编辑丨王多鱼 排版丨水成文 在 肿瘤免疫治疗 领域，除了 T 细胞主导的细胞免疫，由 B 细胞和抗体介导的体液免疫也日益受到重视。 三级淋巴结 构 （ TLS ） 作为肿瘤微环境中的 " 临时淋巴结 " ，是 B 细胞活化与抗体产生的关键场所 。然而，在 局部进展期直 肠癌 （ LARC ） 中，成熟 TLS （ mTLS ） 的功能定位及其在新辅助治疗 （ neoTx ） 干预下的动态变化，仍是领域 内关注的重点。 在临床预后方面，研究证实 mTLS 的存在以及浆细胞标志物 CD138 的高表达，均与患者更长的总生存期 （ OS ） 显 著相关。在公共数据库 （ TCGA-READ ） 中的验证也表明，高表达 TLS 形成关键因子 CXCL13 或浆细胞基因签名 的患者，其预后同样更好。这提示了 mTLS 及其支持的 B 细胞免疫是直肠癌的有利预后标志。 2025 年 11 月 18 日，解放军总医院 普通外科医学部 杜峻峰 课题组与北京协和医院 吴斌 团队合作 （ 田娜 、 王乾 宇 、 吕远 为论文第一作者 ） ，在《柳叶刀》 （The Lancet） 子刊 eBiomedicine 上发表了题为： M ...

Core Viewpoint - Zai Jian Pharmaceutical has received approval from the National Medical Products Administration for clinical trials of its drug ZG006 in combination with PD-1/PD-L1 inhibitors and chemotherapy for small cell lung cancer [1] Group 1: Drug Development - ZG006 (INN name: alveltamig) is a trispecific antibody developed through the company's dual/multi-specific antibody research platform [1] - The drug targets DLL3 on tumor cells and CD3 on T cells, effectively bridging T cells and tumor cells to enhance tumor cell destruction [1] - Preclinical studies have shown significant tumor suppression effects in mouse models, with a notable proportion of tumors completely regressing [1]

编辑丨王多鱼 排版丨水成文 肿瘤新抗原 （Tumour Neoantigen） 是理想的免疫治疗靶标，这些抗原只存在于肿瘤组织中，而在其他组织中不存在。肿瘤新抗原疫苗通过诱导机体产生肿瘤特 异性免疫应答，为精准治疗肿瘤提供了新思路。目前，全世界已有超过 100 项新抗原疫苗相关临床试验。 然而， 由于 新抗原免疫原性低 （仅约 15%–30% 的新抗原能够诱导 T 细胞 产生 ） 、 实体瘤的高度 异质性以及抑制性肿瘤免疫微环境 （ TIME） ，这些个 性化的肿瘤新抗原疫苗在实体瘤的治疗中，响应率低。 相比之下，相比之下，微生物抗原具有明确的定义且免疫原性很强，能够激活特定的记忆 T 细胞以清除肿瘤微环境中的微生物。 受此启发，中国药科大学 杨勇 / 王文广 团队等创新性地构建了一种特异性异源蛋白标记体系，开发了特异性标记 乙型肝炎病毒表面抗原 （ HBsAg ） 的 通用 型肿瘤疫苗系统 （ HBsAg-tagged tumour vaccine system, H-T VAC ） ， 将 肿瘤细胞 " 伪装 " 成高免疫原性的 " 病毒 " ，突破了肿瘤新抗原免疫原性低、 实体瘤异质性强以及抑制性肿瘤免 ...

