Core Insights - GSK announced positive results from two pivotal Phase 3 studies, B-Well 1 and B-Well 2, for bepirovirsen, an investigational antisense oligonucleotide for chronic hepatitis B treatment [1] Company Summary - Ionis Pharmaceuticals partnered with GSK for the development of bepirovirsen, which has shown promising safety and efficacy results in over 1,800 patients across 29 countries [1]

Core Viewpoint - Ionis Pharmaceuticals, Inc. will present a company overview at the 44th Annual J.P. Morgan Healthcare Conference on January 13, 2026, at 8:15 a.m. PT [1] Company Information - The presentation will be led by Brett P. Monia, Ph.D., the chief executive officer of Ionis Pharmaceuticals [1] - A live webcast of the presentation will be available on the Investors & Media section of the Ionis website [1] - A replay of the presentation will be accessible on the Ionis website within 48 hours after the event [1]

Core Insights - Oligonucleotide therapies are emerging as a significant breakthrough in the treatment of rare diseases, with over a dozen therapies approved globally and hundreds in clinical research, promising to benefit more patients in the future [1][14][15] Industry Developments - The global landscape has seen more than ten oligonucleotide therapies approved for rare diseases, providing new treatment options for conditions such as Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), and Hemophilia [1][14] - There are currently over a hundred oligonucleotide therapies in clinical development targeting various rare diseases, including siRNA and antisense oligonucleotide (ASO) therapies [2][14] Recent Approvals and Innovations - In August, Ionis Pharmaceuticals received FDA approval for the LICA drug Dawnzera (donidalorsen) for preventing hereditary angioedema (HAE) attacks in patients aged 12 and older, marking it as the first RNA-targeted drug for HAE [4][18] - Ionis Pharmaceuticals and Sobi announced the approval of ASO drug Tryngolza (olezarsen) in the EU for treating genetically confirmed familial chylomicronemia syndrome (FCS) [4][19] - Alnylam Pharmaceuticals' siRNA therapy Amvuttra (vutrisiran) was approved by the FDA in March for treating patients with transthyretin amyloidosis with cardiomyopathy [5][19] Clinical Trial Progress - NS Pharma reported positive results from the long-term extension study of ASO therapy brogidirsen for DMD, showing effective exon 44 skipping and stable maintenance of motor function in patients [7][21] - RIBOMIC's umedaptanib pegol showed promising results in a Phase 2 trial for achondroplasia in children, with many patients experiencing improved height growth rates [7][21] - Ionis Pharmaceuticals' ASO therapy zilganersen demonstrated significant results in stabilizing walking speed in Alexander disease patients, with plans for a new drug application to the FDA in 2026 [8][22] WuXi TIDES Platform - WuXi TIDES has established an integrated solution for oligonucleotide and peptide therapies, covering custom synthesis, conjugation, process development, and CMC, facilitating the transition of innovative projects into clinical stages [1][11][26] - The platform offers comprehensive CRDMO services from drug discovery to commercial production, supporting high-throughput synthesis and custom synthesis for various oligonucleotides [11][26][27] Future Outlook - The company aims to continue leveraging its integrated CRDMO model to empower the development of various new drugs, including oligonucleotide therapies, to bring more effective treatments to patients [12][27]

