Abelacimab: A Comprehensive Monograph on a Novel Factor XI Inhibitor Poised to Redefine Anticoagulation Safety

Executive Summary

Abelacimab (DrugBank ID: DB16682; CAS: 2098724-83-3) is an investigational, fully human monoclonal antibody representing a potential first-in-class anticoagulant therapy.[1] Its development is predicated on a novel therapeutic hypothesis: achieving "hemostasis-sparing anticoagulation" by selectively targeting the intrinsic coagulation pathway.[4] This is accomplished through a unique dual-inhibition mechanism, targeting both the zymogen Factor XI (FXI) and its activated form, Factor XIa, thereby aiming to uncouple pathological thrombosis from physiological hemostasis—a critical limitation of all currently available anticoagulants.[6]

The clinical development program for abelacimab has been highlighted by the landmark Phase 2b AZALEA-TIMI 71 trial. In this study, abelacimab demonstrated an unprecedented and statistically profound reduction in bleeding events compared to the standard-of-care direct oral anticoagulant (DOAC), rivaroxaban, in patients with atrial fibrillation (AF) at moderate-to-high risk of stroke.[8] This striking safety signal, which led to the trial's early termination, has positioned abelacimab as a leading candidate in a new generation of safer antithrombotic agents.

Building on this foundation, abelacimab is being advanced through a robust and strategically designed Phase 3 program. This program targets patient populations with high unmet medical needs, including AF patients deemed unsuitable for current anticoagulants (LILAC-TIMI 76 trial) and patients with Cancer-Associated Thrombosis (CAT), a setting complicated by high bleeding risk (ASTER and MAGNOLIA trials).[11] The U.S. Food and Drug Administration (FDA) has recognized this potential by granting two separate Fast Track Designations for the CAT and AF indications.[14]

The corporate narrative surrounding abelacimab is as compelling as its clinical data. Originally developed by Novartis, the asset was spun out to Anthos Therapeutics, a company created in partnership with Blackstone Life Sciences, to accelerate its development.[6] Following the successful de-risking of the asset through the AZALEA-TIMI 71 trial, Novartis entered into an agreement in early 2025 to re-acquire Anthos Therapeutics in a multi-billion dollar deal, signaling immense confidence in its blockbuster potential.[15] Pending confirmation of efficacy in its ongoing Phase 3 trials, abelacimab is poised to challenge the current treatment paradigm, offering a potentially transformative shift in the risk-benefit calculus for millions of patients requiring anticoagulation.

Molecular Profile and Pharmacological Mechanism

Structural and Biochemical Characteristics

Abelacimab is a biotechnology-derived therapeutic, classified as a fully human monoclonal antibody (mAb) of the immunoglobulin G1 (IgG1) isotype.[1] It is produced via recombinant DNA technology in Chinese Hamster Ovary (CHO) host cells, a standard platform for manufacturing therapeutic antibodies, and subsequently purified using protein A/G chromatography.[1] Its reported molecular weight is approximately 144–147 kDa.[1]

For identification and tracking purposes, abelacimab is associated with several key identifiers. Its DrugBank Accession Number is DB16682, its Chemical Abstracts Service (CAS) Registry Number is 2098724-83-3, and its Unique Ingredient Identifier (UNII) is KX1N4TV7UY.[2] Throughout its development, it has also been referred to by various codes, most notably MAA-868 (and its variants MAA868 and MAA-868) and NVS250519.[2] While some research-grade biosimilar materials are described with different isotypes, such as IgG1 Lambda or IgG2 kappa, the clinical candidate advanced by Anthos and Novartis is a fully human IgG1 antibody.[17]

The Factor XI Pathway: A Novel Target for Safer Anticoagulation

The scientific rationale for developing abelacimab is rooted in a sophisticated understanding of the human coagulation cascade and the distinct roles of its constituent pathways. The cascade is broadly divided into two initiating arms: the extrinsic pathway and the intrinsic pathway, both of which converge on a common pathway leading to thrombin generation and fibrin clot formation. The extrinsic pathway, initiated by tissue factor at sites of vascular injury, is considered essential for physiological hemostasis—the process that stops bleeding. In contrast, the intrinsic pathway has a more nuanced role.

