Q&A 小核酸药物的技术发展和市场前景如何？ 蓝晓科技 20251216 摘要 小核酸递送技术在 2014 年取得突破，解决了降解问题，扩展了其在常 见病和慢性病治疗中的应用，为市场增长奠定基础。 2020 年诺华英斯可兰的成功上市及罗氏 28 亿美元的投入，显著推动了 小核酸药物的研发和市场认可度。 2024 年小核酸市场规模达 57 亿美元，预计 2030 年将增长至 400- 500 亿美元，小核酸固相合成载体市场规模预计达 5 亿美元。 南晓科技在多肽树脂市场占有 70%份额，并与诺华、GSK 等大型药企 合作，预计在小核酸固相合成载体市场占据至少 50%份额，即 17-18 亿人民币。 南晓科技拥有包括诺华、GSK 等顶尖制药公司的强大客户基础，确保了 稳定且高质量的订单来源，是其竞争优势之一。 南晓科技与日本日东共同占据最齐全的小核酸专利组合，在专利布局方 面处于领先地位，增强了其市场竞争力。 南晓科技预计在 2026 年进入第三个成长加速期，小核酸业务将实现从 0 到 1 的突破，同时盐湖提锂业务有望迎来新的增长。 小核酸药物是由诺贝尔奖技术驱动的第三次医药革命，其研发始于罕见病和遗 传病领域。 ...

（来源：E药资本界） 2025年，中国医药健康产业正式迈入"创新深化+全球突围"双轮驱动的关键阶段。以小核酸、 PROTAC、CGT为代表的新兴疗法从临床验证加速迈向商业化兑现，ADC、双抗、TCE等前沿技术引领 创新药疗法升级；国产高端医疗设备与外周介入器械在中高端市场实现关键突破，国产替代进程持续提 速。 产业变革浪潮中，头部券商的深度研判成为穿透行业迷雾、把握核心机遇的重要指引。 2025年度中国券商十大医药技术研报汇聚来自华福证券、西南证券、国金证券、中信建投证券、国盛证 券、兴业证券、天风证券（维权）、平安证券、开源证券、东吴证券医药首席分析师精选的重磅报告， 覆盖技术迭代、产业趋势、全球化布局等核心议题。 这些报告不仅解码了技术突破的核心逻辑与商业化落地的关键节点，更精准捕捉了行业价值重构的新范 式，为产业从业者、投资者及行业观察者提供了兼具深度与前瞻性的权威参考。 接下来，让我们聚焦十大券商研报的核心精华，共探医药产业创新与增长的核心密码。 01 华福证券研究所副所长、医药首席分析师陈铁林 《小核酸行业深度：技术平台和适应症不断验证，迎来销售和临床密集兑现期》 ▲图为华福证券研究所副所长、医药首 ...

