Ascendis Pharma A/S

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

Manu Tak, operator. And thank you, everyone, for joining our second quarter 2025 financial results conference call. I'm Scott Smith, executive vice president and chief financial officer at Ascendis Pharma. Joining me on today's call are Yen Muller-Mickelson, president and chief executive officer, Sherry Glass, chief business officer, Jay Wu, executive vice president and president, US market, Amy Hsu, executive vice president of Endocrine and Rare Disease Medical Sciences, and chief medical officer. Before we begin, I would like to remind you that this conference call will contain forward-looking statements that are intended to be covered under the safe harbor provided by the Private Securities Litigation Reform Act. Examples of such statements may include, but are not limited to, statements regarding our commercialization and continued development of SkyTrofa and the Orbit Path, as well as certain financial expectations, our pipeline candidates, and our expectations with respect to their continued progress and potential commercialization. Our strategic plans, partnerships, and investments, our goals regarding our clinical pipeline, including the timing of clinical results and trials, our ongoing and planned regulatory filings and our expectations regarding the timing and the results of our regulatory decisions. These statements are based on information that is available to us as of today. Actual results may differ materially from those in our forward-looking statements, and you should not place undue reliance on these statements. We assume no obligation to update these statements as circumstances change, except as required by law. For additional information concerning the factors that could cause actual results to differ materially, please see our forward-looking statement section in today's press release, the risk factors section of our most recent annual report on Form 20F, filed with the SEC on February 12, 2025. Transcon growth hormone, or Transcon HGH, is now approved in the United States by the FDA for the replacement of endogenous growth hormone in adults with growth hormone deficiency. In addition to the treatment of pediatric GHD, and in the EU has received MAA authorization from the European Commission for the treatment of pediatric GHD. Transcon PTH is approved in the US by the FDA for the treatment of hypoparathyroidism in adults, and the European Commission and the United Kingdom's Medicines and Health Products Regulatory Agency have granted marketing authorization for Transcon PTH as a replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism. Otherwise, please note that our product candidates are investigational and not approved for commercial use. As investigational products, the safety and efficacy of the product candidates have not been reviewed or approved by any regulatory agency. None of the statements during this conference call regarding our product candidates shall be viewed as promotional. On the call today, we'll discuss our second quarter 2025 financial results, and we'll provide further business updates. Following some prepared remarks, we'll then open up the call for questions. With that, let me turn it over to Jan.

