Ascendis Pharma A/S (ticker: NASDAQ:ASND) has reported significant growth in the fourth quarter of 2023, with a special emphasis on the strong performance of SKYTROFA in the US market. The company has outlined an ambitious plan for label expansion and market penetration across Europe, while also making strides in their diverse clinical programs. With a 37% sequential increase in SKYTROFA revenue from Q3 to Q4, Ascendis Pharma is demonstrating robust financial health and a clear strategy for continued growth, aligning with their Vision 2030 objectives.
Key Takeaways
- Ascendis Pharma experienced a 37% sequential increase in SKYTROFA revenue, indicating strong US demand.
- Q4 total revenue reached €137.7 million, boosted by a one-time upfront payment of €63.7 million.
- Operating expenses decreased by 12% sequentially to €155 million, while R&D costs were down 18% to €90.9 million.
- The company ended Q4 with €399 million in cash, cash equivalents, and marketable securities.
- Ascendis Pharma projects SKYTROFA revenue for 2024 to be between €320 million and €340 million.
- They plan to submit an SBLA for adult growth hormone deficiency in Q2 2024 and launch TransCon PTH in the US.
Company Outlook
- Ascendis Pharma aims to expand SKYTROFA's label to include adult growth hormone deficiency.
- The company is initiating the launch of TransCon PTH in Europe, beginning with Germany and Austria.
- They are focused on building up the international market in late 2024, with higher penetration expected in 2025 and 2026.
Bearish Highlights
- Uncertainties persist regarding the exact number of patients for TransCon PTH in the US, estimated between 40-60.
Bullish Highlights
- CEO Jan Mikkelsen discussed the positive clinical data on vosoritide and its potential for significant growth in patients.
- The company is confident in the potential of growth hormone treatments to build muscle mass alongside the benefits of the GLP-1 class.
- Ascendis Pharma is not affected by the decreasing investments in daily growth hormone products, maintaining its market share.
Misses
- No specific misses were discussed in the earnings call.
Q&A Highlights
- The company estimates 70,000 adults with chronic hypoparathyroidism in Germany, targeting a population of 22,000 patients.
- Ascendis Pharma addressed the societal burden of diseases and the need to benefit all stakeholders.
- They discussed the cost structure of the Endo business and the efficiency of their operations.
- Mikkelsen emphasized the importance of mimicking endogenous hormone production in hypopara treatments.
Ascendis Pharma's fourth-quarter earnings call highlighted the company's strong financial performance and strategic initiatives aimed at expanding their market presence and product portfolio. With a focus on innovative treatments and a commitment to addressing unmet medical needs, Ascendis Pharma appears well-positioned to achieve its long-term goals and make a significant impact on the biopharmaceutical industry.
InvestingPro Insights
Ascendis Pharma A/S (ASND) has demonstrated a remarkable revenue growth rate in the last twelve months as of Q3 2023, with a stellar increase of 357.91%. This surge is reflected in the company's robust gross profit margin of 80.22%, underscoring their operational efficiency and successful market strategies.
InvestingPro Tips highlight several noteworthy aspects of Ascendis Pharma's current financial status and future prospects. Analysts are optimistic about the company's sales growth in the current year, which aligns with the positive trajectory seen in their recent quarterly results. Additionally, 5 analysts have revised their earnings upwards for the upcoming period, indicating confidence in Ascendis Pharma's ability to sustain its growth momentum.
On the financial health front, Ascendis Pharma operates with a moderate level of debt and possesses liquid assets that exceed its short-term obligations. This financial stability is crucial as the company continues to invest in its clinical programs and market expansion efforts.
InvestingPro Data metrics further reveal that Ascendis Pharma is trading near its 52-week high, with a price 96.1% of this peak value, and has experienced a significant price uptick over the last six months, reflecting investor confidence in the company's performance and future potential.
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Full transcript - Ascendis Pharma AS (ASND) Q4 2023:
Operator: Good day, and thank you for standing by. Welcome to the Fourth Quarter 2023 Ascendis Pharma Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Tim Lee, Senior Director of Investor Relations. Please go ahead.
