证券研究报告 自免行业报告（一）：双靶协同拓展治疗边界， 重视TSLP类双抗迭代潜力 中邮证券研究所 医药团队 行业投资评级：强大于市|维持 盛丽华（首席分析师） SAC编号：S1340525060001 徐智敏（研究助理） SAC编号：S1340125080012 1 1 发布时间：2025-09-29 投资要点 前言：下一个自免领域的blockbuster的潜在分子在于理解现有疗法下自免领域亟待解决的未满足需求是什么。 自免的药物明显的特征在于人数多、DOT长（长期用药），往往能诞生多个blockbuster，如度普利尤单抗、丽生奇珠单抗、 乌司奴单抗等销售超过100亿美元的分子，本系列报告想探讨下一个自免领域的blockbuster的潜在分子会是什么？而关于 这一问题我们认为思考的核心方向在于，现有疗法下自免领域亟待解决的未满足需求是什么以及什么样的药物最有可能率先 满足这些需求。 高患病基数人群孕育大市场，大市场催生药物新需求。 回顾来看，Dupi的成功在于"一药治多症"，进一步来看其覆盖的核心适应症特应性皮炎（AD）、哮喘、COPD患病人数 庞大，均为千万人数级别。在现有疗法下上述适应症仍未满足的关 ...

Core Viewpoint - Chronic Obstructive Pulmonary Disease (COPD) has a high prevalence and mortality rate, indicating a significant unmet medical need for new treatment options [1] Group 1: Unmet Medical Needs in COPD - COPD is a leading cause of disability and death globally, with approximately 300 million cases worldwide and 100 million in China [1] - Current standard treatments (LAMA/LABA/ICS) have been in use for 40 years and carry risks of pneumonia, cardiovascular issues, and urinary tract infections, highlighting the urgent need for new therapies [1] Group 2: PDE3/4 Inhibitors and Market Activity - Merck acquired Verona for $10 billion to obtain Ensifentrine, while GSK spent approximately $12.5 billion to acquire HRS-9821 from Hansoh Pharma, reflecting the importance of the respiratory market and PDE3/4 targeted drugs [2] - PDE3 and PDE4 inhibitors have synergistic effects, potentially improving airway smooth muscle contraction and controlling inflammation, thus showing significant application potential [2] - Ensifentrine received FDA approval in June 2024, with sales reaching $217 million by Q2 2025, representing a 44% quarter-over-quarter growth, indicating substantial market potential [2] Group 3: Targeted Therapies for Eosinophilic Phenotype - Dupilumab (IL-4R) and mepolizumab (IL-5) have been successfully approved for COPD, focusing on high eosinophil count populations [3] - Dupilumab, the first targeted therapy for COPD, was approved by the FDA in 2024, with sales exceeding $14 billion in 2024 [3] - Mepolizumab showed positive results in trials with eosinophilic phenotype patients, demonstrating a correlation between eosinophil count and reduced acute exacerbation rates [3] Group 4: Emerging Targets and Domestic Innovations - TSLP and ST2/IL33 targets currently lack approved drugs, but domestic companies are innovating [4] - Amgen/AZ's tezepelumab is the only TSLP monoclonal antibody on the market, while domestic firms like Zhengda Tianqing and Kangnuo are developing differentiated therapies with promising efficacy [4] - The ST2/IL33 target, which is upstream of IL-4/IL-13, is being explored by domestic companies, with no approved drugs globally yet [4]

Investment Rating - The report does not explicitly state an investment rating for the allergic rhinitis drug industry in China. Core Insights - The Chinese allergic rhinitis drug market is projected to grow from CNY 44 billion in 2019 to CNY 81 billion by 2024, with a compound annual growth rate (CAGR) of 12.9%. By 2030, the market is expected to reach CNY 229 billion, reflecting a growth rate of 19.0% [5]. - The report highlights the increasing importance of biological agents in treating moderate to severe allergic diseases, with significant advancements in drug development and clinical applications [20][23]. Summary by Sections Market Overview - The market for allergic rhinitis drugs in China is expected to grow from CNY 422 billion in 2019 to CNY 462.8 billion by 2024, with a CAGR of 1.9%, and is projected to reach CNY 567.7 billion by 2030 [16]. Treatment Landscape - Current treatment options for allergic rhinitis are categorized into first-line, second-line, and third-line therapies. First-line treatments include nasal corticosteroids and second-generation antihistamines [5][11]. - Immunotherapy is recommended as a first-line treatment for the underlying cause of allergic rhinitis, while symptomatic treatments focus on alleviating symptoms [11]. Drug Development - Biological agents, particularly monoclonal antibodies targeting IL-4Rα and IgE, are gaining traction in the treatment of allergic rhinitis. The first approved IL-4Rα biological agent, Suptuizumab, offers a new treatment option for patients [20][23]. - The report notes that the development of new biological agents is ongoing, with several candidates in various stages of clinical trials [20][23]. Patient Demographics and Treatment Needs - The report indicates that the treatment needs of allergic rhinitis patients vary based on the severity of their condition. A significant portion of patients requires comprehensive treatment strategies, especially those with moderate to severe persistent allergic rhinitis [19]. - The high conversion rate between allergic rhinitis and asthma underscores the importance of long-term management and early intervention in treatment [19]. Innovation and Market Dynamics - The report emphasizes the shift towards targeted biological therapies due to the limitations of traditional treatments. The market for anti-IgE antibodies is evolving with new formulations and biosimilars, enhancing treatment options for patients [23][24]. - The report also highlights the maturity of upstream technologies related to the production of antihistamines and biological agents, which supports industry growth [27][29].

