撰文丨王聪 编辑丨王多鱼 排版丨水成文 蛋白靶向降解嵌合体 （PROTAC） ， 依靠将泛素连接酶招募到细胞内的目标蛋白上，通过蛋白酶体机制促进对致病蛋白的降解，使许多"不可成药"蛋白成为治 疗靶点。迄今已有数十种 PROTAC 药物进入临床试验阶段，其中，靶向雌激素受体 （ER） 的 PROTAC 药物 Vepdegestrant 近日发布了 3 期临床试验结果， 有望于近期上市。 与 PROTAC 类似，科学家们还开发出了 溶酶体靶向降解嵌合体 （LYTAC） 、 自噬体靶向降解嵌合体 （AUTAC） 等技术 。PROTAC 和 AUTAC 主要靶向胞 内蛋白，而 LYTAC 通常专注于捕获分泌蛋白和膜蛋白并进行降解，例如生长因子、疾病相关受体和细胞因子等，这些蛋白质约占人类蛋白质组的 40%，是许多 疾病的重要治疗靶点。 然而，由于溶酶体转运受体的多样性有限，LYTAC 的发展面临着巨大挑战。 2025 年 6 月 13 日 ， 军事医学研究院 周辛波 、 钟武 、 中国医学科学院北京协和医学院 邓洪斌 等人 在 Nature 子刊 Nature Chemical Biology 上发表了题 为 ： P ...

丨2025年6月9日星期一丨 6月8日，安科生物发布的投资者关系活动记录表显示，公司曲妥珠单抗（商品名：安赛汀）处于市场快 速导入阶段，2024年度销售收入超过1亿元。该产品上市以来，销售总体呈现上升趋势，2025年1至5 月"安赛汀"的发货同比持续保持增长，预计2025年"安赛汀"会有较大幅度的同比增长。资料显示，"安 赛汀"是安科生物在抗肿瘤靶向药物领域布局的首款产品。 点评：安科生物的表态背后，是曲妥珠单抗（商品名：安赛汀）市场表现释放出的积极信号。作为公司 抗肿瘤靶向药物领域的首款产品，安赛汀的成功不仅为公司带来新的利润增长点，还提升了其在肿瘤治 疗领域的市场地位和品牌影响力，有望吸引更多投资者关注，推动公司整体估值提升，为后续研发和市 场拓展提供有力支撑。 NO.4 海王生物发布终止控制权变更公告 6月6日晚，海王生物发布了关于终止控制权变更及向特定对象发行股票事项公告。广新集团及丝纺集团 终止认购海王生物本次发行的股份。海王生物表示，上述事项终止后，公司仍会与有意向的国资主体针 对股权合作事宜展开积极洽谈，探讨未来通过优势资源整合、深化业务协同等方式，拓展新的发展空 间，为公司创造新机遇。 NO. ...

Core Viewpoint - Arvinas, Inc. has submitted a New Drug Application (NDA) to the FDA for vepdegestrant, a potential treatment for patients with ESR1-mutated ER+/HER2- advanced or metastatic breast cancer, based on positive results from the Phase 3 VERITAC-2 clinical trial [1][2] Group 1: Clinical Trial Details - The VERITAC-2 trial is a global, randomized Phase 3 study evaluating the efficacy and safety of vepdegestrant compared to fulvestrant in 624 patients across 25 countries who had previously received treatment with a CDK4/6 inhibitor plus endocrine therapy [3][4] - Patients in the trial were randomized 1:1 to receive either vepdegestrant or fulvestrant, with 43% of patients having ESR1 mutations detected [4] - The primary endpoint of the trial was progression-free survival (PFS) in both the ESR1-mutation and intent-to-treat populations, with overall survival as a key secondary endpoint [4] Group 2: Drug Development and Collaboration - Vepdegestrant is an investigational PROTAC protein degrader designed to target and degrade the estrogen receptor, being developed as a potential monotherapy for advanced or metastatic ER+/HER2- breast cancer with ESR1 mutations [5][6] - Arvinas and Pfizer have a global collaboration for the co-development and co-commercialization of vepdegestrant, sharing worldwide development costs, commercialization expenses, and profits [6] Group 3: Regulatory Status and Future Outlook - The FDA has granted vepdegestrant Fast Track designation as a monotherapy for the treatment of adults with ER+/HER2- advanced or metastatic breast cancer previously treated with endocrine-based therapy [6] - The results from the VERITAC-2 study were presented at the 2025 ASCO Annual Meeting and published in the New England Journal of Medicine, highlighting the significance of the findings [2]

