近日，加科思发布公告称，公司与阿斯利康就泛KRAS抑制剂JAB-23E73订立许可及合作协议。 董事会认为，此协议符合公司及股东的整体最佳利益，有助于进一步加强全球合作网络，最大化公司技 术平台的科学及商业价值。 （加科思公告） (编辑：杨燕 林辰) 根据协议，北京加科思（公司非全资附属公司）有权从阿斯利康收取1亿美元的首付款，并在达到若干 开发、监管及商业里程碑后有资格获得额外潜在总对价最高可达19.15亿美元的里程碑付款。此外，在 许可产品成功商业化后，北京加科思将获得基于许可产品净销售额计算的分层特许权使用费。 公告显示，阿斯利康将获得独家许可在全球范围内（除中国（不包括香港、澳门及台湾）外）研究、开 发、注册、制造及商业化JAB-23E73。北京加科思需向阿斯利康提供必要的技术转移、数据及合理协 助。阿斯利康负责其区域内的开发、监管事务及商业化相关主要活动及费用，而在中国的活动及成本将 由双方共同承担。 ...

医药周报 20251221 In Vivo CAR-T 国内外进展大 医药行情回顾&分析&近期判断 > 1) 行情回顾：当周（12.15-12.19）医药生物指数环比-0.14%，跑赢创业板指数和沪深 300 指数, 在所有行业中，当周（12.15-12.19）医药涨跌幅排在第 18 位, V 型走势。周度结构上看, 蚂蚁阿 福、"搞赏经济"主题等相关标的表现较好，周五表现更为强势，CXO、小核酸、部分创新药和 AI 创 新药相对较好。医药成交总额 3898.24 亿元，沪深总成交额为 86901.56 亿元，医药成交额占比沪深 总成交额比例为 4.49%（2013 年以来成交额均值为 7.12%）。 2）原因分析：医药近期暂未有较大的产业催化，板块贝塔效应不明显，但经过一段时间消化，很多 标的进入价值区间，或潜在具备一定的反攻可能，这期间结构性热度会逐步提升。本周蚂蚁阿福带 动相关个股演绎：一类是阿里的持股相关医药公司，一类阿福可能引流的公司（渠道如部分药店、 部分消费端器械、检测服务、药品等 ) ，一类是有数据沉淀未来潜在可能对标公司。全市场 "椅赏经 济"也影射了医药中部分公司，如部分药店。周五医药表现 ...

Core Viewpoint - The competition in the KRAS inhibitor space has shifted from a molecular comparison between Revolution Medicines' RMC-6236 and Adagene's JAB-23E73 to a broader corporate competition between AstraZeneca and Revolution Medicines [2][3]. Group 1: Molecular Comparison - RMC-6236 targets KRAS, HRAS, and NRAS but has significant toxicity issues, with a nearly 90% incidence of rash and 34% of patients experiencing grade 3 or higher treatment-related adverse events (TRAE) in a second-line setting [3][4]. - In contrast, JAB-23E73, still in early development, has shown a cleaner safety profile with no observed dose-limiting toxicities and only grade 1 skin toxicity reported [3][4]. - AstraZeneca's acquisition of JAB-23E73 enhances its potential in combination therapies, as a safer molecule is more likely to succeed in the competitive KRAS landscape [3][6]. Group 2: AstraZeneca's Strategic Position - AstraZeneca has been searching for a KRAS inhibitor for over a decade, previously attempting to develop other KRAS inhibitors that did not progress [5]. - The acquisition of JAB-23E73 fills a critical gap in AstraZeneca's oncology pipeline, positioning it to leverage its extensive resources for clinical development and commercialization [5][6]. - AstraZeneca's goal is to establish JAB-23E73 as a foundational treatment in combination therapies, requiring a broad safety window to withstand the toxicity of various treatment combinations [5][6]. Group 3: Resource Competition - The competition is not just about molecular efficacy but also about the resources available for clinical development, with AstraZeneca having significant financial and operational advantages over Revolution Medicines [7][8]. - AstraZeneca's established global clinical network allows it to conduct multiple phase III trials simultaneously, a capability that Revolution Medicines lacks due to its smaller scale [8][9]. - The financial disparity is stark, with AstraZeneca's revenue exceeding $50 billion and a strong growth trajectory in oncology, while Revolution Medicines has limited cash reserves [7][9]. Group 4: Manufacturing and Cost Considerations - RMC-6236's complex synthesis and high production costs pose challenges for commercialization, potentially leading to pricing pressures and supply chain risks [10]. - JAB-23E73, being a traditional small molecule, offers lower production costs and greater scalability, making it more suitable for widespread use [10]. Group 5: Market Valuation Discrepancies - The market currently values Revolution Medicines at approximately $15 billion, while Adagene's valuation is around HKD 7 billion, reflecting a significant disparity in perceived value [12]. - This valuation gap may stem from outdated perceptions, as the integration of JAB-23E73 into AstraZeneca's portfolio transforms its value proposition from a standalone molecule to a critical component of a larger therapeutic strategy [12]. Group 6: Future Implications - The true value of a drug target like KRAS lies not in the first successful inhibitor but in the ability to establish it as a standard treatment [13][14]. - The collaboration between Adagene and AstraZeneca could lead to significant advancements in cancer treatment, potentially impacting a large patient population and marking a milestone in cancer therapy [15].

