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.

Efficacy Results - TPIP demonstrated a statistically significant 35% placebo-adjusted reduction in pulmonary vascular resistance (PVR) from baseline at Week 16 (p<0001)[20, 33] - The study showed a 355-meter placebo-adjusted improvement in the six-minute walk distance (6MWD) from baseline[20, 36] - TPIP resulted in a statistically significant reduction in NT-proBNP concentrations, a biomarker of cardiac stress, with a placebo-adjusted reduction of 60% at Week 16 (p<0001)[38] - More patients on TPIP achieved an improvement in WHO Functional Class compared to placebo, with 30% of TPIP patients showing improvement versus 15% for placebo[40, 41] - TPIP showed a 15% increase in Cardiac Index (CI) compared to placebo at Week 16 (p=0006)[43] Safety and Tolerability - TPIP was generally well-tolerated, with 899% of participants completing the 16-week study[31] - The most common treatment-emergent adverse events (TEAEs) reported with TPIP were cough (406%) and headache (319%), consistent with the known profile of inhaled treprostinil[45] Study Design and Baseline Characteristics - The Phase 2b study was a randomized, double-blind, multi-center, placebo-controlled trial with 102 patients randomized in a 2:1 ratio (TPIP:Placebo)[25, 26] - Baseline characteristics were reasonably well-balanced across study arms, with a mean age of approximately 48 years and a majority of patients in WHO Functional Class II (approximately 66%)[30] Future Plans - The company plans to advance TPIP to Phase 3 before the end of 2025 for PH-ILD and in early 2026 for PAH[46]

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]

Company Overview - Insmed Incorporated is a global biopharmaceutical company focused on delivering first- and best-in-class therapies for patients with serious diseases [3][4] - The company is advancing a diverse portfolio of approved and investigational medicines, particularly in pulmonary and inflammatory conditions [3] - Insmed's early-stage programs include various technologies such as gene therapy, AI-driven protein engineering, and synthetic rescue [3] Upcoming Event - Management will present at the 2025 Goldman Sachs Annual Global Healthcare Conference on June 11, 2025, at 9:20 a.m. ET [1] - The event will be webcast live and available for 30 days post-event on the company's investor relations website [2]

Core Insights - Insmed Incorporated presented 11 new abstracts at the ATS 2025 International Conference, highlighting the efficacy and safety of brensocatib in treating non-cystic fibrosis bronchiectasis [1][3] - The ASPEN trial demonstrated consistent efficacy across various patient subgroups, reinforcing brensocatib's potential as a foundational treatment for bronchiectasis [2][3] Group 1: Brensocatib and ASPEN Trial Findings - Brensocatib showed a reduction in pulmonary exacerbations and prolonged time to first exacerbation compared to placebo, with a similar safety profile [3][5] - In adolescents aged 12 and older, brensocatib reduced annualized exacerbation rates significantly, with 59% of patients remaining exacerbation-free compared to 35% on placebo [5] - The trial included 391 active sites across 35 countries, with a total of 1,680 adult patients and 41 adolescent patients participating [5][6] Group 2: Additional Research and Data - Insmed presented a post-hoc analysis on the healthcare burden of bronchiectasis and findings from an expanded Phase 2 analysis of TPIP for pulmonary hypertension associated with interstitial lung disease [4] - Real-world outcomes for ARIKAYCE treatment were also shared, demonstrating longitudinal health status improvements in patients with refractory Mycobacterium avium complex lung disease [4] Group 3: Company Overview and Commitment - Insmed is focused on delivering first- and best-in-class therapies for serious diseases, with a diverse portfolio of approved and investigational medicines [29][30] - The company emphasizes its commitment to advancing research that can transform care for patients with serious diseases [3][29]

