NOD样受体蛋白3(NLRP3)作为长期被验证的抗炎靶点，可介导促炎细胞因子IL1β与IL18释放，并处于炎症级联反 应的上游关键位置，被认为是抗炎药物开发的成熟靶点。近期，英矽智能(03696)宣布提名靶向NLRP3的外周限制 性抑制剂ISM5059，该候选药物具有新颖母核，由英矽智能自有Pharma.AI平台驱动设计。 在多个临床前动物模型中，ISM5059表现出优秀的体内疗效，有望在自身免疫性疾病、炎症性疾病、代谢性疾 病、心血管疾病及眼科疾病领域进行后续潜力探索，展现pipeline in a drug潜力。 生物医药领域的管线开发决策，往往是创新性、可行性、投入产出比等因素的多维平衡。其中，"pipeline in a drug"是一种极具吸引力的策略：通过同一药物覆盖多种适应症，形成可持续扩展的商业与临床价值。阿达木单 抗、帕博利珠单抗(K药)等"药王"正是这一策略的典型代表。 随着全球内分泌与代谢市场逼近2000亿美元，NLRP3潜力与海量需求的碰撞是否能诞生下一个"药王"? 透脑VS外周，炎症性疾病治疗的细分化未来 炎症反应在不同疾病中的驱动机制与病灶部位存在显著差异，因此治疗策略也呈现细化、 ...

Market Performance - The pharmaceutical sector increased by +0.29% on January 26, 2025, outperforming the CSI 300 index by 0.19 percentage points, ranking 8th among 31 sub-industries in the Shenwan classification [1] - Among sub-industries, vaccines (+7.99%), in vitro diagnostics (+3.73%), and blood products (+3.47%) showed the best performance, while hospitals (-2.01%), medical R&D outsourcing (-1.36%), and offline pharmacies (-1.18%) lagged behind [1] - Top three individual stock gainers were Maike Biological (+20.03%), Cap Bio (+20.03%), and Zhijiang Biological (+20.01%), while the biggest losers were Weikang Pharmaceutical (-8.50%), Medisi (-7.28%), and Meinian Health (-6.08%) [1] Industry News - Recently, InSilico Medicine announced that its self-developed oral NLRP3 inhibitor ISM8969 has received IND approval from the FDA for the treatment of Parkinson's disease [2] - The upcoming Phase 1 clinical trial will assess the safety, tolerability, and pharmacokinetic characteristics of ISM8969 in healthy volunteers, aiming to determine the recommended dosage for subsequent studies [2] - ISM8969 is an innovative NLRP3 inhibitor with ideal blood-brain barrier penetration characteristics, targeting pathological inflammatory responses to support neuronal survival and function in neurodegenerative disease patients [2] - The drug candidate was discovered and optimized using InSilico Medicine's AI platform, Chemistry42 [2] Company News - Jiuan Medical (002432) expects to achieve a net profit attributable to shareholders of 2.02-2.35 billion yuan in 2025, representing a year-on-year growth of 21.05%-40.83%, with a non-recurring net profit forecast of 2.07-2.40 billion yuan, up 23.18%-42.81% [3] - Sanofi Guojian (688336) anticipates a revenue of 4.20 billion yuan in 2025, a significant year-on-year increase of 251.76%, with a net profit of 2.90 billion yuan, up 311.35%, and a non-recurring net profit of 2.80 billion yuan, reflecting a staggering growth of 1038.21% [3] - Dabo Medical (002901) forecasts a net profit of 580-610 million yuan in 2025, a growth of 62.55%-70.96%, with a non-recurring net profit of 455-485 million yuan, up 59.42%-69.93% [3] - Microchip Biotech (688321) expects a revenue of 910 million yuan in 2025, a year-on-year increase of 38.32%, with a net profit of 53 million yuan, marking a return to profitability, and a non-recurring net profit of 38 million yuan, also indicating a return to profitability compared to the previous year [3]

