Financial Data and Key Metrics Changes - In Q4 2025, total revenue reached $3.2 billion, a 10% increase compared to Q4 2024. For the full year 2025, total revenue was $12 billion, reflecting a 9% increase versus 2024 [32][33] - Non-GAAP net income for Q4 2025 was $1.3 billion, up 24% year-over-year, resulting in earnings per share of $5.03, a 26% increase compared to the prior year [37] - The company ended 2025 with $12.3 billion in cash, cash equivalents, and marketable securities, positioning it well for future investments [37] Business Line Data and Key Metrics Changes - Cystic fibrosis (CF) therapies generated a full year 2025 growth of 7% globally, with U.S. CF revenue growing 11% year-over-year [32][33] - CASGEVY achieved $54 million in revenue in Q4 and $116 million for the full year 2025, demonstrating continued momentum in patient initiations [34][35] - JOURNAVX delivered $27 million in sales in Q4 and $60 million for the full year, with substantial growth in quarterly prescriptions since its launch [34] Market Data and Key Metrics Changes - The CF population has seen a 3% annual increase over the last five years, contributing to revenue growth [22] - In Europe, reimbursement for ALYFTREK has been secured in key countries, including the UK, Germany, and Italy, expanding access to CFTR modulators [22][23] - CASGEVY's reimbursement agreements in the U.S. have reached approximately 90% access for both Medicaid and commercial patients [23] Company Strategy and Development Direction - The company aims to expand leadership in CF, accelerate adoption of CASGEVY, and grow JOURNAVX while advancing its renal franchise [6][29] - The renal pipeline is emerging as a key growth engine, with povetacicept positioned to address significant unmet needs in IgA nephropathy and membranous nephropathy [10][29] - The company is focused on commercial execution and innovation to drive sustained growth across multiple serious disease areas [6][29] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's ability to deliver on significant opportunities and drive sustained growth through commercial execution and innovation [6][40] - The guidance for 2026 anticipates total company revenue in the range of $12.95 billion to $13.1 billion, representing 8%-9% growth versus the prior year [38] - The company expects combined non-GAAP operating expenses to be in the range of $5.65 billion to $5.75 billion as it continues to invest in its late-stage clinical pipeline [39] Other Important Information - The company has initiated a rolling BLA submission for povetacicept, with expectations for expedited regulatory review [11] - The company is committed to maintaining comprehensive patient support programs to facilitate access to its therapies [29] Q&A Session Summary Question: Concerns about hypogammaglobulinemia adverse events related to povetacicept - Management indicated that while BAFF/APRIL inhibitors may decrease IgG levels, data from the RUBY-3 study showed no serious adverse events or infections associated with low IgG levels, suggesting a favorable benefit-risk profile [42][44] Question: Guidance details for CF component and ALYFTREK - Management provided total revenue guidance of $12.95 billion to $13.1 billion, with a non-CF contribution of $500 million or more, but did not break down specifics for ALYFTREK versus other products [49][51] Question: Payer access and reimbursement for povetacicept - Management reported positive engagements with payers, having conducted 74 meetings covering over 210 million lives, indicating strong interest in the upcoming products [55][60] Question: Expected results on proteinuria for povetacicept - Management emphasized the importance of magnitude of proteinuria response, referencing a 56% reduction seen in the RUBY-3 study as a benchmark for expected outcomes [62][64] Question: Differentiation of povetacicept in generalized myasthenia gravis - Management highlighted the engineered profile of povetacicept, which offers better potency and pharmacokinetics compared to existing treatments, positioning it as a promising option in a crowded market [68][70]