Summary of Key Points from the Conference Call on Small Nucleic Acid Drugs Industry Overview - The global small nucleic acid drug market has reached $6.2 billion and is expected to exceed $40 billion by 2033, driven by new drug approvals, commercialization, and breakthroughs in non-liver-targeted therapies [1][9][14] - Major multinational pharmaceutical companies like Novartis and Roche are actively investing in this sector through business development (BD) and acquisitions, with over 20 small nucleic acid drugs already on the market and more than 300 in clinical stages [1][4][9] Core Insights and Arguments - Key technological breakthroughs include GalNAc delivery technology and chemical modification techniques, which significantly enhance drug stability and efficacy, facilitating successful clinical trials [1][5][8] - ASO (Antisense Oligonucleotides) and siRNA (small interfering RNA) are the two main types of small nucleic acids, with siRNA showing rapid development post-delivery technology breakthroughs [1][6][7] - The small nucleic acid drug development process faces challenges in delivering drugs to non-liver tissues, necessitating the development of new delivery systems like AOC (Antibody-Oligonucleotide Conjugates) [1][8] Market Dynamics - The small nucleic acid target landscape is concentrated on metabolic diseases, hyperlipidemia, and hepatitis B, with significant competition in targets like PCSK9 [3][16] - Since 2018, the total BD transaction value in the small nucleic acid field has reached $45.2 billion, indicating strong interest from multinational corporations [3][17] - Domestic companies in China are rapidly emerging, transitioning from follower strategies to gaining leading advantages in certain targets and technologies [3][20] Company-Specific Developments - **Novartis**: Acquired Avidity for $12 billion to obtain AOC delivery technology, indicating a strong commitment to the small nucleic acid sector [3][9][15] - **Domestic Companies**: Companies like Shiyao Group, BoWang Pharmaceutical, and Jingyin Biotechnology are actively pursuing relevant targets and have made significant progress in clinical stages [3][20][21] - **Yuekang Pharmaceutical**: Leading in the domestic A-share market with a revenue of approximately $383.8 billion in 2024 and a focus on small nucleic acid pipelines [22] - **Frontier Biotech**: Concentrating on IGA nephropathy with multiple candidates showing first-in-class potential [24] - **Fuyuan Pharmaceutical**: Focused on generics but also advancing in small nucleic acid innovation, with over 20 patented targets [25] - **Shiyao Group**: Notable for its rapid progress in the SRA field, with three drugs in clinical trials [26][27] - **Rebio**: Recently submitted a listing application and has established significant partnerships, indicating strong growth potential [31] Future Trends - The small nucleic acid field is expected to see a surge in new drug approvals and clinical data readouts in the coming years, with a focus on expanding indications beyond liver-targeted therapies [14] - The market is anticipated to grow significantly, with projections indicating a rise from $6.2 billion to over $40 billion by 2033, driven by new approvals and commercialization efforts [9][14] - Companies are increasingly focusing on innovative delivery systems and expanding their target indications to include CNS and other areas [8][14][30] Additional Important Insights - The sales of existing small nucleic acid products are growing rapidly, with drugs like Inclisiran expected to see sales increase from $754 million in 2024 to over $1.2 billion in 2025 [12][13] - The competitive landscape is intensifying, with domestic companies showing strong potential to emerge as leaders in the small nucleic acid market [10][30]

Summary of Key Points from the Conference Call Industry Overview - The conference call focuses on the **hyperlipidemia treatment market** in China, highlighting the significant unmet medical needs due to the low treatment rate among over **400 million** patients with dyslipidemia [1][2][14]. Core Insights and Arguments - **Current Treatment Limitations**: Existing medications, particularly statins, have efficacy limitations. PCSK9 inhibitors, while effective, are expensive and require injections, which restricts their clinical application [1][2][5][14]. - **Emerging Therapies**: The rise of **small nucleic acid technology** is notable, with new targets such as **LPA** and **APOC3** being explored. Oral PCSK9 inhibitors, like those from Merck, show promising clinical results comparable to injectables, potentially increasing patient acceptance [1][2][3][9][15]. - **Market Potential**: The sales peak for oral PCSK9 inhibitors is projected to exceed **$5 billion**. The innovative drugs targeting non-LDL pathways are expected to significantly advance the field of dyslipidemia treatment [3][9][15]. - **New Treatment Targets**: For hypertriglyceridemia, **NANGPTL3** and **APOC3** are emerging as new therapeutic targets, with clinical data showing positive results for small nucleic acid products [10][15]. Additional Important Insights - **Patient Compliance**: Oral formulations are anticipated to improve patient compliance compared to injectable therapies, which is crucial for chronic conditions like hyperlipidemia [9][14]. - **Technological Advancements**: Companies with strong R&D capabilities and technological advantages are likely to lead in the competitive landscape of the hyperlipidemia market [2][15]. - **Market Dynamics**: The market is characterized by a high barrier to entry for new technologies and targets, indicating that firms with established capabilities in these areas will have a competitive edge [15]. - **Clinical Guidelines**: Current clinical guidelines prioritize LDL-C as the primary treatment target, with other non-LDL targets being addressed subsequently [4][8]. Conclusion - The hyperlipidemia treatment market in China is poised for significant growth driven by innovative therapies and a focus on unmet clinical needs. Companies that can leverage new technologies and address these needs will likely thrive in this evolving landscape [15].

