2025年来，mRNA领域颇有"复苏"的迹象。6月底，艾伯维宣布斥资21亿美元收购体内CAR-T疗法公司 Capstan Therapeutics；而BioNTech、Moderna等更早入局的企业，也已布局了成熟的mRNA疫苗的药物 设计和递送技术等研发平台，探索肿瘤疫苗等产品的研发，进展快者已进入二期临床阶段。 近两年，BD几乎成为国内创新药企的重要"KPI"。相关数据统计，今年以来，全球肿瘤领域授权交易的 首付款中，来自中国的资产贡献了将近50%的份额。"这说明不同于过去，跨国药企现在已经非常认可 中国创新的价值；第二，也证明了中国的自主创新、成本和效率都达到了一定程度。" 具体到mRNA技术领域，该技术集合了软件式平台、通用型生产平台的优势，具备覆盖从肿瘤到自免、 代谢性疾病、传染病等多种难治性疾病的药物开发能力。作为基因技术，mRNA技术可将药物开发 从"分子筛选"转变为"信息设计"，实现了"信息即药物"，可利用人体自身生成药物，使人体成为为自身 生产药物的"智能工厂。 从过往的案例看，在个性化肿瘤疫苗产品领域，国际大药企之间有过很多交易，比较有代表性的是 Moderna和BioNTech两家的对外 ...

Core Viewpoint - The supply of Budesonide enteric-coated capsules, a key product of the innovative pharmaceutical company Cloudy New Horizon, is currently facing shortages due to increased demand and production capacity limitations, with the drug expected to be included in the national medical insurance catalog starting January 1, 2025 [2][3]. Group 1: Company Overview - Cloudy New Horizon was established in 2017 and has listed products including Budesonide enteric-coated capsules, Ilaris, and Icotinib, targeting kidney diseases, infectious diseases, and autoimmune diseases [3]. - As of July 15, 2023, the total market capitalization of Cloudy New Horizon is approximately HKD 23.6 billion [3]. Group 2: Product Details - Budesonide enteric-coated capsules are the first drug globally for the treatment of IgA nephropathy and act as an immunomodulator targeting intestinal mucosal B cells [3]. - The drug was approved for domestic marketing in May 2024 and is included in the 2024 version of the national medical insurance catalog, specifically for adult patients with primary IgA nephropathy at risk of progression [3]. Group 3: Financial Performance - In 2024, Cloudy New Horizon reported revenue of CNY 707 million, representing a year-on-year increase of 461%, primarily driven by rapid sales growth of the antibiotic Ilaris and the launch of Budesonide enteric-coated capsules [4]. - The company incurred a net loss of CNY 1.041 billion in the same year, largely due to one-time, non-recurring impairment losses related to intangible assets associated with mRNA COVID-19 vaccines [4].

Group 1 - The top three companies with the highest short positions are WuXi AppTec (22.57%), CATL (17.76%), and COSCO Shipping Holdings (14.27%) [1][2] - The companies with the largest absolute increase in short positions are Alibaba Health (4.45%), China Liansu (2.54%), and Hong Kong Travel (2.02%) [1][2] - The companies with the largest absolute decrease in short positions are Far East Horizon (-1.62%), ZhongAn Online (-1.55%), and Rongchang Biologics (-1.32%) [1][3] Group 2 - The latest short position data shows that WuXi AppTec has 87.35 million shares, CATL has 27.69 million shares, and COSCO Shipping Holdings has 411 million shares [2] - Alibaba Health's short position increased from 6.97% to 11.42%, while China Liansu's increased from 0.61% to 3.15% [2] - Far East Horizon's short position decreased from 4.43% to 2.82%, and ZhongAn Online's decreased from 7.43% to 5.88% [3][4]

