Market Overview - The S&P 500 Index rose 17.9% in 2025, while the equal-weighted S&P 500 Index gained 11.4% [2] - The Magnificent Seven stocks increased by 24.9% in 2025 [2] - Since the launch of ChatGPT, the cap-weighted S&P 500 has nearly doubled the gains of its equal-weighted counterpart, with the Magnificent Seven surging 332% [3] Performance Analysis - The cap-weighted S&P 500 delivered an annualized total return of 23.0% from December 31, 2022, to December 31, 2025, compared to 12.7% for the equal-weighted S&P 500 [4] - The market is characterized by significant concentration, making it the most concentrated equity market in American history [4] Investment Strategy - The ClearBridge Dividend Strategy has seen healthy gains due to investments in AI-related companies like Alphabet, Broadcom, Meta, Microsoft, and Oracle, although it has not matched the cap-weighted S&P 500's performance [10] - The strategy limits individual holdings to 3%-5% of the portfolio and caps sector exposures at 15%-20%, while the IT sector currently represents 34% of the market [11] AI Market Dynamics - AI is expected to radically change various sectors, but not all AI stocks are considered good investments due to high valuations relative to current revenues [13] - Key questions remain regarding the future of large language models and the competitive landscape, particularly between U.S. and Chinese companies [14] Company-Specific Insights - Oracle's shift to a capital-intensive AI data center business raises concerns about its balance sheet and investment-grade credit rating, leading to a reduction in its position [19] - Broadcom's position as a leading ASICS chip provider allows it to compete effectively in the AI market, with a strategy that aligns with its core competencies [20] Future Outlook - The ClearBridge Dividend Strategy anticipates continued focus on AI in 2026 but aims to find opportunities in overlooked market segments [26] - The strategy continues to trade at a significant discount to the broader market, with an average holding growing its dividend by 10% over the last 12 months [27]

Market Performance - European stocks closed higher, with the pan European Stoxx 600 climbing 0.58% and the U.K.'s FTSE 100 increasing by 1.18% [1] - Several European markets, including Austria, Belgium, and Spain, also recorded gains, while Iceland, Ireland, Poland, and Russia ended weak [2] Company Highlights - Next Plc shares surged 5% after upgrading profit guidance, forecasting after-tax earnings of 738.8 pence per share, driven by a more than 10% surge in sales in December [3] - In the UK market, Fresnillo climbed about 5%, while AstraZeneca, Burberry Group, and several others gained between 3% to 5% [2] - JD Sports Fashion drifted down 4.4%, and Adidas ended lower by about 4.2% following a rating downgrade by Bank of America [4] Sector Performance - In the German market, Daimler Truck Holding gained 5.3%, and Infineon moved up 5% [4] - In France, EssilorLuxottica gained more than 5%, while Edenred and Kering ended higher by about 4.3% and 4%, respectively [5] - Polish parcel locker company shares soared more than 28% after announcing an indicative buyout offer [6] Economic Indicators - The HCOB Composite PMI in Germany decreased to 51.3 in December from 52.4 in November [6] - France's inflation eased to a seven-month low in December, with the consumer price index logging an annual increase of 0.8% [7] - EU harmonized inflation slowed unexpectedly in December to 0.7% from 0.8% in November [8]

Core Insights - BostonGene has announced a strategic collaboration with AstraZeneca to enhance oncology drug development using its multimodal AI platform [1] Group 1: Company Overview - BostonGene is recognized for developing a leading AI foundation model focused on tumor and immune biology [1] - AstraZeneca is a global biopharmaceutical company that emphasizes the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals [1] Group 2: Collaboration Details - The collaboration aims to leverage BostonGene's AI capabilities to advance drug development in oncology [1]

Summary of CES 2026 Keynote Address by AMD CEO Dr. Lisa Su Industry Overview - The keynote was part of CES 2026, a major technology event showcasing innovations across various sectors, particularly focusing on AI and high-performance computing [1][4][5] - AMD is positioned as a central player in the global AI transformation, emphasizing its role in high-performance and AI computing [5][6] Core Points and Arguments AI and Computing Demand - AI is described as the most important technology of the last 50 years, with AMD prioritizing its development [15][16] - The number of active AI users has surged from 1 million to over 1 billion, with projections of reaching over 5 billion users [16][17] - Global compute infrastructure demand is expected to grow from approximately 1 Zettaflop in 2022 to over 100 Zettaflops by 2025, necessitating a further increase to over 10 Yottaflops in the next five years [17][19] - AI's integration into various sectors, including healthcare, education, and productivity, is highlighted as transformative [15][16] AMD's Technological Innovations - AMD's Helios platform is introduced as a next-generation rack scale solution designed for AI, featuring advanced MI455 GPUs and EPYC CPUs [23][30] - The MI455 GPU boasts 320 billion transistors and is designed for high performance, delivering up to 10 times more performance compared to previous generations [27][30] - The Helios rack is designed for optimal serviceability and reliability, weighing nearly 7,000 pounds and integrating cutting-edge technologies [24][25][26] Partnerships and Collaborations - AMD's collaboration with OpenAI is emphasized, showcasing the need for increased compute capacity to support advanced AI models [31][39] - Luma AI's CEO, Amit Jain, discusses their partnership with AMD, highlighting the efficiency and performance improvements achieved through AMD's hardware [50][59] Future Outlook - The demand for compute is expected to continue growing, with AMD's next-gen MI500 series already in development, promising a 1,000x increase in AI performance over four years [63][64] - The Ryzen AI 400 Series is introduced as the most advanced family of AI PC processors, set to enhance productivity and content creation capabilities [67][68] Additional Important Content - The keynote emphasizes the collaborative nature of innovation, stating that AI is not a solo act but a shared pursuit among industry leaders [2][4] - The importance of an open ecosystem for AI development is stressed, with AMD advocating for shared technology standards across hardware and software [48][49] - The potential of AI in personal computing is highlighted, with AI PCs becoming essential partners in productivity and creativity [65][66] This summary encapsulates the key themes and innovations presented during the CES 2026 keynote by AMD's CEO, focusing on the transformative impact of AI and the company's strategic advancements in computing technology.

