Group 1 - The core viewpoint of the article is that Hotgen Biotech has received authorization for a patent related to a small nucleic acid drug aimed at treating Alzheimer's disease [1] Group 2 - The patent is for "siRNA and its conjugates that inhibit APP gene expression" [1] - The patent is held by Beijing Yaojing Gene Technology Co., Ltd., a subsidiary of Hotgen Biotech [1]

Financial Data and Key Metrics Changes - The net loss attributable to common stockholders for Q2 2025 was approximately $24.5 million, compared to approximately $9.7 million for the same period in 2024, indicating a significant increase in losses [33] - Research and development expenses totaled approximately $5.8 million for Q2 2025, down from approximately $7.1 million in Q2 2024 [33] - General and administrative expenses were approximately $2.3 million for Q2 2025, compared to approximately $2.8 million for the same period in 2024 [33] - The impairment of acquired in-process research and development intangible assets was $16.5 million, compared to zero during the same period in 2024 [34] - As of June 30, 2025, the company had cash and cash equivalents of approximately $33.4 million, which is expected to fund operations into 2026 [34] Business Line Data and Key Metrics Changes - The phase two MINDFUL trial for EXPAREL confirmed that Alzheimer's patients with two or more biomarkers of inflammation are optimal candidates, with an estimated 40% to 60% of all Alzheimer's cases fitting this profile [7][8] - In the key subgroup of patients with high inflammation, the trial observed an effect size of 0.27 on the primary endpoint EMAC and 0.23 on a key secondary behavioral endpoint, the neuropsychiatric inventory [15][16] - The company has decided not to pursue treatment-resistant depression at this time and is reevaluating opportunities for EXPAREL beyond Alzheimer's disease [10][11] Market Data and Key Metrics Changes - The company anticipates filing for approval of Cordstrom in both the UK and US by mid-2026, with expectations that it will qualify for a Priority Review Voucher if approved in the US [12] - The company is exploring shorter pathways to market for EXPAREL, including opportunities in rare diseases to maximize impact and accelerate patient access [9] Company Strategy and Development Direction - The company is focused on securing strategic partnerships to advance the EXPAREL program, which requires substantial investment in manufacturing and clinical trials [8][9] - The company aims to prepare for an end of phase two meeting with the FDA to align on the design of the phase three trial for EXPAREL [21] - The company is committed to exploring strategic partnerships to fuel growth and complete trials, while also ensuring the development of Cordstrom and INKmune [36] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of EXPAREL as a first-in-class drug for Alzheimer's disease, emphasizing its unique approach to addressing neuroinflammation [7][8] - The management highlighted the importance of the recent phase two trial results and the potential for strategic partnerships to support the program's advancement [22] - Management acknowledged the challenges of the current operating environment but remains optimistic about the company's robust pipeline and potential value creation [36] Other Important Information - The company plans to publish the trial results in a peer-reviewed journal and prepare a briefing book for the FDA meeting, expected to occur before the end of the year [35] - The company is actively exploring additional indications for Cordstrom beyond recessive dystrophic epidermolysis bullosa [12][26] Q&A Session Summary Question: Confirmation of end of Phase two meeting date with FDA - The specific meeting date has not been set yet, and the briefing book is being prepared [41] Question: Atmosphere at AAIC and feedback from thought leaders - Feedback was positive, with strong interest in the neuropsychiatric inventory and the absence of amyloid-related imaging abnormalities [42][44] Question: Strategic partnerships for EXPAREL - A partnership is not expected until after the end of phase two meeting with the FDA, as partners will want to see the publication and FDA feedback first [46][48] Question: Insights from ongoing statistical analysis for Cordstrom - The statistical analysis plan is expected to yield improved data for submission, and the open-label trial is planned for early 2027 [70][72]

