PresentationTolga TangulerExecutive VP & Chief Commercial Officer Good morning, everyone, and thank you for joining us today. I'm Tolga Tanguler, Chief Commercial Officer at Alnylam, and I'm thrilled to be hosting today's webinar to update you on our leadership journey in delivering transformative therapies for patients living with ATTR amyloidosis. This past Friday marked one year since AMVUTTRA was approved in the U.S. for patients with ATTR cardiomyopathy, a pivotal milestone for Alnylam that has launch ...

Alnylam Pharmaceuticals (NasdaqGS:ALNY) Update / briefing March 24, 2026 09:30 AM ET Company ParticipantsChristine Akinc - Chief Corporate Communications OfficerJohn Kennedy - SVP and TTR Franchise Commercialization LeadMark Soued - SVP, Head of U.S., and TTR LeadSameer Bansilal - VP of Global Medical Affairs and Head of TTR Disease AreaTolga Tanguler - Chief Commercial Officer and EVPTolga TangulerGood morning, everyone, and thank you for joining us today. I'm Tolga Tanguler, Chief Commercial Officer at Al ...

Key Takeaways Alnylam reported $2.99B in 2025 net product revenues, up 81% YoY, driven by four approved drugs.ALNY's cemdisiran hit key phase III endpoints in generalized MG, with partner Regeneron planning U.S. filing.Zilebesiran and mivelsiran advance in late and mid-stage studies, targeting cardiovascular and AD markets.Alnylam Pharmaceuticals (ALNY) currently markets four approved drugs — Onpattro, Givlaari, Oxlumo and Amvuttra — that together generated $2.99 billion in net product revenues, representin ...

Upgrades - Keefe Bruyette upgraded Rocket Companies (RKT) to Outperform from Market Perform with a price target of $22, up from $20, citing valuation as shares are down 25% year-to-date [2] - Keefe Bruyette upgraded PennyMac Financial (PFSI) to Outperform from Market Perform with an unchanged price target of $115, indicating a 38% upside to the price target based on valuation [2] - Berenberg upgraded Ecolab (ECL) to Buy from Hold with a price target of $326, up from $300, expecting swift implementation of price increases to become a "sticky component" of Ecolab's pricing strategy [3] - Arete upgraded Trade Desk (TTD) to Neutral from Sell with a price target of $25, noting pressure on management to restore investor confidence as shares are down 49% in the last 12 months [3] - Clear Street upgraded Circle Internet (CRCL) to Buy from Hold with a price target of $136, up from $92, citing five catalysts for USDC market cap and adoption despite a 44% drawdown in broader crypto markets [4] Downgrades - Seaport Research downgraded Qualcomm (QCOM) to Sell from Neutral with a price target of $100, predicting that the memory crunch will adversely affect Qualcomm's customers and market share [5] - Argus downgraded Adobe (ADBE) to Hold from Buy, despite a 12% growth in operating income in Q1, due to overshadowing concerns from the announcement of CEO Narayan's resignation [5] - Jefferies downgraded Incyte (INCY) to Hold from Buy with a price target of $94, down from $120, citing patent cliff concerns [5] - Jefferies downgraded Alnylam (ALNY) to Hold from Buy with a price target of $330, down from $522, stating that shares are "priced to perfection" despite being impressed with the company's RNAi platform [5] - Jefferies downgraded Immunocore (IMCR) to Hold from Buy with a price target of $33, down from $48, noting that while Kimmtrak is a real product, the total addressable market is moderate and sales are nearing peak [5]

