驱动基因阴性NSCLC专题 下一代治疗范式：双抗、IO+ADC 西南证券研究院 2026年2月 分析师：杜向阳 执业证号：S1250520030002 电话：021-68416017 邮箱：duxy@swsc.com.cn 分析师：雷瑞 执业证号：S1250525110001 电话：021-68416017 邮箱：leir@swsc.com.cn 核心结论 驱动基因阴性空间几何？ 报告目录 1 NSCLC全球第一大癌种，驱动基因阴性占三成 2 从一线治疗看驱动基因阴性市场空间几何 驱动基因阴性指肿瘤样本中未检测到明确可靶向的驱动基因突变，分别占中美患者新发NSCLC患者的31%/31%。基于目前中美指南推荐，一线 治疗驱动基因阴性NSCLC晚期患者主要依赖PD(L)-1±化疗的治疗方案，我们测算2030年用于驱动基因阴性NSCLC晚期一线治疗的免疫用药中美 市场规模分别约为75亿元、180亿元。 NSCLC下一代免疫治疗方案齐头并进——双（多）抗、IO+ADC 从临床指南来看，以帕博利珠单抗、阿替利珠单抗为代表的PD(L)-1药物(不)联用化疗已全面覆盖驱动基因阴性一线及后线治疗，临床地位稳定， 但长期维度下 ...

Core Insights - The iShares Core MSCI Total International Stock ETF (IXUS) and the iShares Core MSCI EAFE ETF (IEFA) provide different exposures to international equities, with IXUS including emerging markets and IEFA focusing solely on developed markets [1][2] Cost and Size Comparison - Both IXUS and IEFA have an expense ratio of 0.07% - As of January 30, 2026, IXUS has a 1-year return of 37.7% while IEFA has a return of 34.9% - IXUS has a dividend yield of 3.2% compared to IEFA's 3.6% - IXUS has assets under management (AUM) of $51.9 billion, while IEFA has $162.6 billion [3][4] Performance and Risk Comparison - Over the past five years, IXUS experienced a maximum drawdown of -30.05%, while IEFA had a drawdown of -30.41% - An investment of $1,000 in IXUS would have grown to $1,305, whereas the same investment in IEFA would have grown to $1,353 [5] Fund Composition - IEFA tracks developed markets in Europe, Australasia, and the Far East, holding 2,589 companies with a sector focus on financial services (22%), industrials (20%), and healthcare (11%) [6] - IXUS holds over 4,100 stocks, providing broader diversification with sector allocations leaning towards financial services, industrials, and basic materials [7] Investor Implications - The choice between IXUS and IEFA depends on the desired exposure; IXUS offers global exposure including emerging markets, while IEFA provides stability and a higher dividend yield from developed markets [8][11] - IEFA's focus on developed markets avoids emerging market volatility but limits growth potential, while IXUS can deliver higher returns due to emerging market growth despite associated risks [9][10]

Core Insights - Roche's experimental drug fenebrutinib has successfully met its primary endpoint in a late-stage trial for patients with primary progressive multiple sclerosis [1] Company Summary - Roche is a Swiss pharmaceutical company that is advancing its research in multiple sclerosis treatments [1] - The successful trial results for fenebrutinib may enhance Roche's position in the competitive pharmaceutical market for neurological disorders [1] Industry Summary - The pharmaceutical industry is witnessing significant advancements in treatments for multiple sclerosis, particularly in progressive forms of the disease [1] - The success of fenebrutinib could lead to increased investment and interest in the development of similar therapies within the industry [1]

Core Insights - Roche announced that fenebrutinib, an investigational BTK inhibitor, met its primary endpoint of non-inferiority compared to OCREVUS in reducing disability progression in patients with primary progressive multiple sclerosis (PPMS), showing a 12% reduction in risk of disability progression [1][5] - The treatment effect was consistent across patient subgroups and observed as early as 24 weeks, particularly benefiting upper limb function [3][5] Study Details - The FENtrepid study was a Phase III multicenter, randomized, double-blind trial involving 985 adult patients with PPMS, comparing daily oral fenebrutinib to intravenous OCREVUS for at least 120 weeks [7] - The primary endpoint was the time to onset of 12-week composite confirmed disability progression (cCDP12), which included measures of functional disability, walking speed, and upper limb function [8] Treatment Efficacy - Fenebrutinib demonstrated a 26% reduction in the risk of worsening upper limb function compared to OCREVUS [2] - A post-hoc analysis indicated fenebrutinib was superior to OCREVUS on a composite endpoint including two components of cCDP12, with a 22% reduction in risk [3] Safety Profile - Adverse events in the fenebrutinib group were comparable to OCREVUS, with infections occurring in 67.0% of patients on fenebrutinib versus 70.9% on OCREVUS [4] - Transient liver enzyme elevations were more common in the fenebrutinib group (13.3% vs 2.9% for OCREVUS), but all cases resolved after discontinuation of the drug [4] Future Developments - Roche plans to submit regulatory applications for fenebrutinib in both PPMS and relapsing multiple sclerosis (RMS) following the readout of the second pivotal RMS study, FENhance 1, expected in mid-2026 [5][6]

