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Investment Rating - The report assigns an "Overweight" rating for the industry [1] Core Insights - The demand for antithrombotic drugs is expanding, driven by the increasing prevalence of thrombotic diseases, particularly due to aging populations and rising cardiovascular disease rates. The global market for antithrombotic drugs reached $52.9 billion in 2023 and is expected to exceed $110 billion by 2033, with a compound annual growth rate (CAGR) of 7.7% from 2023 to 2033 [10][19] - The next generation of anticoagulants is on the horizon, with a focus on drugs targeting Factor XI (FXI) to provide effective anticoagulation with lower bleeding risks. Multiple FXI inhibitors are currently in clinical development, indicating a significant shift in the anticoagulation landscape [3][25] - The report highlights the competitive landscape for FXI inhibitors, which include small molecules, monoclonal antibodies, and siRNA therapies, all aiming to balance efficacy and safety in anticoagulation treatment [30][36] Summary by Sections 1. Expansion of Antithrombotic Drug Market - Thrombotic diseases are a leading cause of death globally, with an estimated 26.7 million cases in 2024, projected to rise to 29.1 million by 2034. Risk factors include aging, obesity, and metabolic disorders [9][10] - The global antithrombotic drug market is projected to grow from $52.9 billion in 2023 to $110.6 billion by 2033, with a CAGR of 7.7% [10][19] 2. Upgrade Window for Anticoagulants - The anticoagulant market is expected to grow from $28 billion in 2020 to $33 billion in 2024, with a CAGR of 4.2%. The Chinese market is also rapidly developing, projected to reach $9 billion by 2024 [15][19] 3. FXI Opens a New Era in Anticoagulation - FXI inhibitors are seen as ideal targets for new anticoagulants due to their ability to reduce thrombotic events without significantly increasing bleeding risks. Current research shows that individuals with low FXI activity have a significantly reduced risk of thrombotic events [25][27] - Multiple FXI inhibitors are in advanced clinical stages, including small molecules like Asundexian and monoclonal antibodies like Abelacimab, indicating a robust pipeline for future anticoagulant therapies [30][32]

Core Insights - CRISPR Therapeutics has achieved significant milestones, including the approval of Casgevy, the first gene-editing therapy using the CRISPR system for rare blood diseases [1] - Despite past achievements, the company has underperformed in the market, but upcoming catalysts in its pipeline have generated investor interest [2] - The company's gene-editing approach has the potential to transform treatment standards in areas with high unmet medical needs, with several promising medicines expected to show progress in the next 12 to 18 months [3] Pipeline Developments - Zugo-cel is a potential treatment for various cancers and autoimmune diseases, designed to overcome limitations of traditional CAR-T therapies by using healthy donor cells instead of patients' own cells [4][5] - Zugo-cel has received the Regenerative Medicine Advanced Therapy designation from the FDA, which aims to expedite the development of treatments with promising early clinical evidence [6] - Other pipeline candidates include CTX310, aimed at lowering bad cholesterol, and SRSD107, a next-generation anticoagulant [6]

Core Viewpoint - Vertex Pharmaceuticals' stock has increased following its fourth-quarter results, but long-term investment potential lies with its partner CRISPR Therapeutics, which developed the gene-editing therapy Casgevy [1][2]. Group 1: Vertex Pharmaceuticals - Vertex reported higher sales projections for Casgevy, a gene-editing therapy for sickle cell disease and beta thalassemia, contributing to its profitability and revenue from cystic fibrosis treatments [2]. - The company's share price experienced a short-term spike but moderated afterward, losing most of its gains [2]. Group 2: CRISPR Therapeutics - CRISPR Therapeutics, based in Switzerland, is the developer of Casgevy, the first CRISPR-based gene therapy approved by the FDA, and stands to benefit from increased sales of this therapy [3]. - The company has a strong position in the market, as evidenced by its significant holding in Cathie Wood's Ark Innovation ETF, indicating investor confidence in its potential [4]. - CRISPR has five additional gene therapy candidates in clinical trials, which target larger patient populations than Casgevy, enhancing its long-term growth prospects [4]. - Notable candidates include CTX310, which has shown to reduce triglycerides and LDL cholesterol by over 80%, and CTX320 for atherosclerotic cardiovascular disease [5]. - The company is also developing SRSD107, a long-acting gene therapy for thrombosis, and CTX211, which aims to restore insulin production in type 1 diabetes patients [6]. - Despite not being profitable and experiencing a 64% decline in share price over the past five years, CRISPR has over $1.9 billion in cash, positioning it well for future development if Casgevy sales increase as anticipated [7].