Investment Rating - The report indicates a positive outlook for the atopic dermatitis (AD) market, highlighting significant unmet medical needs and potential for new therapies, particularly in small molecules and biologics [4][10][12]. Core Insights - Atopic dermatitis is a chronic, recurrent inflammatory skin disease characterized by severe itching, affecting approximately 600-700 million patients globally, with around 67 million in China, indicating a substantial unmet demand for effective treatments [1][18][20]. - Recent advancements in small molecules and biologics have marked a new phase in AD treatment, with several new products entering the market, although the number remains limited [1][10][32]. - JAK inhibitors have shown excellent efficacy but come with safety concerns, while TYK2 inhibitors are emerging as a promising new option due to their selective action and potentially better safety profile [2][11][12]. - Biologics targeting IL-4Rα and IL-13 have demonstrated significant efficacy in improving skin lesions, with IL-31 showing strong itch relief capabilities [3][12][13]. - The development of dual/multi-target antibodies is seen as a new strategy to enhance treatment efficacy by combining the advantages of different targets [4][13][21]. Summary by Sections Investment Highlights - The AD market has immense potential, with a pressing need for effective therapies [4][10]. - The patient population is large, with over 600 million affected globally, necessitating urgent treatment options [1][18]. Disease Characteristics - AD is characterized by chronic inflammation and severe itching, significantly impacting patients' daily lives [1][14]. - The disease burden is heavy, with a complex pathogenesis involving multiple factors, primarily driven by Th2-type inflammation [21][24]. Current Treatment Landscape - Traditional therapies have safety concerns, leading to a shift towards biologics and small molecules [32][35]. - JAK inhibitors are the most approved class of drugs for AD, but they carry black box warnings due to safety issues [11][12]. - Emerging therapies, particularly TYK2 inhibitors, show promise for better safety and efficacy [2][11]. Biologics and Emerging Therapies - Currently approved biologics include IL-4Rα, IL-13, TSLP, and IL-31, with ongoing research into additional targets [3][12][13]. - Dual/multi-target antibodies are being explored to improve treatment outcomes and extend dosing intervals [4][13][21]. Market Potential - The report emphasizes the significant market potential for AD treatments, with projected growth driven by increasing patient numbers and the introduction of innovative therapies [4][10][20].

Core Viewpoint - Sanofi's experimental drug amlitelimab for treating atopic dermatitis failed to meet Wall Street expectations in late-stage clinical trials, resulting in a stock price drop of over 9% [1]. Group 1: Drug Development and Clinical Trials - Sanofi is developing amlitelimab to treat atopic dermatitis, a severe form of eczema, aiming for it to complement or potentially replace its blockbuster drug Dupixent, which has patent protection until 2031 [1]. - Analysts from Jefferies noted that while amlitelimab has good safety data and a convenient dosing schedule of once every 12 weeks, its efficacy in the Phase III trial was inferior to previous trial data and less effective compared to competing biologics [1]. - JPMorgan analysts indicated that the data shows amlitelimab's efficacy is not as strong as Dupixent [1]. Group 2: Market Impact - Sanofi's stock fell by 8.9%, making it the largest decliner among the constituents of the STOXX 600 index [2].