Factor XI, a serine protease, is a crucial component of the intrinsic pathway, where it activates Factor IX, thereby amplifying the coagulation signal.[21] Crucially, evidence from human genetics has provided a powerful natural experiment validating FXI as a therapeutic target. Individuals with a severe congenital deficiency of FXI, a condition known as Rosenthal syndrome or hemophilia C, are significantly protected from venous thromboembolism (VTE) and ischemic stroke compared to the general population.[5] Despite this thromboprotective phenotype, these individuals do not typically suffer from the severe spontaneous bleeding that characterizes deficiencies in common pathway factors or factors involved in the extrinsic pathway.[5] This observation led to the "uncoupling" hypothesis: the intrinsic pathway, and FXI in particular, appears to be more critical for the propagation and stabilization of pathological thrombi than for the initial, necessary response to vascular injury.[4]

This distinction represents the central therapeutic premise for FXI inhibition. Current anticoagulants, such as vitamin K antagonists (e.g., warfarin) and DOACs (e.g., rivaroxaban, apixaban), exert their effects by targeting components of the common pathway (e.g., Factor Xa, thrombin). While effective at preventing thrombosis, their mechanism inherently impairs physiological hemostasis, leading to an increased risk of bleeding as their primary and dose-limiting side effect.[5] The goal of targeting FXI is to develop a new class of anticoagulants that can selectively inhibit pathological clot formation while largely preserving the hemostatic functions of the extrinsic and common pathways, thereby offering a superior safety profile.[5]

Mechanism of Action: Dual Inhibition of Factor XI and Factor XIa

Abelacimab realizes the therapeutic potential of FXI inhibition through a highly specific and potent mechanism of action. It is a dual inhibitor, capable of binding with high affinity to both the inactive zymogen form of the enzyme, Factor XI, and its activated form, Factor XIa.[4]

The core of its innovative mechanism is not simple competitive inhibition but rather a process of "conformational locking." Abelacimab binds to the catalytic domain of FXI and structurally locks the protein in its inactive zymogen conformation.[4] This allosteric-like effect prevents the conformational changes necessary for its activation by either Factor XIIa (the canonical intrinsic pathway activator) or thrombin (a key feedback activator).[4] By neutralizing FXI before it can participate in the cascade and simultaneously inhibiting any FXIa that may have already formed, abelacimab effectively shuts down this amplification loop of coagulation.[22] The structural stability of this antibody-enzyme complex provides a clear biochemical basis for the observed prolonged pharmacodynamic effects. A single administration of abelacimab can produce a profound and sustained suppression of FXI activity for up to 30 days, a key attribute that enables a convenient once-monthly dosing schedule.[5]

This molecular action translates into measurable pharmacodynamic effects that confirm its anticoagulant activity. In vitro, abelacimab prolongs the activated partial thromboplastin time (aPTT), an assay sensitive to the intrinsic pathway, and reduces thrombin generation in human plasma in a concentration-dependent manner.[18] In vivo, administration of abelacimab leads to a rapid (within one hour) and near-complete reduction in the levels of free, circulating FXI, which is maintained for at least four weeks with higher doses.[5]

Characteristic	Description
Generic Name	Abelacimab
DrugBank ID	DB16682
CAS Number	2098724-83-3
Synonyms	MAA-868, MAA868, NVS250519
Drug Type	Biotech, fully human monoclonal antibody (IgG1)
Molecular Target	Coagulation Factor XI (FXI) and activated Factor XI (FXIa)
Mechanism of Action	Binds to the catalytic domain of FXI, locking it in an inactive zymogen conformation, preventing its activation and inhibiting already-formed FXIa.

Clinical Development Program: Efficacy and Safety Evaluation

The clinical development of abelacimab has been pursued through a comprehensive and strategically designed program, investigating its potential across a range of thromboembolic disorders, including atrial fibrillation, cancer-associated thrombosis, and venous thromboembolism prophylaxis.

