Financial Data and Key Metrics Changes - Alnylam reported total net product revenues of $672 million for Q2 2025, representing a 64% year-over-year growth [9][37] - The TTR franchise generated $544 million in revenues, reflecting a 77% increase year-over-year [8][11] - The company increased its total net product revenue guidance for 2025 from a range of $2.05 billion to $2.25 billion to a revised range of $2.65 billion to $2.8 billion, a 27% increase at the midpoint [9][42] Business Line Data and Key Metrics Changes - The TTR franchise in the U.S. saw combined sales of ONPATTRO and Ambutra rise by 80% compared to Q1 2025, driven primarily by the launch of Ambutra [14][16] - The rare franchise, including GIVLAARI and OXLUMO, delivered $128 million in combined Q2 sales, up 24% year-over-year [12][11] - The U.S. TTR franchise grew 125% compared to 2024, primarily due to the demand from the ATTR Centimeters launch [15][11] Market Data and Key Metrics Changes - International markets are expected to contribute to Ambutra's revenues in the second half of 2025, with launches in Germany and Japan [15][27] - The U.S. TTR franchise achieved $383 million in Q2 2025, indicating robust growth dynamics [16][11] - The company has yet to recognize any ATTR Centimeters revenue internationally, but anticipates strong growth as international launches commence [15][11] Company Strategy and Development Direction - Alnylam focuses on three core elements: TTR leadership, growth through innovation, and strong financial performance [6][7] - The company aims to establish long-term leadership in TTR and expand its pipeline of RNAi therapeutics [6][9] - Alnylam is committed to disciplined capital allocation and sustainable growth, with a focus on patient and customer centricity [28][9] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the strong early performance of Ambutra and its potential for sustainable growth [9][28] - The company highlighted the importance of real-world evidence generation and the development of next-generation RNAi therapeutics [27][9] - Management remains optimistic about achieving its Alnylam Pizza Fit by 25 goals, reinforcing its position as a top-tier biotech company [10][9] Other Important Information - The FDA granted fast track designation to nucrisiran for ATTR Centimeters, enhancing its development prospects [9][31] - Alnylam's gross margin on product sales was 79% for the quarter, down from 84% in 2024, primarily due to increased royalties [39][37] - The company ended the quarter with cash, cash equivalents, and marketable securities of $2.9 billion, an increase from $2.7 billion at the end of 2024 [41][37] Q&A Session Summary Question: Can you provide details on the patient profiles for Ambutra? - Management noted broad uptake across first-line patients and stabilizer progressors, with a healthy mix emerging [48][49] Question: How are you thinking about net price for Ambutra moving forward? - The expectation is for a mid-single-digit reduction in net price for Ambutra in 2025 compared to 2024 [56][57] Question: Was there any bolus effect in cardiomyopathy scripts in Q2? - Management confirmed solid commercial execution and emphasized that results are not just a flash in the pan, expecting continued sustainable growth [60][61] Question: Can you comment on the criteria physicians are using for stabilizer progressors? - Clinical evidence suggests that 30% to 50% of patients on stabilizers may progress, and physicians are using a variety of factors to determine treatment [81][82] Question: How should we think about the rate of new patient starts per quarter? - Management expects both categories of patients to continue growing, with a balanced uptake between new patients and stabilizer progressors [97][98]

Financial Data and Key Metrics Changes - Alnylam reported total net product revenues of $672 million for Q2 2025, representing a 64% year-over-year growth [9][35] - The TTR franchise generated revenues of $544 million, reflecting a 77% increase year-over-year [7][35] - The company increased its total net product revenue guidance for 2025 from a range of $2.05 billion to $2.25 billion to a revised range of $2.65 billion to $2.8 billion, marking a $575 million or 27% increase at the midpoint [9][39] Business Line Data and Key Metrics Changes - The TTR franchise in the U.S. saw combined Q2 sales of ONPATTRO and Ambutra rise by 80% compared to Q1, driven primarily by the Ambutra launch [13][35] - The rare franchise, including GIVLAARI and OXLUMO, delivered $128 million in combined Q2 sales, up 24% year-over-year [12][35] - The U.S. TTR franchise grew 125% compared to 2024, primarily due to the ATTR Centimeters launch [14] Market Data and Key Metrics Changes - Approximately 1,400 cardiomyopathy patients were receiving Ambutra by the end of Q2, contributing an estimated $150 million in revenue [13][23] - International markets are expected to begin contributing to Ambutra sales in the second half of the