Summary of Key Points from the Conference Call Industry Overview - The small nucleic acid drug market is rapidly developing, with companies like Namer and IONIS raising their commercialization revenue guidance, indicating significant market potential as product lines expand from rare diseases to chronic diseases [1][2][3] - The small nucleic acid sector has seen a continuous rise in stock prices since mid-year, reflecting investor optimism about the future of small nucleic acid drugs [1][2][3] - Domestic enthusiasm for small nucleic acid drug development is high, with several companies achieving breakthroughs in business development transactions [1][3] Core Insights and Arguments - IONIS is expected to launch nearly 10 products between 2025 and 2028, covering both rare and chronic diseases, such as LGA kidney disease [1][2][15] - Major pharmaceutical companies like Novartis and Sanofi are actively investing in the small nucleic acid field through business development and acquisitions, indicating confidence in the market [2][11][12] - The small nucleic acid technology primarily includes ASO (Antisense Oligonucleotides) and siRNA (small interfering RNA), with siRNA products dominating since 2018 [2][5] Advantages of Small Nucleic Acid Drugs - Small nucleic acid drugs target approximately 70% of human genes, significantly higher than the 0.05% targeted by small molecules and antibodies, providing a broader application space [4] - They offer higher treatment efficiency, greater specificity, and lower toxicity compared to traditional therapies, making them suitable for a wider range of diseases [4] - The long half-life of small nucleic acids allows for less frequent dosing, improving patient compliance [4] Market Trends - The small nucleic acid drug market is experiencing rapid growth, with 19 products launched after 2018, representing 83% of the total, and 13 launched after 2020, representing 57% [8] - The market is expanding from rare diseases to chronic diseases, which not only broadens the market space but also highlights the advantages of reduced dosing frequency [8] Patent and Technology Landscape - Many patents for small nucleic acid modification technologies are expiring or about to expire, while some base modification patents remain valid [6] - The delivery technology for small nucleic acids aims to protect them from degradation, achieve precise targeting, and promote cellular uptake [7] Notable Companies and Developments - Annamira has diversified its pipeline beyond rare diseases into cardiovascular, metabolic, and neurological diseases, showing strong revenue growth [14] - Sanofi has made significant investments in small nucleic acid drugs, including a $3.395 billion acquisition of a small nucleic acid drug from a subsidiary [12] - Domestic companies like Shengnuo Pharmaceutical, Frontier Bio, Tencent BoYao, and Yuekang Pharmaceutical are making notable progress in the small nucleic acid sector [17] Future Outlook - IONIS plans to launch multiple products across various therapeutic areas, including hepatitis B and cardiovascular diseases, from 2025 to 2028 [15] - Companies are increasingly focusing on innovative delivery technologies and expanding their pipelines to capture a larger market share in the small nucleic acid space [16][17]