Core Insights - The New Drug Application (NDA) for savolitinib has been accepted and granted priority review by the China National Medical Products Administration (NMPA) for treating gastric cancer patients with MET amplification who have failed at least two prior systemic treatments [1][2] - Savolitinib is positioned to be the first selective MET inhibitor in China for MET-amplified gastric cancer, which has a poor prognosis [1][3] - The NDA is supported by positive Phase II registration study data demonstrating a significant objective response rate [2][4] Company Overview - HUTCHMED is an innovative biopharmaceutical company focused on the discovery and commercialization of targeted therapies and immunotherapies for cancer and immunological diseases [7] - Savolitinib is being jointly developed by AstraZeneca and HUTCHMED, and it is already approved in China under the brand name ORPATHYS [6][5] - The drug has been included in the National Reimbursement Drug List of China since March 2023, indicating its significance in the market [6] Industry Context - Gastric cancer is one of the most common cancers and a leading cause of cancer death in China, with MET amplification occurring in approximately 4-6% of gastric cancer patients [3] - The annual incidence of MET amplification gastric cancer in China is estimated to be around 18,000 cases [3] - The NMPA granted Breakthrough Therapy Designation to savolitinib in 2023, highlighting its potential advantages over existing therapies [4]

Core Viewpoint - Shares of Greenwich LifeSciences Inc. (GLSI) have seen significant gains as the company advances its financing strategy and prepares to implement modifications to its phase III trial for the breast cancer immunotherapy GLSI-100, pending regulatory approval [1] Company Overview - GLSI-100 is a combination of GP2 peptide vaccine and GM-CSF, aimed at helping the immune system recognize and combat cancer cells expressing the HER2/neu protein, which is present in 75% of breast cancer cases [2] - The drug is targeted at high-risk breast cancer patients post-surgery and standard treatments [2] Clinical Trial Details - The ongoing phase 3 trial, FLAMINGO-01, involves HLA-A*02-positive and HER2/neu-positive breast cancer patients at high risk for recurrence, with about 500 patients planned for random assignment to receive either GLSI-100 or a placebo [3] - A preliminary analysis of the 250-patient open-label non-HLA-A*02 arm showed an approximately 80% reduction in recurrence rate [4] Planned Modifications to the Trial - The company plans to increase the study size to enhance statistical power and reduce risk, despite potentially fewer recurrences being anticipated [4] - Strategies include doubling or quadrupling the enrollment rate to increase patient-years in the study and maintain momentum at clinical sites [5] - The trial's projected completion date is December 31, 2026 [6] Industry Context - Breast cancer is the most common cancer among women in the U.S., with over 4 million survivors [7] - Major pharmaceutical companies like Roche, AstraZeneca, and Pfizer are actively involved in developing HER2-targeted therapies, shaping the breast cancer treatment landscape [9] Financing Strategy - As of September 30, 2025, the company held $3.81 million in cash and is utilizing an At-the-Market (ATM) offering strategy to manage cash efficiently and minimize shareholder dilution [10] - Between January 1, 2025, and September 30, 2025, the company completed ATM offerings, generating gross proceeds of $6.49 million from the sale of 621,674 shares at an average price of $10.44 per share [11] Insider Share Lock-Up - The Board of Directors has extended the lock-up period for shares held by directors, officers, and pre-IPO investors until September 30, 2026, approximately 72 months post-IPO [12] Stock Performance - GLSI shares began trading on the Nasdaq Capital Market at $5.75 on September 25, 2020, and reached a 52-week intraday high of $22.31 on December 26, 2025, closing at $20.68 [13]

