Alnylam Pharmaceuticals FY Conference Summary Company Overview - Alnylam Pharmaceuticals is a pioneer in RNAi therapeutics, with over 20 years of development focused on drug delivery and innovation. The company currently has six commercial products, with four being actively commercialized. The primary focus is on the launch of products targeting cardiomyopathy in the ATTR market, which is significantly larger than previous markets the company has operated in [3][4]. Financial Performance - Alnylam is on the verge of achieving profitability, a goal set five years ago. The company reported a significant increase in top-line growth, with TTR revenue globally reaching $544 million, representing a 77% year-over-year growth. In the U.S., revenue was $383 million, with a $170 million increase from Q1, driven primarily by the cardiomyopathy launch [4][6]. Market Dynamics - The ATTR market has been segmented into hereditary polyneuropathy (PN) and cardiomyopathy (CM). The hereditary market is estimated to have about 50,000 patients, while the CM market is approximately ten times larger. The company has successfully launched its products in the CM segment, with an estimated 1,400 patients on therapy by the end of Q2 [5][6]. Launch Strategy and Execution - The rapid establishment of provider setups and payer coverage was a key driver for the successful launch. The company initially expected a six to nine-month setup period but achieved this in a much shorter timeframe. The focus was on getting the drug on formulary at health systems, which are critical for patient treatment [7][8][10]. Demand and Patient Segmentation - The demand for the product has been balanced between first-line and second-line treatments. Initially, demand was primarily from second-line patients, but by the end of the quarter, first-line demand was building. The company estimates that only about 20% of patients are currently treated, indicating significant growth potential [15][16][17]. Competitive Landscape - The competitive environment includes products from Pfizer and BridgeBio. The majority of patients are still being treated with tafamidis, but there is a growing interest in new products. The company aims to leverage its data from the HELIOS-B study to drive market share [21][22]. Pricing Strategy - Alnylam maintained the same pricing for its new product as for its previous offerings, with expectations of gradual price reductions over time. The company reported that approximately 70% of patients had zero out-of-pocket costs, making the product accessible despite its high cost [24][25][26]. Guidance and Future Outlook - The company raised its net product revenue guidance by $600 million, reflecting strong performance and expectations for continued growth. The TTR franchise is expected to grow by about $1 billion in revenue compared to 2024, with plans to expand into additional markets outside the U.S. starting in 2026 [27][30][31]. Long-term Market Evolution - Alnylam anticipates the entry of generics for tafamidis around the end of 2028, which may shift the market dynamics. The company is preparing for this by focusing on combination therapies and positioning its products effectively [39][40][41]. Pipeline and Future Innovations - The company is developing ALN-TTRsc04, a third-generation TTR product expected to provide better efficacy and convenience with a dosing schedule of once every six months. This product is anticipated to launch around 2030, coinciding with the expected generic entry of tafamidis [43][49]. Conclusion - Alnylam Pharmaceuticals is positioned for significant growth with a strong pipeline and a focus on innovative therapies. The company is committed to achieving long-term profitability and expanding its market presence while navigating competitive dynamics and evolving market conditions [64][65].

Core Insights - Arbutus Biopharma has reported that imdusiran combination therapy has functionally cured eight patients with chronic hepatitis B (cHBV), including two patients who did not receive interferon [1][2] - The company has a strong financial position with cash, cash equivalents, and marketable securities totaling $113 million as of March 31, 2025 [1][9] - Andrew J. Sung has joined Arbutus as General Counsel, bringing over $28 billion in life sciences deal experience [1][8] Clinical Developments - Imdusiran (AB-729) has shown promising results, with eight patients achieving functional cure, particularly notable as two did not receive interferon [2][6] - The oral PD-L1 inhibitor AB-101 demonstrated 100% receptor occupancy in 11 of 13 evaluable healthy volunteers during Phase 1a/1b trials, indicating its safety and tolerability [3][10] - Data presented at the EASL Congress 2025 highlighted that patients with baseline HBsAg <1000 IU/mL had a significant chance of achieving functional cure when treated with imdusiran and low-dose nivolumab [6][22] Financial Performance - For Q1 2025, total revenue was $1.8 million, an increase from $1.5 million in Q1 2024, attributed to revenue recognition from a collaboration with Qilu [10][11] - Operating expenses for Q1 2025 were $27.5 million, with research and development expenses decreasing to $9.0 million from $15.4 million in the same period last year [12][15] - The net loss for Q1 2025 was $24.5 million, compared to a net loss of $17.9 million in Q1 2024, reflecting increased restructuring costs [15][20] Corporate Updates - The company is actively involved in litigation regarding its patented LNP technology against Moderna and Pfizer/BioNTech, seeking fair compensation for their use of this technology [9][10] - Andrew J. Sung's appointment as General Counsel is expected to enhance the company's legal strategy and corporate governance [4][8] - Arbutus continues to streamline its operations, focusing on advancing clinical development while reducing workforce and operational costs [12][14]

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]