Core Viewpoint - Dongyangguang Pharmaceutical's HECN30227, a self-developed siRNA therapy for chronic hepatitis B, has received implied approval for clinical trials, marking a significant advancement as no siRNA drugs for hepatitis B have been approved globally [1][3]. Group 1: Clinical Trial Approval - The National Medical Products Administration's Drug Evaluation Center has granted implied permission for HECN30227 to conduct clinical trials for chronic hepatitis B [1][2]. - Chronic hepatitis B is a severe global public health issue, with approximately 75 million chronic HBV infections in China, highlighting the urgent need for new treatment options [3]. Group 2: Drug Development and Mechanism - HECN30227 is a first-class new drug developed by Dongyangguang, utilizing a small nucleic acid technology platform, targeting both cccDNA and intDNA sources of hepatitis B surface antigen (HBsAg) [3]. - Preclinical data indicate that HECN30227 has pan-genotype activity, effectively reducing HBsAg levels and maintaining efficacy against nucleoside-resistant strains, outperforming clinical competitors [3]. Group 3: Delivery System and Combination Therapy - The drug employs Dongyangguang's unique HEC-GalNova liver-targeted delivery system, ensuring precise liver delivery while significantly reducing off-target risks [3]. - The company is concurrently developing a combination therapy of "siRNA + ASO + immune modulators" to comprehensively suppress HBV and HBsAg, aiming for a functional cure for hepatitis B [3][7]. Group 4: Recognition and Future Directions - Recent preclinical research on the combination of HECN30227 and a high-selectivity hTLR8 immune agonist was recognized at the 2025 AASLD annual meeting, indicating strong international academic validation of its clinical development potential [4][7]. - Dongyangguang continues to focus on the anti-infection field, advancing functional cure strategies centered around HECN30227 and exploring its clinical application potential in broader patient populations [7].

Core Insights - The company is strategically expanding into the small RNA platform to address age-related chronic diseases, aiming to develop a pipeline with long-term value and transition into a Pharma company [1][2]. Group 1: Company Overview - The company has established a partnership with AditumBio to form KalexoBio, focusing on a dual-target siRNA drug, 2MW7141, for cardiovascular diseases, with a total deal value of $1 billion [2]. - The company has a strong asset management background, with the fund managing assets of 16.182 billion yuan and achieving a one-year return of 54.74% for its best-performing fund [1]. Group 2: Product Development - The dual-target siRNA drug 2MW7141 is designed to address unmet clinical needs in cardiovascular treatment, with preliminary data showing strong efficacy in animal models [3][5]. - The siRNA technology platform emphasizes differentiated innovation, utilizing AI for automated design and screening, and optimizing delivery methods for both liver-targeted and extrahepatic applications [4]. Group 3: Research and Clinical Trials - The α-synuclein-targeting PET tracer [18F]-FD4 has received funding from the Michael J. Fox Foundation to accelerate its development for Parkinson's disease and related disorders, with potential for early diagnosis and monitoring [6][7]. - The company is advancing multiple clinical pipelines, including 9MW2821 for bladder cancer and 9MW1911 for COPD, with significant milestones expected in the coming years [8][9].

Group 1 - The company, established in 2013 and listed on the Shanghai Stock Exchange in 2020, has developed a core self-researched HIV drug, Aikening (Aibowei Tai), which was approved in 2018, marking a significant milestone in its development [1] - The company is focusing on an innovative pipeline that combines innovative drugs and high-end generics, covering long-acting HIV drugs, small nucleic acid drugs, high-end generics, and medical devices, enhancing its core competitiveness [1] - The company anticipates steady growth in sales of HIV medications and potential growth from its small nucleic acid innovation pipeline, projecting net profits of -176 million, -171 million, and -164 million yuan for 2025-2027, with corresponding EPS of -0.47, -0.46, and -0.44 yuan, and a current PE ratio of -31.6, -32.6, and -33.8 times [1] Group 2 - The company is advancing in the small nucleic acid field, focusing on chronic disease treatment with self-researched ACORDE delivery carrier siRNA drugs, targeting diseases such as IgA nephropathy and dyslipidemia, with selected targets showing First-in-Class (FIC) or Best-in-Class (BIC) potential [2] - In the IgA nephropathy area, the company has three siRNA drugs targeting complement mechanisms, with FB7013 (single target MASP-2) expected to submit an IND application by the end of 2025, and FB7011 (dual targets MASP-2 and CFB) showing promising preclinical results [2] - The company has developed an innovative siRNA delivery carrier, ACORDE, and is exploring kidney and central nervous system delivery, which may further open growth opportunities [2] Group 3 - Aikening (injection form of Aibowei Tai) is the core product for long-acting HIV treatment, approved in 2018 as the first long-acting HIV fusion inhibitor globally, with potential for expanded market coverage and penetration into lower-tier markets [3] - The company is actively advancing the research and development of new long-acting HIV formulations and is assembling a complete long-acting treatment regimen [3] - The strategic layout of high-end generics and medical devices is expected to continuously contribute to the company's revenue growth [3]