12月22日，阿斯利康与加科思药业宣布就泛KRAS抑制剂JAB-23E73达成全球独家许可协议。阿斯利康 将获得该产品在中国以外市场的独家开发和商业化权利。在中国市场，加科思将与阿斯利康共同开发和 商业化该产品。 根据协议条款，加科思将获得1亿美元的首付款，并有资格额外获得最高达19.15亿美元的开发及商业化 里程碑付款，以及在中国以外市场实现的净销售额分级特许权使用费。阿斯利康将负责JAB-23E73在中 国以外市场的所有临床开发、注册申报和商业化活动。 ...

Investment Rating - The report does not explicitly state an investment rating for the industry or specific companies involved in the development of oral SERDs for breast cancer treatment. Core Insights - The report highlights the recent FDA approval of Imlunestrant, an oral SERD developed by Eli Lilly, for the treatment of ER+/HER2–/ESR1 mutant advanced or metastatic breast cancer, marking it as the second oral SERD approved after Elacestrant [18][19] - The EMBER-3 trial results indicate that Imlunestrant significantly improves progression-free survival (PFS) compared to standard endocrine therapy, with a median PFS of 5.5 months versus 3.8 months for standard therapy [23] - Giredestrant, developed by Roche, has shown positive results in the III phase evERA trial, demonstrating significant benefits in PFS compared to standard treatment in patients previously treated with CDK4/6 inhibitors [27] - Camizestrant, another oral SERD from AstraZeneca, has shown promising efficacy in the SERENA-6 trial, with a median PFS of 16.6 months when combined with CDK4/6 inhibitors [33] Summary by Sections Section 1: Focus on Innovative Drugs - The report reviews the advancements in innovative drugs, particularly in the field of breast cancer treatment, emphasizing the importance of oral SERDs [2][5] Section 2: Current Status of ER+ Breast Cancer Therapies - The report discusses the current landscape of therapies for ER+ breast cancer, including the mechanisms of action for various anti-estrogen therapies and the challenges of resistance faced by patients [10][8] Section 3: Clinical Development of New Oral SERDs - The report details the clinical development progress of several new oral SERDs, including Imlunestrant, Giredestrant, and Camizestrant, highlighting their respective phases and trial outcomes [12][11][33] Section 4: Market Dynamics and Company Performance - The report provides insights into the market dynamics of the biotech sector, including stock performance of key companies involved in the development of innovative cancer therapies [46][49]

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Core Insights - The article discusses a recent study identifying three distinct disease trajectories in severe asthma patients prior to biologic treatment, highlighting the heterogeneity of the disease and its implications for personalized intervention strategies [1][14]. Group 1: Disease Trajectories - The study included 755 severe asthma patients from Denmark, analyzing data from 1995 to 2022, and identified three main disease progression paths: "Chronic Severe Type" (26%), "Gradual Onset Type" (35%), and "Recent Onset Type" (39%) [2][3]. - "Chronic Severe Type" patients have the longest median disease duration of 35 years, the most severe lung function impairment (median FEV1%pred of 64%), and the highest rates of comorbidities related to corticosteroid exposure [2]. - "Gradual Onset Type" patients show a stepwise worsening pattern with a median disease duration of 26 years and a median FEV1%pred of 67%, indicating a progression from mild to severe asthma [3]. - "Recent Onset Type" patients have the shortest median disease duration of 5 years, with a median FEV1%pred of 75%, and a significant proportion of patients (43%) having baseline FEV1%pred > 80% [3]. Group 2: Treatment Response and Prognosis - The study found a clear association between disease trajectories and treatment outcomes, with "Recent Onset Type" patients showing the highest clinical response rate of 32%, compared to 29% for "Gradual Onset Type" and only 17% for "Chronic Severe Type" [4]. - A key barrier for "Chronic Severe Type" patients is the difficulty in restoring lung function, with only 32% achieving normal lung function post-treatment, compared to 56% in "Recent Onset Type" [4]. - The concept of "too late" asthma was introduced, indicating patients who do not achieve FEV1%pred > 80% after 12 months of biologic treatment, with a high occurrence in "Chronic Severe Type" (56%) [4][5]. Group 3: Implications for Early Intervention - The findings suggest that recognizing disease trajectories early can provide actionable intervention opportunities before reaching the "Chronic Severe" stage, potentially preventing irreversible lung damage [5][6]. - The study emphasizes the need to shift the treatment paradigm for severe asthma from a reactive approach to proactive early intervention with biologics, particularly for patients in the early stages of "Recent Onset Type" or "Gradual Onset Type" [6][7]. - Evidence from simulations indicates that initiating biologic treatment 5 years earlier could significantly reduce corticosteroid use, prevent deaths, and lower healthcare costs, highlighting the value of early intervention [7].