Atrial Fibrillation: The Pursuit of Safer Stroke Prevention

The AZALEA-TIMI 71 Trial (Phase 2b): A Paradigm-Shifting Safety Signal

The AZALEA-TIMI 71 study stands as the most pivotal clinical trial for abelacimab to date, providing the foundational evidence for its superior safety profile. This Phase 2b trial was a multicenter, randomized, active-controlled study with a blinded endpoint evaluation, enrolling 1,287 patients with atrial fibrillation and a moderate-to-high risk of stroke (median CHA₂DS₂-VASc score of 5).[8] Participants were randomized in a 1:1:1 ratio to one of two doses of abelacimab (150 mg or 90 mg, administered via subcutaneous injection once monthly) or to open-label rivaroxaban (20 mg orally once daily), a widely used DOAC.[8]

In a dramatic validation of the drug's therapeutic hypothesis, the trial was terminated prematurely in September 2023 on the recommendation of the independent data monitoring committee.[9] The reason for this early stoppage was an "overwhelming reduction in bleeding" observed in both abelacimab arms compared to the rivaroxaban arm, a benefit that was substantially greater than had been anticipated.[8]

The primary endpoint of the study was the composite of major or clinically relevant nonmajor (CRNM) bleeding. The results were striking and highly statistically significant [8]:

• The 150 mg abelacimab dose demonstrated a 62-67% reduction in the primary endpoint compared to rivaroxaban (Hazard Ratio approximately 0.33 to 0.38, ).[8]
• The 90 mg abelacimab dose showed a 69-77% reduction compared to rivaroxaban (HR approximately 0.23 to 0.31, ).[8]

This profound safety benefit was consistent across all secondary bleeding endpoints. Major bleeding alone was reduced by approximately 67-74%.[10] Perhaps most impressively, gastrointestinal (GI) bleeding—a major concern and frequent cause for discontinuation of DOACs—was virtually eliminated, with a reduction of 89-93% in the abelacimab arms.[8] This is a critical point of differentiation, as GI bleeding risk is a significant clinical challenge with existing anticoagulants.[7]

It is crucial to note that AZALEA-TIMI 71 was not powered to definitively assess efficacy. While the overall rates of ischemic stroke or systemic embolism were low (around 1% per year), the event rates were numerically higher in the abelacimab arms (2.3% for the 150 mg dose, 2.4% for the 90 mg dose) compared to the rivaroxaban arm (1.2%).[8] This numerical imbalance, though not statistically significant in this safety-focused trial, highlights the central question that the Phase 3 program must address: whether the profound improvement in safety comes at a cost of antithrombotic potency compared to Factor Xa inhibitors.

Trial Name	AZALEA-TIMI 71 (Phase 2b)
Indication	Atrial Fibrillation (moderate-to-high stroke risk)
Enrollment	1,287 patients
Arms	1) Abelacimab 150 mg SC monthly 2) Abelacimab 90 mg SC monthly 3) Rivaroxaban 20 mg PO daily
Primary Endpoint	Major or Clinically Relevant Non-Major (CRNM) Bleeding
Key Outcomes (vs. Rivaroxaban)
Primary Endpoint (150 mg)	HR 0.33 (95% CI 0.19–0.55),
Primary Endpoint (90 mg)	HR 0.23 (95% CI 0.13–0.42),
Major Bleeding (150 mg)	2.3% vs. 7.2%
GI Bleeding (150 mg)	0.5% vs. 4.2%
Ischemic Stroke (150 mg)	2.3% vs. 1.2% (Not statistically powered)

The LILAC-TIMI 76 Trial (Phase 3): Targeting the Unmet Need

The design of the pivotal LILAC-TIMI 76 trial reflects a highly astute clinical development strategy. Recognizing the potential risk highlighted by the numerical stroke imbalance in AZALEA-TIMI 71, the developers sidestepped a direct, high-risk, non-inferiority efficacy comparison against a DOAC. Instead, they targeted a distinct and underserved "white space" in the market. LILAC-TIMI 76 is a large-scale (approximately 1,900 patients), randomized, double-blind, placebo-controlled, parallel-group Phase 3 study.[11]

Its target population consists of high-risk AF patients who are deemed unsuitable for any currently available oral anticoagulant therapy, either due to an unacceptably high risk of bleeding or other contraindications.[11] This is a population with a significant unmet medical need, as they are often left unprotected from the devastating risk of stroke. In this context, the comparator is placebo, not a potent DOAC, which sets a more achievable bar for demonstrating a positive benefit-risk profile. The intervention being tested is abelacimab 150 mg administered via subcutaneous monthly injection versus a matching placebo.[24] The trial has co-primary endpoints to rigorously evaluate both efficacy (time to the first event of ischemic stroke or systemic embolism) and safety (time to the first occurrence of major bleeding).[11] The trial is currently recruiting patients, with an estimated primary completion date in August 2026.[11]

Cancer-Associated Thrombosis (CAT): A Tailored, Dual-Pronged Strategy

CAT is a leading cause of morbidity and mortality in cancer patients, and its management is frequently complicated by an elevated risk of bleeding from either the underlying malignancy or its treatment.[37] This clinical challenge makes the patient population particularly well-suited for a hemostasis-sparing anticoagulant. Recognizing this, the FDA granted abelacimab Fast Track Designation for the treatment of CAT in July 2022.[38]

The Phase 3 CAT program for abelacimab demonstrates a sophisticated understanding of the clinical heterogeneity of this condition. It comprises two large, complementary trials designed to generate tailored evidence for distinct patient subgroups and standards of care.