Timothy Lee: Thank you, operator and thank you everyone for joining our full year 2023 financial results conference call. I'm Tim Lee, Senior Director of Investor Relations at Ascendis Pharma. Joining me on the call today are Jan Mikkelsen, President and Chief Executive Officer; Scott Smith, Executive Vice President and Chief Financial Officer; Dr. Stina Singel, Executive Vice President and Head of Clinical Development, Oncology; and Joe Kelly, Senior Vice President, Head of US Commercial, Endocrinology. . 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 commercialization and continued development of SKYTROFA for the US and European markets. as well as certain financial expectations for 2024, our commercialization and development of YORVIPATH in the EU and expected timing of the FDA review and potential launch of TransCon PTH in the US, our pipeline candidates and our expectations with respect to their continued progress and potential commercialization, our strategic plans, our goals regarding our clinical pipeline, including the timing of clinical results, our ongoing and planned regulatory filings and our expectations regarding the timing, and the results of regulatory decisions. Our ability to create value in multiple therapeutic areas outside of endocrinology rare disease, our progress towards Vision 2030, and the potential success of Eyconis. These statements are based on information that is available to us as of today. Actual results 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 could cause actual results to differ materially, please see our forward-looking statements section in today's press release and the risk factors section of our most recent annual report on Form 20-F filed with the SEC later today, February 7th, 2024. TransCon Growth Hormone or TransCon hGH, is approved in the US by FDA and the EU has received MAA authorization from the European Commission for the treatment of pediatric growth hormone deficiency. The European Commission has 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 effectiveness of 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 full year 2023 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 Jen.
Jan Mikkelsen: Good afternoon everyone. 2023 was that transformative year for Ascendis Pharma. We streamlined the company, including our structure, our processes, and operating expense allocation. And at the same time, we believe we are on track to achieve our Vision 3x3 by 2025. SKYTROFA is the leading growth hormone product in value in the US. The launch of YORVIPATH in Europe Direct and international markets is underway, beginning with Germany and Austria. And our clinical program for TransCon CNP is progressing to what people were data expected in Q4. We believe Ascendis is advancing to become a leading biopharma company with a strong focus on endocrinology rare diseases and capabilities to also create value in other therapeutic areas as we're doing in oncology, ophthalmology, and metabolic diseases. Because of the decisions we took in 2023, we believe Ascendis is a leaner, more efficient organization in 2024, well-positioned to fulfill Vision 2030 with three independent endocrinology rare disease blockbuster products and expand our engine for future innovation. Now, let me provide an update on each programs. From the beginning, we designed SKYTROFA to be best-in-class growth hormone product by releasing unmodified somatropin. By addressing the needs of the patients, caregivers, physicians, and payers, SKYTROFA achieved US market value leadership in 2023, just two years after launch. We estimated that SKYTROFA penetration in the US pediatric growth hormone deficiency patient population was around 16% at the end of 2023. With SKYTROFA expanding the US growth hormone market to the potential of $3 billion, we believe SKYTROFA has the potential to be a blockbuster on US revenue alone. Built on this value leadership, we expect our first label expansion to be adult growth hormone deficiency. For this, we plan to submit and supplement BLA to the FDA in the second quarter of this year. In addition, we expect topline data from our Phase II trial in Turner syndrome in the fourth quarter of 2024. Now, turning to TransCon PTH. Last week, we initiated the launch of TransCon PTH in Europe direct and international market. Market, as you know YORVIPATH with full commercial availability in Germany and Austria at an initial list price of €105,000 per patient per year. An estimated 70,000 adult patients in Germany are living with chronic hypoparathyroidism and our initial launch will target 22,000 of those. YORVIPATH Europe Direct launch is off to a great start with our first prescription and orders perceived at the first day of launch, demonstrating the severeness of the disease and the unmet medical need. We are continuing to expand our EU Direct infrastructure and expect ability of YORVIPATH across Europe by the end of 2025. In parallel to meet the needs of the patient, we plan to provide commercial reimbursed product to early access routes such as main patient programs. The US PDUFA date for TransCon PTH is May 14th. If approved, we plan to launch our YORVIPATH as quickly as possible thereafter through our status US commercial infrastructure. Moving now to TransCon CNP. Our clinical program is designed to support approval of TransCon CNP as a treatment for patients of all ages with achondroplasia. TransCon CNP dosed at 100 mg per kilo per week has demonstrated superiority compared to placebo in two 52-week trials. In the open-label extension, we observed unexpected strong patient retention of 97% for now up to four years. As a result of this unexpected finding, we continue to review our own data and scientific literature. We believe now that achondroplasia is both a growth disorder and a muscle disorder. As presented at the JPMorgan Conference in January, we showed significant improvement in health and quality of life for children with achondroplasia treated with TransCon CNP compared to placebo. With this growing insight, we have designed our pivotal ApproaCH to evaluate meaningful benefits related to all aspects of achondroplasia. Including linear growth and improvements in comorbidity as measured by