Group 1 - The global anticoagulant market exceeds $20 billion, with existing anticoagulants posing additional bleeding risks while preventing thrombosis. There is room for improvement in both efficacy and safety of these drugs [1] - FXI/FXIa inhibitors are expected to become safer alternatives to current anticoagulants, as they specifically target the intrinsic coagulation pathway, potentially reducing bleeding risks while maintaining anticoagulant efficacy [1] - No FXI/FXIa inhibitors have been approved yet, but several candidates, including Novartis' abelacimab, Bayer's asundexian, and BMS/Johnson & Johnson's milvexian, are in registration clinical trials [1] Group 2 - Bayer's asundexian has shown superior efficacy in phase 3 clinical trials for secondary stroke prevention, marking it as the first FXI/FXIa inhibitor to meet key clinical endpoints [1] - FXI/FXIa inhibitors demonstrate significant safety advantages over DOACs, particularly in patients at high risk of bleeding, and are expected to challenge standard treatments in various indications [1] - FXI small nucleic acid drugs, still in early development, show promising early pharmacokinetic and pharmacodynamic data, with potential for improved patient compliance due to less frequent dosing [2]

Group 1 - The global anticoagulant market exceeds $20 billion, with existing anticoagulants posing additional bleeding risks while preventing thrombosis. There is room for improvement in both efficacy and safety of these drugs [1] - FXI/FXIa inhibitors are expected to become safer alternatives to current anticoagulants, as they specifically target the intrinsic coagulation pathway, potentially reducing bleeding risks while maintaining anticoagulation efficacy [1] - No FXI/FXIa inhibitors have been approved yet, but various drug forms, including monoclonal antibodies and small molecules, are in clinical stages, with several candidates like Novartis' abelacimab and Bayer's asundexian undergoing registration trials [1] Group 2 - Bayer's asundexian has achieved superior efficacy in phase 3 clinical trials for secondary stroke prevention, marking it as the first FXI/FXIa inhibitor to meet key clinical endpoints [2] - FXI/FXIa inhibitors demonstrate significant safety advantages over DOACs, particularly in patients with high bleeding risks, suggesting a competitive edge in these populations [2] - FXI small nucleic acid drugs, still in early development, show promising early pharmacokinetic and pharmacodynamic data, indicating effective FXI activity suppression and potential for improved patient compliance with a quarterly injection schedule [3]

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]

Core Viewpoint - Healthcare stocks have underperformed compared to broader equities this year, but there are still attractive investment opportunities in the sector for long-term investors [1] Group 1: CRISPR Therapeutics - CRISPR Therapeutics is a gene-editing company with potential catalysts for stock price growth, particularly with its therapy Casgevy for sickle cell disease and beta-thalassemia [4] - The company has been enhancing third-party coverage and establishing treatment centers for Casgevy, which is expected to see significant growth next year [5] - CRISPR is also developing SRSD107, a potential anticoagulant with promising phase 1 results, and CTX112, which targets various cancers and autoimmune disorders, both of which could contribute to stock price increases [6][8] Group 2: Vertex Pharmaceuticals - Vertex Pharmaceuticals has faced challenges this year, primarily due to its reliance on its cystic fibrosis (CF) treatments, but these continue to generate steady revenue [10] - In Q3, Vertex reported an 11% year-over-year revenue increase to $3.08 billion and a 4.7% increase in net earnings per share to $4.20, indicating strong performance in its core area [11] - The company is advancing new therapies, including zimislecel for Type 1 diabetes and candidates targeting kidney diseases, with regulatory submissions planned for next year [13][14]

Core Viewpoint - Sirius Therapeutics has submitted its listing application to the Hong Kong Stock Exchange, with a valuation of approximately $253 million after its Series B funding round in April 2025, backed by prominent investors [1][2]. Group 1: Company Overview - Sirius Therapeutics was established in 2021 and focuses on developing siRNA therapies [1]. - The company is co-founded by top healthcare investment firms OrbiMed Entities and Creacion Ventures, holding over 40% of shares, with Tencent's investment arm holding 8.14% and Hancan Capital holding over 13% [1]. - The company reported a net loss of 309 million yuan and 342 million yuan for 2023 and 2024, respectively, totaling 651 million yuan in losses [3]. Group 2: Financial Performance - In the first half of 2025, Sirius Therapeutics achieved a net profit of 34.46 million yuan, marking its first profitable period, primarily driven by non-recurring income [3][4]. - The company generated 144 million yuan in other income, a significant increase from 4.51 million yuan in the same period last year, largely due to a strategic partnership with CRISPR Therapeutics [3][4]. Group 3: Product Pipeline and Challenges - The core product, SRSD107, is in Phase II clinical trials for venous thromboembolism, while two key products, SRSD216 and SRSD384, are also in various stages of development [5][6]. - The company faces significant competition in the FXI/FXIa inhibitor space, with several competitors already in Phase III trials, including drugs from Novartis, Bayer, and Johnson & Johnson [7][8]. - Sirius Therapeutics has 65 patents and applications, but only one has been granted, with 32 critical patents pending, posing potential risks in a competitive biopharmaceutical landscape [9].