Investment Rating - The report maintains an "Overweight" rating for the overseas pharmaceutical industry, indicating a positive outlook compared to the overall market performance [6][11]. Core Insights - Recent adjustments to the Hong Kong Stock Connect list include companies like Weili Zhibo and Jinfang Pharmaceutical, effective from March 9, 2026. Additionally, Kangfang Biotech's first tri-antibody has received clinical trial approval [2][3]. - Kingsray Biotech expects an adjusted net profit of USD 207-242 million for 2025, representing a year-on-year growth of approximately 246.5%-304.3%, primarily driven by licensing revenue growth from USD 2.4 million in 2024 to USD 256-299 million [2][7]. - The Hang Seng Healthcare Index rose by 2.58%, outperforming the Hang Seng Index by 1.02 percentage points [6]. Summary by Sections 1. Overseas Pharmaceuticals - Companies like Weili Zhibo and Jinfang Pharmaceutical have been included in the Hong Kong Stock Connect list, effective March 9, 2026. Kangfang Biotech's AK150 has received clinical trial approval for treating advanced malignant solid tumors [3][8]. - Songli Pharmaceutical's small molecule GLP-1R agonist ASC30 achieved statistically significant weight loss results in a U.S. Phase II trial, with an average weight reduction of 7.5% after three monthly doses [3][8]. 2. Performance Updates - Kingsray Biotech anticipates a significant increase in net profit for 2025, while Lepu Biotech expects to achieve a net profit of no less than RMB 200 million, marking a turnaround from losses [2][7]. - Jike Si's revenue is projected to decline by 65.6% in 2025, with a net loss of RMB 146 million [2][7]. 3. Recommendations - The report suggests focusing on innovative drugs with ongoing commercialization and business development opportunities, particularly companies like Baijie Shenzhou, Xinda Biotech, and Kangfang Biotech [11]. - In the pharmaceutical sector, companies like Sanofi and China Biopharmaceutical are highlighted for their progressive innovation pipelines [11]. 4. Overseas Education - The education index increased by 3.1%, outperforming the Hang Seng China Enterprises Index by 0.3 percentage points [13]. - The report recommends focusing on Chinese Oriental Education, which is expected to see accelerated enrollment growth due to rising demand for vocational training [15]. 5. Overseas Social Services - Macau's total visitor numbers during the Spring Festival reached a record high, with 1.554 million visitors and an average daily visitor count of 173,000, reflecting a year-on-year growth of 5.5% [17].

Investment Rating - The industry investment rating is "Overweight" indicating that the industry is expected to outperform the overall market [2][6]. Core Insights - Recent adjustments to the Hong Kong Stock Connect list include companies such as Weili Zhibo and Jinfang Pharmaceutical, effective from March 9. Kangfang Biologics has received clinical approval for its first tri-antibody [2][3]. - Kingsray Biotech anticipates an adjusted net profit of USD 207-242 million for 2025, representing a year-on-year growth of approximately 246.5%-304.3%, primarily due to licensing revenue increasing from USD 2.4 million in 2024 to USD 256-299 million [2][7]. - The Hang Seng Healthcare Index rose by 2.58%, outperforming the Hang Seng Index by 1.02 percentage points [6]. Summary by Sections 1. Overseas Pharmaceuticals - Companies like Weili Zhibo, Jinfang Pharmaceutical, and others have been included in the Hong Kong Stock Connect list since March 9. Kangfang Biologics' AK150 has received clinical trial approval for treating advanced malignant solid tumors [3][8]. - Alnylam has initiated a clinical trial for ALN-2232 (ALK7 siRNA) aimed at obesity, with an expected completion date in March 2028 [4][9]. - Agilent Technologies has agreed to acquire Biocare Medical for USD 950 million, enhancing its capabilities in clinical pathology [4][9]. 2. Performance Updates - Kingsray Biotech expects a significant increase in net profit for 2025, while Lepu Biotech anticipates a net profit of no less than RMB 200 million, marking a turnaround [7][8]. - The revenue forecast for Jike Si is projected to decline by 65.6% in 2025, with a net loss of RMB 146 million [7][8]. 3. Recommendations - Focus on innovative drugs with ongoing commercialization and active overseas transactions, particularly companies like BeiGene, Innovent Biologics, and Kangfang Biologics [12]. - In the Pharma sector, companies like 3SBio and Hansoh Pharmaceutical are making strides in their innovative pipelines [12]. 4. Education Sector - The education index increased by 3.1%, outperforming the Hang Seng Index by 0.3 percentage points [14]. - China Oriental Education is recommended due to its strong growth prospects and strategic adjustments in response to vocational training demand [17]. 5. Social Services - Macau's visitor numbers during the Spring Festival reached historical highs, with total inbound travelers at 1.554 million and an average daily visitor count of 173,000, reflecting a year-on-year growth of 5.5% [19].