Core Viewpoint - Hunan Maijibio Technology Co., Ltd. has submitted an application for a main board listing on the Hong Kong Stock Exchange, focusing on innovative biopharmaceuticals for allergic and autoimmune diseases, but faces significant challenges including zero commercialization of products, ongoing substantial losses, high debt ratios, patent disputes, and intense competition in its sector [1][2][4]. Company Overview - Established in 2016, Maijibio specializes in developing innovative therapies for allergic and autoimmune diseases through bioreagent technology, with a pipeline of 8 candidate products, including MG-K10, which is in phase III clinical trials [2][3]. - The company reported negligible revenues of 8.72 million yuan, 24,000 yuan, and 0 yuan for 2023, 2024, and Q1 2025 respectively, all from early-stage R&D service collaborations, with no products approved for market sale [2][3]. Financial Performance - Maijibio has incurred net losses of 253 million yuan, 178 million yuan, and 27.27 million yuan for the years 2023, 2024, and Q1 2025, respectively, with cumulative losses exceeding 800 million yuan by March 2025 [2][3]. - The company's debt ratio has been over 100% for an extended period, peaking at nearly 700% at the end of 2023, and still standing at 166.83% by March 2025, indicating severe financial distress [2][3]. R&D and Market Potential - The R&D expenditures for 2023 and 2024 are projected to be 166 million yuan and 150 million yuan, respectively, with the company relying heavily on external financing due to a lack of self-sustaining revenue [3]. - The IL-4Rα targeted therapy market is projected to reach 4.08 billion USD in China by 2030, attracting numerous competitors, including domestic players who have already launched products [6][7]. Competitive Landscape - Maijibio's MG-K10 is a latecomer in a crowded market, facing competition from over 10 companies, including those with products already in late-stage clinical trials [7]. - The company has partnered with Kangzhe Pharmaceutical for the joint development and exclusive commercialization of MG-K10, which provides financial support but also raises concerns about potential internal competition due to overlapping product lines [7][8]. Legal and Governance Issues - The core product MG-K10 has been embroiled in a patent ownership dispute, which raises questions about the originality and independence of its technology [4]. - The founder's salary has seen a dramatic increase from 5.469 million yuan in 2023 to 18.08 million yuan in 2024, contrasting sharply with the company's financial struggles [5]. Investment and Financing - Maijibio has completed seven rounds of financing, raising approximately 730 million yuan, with significant investments from notable institutions [8]. - The company has entered into strict agreements with investors, allowing them to demand share buybacks if the company fails to go public by the end of 2025, with potential repercussions extending to 2027 [9].

Core Insights - The global top-selling drugs for the first half of 2025 have been released, with Novo Nordisk's semaglutide leading the sales at 166.83 billion USD, followed by Merck's pembrolizumab and Eli Lilly's tirzepatide [1][3][4] Group 1: Top-Selling Drugs - Semaglutide from Novo Nordisk achieved sales of 166.83 billion USD, maintaining its position as the "king of drugs" [1][3] - Pembrolizumab from Merck recorded sales of 151.61 billion USD, ranking second [3] - Tirzepatide from Eli Lilly reached sales of 147.34 billion USD, securing the third position [3] Group 2: Sales Growth and Market Dynamics - Semaglutide's sales growth is driven by its three products: Ozempic (95.46 billion USD), Rybelsus (16.79 billion USD), and Wegovy (54.58 billion USD), with Wegovy showing a remarkable growth of 78% [5][6] - Tirzepatide has rapidly gained market share, with Mounjaro's sales skyrocketing from 4.83 billion USD in 2022 to an expected 115.4 billion USD in 2024 [7] - The competition between semaglutide and tirzepatide is intensifying, with both drugs exceeding 140 billion USD in sales for the first half of 2025 [7] Group 3: Market Challenges - The entry of biosimilars has impacted the sales of established drugs, with Janssen's ustekinumab dropping out of the top 10 due to a significant decline in sales [8] - Ustekinumab's sales fell by 38.6% in the first half of 2025, reaching only 32.78 billion USD [8] - Despite challenges, Johnson & Johnson's daratumumab saw a 21.7% increase in sales, reaching 67.76 billion USD, indicating strong demand in the multiple myeloma market [9][10]

Core Insights - The global top-selling drugs for the first half of 2025 have been released, with Novo Nordisk's semaglutide leading the sales at 166.83 billion USD, followed by Merck's pembrolizumab and Eli Lilly's tirzepatide [1][3][4] Sales Performance - Semaglutide achieved sales of 166.83 billion USD, maintaining its position as the top-selling drug [1][3] - Pembrolizumab (K drug) recorded sales of 151.61 billion USD, while tirzepatide reached 147.34 billion USD [3] - Other notable drugs include apixaban at 111.71 billion USD and dupilumab at 80.15 billion USD [3] Market Dynamics - The competition for the title of "King of Drugs" is intensifying, with new entrants like tirzepatide rapidly gaining market share [1][5] - Semaglutide's sales are bolstered by its three product variants, with the weight loss version, Wegovy, showing a remarkable growth of 78% [5][6] - Tirzepatide has been recognized for its rapid market uptake, with sales skyrocketing from 4.83 billion USD in 2022 to an expected 115.4 billion USD in 2024 [7] Product Innovations - Wegovy has recently gained approval for treating metabolic-associated fatty liver disease, which is expected to further enhance its sales [6] - Tirzepatide is the first and only dual-target GLP-1 receptor agonist approved for type 2 diabetes, positioning it as a strong competitor to semaglutide [7] Market Challenges - The entry of biosimilars has impacted the sales of established drugs, with Johnson & Johnson's ustekinumab dropping out of the top 10 due to a significant sales decline [8] - Ustekinumab's sales fell by 38.6% in the first half of 2025, reflecting the challenges faced by original drugs as patents expire [8] Future Outlook - Daratumumab from Johnson & Johnson has shown a 21.7% increase in sales, indicating strong market potential in the multiple myeloma segment [9][10] - The overall trend suggests a shift in market leadership as newer drugs gain traction and established drugs face competitive pressures [1][5][8]

