Summary of Key Points from the Conference Call on Small Nucleic Acid Drugs Industry Overview - The discussion centers around the small nucleic acid drug industry, highlighting its advantages over traditional drug platforms and the potential for various applications in treating diseases. Core Insights and Arguments 1. **Efficacy and Mechanism**: Small nucleic acid drugs can reduce protein expression levels by over 80%-90%, significantly outperforming small molecule and antibody drugs, which only lower activity or clear existing proteins [2][5][8] 2. **Long-lasting Effects**: Some small nucleic acid therapies require administration only once every six months, showcasing their long-lasting effects and low resistance development [2][5] 3. **Delivery Technologies**: The Golang liver delivery technology is currently the mainstream method but is limited to liver applications. New strategies involving peptide and antibody modifications aim to expand delivery beyond the liver [3][4] 4. **Multi-target Strategies**: The potential of multi-target strategies in drug development is significant, as demonstrated by Novartis' Inclisiran, which generated $790 million in revenue in the first three quarters of the year [5][8] 5. **Emerging Markets**: There is a growing market for small nucleic acid drugs in obesity treatment, with drugs like GPS-75 showing promise in altering the current weight loss market dynamics [9][20] 6. **Rare Diseases and CNS Applications**: Small nucleic acid drugs show potential in treating rare diseases and central nervous system disorders, with Novartis' acquisition of RVDP technology indicating strong confidence in muscle disease treatments [8][11] 7. **Challenges in Delivery**: The complexity of delivery systems poses significant barriers to entry for new companies, as effective delivery tools are crucial for the success of small nucleic acid therapies [12][22] 8. **Chemical Modifications**: Chemical modifications are essential for enhancing the stability and bioavailability of small nucleic acids, although current methods do not create significant barriers to entry [13][14] 9. **Market Potential**: The market for small nucleic acid drugs in treating cardiovascular diseases is substantial, as indicated by the $12 billion acquisition of a muscle treatment drug by Novartis [10][22] Other Important Insights 1. **Clinical Trials and Data**: Ongoing clinical trials, such as Wave 007, are showing promising results in weight loss applications, indicating a trend towards combining small nucleic acid drugs with existing therapies like GLP-1 [20][21] 2. **Regulatory and Safety Considerations**: The design of small nucleic acid sequences must consider potential off-target effects, necessitating thorough testing to ensure safety [18][25] 3. **Domestic Innovations**: Domestic companies like Shengyin, Bowang, and Ruibo are making significant strides in small nucleic acid research, with collaborations and innovations that enhance their market positions [28] This summary encapsulates the key points discussed in the conference call, providing a comprehensive overview of the small nucleic acid drug industry, its current state, and future potential.

Core Insights - The small nucleic acid drug industry is entering a new era with a focus on siRNA drugs for common diseases, driven by technological advancements and expanded indications [1][2] - siRNA drugs have transitioned from rare diseases to common diseases, showcasing strong commercial potential in areas like cardiovascular diseases, chronic hepatitis B, weight loss, anticoagulation, and autoimmune diseases [1][3] Group 1: Industry Trends - The small nucleic acid drugs represent the third wave of therapeutics, following small molecules and antibody drugs, characterized by strong target expansion capabilities, robust research extensibility, long-lasting effects, and low resistance [1][2] - The industry is witnessing a surge in business development (BD) transactions, particularly involving multinational corporations (MNCs) leveraging their understanding of indications to acquire pipelines or collaborate on technology platforms [2][3] Group 2: Market Opportunities - The maturation of the liver delivery system and the proven commercial value of small nucleic acid drugs are driving ongoing licensing transactions, as many pharmaceutical companies face patent cliffs and seek new products to mitigate pipeline risks [2][3] - Chinese companies are expected to play a significant role in this space, capitalizing on their engineering advantages and rapid iteration capabilities in chemical synthesis to differentiate their products [2][3] Group 3: Technological Advancements - The current industrialization of siRNA drugs focuses on commercializing common diseases with clear biological mechanisms, where early movers can secure better commercial returns and collaboration opportunities [3] - The efficiency and specificity of the GalNac delivery system present significant opportunities for breakthroughs in new disease areas, particularly those previously challenging to target [3]

Core Insights - The report highlights the significant advantages of ASIC over GPU in terms of cost-effectiveness and energy efficiency, marking a turning point for ASIC development [2][12] - The increasing penetration of AI is driving a surge in inference demand, expanding the market space for ASICs [3][12] - Domestic cloud providers are making strides in self-developed ASICs, indicating a strong demand in the Chinese AI cloud market [12][13] Summary by Sections ASIC vs. GPU - ASICs are specialized chips tightly coupled with downstream applications, focusing on specific needs like text and video inference, while GPUs are general-purpose chips covering a broader range of applications [2][12] - The energy efficiency of Google's TPU v5 is 1.46 times that of NVIDIA's H200, and Amazon's Trainium2 reduces training costs by 40% compared to GPU solutions [2][12] Market Growth and Demand - The global AI ASIC market is projected to reach $125 billion by 2028, with significant contributions from major clients [3][12] - The demand for inference computing is directly linked to throughput, with ChatGPT's weekly active users reaching 700 million by July 2025, driving the need for increased computational power [3][12] ASIC Design Services - ASIC design requires a high level of specialization, with major service providers like Broadcom and Marvell leading the market [3][12] - Broadcom's collaboration with Google on TPU has been pivotal, leveraging a comprehensive IP system and advanced packaging technologies [3][12] Domestic Developments - Leading Chinese cloud providers are achieving results in self-developed ASICs, with significant orders and advancements in technology [12][13] - The trends of PD separation and super nodes are emerging as key developments in the domestic ASIC landscape [12][13] Industry Outlook - The report anticipates a robust growth trajectory for the ASIC market, driven by increasing AI applications and domestic innovation [12][13]