radiological endpoints, physical function, body compensation, and quality of life. We expect to share topline data from this trial, and we plan to submit an NDA in the fourth quarter of this year. In addition, we are pursuing additional treatment opportunities in achondroplasia. Infant trial age zero to two years, first patient already had been enrolled. Combination trial with SKYTROFA age two to 11, week 26 topline annualized growth velocity in the fourth quarter of 2024. Adult plan to file an IND similar in the third quarter of this year. Switching now to oncology. Both TransCon IL-2 β/γ and TransCon TLR7/8 Agonist has shown favorable safety profiles and single-agent clinical activity. We expect 2024 to be an extremely important year for oncology pipeline with data readout in well-defined patient population in the fourth quarter. Also in the fourth quarter, we expect to have completed enrollment of our randomized Phase II trial in neoadjuvant head and neck cancer. Longer term, to maximize this potential reach and value of these oncology product candidate, we aspire to commercialize our oncology assets to partnership with companies with specialized oncology experience and capability in late-stage development and commercialization. Moving now to ophthalmology. We recently announced the formation and launch of an independent company Eyconis to develop and commercialize TransCon ophthalmology products globally. We have received an equity position in the newly formed company and we are electable to receive development, regulatory, and sales milestone plus single-digit royalties. In January, we introduced Vision 2030. Our strategic roadmap to achieve blockbuster status for each of our three endocrinology rare disease products and expand our engine for future innovation. With the broad applicability of the TransCon technology platform, our goal, as laid out in Vision 2030, is to apply our algorithm for product innovation to established opportunities in greater than $5 billion indication as we did with an anti-VEGF and anti-peer bond [ph] classes where we believe we have designed the best-in-class programs. We are pleased with the interest in our once-monthly GPL-1 program and from our platform technologies, we expect to continue to generate many more opportunities in the future. I will now turn the call over to Scott for financial review before we open for questions.
Scott Smith: Hi Jan. We continue making significant progress towards our financial goal of becoming operating cash flow breakeven on a quarterly basis by the end of 2024. I will touch on some key points surrounding our financial results, but for further details, please refer to our Form 20-F filed today. . As we previously announced in early January, SKYTROFA revenue for the fourth quarter of 2023 was €64.2 million compared to €47 million reported in the third quarter and €17.1 million reported in the same period last year. 37% sequential growth in SKYTROFA revenue from Q3 to Q4 was again driven primarily by strong underlying demand in the US. Total revenue for the fourth quarter was €137.7 million, including the one-time $70 million Teijin upfront payment recognized as €63.7 million of license revenue. Turning to expenses. R&D costs in the quarter totaled €90.9 million, down 18% sequentially from the third quarter of 2023, primarily driven by lower endocrinology rare disease related costs as trials and development complete and lower oncology-related costs. SG&A expenses were essentially flat at €64 million compared to the third quarter of 2023, reflecting commercialization synergies and expense controls. Total operating expenses were €155 million for the fourth quarter, down 12% sequentially from the third quarter. Overall, our operating loss for the fourth quarter declined sequentially by 73% to €37 million from €134 million in the third quarter of 2023. We ended the fourth quarter with cash, cash equivalents, and marketable securities totaling €399 million. Last month, we announced the formation and launch together with an investor syndicate of Eyconis to develop, manufacture and commercialize TransCon ophthalmology assets globally. As a result, we expect minimal, if any, P&L burden from ophthalmology in 2024. As a reference point for Q4 2023, external ophthalmology project costs totaled €6.4 million. As previously announced for the full year 2024 based on current plans, we expect SKYTROFA revenue to be in the range of €320 million to €340 million at average 2023 exchange rates. Total operating expenses, SG&A and R&D together to be approximately €600 million and we expect to be operating cash flow breakeven on a quarterly basis by the end of 2024. Let me now also provide a review of selected key program milestones. For TransCon Growth Hormone, we plan to submit an SBLA to FDA for adult growth hormone deficiency in the second quarter of 2024, and we expect to report topline results from our Phase II Turner syndrome trial in the fourth quarter of 2024. For TransCon PTH, in the US, our PDUFA date is May 14, 2024. If approved, we plan to launch it as YORVIPATH as quickly as possible thereafter. Outside the US, we initiated the launch last month of TransCon PTH marketed as YORVIPATH, with full commercial availability in Germany and Austria. We plan to roll out YORVIPATH in our Europe Direct and international markets segments throughout 2024 and 2025. For TransCon CNP, our clinical program evaluating TransCon CNP as a treatment for achondroplasia advances with topline results from the pivotal ApproaCH trial and an expected NDA submission for the treatment of children with achondroplasia, both in the fourth quarter of 2024. In addition, during the fourth quarter of 2024, we expect to report week 26 topline data from the COACH trial in combination with TransCon Growth Hormone and submit an IND or similar for adults with achondroplasia. Within our oncology therapeutic area, we plan to provide a clinical update from indication-specific dose expansion cohorts in the IL Believe and TRANSCEND IT trials during the fourth quarter. In addition, we expect to complete enrollment of our randomized Phase II trial in neoadjuvant head and neck cancer. With that, operator, we are now ready to take questions.