Investment Rating - The report does not explicitly state an investment rating for the small nucleic acid industry Core Insights - Small nucleic acid drugs have transitioned from technical validation to commercial realization, with projected sales of approximately $3.1 billion for ASO and $4.2 billion for siRNA by 2025 [3] - The development paths of ASO and siRNA are shaped by their mechanistic differences, with ASO utilizing a single-strand structure for direct delivery into target cells, while siRNA relies on carrier systems for effective delivery due to its larger size and strong negative charge [3] - Continuous evolution in chemical modifications and delivery platforms has improved the stability, targeting, safety, and convenience of small nucleic acid drugs, expanding their application from rare diseases to chronic conditions [3] - Current advancements in liver-targeting technologies are paving the way for the next phase of delivery to extrahepatic tissues, with future valuations of small nucleic acid companies focusing on platform capabilities and expansion into chronic disease treatments [3] Summary by Sections Small Nucleic Acids Unlock Gene Expression Regulation - Small nucleic acid drugs can target previously undruggable proteins by intervening at the gene expression level, significantly broadening the potential therapeutic targets [9][11] Pathways to Small Nucleic Acid Drug Development - The report outlines the dual pathways of ASO and siRNA, highlighting their distinct mechanisms and therapeutic applications [12][30] Mechanistic Differences: ASO vs. siRNA - ASO employs RNase H-mediated degradation and splicing regulation to inhibit protein expression, while siRNA utilizes the RISC mechanism for mRNA degradation [20][26] Chemical Modifications and Stability - The report details the evolution of chemical modifications across four generations, enhancing the stability and specificity of ASO and siRNA [32][36] Delivery Breakthroughs - The challenges of delivering small nucleic acids across cellular barriers are discussed, emphasizing the need for effective delivery systems [40][44] Safety Optimization - Innovations in toxicity management for ASO and siRNA are crucial for supporting long-term use and chronic disease management [62][64] Commercialization and Boundary Expansion - The report emphasizes the transition from liver-targeted therapies to exploring delivery strategies for other tissues, indicating a strategic shift in the industry [60][61]

Core Insights - The article discusses three significant business development (BD) deals in the small nucleic acid sector in China, highlighting a strategic shift in global pharmaceutical companies' evaluation of Chinese small nucleic acid assets [3][4][5][7]. Group 1: Overview of Recent Transactions - On February 2, 2026, Saintin Biotech entered a global R&D collaboration with Roche's Genentech, receiving a $200 million upfront payment and potential milestone payments up to $1.5 billion [3]. - On February 11, 2026, Rebio Biotech signed a global exclusive licensing agreement with Madrigal, securing a $60 million upfront payment with a total potential value of $4.4 billion [4]. - On February 23, 2026, Frontier Biotech announced an exclusive licensing agreement with GSK, receiving a $40 million upfront payment and a potential total value close to $1 billion [5]. Group 2: Strategic Implications of the Transactions - The rapid succession of these deals indicates that global pharmaceutical companies are reassessing the strategic value of Chinese small nucleic acid assets, moving beyond mere opportunistic licensing [7]. - The core of these transactions lies not in individual products but in the underlying platform capabilities, which are crucial for expanding into new therapeutic areas [10][11]. Group 3: Historical Context and Comparison - The article compares the current transactions to early RNAi industry deals, noting that the upfront payments for Chinese companies are significantly higher than those in the early 2000s, reflecting a shift in perceived value and confidence in technology [13][18]. - The historical context shows that early RNAi deals were primarily exploratory, while current transactions are based on established technology and the ability to produce competitive products [19][20]. Group 4: Risk and Payment Structures - The payment structures of the recent deals show a trend towards backend-weighted milestone payments, indicating that buyers are willing to take on more risk as they recognize the maturity of the technology [24][25]. - Saintin Biotech's high upfront payment suggests strong confidence in the maturity and quality of its LEAD™ platform, which is seen as a critical technology for future developments [26]. Group 5: Strategic Positioning of Global Pharma - The article highlights that global pharmaceutical companies are not merely testing the waters but are strategically positioning themselves to leverage small nucleic acid technologies as essential resources for future competition [28][32]. - Companies like Madrigal and Genentech are actively seeking to build technological moats and enhance their treatment capabilities through these partnerships, indicating a shift from passive to active engagement in the market [29][30]. Group 6: Innovation and Intellectual Property - The article emphasizes the importance of independent intellectual property systems for small nucleic acid platforms, which allow Chinese companies to compete effectively in the global market [36][37]. - The ability of Chinese firms to navigate existing patent landscapes and develop new delivery technologies is crucial for their competitive positioning [38]. Group 7: Conclusion on Market Dynamics - The rapid evolution of Chinese small nucleic acid companies from followers to key technology providers reflects a significant shift in the global innovation landscape, with these firms now being recognized for their differentiated capabilities [41][42].