Core Insights - President Trump announced a set of drug-pricing agreements with nine major pharmaceutical companies, aiming to align U.S. medicine costs with those in Europe [1][2] - The initiative includes a new direct-to-consumer portal, TrumpRx.gov, allowing patients to purchase certain medicines directly from manufacturers [2][4] Group 1: Agreements and Participants - The agreements involve 14 out of 17 drugmakers that Trump previously urged to lower prices, including Amgen, GSK, and Merck [2][3] - Drug companies are motivated to negotiate to avoid potential regulatory measures that could impact their profits [3] Group 2: TrumpRx.gov Functionality - TrumpRx.gov will serve as a central directory for patients to access selected medicines directly from manufacturers' websites [4] - The portal is expected to be fully operational by January, following a promotional launch [4] Group 3: Pricing Details - Highlighted medicines include Amgen's Repatha at $239/month, GSK's Advair Diskus at $89/month, and Merck's Januvia at $100/month [6] - Gilead's Epclusa will be priced at $2,492/month, despite lower costs for insured patients [6] Group 4: Impact on Medicaid and Medicare - Companies committed to launching new medicines in the U.S. at prices comparable to those in other wealthy countries [8] - Medicaid programs are legally entitled to the lowest drug prices, with Bristol Myers Squibb offering Eliquis free to Medicaid [9] Group 5: Industry Response and Future Outlook - Health policy experts express skepticism about the agreements' impact on overall drug prices for most Americans [10] - The agreements do not impose mandatory price controls and leave many brand-name drug costs unchanged [15] - Ongoing discussions with additional manufacturers like AbbVie and Johnson & Johnson may lead to further agreements [14]

Core Insights - Donald Trump and nine major pharmaceutical companies have reached agreements to significantly reduce drug prices for the Medicaid program and cash payers, aiming to align US costs with those in other wealthy nations [1][2] Group 1: Price Reductions and Agreements - Drugmakers will cut prices on most drugs sold to Medicaid, promising "massive savings" on commonly used medicines, although specific figures were not disclosed [2] - The deals include agreements to lower cash-pay prices for select drugs, launch drugs in the US at prices equal to those in other wealthy nations, and increase manufacturing [3] - Merck plans to sell its diabetes drugs at approximately 70% off list prices directly to US consumers, with potential for its experimental cholesterol drug to be offered through direct channels [4] Group 2: Previous and Current Deals - Five companies had previously made agreements with the administration to control prices, while three companies have yet to announce deals [6] - Drugmakers committed to "most-favored-nation" pricing for all new US drug launches across various markets, including Medicare [7] Group 3: Financial Commitments and Investments - Companies pledged to invest over $150 billion in US research and development and manufacturing, with Merck contributing $70 billion of that total [8] - A portion of revenues from foreign sales will be remitted to the US to help offset costs [8] Group 4: Medicaid and Market Impact - Medicaid, which represents about 10% of US drug spending, already benefits from significant price discounts, sometimes exceeding 80% [9] - Pfizer indicated that Medicaid discounts would lead to price and margin compression in the upcoming year [9]

US President Donald Trump on Friday (December 19) announced agreements with nine major pharmaceutical companies to sharply cut the prices of medicines sold through the government’s Medicaid program and to cash-paying consumers, marking his latest push to bring US drug costs in line with those in other wealthy nations.The deals were unveiled at a White House press conference, where Trump appeared alongside senior executives from the participating drugmakers.“We were subsidizing the entire world. We’re not do ...