Financial Data and Key Metrics Changes - For Q3 2025, total revenue was $14.3 million, a significant increase from negative revenue of $1.8 million in Q3 2024 [18] - Net YCANTH revenue for Q3 2025 was $3.6 million, compared to negative $1.9 million in Q3 2024, reflecting improved demand and sales [18][19] - GAAP net loss for Q3 2025 was $0.2 million, or $0.03 per share, compared to a GAAP net loss of $22.9 million, or $4.88 per share in Q3 2024 [21] - Non-GAAP net income for Q3 2025 was $1.2 million, or $0.13 per share, compared to a net loss of $20.2 million, or $4.30 per share in Q3 2024 [21] Business Line Data and Key Metrics Changes - Dispensed applicator units of YCANTH reached 14,093 in Q3 2025, representing approximately 5% sequential growth over the prior quarter [10] - Year-to-date dispensed applicator units increased to 37,642 for the nine months ended September 30, 2025, a 120% increase compared to the same period in 2024 [6] Market Data and Key Metrics Changes - The approval of YCANTH in Japan for molluscum is expected to lead to multiple approvals across major pharmaceutical markets, including the EU [8] - Feedback from the European Medicines Agency indicated no further phase III studies are needed for YCANTH's approval for molluscum, with a filing anticipated as early as Q4 2026 [8] Company Strategy and Development Direction - The company aims to establish YCANTH as a leading therapy for multiple types of skin lesions, leveraging its existing clinician relationships [6] - The development of VP-315 for basal cell carcinoma is positioned as a potential standard of care, with plans for a phase III study design confirmed by the FDA [10][16] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the growth trajectory of YCANTH and the potential for VP-315, highlighting a strong foundation for future growth [4][17] - The company is focused on optimizing its cost structure while expanding its commercial strategy, which has led to reduced spending and increased product adoption [5][20] Other Important Information - The company received $18 million in cash milestone payments from Torii in 2025, with $10 million received in Q3 upon YCANTH's approval in Japan [7] - A new non-dispensing pharmacy, YCANTH Rx, is expected to launch in Q4 2025 to streamline the prescription process for healthcare providers [12][13] Q&A Session Summary Question: Can you further speak to the YCANTH demand that you're seeing in Q4? - Management noted that momentum from September has continued into Q4, with expectations for increased demand as the cold and flu season approaches [24][25] Question: What kind of counter-detailing are you seeing, and what has been the prescriber feedback on Zilretc? - Management views the Zilretc launch positively, as it raises awareness about the need to treat molluscum, while YCANTH remains a best-in-class option [25] Question: When do you expect sales force productivity to fully ramp? - It typically takes a few months for new sales representatives to become fully productive, with expectations for many to be effective early in 2026 [26][27] Question: Why is there a 12-month timeline for the EU filing despite no additional clinical trials required? - The timeline includes necessary sequential steps, such as securing a pediatric waiver, which adds time to the process [27][28] Question: What feedback has been received regarding YCANTH Rx? - Feedback has been positive, with the new pharmacy model expected to simplify the prescription process for clinicians and patients [29][30] Question: How should we think about seasonality impact in Q4 sales? - Traditional seasonal slowdowns are expected in November and December, but increased doctor visits during the cold and flu season may boost diagnoses of molluscum [32][33]

2025年，就在国内Biotech还沉浸在大额BD频发、港股重新开闸的热闹之时，大洋彼岸的美国Biotech却在经历一场劫难。 | 序号 | रूना | 关停时间 | 倒闭原因 | 创立时间 | 专注领域 | | --- | --- | --- | --- | --- | --- | | 1 | Velia Therapeutics | 2025年1月 | 临床研究失败,资金链断裂 | 2021 | 自身免疫病和肿瘤领域靶点 | | 2 | Viracta Therapeutics | 2025年2月 | 股价低于1美元,退市 | 1998 | 肿瘤领域小分子药物研发 | | 3 | kojin Therapeutics | 2025年2月 | 技术过于创新,融资困难 | 2019 | 专注铁死亡药物研发 | | 4 | spotlight Therapeutics | 2025年2月 | 临床研究失败,合作被终止 | 2017 | 致力于体内CRISPR基因编辑疗法 | | 5 | HC Bioscience | 2025年3月 | 技术过于创新,融资困难 | 2021 | tRNA技术研发 | | 6 ...

