Ascendis Pharma A/S Q3 2024 Earnings Call Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Jessica Fye - JPMorgan Chase & Co - Analyst : Hey guys, good afternoon. Thanks for taking my questions. You laid out a case for a strong initial US launch for YORVIPATH, and we're clearly seeing that ex-US already. Can you talk about why you have confidence that you'll be able to keep the patients that you pick up in light of various competitors potentially entering the market? And my second one or a follow-up is just in the past, you've talked about an expectation to reach operating cash flow breakeven by the end of 2025. Is that still your expectation? Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board Thanks, Jess. I will take the first question, and then I'll delegate it to Scott to take the second question. And I think yes, we basically some way reflected that in the -- our initial remarks. Because what we described, what is really a true replacement therapy because we are talking about patients that is not have sufficient industrious hormone to really -- to have a normal functional life, like a type 1 diabetes. And when we look at the characteristics, which have been proven in multiple publications, specific from NIH, where they used infusion pumps, taking PTH into short-acting PTH, but they can keep up the physiological concentration 24 hours, 7 days a week. So when we think about what need to be taken as what we call a true replacement therapy is that you need to have the same mode of action, like you have in the (inaudible) hormone. And basically, you need it because there are so many multiple organs that need some way to get the right receptor activating, signal pathway activating to have the normal physiological function. The second thing is that you need also to have the right distribution. Because it needs to hit both, for example, just an organ and kidney, both in the blood and the urine side need to go to the brain, it need to go everything else to. And the last thing is basically the PK profile. You need to have the right concentrating 24 hours, 7 days a week. And whatever I do, when I look on the clinical program [that is] I cannot find anyone that's just living up to the level of what I call a replacement therapy. That was for first question. I think Scott will take the second one.

Question: Tazeen Ahmad - BofA Securities Inc - Analyst : Hi, guys, good evening. Thanks for taking my question. Mine's on CNP. Can you just give us an update on where you are in preparing for your meeting with FDA and/or your application, what are the open items that need to be completed before you can guide us to whether or not the data that you have is indeed going to sufficient for application? And also, could there be potentially a pathway where you start your submission and provide data on a rolling basis if the agency is looking for extended data? Thanks. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 14, 2024 / 9:30PM, ASND.OQ - Q3 2024 Ascendis Pharma A/S Earnings Call Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board Thanks a lot for the question. And to our knowledge, and that is after interaction with both regulatory agencies in Europe, and US, we have the integrated data packet that need to be part of the submission. So we basically have no missing data that we actually need to be generating for basic to finalize the application here, for example, with FDA. We've been doing that and we're getting ready to the filing, what will happen in Q1 is pretty near now. And when I look on the packet, we really are providing a packet that not only providing the best-in-class growth of the children, but we also, for first time, can address comorbidities. And I think this is something we will continue to share with you how we really are providing a treatment of achondroplasia instead of just providing linear growth. If you just wanted to have linear growth, I would just give them growth hormone is the best hormone to provide linear growth. And I think this is why we are unique position because we have the opportunity really to address the comorbidities. And we will continue to give you data how really that is really coming from the data package we are submitted to the regulatory agencies.

Question: Yaron Werber - TD Cowen - Analyst : Yeah. Hi, great. Thanks for taking my question. Jan, maybe just a couple on YORVIPATH. I think in the past, we were expecting that the pair will get pulled off the market by Takeda by the end of this year. Can you give us a little bit of a sense, how is this going to work? Is it driven by the hard date like December 31? Or is it just driven by when they run out of supply? And then also in Europe, I know you're waiting for the NATPARA inventory to run out before YORVIPATH really takes off. Can you give us a little bit of an update on timing, your expectations? Thank you. Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board Yes. You're asking me a question, that is outside my control. Because I cannot control when NATPARA is running out of stock. We know they are staying everywhere. They are ceased the production and they're running out batches. We know now we are in a position in the US. I believe they will try to get out of the US market as fast as possible because they basically provide free drug out to each single patient in the US. In Europe, we have seen an interesting pattern to them where they are trying to come out with every inventory they are doing as fast as possible and using all different means to do that. And to our best estimate, it somewhere will be in next year, you will see the big transition happening. But at the same time, we saw in the two different patterns in two different countries. In Germany, they switched NATPARA patients because I said there was an improved treatment. Now in Germany, they are over and taking new patients now because the pool of NATPARA patients is running out. Austria different. They said, let's keep the NATPARA patient on NATPARA as long as possible and then take new patients. So what is going to happen in the US when I see these two countries, two different patterns, and we believe from the four groups we talked about, all of them will be switched.