Core Insights - AbbVie is poised to fill the $20 billion gap left by Humira with its new immunology drugs Skyrizi and Rinvoq, which are expected to generate over $25 billion in combined sales this year, significantly exceeding initial forecasts [1][4] - Skyrizi's sales reached $4.4 billion in Q2, showing a year-on-year growth of 61.8%, while Rinvoq generated $2 billion, indicating strong momentum for both products [4][5] - The rapid growth trajectory of Skyrizi suggests it could surpass $20 billion in sales by 2026, establishing it as a potential new leader in the immunology market [2][4] Sales Performance - Skyrizi's global sales are projected to exceed $10 billion in 2024, driven by its expanding indications in inflammatory bowel disease (IBD) and dermatological conditions, with a year-on-year growth of 50.9% [3][4] - AbbVie has raised Skyrizi's 2025 sales forecast to $17.1 billion, a 46% increase from the previous year, with $4 billion of this growth attributed to IBD indications [4][6] - Rinvoq is also expected to contribute significantly, with a clear three-phase strategy targeting various indications, including rheumatoid arthritis and IBD [5][6] Competitive Landscape - The immunology market is becoming increasingly competitive, with major players like Johnson & Johnson and Eli Lilly entering the IL-23 target space, raising concerns about market share and growth sustainability [7][8] - AbbVie maintains confidence in Skyrizi's market position, citing its increasing share among treated patients and its differentiated advantages over competitors [7][8] - The rapid pace of innovation in the immunology sector is compressing the window for new entrants, making it crucial for companies to establish strong clinical differentiation and market presence [10][11] Future Outlook - The transition from Humira to Skyrizi and Rinvoq exemplifies the need for continuous innovation in the pharmaceutical industry, as the market dynamics shift rapidly [10][11] - AbbVie is entering a new phase with its immunology portfolio, having no major patent expirations in the next decade, providing it with more strategic options [4][10] - The success of Skyrizi and Rinvoq highlights the importance of robust clinical data and broad indications in driving growth in the competitive landscape of immunology [6][9]

Core Insights - The innovative drug market in China is experiencing significant growth, with the total amount of License out transactions for innovative drugs expected to reach nearly $66 billion by the first half of 2025, surpassing the total BD transaction amount for 2024 [1] - The immune system drug market is the second largest prescription drug market globally, with an increasing share of BD transactions, particularly in the autoimmune disease sector, which is gaining attention due to unmet medical needs [2][23] - The emergence of bispecific antibodies (dual antibodies) in the autoimmune disease field is anticipated to create new blockbuster drugs, as they can target multiple antigens simultaneously, enhancing treatment efficacy [7][8][23] Group 1: Market Dynamics - The market for autoimmune disease treatments is projected to reach $119.35 billion by 2027, driven by high demand and long treatment cycles for conditions like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) [2] - The TNFα inhibitors, particularly AbbVie's Humira, have generated over $200 billion in revenue over its lifecycle, showcasing the potential for successful drug development in the immune market [2][4] - The competition in the immune drug market is intensifying, with a growing number of patented drugs and a shift towards precision medicine in clinical and commercial strategies [5] Group 2: Bispecific Antibodies - Bispecific antibodies are gaining traction in autoimmune disease treatment, with the ability to simultaneously target different antigens, potentially leading to more effective disease management [7][8] - Clinical data from Roche's bispecific antibody shows significant efficacy in treating refractory SLE patients, indicating the potential of this class of drugs in the autoimmune sector [8] Group 3: Company Insights - Kangnuo Pharmaceutical is positioned as a leading player in the autoimmune field, with its core product CM310 being the first domestically approved IL-4Rα antibody, currently in the commercialization stage [13][23] - The success of CM310 in the market is contingent on its inclusion in the medical insurance negotiation, which is crucial for its sales growth [16][23] - Kangnuo's innovative approach through the NewCo model for licensing out its products has proven beneficial, providing cash flow support and reducing risks for the company [22][23] Group 4: Future Outlook - The potential for Kangnuo's CM310 to achieve significant sales in the Chinese market is optimistic, with projections suggesting it could reach nearly $5 billion by 2030 if it successfully navigates the insurance landscape [23] - The company's advancements in the ADC drug CMG901 for cancer treatment are also noteworthy, with clinical progress ahead of competitors [19][23]