Core Viewpoint - The enthusiasm of mainland companies for listing on the Hong Kong stock market has surged, with 248 out of 450 companies applying for IPOs, indicating strong interest in the market [1] Group 1: IPO Trends and Market Dynamics - The Hong Kong market has seen a record IPO fundraising amount exceeding HKD 56 billion since March 2021, with a total fundraising scale of HKD 77.4 billion this year, nearing last year's total [1] - The increasing number of listing applications has led to regulatory review congestion, with an average filing time of 5-6 months, resulting in many companies needing to submit applications multiple times [1][2] - The trend of "secondary submissions" is widely accepted in the market and does not significantly hinder the final listing process [1] Group 2: Company Overview - Weili Zhibo - Weili Zhibo has completed 8 rounds of financing, raising a total of CNY 1.084 billion, attracting notable investment from firms like Enran Venture Capital and Shenzhen Capital Group [2] - The company focuses on innovative therapies for cancer and autoimmune diseases, with a diverse pipeline that includes 14 candidate drugs [2][5] - Weili Zhibo has established three core technology platforms: ADC, IO 2.0, and TCE, enhancing its competitive edge in the biopharmaceutical field [3][5] Group 3: Product Pipeline and Clinical Development - The core product LBL-024 is the first targeted 4-1BB therapy in the registration clinical stage globally, with significant market potential in treating various solid tumors [5][7] - LBL-034, a TCE targeting GPRC5D, is in I/II phase clinical trials in China and is positioned to be the first domestic TCE therapy targeting GPRC5D [8] - The ADC product LBL-058 has shown strong efficacy in preclinical models, indicating potential in treating DLL3-positive small cell lung cancer [9] Group 4: Market Potential and Future Outlook - The global market for 4-1BB antibody drugs is projected to reach USD 2.9 billion by 2030, with a CAGR of 284.9% from 2026 to 2030, driven by a large patient population across various cancer types [5] - The ongoing clinical studies for LBL-024 aim to expand its indications into high-incidence cancer areas, further broadening its market reach [6][7] - The comprehensive innovation capabilities of Weili Zhibo across its technology platforms reflect the core driving force behind the transformation and upgrading of the Chinese pharmaceutical industry [9][10]

Core Viewpoint - The recent controversy surrounding the clinical trial drug Cardunilumab from Kangfang Biopharma has raised significant industry attention due to issues of compliance and clinical trial results [2][6]. Compliance Issues - A patient purchased 70 doses of Cardunilumab for 79,320 yuan, most of which were labeled for "clinical research use only" [3][4]. - Kangfang Biopharma stated that the sales representative forged documents to obtain the drugs and provided them to the patient without charge, emphasizing that no fees were collected from the patient [4][5]. Clinical Trial Results - The Phase III trial HARMONi showed significant improvement in progression-free survival (PFS) with a risk ratio of 0.52, but did not achieve statistical significance in overall survival (OS) with a risk ratio of 0.79 [6][8]. - Despite the OS results, both Kangfang and its partner Summit Therapeutics expressed confidence in the drug's potential, noting that no FDA-approved treatments have significantly improved OS in this patient group [7][8]. Financial Performance - In 2024, sales revenue for Cardunilumab reached 1.713 billion yuan, a year-on-year increase of 16.53%, while the newly launched Ivosidenib generated 289 million yuan in just seven months, accounting for 14.44% of total revenue [8][9]. - The company's R&D expenditure decreased by 5.29% to 1.188 billion yuan, while sales and marketing expenses increased by 12.51% to 1.002 billion yuan, indicating a strategic shift [9]. Future Outlook - Kangfang Biopharma plans to continue advancing clinical research for Ivosidenib and other products, with a focus on global development in the oncology immunotherapy field [10]. - The recent licensing agreement between 3SBio and Pfizer for a competing PD-1/VEGF dual antibody adds competitive pressure in the market, necessitating careful global strategy planning by Kangfang [10].