Operator: Thank you. And this time, we'll conduct a question-and-answer session. [Operator Instructions] Our first question will come from the line of Jessica Fye from JPMorgan. Your line is open.
Jessica Fye: Hey guys. Good afternoon. Thanks for taking my questions. I realize it's early days, but -- what can you share with us about the German PTH launch so far? And the second one is, are you seeing any external interest in your TransCon GLP-1 program and -- can you remind us what the target profile you're looking to achieve is with that program? thank you.
Jan Mikkelsen: Thanks, Jess. Yes, as I've said before, this is one week into our launch. We know the unmet medical need is there for the patients. We know how we really are providing a treatment that really are providing a meaningful differentiation for the patient, both on short-term and really also are helping in eliminating the long-term risk of the disease. And what we observed was that exactly as what we had hoped for the physician, the day one of the launch make the prescription, got the material from our distributor already the first day. In US, you need to go to a prescription and then reimbursement and then to begin to get the drop in Germany is different. Immediately, you get a prescription, you basically have access to be get the drop immediately at that time. So, the launch, we really look forward to provide much better update when we come to Q1, much better after Q2 and much, much better again after Q3. So, we're really, really feeling that the launch in Germany and Austria. This is the starting point for basic being positioned to be everywhere on the globe where there are patients, and we will reach them or other places. Related to how we're using licing of the TransCon technology outside rare disease. Endocrinology, yes, we have our oncology with I'm really moving forward as we only have hoped for. And we're really looking forward to 2024, where we can give you the proof really to patient data, how we are differentiated. You saw our differentiation in ophthalmology, we made cost has been our company, and we really feel that they are really in an optimal value both to create value and really help the patient in this area. When we come to the third area that we have disclosed, we are working on, we basically have the DPL 1 class were going for the once-monthly profile. And it's not only for obesity. There's also for metabolic diseases, and we feel really, really that we are getting the interest that such a product really deserve. But it's not a product, it's a platform, a platform that can be utilized basically for the class of -- once.
Jessica Fye: Thank you.
Operator: Thank you. Our next question will come from the line of Tazeen Ahmad from Bank of America. Your line is open.
Tazeen Ahmad: Hi guys, good afternoon. Thanks for taking my questions. I wanted to get your updated thoughts about competition from recently approved growth hormone therapies, in particular, what is your market data that's telling you about Novo [indiscernible], how is that, if in any way, impacting your launch? And then -- can you give us some data about what percent of adults currently take growth hormone replacement therapy? And on average, how long does the person stay on therapy? Thanks.
Jan Mikkelsen: Thanks. It's really a pleasure to take up again the competitive landscape in the growth hormone market. And when we launched, we had a competition, the short acting. It was all the different six daily growth hormone that we were competing against. We showed how we were clinically differentiated to this established standard of treatment. How we provided a better outcome. We built the market basic to a lot to medical exception because of the product strength of SKYTROFA. Now, we see two emerging therapies coming in, in the long-acting spare, two products, one coming in and we don't see it really impacting us because we're still best-in-class. We actually believe that these two products have never proven that can show the same outcome as a normal daily growth hormone treatment that you get in the US. So for us, the bearer for medical exception is just improving. So, for me and Ascendis, we don't see that it's really changing anything about how we are progressing to continue and build us to a blockbuster potential just in the US, and we will continue to do it because of our product strengths. Related to the adult, the adult is different compared to the pediatric in many different ways. One of the things, the majority of pediatric typically will have a treatment for a limit year. It can be four, five, six, seven, eight dependent on the initiation of treatment, where the adult is a chronic disease, where typical will be needing a treatment for rest of your life. So, I would call it a chronic disease when you're diagnosed and start the treatment. So, there is a big difference related to that. We often talked about penetration degree with growth hormone treatment and what there is a huge difference to between the pediatric and adult is that pediatric, in my view, is penetrated to 60%, 70%, 80%, where the adult potential is under 10%. And I think this is a big difference for basic your modeling how really to see and how we can develop the adult growth hormone deficiency market. As you said, this is our first label expansion. We will build up. So, we basically have access to all places where it's possible to use growth hormone because all the patients deserve to have the best product.
Operator: Thank you. Our next question is coming from the line of Li Watsek from Cantor. Your line is open.
Li Watsek: Hey great. Thanks for taking our questions. Maybe just to follow-up on TransCon PTH's launch in Germany. Understanding it's early days, but what could be a good framework for us to think about the rent in the market? Any clarity that you can give us around experienced patients and how quickly you may be able to onboard them? And then in terms of the patients that are enrolled in the early access program in Germany, do you have any color there as well?