Core Insights - The Vanguard FTSE Developed Markets ETF (VEA) and the iShares Core MSCI EAFE ETF (IEFA) target developed markets outside the U.S. but differ in index rules, impacting portfolio construction [1][10] - VEA has a lower expense ratio and broader country coverage, while IEFA offers a higher dividend yield [2][4] Cost & Size Comparison - VEA has an expense ratio of 0.03% and assets under management (AUM) of $260.0 billion, while IEFA has an expense ratio of 0.07% and AUM of $160.6 billion [3][4] - The one-year return for VEA is 29.1%, compared to IEFA's 25.8%, and the dividend yield for VEA is 2.7% versus IEFA's 2.93% [3][4] Performance & Risk Metrics - Over five years, VEA's maximum drawdown is 29.71%, while IEFA's is 30.41% [5] - A $1,000 investment in VEA would grow to $1,324, while the same investment in IEFA would grow to $1,284 over five years [5] Holdings & Sector Allocations - IEFA holds 2,593 stocks with significant allocations in Financial Services (22%), Industrials (20%), and Healthcare (10%), with top positions including ASML Holding and Roche Holding [6] - VEA includes 3,873 companies, with sector weights of 24% in Financial Services, 19% in Industrials, and 11% in Technology, featuring top positions in ASML Holding and Samsung Electronics [7] Investment Implications - The choice between VEA and IEFA hinges on how investors define developed markets, with VEA including Canada and South Korea, while IEFA adheres to the MSCI EAFE framework [11]

Core Insights - The approval of Novo Nordisk's oral Wegovy marks a significant development in the GLP-1 market, attracting interest in healthcare and pharmaceutical ETFs [1][5] - The market for obesity treatments is projected to exceed $150 billion annually by the early 2030s, with Novo Nordisk gaining an early advantage [5] Group 1: Market Impact - The FDA's approval of Novo Nordisk's oral Wegovy is the first GLP-1 pill approved for chronic weight management, which is expected to increase access to obesity treatments [5] - In a 64-week trial, patients using the oral pill lost an average of 16.6% of their body weight compared to 2.7% for the placebo group, leading to a more than 7% increase in Novo shares during premarket trading [6] Group 2: Competitive Landscape - Eli Lilly is advancing its oral GLP-1 candidate, orforglipron, which is under accelerated review by U.S. regulators, with potential approval as early as March [7] - Other companies, including AstraZeneca and Roche, are also developing oral obesity treatments, indicating a competitive shift from injectable to oral medications [7][8] Group 3: Investment Opportunities - Broad healthcare ETFs like XLV and VHT provide diversified exposure to major drugmakers and health service providers benefiting from improved obesity outcomes [2] - More focused pharmaceutical ETFs, such as PPH and biotech funds like IBB and XBI, offer varying levels of sensitivity to drug development milestones, appealing to investors seeking targeted exposure [3][4]

Core Insights - AstraZeneca PLC and Daiichi Sankyo received FDA approval for Enhertu as a first-line treatment for HER2-positive breast cancer, in combination with Roche's Perjeta [2][7] - The approval is based on the DESTINY-Breast09 study, which showed a significant improvement in progression-free survival (PFS) [5][8] - AstraZeneca will pay Daiichi Sankyo a $150 million milestone payment following this approval [3][7] Regulatory Approval - Enhertu was reviewed under the FDA's real-time oncology review (RTOR) program [3] - The drug is already approved in over 85 countries for second-line treatment of HER2-positive breast cancer and for other cancers [3] Clinical Study Results - The DESTINY-Breast09 study demonstrated a median PFS of 40.7 months for the Enhertu-Perjeta combination, compared to 26.9 months for the standard regimen [5][8] - The combination reduced the risk of disease progression by 44% compared to the current standard treatment [5][7] Market Performance - Over the past year, AstraZeneca's shares increased by 36.3%, outperforming the industry average rise of 12.1% [4]

Core Insights - The FDA has granted Breakthrough Therapy designation to AstraZeneca and Daiichi Sankyo's Enhertu for expanded use in treating HER2-positive early breast cancer with residual invasive disease [1][2][7] - This marks the tenth Breakthrough Therapy designation for Enhertu, highlighting its potential to transform breast cancer treatment [2] - The designation is based on phase III DESTINY-Breast05 data, which indicates Enhertu may reduce invasive disease recurrence compared to current standard care [3] AstraZeneca's Stock Performance - AstraZeneca's shares have increased by 29.3% over the past six months, outperforming the industry average rise of 26.2% [4] Enhertu's Current Approvals and Developments - Enhertu is approved in over 85 countries for second-line treatment of HER2-positive breast cancer and has additional approvals for lung and gastric cancers [8] - Recently, the FDA approved Enhertu in combination with Roche's Perjeta as a first-line treatment for unresectable or metastatic HER2-positive breast cancer based on phase III DESTINY-Breast09 data [9] Partnership and Development Strategy - AstraZeneca and Daiichi Sankyo are jointly responsible for developing and marketing Enhertu globally, except in Japan where Daiichi has exclusive rights [11] - Both companies are pursuing extensive development programs for Enhertu and Datroway across multiple tumor types [11] Recent Study Outcomes - AstraZeneca's phase III LATIFY study, evaluating ceralasertib with Imfinzi in lung cancer, did not meet its primary overall survival goal [12] - The LATIFY study focused on patients without actionable genomic alterations whose disease progressed after prior treatments [13] Imfinzi Sales Performance - Imfinzi generated $4.32 billion in sales during the first nine months of 2025, reflecting a 25% increase driven by demand in lung and liver cancer indications [14]