Financial Data and Key Metrics Changes - The company has achieved significant growth, reaching over 3.4 million patients treated globally with its oncology medicines, supported by strong commercial execution [56] - Keytruda is approved in 56 indications in the US, 44 in the EU, and 41 in Japan, showcasing its leadership in immuno-oncology [56][59] Business Line Data and Key Metrics Changes - The oncology portfolio has yielded 35 phase three trials with statistically significant overall survival and 56 FDA approved indications [7] - The development of subcutaneous pembrolizumab with barahyaluronidase alfa has shown comparability to IV Keytruda, with a median injection time of two minutes [17][19] Market Data and Key Metrics Changes - The company is focusing on expanding its presence in earlier stage diseases, particularly in head and neck cancer, where there is a significant unmet medical need [60] - The anticipated peak uptake of subcutaneous pembrolizumab in the US is expected to reach between 30-40% within 18 to 24 months [62] Company Strategy and Development Direction - The company aims to diversify its oncology portfolio beyond Keytruda, focusing on additional therapeutic areas such as HIV vaccines, immunology, cardiovascular, and ophthalmology [6] - The strategy includes leveraging the proven track record of Keytruda to sustain leadership in oncology beyond its loss of exclusivity in 2028 [8] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing development of innovative therapies and the potential for significant impact on cancer care through a diversified pipeline [55] - The company is committed to maximizing patient access and improving outcomes through its robust commercial engine and innovative product offerings [63] Other Important Information - The company has a strong focus on biomarker development, which is crucial for patient selection and optimizing treatment outcomes [36] - There are ongoing phase III studies for various agents, including MK1084 and Sac TMT, which are expected to read out in the near future [53][64] Q&A Session Summary Question: What is the company's perspective on the evolving market for PD-1, PD-L1, and VEGF bispecifics? - Management highlighted the consistent improvements in progression-free survival across multiple indications and expressed optimism about the ongoing trials in China, with plans to expand to the US [75][78] Question: How does the company view the market opportunity for head and neck cancer treatments? - Management clarified that patients receiving preoperative Keytruda did not lose the opportunity for surgery, and emphasized the safety and efficacy of the treatment [79]

Core Viewpoint - The announcement highlights the clinical data and latest progress of ZG006 and ZG005, which will be presented at the 2025 ASCO annual meeting, indicating the company's ongoing commitment to advancing its innovative oncology therapies [1]. Group 1: ZG006 Overview - ZG006, also known as Alveltamig, is a trispecific antibody drug developed by the company and its subsidiary, Gensun Biopharma Inc., targeting DLL3 and CD3, and has received orphan drug designation from the FDA [1][2]. - ZG006 is the first-in-class molecule targeting DLL3, showing potential to be a best-in-class therapy [1]. Group 2: ZG006 Clinical Data - In the ZG006-002 study, 48 patients with refractory advanced small cell lung cancer were randomized to receive either 10 mg or 30 mg Q2W treatment, with objective response rates (ORR) of 62.5% and 58.3%, respectively [2][3]. - The disease control rates (DCR) were 70.8% for the 10 mg group and 66.7% for the 30 mg group, with safety profiles showing no treatment-related adverse events leading to permanent discontinuation [3]. - In the ZG006-001 study, 47 patients received varying doses of ZG006, with confirmed ORR of 75.0% for 10 mg, 53.8% for 30 mg, and 58.3% for 60 mg, indicating strong anti-tumor activity [4][5]. Group 3: ZG005 Overview - ZG005, known as Nilvanstomig, is a recombinant humanized bispecific antibody targeting PD-1 and TIGIT, positioned as an innovative immunotherapy for various solid tumors [6][7]. - ZG005 is among the first of its kind to enter clinical research globally, with no similar mechanism drugs approved yet [6]. Group 4: ZG005 Clinical Data - In the ZG005-001 study, 55 patients with advanced cervical cancer were treated, showing an ORR of 40.9% and DCR of 68.2% in the 20 mg/kg group [7]. - The safety profile was favorable, with 83.6% of patients experiencing treatment-related adverse events (TRAE), predominantly grade 1-2 [7]. - In the ZG005-003 study, 60 patients with first-line cervical cancer were treated, with the 20 mg/kg group showing an ORR of 82.1% and DCR of 96.4% [8][9]. Group 5: ZGGS15 Overview - ZGGS15 is a recombinant humanized bispecific antibody targeting LAG-3 and TIGIT, representing a novel approach in tumor immunotherapy [10][11]. - It is the first of its kind to enter clinical research globally, with no similar mechanism drugs approved yet [10]. Group 6: ZGGS15 Clinical Data - In the ZGGS15-001 study, 22 patients were enrolled, with a DCR of 35.3% among evaluable patients [12]. - The safety profile showed that 90.1% of patients experienced TRAE, with no dose-limiting toxicities observed [12][13].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 卡介苗 （BCG） ，是一种由减毒 牛分枝杆菌悬浮液制成的活菌疫苗，被用于预防 肺结核 。此外，它还具有增强巨噬细胞活性及其杀灭肿瘤细胞的能力，活化 T 淋巴细胞，增强机体细胞免疫的功能，因此，还作为治疗 膀胱癌 的免疫疗法。 当通过静脉注射给药时，卡介苗会重新编程骨髓中的造血干细胞/祖细胞 （HSPC） ，从而对感染产生异源性保护作用。但目前尚不清楚膀胱内给药卡介苗的抗肿 瘤作用是否与其对 HSPC 的重编程有关。 2025 年 5 月 29 日，威尔康奈尔医学院的研究人员在 Cell 子刊 Cancer Cell 上发表了题为： Microbial cancer immunotherapy reprograms hematopoiesis to enhance myeloid-driven anti-tumor immunity 的研究论文。 该研究表明，微生物癌症免疫疗法—— 卡介苗 ，通过重编程的造血干细胞/祖细胞 （HSPC） ，增强抗肿瘤免疫。 经卡介苗重编程的造血干细胞/祖细胞 （HSPC） 足以通过生成中性粒细胞、单核细胞和树突状细胞来增强抗肿瘤免疫，这 ...