Core Viewpoint - The recent study from Harvard Medical School suggests that lithium deficiency in the brain is linked to cognitive decline and the onset of Alzheimer's disease, indicating that lithium supplementation, specifically lithium orotate, may reverse memory loss and restore brain health [2][6][9]. Group 1: Alzheimer's Disease Overview - Alzheimer's disease (AD) accounts for 60%-80% of dementia cases, affecting approximately 10% of individuals over 65 years old [2]. - Current FDA-approved antibody therapies for AD have limited effectiveness and potential severe side effects, highlighting the need for alternative treatments [2]. Group 2: Lithium's Role in Cognitive Health - Historical context shows lithium was once promoted as a mood enhancer and later recognized as a standard treatment for bipolar disorder, with epidemiological studies suggesting lower dementia rates in areas with trace lithium in drinking water [5]. - The recent study confirms that lithium is naturally present in the brain and plays a crucial physiological role, with lower lithium levels found in areas affected by Alzheimer's compared to unaffected regions [6]. Group 3: Research Findings - The study found that lithium deficiency leads to increased formation of amyloid plaques in mouse models, creating a vicious cycle where lower lithium levels result in more plaque formation, further exacerbating cognitive decline [6][7]. - Lithium orotate was shown to be more effective than lithium carbonate in reversing Alzheimer's-related brain damage and memory loss in mice, potentially explaining inconsistent results in previous clinical trials [6][9]. Group 4: Implications and Future Research - The study did not find toxic effects associated with lithium supplementation, which could simplify future clinical trials for Alzheimer's treatment [9]. - The potential benefits of lithium may extend beyond Alzheimer's, as higher lithium levels were associated with better performance in memory tests among individuals without cognitive impairment [9].

Investment Rating - The report maintains an "Outperform" rating for the pharmaceutical and biotechnology sector [5][4]. Core Insights - The pharmaceutical sector has shown stronger performance compared to the overall market, with a 2.95% increase in the biopharmaceutical sector while the total A-share market declined by 1.01% [28][4]. - The report highlights significant advancements in Alzheimer's disease treatments presented at the 2025 AAIC conference, with multiple drugs updating their clinical research data [11][5]. - Roche's Trontinemab, a new generation Aβ antibody, demonstrated a 91% clearance rate of Aβ plaques in high-dose groups during Phase 1b/2a trials, indicating promising safety and efficacy [2][12]. Market Performance - The overall A-share market decreased by 1.01%, while the biopharmaceutical sector increased by 2.95%, with chemical pharmaceuticals leading with a 5.01% rise [28][4]. - The current price-to-earnings (P/E) ratio for the pharmaceutical sector is 39.10x, which is at the 80.69th percentile of its historical valuation over the past five years [33][4]. Key Companies and Investment Ratings - Mindray Medical (300760.SZ): Outperform, market cap 275.5 billion, projected net profit for 2024A is 11.67 billion [4]. - WuXi AppTec (603259.SH): Outperform, market cap 267 billion, projected net profit for 2024A is 9.35 billion [4]. - New Industries (300832.SZ): Outperform, market cap 42.6 billion, projected net profit for 2024A is 1.83 billion [4]. - Huatai Medical (688617.SH): Outperform, market cap 39.4 billion, projected net profit for 2024A is 670 million [4]. - Aier Eye Hospital (not listed): Outperform, focusing on rapid expansion in the ophthalmology service sector [37]. Clinical Research Developments - Trontinemab's Phase 1b/2a study showed significant reductions in Aβ plaque levels, with the 3.6 mg/kg dose group achieving a mean reduction from 119 CL to 21 CL after 12 weeks [14][12]. - The report emphasizes the strategic focus of overseas pharmaceutical companies on CNS (central nervous system) drug development, particularly in Alzheimer's treatments [2][25]. Recommendations - The report suggests monitoring the domestic and international AD detection and treatment drug-related industry chain, highlighting the potential for growth in this area [2][25].