Core Insights - The emerging autologous CAR-T therapy significantly reduces costs compared to traditional CAR-T therapies, which can exceed hundreds of thousands of yuan, but it faces high technical barriers [1][4]. Industry Developments - AbbVie announced a $2.1 billion acquisition of Capstan Therapeutics to expand its product line in autoimmune disease therapies, marking the highest transaction record in the cell therapy sector for 2025 [1]. - CloudTop New Horizon (01952.HK) reported advancements in its autologous CAR-T projects, which utilize a proprietary targeted LNP (tLNP) system for treating tumors and autoimmune diseases, achieving effective tumor cell clearance in humanized mouse models and validating T cell transfection in non-human primate models [1]. Advantages of Autologous CAR-T Therapy - Compared to traditional CAR-T therapies, autologous CAR-T therapy offers multiple advantages, including large-scale production capabilities, no need for lymphodepleting chemotherapy prior to treatment, predictable pharmacokinetics/pharmacodynamics, adjustable dosing, and better overall quality control [4]. - The mRNA technology in autologous CAR-T therapy allows for a shift from "molecular screening" to "information design," enabling the body to produce its own drugs, thus marking a new era in biopharmaceuticals [4]. Cost Reduction Potential - The core advantage of in vivo CAR-T cell manufacturing lies in significantly simplifying the process and reducing costs, potentially lowering the cost of a single treatment by an order of magnitude compared to currently commercialized CAR-T therapies [4]. Challenges in Autologous CAR-T Therapy - The main challenge for autologous CAR-T therapy is the precise, efficient, and safe delivery of CAR-T constructs to target T cells [5]. - Two primary technical routes have emerged: lentiviral vectors and RNA delivery. Lentiviral vectors can achieve permanent CAR expression but may lack targeting precision, while RNA delivery offers higher safety but only transient CAR protein synthesis [5]. - The high technical barriers in autologous CAR-T technology limit participation to a few companies, requiring proprietary cationic lipids and stringent delivery technology to target spleen and peripheral T cells while avoiding safety risks associated with liver expression [5].

Group 1 - The core viewpoint of the news highlights the recent stock performance of CloudTop New Horizon (01952.HK), which closed at HKD 67.000, a slight decrease of 0.15% from the previous trading day, with an intraday high of HKD 69.800, marking a new high in nearly a year [1] - The company experienced a net outflow of HKD 37.6499 million in capital on the day, with unspecified amounts flowing in and out [1] Group 2 - CloudTop New Horizon Limited is a Hong Kong-listed biopharmaceutical company focused on the research, clinical development, manufacturing, and commercialization of innovative drugs and vaccines, aiming to meet unmet medical needs in Greater China and other Asian markets [2] - The management team possesses extensive expertise and experience in high-quality research and development, clinical development, regulatory affairs, chemical manufacturing and control (CMC), business development, operations, and commercialization within the pharmaceutical industry [2] - The company has established a portfolio of globally first-in-class or best-in-class drugs and vaccines in areas such as nephrology, mRNA platforms, infectious and communicable diseases, and autoimmune diseases [2] - CloudTop New Horizon initiated commercial listing in 2021 and is building a professional and efficient commercialization team to accelerate product commercialization in Greater China and other Asia-Pacific markets [2] - The company is committed to becoming a leading biopharmaceutical company in Asia, focusing on the development and commercialization of innovative drugs and vaccines to meet the growing medical needs in China and globally, with a mission to enhance human health and well-being [2]