The ASTER Trial (Phase 3, NCT05171049)

The ASTER study is a multicenter, randomized, open-label trial with blinded endpoint evaluation that compares abelacimab to apixaban, a leading DOAC.[24] It is designed to enroll patients with CAT for whom a DOAC is the recommended standard of care.[29] The treatment regimen consists of abelacimab (150 mg IV on day 1, followed by monthly SC injections) versus standard-dose apixaban for a duration of six months.[24] The primary endpoints are the recurrence of VTE and the incidence of bleeding events.[12] The trial is expected to be completed in 2027.[12]

The MAGNOLIA Trial (Phase 3, NCT05171075)

The MAGNOLIA study complements ASTER by focusing on a higher-risk subset of the CAT population. This multicenter, randomized, open-label, blinded-endpoint trial enrolls patients with non-resectable gastrointestinal or genitourinary (GI/GU) cancers, where the risk of bleeding is particularly high.[13] In this population, low-molecular-weight heparin (LMWH) is often the preferred standard of care over DOACs. Accordingly, MAGNOLIA compares abelacimab (using the same dosing regimen as ASTER) to daily injections of dalteparin (an LMWH) for six months.[13] The primary endpoints are also VTE recurrence and bleeding events.[13] This dual-trial strategy allows for the generation of direct comparative data against both major standards of care in CAT, positioning abelacimab to potentially capture a broad market share across different clinical scenarios.

Venous Thboembolism (VTE) Prophylaxis: Initial Proof-of-Concept

The foundation for abelacimab's broader clinical development was laid by a successful Phase 2 proof-of-concept study in VTE prophylaxis. The trial was conducted in patients undergoing total knee arthroplasty (TKA), a standard high-risk surgical model used to evaluate the efficacy of new anticoagulants.[29] The study demonstrated that a single post-operative intravenous dose of abelacimab (at both 75 mg and 150 mg) was statistically superior to the standard-of-care, enoxaparin (an LMWH), in preventing VTE.[4] The rate of VTE was reduced by approximately 80% compared to enoxaparin, a highly significant efficacy signal.[29] Importantly, this potent antithrombotic effect was achieved with a favorable safety profile, as bleeding events were insignificant in all study arms.[29] This trial was a critical de-risking event, providing the first clinical validation that FXI inhibition with abelacimab could effectively prevent thrombosis in humans without causing excessive bleeding, thereby justifying the significant investment in the comprehensive Phase 3 program.

Trial	LILAC-TIMI 76	ASTER	MAGNOLIA
Indication	Atrial Fibrillation	Cancer-Associated Thrombosis	Cancer-Associated Thrombosis
Population	High-risk, unsuitable for OACs	General CAT population (DOAC recommended)	High bleeding risk (GI/GU Cancers)
Comparator	Placebo	Apixaban (DOAC)	Dalteparin (LMWH)
Primary Efficacy Endpoint	Ischemic Stroke / Systemic Embolism	VTE Recurrence	VTE Recurrence

Integrated Safety and Tolerability Profile

The defining characteristic of abelacimab, and the primary driver of its clinical and commercial potential, is its remarkably favorable safety profile, particularly with respect to bleeding risk. The integrated analysis of safety data, anchored by the compelling results of the AZALEA-TIMI 71 trial, paints a consistent picture of a hemostasis-sparing anticoagulant.