Core Insights - The pharmaceutical industry in the first half of 2025 is characterized by deepening centralized procurement and intense market competition, with companies balancing between stabilizing their fundamentals and seeking growth [2] - Haizheng Pharmaceutical (600267.SH) reported a mid-year performance that stands out, achieving slight revenue growth despite industry pressures, while net profit declined [2][3] - The company plans to divest Zhejiang Pharmaceutical Industry Co., aiming to lighten its operational burden for future development [2][7] Financial Performance - In the first half of 2025, Haizheng Pharmaceutical achieved revenue of 5.25 billion yuan, a slight increase of 0.13% year-on-year, maintaining a stable business foundation amid industry challenges [3] - Net profit decreased by 31.29% year-on-year, influenced by reduced convertible bond repurchase income; however, the adjusted net profit excluding non-recurring items grew by 23.92% to 321 million yuan [3] - The gross profit margin improved to 43.94%, driven by product structure optimization and cost management [4] Business Segments - The core pharmaceutical manufacturing segment remains a key revenue driver, with steady sales growth from major products like "Saismei" and "Meiman" [3] - The pet health sector emerged as a new growth area, with over 60% year-on-year growth in pet business, and the e-commerce segment surpassing 100 million yuan in sales [3] Strategic Initiatives - The company is focusing on long-term competitiveness through R&D innovation and emerging business layouts, including the development of a first-class innovative drug HS387 for oncology [6] - Haizheng Pharmaceutical is pursuing a "self-research + collaboration" model, with significant investments in synthetic biology and AI drug development [6] - The divestiture of Zhejiang Pharmaceutical Industry Co. is part of a strategy to concentrate resources on high-value areas, despite potential short-term revenue impacts [7]

Investment Rating - The investment rating for the company is "Buy" and the rating has been maintained [4][7]. Core Views - The company's operating performance is recovering positively, with a strong growth in CDMO (Contract Development and Manufacturing Organization) business [2][3]. - The company reported a revenue of 2.871 billion yuan for the first half of 2025, a year-on-year increase of 3.86%, and a net profit attributable to the parent company of 526 million yuan, up 10.70% year-on-year [2]. - The cash flow from operating activities showed significant improvement, reaching 845 million yuan, a year-on-year increase of 164.50% [2]. Summary by Sections Financial Performance - In the first half of 2025, the company achieved a revenue of 2.871 billion yuan, with CDMO business sales revenue at 2.291 billion yuan, growing 16.27% year-on-year [2][3]. - The API (Active Pharmaceutical Ingredient) and intermediate business revenue was 523 million yuan, down 28.48% year-on-year, but the gross margin improved by 2.07 percentage points to 23.26% [2][6]. - The company expects a net profit attributable to the parent company of 933 million yuan in 2025, with an EPS of 0.97 yuan per share [7]. Business Development - The CDMO project pipeline continues to expand, with new customer acquisitions progressing smoothly [3][5]. - As of June 30, 2025, the company has 38 launched projects and 1,086 projects in clinical phases, showing significant growth compared to 2024 [3]. - The TIDES division and related technology platforms are rapidly developing, with plans for capacity expansion to meet increasing demand [5]. Market Outlook - The company is well-positioned to benefit from the growth in the global market for peptides and conjugated drugs, with expectations for continued project acquisition [5]. - The forecast for net profit from 2025 to 2027 is 933 million, 1.076 billion, and 1.156 billion yuan respectively, indicating a positive growth trajectory [7].