Jan Mikkelsen: Thanks a lot for the question. I can be bullish now and saying in the years that all patients in Germany that have hypoparathyroidism should be on treatment. Because I think that is -- and hormone replacement therapy as everyone that had Type 1 diabetes. Would all of them come on treatment? Likely not. But what we want to do, we are dedicated to help the patient and building up to scientific clinical data, our dedication to really to develop this market to ensure as many as possible will be treated with TransCon PTH or YORVIPATH. And it's not only in Germany and Austria, rest of Europe, rest of the international market, is basic also in US. So, when we see this year, I think there is different elements how we see the penetration will happen. We always see the benefit of physician really getting the benefit seen in their own eyes that take patients, take them on treating typical two to five really to see how the product function. The benefit with TransCon PTH after a few weeks, they will receive a benefit. So, then there is some kind of logical thing, how to get patient in, how to ensure there is capacity in -- really from the different physician sites, really to take the patients in. So, when we come into Q2 -- Q3, I think we will start to see the trend coming in, and you can follow our revenue development, mainly coming from where we have full reimbursement in Germany and Austria. And then you can see how we penetrate rest of Europe Direct end of 2024, 2025 and how we basically are building up the international market in the later part of 2024 and really starting to be really penetrated in a much higher level in 2025 and 2026.
Operator: Thank you. And our next question will come from the line of David Lebowitz from Citi. Your line is open.
David Lebowitz: Thank you for taking my question. Given the emergence of GLP-1s and their effect on lean muscle mass, is there a potential role for growth hormone due to the success of the GLP-1s?
Jan Mikkelsen: Excellent question that basically are going back to the mode of action and the benefit you see with the GLP-1. I personally was a little bit skeptical about the entire GLP-1 Trans in obesity, but it's typical because I'm pretty conservative in many ways. But what I'm 100% assured now is going to be a huge, huge class. And we see the benefit coming out really on a lot of different treatment aspect. It's not only just losing weight. There's a lot of other treatment benefit with this class. The negative part is that is you basically are in a position that you're losing a large amount of muscle mass and specific, if you're not adhere to the treatment and make period of break start-up again, period of break, you can basically be in position that when you're not taking you build up the fat faster than the muscle weight. And I think it's a really, really interesting perspective at base you could see growth hormone treatment because that is really where the benefit of growth hormone is that it really can build up the muscle mass in a much more stronger mass in a very, very normalized manner. And I think you are right, and I would like to explore such a possibility.
David Lebowitz: Thanks for taking my question.
Operator: Thank you. And our next question will come from the line of Joseph Schwartz from Leerink Partners. Your line is open.
Joseph Schwartz: Hi there. Thanks very much. I was wondering if you could talk about the work you did to arrive at your estimate that 70,000 adults have chronic hypoparathyroidism in Germany. And who were the 20,000 patients that you're targeting there? And how does the target population in the United States compared to the total hypopara population in the US where we have some guidelines, I'm wondering if that influences the proportion of the market that you think is most addressable here in the United States? Thanks.
Jan Mikkelsen: Thanks. I think you got all the questions into it. And when we compare the demographic between Germany and US, it consists of the basic two group, the post-[indiscernible] with one group. And then you can say the more hemological genetic, idiopathic background where you typical will see a rise much earlier in states of life. Germany potentially is a little bit unique with the last number of patients because -- and I think it potentially is built on the high level of intensive head and neck operation because of really, really strong folks of diagnosis. And from that perspective is, yes, there is potentially more positive patients in Germany than you see in the US and other -- for example, if you take a country like France, France will much more relate to what you will see of treatment way that you see in the US. So, -- when we see this different patient population, all of them will benefit of the TransCon PTH treatment or YORVIPATH. It's not like one group or the other one are less beneficial in the treatment on it. So, all of them deserve to have a life with TransCon PTH. Going back to what you say when we talk about 22,000 patients. And it's not because we see subpopulation that see more benefit or less benefit from that. When we talk about the 22,000 patients, which we try to address first is the patient that from a pharmacoeconomic perspective, have a really, really hard type on the society that can be -- potentially come to the state of real impairment that can come to a state that visit hospitalization a lot. They come to a state where they cannot function because of cognitive effect, they cannot get a normal life. So, out from that perspective is not really a treatment benefit. This is more that the burden for this society. And this is where we always need to be. We need to benefit the patient, the society and everyone as all stakeholders. And this is the burden for society as much, much higher for this 22,000 patients.
Joseph Schwartz: Very helpful. Thank you.
Operator: Thank you. And our next question will come from the line of Derek Archila from Wells Fargo.
