Corporate Presentation May 2025 Forward Looking Statements These slides contain forward-looking statements that involve risks and uncertainties. These statements relate to future events or our future financial or operational performance and involve known and unknown risks, uncertainties and other factors that could cause our actual results or levels of activity, performance or achievement to differ materially from those expressed or implied by these forward-looking statements. In some cases, you can identif ...

Core Viewpoint - Alnylam Pharmaceuticals reported better-than-expected financial results for Q1 2025, with adjusted losses narrower than estimates and significant revenue growth driven by strong product sales, particularly for Amvuttra [1][2][16]. Financial Performance - The company reported total revenues of $594.2 million, exceeding the Zacks Consensus Estimate of $588.2 million, and reflecting a 20% year-over-year increase [2]. - Net product revenues reached $468.5 million, up 28% year-over-year, primarily due to increased demand for Amvuttra, Givlaari, and Oxlumo [2][6]. - Net revenues from collaborators were $99.2 million, down 16% from the previous year, largely due to a prior milestone payment from Roche [3]. Product Sales - Amvuttra generated sales of $310 million, a 59% increase year-over-year, and surpassed estimates [6]. - Givlaari recorded sales of $67 million, a 15% increase year-over-year, but slightly missed estimates [7]. - Oxlumo's sales were $42.1 million, remaining flat year-over-year and missing estimates [7]. Expenses and Cash Position - Adjusted R&D expenses were approximately $241.3 million, remaining stable year-over-year [10]. - Adjusted SG&A expenses increased by 12% to $207 million, driven by marketing efforts for Amvuttra [11]. - Cash, cash equivalents, and marketable securities totaled $2.63 billion as of March 31, 2025, down from $2.69 billion at the end of 2024 [11]. Guidance and Collaborations - The company reiterated its 2025 financial guidance, expecting net product revenues between $2.05 billion and $2.25 billion, and collaboration revenues between $650 million and $750 million [12]. - Alnylam is advancing several collaborations, including with Regeneron and Roche, which are expected to enhance its product pipeline and revenue streams [13][14][17]. Market Performance - Year-to-date, Alnylam's stock has gained 8.4%, outperforming the industry, which has seen a decline of 1.8% [8].

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]