Ascendis Pharma A/S

Good day and thank you for standing by. Welcome to the fourth quarter and full year 2024 Ascendus Pharma earnings conference call. At this time, all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 1 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1 1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to Scott Smith, Chief Financial Officer. Please go ahead.

Thank you very much, operator. And thank you, everyone, for joining our full year 2024 financial results conference call. I'm Scott Smith, Chief Financial Officer at Ascendus Pharma. Joining me on the call today are Yen Mickelson, President and Chief Executive Officer, Sherry Glass, Chief Business Officer, Jay Wu, President, U.S. Market, and Amy Hsu, Chief Medical Officer. Before we begin, I would like to remind you that this conference call will contain forward-looking statements that are intended to be covered under the Safe Harbor provided by the Private Securities Litigation Reform Act. Examples of such statements may include, but are not limited to, statements regarding our commercialization and continued development of Skytropha and YorvaPath for the U.S., European, and other markets, as well as certain financial expectations, our pipeline visits, and our expectations with respect to their continued progress in potential commercialization, our strategic plans, partnerships, and investments, our goals regarding our clinical pipeline, including the timing of clinical trials and results, our ongoing and planned regulatory filings, and our expectations regarding the timing and the results of regulatory decisions, expected market developments in our exploration of market opportunities and therapeutic areas outside of endocrinology rare disease. These statements are based on information that is available to us today. Actual results may differ materially, 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 statement section in today's press release and the risk factors section of our most recent annual report on Form 20F filed with the SEC today, February 12, 2025. Transcon Growth Hormone, or Transcon HGH, is approved in the U.S. by FDA and in the EU, has received MAA authorization from the European Commission for the treatment of pediatric growth hormone deficiency. Transcon PTH is approved in the US by the FDA for the treatment of hypoparathyroidism in adults, and the European Commission and the United Kingdom's Medicine and Healthcare Products Regulatory Agency have granted marketing authorization for Transcon PTH as a replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism. Otherwise, please note that our product candidates are investigational and not approved for commercial use. As investigational products, the safety and 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 2024 financial results and we'll provide further business updates. Following some prepared remarks, we will then open up the call for questions. With that, let me turn it over to Jens.

