从靶点到管线，FXI 引领抗凝产业新变革 [Table_Industry] 医药 FXI/FXIa 抑制剂行业研究报告 | [Table_Invest] | | | --- | --- | | 评级： | 增持 | | | | | [姓名table_Authors] | 电话 | 邮箱 | 登记编号 | | --- | --- | --- | --- | | 彭娉(分析师) | 021-23185619 | pengping@gtht.com | S0880525040080 | | 余文心(分析师) | 021-38676666 | yuwenxin@gtht.com | S0880525040111 | 本报告导读： 靶向 FXI 的药物可在不显著增加出血风险的前提下防治血栓，有望为患者提供更安 全的抗凝选择。当前该领域的研发活跃，2026 年起预计有多个药物进入关键数据读 出的阶段，静待抗凝领域新一代"大药"的诞生。 投资要点： [Table_Report] 相关报告 医药《医疗设备招采规模高基数影响部分回落， 关注手术机器人市场机遇》2026.02.09 医药《高景气延续，持续推荐创新药械产业链》 2 ...

CRISPR Therapeutics (NASDAQ: CRSP) already has notable achievements under its belt. For instance, it developed Casgevy, a medicine for a pair of rare blood diseases, which became the first gene-editing therapy to use the famous, Nobel Prize-winning CRISPR gene-editing system to earn approval. CRISPR Therapeutics has lagged the market since that breakthrough, but with some highly promising gene-editing medicines in its pipeline and potential upcoming catalysts, some investors are excited about the biotech's ...

Vertex Pharmaceuticals' (NASDAQ: VRTX) stock price is up, but its Casgevy sales partner, CRISPR Therapeutics (NASDAQ: CRSP), is the real buy for long-term investors. Shares of Vertex, a biotech based in Boston, popped last week after it reported its fourth-quarter results, which included higher 2025 sales for Casgevy, a gene-editing therapy for two genetic blood disorders: sickle cell disease and beta thalassemia. Vertex is already profitable, and makes most of its revenues by selling the only approved dru ...

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].

Core Insights - CRISPR Therapeutics reported a narrower loss of $1.17 per share for Q3 2025, compared to the Zacks Consensus Estimate of a loss of $1.32, but wider than the loss of $1.01 per share in the same quarter last year [2][8] - Total revenues for the quarter were $0.9 million, significantly missing the Zacks Consensus Estimate of $6.7 million, and up from $0.6 million in the year-ago period [2][8] Financial Performance - The company experienced a 28% year-over-year decline in R&D expenses to $58.9 million, attributed to reduced manufacturing and employee-related costs [9] - General and administrative expenses fell 3% year-over-year to $16.9 million [9] - Net collaboration expenses increased to $57.1 million from $11.2 million in the previous year, primarily due to reaching a deferral limit on costs related to the Casgevy program [9] - As of September 30, 2025, the company had cash, cash equivalents, and marketable securities totaling $1.94 billion, up from $1.72 billion as of June 30, 2025 [10] Product Development and Pipeline - CRISPR Therapeutics and Vertex Pharmaceuticals' Casgevy therapy has been approved for sickle cell disease and transfusion-dependent beta thalassemia, with Vertex expecting over $100 million in revenues for Casgevy this year [5][6] - The company completed enrollment for pediatric trials of Casgevy and plans to present initial data at the American Society of Hematology annual meeting on December 6, 2025 [11] - CRISPR is advancing two next-generation CAR-T therapy candidates, CTX112 and CTX131, with updates expected by year-end [12] - The company is also studying in-vivo candidates CTX310 and CTX320, with CTX310 showing significant reductions in ANGPTL3, LDL, and triglyceride levels [13] - A collaboration with Sirius Therapeutics is diversifying the pipeline into RNA therapeutics, with an investigational RNA therapy SRSD107 in mid-stage studies [14] Market Performance - Shares of CRISPR Therapeutics have increased by 39% year-to-date, outperforming the industry growth of 11% [3]

Core Insights - CRISPR Therapeutics has reported strong progress across its portfolio, particularly with CASGEVY® and CTX310®, indicating a robust pipeline and potential for significant revenue growth in the coming years [2][3] CASGEVY® Developments - CASGEVY® is a CRISPR/Cas9 gene-edited cell therapy for sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT), approved in multiple regions including the U.S. and Europe [3][13] - Nearly 300 patients have been referred to Authorized Treatment Centers (ATCs), with approximately 165 completing their first cell collection and 39 receiving infusions [5][3] - The company anticipates over $100 million in total CASGEVY revenue for this year, with significant growth expected in 2026 [5][3] Clinical Trials and Pipeline - Positive Phase 1 data for CTX310®, targeting ANGPTL3, was presented at the AHA Scientific Sessions, showing potential to lower triglycerides and LDL [5][3] - Enrollment in two global Phase 3 studies for pediatric development of exa-cel has been completed, with initial data to be presented at the ASH annual meeting [5][3] - Ongoing clinical trials for CTX112™, targeting CD19, are expected to provide broad updates by year-end [5][10] Financial Performance - As of September 30, 2025, the company reported approximately $1.9 billion in cash, cash equivalents, and marketable securities [5][12] - R&D expenses decreased to $58.9 million for Q3 2025 from $82.2 million in Q3 2024, indicating improved cost management [12][26] - The net loss for Q3 2025 was $106.4 million, compared to a net loss of $85.9 million in Q3 2024, reflecting ongoing investment in R&D [12][26] Innovative Technologies - The company is advancing its proprietary SyNTase™ editing platform, which aims to enable precise in vivo gene correction, with CTX460™ expected to enter clinical trials in mid-2026 [5][3] - CTX340™, targeting AGT for refractory hypertension, has shown promising preclinical results, including significant liver editing and blood pressure reduction [6][5] Strategic Collaborations - CRISPR Therapeutics has a strategic collaboration with Vertex Pharmaceuticals for the development of CASGEVY, sharing program costs and profits [14][3] - A partnership with Sirius Therapeutics is focused on developing SRSD107, a long-acting siRNA targeting Factor XI for thromboembolic disorders [19][18]