Summary of Insmed (INSM) 2025 Conference Call Company Overview - **Company**: Insmed (INSM) - **Event**: 2025 Conference on May 13, 2025 - **Key Speaker**: Will Lewis, Chair and CEO of Insmed Key Points Discussed 1. Focus on TPIP Phase Two Asset - Investors are particularly interested in the phase two asset TPIP, with data expected in June 2025 [2][24] - A success benchmark for TPIP is set at a 20% reduction in pulmonary vascular resistance (PVR) [3][4] - The six-minute walk test improvement of 15 to 20 meters is also considered a win [5] 2. Differentiation of TPIP - TPIP is designed as a once-a-day medication, contrasting with current inhaled prostanoids that require four times a day administration [6][7] - The formulation aims to provide nighttime coverage, which is a significant improvement for patient compliance [7] 3. Rationale for Study Design - The focus on PVR as a primary endpoint is due to its direct measurement of pulmonary vascular resistance, which is critical for patients with pulmonary arterial hypertension (PAH) [9][10] - The study duration of 16 weeks may not capture the full benefit of the six-minute walk improvement, hence the emphasis on PVR [10] 4. Safety Profile - Safety is crucial, especially for inhaled drugs, with common side effects leading to discontinuation in existing therapies [12] - The design of TPIP aims to reduce cough sensitivity, a common issue with inhaled drugs [13][16] 5. Market Potential and Growth Strategy - Insmed has $1.2 billion in cash and forecasts ARIKAYCE to generate over $400 million in revenue [27] - The potential market for ARIKAYCE could expand significantly with upcoming phase three data [27] - Brensocatib is expected to target multiple indications, including bronchiectasis and hidradenitis suppurativa, with significant market potential [28][52] 6. Regulatory Engagement - The FDA review process for Insmed's products has been smooth, with no significant issues raised [33][34] - The company is on track for timely submissions and approvals, with a focus on market access strategies [39][40] 7. Market Access and Pricing Strategy - The market access strategy is focused on patients with two or more exacerbations and a definitive diagnosis of bronchiectasis [37][40] - Insmed is optimistic about the drug's ability to preserve lung function and improve quality of life, which is appealing to payers [49][50] 8. Future Indications and Research - Insmed is exploring additional indications for brensocatib, including neutrophil-driven diseases like CRS and HS [52][54] - The company is developing new DPP-1 inhibitors for various diseases, indicating a robust pipeline for future growth [54][55] 9. Confidence in Execution - The growth of Insmed's workforce and deliberate hiring practices contribute to the company's confidence in executing its strategic plans [56] Additional Insights - The skepticism from the investment community regarding TPIP's dosing and efficacy is acknowledged, but the company remains optimistic about upcoming data [24][22] - The potential for a truncated phase three trial is discussed, contingent on the strength of the phase two data [30] This summary encapsulates the critical discussions and insights from the Insmed conference call, highlighting the company's strategic focus, product pipeline, and market positioning.

Core Viewpoint - Insmed reported a wider-than-expected loss in Q1 2025, with total revenues showing a year-over-year increase driven by its sole marketed drug, Arikayce [1][4][5]. Financial Performance - Insmed's Q1 2025 loss was $1.42 per share, compared to the Zacks Consensus Estimate of a loss of $1.36 and a loss of $1.06 per share in the same quarter last year [1]. - Total quarterly revenues reached $92.8 million, reflecting a 23% increase year over year, aligning with the Zacks Consensus Estimate [1]. - The company's stock declined by 4% following the earnings miss, and year-to-date, the stock has lost 9%, while the industry has seen a 5% decline [2]. Revenue Breakdown - All revenues in the reported quarter were generated from Arikayce, which is approved for treating refractory mycobacterium avium complex lung disease [4]. - Sales of Arikayce increased by 14% to $64.3 million in the U.S., 48% to $22.1 million in Japan, and 52% to $6.5 million in Europe and the rest of the world [5]. Expense Analysis - Research and development expenses rose by 26% year over year to $152.6 million, while selling, general, and administrative expenses increased by 58% to $147.5 million [6]. - The increase in expenses is attributed to a rise in employee headcount, leading to higher compensation and benefit-related expenses, as well as stock-based compensation costs [6]. Cash Position - As of March 31, 2025, Insmed had cash, cash equivalents, and marketable securities totaling approximately $1.2 billion, down from $1.4 billion as of December 31, 2024 [7]. Guidance and Future Outlook - Insmed maintained its sales guidance for Arikayce for the full year, expecting product sales to be between $405 million and $425 million, indicating a 14% year-over-year growth at the midpoint [9]. - The company is progressing with its pipeline, including a confirmatory phase III study for Arikayce and regulatory filings for brensocatib [10][11].

Insmed (INSM) came out with a quarterly loss of $1.42 per share versus the Zacks Consensus Estimate of a loss of $1.36. This compares to loss of $1.06 per share a year ago. These figures are adjusted for non-recurring items.This quarterly report represents an earnings surprise of -4.41%. A quarter ago, it was expected that this biopharmaceutical developing inhaled treatments for patients battling rare lung diseases would post a loss of $1.15 per share when it actually produced a loss of $1.32, delivering a ...