Core Insights - The RNAi therapy market is projected to reach a global market size of $25 billion by 2030, with a significant share in common diseases and tumors, accounting for 54% of the total market size [3] - The Chinese RNAi therapy market is expected to grow from approximately $4 million in 2022 to over $300 million by 2025, with a CAGR exceeding 300%, and is projected to reach around $3 billion by 2030 [3][1] Group 1: Market Trends - The global RNAi therapy market has seen a substantial increase from $12 million in 2018 to $362 million in 2020, with a CAGR of 449.2% [3] - The recent surge in small nucleic acid drugs has led to a wave of business development (BD) activities, with major pharmaceutical companies like Novartis, AZ, and others investing heavily in this field [4] Group 2: Technological Advancements - Recent breakthroughs in small nucleic acid drug design have addressed challenges such as vascular degradation, immune activation, and delivery mechanisms, enhancing the potential for effective treatments [2] - Successful approvals of multiple small nucleic acid drugs, such as Nusinersen with $1.6 billion in sales, Vutrisiran with $970 million (yoy +73%), and Inclisiran with $750 million (yoy +112%), demonstrate their efficacy and safety [2] Group 3: Investment Opportunities - The current landscape shows a limited number of approved small nucleic acid drugs, with 22 drugs expected to be approved by mid-2025, indicating a potential for market expansion [5] - Companies with innovative pipelines and technology platforms, such as Yuyuan Pharmaceutical and Chengdu XianDao, are highlighted as potential investment targets [6]

Investment Rating - The report suggests a positive investment opportunity in the small nucleic acid drug industry, highlighting its unique advantages and potential for growth [2]. Core Insights - Small nucleic acid drugs possess unique advantages such as broad target accessibility, strong specificity, high development efficiency, and prolonged dosing intervals, which significantly enhance patient compliance and open up potential clinical demand [2]. - Recent technological breakthroughs in small nucleic acid drug design have addressed challenges such as vascular degradation, immune activation, and delivery difficulties, leading to successful market approvals and showcasing excellent efficacy and safety [2]. - The global market for RNAi therapies is projected to grow from $12 million in 2018 to $25 billion by 2030, with a CAGR of 449.2%, indicating a rapid expansion phase for small nucleic acid drugs [2]. - Major multinational corporations (MNCs) are increasingly investing in the small nucleic acid field, with significant collaborations and development projects emerging, particularly in China [2]. - The report emphasizes the limited number of approved small nucleic acid products, suggesting that Chinese companies have the potential to capture a significant share of the global market [2]. Summary by Sections 1. Introduction and Core Technology of Small Nucleic Acid Drugs - Small nucleic acid drugs are defined as short-chain nucleic acids composed of dozens of nucleotides, targeting RNA to regulate protein expression [10]. - The report outlines the unique characteristics of small nucleic acid drugs, including their ability to target a wide range of disease-related genes and their potential to become a third major class of therapeutics after small molecules and antibody drugs [19]. 2. Market Overview of Small Nucleic Acid Drugs - The small nucleic acid drug market is experiencing rapid growth, with the global market size expected to reach $52.47 billion in 2024, reflecting an 18% year-on-year increase [50]. - The report forecasts that the RNAi therapy market in China will grow from approximately $4 million in 2022 to over $300 million by 2025, with a CAGR exceeding 300% [50]. 3. Disease Areas for Small Nucleic Acid Drugs - The report identifies genetic rare diseases as the most common indication for approved small nucleic acid drugs, with 16 out of 22 approved products targeting this area [51][52]. 4. Leading Overseas Companies in Small Nucleic Acid - The report highlights several leading companies in the small nucleic acid space, including Alnylam, Ionis, and Arrowhead, which are at the forefront of innovation and development [2]. 5. Recommended Companies to Watch - The report suggests monitoring companies with proprietary technology platforms and innovative pipeline layouts, such as Yuyuan Pharmaceutical, Rejuve Biotech, and others, as potential investment opportunities [2].

Investment Rating - The report maintains a "Positive" outlook for the pharmaceutical and biotechnology industry in China [6]. Core Insights - Small nucleic acid drugs are expected to become the third major class of drugs after small molecules and antibodies, with unique advantages such as broad targets, strong specificity, high development efficiency, and long dosing intervals [9][38]. - The commercialization of rare diseases is maturing, and the long-term advantages for chronic diseases are becoming evident, with significant sales growth for products like Spinraza and Leqivo [9][60]. - There is a notable increase in business development (BD) activities, highlighting the potential of early-stage chronic disease pipelines [9]. Summary by Sections 1. Small Nucleic Acids: Potential as a New Drug Class - Small nucleic acid drugs, including ASO, siRNA, and Aptamer, interact with mRNA to regulate gene expression, offering a new technological pathway for drug development [13]. - The global market for small nucleic acid drugs has grown from $1.04 billion in 2017 to $5.09 billion in 2024, with a CAGR of 25.5% [60]. 2. Milestones in Overseas and Domestic Markets - In the overseas market, significant developments are expected in the TTR field and cardiovascular diseases, with drugs like Vutrisiran and Pelacarsen showing promise [9]. - In China, new therapies for chronic hepatitis B and competitive advancements in cardiovascular drugs are emerging, with several companies making progress in their pipelines [9][60]. 3. Investment Recommendations and Targets - The report suggests focusing on high-quality domestic companies involved in the development of small nucleic acid drugs targeting chronic hepatitis B and cardiovascular diseases, such as HengRui Medicine, China National Pharmaceutical Group, and others [9].