Financial Data and Key Metrics Changes - In Q4 2025, total revenue reached $3.2 billion, a 10% increase compared to Q4 2024, while full-year revenue was $12 billion, reflecting a 9% growth versus 2024 [32][33] - Non-GAAP net income for Q4 2025 was $1.3 billion, up 24% year-over-year, resulting in earnings per share of $5.03, a 26% increase compared to the prior year [37] - The company ended 2025 with $12.3 billion in cash, cash equivalents, and marketable securities, positioning it well for future investments [37] Business Line Data and Key Metrics Changes - Cystic fibrosis (CF) therapies generated full-year 2025 growth of 7% globally, with U.S. CF revenue growing 11% year-over-year [32][33] - CASGEVY achieved $54 million in revenue in Q4 and $116 million for the full year 2025, indicating strong patient initiations and first cell collections [34] - JOURNAVX delivered $27 million in sales in Q4 and $60 million for the full year, with significant growth in quarterly prescriptions since its launch [34][35] Market Data and Key Metrics Changes - The CF population has seen a 3% annual increase over the last five years, contributing to revenue growth [20] - In Europe, reimbursement for ALYFTREK has been secured in key countries, enhancing market access [21] - The company has engaged with payers covering over 210 million lives regarding the renal pipeline, indicating strong interest and education on IgAN [60] Company Strategy and Development Direction - The company aims to expand leadership in CF, accelerate adoption of CASGEVY, and grow JOURNAVX while advancing its renal franchise [6][29] - The renal pipeline is expected to rival the scale of the CF business, with a focus on patient-centric approaches and securing reimbursement [29][30] - The company is committed to serial innovation and comprehensive patient support programs to enhance access to its therapies [29][30] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's ability to deliver sustained growth through commercial execution and innovation [6] - The guidance for 2026 anticipates total revenue in the range of $12.95 billion to $13.1 billion, representing 8%-9% growth versus the prior year [38] - The company expects combined non-GAAP operating expenses to be in the range of $5.65 billion to $5.75 billion as it continues to invest in its late-stage clinical pipeline [39] Other Important Information - The company has initiated a rolling BLA submission for povetacicept in IgAN, with breakthrough therapy designation granted by the FDA [11][12] - The company plans to double the size of its field force for JOURNAVX in Q2 2026 to drive prescription growth [26] Q&A Session Summary Question: Concerns about hypogammaglobulinemia adverse events related to pove - Management indicated that while low IgG levels are expected, data from the RUBY-3 study showed no serious adverse events or infections associated with low IgG levels, suggesting a favorable benefit-risk profile [43][44] Question: Guidance details for CF component and ALYFTREK performance - Management provided total revenue guidance of $12.95 billion to $13.1 billion, with a non-CF contribution of $500 million or more, while noting strong international launch contributions for ALYFTREK [49][51][52] Question: Payer access and reimbursement for pove - Management reported positive engagements with payers, indicating strong interest in the product and ongoing discussions to ensure access [59][60] Question: Expected results on proteinuria for pove - Management emphasized the importance of proteinuria response magnitude, referencing RUBY-3 results as a benchmark for expected outcomes in the RAINIER trial [62][64] Question: Rationale for studying pove in generalized myasthenia gravis - Management highlighted the significant patient population and limitations of current treatments, positioning pove as a potentially superior option due to its mechanism of action [70][72]

