Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY) Q1 2022 Earnings Conference Call April 28, 2022 8:30 AM ET Company Participants Christine Lindenboom - Senior Vice President of Investor Relations and Corporate Communications Yvonne Greenstreet - Chief Executive Officer Tolga Tanguler - Chief Commercial Officer Pushkal Garg - Chief Medical Officer Jeff Poulton - Chief Financial Officer Conference Call Participants David Lebowitz - Citigroup Maury Raycroft - Jefferies Salveen Richter - Goldman Sachs Paul Matteis - ...

Financial Performance - Alnylam's Q1 2022 net product revenues were $186.9 million, a 38% increase compared to Q1 2021[55] - At constant exchange rates (CER), net product revenues grew by 43%[55] - Total revenues for Q1 2022 were $213.3 million, a 20% increase compared to Q1 2021[55] - At CER, total revenues grew by 24%[55] - Alnylam updates its full year 2022 net product revenue guidance to $870 million - $930 million[56] Product Performance - ONPATTRO global Q1 2022 net product revenues are not specified in the provided content, but it shows a YoY growth of 34% and a QoQ growth of -1%[15, 17] - GIVLAARI global Q1 2022 net product revenues were $15 million, with a YoY growth of 43% and a QoQ growth of -13%[21, 23] - OXLUMO global Q1 2022 net product revenues were $15 million, with a YoY growth of 59% and a QoQ growth of -24%[24, 26] Clinical Development - Enrollment is complete for the Patisiran Phase 3 study in ATTR amyloidosis patients with cardiomyopathy, with topline results expected mid-2022[29] - The Vutrisiran Phase 3 study in hereditary ATTR amyloidosis with polyneuropathy met its primary endpoint of change from baseline in mNIS+7 at Month 9[30] - Enrollment is complete for the Vutrisiran Phase 3 study in ATTR amyloidosis patients with cardiomyopathy, with topline results on the 30-month endpoint expected early 2024[46]

Financial Data and Key Metrics Changes - Alnylam achieved $662 million in net product revenue for 2021, representing year-over-year growth of 83% [6][30] - Non-GAAP R&D expenses increased by 34% in Q4 2021 compared to Q4 2020, primarily due to investments in mid and late-stage pipeline programs [31] - Non-GAAP operating loss for 2021 was $528 million, showing a $121 million improvement compared to 2020 [32] - Cash, cash equivalents, and marketable securities at the end of 2021 were $2.4 billion, up from $1.9 billion at the end of 2020 [33] Business Line Data and Key Metrics Changes - ONPATTRO generated $139 million in global net product revenues in Q4 2021, a 15% increase quarter-on-quarter and 53% year-over-year [10] - GIVLAARI achieved $41 million in global net product revenues in Q4 2021, representing 28% quarter-on-quarter growth and 84% growth versus Q4 2020 [13] - OXLUMO reported $19 million in global net product revenues in Q4 2021, a 29% increase compared to Q3 2021 [14] Market Data and Key Metrics Changes - In the U.S., ONPATTRO sales increased by 17% versus Q3 2021, driven by patient demand and inventory stocking [11] - GIVLAARI's U.S. sales increased by 35% compared to Q3 2021, influenced by patient demand and inventory stocking [13] - OXLUMO's international markets saw a 40% growth in Q4 2021 compared to Q3 2021, benefiting from increased patient treatment and geographic expansion [15] Company Strategy and Development Direction - Alnylam aims to expand its TTR franchise and become a global leader in delivering impactful medicines [8] - The company plans to expand beyond rare diseases into prevalent diseases, leveraging its sustainable innovation engine [8][29] - Upcoming milestones include the potential approval of vutrisiran and continued advancement of the ATTR franchise [36] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the growth potential of the TTR franchise, particularly with the upcoming launch of vutrisiran [46] - The company anticipates combined net product revenues for 2022 to be between $900 million and $1 billion, reflecting a 44% growth compared to 2021 [34] - Management acknowledged the ongoing pandemic's impact on operations but remains optimistic about patient demand and product growth [34] Other Important Information - Alnylam's pipeline includes late-stage candidates for ATTR amyloidosis and hypertension, with significant progress in clinical trials [17][26] - The company is also exploring new opportunities in prevalent diseases, such as hypertension, with its investigational product zilebesiran [26] Q&A Session Summary Question: Thoughts on vutrisiran approval and potential label inclusion - Management is excited about vutrisiran's launch and believes it will enhance the TTR franchise without cannibalizing existing products [40][41] Question: Guidance assumptions for ONPATTRO and vutrisiran - The TTR franchise is expected to drive growth, with management confident in the appeal of vutrisiran's profile to patients [46][47] Question: KARDIA-1 Phase 2 study expectations - Management is optimistic about achieving clinically meaningful results in KARDIA-1, with a focus on blood pressure control and patient adherence [50][51] Question: Confidence in APOLLO-B trial design - Management expressed confidence in the study design and execution, citing a strong track record in the TTR space [59][60] Question: Comparison of ramp speed between patisiran and vutrisiran - Management believes vutrisiran has the potential for a faster ramp speed due to its compelling profile and reduced treatment burden [66][67]