Investment Rating - The report maintains an "Outperform" rating for the pharmaceutical and biotechnology sector [5][4]. Core Insights - The pharmaceutical sector has shown stronger performance compared to the overall market, with a 2.95% increase in the biopharmaceutical sector while the total A-share market declined by 1.01% [28]. - The report highlights significant advancements in Alzheimer's disease treatments presented at the 2025 AAIC conference, with multiple drugs updating their clinical research data [11][25]. - Roche's Trontinemab, a new generation Aβ antibody, demonstrated a 91% clearance rate of Aβ plaques in high-dose groups during Phase 1b/2a trials, indicating promising efficacy and safety [2][12]. Market Performance - The overall A-share market decreased by 1.01%, while the biopharmaceutical sector increased by 2.95%, with chemical pharmaceuticals leading with a 5.01% rise [28]. - The current price-to-earnings (P/E) ratio for the pharmaceutical sector is 39.10x, which is at the 80.69th percentile of its historical valuation over the past five years [28][33]. Key Companies and Investment Ratings - Mindray Medical (300760.SZ): Outperform, market cap 275.5 billion, projected net profit for 2024A is 11.67 billion [4]. - WuXi AppTec (603259.SH): Outperform, market cap 267 billion, projected net profit for 2024A is 9.35 billion [4]. - New Industries (300832.SZ): Outperform, market cap 42.6 billion, projected net profit for 2024A is 1.83 billion [4]. - Huatai Medical (688617.SH): Outperform, market cap 39.4 billion, projected net profit for 2024A is 670 million [4]. - Aier Eye Hospital (not listed in the table): Outperform, focusing on rapid expansion in the ophthalmology service sector [37]. Recommended Stocks - Mindray Medical: Strong R&D and sales capabilities, benefiting from domestic medical infrastructure and product upgrades [37]. - WuXi AppTec: Comprehensive service capabilities in new drug R&D, poised to benefit from the global outsourcing market [37]. - Aier Eye Hospital: Leading position in the domestic ophthalmology service sector, with a rapid expansion strategy [37].

Investment Rating - The report maintains an "Outperform" rating for the pharmaceutical and biotechnology sector [5][4]. Core Insights - The pharmaceutical sector has shown stronger performance compared to the overall market, with a 2.95% increase in the biopharmaceutical sector while the total A-share market declined by 1.01% [28]. - The report highlights significant advancements in Alzheimer's disease treatments presented at the 2025 AAIC conference, including promising data from various clinical trials [11][25]. - The current price-to-earnings (P/E) ratio for the pharmaceutical sector is 39.10x, which is at the 80.69th percentile of its historical valuation over the past five years [33]. Summary by Sections Market Performance - The overall A-share market decreased by 1.01%, with the Shanghai Composite Index down 1.75% and the ChiNext Index down 0.74%. In contrast, the biopharmaceutical sector increased by 2.95% [28]. - Within the biopharmaceutical sector, chemical pharmaceuticals rose by 5.01%, while medical devices saw a slight decline of 0.07% [28]. Clinical Research Updates - Roche's Trontinemab, a new generation Aβ antibody, demonstrated a 91% clearance rate of Aβ plaques in high-dose groups during Phase 1b/2a trials, with a low incidence of ARIA-E side effects [2][17]. - The report emphasizes the strategic focus of international pharmaceutical companies on Alzheimer's treatments, with FDA approvals for Biogen/Easai's Lecanemab and Lilly's Donanemab [25]. Company Earnings Forecasts - Major companies in the sector, such as Mindray Medical and WuXi AppTec, are projected to maintain strong earnings growth, with P/E ratios expected to decrease over the next few years [4]. - Mindray Medical is highlighted for its robust international expansion and product upgrades, while WuXi AppTec is noted for its comprehensive drug development services [37][38]. Recommended Stocks - The report recommends several companies, including Mindray Medical, WuXi AppTec, and Aier Eye Hospital, citing their strong market positions and growth potential in the pharmaceutical and medical services sectors [37][38].

Core Insights - Early use of the drug Donanemab significantly benefits Alzheimer's patients, reducing the risk of disease progression to the next stage by 27% compared to those who start treatment later [1] Group 1: Drug Efficacy - Over 75% of early users of Donanemab achieved amyloid clearance within 76 weeks of treatment [2] - The rate of amyloid plaque re-deposition in patients who completed treatment was approximately 2.4 CL/year over a maximum observation period of 2.5 years [2] - Long-term follow-up showed no new safety signals during the extended phase of the study [2] Group 2: Safety Concerns - Previous treatments targeting amyloid have shown imaging-related abnormalities (ARIA), including edema/exudate (ARIA-E) and bleeding/hemosiderin deposition, which may lead to severe symptoms [2] - Brain swelling and bleeding related to amyloid-clearing drugs primarily occur within the first six months of treatment [2] Group 3: Market Context - Donanemab was officially introduced for clinical treatment in China at the end of March this year, with ongoing validation of its long-term efficacy in the Chinese patient population [2] - Another Alzheimer's drug, Lecanemab, has been in clinical use in China for over a year, showing a 34% slower cognitive decline compared to untreated patients after four years [3] - China has approximately 9.83 million Alzheimer's patients, with an estimated 20% being in the early stages of the disease, potentially benefiting from innovative treatments [3]