Core Viewpoint - AstraZeneca announced the approval of Ipupronit Sodium Injection (brand name Wainua) in China for the treatment of adult hereditary transthyretin amyloidosis polyneuropathy (ATTRv-PN), marking a significant milestone as it is the only gene-silencing agent approved for this condition in the country [1][6]. Group 1: Approval and Treatment Benefits - The approval is based on positive results from the NEURO-TTRansform Phase III clinical study, which demonstrated consistent and sustained clinical benefits in patients treated with Ipupronit Sodium compared to a placebo over a 66-week observation period [3][8]. - Key endpoints showed improvements in serum transthyretin (TTR) levels and neuropathy impairment scores, as well as quality of life assessments, indicating the drug's effectiveness [3][8]. Group 2: Disease Context and Treatment Mechanism - ATTRv-PN is a debilitating disease that can lead to peripheral nerve damage, with patients typically experiencing motor function impairment within five years of diagnosis and an average life expectancy of ten years without treatment [4][9]. - Ipupronit Sodium is administered monthly via an automatic injector, enhancing medication convenience and potentially improving patients' quality of life [1][6]. - The drug works by upstream inhibition of TTR production in the liver, making it a promising treatment for various types of transthyretin amyloidosis [4][9]. Group 3: Global Development and Ongoing Research - Ipupronit Sodium has also been approved in the United States and the European Union, with ongoing efforts to secure approvals in more countries [5][9]. - The drug is currently undergoing the CARDIO-TTRansform Phase III clinical study to evaluate its efficacy in treating adult transthyretin cardiac amyloidosis (ATTR-CM), which is the largest clinical study of its kind with over 1,400 participants [5][9].

依普隆特生钠为每月一次用药的基因沉默剂，通过上游抑制转甲状腺素蛋白(TTR)的生成发挥作用。作 为RNA靶向治疗药物，它可在肝脏源头减少TTR蛋白的产生，因而具有潜力用于治疗各类型的转甲状腺 素蛋白淀粉样变性。北京协和医院院长张抒扬教授表示："转甲状腺素蛋白淀粉样变性已被纳入国家第 二批罕见病目录。长期以来，我国ATTRvPN患者深受神经系统症状和生活质量显著下降的影响，而可 选择的治疗方案十分有限。依普隆特生钠的获批为患者带来了新的希望，临床证据显示其能够阻止神经 病变进展，并显著改善神经功能与生活质量。" 新京报讯(记者张秀兰)12月25日，由阿斯利康与Ionis公司联合开发的万诺维(通用名为依普隆特生钠注射 液)获国家药监局批准，用于治疗成人遗传性转甲状腺素蛋白淀粉样变性多发性神经病(ATTRv-PN)患 者。依普隆特生钠也成为中国首个且目前唯一获批用于ATTRv-PN治疗的基因沉默剂。 ATTR(转甲状腺素蛋白淀粉样变性)是由肝脏产生的、错误折叠的TTR蛋白在心脏和周围神经等组织中 积聚所引起的，会造成器官损伤和衰竭。ATTR会引起多种并发症，导致心血管、神经和肾脏疾病，患 者也被称为"淀粉人"。AT ...

Core Viewpoint - The approval of Wainua® (eplontersen) by AstraZeneca and Ionis for the treatment of ATTRv-PN in China represents a significant advancement in addressing a previously underserved medical need for patients suffering from this debilitating disease [1] Group 1: Product Approval - Wainua® is the first and currently the only gene-silencing agent approved in China for the treatment of ATTRv-PN [1] - The drug was officially approved on December 22, 2025, marking a milestone in the treatment options available for patients [1] Group 2: Disease Impact - ATTRv-PN is a debilitating disease that can lead to peripheral nerve damage, with patients typically experiencing motor function impairment within five years of diagnosis and a general mortality rate within ten years if untreated [1] - The disease has been included in China's second batch of rare disease catalog, highlighting its significance and the need for effective treatments [1] Group 3: Expert Commentary - Professor Zhang Shuyang, the chief researcher of EPIC-ATTR in China, emphasized the long-standing impact of ATTRv-PN on patients' neurological symptoms and quality of life, noting the limited treatment options available prior to the approval of Wainua® [1]