Financial Data and Key Metrics Changes - In Q4 2025, total revenue reached $3.2 billion, a 10% increase compared to Q4 2024. For the full year 2025, total revenue was $12 billion, reflecting a 9% increase versus 2024 [33] - Full year 2025 growth in cystic fibrosis (CF) therapies was 7% globally, with U.S. CF revenue growing 11% year-over-year [34] Business Line Data and Key Metrics Changes - CASGEVY generated $54 million in revenue in Q4 and $116 million for the full year 2025, with continued momentum in patient initiations and first cell collections [34] - JOURNAVX delivered $27 million in sales in Q4 and $60 million for the full year, showing substantial growth in quarterly prescriptions since its launch [34] Market Data and Key Metrics Changes - Internationally, CF revenue grew 2% year-over-year, driven by the penetration of KAFTRIO and contributions from ALYFTREK, partially offset by a $200 million decline in Russia sales [34] - The company secured reimbursement for ALYFTREK in key European countries, enhancing access for patients [21] Company Strategy and Development Direction - The company aims to expand leadership in CF, accelerate adoption of CASGEVY, and grow JOURNAVX while advancing its renal franchise, starting with povetacicept in IgAN [5] - The renal pipeline is expected to become a key growth engine, potentially rivaling the scale of the CF business [29] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's ability to deliver sustained growth through commercial execution and innovation across multiple serious disease areas [5] - The guidance for 2026 anticipates total company revenue in the range of $12.95 billion to $13.1 billion, representing 8%-9% growth versus the prior year [39] Other Important Information - The company ended 2025 with $12.3 billion in cash, cash equivalents, and marketable securities, positioning it well for future investments [38] - The fourth quarter gross margin was 85.7%, reflecting the product mix and investments in manufacturing optimization [35] Q&A Session Summary Question: Concerns about hypogammaglobulinemia adverse events related to povetacicept - Management indicated that while BAFF/APRIL inhibitors may decrease IgG levels, data from the RUBY-3 study showed no serious adverse events or infections associated with low IgG levels, suggesting a favorable benefit-risk profile [44][45] Question: Guidance details for CF component relative to ALYFTREK and TRIKAFTA - Management provided total revenue guidance of $12.95 billion to $13.1 billion, with a non-CF contribution of $500 million or more, but did not break down specifics for ALYFTREK versus other products [52] Question: Payer access and reimbursement for povetacicept - Management reported positive engagement with payers, having conducted 74 engagements covering over 210 million lives, indicating strong interest in the upcoming products [62] Question: Expected results on proteinuria for povetacicept - Management highlighted that a significant reduction in proteinuria, similar to the RUBY-3 study results, would be clinically meaningful and important for long-term outcomes [66] Question: Mix between retail and hospital settings for JOURNAVX - Management noted that the prescription mix concluded at about 50/50 between retail and hospital settings in 2025, with expectations for a shift towards retail in the future [83]

FIRST QUARTER 2025 FINANCIAL RESULTS Fourth Quarter and Full Year 2025 Financial Results ©2026 Vertex Pharmaceuticals Incorporated ©2026 Vertex Pharmaceuticals Incorporated ©2025 Vertex Pharmaceuticals Incorporated Presentation intended for the investment community Agenda Introduction Susie Lisa, CFA, Senior Vice President, Investor Relations CEO Perspective and Pipeline Update February 12, 2026 Reshma Kewalramani, M.D., Chief Executive Officer and President Commercial Update Duncan McKechnie, Executive Vic ...

Core Viewpoint - Vertex Pharmaceuticals forecasts 2026 revenue largely in line with analysts' estimates, driven by growth in cystic fibrosis treatments and contributions from newer products [1] Group 1: Revenue Forecast - The company anticipates revenue for 2026 to align closely with analyst expectations [1] - Growth is expected primarily from cystic fibrosis treatments [1] Group 2: Product Contributions - Newer products are also expected to contribute to the revenue growth [1]