Investment Rating - The overall industry investment rating is neutral, with specific sub-industry ratings as follows: Chemical Pharmaceuticals - No rating, Traditional Chinese Medicine - No rating, Biopharmaceutical II - Neutral, Other Pharmaceuticals - Neutral [3][9] Core Insights - The pharmaceutical sector experienced a slight increase of +0.29% on January 26, 2025, outperforming the CSI 300 index by 0.19 percentage points, ranking 8th among 31 sub-industries in the Shenwan classification. Notable performers included vaccines (+7.99%), in vitro diagnostics (+3.73%), and blood products (+3.47%), while hospitals (-2.01%), medical R&D outsourcing (-1.36%), and offline pharmacies (-1.18%) lagged behind [4][5] - Recently, the company InSilico Medicine announced that its oral NLRP3 inhibitor ISM8969 received FDA approval for clinical trials aimed at treating Parkinson's disease. The upcoming Phase I trial will assess the safety, tolerability, and pharmacokinetics of ISM8969 in healthy volunteers, highlighting its potential to modulate pathological inflammatory responses in neurodegenerative diseases [5] - Ji'an Medical (002432) expects a net profit of 2.02-2.35 billion yuan for 2025, representing a year-on-year growth of 21.05%-40.83%. Meanwhile, Sangfor Health (688336) anticipates a revenue of 4.2 billion yuan, a 251.76% increase, and a net profit of 2.9 billion yuan, reflecting a 311.35% growth [6]

Investment Rating - The report does not explicitly state an investment rating for the industry or specific companies. Core Insights - The report highlights significant developments in the overseas pharmaceutical sector, including the collaboration between Insilico Medicine and Heng Tai Biopharma to develop a novel NLRP3 inhibitor for central nervous system diseases [2][6]. - The report notes that MicroPort Robotics expects a revenue growth of approximately 110%-120% year-on-year for 2025, with an adjusted net loss not exceeding 240 million yuan, representing a reduction of over 50% [5][6]. - GSK has reached a final agreement to acquire RAPT Therapeutics for approximately 2.2 billion USD, focusing on a long-acting monoclonal antibody currently in clinical trials [7][8]. Summary by Sections 1. Overseas Pharmaceuticals - Insilico Medicine and Heng Tai Biopharma have entered a partnership to develop ISM8969, a novel oral NLRP3 inhibitor, with both companies holding 50% global rights [2][6]. - The Hong Kong Stock Exchange has approved the full circulation of 182,645,856 H shares for Fuhong Hanlin, representing about 33.61% of the company's total issued shares as of January 19 [2][6]. - The new drug application for TLX591-CDx, a radiopharmaceutical for prostate cancer diagnosis, has been accepted by the NMPA [2][6]. 2. Company Updates - MicroPort Robotics has reported over 180 commercial orders and more than 120 installations globally as of January 21 [5][6]. - Legend Biotech, a joint venture of Genscript Biotech, reported a trade sales net of approximately 555 million USD for the quarter ending December 31, 2025 [5][6]. - GSK's acquisition of RAPT Therapeutics includes a payment of 58.00 USD per share, with an expected upfront investment of 1.9 billion USD after cash adjustments [7][8]. 3. Market Performance - The Hang Seng Healthcare Index fell by 4.35%, underperforming the Hang Seng Index by 3.26 percentage points [4]. - The report indicates a strong performance in the overseas education sector, with GMV for Dongfang Zhenxuan reaching approximately 310 million yuan, a 42.8% increase week-on-week [15][16]. 4. Recommendations - The report suggests focusing on innovative drugs and the ongoing clinical progress of key pipelines from companies such as BeiGene, Innovent Biologics, and others [12]. - It also recommends monitoring the performance of educational companies like Dongfang Zhenxuan and China Oriental Education, which are expected to benefit from improved operational strategies and increased enrollment [16].

