AI & Technology - Google: Gemini is favored to win in AI, benefiting YouTube and Google Cloud; Waymo's automation potential is not fully valued; Sergey Brin's return is noted [1] - Alibaba: Impressed with their AI (Qwen), considered a top 3 AI lab in China [2] - Tencent: Owns the largest social network in China, a great business with founder-led management, also considered a top 3 AI lab in China [2] - Xiaomi: A pure play on EVs, especially with Elon Musk's focus shift; offers great inexpensive cars; behind on FSD but expected to catch up in a couple of years; founder-led [2] Healthcare & Pharmaceuticals - Eli Lilly: GLP-1 drugs may cure chronic diseases beyond fat loss; the market is too big to ignore; based in the US, which has a large chronically unhealthy population; has been consolidating for a year [2] Investment Strategy - Avoiding US tech stocks generally due to valuation, but Google is reasonably priced [1] - Investments in stocks are to force attention to interesting things [2]

除了改善OSA症状外，接受替尔泊肽治疗的成人患者平均体重减轻了18.1%，同时接受替尔泊肽和PAP 治疗的成人患者平均体重减轻了20.1%；而安慰剂组的成人患者平均体重分别减轻了1.3%和2.3%。 此外，替尔泊肽的安全性和耐受性与此前试验中报告的替尔泊肽安全性一致。最常见的不良事件是胃肠 道不良事件，程度为轻至中度。 礼来全球高级副总裁、礼来中国药物开发及医学事务中心负责人王莉博士表示："OSA是一种高发疾 病，其治疗主要集中在生活方式干预和器械治疗上，但这些方法可能无法解决OSA相关的部分致病风险 因素，如肥胖。替尔泊肽是首个且目前唯一治疗成人肥胖患者的中重度OSA的处方药，半数患者经治疗 后不再有OSA相关症状，为临床和患者提供了突破性的治疗选择，填补了该领域的药物治疗空白。" 据记者了解，此次获批主要基于SURMOUNT-OSA临床3期试验的结果。该试验为期一年，评估了替尔 泊肽(10mg或15mg)用于正在接受或不愿接受气道正压通气(PAP)的成人肥胖患者的中度至重度阻塞性睡 眠呼吸暂停的治疗有效性。对于未使用PAP治疗的成人患者中，替尔泊肽在减少呼吸暂停低通气的效果 是安慰剂的5倍，即替尔泊肽可使 ...

Core Viewpoint - Tirzepatide, developed by Eli Lilly, is a dual agonist for GIP and GLP-1 receptors, recently approved by the FDA for weight loss under the brand name Zepbound™ and previously for type 2 diabetes as Mounjaro™. It is noted as the most effective weight loss drug currently available, having set multiple records in clinical trials for weight reduction [2]. Summary by Sections FDA Approval and Indications - Tirzepatide received FDA approval in November 2023 for weight loss and has also been approved for type 2 diabetes treatment. It has now gained a third indication for moderate to severe obstructive sleep apnea (OSA) in adults, as announced by the NMPA in China [2]. Clinical Trial Results - The SURMOUNT-OSA trial demonstrated that Tirzepatide significantly reduced the apnea-hypopnea index (AHI) and body weight in patients with moderate to severe OSA and obesity. In a 52-week treatment period, patients lost an average of 20% of their body weight, and AHI decreased by an average of 27 times per hour [2][7][11]. Efficacy Metrics - In the SURMOUNT-OSA study, patients treated with Tirzepatide experienced a 55% reduction in AHI compared to a 5% reduction in the placebo group. The average weight loss in the Tirzepatide group was 18.1%, while the placebo group saw only a 1.3% reduction [8][9]. Safety Profile - The overall safety of Tirzepatide in the SURMOUNT-OSA studies was consistent with previous trials, with gastrointestinal issues being the most commonly reported adverse events, generally mild to moderate in severity [12]. Market Potential - The success of the SURMOUNT-OSA trials indicates a significant advancement in addressing the unmet clinical need for OSA treatment, positioning Tirzepatide as a potential first pharmacological therapy for this condition [12]. Demographics of Study Participants - Approximately 70% of participants in the studies were male, with evidence suggesting that Tirzepatide may have a more pronounced weight loss effect in females [11].

