo.

Let me add my congrats on the approval. I just want to know how much do you think NATPARA's removal from the market later this year may factor into the FDA's decision to potentially approve your currently manufactured products. I guess, do you think it increases the odds that they will?

I believe FDA will always take the right decision. And from that perspective, I hope everyone see the unmet medical need, everyone see the situation this group of patients are in. So I think everyone is in the same boat. Everyone wants to do the right thing for the patients. And therefore, I'm always a bare positive person when I think about how we can come out to the patients as fast as possible.

And our next question will come from Alex Thompson from Stifel.

Congrats on the approval as well. I guess just a follow-up on the manufacturing part of this. Could you walk through sort of the time line around when FDA might be able to approve the currently manufactured product and when you'd be able to disseminate that to The Street?

And just to clarify, as we said in the press release, we have already planned manufacturing, they are already on Wires, they are getting released on everything, and we will be ready for the market in Q1 '25 with all the new criteria. Currently, we have existing manufacturing batches that we, for example, are utilizing other places in the world, 2 patients there. And that is what we would like to discuss if we can move them into the patients in the U.S. until the basic will be in a position. We can have the planned manufacturing facility ready in Q1.

Our next question will come from Paul Choi from Goldman Sachs.

Congratulations. My first question is, as you think about your marketing efforts, which in the minds of patients and physicians as most important in terms of promotions with regard to symptomatic relief among PTH patients. And my second question is for Scott. As you look at the guidance here for the remainder of the year, are you comfortable with more of the upper band and band of the range at this point? Or just any thoughts on regard to incremental OpEx or [ through ] the top end of the range would be appreciated.

I think, Aimee, will you take the first question? And I think, Scott, you are being asked with the second question.

Sure. I think Paul, it's actually quite variable, what might be most important for each patient and physician combination. And among the many things mentioned, for instance, in the label, and the many manifestations across the systemic situation with hypoparathyroid, any of those can be compelling. So I think once again, would go along with what one could see in the label and from the guidelines -- consensus statement guidelines.

And Paul, for your second question on guidance updates, I would refer to prior statements even on this call that we have an existing infrastructure through which we will commercialize YORVIPATH. So that's been in place for a while. Incremental changes to the infrastructure and/or changes to guidance, we'll come with you on our Q2 call. But just keep in mind, we've had infrastructure in place in the U.S. ready to launch a second product for some time.

Our next question will come from Vikram Purohit from Morgan Stanley.

This is Gospel on for Vikram. Congrats on the approval. Could you talk a bit more detail what the size of the field force is that will be detailing on YORVIPATH? And how you will be phasing in the targeted effort for the 6,000 HCPs you mentioned in the presentation?

Yes. So our sales force is basically consisting of 2 parts, what we call direct and what we call the virtual sales force. And we are already building up the sales force now. We have had the first part of that. So we are ensuring that we basically can be ready all the places where we want to be rating. And from my perspective is that we have shown it how we did it with SKYTROFA, where we get the same strategy, trying to address 80% of the prescribing physicians. And I think we will do the same successful way at this time. We never really discussing how many we have in our sales force. But you know this is a rare disease and it's typical -- pretty much specialized. So I feel that is exactly the same structure we will use here compared to what we did in SKYTROFA. No surprises, I can guarantee.

We'll take our final question from Yaron Werber from TD Cowen.

I have two sort of related. Just the first one, you mentioned that you look to get the normal exploration debt that you want and depends. Can you discuss with what that is relative to what you used in the Phase III? And then secondly, for the patients that did take BID dosing in the Phase III, what was the reason to do BID dosing?

The first question is that, initially we will start with the 12 months expiration data. And what we often will do and we already have established when we will do it, and that is basically as fast as possible. We will go for 18 months and then we go for 20 months, and then you can really invest in -- we'll try to go for 36 months. And this is a typical way where you basically are building a longer and longer expiration date when you get more and more data, and that's exactly the manner that is required by basic regulatory agencies. And your second question, I forgot it.

And the patients that -- the few patients that did take more than 1 injection, presumably 2 injections per day in development, I think, what was the reason for that?

It should -- because the reason was that you had [indiscernible] less than [ 8.3% ]. Many patients have been used to be lower than 8.3%, I would say, Aimee, you can correct me, but I believe that the majority of patients are under 8.3% before they come into treatment. But because from the protocol perspective is that it was aiming them always to be higher than 8.3%, to basically increase the dosing. Will we see the same thing happening in what I call the more real life situation? That is a good question. And therefore, it was a very, very relevant question. What is now happening in Germany now where we have more than 250 patients in treatment, are they really moving up to adopt the dose? So first of all, I just need to clarify. There was not a BID injection. It was basically just very used to get the right dose they use 2 pen. It was not because anything else. So it was basically a 2 pen system, you used to have it in this way.

Thank you. This does conclude today's conference call. Thank you for your participation. You may now disconnect. Everyone, have a wonderful day.