Industry Overview - The drug and biotech sector regained momentum in the latter part of 2025 after a weak first half, setting the stage for a strong year for select stocks [1] - Improved policy clarity following drug pricing agreements with the Trump administration reduced uncertainty, while a rebound in mergers and acquisitions revived investor appetite for risk [1] - Innovation accelerated across high-growth areas such as obesity, gene therapy, inflammation, and neuroscience, with the FDA approving 43 novel therapies as of December 22, 2025 [2] Company Highlights Ionis Pharmaceuticals - Ionis Pharmaceuticals' shares surged 127.6% in 2025, significantly outperforming the industry growth of 5% [5][6] - The company advanced its wholly-owned portfolio, highlighted by the FDA approval of Tryngolza for familial chylomicronemia syndrome, generating $57.4 million in sales in the first nine months of 2025 [9] - Ionis is evaluating Tryngolza in late-stage studies for severe hypertriglyceridemia, with plans to file for FDA label expansion soon [10] - The FDA approved Ionis' second drug, Dawnzera, for hereditary angioedema, with a regulatory filing in the EU expected in early 2026 [11] Structure Therapeutics - Structure Therapeutics' shares surged 127.2% in the past year, compared to the industry's 15.6% growth [13] - The stock rally was driven by positive data from the ACCESS clinical program for aleniglipron, showing up to 15.3% placebo-adjusted weight loss [15][16] - The company plans to initiate phase III development for aleniglipron in mid-2026 and is also developing other candidates for obesity treatment [18] Monopar Therapeutics - Monopar Therapeutics' shares rallied 185.9% in the past year, significantly outperforming the industry [20] - The stock price increase was fueled by positive expectations regarding its lead candidate ALXN-1840 for Wilson disease, following a licensing agreement with AstraZeneca [22] - Monopar plans to submit a regulatory filing with the FDA in early 2026 based on favorable long-term data for ALXN-1840 [26] Kodiak Sciences - Kodiak Sciences' shares rallied 181.1% in the past year, contrasting with the industry's 15.7% decline [27] - The stock's performance reflects growing investor confidence in its late-stage pipeline assets, particularly tarcocimab and KSI-501 [29] - Kodiak plans to submit a regulatory filing for tarcocimab for multiple indications, with top-line data from pivotal studies expected in 2026 [31][33]

Investment Rating - The report maintains an "Outperform" rating for the industry [1] Core Insights - The global anticoagulant market exceeds $20 billion, primarily driven by stroke prevention in atrial fibrillation patients, with other indications including VTE prevention after knee/hip replacement and prevention of ischemic complications in myocardial infarction [2][5] - FXI/FXIa inhibitors are expected to become safer anticoagulants, as they target the intrinsic pathway of coagulation, potentially reducing bleeding risks while maintaining efficacy [2][21] - Several FXI/FXIa inhibitors are in clinical stages, with promising safety profiles demonstrated in various indications, including Bayer's asundexian achieving key clinical endpoints in secondary stroke prevention [2][26] - FXI small nucleic acid drugs may offer differentiated competitive advantages, with early-stage clinical data showing effective FXI activity suppression and potential for improved patient compliance [2][26] Summary by Sections Anticoagulant Drugs: Applications and Market Size - Anticoagulants are used in various medical scenarios, with a global market size exceeding $20 billion, driven by stroke prevention in atrial fibrillation patients [5][7] - Current anticoagulants include DOACs and low molecular weight heparins, with existing drugs presenting bleeding risks alongside their efficacy [5][21] FXI Inhibitors as Next-Generation Anticoagulants - FXI inhibitors are positioned to challenge standard treatments, with clinical trials indicating superior safety profiles compared to existing DOACs [2][26] - Notably, Bayer's asundexian has shown efficacy in secondary stroke prevention, marking a significant advancement in the field [2][69] Domestic FXI Small Nucleic Acid Drug Development Progress - Domestic companies are advancing in FXI small nucleic acid drug development, with promising early clinical results indicating effective FXI suppression and potential for improved dosing schedules [2][26] Investment Recommendations - FXI/FXIa inhibitors are projected to represent an upgrade and complement to existing anticoagulants, with a potential market space exceeding $10 billion [2][26] - The report suggests focusing on companies like HengRui Medicine, which is leading in domestic FXI monoclonal antibody development [2][26]