Core Insights - Arvinas, Inc. is set to present new preclinical data for ARV-393, an investigational oral PROTAC BCL6 degrader, at the European Hematology Association meeting in June 2025 [1][2] - ARV-393 targets the B-cell lymphoma 6 protein (BCL6), which is a significant driver of B-cell lymphomas, and aims to address the challenges of traditional undruggable targets [3][4] Company Overview - Arvinas is a clinical-stage biotechnology company focused on developing therapies that utilize targeted protein degradation to treat life-threatening diseases [4] - The company is advancing multiple investigational drugs, including ARV-393 for relapsed/refractory non-Hodgkin lymphoma, vepdegestrant for ER+/HER2- breast cancer, and ARV-102 for neurodegenerative disorders [4] Presentation Details - The presentation of ARV-393 will occur on June 13, 2025, during a session focused on lymphoma biology and translational research [2]

Core Viewpoint - Pfizer's stock has declined approximately 25% from its 52-week high, primarily due to pipeline setbacks and management concerns regarding R&D spending and acquisitions [1][2][11] Valuation - Pfizer's current price-to-sales (P/S) ratio is 2.1, compared to 3.0 for the S&P 500, indicating it is slightly undervalued [8] - The price-to-free cash flow (P/FCF) ratio stands at 9.5 versus 20.5 for the S&P 500, and the price-to-earnings (P/E) ratio is 16.8 compared to 26.4 for the benchmark [8] Revenue Performance - Pfizer's revenues have seen a marginal decline over recent years, with an average shrinkage of 9.0% over the last three years, while the S&P 500 experienced a growth of 5.5% [8] - However, revenues grew by 11.7% from $60 billion to $64 billion in the last 12 months, outperforming the S&P 500's growth of 5.5% [8] Profitability - Pfizer's profit margins are around the median level for companies in the Trefis coverage universe, with an operating margin of 24.3% compared to 13.2% for the S&P 500 [8] Financial Stability - The company's balance sheet is considered weak, with a debt figure of $61 billion and a poor debt-to-equity ratio of 46.2% compared to 19.9% for the S&P 500 [13] - Cash and cash equivalents amount to $17 billion, yielding a cash-to-assets ratio of 8.3% versus 13.8% for the S&P 500 [13] Downturn Resilience - Pfizer's stock has historically underperformed the S&P 500 during market downturns, with a peak-to-trough decline of 57.3% from a high of $61.25 to $26.13 [14][15] - The stock has not yet recovered to its pre-crisis high, currently trading around $23 [14] Future Outlook - Despite current challenges, Pfizer has a robust pipeline, particularly in oncology, with potential blockbuster drugs that could enhance future revenues [12] - The acquisition of Seagen is beginning to positively impact sales and earnings, although it has not fully offset the revenue loss from COVID-19 products [10][12]

Core Insights - The Phase 3 VERITAC-2 clinical trial results indicate that vepdegestrant monotherapy shows a statistically significant improvement in progression-free survival (PFS) for patients with ESR1 mutations compared to fulvestrant [2][4][6] - Vepdegestrant is positioned as a potential best-in-class treatment option for patients with ER+/HER2- advanced or metastatic breast cancer, particularly in the second-line setting [4][7][12] Group 1: Clinical Trial Results - Vepdegestrant reduced the risk of disease progression or death by 43% in patients with ESR1 mutations, with a median PFS of 5.0 months compared to 2.1 months for fulvestrant [2][3] - In the intent-to-treat population, the median PFS was 3.7 months for vepdegestrant versus 3.6 months for fulvestrant, which did not reach statistical significance [2][4] - The clinical benefit rate (CBR) for vepdegestrant was 42.1% compared to 20.2% for fulvestrant, and the objective response rate (ORR) was 18.6% versus 4.0% respectively [4][6] Group 2: Safety and Tolerability - Vepdegestrant was generally well tolerated, with low rates of gastrointestinal adverse events such as nausea (13.5%), vomiting (6.4%), and diarrhea (6.4%) [3][5] - The incidence of grade 4 treatment-emergent adverse events (TEAEs) was 1.6% in the vepdegestrant arm compared to 2.9% in the fulvestrant arm [3][5] - TEAEs leading to treatment discontinuation occurred in 2.9% of patients taking vepdegestrant versus 0.7% for fulvestrant [3][5] Group 3: Market and Development Potential - Approximately 2.3 million new breast cancer diagnoses were reported globally in 2022, with ER+/HER2- breast cancer accounting for about 70% of cases [6][12] - The companies plan to submit a New Drug Application (NDA) for vepdegestrant to the FDA in the second half of 2025 [7][12] - Vepdegestrant is the first PROTAC evaluated in a Phase 3 clinical trial, indicating a novel approach in treating breast cancer [5][7]

