Insmed (INSM) Phase 2b PAH Top Line Results Conference Call Summary Company Overview - **Company**: Insmed (INSM) - **Focus**: Development of TPIP for the treatment of pulmonary arterial hypertension (PAH) Key Industry Insights - **Industry**: Pharmaceutical, specifically focusing on treatments for pulmonary arterial hypertension (PAH) - **Current Treatment Landscape**: TPIP aims to improve upon existing prostanoid therapies, which have limitations in dosing frequency and side effects Core Findings from the Conference Call 1. **Study Success**: The Phase 2b TPIP study in PAH was declared a historic success, with all primary and secondary efficacy endpoints achieving clinically meaningful improvements, with p-values well below 0.05 [4][5][6] 2. **Pulmonary Vascular Resistance (PVR) Reduction**: TPIP demonstrated a placebo-adjusted PVR reduction of 35%, the largest ever recorded in a controlled clinical trial for PAH [5][20] 3. **Six-Minute Walk Distance**: Patients on TPIP showed a placebo-adjusted improvement of 35.5 meters in six-minute walk distance, with a p-value of 0.003, exceeding initial expectations [6][22] 4. **NT proBNP Levels**: TPIP treatment resulted in a 60% reduction in NT proBNP levels compared to placebo, indicating significant cardiac stress reduction [23] 5. **Functional Class Improvement**: 30% of patients in the TPIP group showed an improvement in functional class, compared to 15% in the placebo group [24][25] 6. **Safety Profile**: TPIP had a low treatment discontinuation rate (10%) and a favorable safety profile, with common adverse events being mild [27][28] Additional Important Insights 1. **Patient Population**: The study included a heavily pretreated population, with 66% classified as functional class two and 80% on two background PAH medications, indicating a challenging patient demographic [17][19] 2. **Dosing Strategy**: TPIP was designed for once-daily dosing, which is expected to improve patient adherence compared to existing therapies that require multiple daily doses [12][31] 3. **Future Development Plans**: Insmed plans to initiate Phase 3 trials for both PAH and PH ILD, with an increased maximum dose of TPIP up to 1280 micrograms [32][34] 4. **Market Positioning**: The results position TPIP as a potential cornerstone therapy for PAH, with implications for changing treatment paradigms and possibly displacing existing therapies [38][42] 5. **Regulatory Strategy**: Insmed intends to engage with the FDA to discuss the implications of the Phase 2b results for future regulatory submissions [47][52] Conclusion - The Phase 2b results for TPIP in PAH are promising, indicating significant efficacy and a favorable safety profile. The company is poised to advance to Phase 3 trials, with the potential to redefine treatment standards in the PAH space.

Core Insights - Insmed announced positive topline results from its Phase 2b study of treprostinil palmitil inhalation powder (TPIP) for pulmonary arterial hypertension (PAH), meeting primary and all secondary efficacy endpoints [1][2][3] - The study demonstrated a 35% placebo-adjusted reduction in pulmonary vascular resistance (PVR) and a 35.5-meter improvement in six-minute walk distance (6MWD) [5][6] - Insmed plans to engage with the FDA for Phase 3 trial design, with trials for pulmonary hypertension associated with interstitial lung disease (PH-ILD) expected to start before the end of 2025 and for PAH in early 2026 [2][3] Study Results - The Phase 2b study was randomized, double-blind, and placebo-controlled, involving 102 patients across 44 sites [3][12] - Patients were titrated from an initial dose of 80 µg to a maximum of 640 µg once daily, with 75% reaching the maximum dose [3][12] - Treatment-emergent adverse events (TEAEs) occurred in 88.4% of TPIP patients, with serious TEAEs in 7.2% and severe TEAEs in 5.8% [4][6] Future Plans - Insmed will host an investor call to discuss the Phase 2b study results and future plans [8][9] - A long-term open-label extension study will evaluate TPIP at doses up to 1,280 µg once daily, with 95% of Phase 2b completers enrolling [7][12] - Detailed results from the Phase 2b study and the open-label extension will be presented at future medical meetings [7]