Core Viewpoint - Shimai Pharmaceutical has submitted an application to the Hong Kong Stock Exchange for its main board listing, with Huatai International acting as the sole sponsor [1] Industry Summary - The T-cell engaging (TCE) therapy market is projected to grow significantly, from $3 billion in 2024 to $121.1 billion by 2035, representing a compound annual growth rate (CAGR) of 40.0% [1] Company Summary - As of November 5, 2025, Shimai Pharmaceutical has four self-developed clinical-stage candidate drugs, including DNV3 targeting LAG3, SMET12 for intravenous use targeting EGFR×CD3, CMD011 targeting GPC3×CD3, and the next-generation cloaked TCE CMDE005 [1] - The company is also developing two preclinical next-generation multifunctional/logic-gated TCE candidates, CMDE101 and CMDE102, targeting FOLR1×PD-L1×CD3 and PSMA×PD-L1×CD3, respectively [1] - Shimai Pharmaceutical emphasizes that its TCE therapies feature selective activation, zero immune cell toxicity, precise tumor recognition, and prevention of tumor recurrence, aiming to become a cornerstone therapy in future tumor immunotherapy [1]

Core Insights - Merck's PD-1 monoclonal antibody, Keytruda, has achieved over $20 billion in annual sales for both 2023 and 2024, solidifying its position as a leading drug in the lung cancer treatment market [2] - A competitive race is underway among pharmaceutical companies to establish the next generation of immune therapies for lung cancer, with significant advancements being made in the field [3][4] Group 1: Company Developments - Jun Zhu, CEO of Junshi Biosciences, announced promising results for their PD-L1 ADC HLX43 in treating non-small cell lung cancer (NSCLC), with an objective response rate (ORR) of 33.3% and a disease control rate (DCR) of 75.8% in squamous NSCLC patients [3] - HLX43 demonstrated even better efficacy in non-squamous patients, achieving an ORR of 48.6% and a DCR of 94.3% [3] - Junshi plans to advance at least eight Phase III clinical trials for HLX43 in the lung cancer domain [3] Group 2: Industry Trends - Lung cancer remains the leading malignancy globally, with 2.4 million new cases annually, and is a critical area for pharmaceutical breakthroughs [4] - The rise of targeted and immune therapies has transformed the treatment landscape for lung cancer, with new modalities such as ADCs, bispecific antibodies, and tumor vaccines expanding treatment options [4] - Several domestic companies, including Junshi Biosciences, CanSino Biologics, and Innovent Biologics, are competing to develop next-generation immune therapies, focusing on PD-(L)1 combinations with ADCs or PD-1 bispecific antibodies [4][5] Group 3: Clinical Research and Development - CanSino Biologics is conducting eight Phase III clinical trials for their PD-1/VEGF bispecific antibody, Ivoris, in lung cancer [6] - Innovent Biologics announced a collaboration with Takeda Pharmaceutical to co-develop a new generation immune therapy, IBI363, which targets PD-1 and IL-2α-bias [7] - Junshi's HLX43 is currently leading in global development for PD-L1 ADCs, with plans for clinical studies in cervical cancer, esophageal squamous cancer, and colorectal cancer [8]

Core Insights - Merck's PD-1 monoclonal antibody, Keytruda, has achieved global sales exceeding $20 billion in both 2023 and 2024, solidifying its position as the leading drug in the lung cancer market [1] Industry Overview - Lung cancer remains the leading cause of cancer globally, with 2.4 million new cases each year, and China reporting significantly higher new cases than other countries [3] - The rise of targeted and immunotherapy treatments has transformed the treatment landscape for lung cancer, with new therapies such as ADCs, bispecific antibodies, and tumor vaccines expanding treatment options [3] Competitive Landscape - A race is underway among pharmaceutical companies to establish the next generation of immunotherapy leaders in lung cancer, with companies like Junshi Biosciences, Kintor Pharmaceutical, and Innovent Biologics actively competing [2][3] - Junshi Biosciences has reported promising results for its PD-L1 ADC, HLX43, showing an objective response rate (ORR) of 33.3% in squamous non-small cell lung cancer (NSCLC) patients and 48.6% in non-squamous patients [2] - Kintor Pharmaceutical's PD-1/VEGF bispecific antibody, Ivoris, is currently undergoing eight pivotal phase III clinical trials [5] - Innovent Biologics has announced a collaboration with Takeda Pharmaceutical to co-develop a new generation of immunotherapy, IBI363, which targets PD-1 and IL-2α [6] Clinical Development - Junshi Biosciences plans to initiate at least eight phase III clinical trials for HLX43 in the lung cancer space, with additional studies planned for cervical cancer, esophageal squamous cancer, and colorectal cancer [2][7] - The cost of each global phase III clinical trial is estimated to be around $200 million, presenting a significant financial challenge for companies [7] Financial Performance - Junshi Biosciences reported revenue of 2.82 billion yuan in the first half of the year, a year-on-year increase of 2.7%, with net profit remaining stable at 390 million yuan [7]