Financial Performance - Full year total revenue for 2025 was $12.0 billion, a 9% increase compared to 2024; fourth quarter total revenue was $3.19 billion, a 10% increase compared to Q4 2024[1][3][8] - In the U.S., total revenue for 2025 increased 13% to $7.55 billion, driven by strong CF patient demand and higher realized net prices[3][8] - Vertex reported total revenues of $3,190.0 million for the three months ended December 31, 2025, an increase of 9.6% compared to $2,912.0 million for the same period in 2024[40] - GAAP net income for Q4 2025 was $1.2 billion, compared to $913 million in Q4 2024, primarily driven by increased product revenue[7] - Vertex's net income for the twelve months ended December 31, 2025, was $3,953.2 million, compared to a net loss of $535.6 million for the same period in 2024[40] - GAAP operating income for Q4 2025 was $1,205.9 million, compared to $1,026.0 million in Q4 2024, representing a 17.5% increase[48] - Non-GAAP operating income for the twelve months ended December 31, 2025 was $5,263.1 million, up from $695.6 million in 2024, indicating a significant growth[48] - GAAP net income for the twelve months ended December 31, 2025 was $3,953.2 million, compared to a net loss of $535.6 million in 2024[48] - Cash, cash equivalents, and marketable securities increased to $6,608.1 million as of December 31, 2025, from $6,115.9 million in 2024, showing a growth of 8.1%[51] - Total assets rose to $25,643.0 million in 2025, up from $22,533.2 million in 2024, reflecting a 13.4% increase[51] Revenue Guidance and Expectations - The company provides full year 2026 total revenue guidance of $12.95 billion to $13.1 billion, with non-CF products expected to contribute $500 million or more in revenue[1][13][14] - Vertex's financial guidance for combined GAAP R&D, AIPR&D and SG&A expenses in 2026 is $6.3 to $6.45 billion, including approximately $100 million of anticipated AIPR&D expenses[14][15] - The company anticipates over $500 million in non-CF product revenue in 2026, indicating a focus on expanding its product portfolio[54] Product Development and Approvals - Vertex expects to submit for approval of ALYFTREK in children 2 to 5 years of age in the first half of 2026, following positive pivotal study results[18] - Vertex initiated the rolling BLA filing for U.S. accelerated approval of povetacicept in IgAN in Q4 2025, with interim analysis data expected in the first half of 2026[24][27] - The company expects to complete the Phase 2 portion of the OLYMPUS study for povetacicept in mid-2026, with the Phase 3 portion anticipated to start thereafter[30] - Vertex plans to initiate a Phase 2 proof-of-concept study for povetacicept in gMG in the first half of 2026[30] - Vertex completed enrollment in the AMPLITUDE Phase 2/3 trial of inaxaplin and expects to share interim analysis data in late 2026 or early 2027[30] - The AGLOW study, evaluating VX-407 in patients with specific PKD1 gene variants, is expected to complete enrollment by the end of 2026, targeting approximately 30,000 patients[36] Research and Development Expenses - Combined GAAP and non-GAAP R&D, Acquired IPR&D and SG&A expenses for Q4 2025 were $1.52 billion and $1.36 billion, respectively, compared to $1.46 billion and $1.30 billion in Q4 2024[4] - Vertex's combined non-GAAP R&D, AIPR&D, and SG&A expenses for the twelve months ended December 31, 2025, were $5,118.2 million, a decrease from $8,821.7 million in 2024[46] Strategic Partnerships and Coverage - Vertex secured commercial coverage for JOURNAVX with all three national PBMs, providing access for over 200 million individuals across commercial and government payers[20] - The company has received multiple designations for zimislecel, including RMAT and Fast Track from the FDA, and PRIME from the EMA[30] - Vertex entered into an exclusive global license agreement with WuXi Biologics for the development of a trispecific T cell engager for autoimmune diseases, currently in preclinical development[35] Product Revenue Performance - Product revenues from TRIKAFTA/KAFTRIO were $2,572.5 million for the three months ended December 31, 2025, a decrease of 5.4% from $2,720.8 million in the same period of 2024[43] - Expectations for continued growth in cystic fibrosis (CF) treatments include increasing patient access through new approvals and reimbursement agreements[54]

Core Insights - Vertex Pharmaceuticals has established itself as a leader in the cystic fibrosis (CF) market, demonstrating consistent revenue and profit growth over the past decade [1] - The company has successfully expanded its treatment portfolio beyond CF, gaining approvals for gene editing treatment Casgevy and non-opioid pain management drug Journavx [2] - Vertex's stock has seen significant appreciation, climbing over 60% in the past three years, as investor confidence has returned following successful product launches [3] Company Strengths - Vertex's ongoing strength in the CF market is a primary reason for long-term investment, with the company expected to maintain its leadership through the late 2030s due to strong intellectual property [5] - The latest CF drug, Alyftrek, has shown even greater efficacy than its previous blockbuster, Trikafta, contributing to the company's growth [5] - Vertex's drugs, Alyftrek and Trikafta, are effective for 90% of CF patients, and the company is actively working on a candidate, VX-522, to address the needs of patients who cannot take current treatments [6]