Group 1: Market Overview - The Hong Kong stock market showed a collective rebound with the Hang Seng Index rising approximately 0.6%, the Hang Seng China Enterprises Index increasing about 1%, and the Hang Seng Tech Index up around 0.8% [2][3] - Market sentiment improved significantly compared to previous days, with total market turnover rising to approximately 210.4 billion HKD and the short-selling amount on the main board decreasing to about 15.74% of total turnover [2] - Southbound capital flows remained weak, with net inflows from northbound trading at around 1.3 billion HKD on Friday [2] Group 2: Sector Performance - Resource and cyclical stocks led the market rally, with rare earth, non-ferrous metals, and gold stocks performing well due to the implementation of export licenses and increased copper stockpiling by global commodity traders [3] - The financial sector also played a crucial role in driving the market upward, with insurance stocks, Chinese brokerage firms, and domestic banks generally showing strong performance [3] - Energy-related sectors, including electric power equipment, wind power, and nuclear power, were active, reflecting ongoing interest in energy transition and equipment investment opportunities [3] Group 3: Economic Indicators - The U.S. core PCE year-on-year growth rate fell to 2.8%, providing strong support for the Federal Reserve's potential interest rate cut [4] - Personal consumption expenditures in the U.S. showed almost no growth in September, indicating a cooling consumer market, with significant declines in spending on durable and non-durable goods [5] - The income distribution in the U.S. is becoming polarized, with lower-income households reducing spending while high-income groups maintain purchasing power due to asset appreciation [5] Group 4: Industry Insights - The small nucleic acid drug sector is emerging as a significant investment theme for 2026, characterized by rapid global market growth and advantages such as broad target coverage and high clinical trial success rates [7] - The global small nucleic acid drug market is projected to grow from 2.7 billion USD in 2019 to 5.7 billion USD in 2024, with a compound annual growth rate of 16.2% [7] - The market for siRNA drugs is expected to increase its share from 6.2% in 2019 to 44.5% in 2024, driven by advancements in delivery technologies and expanding indications [7] Group 5: Collaboration and Market Dynamics - The small nucleic acid field is becoming a hub for business development collaborations, with nearly 100 deals in the past three years and increasing transaction values [8] - Leading companies in the small nucleic acid market, such as Alnylam and Ionis, are setting the pace for global technological development, with Alnylam reporting a 149% year-on-year revenue increase in Q3 2025 [9] - Domestic pharmaceutical companies are also focusing on small nucleic acid drugs, with several candidates in clinical trials targeting conditions like high cholesterol [9] Group 6: Investment Recommendations - The report suggests that small nucleic acid drugs may become a major investment theme next year, with opportunities in both domestic and international markets [10] - Key companies to watch include overseas leaders like Alnylam, Arrowhead, and Ionis, as well as domestic firms like CSPC Pharmaceutical Group and Hengrui Medicine [10]

Core Points - Ionis Pharmaceuticals has received Breakthrough Therapy designation from the U.S. FDA for zilganersen, aimed at treating Alexander disease, a rare and often fatal neurological condition [1][2] - The company plans to submit a new drug application (NDA) in Q1 2026 [1][3] Company Overview - Ionis Pharmaceuticals is recognized for its innovative approach in developing treatments for serious diseases, including neurological conditions [3][9] - The company has a strong pipeline, including marketed medicines and investigational therapies, positioning it for revenue growth and value creation [3][9] Zilganersen Study Details - The pivotal study for zilganersen involved 54 participants aged 1.5 to 53 years across 13 sites in eight countries, primarily focusing on children due to the early onset of Alexander disease [4][5] - The study demonstrated a statistically significant improvement in gait speed, with a mean difference of 33.3% (p=0.0412) at week 61 for the 50 mg dose compared to control [2][5] Alexander Disease (AxD) Insights - Alexander disease affects approximately 1 in 1 to 3 million people globally and is characterized by progressive neurological deterioration, leading to loss of mobility and independence [7] - There are currently no approved disease-modifying treatments for Alexander disease, highlighting the significance of zilganersen's potential [7][6]