Market Overview - The domestic market indices showed a decline, with the Shanghai Composite Index closing at 3,954.79, down 0.81% [2] - The Shenzhen Component Index and the CSI 300 also experienced declines of 1.14% and 1.47% respectively [2] Agricultural Sector - The company "Juxing Agriculture" reported a continuous increase in pig output, with a total of 293,000 pigs sold in the first three quarters of 2025, generating sales revenue of 5.153 billion [6] - The company aims to control breeding costs through various efficiency measures, despite a decline in pig prices leading to a drop in profitability in Q3 [6] New Materials Sector - "Jundingda" achieved a revenue of 728 million in the first three quarters of 2025, marking a year-on-year growth of 23.43% [5] - The company reported a net profit of 137 million, up 18.82%, with a gross margin of 40.38% and a net margin of 18.86% [5] Military Industry - "Inner Mongolia Yijian" reported a revenue of 7.894 billion in the first three quarters of 2025, a year-on-year increase of 11.07% [10] - The net profit reached 386 million, up 6.18%, driven by improvements in profit margins and growth in unmanned and military trade sectors [10][11] Technology Sector - "Dameng Data" reported a revenue of 2.167 billion in Q3 2025, a decrease of 6.59% year-on-year, but with an improved gross margin of 14.77% [16] - The company is focusing on expanding its military trade market and enhancing its position in high-tech weaponry [16] Energy Sector - "Baofeng Energy" achieved a revenue of 35.54 billion in the first three quarters of 2025, a year-on-year increase of 46.4% [27] - The net profit reached 8.95 billion, up 97.3%, driven by capacity release and steady progress on ongoing projects [27] Chemical Sector - "Zanyu Technology" reported a revenue of 9.676 billion in the first three quarters of 2025, with a year-on-year growth of 27.92% [20] - The net profit for the same period was 151 million, reflecting a 24.96% increase, attributed to the recovery in palm oil prices [20] Textile and Apparel Sector - "Weixing Co." reported a revenue of 36.33 billion in the first three quarters of 2025, a slight increase of 1.46% [24] - The net profit was 5.83 billion, down 6.46%, but the company is optimistic about future growth due to new factory efficiencies [24] Clinical Data Update - The clinical data for HLX43 shows promising safety advantages and potential as a cornerstone drug for tumors, with an overall response rate of 47.4% in specific patient groups [33][35]

Core Viewpoint - The company's performance in the first three quarters of 2025 aligns with expectations, showing significant revenue growth and reduced net loss compared to the previous year [1][2]. Financial Performance - Revenue for 1-3Q25 reached 1.806 billion yuan, representing a year-on-year increase of 42.1% [1]. - The net profit attributable to the parent company was -596 million yuan, reflecting a year-on-year reduction in loss of 35.7% [1]. Development Trends - The core product, Tuoyi, continues to see strong sales growth, with domestic market revenue of 1.495 billion yuan in 1-3Q25, up approximately 40% year-on-year [1]. - Tuoyi has received approval for 12 indications in China, with a new indication for HER2-expressing urothelial carcinoma under review by NMPA [1]. - Tuoyi has been approved in 40 countries and regions globally, including Hong Kong, the US, the EU, India, and the UK, with expectations for continued revenue contribution as more indications are approved [1]. Clinical Research and Innovation - The FDA has approved the initiation of clinical research for JS207, a PD-1/VEGF dual-target drug, marking a significant step in its development for operable patients [1]. - The company showcased over 20 research studies at the 2025 ESMO conference, with two studies selected for oral presentations, indicating strong engagement in international academic forums [2]. - Upcoming data updates for JS107 and JS207 at the 2025 ESMO Asia conference highlight the company's commitment to advancing cancer immunotherapy [2]. Profit Forecast and Valuation - The company maintains its net profit forecasts for 2025 and 2026 at -917 million yuan and -315 million yuan, respectively [2]. - The company retains an "outperform" rating based on DCF valuation, with a target price of 36.98 HKD, indicating a potential upside of 47.6% from the current stock price [2].