曾经的肿瘤霸主正从"青黄不接"的焦虑中走出。 在肿瘤腹地，Phesgo以48%的增速证明HER2防线依然坚固；在血液瘤战场，Polivy正攻城略地，复兴之势持续。罗氏 CEO更是反复提及的"不会遭遇专利悬崖"，因为2030年之前将推出19款新药，其中 16 款具备重磅炸弹潜力，9 款销售 峰值将突破 30 亿美元。 这其中，乳腺癌领域诞生新王牌giredestrant，罗氏对其信心满满；尤其是在兵家必争的减重领域，罗氏再次高调宣布 要成为"第三极"。 当罗氏将百亿美元赌注押向肥胖、阿尔茨海默病等慢性病领域时，一场关乎未来十年的战略豪赌已然展开。成功，则 河山永固；若有差池，下一个悬崖或许已在视野之中。 无论如何，罗氏让我们在行业史上最严峻专利悬崖面前看到了一种思路：保持战略定力，敢于突破舒适区，才能在不 确定性中找到新的增长答案。毕竟，在创新药的战场上，从来没有永恒的王者，只有不断进化的幸存者。 乳腺癌新王牌 罗氏这个昔日的肿瘤霸主，交出了一份营收增长7%、制药业务增长9%的稳健答卷。更重要的是，数字背后是一幅"重 整河山"的清晰图景。Phesgo、Xolair、Ocrevus、Hemlibra、Vabysm ...

FDA Approvals & Rejections - Intellia Therapeutics has received FDA approval to resume its MAGNITUDE-2 Phase 3 trial for nexiguran ziclumeran (nex-z) targeting hereditary transthyretin amyloidosis with polyneuropathy, increasing target enrollment from 50 to 60 patients [2][4] - Outset Medical's next-generation Tablo Hemodialysis System has been granted FDA 510(k) clearance, making it the first dialysis device to meet enhanced cybersecurity standards, with shipping expected to begin in Q2 2026 [6][7] - OKYO Pharma has received positive feedback from the FDA for its Phase 2b/3 trial design for Urcosimod, a candidate for neuropathic corneal pain, with plans to start the trial in the first half of 2026 [8][9] - REGENXBIO has faced clinical holds on its RGX-111 and RGX-121 gene therapy programs due to a case of CNS tumor in a child treated with RGX-111, although no similar findings were reported in other patients [10][11] - Almirall has received NMPA approval for Seysara in China for treating moderate-to-severe acne vulgaris, expanding its dermatology portfolio in the region [12][13] Clinical Trials - Breakthroughs - Aprea Therapeutics reported early clinical activity for APR-1051 in endometrial cancer, achieving a 50% reduction in target lesion size in a patient with PPP2R1A-mutated uterine serous carcinoma [19][21] - Fractyl Health's Revita demonstrated positive results in weight maintenance after GLP-1 drug discontinuation, showing a 4.5% weight regain compared to 7.5% in the sham group [22][24] - Ascletis Pharma announced positive Phase 3 results for Denifanstat in moderate-to-severe acne vulgaris, focusing on long-term safety in a trial with 240 patients [25][26] - GRI Bio reported new gene expression data from its Phase 2a study of GRI-0621 in idiopathic pulmonary fibrosis, showing significant improvements in lung injury and fibrosis progression [27][28] - Cardiff Oncology announced encouraging results from its Phase 2 trial of Onvansertib in RAS-mutated metastatic colorectal cancer, with a well-tolerated regimen and plans to advance to a registrational program [31][32] - Genentech's CT-388 Phase 2 trial for obesity showed a significant placebo-adjusted weight loss of 22.5% at 48 weeks, with a high percentage of participants achieving significant weight loss [34][36] - Sarepta Therapeutics reported positive three-year results from its EMBARK study for ELEVIDYS in Duchenne muscular dystrophy, showing significant slowing of disease progression in treated patients [38][41] Deals - YD Bio Limited has signed a letter of intent to acquire Safe Save Medical for approximately $26.87 million, aiming to enhance its capabilities in advanced cellular therapeutics [14][15][17]