year, with launches in Germany and Japan [8][26] - The U.S. TTR franchise achieved $383 million in Q2, representing an 80% quarter-over-quarter growth [15] Company Strategy and Development Direction - Alnylam is focusing on TTR leadership, growth through innovation, and strong financial performance as key strategic pillars [4][6] - The company aims to establish itself as a top-tier biotech firm by delivering sustainable innovation and value creation [5][10] - The launch of Ambutra is seen as a flagship commercial franchise with robust long-term growth potential [6][27] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the strong early launch performance of Ambutra and the potential for continued growth [9][39] - The company remains committed to advancing care through real-world evidence generation and the development of next-generation RNAi therapeutics [26][34] - Management highlighted the importance of disciplined execution and patient-centricity in driving long-term growth [27][39] Other Important Information - The FDA granted fast track designation to nucrisiran for ATTR Centimeters, which is expected to streamline the review process [9][31] - The gross margin on product sales was reported at 79%, down from 84% in the previous year, primarily due to increased royalties on Ambutra [37] Q&A Session Summary Question: Details on patient profiles for Ambutra - Management noted broad uptake across first-line patients and stabilizer progressors, with a healthy share of first-line patients emerging [45][46] Question: Thoughts on net price for Ambutra - The expectation is for a mid-single-digit reduction in net price for Ambutra in 2025 compared to 2024 [50][52] Question: Bolus effect in cardiomyopathy scripts - Management indicated solid commercial execution and emphasized that results are not just a flash in the pan, expecting continued sustainable growth [56][57] Question: Assumptions underpinning updated TTR franchise guidance - Management expects steady growth in both first-line and second-line patient flows, with a healthy trend in first-line use observed [65][70] Question: Criteria for stabilizer progressors - Clinical evidence suggests that one-third to half of patients on stabilizers progress, and physicians are using a variety of factors to determine eligibility for Ambutra [76][82] Question: Rate of new patient starts per quarter - Management is pleased with the initial uptake and expects both categories of patients to continue growing, though specific numbers will not be reported [91][94] Question: Payer requirements for Ambutra treatment - Broad coverage is reported across Medicare and commercial payers, with minimal step edits required for access [98][102]

Financial Data and Key Metrics Changes - The company is preparing for the PDUFA date of September 22 for apategromab in SMA, indicating a significant milestone in its financial outlook [11] - The management has emphasized a strong cash position, with a runway extending into early 2027, allowing for strategic investments without immediate equity issuance [42][44] Business Line Data and Key Metrics Changes - The company has seen robust clinical development for ipilimumab in SMA, with a Phase III SAFIRE trial enrolling 188 patients, demonstrating clinically meaningful benefits [12][13] - The obesity program is set to share Phase II data from the EMBRAZE trial, focusing on the preservation of lean mass in patients receiving tirzepatide [28][29] Market Data and Key Metrics Changes - The company is under review with the FDA and the European Medicines Agency, with plans for a substantial launch in the U.S. and thoughtful expansion into Europe and Asia Pacific [25][26] - There are approximately 35,000 patients worldwide who have received at least one SMN targeted therapy, highlighting a significant market opportunity for the company's products [26][40] Company Strategy and Development Direction - The company aims to scale its growth into global commercialization, focusing on the approval of ipilimumab in multiple countries [3][25] - The strategy includes leveraging existing assets while exploring new indications for ipilimumab and SRK-439 in rare neuromuscular disorders [9][38] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of ipilimumab to reverse the trend of motor function loss in SMA patients, positioning it as a new standard of care [15][19] - The company is committed to making a meaningful difference for patients and ensuring that no patient is left behind in accessing their therapies [27][44] Other Important Information - The company is considering the implications of pricing strategies based on the rarity and severity of diseases like SMA, as well as the clinical benefits demonstrated [39][40] - The management is cautious about the investment in cardiometabolic and obesity indications, focusing instead on rare severe neuromuscular disorders [33][44] Q&A Session Summary Question: What are the expectations for the label regarding apategromab in