The Defining Feature: A Superior Bleeding Profile

The centerpiece of abelacimab's safety dossier is the head-to-head comparison against rivaroxaban in the AZALEA-TIMI 71 trial. The data demonstrated a profound reduction in bleeding events that was consistent across both the 90 mg and 150 mg monthly doses.[8] The 62-77% relative risk reduction in the primary composite endpoint of major or CRNM bleeding is a result seldom seen in cardiovascular trials and underscores the fundamental difference in the mechanism of action compared to Factor Xa inhibitors.[8]

Site-Specific Bleeding Analysis

A more granular analysis of the bleeding events prevented reveals clinically significant advantages. The near-elimination of major gastrointestinal (GI) bleeding, with an 89-93% reduction compared to rivaroxaban, is a paramount finding.[8] GI bleeding is a major dose-limiting toxicity for DOACs, a frequent reason for treatment discontinuation or dose reduction in clinical practice, and a source of significant anxiety for both patients and clinicians.[7] By largely mitigating this risk, abelacimab could offer a much-needed solution for patients with a history of GI bleeding or those at high risk. Rates of intracerebral hemorrhage were low across all groups in the trial.[8]

Safety in High-Risk Subgroups

Crucially, the safety benefits of abelacimab appear to be most pronounced in the very patient populations who are at the highest risk of bleeding with conventional anticoagulants. Prespecified analyses from AZALEA-TIMI 71 have shown that the relative reduction in bleeding with abelacimab is consistent regardless of patient age or concomitant use of antiplatelet therapy.[25] Furthermore, because the baseline bleeding risk is higher in these subgroups, the absolute risk reduction afforded by abelacimab is even greater. For example, patients aged 75 years or older and those requiring concomitant antiplatelet medications derived a larger absolute benefit from abelacimab compared to younger patients or those not on antiplatelet therapy.[25] This suggests that abelacimab could be particularly valuable for complex, elderly patients with multiple comorbidities who are often undertreated due to bleeding concerns.

General Tolerability

Beyond bleeding, abelacimab has been generally well-tolerated in clinical trials. The overall rates of non-bleeding adverse events reported in the AZALEA-TIMI 71 study were similar between the abelacimab and rivaroxaban groups, with no new or unexpected safety signals emerging.[27] This comprehensive safety profile supports its potential use as a long-term therapy for chronic conditions like atrial fibrillation.

Regulatory and Commercial Landscape

Regulatory Status and Pathway to Approval

Abelacimab is on a well-defined and expedited path toward potential regulatory approval, underscored by significant engagement with and recognition from key global health authorities.

FDA Fast Track Designations

The U.S. FDA has granted abelacimab two separate Fast Track Designations, a clear signal that the agency recognizes its potential to address serious conditions and fill an unmet medical need.[15]

1. July 2022: Granted for the treatment of thrombosis associated with cancer.[38]
2. September 2022: Granted for the prevention of stroke and systemic embolism in patients with atrial fibrillation.[14]

This designation is designed to facilitate development and expedite the review process. It allows for more frequent meetings with the FDA to discuss the drug's development plan, eligibility for Accelerated Approval and Priority Review if relevant criteria are met, and the option of a Rolling Review, where the company can submit completed sections of its Biologics License Application (BLA) for review rather than waiting until every section is complete.[14]

European Medicines Agency (EMA) Engagement

The development strategy for abelacimab is global in scope. In April 2022, the company reached an agreement with the EMA on a paediatric investigation plan (PIP), a required step for any new medicine being developed for the European market.[52] Furthermore, the ongoing Phase 3 trials are actively enrolling patients at numerous sites across Europe, ensuring that the data generated will be applicable to a global patient population and supportive of a future Marketing Authorisation Application (MAA) to the EMA.[24]

Path to Submission

The clinical development program is structured to provide the necessary data for regulatory submissions. The LILAC-TIMI 76 trial is designed to serve as the pivotal study for a BLA submission to the FDA for the AF indication, with final data anticipated in 2026.[30] Similarly, the ASTER trial is expected to form the basis for approval in the broader CAT population, with its completion anticipated in early 2027.[30]

Corporate Strategy: The Novartis Boomerang

The corporate journey of abelacimab is a compelling case study in modern pharmaceutical R&D strategy, characterized by a strategic "boomerang" from a large pharmaceutical company to a nimble biotech and back again.

Origin and Spin-Out

The abelacimab molecule was originally discovered and developed in the research laboratories of Novartis Pharmaceuticals.[15] In 2019, at a stage when FXI inhibition was still a high-risk, albeit promising, scientific hypothesis, Novartis made a strategic decision. It partnered with Blackstone Life Sciences to launch Anthos Therapeutics, a new, focused biotechnology company.[6] Novartis licensed abelacimab to Anthos, which was capitalized with $250 million from Blackstone, to carry the asset through its high-risk, mid-stage clinical development.[28] This spin-out strategy allowed Novartis to externalize the significant financial risk and operational burden of the proof-of-concept studies while retaining a strategic interest in the asset's future success.

