Executive Summary / Key Takeaways

• Ascendis Pharma is rapidly transforming its financial profile, driven by the robust global launch of YORVIPATH and the expanding market presence of SKYTROFA, positioning the company for quarterly cash flow positivity in 2025.
• The proprietary TransCon technology platform is a core competitive advantage, enabling the development of differentiated, long-acting therapies like YORVIPATH and SKYTROFA, which offer superior patient convenience and physiological benefits over conventional treatments.
• YORVIPATH is establishing itself as the standard of care for chronic hypoparathyroidism, demonstrating strong U.S. uptake with approximately 3,100 unique patients and over 1,500 prescribers by Q2 2025, and is projected to achieve multi-billion euro annual peak sales.
• The pipeline, particularly TransCon CNP for achondroplasia, shows significant promise, with the FDA granting Priority Review and interim data from the COACH combination trial demonstrating unprecedented growth velocity, setting a new bar for treatment.
• Strategic collaborations, notably with Novo Nordisk for a once-monthly GLP-1, validate the TransCon platform's broad applicability and open avenues into multi-billion dollar metabolic and cardiovascular markets, diversifying future revenue streams.

The TransCon Advantage: Reshaping Rare Disease Treatment

Ascendis Pharma A/S, established in 2006, has carved a distinct niche in the biopharmaceutical landscape by leveraging its innovative TransCon technology platform. This proprietary technology is the bedrock of Ascendis's strategy, designed to create prodrugs that provide sustained, predictable release of unmodified active parent drugs. This approach offers significant advantages over conventional therapies, primarily through improved patient convenience with less frequent dosing and enhanced physiological benefits by maintaining therapeutic levels consistently over time. The "TransCon" (Transient Conjugation) platform temporarily links an inert carrier to a parent drug, releasing the active drug at a controlled rate. This mechanism is crucial for conditions requiring chronic hormone replacement or sustained pathway modulation.

The tangible benefits of this technology are evident across Ascendis's portfolio. For instance, SKYTROFA, a once-weekly growth hormone, contrasts sharply with daily injections, significantly reducing treatment burden and improving adherence. Similarly, YORVIPATH, a once-daily parathyroid hormone replacement, is designed to mimic endogenous PTH levels 24 hours a day, 7 days a week, a critical differentiator in hypoparathyroidism. This sustained physiological exposure normalizes key biochemical markers, kidney function, bone turnover, and quality of life, which traditional therapies often fail to achieve. The company's R&D initiatives continue to push the boundaries of this platform, developing next-generation TransCon technologies and expanding into protein degraders, a promising area for future blockbuster candidates. For investors, this technological differentiation translates into a robust competitive moat, enabling premium pricing, fostering strong patient and physician loyalty, and supporting long-term market leadership in its targeted therapeutic areas.

Competitive Landscape and Strategic Positioning

Ascendis operates in highly competitive biopharmaceutical markets, but its TransCon platform provides a distinct edge. In the growth hormone market, SKYTROFA competes with established players like Novo Nordisk , Pfizer (PFE), and Eli Lilly (LLY), which also have GHD treatments. While these larger pharmaceutical companies benefit from extensive global distribution and broader product portfolios, SKYTROFA's once-weekly dosing and premium net pricing (approximately 3x that of daily growth hormone) position it as a preferred choice, particularly as the daily growth hormone market undergoes consolidation with some competitors exiting. This trend allows Ascendis to capture market share from the 85% of prescriptions still written for daily growth hormone.

For hypoparathyroidism, YORVIPATH stands as the first and only FDA-approved replacement therapy, giving Ascendis a significant first-mover advantage. Management asserts that no other publicly disclosed drug in clinical development has the potential to meet YORVIPATH's efficacy and safety bar, particularly in its ability to maintain endogenous PTH-like mode of action and sustained physiological levels. Competitors attempting to develop once-weekly PTH products or calcilytics face scientific and mechanistic challenges that Ascendis believes cannot replicate YORVIPATH's comprehensive benefits. This strong differentiation, coupled with a patent lifespan extending into the 2040s, underpins YORVIPATH's potential for durable global leadership.