Investment Rating - The report maintains a "Positive" outlook on the overseas pharmaceutical sector, highlighting significant developments and collaborations in the industry [1]. Core Insights - The collaboration between Insilico Medicine and Heng Tai Biologics to develop an innovative brain-penetrating NLRP3 inhibitor is a key highlight, with potential applications in treating central nervous system diseases [2][7]. - The approval of full circulation for Fuhong Hanlin's H shares is noted, which involves a significant number of shares and stakeholders [2][7]. - The report emphasizes the strong revenue growth projections for companies like MicroPort Robotics and King’s Ray Biotech, with expected revenue increases of approximately 110%-120% year-on-year for 2025 [6][10]. Summary by Sections 1. Overseas Pharmaceuticals - Insilico Medicine and Heng Tai Biologics have entered a partnership to develop ISM8969, a novel oral NLRP3 inhibitor, with a 50% global rights share and potential milestone payments exceeding HKD 500 million [2][7]. - Fuhong Hanlin's H shares have received approval for full circulation, involving 182,645,856 shares, which represents about 33.61% of the company's total issued shares [2][7]. 2. Company Performance Updates - MicroPort Robotics anticipates a revenue increase of 110%-120% for 2025, with adjusted net losses expected to narrow by over 50% [6][10]. - King’s Ray Biotech's joint venture, Legend Biotech, is projected to generate approximately USD 555 million in trade sales for the quarter ending December 31, 2025 [6][10]. 3. Recent Developments in Overseas Pharmaceutical Companies - GSK has reached an agreement to acquire RAPT Therapeutics for approximately USD 2.2 billion, focusing on a long-acting IgE monoclonal antibody currently in clinical trials [3][8]. - Corvus has reported positive results from a Phase I trial of its ITK inhibitor for moderate to severe atopic dermatitis, showing good safety and efficacy [3][9]. - Eli Lilly's FRα ADC has received breakthrough therapy designation from the FDA for treating platinum-resistant ovarian cancer [3][9]. 4. Recommendations - The report suggests monitoring innovative drug companies with active commercialization and business development opportunities, including companies like BeiGene, Innovent Biologics, and Fuhong Hanlin [13]. - It also highlights the importance of ongoing clinical progress in innovative pipelines for pharmaceutical companies transitioning towards innovation [13].

ISM8969作为一款潜在同类最佳(best-in-class)的NLRP3抑制剂，是透过英矽智能自主研发的生成式化学 引擎Chemistry42发现并优化。该分子于临床前研究中展现卓越疗效与良好安全性，且于多种疾病模型 中表现显著抗炎活性。值得注意的是，ISM8969具理想血脑屏障(BBB)渗透能力，使其能够穿过血脑屏 障，为神经炎症相关疾病治疗带来潜在受益。 基于具有前景的临床前数据，英矽智能已确认ISM8969为该项目的临床前候选化合物，并于多种神经系 统疾病模型中对该分子进行广泛评估。 英矽智能(03696)发布公告，用于炎症及神经退行性疾病治疗的口服NLRP3抑制剂ISM8969的临床试验申 请获得美国食品药品监督管理局(FDA)批准，用于帕金森病治疗。即将开展的这项I期临床研究旨在评估 ISM8969在健康人群中的安全性、耐受性及药代动力学表现，并找到临床推荐最佳剂量以供后续的进一 步研究。 ...

ISM8969作为一款潜在同类最佳(best-in-class)的NLRP3抑制剂，是透过英矽智能自主研发的生成式化学 引擎Chemistry42发现并优化。该分子于临床前研究中展现卓越疗效与良好安全性，且于多种疾病模型 中表现显着抗炎活性。值得注意的是，ISM8969具理想血脑屏障(BBB)渗透能力，使其能够穿过血脑屏 障，为神经炎症相关疾病治疗带来潜在受益。基于具有前景的临床前数据，英矽智能已确认ISM8969为 该项目的临床前候选化合物，并于多种神经系统疾病模型中对该分子进行广泛评估。 格隆汇1月23日丨英矽智能(03696.HK)宣布，用于炎症及神经退行性疾病治疗的口服NLRP3抑制剂 ISM8969的临床试验申请获得美国食品药品监督管理局(FDA)批准，用于帕金森病治疗。即将开展的这 项I期临床研究旨在评估ISM8969在健康人群中的安全性、耐受性及药代动力学表现，并找到临床推荐 最佳剂量以供后续的进一步研究。 ...