Anthos's Execution

Operating as an agile, dedicated entity, Anthos Therapeutics successfully executed on its mandate. The company partnered with manufacturing expert Lonza to ensure a robust supply chain and advanced abelacimab through its clinical program.[56] The crowning achievement of Anthos was the design and execution of the AZALEA-TIMI 71 trial, which delivered the spectacularly positive safety data that served as the key value inflection point for the asset, transforming it from a high-risk bet into a de-risked, potential best-in-class therapy from a safety perspective.[3]

The Strategic Re-Acquisition

With the primary risk of the program—a potential failure to demonstrate a differentiated safety profile—now decisively mitigated, the strategic calculus for Novartis changed entirely. In early 2025, Novartis announced that it had entered into an agreement to acquire Anthos Therapeutics and bring abelacimab back into its internal cardiovascular pipeline.[15] The terms of the deal reflect the immense value created by Anthos: Novartis agreed to an upfront payment of USD 925 million, with up to an additional USD 2.15 billion in potential regulatory and sales milestones.[15] This high-value transaction was a direct result of the positive AZALEA data and aligns perfectly with Novartis's strategic focus on strengthening its late-stage cardiovascular portfolio, where it can leverage its global development and commercialization expertise.[15]

Synthesis and Future Outlook

Abelacimab stands at the forefront of a potential paradigm shift in anticoagulation. Its development has successfully translated a compelling biological hypothesis—that of hemostasis-sparing anticoagulation via FXI inhibition—into a clinically validated reality, at least from a safety perspective. The results of the AZALEA-TIMI 71 trial represent a major scientific and clinical achievement, demonstrating that it is possible to profoundly inhibit a component of the coagulation cascade while causing significantly less bleeding than the current standard of care.[5]

Defining the Clinical Niche

The most direct path to market for abelacimab lies in the patient populations being studied in its Phase 3 program, where the unmet need is clearest. The population of the LILAC-TIMI 76 trial—AF patients at high risk of stroke but deemed unsuitable for existing anticoagulants due to bleeding risk—represents an ideal initial market. For these patients, who currently have no good options, an anticoagulant with the safety profile of abelacimab could be transformative. Similarly, in CAT, particularly in patients with high-risk GI/GU cancers where bleeding is a paramount concern, abelacimab could rapidly become the new standard of care, displacing LMWH and challenging DOACs.

The Efficacy Question

The primary uncertainty that clouds abelacimab's future is efficacy. The numerical, albeit non-significant, imbalance in ischemic stroke events in AZALEA-TIMI 71 raises the critical question of whether its superior safety comes at the cost of antithrombotic potency when compared directly to Factor Xa inhibitors.[8] The ongoing Phase 3 trials are designed to provide the definitive answer. The readouts from LILAC-TIMI 76 (versus placebo), ASTER (versus apixaban), and MAGNOLIA (versus dalteparin) will be the ultimate arbiters of its efficacy profile and will determine its precise place in the therapeutic armamentarium.

Competitive Landscape

Abelacimab is a leading contender but not the only agent in the race to develop FXI inhibitors. The field has seen both progress and setbacks; for instance, Bayer's oral FXIa inhibitor, asundexian, faced a setback in one trial, while other oral agents remain in late-stage development.[16] Abelacimab's profile as a long-acting, once-monthly subcutaneous injection differentiates it from the daily oral small molecules being developed by competitors, offering a different value proposition in terms of adherence and administration.

Final Verdict

Abelacimab is not an incremental improvement; it is a potentially disruptive therapeutic built on a novel biological principle. It has already shifted our understanding of what is possible in anticoagulation. Its ultimate success now hinges entirely on the forthcoming Phase 3 efficacy data. If abelacimab can demonstrate a clinically meaningful reduction in thrombotic events versus placebo in the LILAC population and establish at least non-inferiority to active comparators in the CAT population, its unparalleled safety profile will likely secure it a dominant position in these high-need markets. Such a result would not only promise a multi-billion dollar commercial opportunity but would, more importantly, fundamentally change the risk-benefit calculus for millions of vulnerable patients worldwide, heralding a new, safer era of anticoagulation.

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