Investment Rating - The industry investment rating is "Positive" (maintained) [2] Core Insights - The report highlights the acquisition of Capstan Therapeutics by AbbVie for up to $2.1 billion, focusing on in vivo CAR-T therapy development [6][15] - The report emphasizes the growing interest and investment in in vivo CAR-T technology, with multiple companies actively pursuing diverse delivery systems [7][26] - The pharmaceutical and biotechnology sector saw a weekly increase of 3.64%, outperforming the CSI 300 index by 2.1 percentage points, ranking 4th among 31 sub-industries [8][31] Summary by Sections 1. AbbVie Acquisition of Capstan - AbbVie announced the acquisition of Capstan Therapeutics for a maximum of $2.1 billion, focusing on in vivo CAR-T therapies [6][15] - Capstan's main asset, CPTX2309, is an RNA delivery candidate for anti-CD19 CAR-T therapy, currently in Phase I clinical trials [15][20] 2. MNC's Active Layout in In Vivo CAR-T Technology - MNC has been actively investing in in vivo CAR-T technology through collaborations and acquisitions, focusing on both lentiviral and lipid nanoparticle delivery systems [7][26] - The report notes that over 20 disclosed mRNA technology projects in in vivo CAR-T are primarily concentrated in the lipid nanoparticle direction [22][30] 3. Weekly Performance of the Pharmaceutical Sector - The pharmaceutical sector increased by 3.64% in the first week of July, outperforming the CSI 300 index [31] - Among sub-sectors, other biological products saw the highest increase of 8.28%, while medical equipment experienced the largest decline of 0.21% [35][36] 4. Recommended Stocks - Recommended stocks include major pharmaceutical and biotechnology companies such as Heng Rui Medicine, East China Medicine, and others [9]

Core Viewpoint - The company, Ginkgo Bioworks, is balancing operational sustainability with future growth through a dual strategy of "licensing in + independent research and development" to drive innovation and revenue generation [1][2]. Group 1: Business Strategy - Ginkgo Bioworks has achieved stable cash flow through the introduction of large commercial products while focusing on cutting-edge mRNA therapies, resulting in the development of key products such as EVM14, EVM16, and CAR-T [1][3]. - The company has established a comprehensive technology platform that includes antigen design, mRNA sequence optimization, lipid nanoparticle delivery technology, and industrial production capabilities, making it one of the few companies with end-to-end capabilities in the industry [3][6]. Group 2: Financial Performance - Financial data indicates that Ginkgo Bioworks expects to generate revenue of 707 million yuan in 2024, representing a year-on-year increase of 461%, driven by three commercialized products [3]. - The company aims to achieve sales of 10 billion yuan by 2030, leveraging its existing product portfolio [3]. Group 3: Competitive Advantage - Ginkgo Bioworks possesses a proprietary lipid library of over 500 types, which supports various projects including vaccines and CAR-T therapies [5][6]. - The company has developed an AI algorithm for efficient antigen sequence design, with its algorithm system now in its third generation, and has established a lipid nanoparticle delivery technology platform with patent protections [6]. Group 4: Market Position - Major pharmaceutical companies like AbbVie, Eli Lilly, Johnson & Johnson, and AstraZeneca are investing in mRNA therapies and CAR-T technologies, indicating a competitive landscape [4]. - Ginkgo Bioworks is one of the few domestic companies capable of full-process localized production of mRNA therapy drugs, enhancing its market position [6].

Group 1 - BioNTech's research on mRNA neoantigen vaccines shows potential in treating pancreatic cancer by inducing long-lived CD8+ T cell responses, offering new hope for cancer immunotherapy [1] - The challenge of tumor recurrence and metastasis remains significant in clinical treatment, highlighting the importance of mRNA technology in immune response [1] - Cloud Health's CEO discusses how mRNA technology stimulates T and B cells to create specific immune responses against tumor cells, forming immune memory to reduce recurrence risk [1] Group 2 - mRNA technology shifts drug development from "molecular screening" to "information design," transforming the human body into a smart factory for protein drug production [2] - Despite its advantages, the delivery system poses a major barrier for mRNA technology, as synthesized mRNA is prone to degradation when entering the human body [2] - Cloud Health has made breakthroughs in delivery technology, establishing a proprietary LNP (lipid nanoparticle) delivery platform with patents in ionizable and stealth lipids [2] Group 3 - The third-generation AI algorithm significantly enhances target protein expression levels, enabling Cloud Health to advance mRNA tumor drug development [3] - EVM16 is Cloud Health's first personalized mRNA tumor vaccine entering clinical stages, with the first patient dosing completed in March 2025 [3] - EVM14 is a universal therapeutic vaccine targeting five tumor-related antigens, intended for the treatment of squamous cell carcinoma [3]