Core Insights - The article promotes a weekly newsletter focused on stocks in the biotech, pharma, and healthcare sectors, highlighting key trends and catalysts that influence market valuations [1] Group 1 - The newsletter is led by a biotech consultant with over 5 years of experience covering the industry and has compiled detailed reports on more than 1,000 companies [1] - The investing group, Haggerston BioHealth, caters to both novice and experienced biotech investors, providing insights on catalysts for buying and selling [1] - The group offers forecasts for product sales and financial statements for major pharmaceutical companies, including discounted cash flow analysis and market-specific evaluations [1]

Core Insights - Roche Holding AG is a leading Swiss pharmaceutical company with a strong market position, reflected in its P/E ratio of 46.89 and price-to-sales ratio of 5.72 [1] - The company reported core EPS growth and anticipates high single-digit growth in core EPS for 2026, supported by a robust drug pipeline [2][4] - Roche's revenue for 2025 was CHF 61.5 billion (approximately $80 billion USD), with a 7% increase in group sales at constant exchange rates [2][4] Financial Performance - Core operating profit rose by 13%, contributing to a 58% increase in IFRS net income, aided by the base effect of impairment charges in 2024 [3] - The Pharmaceuticals Division saw a 9% rise in sales to CHF 47.7 billion, driven by demand for key products like Phesgo, Xolair, and Ocrevus [2] - Roche's sales increased by 8% in the fourth quarter of 2025, indicating continued positive momentum [2] Future Outlook - Roche projects a mid single-digit increase in group sales for 2026 and plans to increase its dividend [3][4] - The company's financial health is strong, with a debt-to-equity ratio of 1.21 and a current ratio of 1.29, indicating effective debt management and ability to cover short-term liabilities [3][4]

Core Insights - Roche Holding AG's 2025 results were negatively impacted by currency fluctuations, with total sales of $74.4 billion falling short of the Zacks Consensus Estimate of $81.4 billion and earnings per American Depositary Receipt at $2.94, below the expected $3.06 [1] Sales Performance - Sales increased by 7% year over year at constant exchange rates (CER) to CHF 61.5 billion, driven by robust demand for both pharmaceuticals and diagnostics [2] - The Pharmaceuticals Division saw a 9% growth to CHF 47.7 billion, fueled by strong demand for key drugs such as Phesgo, Xolair, Ocrevus, Hemlibra, and Vabysmo [3][8] - The Diagnostics Division's sales reached CHF 13.8 billion, up 2%, as demand for pathology and molecular solutions outweighed the effects of healthcare pricing reforms in China [3] Key Drug Performance - The top five growth drivers—Phesgo, Xolair, Hemlibra, Vabysmo, and Ocrevus—generated total sales of CHF 21.4 billion, an increase of CHF 3.2 billion at CER compared to 2024 [6] - Ocrevus sales reached CHF 7 billion, up 9%, while Hemlibra surged 11% to CHF 4.7 billion, and Vabysmo grew 12% to CHF 4.1 billion [9] - Xolair sales increased by 32% to CHF 3.1 billion, driven by strong uptake in food allergies, although a biosimilar launch is anticipated in the second half of 2026 [10] - Phesgo's sales skyrocketed 48% year over year to CHF 2.4 billion, attributed to strong conversion rates [11] Future Outlook - Roche anticipates mid-single-digit sales growth at CER for 2026, with core earnings per share expected to grow in the high single-digit range [14] - The company has made progress in its pipeline, with approvals for Gazyva/Gazyvaro and Lunsumio, as well as positive results for breast cancer candidate giredestrant and multiple sclerosis candidate fenebrutinib [15][16][17] Market Position - Roche's shares have increased by 36.5% year to date, outperforming the industry growth of 18% [4] - The company is entering the competitive obesity market with its investigational drug CT-388, which has shown promising results in early trials [20][21]

How Roche Hopes To Go Toe-To-Toe With Eli Lilly, Novo Nordisk In Obesity | Investor's Business DailyBREAKING: [Futures Rise Amid Huge Earnings]---Roche (RHHBY) hopes to go toe-to-toe with Eli Lilly (LLY) and Novo Nordisk (NVO) in the red-hot weight-loss space. The Swiss drug giant said Thursday it expects to seek approval for four new obesity drugs in 2028. "Every patient is on an individual weight-loss journey," Teresa Graham, chief executive of Roche's pharma division, said during the earnings conference ...