Summary of United Therapeutics Conference Call on Phase III ADVANCE OUTCOMES Clinical Trial Results Company Overview - **Company**: United Therapeutics Corporation - **Ticker**: NasdaqGS: UTHR - **Event Date**: March 02, 2026 - **Focus**: Results of the Phase III ADVANCE OUTCOMES Clinical Trial for ralinepag, a treatment for pulmonary arterial hypertension (PAH) Key Points Clinical Trial Results - **Ralinepag Efficacy**: Ralinepag is over 3 times more likely to avoid disease progression events in PAH compared to standard double therapy (ETRA and PDE5 inhibitor) [4][5] - **Primary Endpoint Achievement**: The trial met its primary endpoint with a hazard ratio of 0.45, indicating a 55% reduction in the risk of clinical worsening events [20] - **Statistical Significance**: The results were statistically significant with a P value of less than 0.0001 [5] - **Secondary Endpoints**: The treated group showed a 47% higher likelihood of clinical improvement compared to background therapy [5] Patient Population and Study Design - **Demographics**: Predominantly female participants in their 50s, with an average time since diagnosis of about 4.5 years [15][18] - **Background Therapy**: 80% of participants were on dual background therapy, indicating a heavily pre-treated population [15] - **Functional Class**: Most participants were classified as functional class 2, with some in class 3 [18] Treatment Characteristics - **Dosing**: Ralinepag is a once-daily oral medication, which is expected to improve patient compliance compared to multiple daily doses of other therapies [4][39] - **Pharmacokinetics**: It has best-in-class pharmacokinetics with a long half-life and stable plasma concentrations, allowing for effective once-daily dosing [5] Safety Profile - **Adverse Events**: Common side effects included headache, diarrhea, nausea, and jaw pain, consistent with other prostacyclins. Discontinuation due to adverse events was reported at less than 10% in the active group [27][53] - **No New Safety Signals**: The safety profile was as expected, with no unexpected side effects reported [27][54] Market Implications - **Potential Market Expansion**: Ralinepag is expected to expand the oral prostacyclin market, potentially treating patients who previously could not justify oral prostacyclin therapy due to milder disease status [81] - **Prescriber Uptake**: The ease of use and significant efficacy results are anticipated to lead to high prescriber uptake, especially for new patients diagnosed with PAH [48][62] Future Directions - **Combination Therapies**: Discussions are ongoing regarding the potential for ralinepag to be used in combination with other therapies, including Winrevair [74] - **Regulatory Approval**: The company plans to seek FDA approval for ralinepag, with expectations for it to be used early in treatment regimens for PAH patients [62] Conclusion - **Transformative Impact**: The results from the ADVANCE OUTCOMES trial are seen as transformative for the treatment of PAH, with the potential to significantly improve patient outcomes and quality of life [6][8]

Financial Data and Key Metrics Changes - In 2025, the company achieved record-breaking revenue, surpassing $3 billion for the first time, with an 11% total revenue growth over 2024 [8] - For Q4 2025, total revenue was $790 million, representing a 7% increase from Q4 2024 [8] Business Line Data and Key Metrics Changes - Tyvaso revenue for Q4 was $464 million, a 12% increase year-over-year, driven by a 24% growth in Tyvaso DPI [9] - Orenitram and Remodulin continue to be foundational therapies in treating pulmonary hypertension, with ongoing studies reinforcing their benefits [12] Market Data and Key Metrics Changes - The referral rate for Tyvaso reached its highest level in two years, indicating strong underlying demand [10] - The company noted that sales trends can vary seasonally, with Q1 and Q4 typically being lighter ordering quarters [9] Company Strategy and Development Direction - The company is focused on launching three transformative products in 2027: a once-daily super prostacyclin for PAH, a cough-less inhaler for ILD, and a new treatment for IPF [7] - The company is also engaged in discussions with pharmaceutical companies regarding its AI-enabled digital lung model, which can predict trial outcomes more efficiently [32] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about upcoming clinical trial results and the potential for new product launches to drive future growth [6][7] - The company is committed to double-digit revenue growth and aims to reach a $4 billion revenue run rate by the end of 2027, independent of new product contributions [56] Other Important Information - The company is actively involved in transplantation research, with ongoing clinical trials for new organ products [35] - The Tresmi product, a soft mist inhaler, is expected to significantly improve patient adherence by reducing coughing, a common side effect of existing therapies [5][37] Q&A Session Summary Question: Confidence in Teton-1 data for IPF - Management expressed strong confidence in the Teton-1 study outcomes, citing similarities with Teton-2 results [18][19] Question: Impact from Uptravi on patient ads and competition - Management noted that Tyvaso remains the market leader, with strong referral rates and physician confidence despite initial curiosity about new entrants [46] Question: Details on soft mist inhaler studies - Management indicated that physicians will likely welcome the soft mist inhaler due to its ease of use and effectiveness, with further details to be disclosed post-FDA approval [50][51] Question: Contribution of new product launches to long-term growth - Management confirmed that the new product launches will enhance revenue growth beyond the projected $4 billion run rate, emphasizing their transformative nature [54][56] Question: Key outcomes to watch for Ralinepag - Management highlighted the importance of clinical worsening metrics and hospitalizations as key outcomes for Ralinepag, with anticipation for upcoming data [59][62]