Financial Data and Key Metrics Changes - In Q3 2021, Alnylam Pharmaceuticals generated $120.3 million in net revenue from ONPATTRO, reflecting a 6% increase from Q2 2021 and a 46% increase compared to Q3 2020 [34] - Total combined product sales for the quarter were $167 million, representing a 68% growth versus Q3 2020 [37] - Cash, cash equivalents, and marketable securities stood at $2.3 billion as of September 30, 2021, up from $1.9 billion at the end of 2020 [38] Business Line Data and Key Metrics Changes - ONPATTRO saw a 12% growth in demand in the U.S., with over 1,875 patients on commercial treatments [13] - GIVLAARI achieved $31.8 million in net revenue, a 4% increase from Q2 2021 and a 91% increase from Q3 2020 [35] - OXLUMO generated $14.9 million in net revenue, a 9% decrease from Q2 due to the transition of patients from monthly loading doses to quarterly maintenance doses [36] Market Data and Key Metrics Changes - Market access for ONPATTRO has been achieved in over 30 countries, with significant growth in Europe, Canada, and Japan [15] - GIVLAARI's U.S. sales were flat versus Q2 2021, but the product is seeing strong progress in establishing Value-Based Agreements with commercial payers [17] - OXLUMO is experiencing steady geographic expansion, with recent launches in Germany and France [19] Company Strategy and Development Direction - The company aims to bring its fifth RNAi therapeutic to market and expand its TTR franchise significantly [11] - Alnylam is focused on sustainable innovation and plans to file a CTA for ALN-APP, targeting Alzheimer's disease, by the end of 2021 [32] - The P5x25 strategy remains a guiding roadmap for delivering transformative medicines and achieving excellent financial performance [73] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the positive results from the HELIOS-A study of Vutrisiran, which strengthens the outlook for future studies [45] - The leadership transition is seen as timely, with the company in a strong position to continue its growth trajectory [71] - The management team remains committed to executing the existing strategy without loss of momentum [73] Other Important Information - The company plans to present full results from the HELIOS-A study at a medical conference in early 2022 [39] - Alnylam is on track to file a CTA for ALN-XDH for gout treatment by late 2021 [32] Q&A Session Summary Question: Contextualization of HELIOS-A data relative to APOLLO-A - Management highlighted that the current data strengthens confidence in Vutrisiran, with encouraging exploratory data on cardiac endpoints [45] Question: Definition of the cardio subpopulation in HELIOS-A - The majority of patients in HELIOS-A would have New York Heart Association class one or two level disease [50] Question: Enrollment progress in the KARDIA-1 trial - Enrollment in KARDIA-1 is progressing well, with a clear line of sight on the last patient in before further guidance is provided [55] Question: Statistical plan for APOLLO-B regarding tafamidis drop-in - The study design accounts for potential drop-ins, with conservative assumptions made to ensure robustness [66] Question: CNS delivery capabilities for ALN-APP - The company has shown promising CNS delivery in preclinical studies, with plans to file an IND for ALN-APP by the end of the year [69]