Core Insights - Eli Lilly announced long-term extension results from its TRAILBLAZER-ALZ2 Phase 3 clinical study, showing significant disease progression slowdown in participants treated with donanemab compared to an untreated cohort from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database [1] - The benefits of donanemab treatment continued to enhance over a three-year period, indicating sustained efficacy [1] - Participants who started treatment later still experienced benefits, but those who received early treatment had a significantly lower risk of progressing to the next stage of the disease compared to the delayed treatment group [1] - These findings were presented at the 2025 Alzheimer's Association International Conference (AAIC) held in Toronto [1]

Core Viewpoint - 康哲药业's new drug ZUNVEYL has received acceptance for its New Drug Application (NDA) from the National Medical Products Administration (NMPA) in China, aimed at treating mild to moderate Alzheimer's disease symptoms [1] Group 1: Product Details - ZUNVEYL is a new generation acetylcholinesterase inhibitor (AChEI) that improves cognitive and memory functions in Alzheimer's patients by increasing central acetylcholine levels [2] - The drug is a prodrug of galantamine, designed to reduce gastrointestinal side effects and improve patient tolerance, with recorded gastrointestinal adverse events below 2% [2] - ZUNVEYL is the second oral therapy for Alzheimer's approved by the FDA in the last decade, potentially enhancing medication adherence among patients [2] Group 2: Market Context - Alzheimer's disease is a chronic neurodegenerative condition, with Alzheimer's-type dementia accounting for 50% to 70% of all dementia cases, affecting approximately 9.83 million patients in China [3] - The increasing aging population is expected to raise the number of Alzheimer's patients, intensifying the disease burden [3] - Current Alzheimer's medications primarily focus on improving cognitive symptoms, with a significant demand for safer treatment options due to high side effect rates of existing drugs [3] Group 3: Strategic Partnerships - 康哲药业 has signed a licensing and collaboration agreement with Alpha Cognition Inc. for ZUNVEYL, granting exclusive rights for development and commercialization in Asia (excluding Japan and the Middle East), Australia, and New Zealand [4] - The agreement is set for an initial term of twenty years, with automatic five-year extensions unless terminated by either party [4] - ZUNVEYL is expected to diversify 康哲药业's innovative drug portfolio and enhance its competitive strength in the market, potentially benefiting the company's performance upon approval [4]

自願性及業務進展公告 就治療輕度至中度阿爾茨海默型癡呆症狀的 改良型新藥ZUNVEYL中國上市許可申請已獲受理 China Medical System Holdings Limited（「本公司」，連同其附屬公司統稱為「本集團」） 欣然宣佈，改良型新藥ZUNVEYL（擬定通用名：葡萄糖酸苯加蘭他敏腸溶片） （「ZUNVEYL」或「產品」）新藥上市許可申請（NDA）已於二零二五年七月二十八 日獲得中國國家藥品監督管理局（NMPA）受理。產品擬用於治療成人輕度至中度阿爾 茨海默型癡呆症狀。 香港交易及結算所有限公司及香港聯合交易所有限公司對本公告的內容概不負責，對其 準確性或完整性亦不發表任何聲明，並表明概不就因本公告全部或任何部分內容而產生 或因倚賴該等內容而引致的任何損失承擔任何責任。 本公告乃由本公司自願刊發，旨在向潛在投資者及本公司股東通知本集團最新業務進 展，建議股東和投資者在進行本公司股票及其他證券的交易時謹慎操作。 ZUNVEYL於二零二四年七月獲得美國食品和藥物管理局（FDA）批准上市用於治療成 人輕度至中度阿爾茨海默型癡呆症狀，屬於新一代乙酰膽鹼酯酶抑制劑（AChEI），通 過抑制乙酰膽鹼酯酶 ...