Investment Rating - The report assigns a "Buy" rating to the company, with a target price of HKD 72.50, indicating a potential upside of 16.6% from the current closing price of HKD 62.20 [1][27]. Core Insights - The mRNA platform development is progressing steadily, with excellent data on the reversible BTK inhibitor for membranous nephropathy. The target price has been raised to reflect these developments [2][6]. - The company has showcased its fully integrated and localized AI + mRNA platform, highlighting several mRNA tumor drug developments, including personalized and universal therapeutic vaccines [6]. - The reversible BTK inhibitor EVER001 has shown promising results in clinical trials for treating membranous nephropathy, with significant reductions in anti-PLA2R antibody levels and urinary protein levels [6]. Financial Overview - Revenue projections for the company are as follows: - 2023: RMB 126 million - 2024: RMB 707 million - 2025E: RMB 1,660 million - 2026E: RMB 2,552 million - 2027E: RMB 3,752 million - Year-on-year growth rates are projected at 884.5% for 2023, 461.2% for 2024, and 134.9% for 2025 [5][28]. - The net profit (loss) is expected to improve from a loss of RMB 844 million in 2023 to a profit of RMB 743 million by 2027 [5][28]. - The company’s market capitalization is approximately HKD 20.2 billion, with an average daily trading volume of 13.36 million shares [3]. Valuation Metrics - The report indicates a peak sales estimate for EVER001 exceeding RMB 1.5 billion, with a target valuation of HKD 72.50 corresponding to a market cap of HKD 237 billion and a price-to-sales ratio of 1.8 times at peak revenue [6][24]. - The company’s financial forecasts have been adjusted, reflecting a more cautious outlook on product revenue ramp-up, with slight downward revisions in revenue estimates for 2025-2027 [6][23].

Core Viewpoint - CICC maintains the profit forecast for CloudTop New Horizon (01952) for 2025 and 2026, adjusting the target price by 14.3% to HKD 80.0, indicating a potential upside of 28.6% from the current stock price [1] Company Status - On June 27, CloudTop New Horizon held an mRNA innovation technology platform R&D day, showcasing three core product lines: the universal on-demand therapeutic vaccine EVM14, the personalized therapeutic vaccine EVM16, and the autologous CAR-T project. The company has established extensive contacts with global top 20 pharmaceutical companies, focusing on leveraging international partnerships to promote the global layout of innovative drugs [2] Complete mRNA R&D and Production Platform - The company has successfully built a comprehensive mRNA platform covering antigen design, algorithm optimization, LNP delivery systems, CMC process development, and GMP industrial production. Key patents include: 1) self-developed third-generation AI algorithm optimization, significantly enhancing target protein expression; 2) proprietary LNP delivery platform with over 500 internal lipid types, capable of liver and extrahepatic delivery, supporting both "passive" and "active" targeting strategies; 3) two major bases in Zhangjiang and Jiashan ensuring process development and industrial production [3] Project Progress - EVM16: Utilizes the company's self-developed EVER-NEO-01 "MiaoSuan" AI algorithm system to identify patient-specific tumor cell mutations and design mRNA vaccines encoding dozens of new tumor antigens. Preclinical data indicates good safety and strong immunogenicity, with IIT research completing the first patient dosing in March this year [4] - EVM14: A universal on-demand therapeutic bivalent vaccine targeting five tumor-related antigens, intended for squamous cell carcinoma, including non-small cell lung cancer and head and neck cancer. Preclinical data shows EVM14 can induce a strong immune response and can be combined with IO drugs to enhance anti-tumor activity, with FDA approval for clinical trials obtained in March [4] - Autologous CAR-T: Developed based on the proprietary LNP (tLNP) system, demonstrating efficient T cell transfection, CAR expression, and B cell clearance effects in monkey models [4]