Financial Data and Key Metrics Changes - Insmed reported strong commercial performance with ARIKAYCE achieving double-digit year-over-year revenue growth in Q1 2025, marking the sixth consecutive quarter of such growth [6][25] - The company maintains its full-year ARIKAYCE net revenue guidance of $400 to $425 million, excluding any contributions from brensocatib if approved [26] - As of the end of Q1 2025, Insmed's cash balance stood at approximately $1.2 billion, positioning the company well for upcoming clinical and commercial catalysts [26][28] Business Line Data and Key Metrics Changes - ARIKAYCE experienced a 14% growth in the U.S. market, with Japan and Europe showing impressive growth rates around 50% [25][26] - The company is advancing three mid to late-stage programs: brensocatib, TPIP, and ARIKAYCE, with all programs on or ahead of schedule [6][7] Market Data and Key Metrics Changes - The disease state awareness website for bronchiectasis received over one million unique visits, indicating strong patient interest and engagement [10] - Insmed has successfully engaged with over 27,000 healthcare professionals in the U.S. regarding bronchiectasis and ARIKAYCE [10] Company Strategy and Development Direction - Insmed is focused on a frictionless launch for brensocatib, aiming for easy access and rapid uptake among patients [41][96] - The company is expanding its U.S. manufacturing footprint to mitigate tariff impacts and ensure a robust supply chain for brensocatib [24][81] - Insmed is also exploring next-generation DPP1 inhibitors for conditions like COPD and rheumatoid arthritis, indicating a commitment to addressing unmet medical needs [70][72] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming FDA decision on brensocatib, expected by August 12, 2025, and highlighted the positive reception from regulatory authorities [6][9] - The company is well-positioned to thrive amid geopolitical uncertainties, with minimal tariff exposure anticipated [23][24] Other Important Information - Insmed's operating expenses for Q1 2025 were consistent with historical performance, with a cost of product revenues at 22.9% of revenues [29] - The company announced the calling of $570 million of convertible debt, which could lead to the issuance of approximately 17.8 million additional shares if converted [28] Q&A Session Summary Question: What factors influence brensocatib pricing in the U.S. and abroad? - Management indicated that pricing flexibility exists due to the sequential pricing strategy across regions, allowing for adjustments based on market conditions [36] Question: What trends are observed from the bronchiectasis disease awareness website? - There is a favorable backdrop with high patient interest and enthusiasm, paralleling physician engagement [40] Question: What are the key levers for transitioning interested patients to therapy? - The focus is on connecting diagnosed patients with treatment, particularly those with two or more exacerbations [46] Question: How does the company view the importance of PVR versus six-minute walk in TPIP trials? - PVR is considered the most definitive measure, while six-minute walk is viewed as a less specific but still relevant measure [58] Question: What is the status of inspections related to brensocatib's review? - No surprises were reported from the mid-cycle review, and inspections are ongoing as part of the approval process [75] Question: Can you clarify the patient population for bronchiectasis in the U.S.? - Approximately 500,000 patients are diagnosed with bronchiectasis, with about half having had two or more exacerbations in the last twelve months [90]

Financial Data and Key Metrics Changes - Insmed reported strong commercial performance with double-digit year-over-year growth in ARIKAYCE across all geographic regions, marking the sixth consecutive quarter of such growth [22][24] - The cash balance at the end of the quarter was approximately $1.2 billion, indicating a well-capitalized position as the company approaches upcoming clinical and commercial catalysts [24] - Operating expenses for Q1 2025 were $21.3 million, or 22.9% of revenues, consistent with historical performance, although R&D and SG&A expenses were higher than the previous year due to growth initiatives [27][28] Business Line Data and Key Metrics Changes - ARIKAYCE achieved a remarkable 14% growth in the U.S. market, with Japan and Europe showing growth rates around 50% [22][23] - The company anticipates ARIKAYCE net revenue guidance for 2025 to be between $400 million and $425 million, exclusive of any contributions from brensocatib [24] Market Data and Key Metrics Changes - The disease state awareness website for bronchiectasis received over one million unique visits, with more than 53,000 patients taking action to stay informed [8] - The company has engaged with over 27,000 healthcare professionals in the U.S. to educate them about bronchiectasis and ARIKAYCE [8] Company Strategy and Development Direction - Insmed is focused on advancing three mid to late-stage programs: brensocatib, TPIP, and ARIKAYCE, with positive clinical data supporting their potential [5][6] - The company is preparing for the launch of brensocatib, with regulatory reviews progressing in the U.S., Europe, and Japan, aiming for potential approvals in 2026 [9][10] - Insmed is expanding its U.S. manufacturing footprint to mitigate tariff impacts and ensure a robust supply chain for brensocatib [21][22] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's position to thrive despite geopolitical uncertainties and tariff impacts, estimating a minimal annual impact in the single-digit millions [20][21] - The management team is optimistic about the upcoming launch of brensocatib, expecting a favorable landscape for patient uptake and physician engagement [37][39] Other Important Information - The company is actively working on next-generation DPP1 inhibitors, targeting conditions like COPD and rheumatoid arthritis, with potential clinical trials expected to start next year [12][70] - Insmed plans to finalize clinical plans for phase three trials of TPIP based on data from ongoing phase two trials, with expectations for significant efficacy [16][17] Q&A Session Summary Question: What factors will influence the pricing of brensocatib in the U.S. and abroad? - Management indicated that pricing will be set in the U.S. first, allowing flexibility to respond to market conditions, with ARIKAYCE priced at parity across regions during its launch [34][35] Question: What trends are observed from the bronchiectasis disease awareness website? - Management noted a favorable backdrop with high patient interest and engagement, indicating readiness for a successful launch [37][39] Question: What are the key levers for transitioning interested patients to therapy? - The company is focusing on connecting diagnosed patients with treatment options and leveraging existing relationships in the pulmonology community to facilitate access [42][45] Question: How is the company preparing for the TPIP update? - Management emphasized the importance of pulmonary vascular resistance (PVR) as a key measure, with expectations for a placebo-adjusted reduction of 20% to indicate success [55][56] Question: What is the status of the brensocatib review process? - The FDA review process is on track, with no surprises reported during the mid-cycle review, and ongoing inspections are expected until the approval date [74][75]