SMA? - Management expects a broad label based on the robust data from the Phase III SAFIRE trial and the consistency of results across patient subgroups [12][13] Question: How does the drug fit into the existing treatment paradigm for SMA? - The company believes ipilimumab can provide significant benefits beyond existing SMN targeted therapies, particularly for patients who have started to lose motor function again [14][15] Question: What is the company's strategy for the obesity program? - The company plans to present Phase II data from the EMBRAZE trial, focusing on the preservation of lean mass in patients receiving tirzepatide [28][29] Question: How does the company view the regulatory pathway for obesity treatments? - Management acknowledges the evolving view of the FDA and the need to demonstrate both weight loss and preservation of lean mass in future trials [32][33] Question: What is the current cash position and runway for the company? - The company has a strong cash position with a runway extending into early 2027, allowing for strategic investments without immediate equity issuance [42][44]

Summary of Alnylam Pharmaceuticals (ALNY) FY Conference Call - June 09, 2025 Company Overview - **Company**: Alnylam Pharmaceuticals (ALNY) - **Industry**: Biotechnology - **Key Product**: Ambutra for TTR cardiomyopathy Core Points and Arguments 1. **European Approval**: Alnylam secured European approval for Ambutra for cardiomyopathy, enhancing its global momentum in the TTR franchise [3][4] 2. **Five-Year Strategy**: The company is on track to achieve its 2021 five-year goals, including sustainable non-GAAP profitability by the end of 2025 [5][6] 3. **Revenue Growth**: Alnylam's revenues are primarily driven by the TTR franchise, with a robust pipeline for future growth [6][7] 4. **Pipeline Programs**: - Zarbisiran for hypertension and a program for Huntington's disease are highlighted as significant growth levers [10][11] - ARN 6400 targeting plasminogen is noted for its potential as a vessel hemolytic agent [12] 5. **Market Dynamics**: The company is experiencing rapid progress in treating patients with TTR cardiomyopathy, with over 50% of priority health systems having Ambutra on formulary [16][17] 6. **Financial Guidance**: Alnylam provided guidance for TTR revenue between $1.6 billion and $1.725 billion, representing approximately 36% year-over-year growth at the midpoint [22] 7. **Polyneuropathy Growth**: The polyneuropathy segment is growing at a rate of 28-34% year-over-year, with expectations for continued growth alongside cardiomyopathy [23][24] 8. **Patient Access**: The company reports broad access across payer types, with the majority of patients paying $0 out of pocket [33][35] 9. **Patient Services**: Alnylam has a comprehensive patient services organization to support access and adherence, with over 95% adherence rates in polyneuropathy [31][38] 10. **Pricing Strategy**: The company anticipates modest adjustments to Ambutra pricing over time, but specifics are not yet available [42] 11. **Global Launch Plans**: Alnylam plans to launch Ambutra in Germany and Japan in the second half of 2025, with additional launches expected throughout 2026 [45] 12. **Clinical Data**: The HELIOS B trial data shows a 36% reduction in all-cause mortality and a 33% reduction in cardiovascular mortality, reinforcing the drug's value proposition [47][48] 13. **Pipeline Expansion**: Alnylam is committed to advancing its pipeline, with multiple programs in various stages of development, including obesity and diabetes treatments [62][64] Additional Important Content - **Regulatory Strategy**: The orphan drug designation for Alnylam's products has positioned the company favorably in negotiations related to pricing and access [14] - **Commercial Strategy**: The company emphasizes a "buy and build" approach for its products, focusing on establishing a strong commercial footprint [20] - **Innovation Engine**: Alnylam aims to deliver 2-4 new INDs per year, expanding its siRNA technology across various tissues [59][60] - **Capital Allocation**: The company plans to focus on progressing its existing pipeline rather than pursuing significant business development opportunities at this time [64]