In achondroplasia, TransCon CNP is positioned against existing and emerging therapies. Ascendis emphasizes that TransCon CNP is the only product to show statistically significant improvement beyond linear growth compared to placebo in a pivotal trial, including benefits in leg bowing and quality of life. The company's combination therapy, TransCon CNP with TransCon Growth Hormone, further differentiates its approach by leveraging synergistic biological pathways to achieve unprecedented growth velocities, exceeding the 97th percentile for growth of an average child. This innovative strategy aims to set a new standard of care, addressing both linear growth and associated complications, a holistic approach that competitors may struggle to match with monotherapies.

Product Portfolio and Performance Drivers

Ascendis Pharma's growth is primarily fueled by its three core endocrinology rare disease programs: SKYTROFA, YORVIPATH, and TransCon CNP.

SKYTROFA: Expanding Leadership in Growth Hormone Deficiency

SKYTROFA (lonapegsomatropin-tcgd) has firmly established itself as a high-value brand and the preferred treatment for pediatric growth hormone deficiency (GHD). In Q2 2025, SKYTROFA generated EUR 50.7 million in revenue, even with a EUR 1.8 million negative currency impact. The product holds approximately 7% of the total U.S. growth hormone market and 43% of the U.S. long-acting growth hormone market. The recent FDA approval for adult GHD in July 2025 marks a significant label expansion, expected to drive long-term growth, though its contribution in 2025 will be modest. Ascendis aims to replicate SKYTROFA's "treatment of choice" status in the adult GHD market, which is highly underpenetrated with only 5-8% of patients currently treated. Further expansion is planned with a Phase III basket trial for indications like idiopathic short stature, SHOX deficiency, Turner syndrome, and small for gestational age, slated to begin later in 2025. This multi-pronged strategy underscores Ascendis's commitment to making SKYTROFA a blockbuster product by capturing a larger share of the overall growth hormone market.

YORVIPATH: Rapid Ascent in Hypoparathyroidism

YORVIPATH (palopegteriparatide) is proving to be a transformative product for Ascendis, demonstrating exceptional launch performance. In Q2 2025, YORVIPATH revenue more than doubled sequentially to EUR 103 million, up from EUR 44.7 million in Q1 2025, despite a EUR 5.8 million negative currency headwind. This rapid uptake reflects a deep unmet medical need among the estimated 70,000 to 90,000 U.S. patients with chronic hypoparathyroidism, a population where 95% are considered candidates for PTH treatment per international guidelines.

By June 30, 2025, over 1,500 prescribers in the U.S. had written prescriptions for approximately 3,100 unique patients. The majority of U.S. patients are receiving payer approval within three months, a testament to the product's compelling profile and Ascendis's experienced commercial team. Outside the U.S., YORVIPATH is seeing steady growth with full commercial launches in Germany, Austria, and Spain, and additional launches anticipated in Europe and international markets later in 2025. Japan, through its partner Teijin, also expects approval in Q3 2025. The company has initiated the PaTHway 60 trial to support a higher 60 microgram dose in the U.S., addressing a clinical need beyond the current 30 microgram label. With an "extremely low" discontinuation rate in Europe, YORVIPATH is poised for durable global leadership and is expected to achieve multiple billions of euros in annual peak sales.

TransCon CNP: A New Paradigm for Achondroplasia

TransCon CNP (navepegritide) is poised to become the third pillar of Ascendis's rare disease portfolio. The FDA accepted the New Drug Application (NDA) for Priority Review in June 2025, with a PDUFA date of November 30, 2025, acknowledging its potential for significant improvement in achondroplasia treatment. The product's once-weekly dosing and safety profile, comparable to placebo, are key differentiators.