Core Insights - The article discusses the current stock market performance and highlights five stocks as prime candidates for investment: Nvidia, Tesla, Broadcom, Quanta Services, and Alnylam Pharmaceuticals [1][18]. Market Overview - The stock market has performed well in 2023 and 2024, recovering from initial pressures due to Donald Trump's tariff agenda and benefiting from recent tariff easements [2]. - The S&P 500 and Nasdaq composite have surpassed their 50-day and 200-day moving averages, indicating a bullish trend [8]. Investment Strategy - The IBD Methodology suggests investing in stocks with quarterly and annual earnings growth of at least 25%, focusing on companies with innovative products and strong institutional support [4][5]. - Investors should monitor market trends and sell stocks that decline by 7% to 8% from their purchase price [9]. Stock Analysis Nvidia (NVDA) - Nvidia stock is currently above an ideal entry point of 184.48 and has shown strong performance with a 41% increase in 2025 [12][13]. - The stock has an IBD Composite Rating of 99, with earnings growth averaging 53% over the past three quarters [14]. - Analysts have a consensus strong buy rating with a price target of 211.26, citing Nvidia's leading position in AI technology [15][16]. Tesla (TSLA) - Tesla stock is forming a cup-with-handle base with an early buy point of 451.68 [20]. - The stock has an IBD Composite Rating of 77, with a 7% increase in 2025 and a significant rise from its April lows [21]. - Institutional ownership is at 34%, with notable funds holding shares [23]. Broadcom (AVGO) - Broadcom is forming a cup-with-handle base with an ideal entry point of 363.24 and has an IBD Composite Rating of 99 [25][27]. - Earnings are expected to grow by 39% this year, with a 53% increase in 2025 [28]. - The company has secured a deal to supply AI processors for OpenAI, enhancing its market position [30][31]. Quanta Services (PWR) - Quanta Services has rallied back into the buy zone above a cup base entry of 424.94, with an IBD Composite Rating of 96 [33][34]. - Earnings are projected to rise by 18% in 2025, with institutional ownership at 59% [35][36]. - The company has been expanding through acquisitions and is well-positioned in the energy infrastructure market [37]. Alnylam Pharmaceuticals (ALNY) - Alnylam is near a flat base ideal entry point of 484.21, with an IBD Composite Rating of 83 [38][39]. - The company is expected to swing from a loss to an EPS of $1.44 this year, with significant institutional backing at 74% [40][41]. - Alnylam has received FDA approval for its drug Amvuttra, expanding its market potential [42][43].

Core Insights - Tenaya Therapeutics, Inc. shares have increased due to a positive market reaction to a research collaboration with Alnylam Pharmaceuticals focused on cardiovascular disease treatments [1][2] Group 1: Collaboration Details - The collaboration aims to discover human genetic targets for potential cardiovascular disease treatments, with Tenaya validating up to 15 gene targets [2] - Tenaya will receive up to $10 million in upfront payments, with potential milestone payments reaching up to $1.13 billion [2] Group 2: Tenaya's Capabilities - Tenaya utilizes human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) for high-throughput identification of genetic targets and employs human-engineered heart tissue and preclinical in vivo models for validation [3] - The company has identified over 150 genetic targets, contributing to the development of clinical-stage candidates such as TN-201, TN-401, and TN-301, along with several early-stage programs [4] Group 3: Clinical Trials and Data - Interim data from the ongoing RIDGE-1 Phase 1b/2 trial of TN-401 gene therapy for rare inherited heart disease was shared in December 2025, including safety and biopsy results from three patients [4][5] Group 4: Alnylam Pharmaceuticals Strategy - Alnylam Pharmaceuticals has announced a five-year roadmap, "Alnylam 2030," focusing on establishing leadership in transthyretin (TTR) diseases and aims to lead the TTR market in revenue by 2030 [6] Group 5: Technical Analysis - Despite recent gains, Tenaya Therapeutics is trading 29.1% below its 100-day SMA and 23.6% below its 200-day SMA, indicating a bearish trend [7] - The stock's RSI is at 40.21, suggesting it is neither overbought nor oversold, while the MACD indicates bearish momentum [7] - Tenaya Therapeutics shares were up 31.20% at 76 cents at the time of publication [7] Group 6: Analyst Ratings - Analysts have given Tenaya Therapeutics a Buy rating, with recent target adjustments from Canaccord Genuity ($5), HC Wainwright & Co. ($3), and Chardan Capital ($8) [8]