Financial Data and Key Metrics Changes - In 2025, the company achieved record-breaking revenue, surpassing $3 billion for the first time, with an 11% total revenue growth compared to 2024 [8] - For Q4 2025, total revenue was $790 million, reflecting a 7% increase from Q4 2024 [8] - Tyvaso revenue for Q4 was $464 million, a 12% year-over-year increase, driven by a 24% growth in Tyvaso DPI [9] Business Line Data and Key Metrics Changes - Tyvaso's strong performance is attributed to its strategic positioning in the pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD) markets, with expectations for continued double-digit growth [9][10] - Orenitram and Remodulin remain foundational therapies in treating pulmonary hypertension, with ongoing studies reinforcing their benefits [12] Market Data and Key Metrics Changes - The referral rate for Tyvaso reached its highest level in two years, indicating strong underlying demand [10] - The company noted that initial curiosity about new market entrants has not significantly impacted Tyvaso's market leadership, with referrals returning to pre-competitive launch levels [46] Company Strategy and Development Direction - The company is focused on innovative product development, with plans to launch three transformative products by 2027: a once-daily super prostacyclin for PAH, a cough-less inhaler for ILD, and a new treatment for IPF [7][56] - The company is also engaged in discussions with pharmaceutical companies regarding its AI-enabled digital lung model, which can predict trial outcomes more efficiently [32] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about upcoming clinical trial results, particularly for the TETON studies, and their potential to translate into successful outcomes [19][44] - The company is committed to maintaining double-digit revenue growth and anticipates reaching a $4 billion revenue run rate by the end of 2027, driven by existing products and new launches [56] Other Important Information - The company is actively involved in transplantation research, with ongoing clinical trials for innovative organ transplantation solutions [35] - The Tresmi product, a soft mist inhaler, is expected to significantly improve patient adherence by reducing coughing, a common side effect of existing therapies [5][37] Q&A Session Summary Question: Confidence in TETON-1 data and impact from Yutrepia - Management expressed strong confidence in the TETON-1 study outcomes based on positive results from TETON-2, with similar baseline characteristics [18][44] - The competitive impact from Yutrepia is being monitored, with Tyvaso maintaining its market leadership despite initial curiosity about new entrants [46] Question: Details on soft mist inhaler studies - Management indicated that physicians will likely respond positively to the soft mist inhaler due to its ease of use and effectiveness, with further details to be disclosed post-FDA approval [50][51] Question: Contribution of new product launches to long-term growth - The company reaffirmed its commitment to a $4 billion revenue run rate, with new product launches expected to enhance growth beyond this target [56] Question: Key outcomes to watch for Ralinepag - Management highlighted the importance of clinical worsening metrics, hospitalizations, and mortality rates as key outcomes for Ralinepag, with anticipation for upcoming trial results [60][62]

Financial Data and Key Metrics Changes - In 2025, the company achieved record-breaking revenue, with an 11% total revenue growth over 2024, surpassing $3 billion for the first time [7][8] - For Q4 2025, total revenue was $790 million, representing a 7% increase from Q4 2024 [7][8] Business Line Data and Key Metrics Changes - Tyvaso revenue for Q4 was $464 million, a 12% increase year-over-year, driven by a 24% growth in Tyvaso DPI [8][9] - Orenitram and Remodulin continue to be foundational therapies in treating pulmonary hypertension, with ongoing studies reinforcing their benefits [11] Market Data and Key Metrics Changes - The referral rate for Tyvaso reached its highest level in two years, indicating strong underlying demand [9] - The company noted that sales trends can vary seasonally, with Q1 and Q4 typically being lighter ordering quarters [8] Company Strategy and Development Direction - The company plans to launch three transformative products in 2027: a once-daily super prostacyclin for PAH, a cough-less inhaler for ILD, and a new treatment for IPF [6][35] - The company is focused on innovation, utilizing an AI-enabled digital lung model to enhance product development and reduce trial times [30] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about upcoming clinical trial results, particularly for the TETON-1 study, and expects to see similar positive outcomes as in TETON-2 [40][41] - The company anticipates continued double-digit revenue growth, supported by existing products and new launches [12][52] Other Important Information - The company is actively engaged in discussions with pharmaceutical companies regarding its AI-enabled digital lung model, which can predict trial outcomes more efficiently [30] - The company is also advancing its transplantation initiatives, with successful trials and plans for regulatory approval of new products [33][34] Q&A Session Summary Question: Confidence in TETON-1 data and impact from Uptravi - Management expressed strong confidence in TETON-1 outcomes based on TETON-2 results and noted that Tyvaso remains a market leader despite competition from Uptravi [16][43] Question: Details on the soft mist inhaler product - Management indicated that the soft mist inhaler is expected to be well-received by physicians and patients, with plans for FDA filing this year and launch next year [47] Question: Contribution of new product launches to long-term growth - Management confirmed a commitment to a $4 billion revenue run rate by 2027, with new product launches expected to enhance growth beyond this target [50][52] Question: Important outcomes for Ralinepag data - Management highlighted the importance of clinical worsening, hospitalizations, and mortality as key outcomes to watch for Ralinepag [55][58]