Derek Archila: Hey good afternoon and thanks for taking the questions. Just two from us. I just wanted to clarify, is SKYTROFA a $1 billion product in the US just on pediatrics alone? Or does that assume contribution from adult EHG as well? And then just in terms of the cost structure of the Endo business, is this 600 million cost base now, how we should be thinking about it for the future? And just your thoughts about profitability of that business?
Jan Mikkelsen: Thanks, I will take the first question, and then Scott is really happy today now because he actually has an opportunity to come to some of the financial numbers is running, so dedicated over time. When we look on the potential market, yes, you can see we will have adult growth hormone deficiency. We will pursue some of the other indications, too. But we also need to say that we are liberating a normal somatropin molecule, which are well-known entity for all different indication that seen the benefit on growth hormone. And if you go to the market of the daily growth hormone and see what is the dynamic there? The dynamic is that none of the daily growth hormone basic -- because they're all so much hoping to -- all of them basically are in a position, none of them have all the indication where they're actually being reimbursed or used today because none have really take the effort to go through all the different indications. So, it could be potential. The same thing will be applied also on the long-acting products that are providing the same somatropin molecule. Scott, will you talk a little bit about expenses and numbers in less than 10 minutes.
Scott Smith: How much time do we have? Thanks, Derek. So, it's good to get a finance question. So, as you saw here in the Q4, we're realizing now the benefits of the streamlined operational changes and processes that Jan has talked about with OpEx going down to about €155 mi total. And then, of course, next year, you'll see more come off as a result of basically no P&L burden from ophthalmology. I think you should look at this as a product of the way that we've developed our portfolio and how efficient it can be. I think if you look at our cost for TransCon growth hormone and realize the stage of that product and how mature it is, the costs should be dropping pretty substantially in the coming years. And overall, we're going to be pretty efficient in R&D. So, I would expect more shift from 60/40 R&D, SG&A in 2023 to maybe 50/50 or so in 2024. Longer run, will be efficient in R&D. And as we expand globally, I would expect some increase in SG&A as we add people in 30, 40, 50 countries, but it should be pretty minimal. And as you saw going from Q3 to Q4, our SG&A was basically flat even if we launched an additional product and got ready to launch a second product in Germany.
Jan Mikkelsen: One comment. What you see the result of something was basic element that happened in 2023. You don't suddenly change the company. You don't suddenly streamline the company. It takes a lot of effort. It took us -- started in the beginning of 2023, really find out how can we build a leaner Ascendis more productive, really focused on really optimizing processes, administration and everything like that. And we were very, very, very successful to that. It was a hard task, not already always pleasant, probably there now. We are where we want to be now. We're still optimizing our processes because we're scaling for potentially having 5,000 to have 50,000 processes. And you cannot use the same PV system that you use to 5,000 to 50,000. So this is why we really are still optimizing process, changing the company because we cannot be a leading biopharma company at the same way we operate it as a large biotech company, where we basically were focused on clinical development and few commercialization. So, we are still transforming. We're still changing our processes, and that is what we need to continue to be truly competitive in this landscape.
Operator: Thank you. Our next question will come from the line of Kelly Shi from Jefferies. your line is open.
Kelly Shi: Thank you for taking my questions. Maybe switch topic or two TransCon CNP, you have talked about the improvement on muscle function and other companies, we feel like talk about mal proportionality like upper to lower body ratio. I'm just curious, have you also looked at a proportionality as well? And also, when it comes to the combination with SKYTROFA what would be the most differentiated clinical benefit compared to TransCon CNP alone? Thank you.