Thanks, Scott. Good afternoon, everyone. The second quarter of 2025 demonstrated strong momentum towards fulfilling our vision 2030. As we progress towards blockbuster status for multiple products and expand our engine for future innovation, the continued strong global launch of Europass increases our confidence that Europass is on the way to become a blockbuster product with doable global leadership of the treatment of hyperparatarrhism. FDA granting us priority review for TransconCMP, recognizing its potential, if approved, to provide a significant improvement in the safety and or effectiveness of the treatment of acondroplasia. The announcement of the interim phase two result from the first combination therapy trial of TransconCMP and TransconGrowthomo highlights our potential to boost healthy growth in acondroplasia. And we achieved the first of many planned label expansion for Skytofa when the FDA approved it for treatment of adult growth hormone deficiency. I will review these key developments in more detail in my prepared remarks. Beginning with Europass, revenues in the second quarter reached 103 million euros, more than double of Q1, despite a strong currency headwind. In the US, from long to June 30, more than 1,500 prescribers wrote prescription for around 3,100 unique patients, reflecting both the deep unmet medical need and compelling product profile. For US patients receiving a prescription for Europass, the majority have received payer approval within three months. Outside of the US, we continue to see steady Europass revenue growth in both our Europe Direct and international market. And we currently expect further acceleration of the revenue growth when Europass reimbursement becomes available in additional Europe Direct countries. With a broad label calling all types of chronic hyperpare, supported by international guidelines and a prominent reference to Europass in recently published best practice consensus statement, we expect growth to continue. We have ongoing clinical programs to support label expansion. For example, in older children and initiated Partway 60 trials as single arm safety and efficacy trial to support titration up to 60 microgram doses in the US. The primary endpoint of this trial will be efficacy at 26 weeks, the same as our pupil phase three trial input. We are building towards Europass long-term global leadership based on three key pillars. Differentialization, demand and access. I will first speak about differentiation through mode of action. A replacement therapy for hyperpare must maintain the same mode of action as in DOS's PTA throughout the body and sustain physiological level of PTA 24 hours, seven days a week. Based on all the data we have seen, Europass is the only product to demonstrate it can do this with normalization of key elements such as serum calcium, phosphate, kidney function, bone turnover and quality of life. Second is demand. Where Europass is available, we see strong interest and growing enrollment. For the US market in just two full quarters, we had around 3,100 unique patients enrolled across more than 1,500 subscribers. We're seeing a broad uptake across the entire country. And with our estimate of 70 to 90,000 patients in the US, we still have ample room to grow. Outside the US, we have recognized revenue from more than 30 countries. And currently we have commercial agreement covering more than 75 countries. Third is access. In the US, we see favorable access continue to improve with approvals coming across all payer segments. In Europe Direct, we have full commercial loans in Germany, Austria and now Spain. We expect additional commercial loans later this year, both in Europe Direct and international market. In Japan, our partner, Taiteng, expect approval for Europass later this quarter. We consistently hear about how transformative Europass has been for patients. And do not believe that any public disclosed drug and clinical development have the potential to meet this efficacy and safety bar set by Europass. As shown in our clinical trial, they have been extended for all patient groups, post-surgery HP patients, to small genetic subtypes like D. George's syndrome, ADS-1 and idiopathic hyperpare. Notably, Europass has brought approval from the FDA, the European Commission and other regulatory authorities for the treatment of all forms of chronic hyperpare. For all of the above reason, we are confident that Europass has the potential to become a doable blockbuster over time. And we continue to expand our global leadership position in the treatment of hyperpare. Moving now to TransconCMP. We believe TransconCMP is moving the bar on safety, efficacy and tolerability and reducing treatment burden. And we believe TransconCMP is well positioned to become the leading monotherapy treatment for end acrylplasia. In clinical trials, we have seen the desired linear growth across all ages. And to our knowledge, once weekly TransconCMP is the only product to show statistical significant improvement beyond linear growth compared to placebo in a pivotal trial, for example, improvements in leg-bowing and quality of life. We have demonstrated a safety and tolerability profile comparable to placebo, including no evidence of hypotensive effect and extremely low frequency of mild, injection-side reaction. Since our announcement of monotherapy data, we have engaged with patients, advocates, physician and regulators. All have appreciated the differentiating ability of TransconCMP in comparison to placebo to increase linear growth, while also leading to stronger muscle function, improved body proportionality and leg-bowing. And reducing overall the burden of acrylplasia related complications for the majority of treated children. And of course, patient and caregivers appreciate the much lower burden of one-weekly injection. During the second quarter of 2025, FDA accepted our NDA submission for priority review with a perduous date of November 30, recognizing TransconCMP as a therapy that could, if approved, provide a significant improvement in safety and or effectiveness. Next, I will review our combination trial results. As we look forward to the anticipated approval of TransconCMP as monotherapy, we are investigating it in combination with our one-weekly TransconCMP. In children with acrylplasia, in our COAS trial, in June 2025, we announced week 26 inter-rein results, which showed a clear boost in linear growth and body proportionality improvement, with a safety and tolerability profile consistent with those observed for monotherapies. In the combination trial, both treatment groups exceeded the 97% factor for growth. Of an average state of children, meaning they are achieving linear growth at a rate higher than an average child. The week 26 data demonstrate the potential to boost growth of around 3x, or three times, above that observed with monotherapies addressing the hyperactive FDR3 receptor pathway. Supporting the scientific rationale for treating the TransconCMP and Transcon growth hormone combined. These results are without precedence in acrylplasia. Importantly, we see clear indication that it's healthy growth, with linear growth accommodated by improvement in body proportionality and without acceleration of bone age. All patients continue in the study as of today. These results enforce the role of TransconCMP as a strong fundamental therapy in acrylplasia. We look forward to our 12 month laser release later this year, and plan to start a phase three study of the combination therapy in children with acrylplasia by the end of 25. In addition, we also expect to initiate a pupil combination trial in hypercantroplasia. I will now turn to Skytofa. Skytofa is established as a high value brand and a treatment choice for pediatric growth hormone deficiency. We recently received FDA approval for adult growth hormone deficiency, and with further label expansion planned, Skytofa remains a fundamental pillar in our strategy to become the global leader in treatment of growth disorder. Q2 revenue for Skytofa were 51 million euros. We continue to see growth in the number of people treated with Skytofa based on new patients' data. We expect that recent label expansion for adult growth hormone deficiency to further drive long-term growth. Our market research shows Skytofa is the treatment and choice for pediatric growth hormone deficiency among patient and physician. And we believe we can achieve the same status for treatment of adult growth hormone deficiency. Our Phase III basket time of Skytofa planned to begin later this year will include a range of established daily growth hormone indications, including ISS, shock-deficient, TURNR, and SDA. I often say that as soon as we're just getting started. Falling closely behind this major growth opportunity, our research team is developing the next day of innovative transplant technology and product candidates. In addition, our ongoing collaboration with NOMONODIS for the development and conversation of transplant-based product in metabolic and cardiovascular diseases continue to make progress toward the clinic. Ascendis is demonstrating a significant inflection in revenue growth. We are generally importing new clinical data, working towards additional key label expansion. We are advancing new blockbuster opportunity to drive growth for many years to come and fulfill our vision 2030. And we are already preparing for our next vision. I will now turn over to Scott.