从二线单药治疗到一线联合化疗的临床数据连番释放，本质上亦映射出中国创新药企在双抗领域从"技术可行性验证"到"临床价值深挖"的进阶能力。 在全球创新药投资逻辑向"真创新、高壁垒"切换的背景下，中国创新药企在双抗等前沿领域持续突破，开始在国际顶级学术舞台展露锋芒。 继去年美国临床肿瘤学会（ASCO）年会以单药疗法惊艳亮相后，维立志博研发的抗PD-L1/4-1BB双抗LBL-024在2025年ASCO舞台再获突破性验证。 那么站在投资者的视角而言，应当如何来看待这一最新临床数据的表现？该数据对于维立志博又有何意义？ 潜在全球首创，真正源头创新锚定临床价值 不同于传统单抗疗法的线性突破逻辑，LBL-024通过PD-L1靶向锁定肿瘤微环境、4-1BB共刺激激活T细胞的"双引擎"设计，实现肿瘤微环境里的条件激活T 细胞，开创性地解决了4-1BB靶点系统性激活引发肝毒性的痛点。这种肿瘤微环境精准调控机制，使其成为全球首个有望实现4-1BB靶点商业化突破的免疫 疗法。 2024 ASCO大会，LBL-024单药在针对二线治疗、三线及以上治疗肺外神经内分泌癌（EP-NEC）的患者中，展现出良好的安全性和强有力的有效信号。 数据 ...

Core Viewpoint - Kewang Pharmaceutical Group has submitted an application for an IPO on the Hong Kong Stock Exchange, aiming to raise funds for drug development and operational needs, despite facing significant financial losses and a lack of profitability [1][2][15]. Company Overview - Kewang Pharmaceutical was founded in 2017, focusing on innovative immunotherapy products for cancer treatment, led by a team of prominent scientists and entrepreneurs [5][9]. - The company has experienced a remarkable increase in valuation, growing 23 times from $24.8 million to approximately $599 million over three and a half years [6][8]. Financial Performance - Kewang Pharmaceutical has reported cumulative losses of 1.712 billion yuan over three years, with no approved commercial products and a projected revenue of 106.566 million yuan in 2024 [12][11]. - The company had cash and cash equivalents of 32.82 million yuan as of the end of 2024, indicating a critical need for additional financing [14][15]. Funding History - The company has completed four rounds of financing, raising a total of $252 million (approximately 1.811 billion yuan) from notable investors, including Eli Lilly Asia Fund and Hillhouse Capital [6][8]. - The funding rounds have significantly increased the company's post-money valuation, reflecting strong investor interest despite its ongoing losses [6][7]. Product Pipeline - Kewang's core product, ES102, is a clinical-stage OX40 agonist antibody aimed at treating cancer patients who do not respond well to immune checkpoint inhibitors, with commercialization expected by 2028 [9][10]. - The company also has multiple pipeline assets, with three in clinical stages, including ES014, a first-in-class dual-specific antibody [10]. Management Compensation - The founders of Kewang Pharmaceutical have received substantial compensation, with total earnings exceeding 42 million yuan over two years, highlighting the disparity between executive pay and company performance [8][9].