Core Viewpoint - Vertex Pharmaceuticals (VRTX) is expected to exceed expectations in its fourth-quarter and full-year 2025 results, with revenue estimates at $3.17 billion and earnings at $5.07 per share [2]. Group 1: Revenue Drivers - The anticipated revenue growth for VRTX in Q4 is primarily driven by strong demand for its cystic fibrosis (CF) medication, Trikafta/Kaftrio, with sales estimated at $2.57 billion [3]. - Despite the growth in Trikafta/Kaftrio sales, there may be a decline in sales for other CF drugs such as Symdeko, Orkambi, and Kalydeco due to market competition [4]. - The sales performance of VRTX's fifth CF drug, Alyftrek, is also a focal point, with expectations of continued sequential sales growth following a positive launch in the U.S. and Europe [5]. Group 2: New Product Sales Expectations - VRTX's gene therapy, Casgevy, is projected to generate around $40 million in sales for Q4 2025, following a successful launch and reimbursement efforts globally [10]. - The non-opioid pain medicine Journavx is expected to see increased sales in Q4 as prescription volumes rise, despite a slower start in the previous quarter [11]. - Updates on VRTX's pipeline candidates for various diseases are anticipated during the upcoming earnings call, indicating ongoing development in multiple therapeutic areas [12]. Group 3: Earnings Surprise History - VRTX has a mixed earnings surprise history, having beaten estimates in two of the last four quarters, with an average surprise of 2.01% [13]. - The company is predicted to achieve an earnings beat this time, supported by a positive Earnings ESP of +5.38% and a Zacks Rank of 3 [16].

Core Viewpoint - Vertex Pharmaceuticals has underperformed the market with a less than 2% increase over the past year and is set to report earnings on February 12, raising questions about whether it is a good time for investors to buy the stock [1] Group 1: Recent Earnings Performance - In the third quarter earnings report on November 3, Vertex reported a revenue increase of 11% year over year, reaching $3.08 billion, while earnings per share (EPS) rose by only 4.7% to $4.20 due to increased research and development expenses [2] - The market reacted negatively to the earnings report, with the stock dropping over 1% on the announcement day and continuing to decline by more than 3% in the following days, primarily due to disappointing sales of newer therapies [2] Group 2: Product Portfolio and Sales - Vertex has five cystic fibrosis (CF) therapies, with Trikafta being the largest revenue generator, bringing in over $7.7 billion in revenue through the first nine months of 2025 and having patent protection until 2037 [3] - Alyftrek, recently approved by the FDA in December 2024, is viewed as a potential successor to Trikafta, but its sales of $247 million in the third quarter fell short of analysts' expectations [4] - The launch of the non-opioid pain therapy Journavx has also been underwhelming, with sales of $33 million in the quarter, disappointing some analysts [5] Group 3: Future Expectations - For the full year 2025, Vertex is forecasting revenue between $11.9 billion and $12 billion, requiring fourth-quarter revenue of $3.1 billion to $3.2 billion to meet this target [6] - Analysts predict quarterly revenue of $3.17 billion, representing an 8.9% year-over-year increase, and an EPS of $5.07, a 27.4% rise compared to the same period last year [6]

Core Viewpoint - Vertex Pharmaceuticals has faced challenges over the past year, including disappointing quarterly updates and clinical trial failures, leading to a slight decline in its stock price over the trailing 12 months [1]. Financial Performance Expectations - Vertex Pharmaceuticals is set to release its fourth-quarter and full-year 2025 financial results on February 12, with projected revenues between $11.9 billion and $12 billion, indicating at least 8% year-over-year growth [2][5]. - The company remains the sole leader in the cystic fibrosis (CF) medication market, with its CF drug portfolio expected to contribute to solid top-line growth in the upcoming quarterly update [5]. Product Development and Market Dynamics - There is potential for Vertex to exceed its revenue guidance, possibly due to advancements in other products like Casgevy and Journavx, which treat blood-related disorders and acute pain, respectively [6]. - Journavx has already gained third-party coverage for over 170 million U.S. patients, while Casgevy's uptake has been slower due to its complex gene-editing nature [6][7]. Future Clinical Progress - Significant clinical advancements are anticipated for Vertex in 2025, particularly with zimislecel for Type 1 diabetes, inaxaplin for kidney disease, and povetacicept for IgA nephropathy [8]. - Clinical or regulatory updates for zimislecel may be expected in the upcoming quarterly update, but the stock's short-term movement remains uncertain [8].