Jan Mikkelsen: Thanks. I will start from the back because if you have a child born with achondroplasia being started treatment as a newborn, our belief is that basic will nearly have normal growth in this period of time where you have growth related to linear growth. You will not really address and stop or can stop to address the comorbidities because they will exist rest of the life. And this is when we see on the integrated aspect of achondroplasia, we see the linear growth as one part of the disease, and we see the other impact of the hyperactive pathway have another aspect, like, for example, muscle weakness and other aspects, which are really from a mode of action is different compared to what you see on the achondroplasia that really are limited in the way, they get linear growth. So, when we think about how we are positioning our combination trial is that what everyone have seen of data for the impressive amount of clinical data that's come out from BioMarin related to vosoritide, all of that showing that you normalize growth for the vast, vast majority of the patients. But if you have a child that got born and first started treatment of eight years, they still have a lack of growth. So, when we saw all the data that has been generated by daily growth hormone, more than 30-40 publication, really intensive trial with 40, 50 children. And we see that that basically can induce catch-up growth as you can do in growth hormone deficiency because that is what we do in growth hormone deficiency. The more of growth hormone is that you can reset the growth to be normal as a final height if you are on a good adherent treatment. But you can only do that in other growth hormone deficiency, if you have a catch-up growth, meaning that you grow more in the first two, three years then you basic will see of a normal growth. That is why when you think about a child with growth hormone deficiency, not have been treated for eight, nine years, starting potential treatment and then suddenly hit the parents' height as expected. This is because of catch-up growth. And you see the same thing in achondroplasia. If you start to give them growth hormone. I see growth effect up to seven, eight centimeters, not as fast as you see in growth hormone deficiency and is likely because they still have a block down on the achondroplasia, because they also need CNP. So, when we think about the perspective of combination trials, this is the children that not get treated, and this is basically the majority of children today. That is not got treated from they got newborn and really need some catch-up growth really to get a burst in the growth. And this is why we are running this trial. My expectation and now I can be trying to do something that is very, very dangerous. But I believe you can potentially grow them up to eight, nine centimeters just by combination treatment because you get the catch-up growth for the first one, two years. And this is the rationale really for us to go out and make that treatment regime because we do the same as vosoritide, we normalize growth. So, proportionality, yes, we see the same positive trend in proportionality that we have seen and expected to see. And we will see more and more when we see more data from longer part of treatment because it takes longer time to really to see the right benefit on this or change of this proportionality, but we definitely are seeing the same positive development.
Kelly Shi: Thank you.
Operator: Thank you. Our next question will come from the line of Paul Choi from Goldman Sachs. Your line is open.
Paul Choi: Hi, good afternoon and thanks for taking our questions. I also want to ask on TransCon CNP for the -- your Phase III ApproaCH study. Can you maybe just share what metrics or details you'll provide with the topline results? And what is your medical conference presentation plans for that data? And then second, on the regulatory strategy. Can you maybe just help us understand the urgency to file the NDA in the same quarter? Just kind of what the reasoning behind that is just potentially concerned about a full approval for BioMarin's, VOXZOGO? And just maybe some color there would be helpful. Thank you very much.
Jan Mikkelsen: It's pretty simple about the filing. Ascendis' process to do it as fast as possible in the highest quality. And if anyone else is working with the company and not living up to this aspect, they should leave. So, if I can get someone to do the filing in the same quarter, we get the data, we should do it. When we come to the Phase III data, yes, we have a primary endpoint because that got established as a traditional way of our primary endpoint is that really an rational endpoint for achondroplasia? I have my doubt. I think it's more a third grade marker annualized height velocity. A treatment is to change the comorbidity of the disease. So, the primary end point for me is like a surrogate mother as [indiscernible] is for adult growth hormone deficiency. This is not really the key treatment objective in adult growth hormone deficiency. You see other aspect of the treatment that's more important. But it's an established endpoint. So, when we go to the secondary endpoint, and I said it's really very, very, very simple in my text. We're going in and look on the effect on comorbidities. And we do it on a lot of different anchors. And we want to be sure that we're calling in the best possible way. And the best possible way we can do it is to look on the comorbidities basic that is developed into what we can measure in different physical function, daily function. We do a lot of radiological because we know the texture of the child needs to be perfect. So, we're 100% sure, we had developed different health-related outcome measuring. And I believe that taking all this aspect into it, we will find benefit that never had been seen and I hope it will both come for quality of life, body composition, physical function, and also the radiological endpoint that basically providing a different way of how we improve the texture.
Paul Choi: And on the medical meeting--
Jan Mikkelsen: I think the summary are not driven by medical meetings. There are some people that are saying that delay data out because of medical meeting. I think when you have material data, you should come out it, so everyone can see the data. We are not waiting with disclosing data just because of medical meetings.
Operator: Thank you. Our next question comes from the line of Andreas Argyrides from Wedbush. Your line is open.
Andreas Argyrides: Hey guys. Congrats on all the progress and thanks for taking our questions. Just a couple here from us. When you think about CNP, can you give us a little bit of your thoughts around the rationale to expand into adults with achondroplasia instead of going into hypochondroplasia like the other companies in this space? And then looking at VOXZOGO and the growth that they've seen primarily driven by ex-US. Maybe you can give us a sense of why it's offered off to a slower start in the US? And is it driven by the fact that they have been focusing on height versus other quality of life measures? And then just one last one on the oncology programs. If you don't find a partner to bring these programs, so would you consider spinning them off like you did with the ophthalmology programs? Thanks.
Jan Mikkelsen: Okay. Let me start on the last one because it's very easy. We are here to do the optimal for the patient to get our product being penetrated to as many as possible patients. And we believe that we are in a position when we have seen all the data that will come out end of this year. We already have seen the interest in our programs now. We feel pretty confident we will do the optimum where we see the fastest, best way to come out to the patient and we create most value for Ascendis shareholders. That will be the driver from our decision. Then you had two comments to CNP. The first one was.