Ascendis is also pioneering combination therapy with TransCon CNP and TransCon Growth Hormone in the COACH trial. Interim Week 26 results, announced in June 2025, showed a "clear boost in linear growth and body proportionality improvement," with both treatment groups exceeding the 97th percentile for growth of an average child. This combination demonstrated the potential to boost growth by approximately 3x above monotherapies, a result "without precedent in achondroplasia." The company plans to initiate a Phase III study for this combination in achondroplasia and a pivotal combination trial in hypochondroplasia by the end of 2025, aiming to establish a new, more comprehensive treatment standard.

Financial Health and Outlook

Ascendis Pharma is undergoing a significant financial inflection, transitioning towards profitability. Total product revenue for Q2 2025 reached EUR 153.7 million, a substantial increase driven primarily by YORVIPATH's strong performance. While SKYTROFA contributed EUR 50.7 million, YORVIPATH's revenue of EUR 103 million more than doubled from the previous quarter.

Operating expenses in Q2 2025 were approximately EUR 180 million, with R&D costs decreasing to EUR 72 million due to lower growth disorder development costs, while SG&A increased to EUR 107.6 million due to global commercial expansion. The company's gross profit margin (TTM) stands at a robust 84.88%, reflecting the high-value nature of its products. However, the net profit margin (TTM) remains negative at -55.25% as the company continues to invest heavily in commercialization and pipeline development.

Ascendis ended Q2 2025 with EUR 494 million in cash and cash equivalents. Despite a sequential decrease, largely due to currency translation, the company expects to become cash flow positive on a quarterly basis in 2025, a critical milestone driven by the strong revenue growth from YORVIPATH and SKYTROFA. This financial strength is further bolstered by strategic collaborations, such as the $100 million upfront payment from Novo Nordisk (NVO) for a multi-product partnership in metabolic and cardiovascular diseases, including a once-monthly TransCon semaglutide. This collaboration not only provides non-dilutive capital but also validates the TransCon platform's potential in the multi-billion dollar GLP-1 market, which is projected to exceed $50 billion and potentially triple in the next decade.

Risks and Challenges

Despite the compelling growth trajectory, Ascendis faces several risks. The successful commercialization of YORVIPATH and TransCon CNP depends on continued market acceptance and favorable reimbursement policies. While the majority of U.S. YORVIPATH patients receive payer approval within three months, a "long tail" of patients may still face reimbursement difficulties. The company is actively working to streamline the process, but the heterogeneity of payer plans presents an ongoing challenge.

Competition, while currently less direct for YORVIPATH, could intensify if rivals overcome scientific hurdles. For TransCon CNP, while its data is strong, the achondroplasia market is evolving, and the long-term competitive landscape will depend on the efficacy and safety profiles of other emerging therapies. Furthermore, as a biopharmaceutical company, Ascendis is exposed to inherent risks associated with clinical development, regulatory approvals, manufacturing, and intellectual property protection. Global economic and geopolitical factors, including potential tariffs, could also impact operations, though Ascendis believes its U.S. manufacturing strategy mitigates some of these risks.

Conclusion

Ascendis Pharma is at an exciting inflection point, transitioning from a development-focused entity to a commercial-stage biopharmaceutical leader. The company's proprietary TransCon technology platform is a powerful engine, consistently delivering differentiated, best-in-class therapies that address significant unmet medical needs. The strong global launch of YORVIPATH, coupled with the expanding market presence of SKYTROFA and the promising pipeline candidate TransCon CNP, forms a robust foundation for sustained revenue growth and a clear path to quarterly cash flow positivity in 2025.

With a strategic focus on expanding labels, pursuing innovative combination therapies, and leveraging its technology through high-value collaborations, Ascendis is well-positioned to achieve its Vision 2030 goals. While competitive pressures and reimbursement complexities remain, Ascendis's technological leadership and patient-centric approach provide a compelling investment thesis, offering significant upside potential as it continues to unlock blockbuster opportunities across multiple rare disease markets.