Core Insights - Eli Lilly's drug Mounjaro (tirzepatide) has received approval from China's National Medical Products Administration (NMPA) for a new indication to treat moderate to severe obstructive sleep apnea (OSA) in obese adults, marking it as the first and only prescription medication for this condition in China [1] - The approval is based on the results of the SURMOUNT-OSA Phase 3 clinical trial, which evaluated the drug's effectiveness in obese adults with OSA who were either receiving or unwilling to receive positive airway pressure (PAP) therapy [1] Group 1: Clinical Trial Results - Tirzepatide reduced the number of apnea-hypopnea events by five times compared to placebo in adults not using PAP, with a reduction of 27 events per hour versus 5 for placebo [2] - In adults using PAP, tirzepatide led to a reduction of 30 events per hour compared to 6 for placebo [2] - After one year of treatment, 43% of patients using tirzepatide alone achieved complete resolution of OSA symptoms or a mild OSA state, while 52% of those using both tirzepatide and PAP achieved similar results; the placebo group had rates of 15% and 14% respectively [2] Group 2: Weight Loss and Safety - Patients treated with tirzepatide alone experienced an average weight loss of 18.1%, while those receiving both tirzepatide and PAP lost an average of 20.1%; the placebo group saw weight losses of 1.3% and 2.3% respectively [2] - The safety and tolerability profile of tirzepatide remained consistent with previous trials, with gastrointestinal adverse events being the most common, typically mild to moderate in severity [2]

Core Insights - The approval of tirzepatide (brand name: Mounjaro) by the NMPA for treating moderate to severe obstructive sleep apnea (OSA) in adults marks a significant milestone as it is the first and only prescription drug for OSA globally [1] - Clinical data from Eli Lilly indicates that adult patients receiving tirzepatide treatment experience an average weight loss of 20% and a reduction of at least 27 episodes of hypopnea or apnea per hour during sleep [1] - The prevalence of OSA in China is estimated at 23.6%, with 8.8% being moderate to severe cases, and approximately 41% of these patients are also obese [2] Company Developments - Eli Lilly has received approval for tirzepatide for two indications in the past year: type 2 diabetes and long-term weight management, with the latest approval for OSA requiring dietary control and increased physical activity [1] - The FDA approved the OSA indication for tirzepatide in December last year, and further approvals in more countries will enhance Eli Lilly's competitive position in the weight loss drug market [3] Industry Context - OSA is characterized by airway obstruction during sleep, leading to breathing interruptions, and is associated with various cardiovascular diseases [2] - The number of individuals suffering from OSA in China is projected to exceed 200 million this year, indicating a growing public health concern [2]

Core Viewpoint - Eli Lilly announced that Mounjaro (tirzepatide injection) has received approval from the National Medical Products Administration (NMPA) in China, becoming the first and currently the only prescription medication for treating moderate to severe obstructive sleep apnea (OSA) in adult patients with obesity [1] Group 1 - Tirzepatide can improve sleep disorders in adult patients with moderate to severe obstructive sleep apnea and obesity [1] - The use of this indication requires a foundation of dietary control and increased physical activity [1]

Core Viewpoint - Analyst recommendations, particularly for Eli Lilly (LLY), are influential but may not be reliable indicators for investment decisions [1][5][10] Brokerage Recommendations - Eli Lilly has an average brokerage recommendation (ABR) of 1.46, indicating a consensus between Strong Buy and Buy, based on 27 brokerage firms [2] - Out of the 27 recommendations, 20 are Strong Buy and 2 are Buy, accounting for 74.1% and 7.4% respectively [2] Limitations of Brokerage Recommendations - Solely relying on ABR for investment decisions is cautioned against, as studies show these recommendations often fail to guide investors effectively [5][10] - Brokerage analysts tend to exhibit a strong positive bias due to vested interests, leading to a disproportionate number of Strong Buy recommendations compared to Strong Sell [6][10] Zacks Rank vs. ABR - Zacks Rank is a more reliable indicator of near-term stock performance, based on earnings estimate revisions, and is distinct from ABR [8][9] - The Zacks Rank is timely and reflects current business trends, while ABR may not be up-to-date [12] Earnings Estimates for Eli Lilly - The Zacks Consensus Estimate for Eli Lilly has declined by 0.5% to $21.95 over the past month, indicating growing pessimism among analysts [13] - This decline in earnings estimates has resulted in a Zacks Rank of 4 (Sell) for Eli Lilly, suggesting caution despite the Buy-equivalent ABR [14]

Core Insights - The healthcare sector is highlighted as having significant growth opportunities, particularly in the weight loss drug market and gene editing technologies [2][4]. Group 1: Weight Loss Drug Market - Eli Lilly is positioned to potentially lead the GLP-1 agonist market, currently holding approximately 35% market share, while Novo Nordisk leads with 65% [4]. - The GLP-1 market is projected to grow to a $150 billion opportunity over the next decade, representing a tenfold increase from last year's sales [4]. - Eli Lilly is developing two promising drugs: Orforglipron, an oral GLP-1 pill, and Retatrutide, which targets multiple hormones and is in phase 3 studies [5][6]. - Analysts anticipate Eli Lilly will achieve 32% annualized earnings growth over the long term, despite a high price-to-earnings (P/E) ratio of nearly 65 [7][8]. Group 2: Gene Editing Technology - CRISPR Therapeutics is advancing its commercialization efforts for Casgevy, a therapy for sickle cell disease and beta-thalassemia, which is the first CRISPR-based treatment to receive FDA approval [10]. - The company has five additional therapies in clinical trials, indicating potential for significant growth if successful [11]. - Analysts project CRISPR Therapeutics will achieve $173 million in revenue next year, with an enterprise value of $2.2 billion, suggesting a reasonable price for the stock given its potential [12].