Summary of Alnylam Pharmaceuticals (ALNY) 2025 Conference Call Company Overview - **Company**: Alnylam Pharmaceuticals (ALNY) - **Event**: Bank of America Healthcare Conference - **Date**: May 14, 2025 Key Industry Insights - **Impact of Executive Orders**: The recent executive order regarding most favored nation pricing is still developing, making it difficult to assess its implications for Alnylam. However, the company benefits from having orphan drugs in the U.S., which may exempt them from future price negotiations under the IRA [3][4] - **Tariffs**: Current tariffs do not materially impact Alnylam's guidance, as the majority of their manufacturing is done in the U.S. through contract manufacturing organizations (CMOs) [8][9] Product Launch and Market Dynamics - **Cardiomyopathy Launch**: The launch of the cardiomyopathy product is a significant focus. Initial metrics show that 50% of health systems have completed the PNT process and are on formulary within five weeks of launch, which is faster than anticipated [18][19] - **Revenue Guidance**: Alnylam has guided for TTR revenue between $1.6 billion and $1.725 billion for the year, representing a 36% growth at the midpoint [23] - **Patient Access**: Approximately 70% of patients on the drug have zero out-of-pocket costs, primarily due to Medicare fee-for-service coverage [30] Competitive Landscape - **Market Size and Segmentation**: There are about 18,000 new patients initiating therapy annually, with a significant opportunity to increase diagnosis rates, currently at a 20% diagnosis rate [48] - **First-Line vs. Second-Line Treatment**: Alnylam is focused on first-line treatment due to the progressive nature of the disease and the need for effective early intervention [49] Patient and Physician Engagement - **Patient Compliance**: Alnylam has observed good compliance rates with their injectable therapies, which may be more effective than oral alternatives in ensuring patients receive the necessary treatment [58][60] - **Physician Awareness**: There is a good level of awareness among physicians regarding Alnylam's products, but further education is needed as the company expands its prescriber base [74] Future Outlook - **Revenue Reporting**: Alnylam will not be able to report revenue separately for Ambutra PN and Ambutra Centimeters due to them being the same product under one SKU [67] - **Market Positioning**: Alnylam is uniquely positioned to capture a broad patient base, including both hereditary and wild-type patients, due to its comprehensive label [72][73] Additional Considerations - **Direct-to-Consumer (DTC) Marketing**: Alnylam is engaging in targeted DTC marketing but is not heavily investing in broad campaigns like some competitors [65] - **Value-Based Agreements (VBAs)**: The company is extending its VBAs to ensure adherence and compliance, which is favorable for both patients and payers [60][61]

Financial Data and Key Metrics Changes - In Q1 2025, Alnylam Pharmaceuticals reported total product revenues of $469 million, representing a 28% year-over-year growth, driven by a 36% increase in the TTR franchise revenues [8][40] - Collaboration revenue decreased by 16% to $99 million compared to the previous year, primarily due to a milestone achieved in Q1 2024 [41] - Non-GAAP operating profit for the quarter was $75 million, reflecting a $73 million improvement year-over-year [43] Business Line Data and Key Metrics Changes - The TTR franchise generated $359 million in global net revenues, a 36% increase compared to Q1 2024, with U.S. sales growing by 45% year-over-year [15][16] - The rare disease franchise, including GIVLAARI and OXLUMO, delivered $109 million in combined product sales, representing an 8% growth year-over-year [14] Market Data and Key Metrics Changes - In the U.S., the TTR franchise saw a 32% increase in demand driven by ongoing ONPATTRO patient uptake, with Ambutra capturing approximately 70% of new patient starts in Q1 2025 [16][19] - Internationally, the TTR franchise grew by 24% compared to Q1 2024, primarily due to increased demand for Ambutra [17] Company Strategy and Development Direction - Alnylam aims to become the global leader in TTR, focusing on broad access, driving awareness, and supporting treatment initiation for patients [7][10] - The company is committed to achieving sustainable non-GAAP profitability in 2025 and emphasizes a disciplined approach to capital allocation [9][11] Management's Comments on Operating Environment and Future Outlook - Management acknowledged uncertainties related to potential policy changes, including tariffs and FDA personnel reorganization, but expressed confidence in Alnylam's positioning to mitigate impacts [9][45] - The management reiterated guidance for continued growth and a strong launch in ATTR cardiomyopathy, projecting a robust 36% year-over-year growth in TTR franchise revenues [27][39] Other Important Information - Alnylam received FDA approval for Ambutra as the first and only silencer approved in the U.S. for ATTR Centimeters, with a successful launch underway [20][30] - The company is advancing its pipeline with several pivotal studies planned, including TRITON Centimeters and TRITON PN [47] Q&A Session Summary Question: Initial patients starting treatment and prescriber base - Management noted a broad uptake among both experienced and new prescribers, indicating strong early momentum in the cardiomyopathy launch [51][53] Question: Revenue benchmarks for ATTR cardiomyopathy - Management clarified that the revenue contribution from ATTR cardiomyopathy was not included in Q1 results, as the approval came late in the quarter [57][62] Question: Commercial strategies to capture market share - Management