Andreas Argyrides: Why not hypochondroplasia?
Jan Mikkelsen: Why not hypochondroplasia, that is a pretty good interesting perspective for us because this is something we are discussing a lot because hypochondroplasia is a mild form for achondroplasia. And I think we will not move over to hypochondroplasia before we really have provided the optimal treatment, the best treatment that really addressing comorbidity in achondroplasia. Why jump over to something where your basic have not provided a treatment option, but potentially only providing some few linear growth. And the linear you could get that for the last 20 years, just by giving daily growth hormone. So, I don't see that as really a treatment benefit that is just providing linear growth. What we're trying to address is basic -- the comorbidity of the disease. And we will continue to do that until we find the best possible solution to give them a meaningful improvement in quality of life. And the other thing is that I think these two things are related to each other. I don't believe being short is a disease, even I'm pretty tall. So, I actually don’t believe being short is a disease. And I have to think you should never consider short to be in disease. I believe that taking just a linear growth, in some way is more appealing in some countries than others. And definitely in US, it's not a disease to be sure.
Operator: Thank you. And our next question will come from the line of Yaron Werber from TD Cowen. Your line is open.
Unidentified Analyst: Hey guys. This is [Indiscernible] on for Yaron. Thanks for taking our question. Just maybe hoping to get your thoughts on the emerging competitive landscape for hypopara, you're clearly had market, but there's another one PTH analog in Phase III. And then there are a couple of others in the pipeline behind it, some looking to develop oral candidates or once-weekly candidates. So just any thoughts or comments there would be great. Thank you.
Jan Mikkelsen: Thanks a lot. When I took a look from endocrinology perspective and look on the biological system in the body, the complexity of that, how really to provide an treatment of an hormone replacement therapy in a situation where the biology has been extremely, extremely multiple organs effect, having the right growth, not too hyper, not too hypo and see what we did in -- with SKYTROFA. We provided the somatropin molecule that really are being produced by the endogenous client. And I believe -- when I also go to hypopara, this patient needs to have a physiological level of PTH than providing the same mode of action. I actually went to a conference and heard some of the questions for physicians on some of the other competitive products. And one of the key questions that came up, we know PTHs have effect on so many, many different organs. When you change the entire mode of action, how can you really prove and believe you can create the same normal physiological system that you will expect to get with a normal endogenous PTH. First, how we designed TransCon PTH to provide a normal same as endogenous PTH with exactly the same part to give the mode of action in the physiological levels. And I don't think any treatment that changing that will provide the same holistic benefit on all aspects of hypopara for any patient.
Unidentified Analyst: Thank you.
Operator: Thank you. And our next question comes from line of Leland Gershell from Oppenheimer. Your line is open.
Leland Gershell: Hey thanks for taking our questions. Two from us, one each on SKYTROFA and TransCon PTH. On SKYTROFA, Jan, you mentioned in the past commentary about the decreasing investment among the daily growth hormone companies and products. Wanted to just hear any updated color you may be able to share with respect to the marketplace in terms of the dailies if that's a continuing trend that you're seeing? With respect to TransCon PTH, as we anticipate approval and then launch third quarter this year, if you could remind us the number of patients you have available in the states between both those in the open-label studies as well as those who are in the EAP? Thank you.
Jan Mikkelsen: Yes. You're right. We have discussed a lot what we call the long-term or many years perspective of the consolidation in the growth hormone market. And the trend is happening exactly as expected. Specific with the entrance of the two other long-acting the basic, the daily growth hormone is starting to disappear more and more. Because these two companies that is providing them the key element where we have seen them taking market is basically taking their own product, their own product on the daily growth hormone class and then transform over to the long-acting where we take it from everywhere because our improved treatment outcome. So, I see our market share being basic, the same as we somewhere predicted from three, four years. What is happening is that the two other long-acting will just take part of the daily growth hormone. We never thought we actually face it having access to. And so our market penetration, our market share, our market value of SKYTROFA is basically unaffected to what we have seen. Go to -- TransCon PTH and the US specific, the question you are providing me is -- because our both Phase II and Phase III, which have -- should be high retention and continue to have extremely high retention now on fourth or fifth years. I cannot remember now more. The problem is that I cannot really remember how many patients that is in Europe and US between the different trials. So therefore, in my numbers are a little bit weak in that, I would think it's about 40-60 or something like that, but I'm not 100% sure about that. So, please Scott can give you the number when he is finished here and send it to you.
Leland Gershell: Great. Thank you very much.
Operator: Thank you. And that's all the time we have for questions and Q&A today. Thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone, have a great day.
Jan Mikkelsen: Have a great day.
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