Question: Gavin Clark-Gartner - Evercore Inc - Analyst : Hey, guys. Congrats on all the progress. So I just wanted to ask about the 4,000 to 5,000 PTH experienced patients in the US that you've noted. Are all these patients actively managed in the health care system? And I guess more specifically, how long do you believe it could take to get the majority of these patients on to YORVIPATH? Could it be within the first year, two years? Any estimate would be helpful. Thank you. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 14, 2024 / 9:30PM, ASND.OQ - Q3 2024 Ascendis Pharma A/S Earnings Call Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board Thanks for the question. I believe this PTH experience group, they're used to do a daily [demonstration] If you're coming from, for example, Forteo some patients are doing injection four times a day. But you know the Forteo and all short acting, many of them have a limited time frame for only two years because of the superficial logical PTH level they're providing. So when I look on the 4,000 to 5,000, the majority is NETPARA patients that couldn't come into the program that basically got started when they have the record. So when that pass special use program to our best estimate only could take 1 out of 10 patients. So we were certainly sitting without any kind of PTH treatment option. I believe this patient group will try to be -- coming into an endocrinologist as fast as possible. This is why we talking with the patient organization. We're talking now that here in the middle of January, you basically will have product availability here in the US and really go in and start to get the prescription. We have our hub, the [ESO] program really and unique element that will help the patient in the journey from the prescription to basic to be in a position they are fully reimbursed and be on drug. We have the infrastructure to it. We know how to get it done and we believe there are so many patients that are just waiting for this opportunity to get a treatment.

Question: Li Watsek - Cantor Fitzgerald LP - Analyst : Hey, guys. Thank you for taking my questions. I guess relative to the pediatric growth hormone market, how should we think about the revenue contribution from the adult market as well as the Turner syndrome. And it sounds like you're initiating a basket trial. Maybe just comment on the market opportunity there relative to the growth hormone market? Thanks. Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board Yeah. When we look on the growth hormone market, on label, we only have access to the market segment that is covering by pediatric growth hormone deficiency. We have now filed the adult growth hormone deficiency, which open up for a complete interesting segment currently only established at 10% of the growth hormone market, but it's a highly, highly underpenetrated treatment population in the US. Best estimate we have is about 5% to 8% is being treated with adult growth hormone deficiency. So it's really to develop a market that can be nearly the same size as the pediatric market. We focused on being quite sure. We are -- SKYTROFA should be the choice in all indications where we have the growth hormone market. And this is why we're making the basket trial where we're taking the ISS, SCA and shock, which include Turner. By having this label expansion, we will be in a position that we nearly covering the entire growth hormone market. And this is our vision to build SKYTROFA to the blockbuster it should be. Going to PTH, going to hypopara, it's quite different because the adult segment is basically the majority of the market. Patients are coming with pediatric, what we call hypopara. The majority were not coming from post-surgery but more coming from immunological genetic diseases. So it's a quite different segment in this way and is much more smaller than the adult segment. We are initiating a trial in the pediatric segment. It will be just in the planning now and it's a part of also our obligation to the European authorities also make it available in the pediatric segment. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 14, 2024 / 9:30PM, ASND.OQ - Q3 2024 Ascendis Pharma A/S Earnings Call

Question: Joe Schwartz - Leerink Partners LLC - Analyst : Great. Thanks so much. First question is on YORVIPATH. I was just wondering, how do you expect the launch of YORVI in the US to compare to Europe in general? And then is the monthly serum calcium monitoring requirement in the US likely to be a significant deterrent for patients, which impacts the launch curve at all in your view? Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board Let me start on the last question, Joe. What I've seen, I've seen the UM criteria for some of the places. And I have never seen that being installed as any kind of criteria. So I don't think this is really the case. I know the patients often will have this kind of missing. So it's not like it will be a burden to have it, but I'm not seeing it in the UM criteria from anyone. Related to the US market is quite different than the German, Austrian market, penetration curves from Germany or Austria compared to US had quite different slopes. So from that perspective is that it's such a unified market segment in the US, if things goes faster in the US, there is much more open mindset to try new treatment than what we're seeing now in Germany, everyone tried with 1 or 2 patients, now it's going up. So the average patient per physician was between 1 and 2. Now we first come into the states where they're going to be in 2 and 3 for the physician. And this is some kind of, what I call, you first penetrate, then you broaden it. But what we expect to see in the US is a much, much larger and faster uptake.