Thanks Scott and good afternoon everyone. 2024 was a pivotal year for Ascendis as we achieved key milestones that set us up to deliver strong growth and value creation in 2024 and beyond. With Scott Hofer firmly established as a high value growth hormone brand in 2024, Volume growth sustainable with revenue reaching around €200 million on a 6.5% market share of the total growth hormone market in the US and around 45% of the total US non-acting growth hormone market based on third-party prescription data. With further penetration in pediatric growth hormone deficiency, and a planned commercial launches across multiple indications and countries. We expect sustained valuation for the Transcron growth hormone Francis in the coming year as outlined in our vision 2030. Importantly, Uropat, the only FDA-approved treatment for hypothyroidism in adults, is now launched in the U.S. and has already begun to establish itself as the new standard of care. Given the long-standing need for a treatment option like UR-PATS, we are seeing significant early demand in both the patient and physician communities, and we are pleased with the PACE or PAER approval so far. The large global population living with a significant hypopara-disease burden underscores the potential for UROPADS to grow into a multi-billion dollar product over time. Rounding out our endocrine rare disease portfolio, Transcon-CMP clinical data demonstrated it could be a highly differentiated product with a unique profile. that represent a major step forward in the treatment of achondroplasia and other growth disorders. We believe the once-weekly Transcon-CMP data demonstrating superior linear growth and benefits beyond linear growth, supporting our proposed label for treatment of achondroplasia. For this reason, following our pre-NDA meeting with FDA, we are on track to submit an NDA to FDA this quarter, followed by an MAA submission to the EMEA in the third quarter of this year. All three of these endocrine rare disease medicines demonstrate the value of our Transcon technology platform and its potential to address major medical needs with highly differentiated products. We are also bringing the Transcon technology platform beyond endocrine rare diseases. In large patient population, through our collaboration with Novo Nordisk in metabolic diseases such as obesity, type 2, diabetes, and cardiovascular diseases, in optimality to the creation of ICONIS. We have also expanded the Transcon technology platform to incorporate protein degraders a very promising era where we believe that the new Transcom technology platform will expand our pipeline with additional potential blockbusters. We entered 2025 with a very strong financial position, with a cash of €665 million on our balance sheets, including the $100 million off-bank payment that we received from Novo Nordisk last month. As a result, we are in a strong position to invest in commercial uptake and new product development to drive continued revenue growth. Let me review our key programs in rare endocrine disease in more detail. In the US, Skytober was launched just over three years ago. Today is the treatment of choice and at the same time growing the growth hormone market. With the pediatric growth hormone deficiency indication alone, we are currently addressing only half of the existing U.S. growth hormone market, but are on path to expand CRYTOFER's addressable market in multiple ways. Near term, we expect U.S. approval in adult growth hormone deficiency this year with our CRYTOFER date on July 27. Longer term, we will investigate SCARTOFA in additional therapeutic areas through a basket trial including idiopathic short-stage shock deficiencies, Turner syndrome, and SDA. In the third quarter of this year, we plan to submit an IND application for this basket trial to the US FDA. Planned commercial launches across multiple countries. In 2024, Skytofa's volume increased 84% in the United States, with premium net pricing of 3x compared to one steady growth hormone. Skytofa achieved revenue of around €200 million in 2024, supporting the potential for it to become a blockbuster product over time. Moving to UiPaths. 2024 was a critical year for EUROPATH with commercial availability in Europe starting early in 2024 and then this past December in the US. With EUROPATH also available to name patient programs. Patients in multiple countries living with hyperparathyroidism can begin to assess this long-awaited treatment option. Hypoparathyroidism represents a large global market of opportunity for scientists to address a major unmet medical need for an effective and well-tolerated treatment option. To create durable long-term leadership for uropaths, we are building this market by educating physicians about the well-documentated limits on risk of conventional therapy and the clinical benefits seen with our PTH treatment. In the US, we estimate there is about 70,000 to 90,000 patients with chronic hyperparathyroidism, most of whom are currently using conventional therapy of oral calcium and active vitamin D. Our claims analysis demonstrate that 10,000 to 15,000 of these US patients are uncontrolled, and 30,000 to 35,000 thousands are partly controlled. We believe EUROPAD can sustain growth over a long time as the vast majority of patients with hyperparathyroidism qualify for PTH treatment per the current international guidelines. Less than two months in the U.S., EUROPAD longs. Initial demand is strong. 108 patients with prescriptions as of February 7, 2025. This includes prescriptions from 539 unique prescribers in around 44 states. Nearly 80% of the movements are new to Europe. The majority of whom are switching from conventional therapy, with the remaining being existing patients from the Transcon PTH clinical trial or expanded access program. Discussion with payers are ongoing. And as expected, with a novel specialty product, we estimate the majority of insurance approval will take about four to eight weeks. We are pleased with the initial pace of insurance approval across commercial and government payers. and have shipped reimbursed drug to patients in around 35 states. Outside the US, we remain on track for additional commercial launches in what we call European countries, where we expect to add five or more countries this year. We also expect launches in multiple international markets in 2025. further expanding our global reach, where we have signed eight exclusive distribution agreements covering 50-plus countries so far. UroPath is a unique product. Our broad and extensive clinical data includes three successful phase 3 trials in the US, Europe, Japan, and China, covering diverse disease groups, including post-surgery, autoimmune ADH1, idiopathic hypoparathyroidism. Last year, we presented three years' data from our phase two path forward trial. And later this year, we plan to present four years' data demonstrating excellent patient retention and sustained serum calcium control and bone health. Sustained reduction of calcium phosphate product, independent from conventional therapy, and normalization of 24-hour UNAIR casualty creation. The data also showed sustained improvement in kidney function. Listening to Transcon-CMP, acondalplasia remains a disease with high unmet medical need. And we believe Transcon-CMP has the potential to be a highly differentiated treatment option. In the pivotal approach trial, Transcon-CMP demonstrated significant improvements in linear growth and body proportionality compared to placebo, as well as benefit beyond linear growth. As one example of benefits beyond linear growth, we have shown data that demonstrate significant improvement with triscom CMP treatment on leg bone and common and devastating complication in acroendoplasia that can result in pain impaired physical function, need for corrected surgery, and a negative impact on quality of life. Transcon-CMP has shown a safety and durability profile comparable to placebo, with low frequency of injection site reaction, all of which were mild, and no evidence of hypertension effect, supporting Transcon-CMP potential as a best-in-class treatment for achondroplasia. Following our productive pre-NDA meeting with FDA, we plan to submit an NDA for the treatment of acroendoplasia during the first quarter of 2025 and submit an MAA for treatment of children with acroendoplasia to the EMEA during the third quarter of 2025. We believe Transcon CFE will be setting a new bar for treatment of acroendoplasia. to further raise this bar for linear growth and other clinical benefits. We are also working on a combination treatment of Transcon-CMP and Transcon-Glutamone in achondroplasia. Centis is uniquely positioned to bring these two once-weekly medicines together in a combination treatment, providing two different modes of action. to potentially improve outcome in acromioplasia and other growth disorder. We look forward to sharing top line week 26 results from phase 2 co-trial of Transcon-CMP in combination with Transcon growth hormone, which we expect in the second quarter of 2025. Additionally, during the fourth quarter of 2025, we plan to submit an IND, or similar Investigate Transcon CMPLO and in combination with Transcon growth hormone for the treatment of hypochondriplasia. Looking to how we are expanding our pipeline in endocrine rare disease. We are expanding into additional product candidates beyond our first three successful in medicine as we disclose at the JPMorgan conference. In addition, we continue to broaden the reach of our platform outside endocrine rare disease and true collaboration in therapeutic area affecting much greater patient number. For oncology, our internal development continues to focus on Transcon IL-2 beta gamma aiming for accelerated approval in one or more indications. In early 2024, We announced the formation of CONIS to explore the development of transcon-based therapies in ophthalmology. In November, we announced a multi-product collaboration with NovoLotus, covering metabolic and cardiovascular diseases, with a lead program to develop once-a-monthly transcon semi-glutide. This entitled us to escalating tiered mid-single-digit royalties on global net sales of approved products. Finally, as I mentioned earlier, we have expanded Transcon to incorporate protein degraders, a technology with very promising potential within as well as outside rare endocrine diseases. As seen today with approved commercial products, a strong pipeline, and guided by our values of patience, science, and passion, these positions of Kenyon continue driving rapid and sustained growth in the years ahead. I will now turn it over to Scott Smith.