Company Overview - Arvinas, Inc. is a clinical-stage biotechnology company focused on developing a new class of drugs based on targeted protein degradation [3] - The company is headquartered in New Haven, Connecticut and is listed on Nasdaq under the ticker ARVN [3] Drug Development - Arvinas is pioneering the PROTAC (PROteolysis Targeting Chimera) protein degrader platform, which aims to selectively and efficiently degrade disease-causing proteins [3] - The company is advancing multiple investigational drugs through clinical development, including: - Vepdegestrant, targeting the estrogen receptor for patients with locally advanced or metastatic ER+/HER2- breast cancer [3] - ARV-393, targeting BCL6 for relapsed/refractory non-Hodgkin Lymphoma [3] - ARV-102, targeting LRRK2 for neurodegenerative disorders [3] Upcoming Events - Management will participate in a fireside chat at the Jefferies Global Healthcare Conference on June 5 at 2:35 p.m. ET in New York City [1] - A live audio webcast of the presentation will be available on the company's website [2]

28 May 2025 | 5:02AM BST Europe Healthcare: Pharmaceuticals Setting the scene for SERDs ahead of ASCO updates We expect developments in the SERD (Selective Estrogen Receptor Degrader) class of breast cancer therapies to be a key focus for investors as we enter a catalyst rich 12-24 month period for the class that has relevance to multiple companies. With a 500K+ eligible patient population globally, we believe the class could be worth $15bn+ by 2035. Specifically in our European BioPharma coverage, AZN and ...

癌症是现代社会挥之不去的阴影。 与健康细胞相比，癌细胞行为的改变是由蛋白质过度表达引起的。这些蛋白质具有促进细胞增殖、存活 和迁移等功能，其中一些蛋白质很容易被靶向和抑制，而另一些蛋白质则不易被小分子或抗体接近，因 此被认为是"不可成药"。 现在，这一困境正在被一种革命性技术打破。科学家将希望寄托于靶向蛋白降解技术，这种技术能够攻 克传统药物无法触及的"不可成药"靶点，并对抗由这些蛋白质过度表达引起的癌症，或将为癌症治疗带 来全新可能。 破解"不可成药"蛋白难题 蛋白水解靶向嵌合体（PROTAC）是一种新兴的靶向降解蛋白质的治疗策略。 首个进入Ⅲ期临床试验的PROTAC是Arvinas和辉瑞公司联合开发的vepdegestrant，它能降解大多数乳腺 癌生长所依赖的雌激素受体。今年3月初，Arvinas及辉瑞报告称，在带有一种乳腺癌相关突变的试验参 与者中，这种降解剂比标准的抗雌激素药物更能延长患者的无病生存期。 与此同时，还有另外两种PROTAC也进入了Ⅲ期临床试验。一种能降解驱动大多数转移性前列腺癌的雄 激素受体；另一种则能降解慢性淋巴细胞白血病所需的BTK酶。针对这些靶点的药物虽已存在，但晚期 癌症最终 ...

– Reported positive topline results from the Phase 3 VERITAC-2 trial that support global regulatory filings – – Presented first-in-human data for the Company’s first neuroscience program with ARV-102 showing blood-brain barrier penetration and central and peripheral LRRK2 degradation – – Announced the re-prioritization of its vepdegestrant development plan and research portfolio and initiated cost reductions, including a workforce reduction of approximately one-third, to extend the Company’s cash runway int ...