Question: Joe Schwartz - Leerink Partners LLC - Analyst : Okay. Thank you. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 14, 2024 / 9:30PM, ASND.OQ - Q3 2024 Ascendis Pharma A/S Earnings Call

Question: Vikram Purohit - Morgan Stanley - Analyst : Hi, good afternoon. Thank you for taking our questions. So we had one on the recently announced Novo Nordisk collaboration. We were just curious as that moves forward, what the next public disclosures there could be, what we can expect to learn from yourself and/or Novo Nordisk? And then secondly, for the oncology pipeline, we were curious what the next milestones there might be and how you're thinking about progressing the oncology efforts you have in place with potential partnerships and what partnership economics or a good partner for those efforts might look like in the future? Thank you. Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board Thanks for the questions. Related to the first question, we have seen stream powerful TransCon technology, making 3 out of 3 endocrinology product from idea states until basic pivotal data and two of them are approved now. And this is the TransCon technology with our algorithm for product innovation and Novo Nordisk took that up too. So we basically are in a position when I see what we can provide with our TransCon technology in obesity, in metabolic diseases like diabetes is we can take a peptide, well-known properties, already proven safety, proven efficacy and do exactly the same thing. And at the same time, we can make it to a once monthly but potentially also improve tolerability to potential efficacy in the same time. And we're really proud to have a partner like Novo Nordisk. There's only two companies in the world in my view that have the manufacturability capacity really to make -- and commercial infrastructure to really to make this in a $1 billion product. And these two companies we actually have a unique great collaboration with. And they're not only using it for one of the product, they will continue to apply multiple product on it. Related to specific progress, related to a specific update about progress on how they're utilizing the TransCon technology, I believe the best one to answer that will be Novo Nordisk in this case. Going back to oncology. We have been extremely encouraged by the effect we have seen in platinum-resistant ovarian cancer in late-stage patients that basically have no hope. We actually see meaningful clinical benefit in this, and this is what we're really trying to focus on and really pursuing in the fastest and best possible manner to really help these patients. As we said, we are open in the way we will create value out of oncology pipeline in all different structures and we will pursue the structure that focus on getting out to as many patients as possible as fast as possible while also creating most value for our stakeholders.

Question: Kelly Shi - Jefferies Group LLC - Analyst : Thank you for taking my questions. So I just want to confirm, like several numbers in the press release, it was mentioned that the first three quarters of 2024 totaled at EUR138.5 million and the full year guidance at EUR200 million to EUR220 million. So that gives Q4 sales to be EUR61.5 million and to reach the lower bound. And is this the sales without adjustment? And secondly, for the TransCon CNP NDA submission, just curious, have you talked to regulatory agencies that 12-month data is enough for the submission? Thank you. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 14, 2024 / 9:30PM, ASND.OQ - Q3 2024 Ascendis Pharma A/S Earnings Call Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board I think I will delegate the first part of the question to Scott, and he just wrote down all your numbers, and double checking them now.

Question: David Lebowitz - Citigroup Inc - Analyst : Thank you very much for taking my question. I got two for you. First, on the long-acting GLP-1 agonist. Given that GLP-1s are titrated as part of normal treatment, what type of challenges does the long-acting present in this regard? And then the second question will be is on SKYTROFA. Could you, I guess, give us perspective on how the net or average price has evolved as you've added new payers and to give us perspective just for modeling purpose and how we should view this going forward? Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board Okay. Thanks a lot. When you talk about long-acting GLP-1, I would like to refer back to the basic biology of the GLP-1 because what is really driving the tolerability issue in. And through our knowledge is that is basically when you go from the trough level, this is called the lowest level or at the peak level and how fast you really are doing that. This is where you see the tolerability issue in it. So therefore, you see when patients stopping treatment have problem with the treatment is because they're going fast up from a trough to a peak. This is why you have titration where you start on a lower dose, go up to the next dose, just to be sure you acclimating, that you deal with this tolerability. When you think on our profile that you saw in our JPMorgan Tech or also other places, you can see one of the uniqueness with our TransCon technology is that we have an extremely long Tmax. And what do that mean? It means that it takes extremely long basic for being a position that you go from a trough to a peak level. And therefore, which we also have seen in our own data in animal studies that you basically have a much better tolerability profile than you have in more short-acting where you go very fast up to the element of the max dose. I think it's pretty clear. We had a clear statement in our prepared remarks that if you take the legal level of daily growth hormone and take it to 1x, SKYTROFA has still 3x value. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 14, 2024 / 9:30PM, ASND.OQ - Q3 2024 Ascendis Pharma A/S Earnings Call