Group 1 - The company announced adjustments to the fundraising amounts for certain clinical trial sub-projects within its "Innovative Drug R&D Project" while keeping the total fundraising amount unchanged [1][2] - New sub-projects such as "JS207 domestic and overseas R&D," "JS107 domestic and overseas R&D," and "JS125 domestic and overseas R&D" have been added, while funding for several other drug developments has been reduced [1] - JS207 is a recombinant humanized anti-PD-1 and VEGF bispecific antibody developed by the company, primarily for the treatment of advanced malignancies, currently in Phase II clinical trials [1] Group 2 - The adjustments in fundraising project sub-items and amounts are based on the company's development strategy and product R&D progress, aimed at improving fundraising efficiency and optimizing resource allocation [2] - The changes are expected to provide financial support for the company's product development and contribute to its long-term growth [2]

Core Viewpoint - 科望医药集团 is seeking to list on the Hong Kong Stock Exchange after previously withdrawing its application for a U.S. IPO, highlighting its growth and interest from major investors like Eli Lilly and Tencent [1][2] Company Overview - Founded in 2017, 科望医药 is a clinical-stage biopharmaceutical company focused on innovative therapies targeting the tumor microenvironment (TME) [1][2] - The company has achieved a valuation of $600 million after multiple funding rounds, with significant backing from prominent investors [1] Unique Approach - The company differentiates itself by focusing on TME rather than competing in popular target areas, aiming to develop immune therapies based on myeloid cells for cancer and autoimmune diseases [2][3] - 科望医药 aims to convert "cold" tumors into "hot" tumors by eliminating suppressive factors in the TME to induce stronger immune responses [3] Product Strategy - The company employs a "self-research + introduction" strategy to quickly address unmet medical needs while supporting its own product development [4] - Six main products have been disclosed, with four in clinical stages, including self-developed products and those licensed from other companies [4][5] Key Product Insights - The core product, ES102, is a hexavalent OX40 agonist showing promising safety and anti-tumor activity in clinical trials for non-small cell lung cancer (NSCLC) and esophageal squamous cell carcinoma (ESCC) [5][6] - The OX40 agonist market in China is projected to reach RMB 16.5 billion by 2035, with a compound annual growth rate of 99.6% starting from 2029 [6] Clinical Development Challenges - Despite the potential, the development of OX40 agonists has faced setbacks, with previous candidates from other companies failing to demonstrate sufficient efficacy [8][9] - ES102's early clinical trial results show a complete response rate of 3.7% and a partial response rate of 7.4%, which raises concerns about its competitive edge [8][10] Financial Status - The company is currently facing financial pressure, with cash and cash equivalents of only 32.82 million yuan as of December 31, 2024, against a research expenditure of 117 million yuan for the same year [12] - Cumulative losses from 2022 to 2024 amount to 1.712 billion yuan, indicating a challenging path to profitability [12]

论文展示了前沿生成式人工智能平台及其集成工作流程在快速开发ISM5939中的赋能，验证了人工智能在药 物发现中的潜力。 不同于直接STING激动剂，ISM5939通过靶向ENPP1精准调控肿瘤组织内的STING信号通路，恢复局部免疫 激活，从而增强抗肿瘤免疫反应。 首次证实ENPP1抑制剂能够克服对免疫检查点抑制剂和化疗的双重耐药性，为难治性肿瘤患者带来新的治疗 希望。 自2025年以来，这已是英矽智能第三篇以AI驱动药物研发实践为主题、发表在Nature子刊的研究成果。 免疫检查点抑制剂为肿瘤治疗带来范式变革，使得多种恶性肿瘤患者获益。然而，接受免疫检查点抑制剂治 疗的患者中仅有10%-35%可以获得显著持久的治疗效果，亟需创新治疗策略。 | Received: 28 August 2024 | Congying Pu16, Hui Cui15, Huaxing Yu15, Xin Cheng', Man Zhang', Luoheng Qin', | | --- | --- | | Accepted: 7 May 2025 | Zhilin Ning', Wen Zhang', Shan Chen', Y ...