Market Dynamics & Competitive Landscape - CVS, through its PBM (Pharmacy Benefit Manager), is preferring Wegovy over Zepbound (Lilly) due to interchangeability and leveraging its coverage of millions of lives to negotiate better economic deals [1][3] - Lilly downplays the impact, stating only about 200,000 patients will be affected [5] - The shift is happening because drugs like Wegovy and Zepbound cost about $1,000 per month [3] PBM Strategy & Negotiation - PBMs negotiate drug prices in bulk, covering potentially tens of millions of lives, to bring prices down [4][5] - The prices are confidential, but some discount is surely involved [4] - Pharmacy benefits managers negotiate prices in bulk for millions of people [4] Patient Impact & Access - Patients have been scrambling to refill prescriptions, potentially seeking 90-day supplies, due to the change [6] - Patients are trying to determine if they are still covered, can get the drug at a discounted price, or qualify for a medical exemption [6]

Summary of Conference Call on Weight Loss Target Technologies and Future Prospects Industry Overview - The conference focuses on the weight loss pharmaceutical industry, particularly the development of GLP-1 receptor agonists and multi-target weight loss drugs [1][2][3]. Key Points and Arguments 1. **Potential of Oral Small Molecule GLP-1 Receptor Agonists** - Eli Lilly's oral small molecule GLP-1 receptor agonists show promising results in clinical trials with significant glucose-lowering and weight loss effects, averaging a weight reduction of 7.3 kg [5]. 2. **Multi-Target Weight Loss Drugs** - The industry is shifting towards multi-target drugs, particularly GIP/GLP-1 dual agonists, to enhance efficacy and reduce side effects. Companies like Novo Nordisk and AstraZeneca are actively researching Amylin-related compounds [1][3][6]. 3. **Patient Experience Improvement** - Reducing injection frequency significantly enhances patient experience and treatment adherence. Long-acting formulations are becoming a key focus in development [7]. 4. **Safety and Efficacy of Novo Nordisk's NN1,213** - Novo Nordisk's NN1,213 shows reduced gastrointestinal side effects and demonstrated a 22.7% average weight loss in the Redefine 1 trial, with 40% of participants losing over 25% of their body weight [8]. 5. **Eli Lilly's GLP-1 Modifications** - Eli Lilly's C20 fatty acid-modified GLP-1 receptor agonists exhibit lower gastrointestinal side effects, with diarrhea, nausea, and vomiting rates at 10%, 8%, and 4% respectively, significantly lower than Novo Nordisk's products [9]. 6. **Myostatin and Semaglutide Combination** - The Believe trial indicates that combining Myostatin with Semaglutide can significantly reduce body fat and increase lean mass, with 70% of patients achieving over 20% weight loss [10][11][13]. 7. **Bimagrumab's Efficacy** - Bimagrumab shows significant effects in weight loss and visceral fat reduction, with a maximum dose reducing waist circumference by 21.7 cm and achieving a 45.1% reduction in visceral fat [12][14]. 8. **Amylin's Role in Weight Loss** - Amylin enhances sensitivity to leptin and reduces glucagon secretion, showing potential when combined with GLP-1 for synergistic effects. Companies like Novo Nordisk and AstraZeneca are heavily investing in Amylin research [6]. 9. **FDA's Stance on New Weight Loss Drugs** - The FDA is focusing on safety over weight loss magnitude, welcoming new drugs that can benefit populations not served by existing medications [18]. 10. **Challenges with Bimagrumab** - Bimagrumab faces challenges such as high dosing requirements and gastrointestinal side effects, necessitating the development of new molecular forms to optimize delivery [17]. Other Important Insights - The industry is moving towards differentiated molecular forms to enhance the appeal of new weight loss drugs, as traditional molecules are losing attractiveness [17]. - Current oral peptide technologies are not yet effective, with significant challenges in overcoming digestive enzymes and maintaining intestinal permeability [19]. - Novo Nordisk aims to solidify its position in the weight loss market by exploring multi-target GLP-1 receptor agonists and extending the lifespan of existing products [20].