Question: Paul Choi - The Goldman Sachs Group Inc - Analyst : Hi, good afternoon, and thank you for taking our questions. I also want to ask on your recent Novo licensing deal. And given that GLP-1s are validated, it would seem like the 505(b)(2) development pathway is open to a potential monthly GLP-1 agonist. And so development times might be shorter than a full clinical development program for a monthly GLP-1. Do you agree with this? And if that's the case, do you have any sense of what timelines might be for development here? When you might start to recognize royalty revenue from your partners? Any comment there would be super helpful. Thank you. Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board Thank you, and I can only agree 100% with your comments. It is exactly how many cases you will take a development pathway, and it will be shorter than a normal development pathway. And also you have the potential opportunity to get a broad labeling for the beginning with only one indication. That is the benefit of using a 505(b)(2). Related to specific timeline, we need to refer to Novo Nordisk for this discussion.

Question: Leland Gershell - Oppenheimer & Co Inc - Analyst : Hey, thanks for squeezing me in and for taking the questions. Just one from us. I think, Jan, you had mentioned that commercialization in France might be starting by the end of this year. I'm not sure if I missed it in your prepared comments. Is that on track? And I was also wondering as you further pursue European commercialization, if you have any further clarity on the cadence of rollout in various countries through 2025? Thanks. Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board Yeah, you are right. What we have been established as what we call full commercial air is only Germany and Austria. In France, we got elected to a special program called AP2. This is a program that basically are non-promotional, but we can give them commercial reimbursed drug. And it's got established for about 3, 4 weeks since in France. And the number we have seen coming in where physicians really say, I believe, because it needs to be physician-driven, we cannot commercialize is really unique. Going forward, we will have fully commercial countries where we call in Europe direct where there will be full commercial countries and it will be the majority of the countries in Europe, EU. There will be basic full commercial next year in different quarters, a lot of them coming into Q2, Q3 next year. So what you saw of our success in Austria and Germany, we basically are repeating that in about 8, 10 other Europe direct countries. In our international market, we see a lot of named patient program, but we are also in the international market where we now have countries covered REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 14, 2024 / 9:30PM, ASND.OQ - Q3 2024 Ascendis Pharma A/S Earnings Call by distribution agreement about 30 to 35 countries. And there are currently giving patients through named patient program. And also next year, we will start to see more or more of this country also going into full-blown commercialization. It's dependent on what we are spending a lot of resources on now is basically getting filing, which we have done in many, many countries, but also getting approval in all of these countries. And we're getting approval already beginning this year. And meaning is that we know we will be full commercial this year -- next year.

Question: Alex Thompson - Stifel Financial Corp - Analyst : Hey, great. Thanks for taking our questions. I guess for YORVIPATH, can you talk a little bit about your supply -- commercial supply readiness for the mid-January launch. I think you mentioned that you're going to take scripts from current YORVIPATH patients in December. Could you open that up to all? Or are there supply constraints or some other constraints? And then on CNP, do you still have an appetite for running a broader basket study of additional indications? Or are you now focused on SKYTROFA there? Thanks. Jan Moller Mikkelsen - Ascendis Pharma A/S - President, Chief Executive Officer, Executive Director, Member of the Executive Board PTH, we have unlimited supply. We can take all patients in every one. There is no limitation in manufacturing. We already have laid out the entire year's manufacturing batches, locked every time point we want to have to be sure that we're building out the same robust supply chains that we have done with SKYTROFA, which has been unique even if we suddenly got major more demand suddenly. So the same thing is happening for YORVIPATH, and we are really on top to be sure no patient ever should go in and not can get the prescription fulfilled of YORVIPATH. Going to CNP, I ask -- you're right. We think some indication is best treated with SKYTROFA. But definitely, there is also indication that is best treated with CNP. And some of them are best treated with the combination of both of them, either on a constant basis or only on a short duration. So we are planning to go into what we call CNP-related diseases, meaning as that this is diseases where the growth disorder or what we call other element of missing CNP only can be functional back to what we will see in a normal physiology by providing CNP back. So besides planning a trial in hypochondroplasia, which will be initiated next year, we are also planning for a basket trial. We think that is easy way where we can take multiple indication of CNP-related diseases into one single trial that we also is in the planning for doing now. So we are not restricting us just to SKYTROFA label expansion. We dedicated to be a leader in growth disorder. We have plus 20 diseases to go through. And some of them, we will take SKYTROFA. Some of them, we will take TransCon CNP. And some of them, we receive the optimal treatment happening with a combination of both of them either on a constant base or on shorter duration, one or the other.