highlighted the unique mechanism of action of Ambutra and its potential as a first-line treatment, which is driving physician interest [64][66] Question: Use of Quick Start program and formulary access - Management reported limited use of the Quick Start program, with most patients paying zero copay, and confirmed no price difference between indications [70][72] Question: Impact of TrueBee on Ambutra's launch - Management indicated no headwinds from TrueBee's launch, emphasizing the growing and unsatisfied market for ATTR treatments [76][78] Question: Metrics on health systems and patient initiation - Management confirmed that over half of the 170 priority health systems have Ambutra on formulary, with many already initiating treatments [97][99]

Financial Data and Key Metrics Changes - In Q1 2025, Alnylam Pharmaceuticals reported total product revenues of $469 million, representing a 28% year-over-year growth, driven by a 36% increase in the TTR franchise revenues [6][37] - Collaboration revenue decreased by 16% to $99 million compared to the previous year, primarily due to a milestone achieved in Q1 2024 [38] - Gross margin on product sales remained at 85%, consistent with Q1 2024, but is expected to decrease for the remainder of the year due to escalating royalty rates [39][41] Business Line Data and Key Metrics Changes - The TTR franchise generated $359 million in global net revenues, a 36% increase year-over-year, with U.S. sales growing by 45% [14][15] - The rare disease franchise, including GIVLAARI and OXLUMO, delivered $109 million in combined product sales, reflecting an 8% growth year-over-year [13] - The TTR franchise's growth was primarily driven by increased demand for ONPATTRO and Ambutra, with a 32% increase in demand noted [15][16] Market Data and Key Metrics Changes - In the U.S., Ambutra captured approximately 70% of new patient starts in the first quarter of 2025, indicating strong market leadership despite new competition [18] - Internationally, the TTR franchise grew by 24% compared to the first quarter of 2024, driven by robust patient uptake [16] - The company noted that about 80% of the global addressable population remains untreated, presenting significant growth opportunities [19] Company Strategy and Development Direction - Alnylam aims to become the global leader in TTR, focusing on broad access, driving awareness, and supporting treatment initiation for patients [5][9] - The company is committed to achieving sustainable non-GAAP profitability in 2025 while continuing to advance its high-value pipeline [7][10] - Alnylam's strategy includes leveraging its innovative pipeline with multiple multibillion-dollar opportunities and maintaining strong financial performance through disciplined capital allocation [9][10] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's positioning despite uncertainties related to potential policy changes, tariffs, and FDA reorganizations [7][8] - The management highlighted the strong early progress in the launch of Ambutra for ATTR cardiomyopathy and reiterated guidance for continued growth [6][37] - The company remains optimistic about achieving its 2025 goals, which include expanding access to its therapies and enhancing patient outcomes [10][26] Other Important Information - Alnylam received FDA approval for Ambutra as the first and only silencer approved in the U.S. for ATTR cardiomyopathy, with positive opinions from regulatory bodies in Brazil and the EU [20][29] - The company is advancing its pipeline with new clinical programs targeting various diseases, including a Phase I study for ALN434 targeting Type 2 diabetes [34][35] Q&A Session Summary Question: What is the profile of prescribers for Ambutra? - Management noted a broad uptake among both experienced prescribers and new doctors, indicating strong initial engagement with the product [48][51] Question: How does the revenue from ATTR cardiomyopathy compare to previous products? - Management clarified that the revenue from ATTR cardiomyopathy did not contribute to Q1 results, as the approval came late in the quarter [55][60] Question: What strategies are being employed to compete with tafamidis? - Management emphasized the unique mechanism of action of Ambutra and its compelling clinical data, which positions it as a first-line treatment option [62][64] Question: What are the dynamics of reimbursement for Ambutra? - Management explained that Ambutra has a single price across indications and highlighted the effectiveness of their patient support programs in facilitating access [68][70] Question: What are the expectations for formulary inclusion? - Management aims to complete formulary inclusion for all priority health systems by year-end, with encouraging early results already seen [81][82] Question: How is the early uptake of Ambutra characterized? - Management indicated that early uptake includes both switch patients and new patients, reflecting a strong initial market response [100][102]