Policy Developments - The National Healthcare Security Administration has issued a guideline for the pricing of surgical and treatment auxiliary operations, focusing on medical technology innovations such as robotic surgery and 3D printing, establishing 37 pricing items and guiding the transition from traditional to precision medicine [2] Drug and Device Approvals - Bailitianheng's drug application for iza-bren, a first-in-class EGFR×HER3 dual antibody ADC for treating recurrent or metastatic esophageal squamous cell carcinoma, has been accepted and prioritized for review by the National Medical Products Administration [4] - Heng Rui Medicine has received clinical trial approval for SHR-9839, a humanized antibody for advanced solid tumors, and HRS-4642, a KRAS G12D inhibitor [5] - Fosun Pharma's subsidiary has been approved to conduct clinical trials for HLX701 in combination with chemotherapy for advanced colorectal cancer [6] Capital Market Activities - InnoCare Pharma has entered a collaboration agreement with Shenzhen Hengtai Biotechnology for the ISM8969 project, a new NLRP3 inhibitor for CNS diseases, with a potential total payment of up to $66 million [8][9] - Zhejiang Dejin Bio completed a multi-million A round financing to advance its core product, a recombinant botulinum toxin, and for international expansion [10] Industry Developments - Ant Group's Antifor has launched a DeepSearch feature on its PC platform to assist medical professionals with literature searches and clinical diagnosis [12] - Guangzhou's political advisor has proposed a plan to develop the brain-computer interface industry, aligning with national strategies and leveraging local resources [13] Shareholder Actions - Meihua Medical announced that shareholders plan to reduce their holdings by up to 2.51% of total shares due to personal financial needs [15] - Kain Technology has voluntarily withdrawn its drug registration application for a new hepatitis B indication, which will impact its 2025 profits [16]

Core Viewpoint - The announcement of a strategic partnership between InSilico Medicine (英矽智能) and HengTai Biopharma for the joint development of ISM8969, a novel NLRP3 inhibitor aimed at treating central nervous system diseases, has positively impacted the company's stock price, leading to a nearly 5% increase in early trading [1] Group 1: Partnership Details - InSilico Medicine has entered into a collaboration agreement with HengTai Biopharma to accelerate the global development of ISM8969 [1] - The agreement grants HengTai Biopharma 50% rights for research, development, registration, production, and commercialization of ISM8969 worldwide [1] Group 2: Financial Implications - InSilico Medicine is set to receive over HKD 500 million in upfront and milestone payments, including an expected upfront payment of HKD 78 million to be paid within 30 days of the agreement's effective date [1]

Market Overview - On January 20, the Hang Seng Index fell by 76 points (0.3%) to close at 26,487 points, influenced by a decline in technology stocks[1] - The Hang Seng Tech Index dropped by 66 points (1.1%) to close at 5,683 points, with total market turnover reaching HKD 237.8 billion, an increase of HKD 12.1 billion from the previous day[1] - Southbound capital recorded a net inflow of HKD 3.66 billion[1] Sector Performance - Gold and precious metal stocks surged due to international gold prices hitting a record high, with Zijin Mining (2899 HK) up 1.7%, Shandong Gold (1787 HK) up 2.7%, and Zijin Gold International (2259 HK) up 5.5%[1] - Real estate stocks rose as China announced financial measures for the sector, including a 25 basis point cut in the re-lending rate and a reduction in the minimum down payment ratio for commercial real estate from 50% to 30%[1] - Greentown China (3900 HK) increased by 5.6%, China Resources Land (1109 HK) by 3.7%, and China Overseas (688 HK) by 2.6%[1] U.S. Market Reaction - The Dow Jones Index fell by 870 points (1.8%) to close at 48,488 points, while the Nasdaq Index dropped by 561 points (1.5%) to 22,954 points, and the S&P 500 Index decreased by 143 points to 6,796 points[2] - Technology stocks faced significant declines, with Tesla (TSLA US) down 4.2%, Amazon (AMZN US) down 3.4%, and Google (GOOG US) down 2.5%[2] Macroeconomic Data - The National Bureau of Statistics reported that the per capita disposable income for residents in 2025 is projected to be RMB 43,377, with a real year-on-year growth of 5%[3] - Urban residents' per capita disposable income is expected to be RMB 56,502, reflecting a real growth of 4.2%, while rural residents' income is projected at RMB 24,456, with a real growth of 6%[3] Industry Developments - Pop Mart (9992 HK) shares rose by 9.1% following the announcement of a share buyback of 1.4 million shares at prices between HKD 177.7 and 181.2, totaling approximately HKD 250 million[4] - Weisheng Holdings (3393 HK) increased by 5.5% amid news of a planned investment of RMB 4 trillion by the State Grid during the 14th Five-Year Plan[4] - In the healthcare sector, the Hang Seng Healthcare Index fell by 0.8%, but Insilico Medicine (3696 HK) rose by 1.9% due to a collaboration agreement with Shenzhen Hengtai Biotechnology[5]