cenvacibart (REGN7508) / Regeneron - LARVOL DELTA

ROXI-EVEREST: Stroke and Systemic Embolism Prevention in Adult Participants With Atrial Fibrillation (clinicaltrials.gov) - P3 | N=15364 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Atrial Fibrillation • Cardiovascular

Study of 3 Monoclonal Antibodies (REGN9933, REGN7508, and REGN9533) in Adult Participants With End-Stage Kidney Disease on Hemodialysis (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P1 trial • Chronic Kidney Disease • Nephrology • Renal Disease

Factor XI Inhibitors for Preventing Postoperative Venous Thromboembolism in Patients Undergoing Elective Total Knee Arthroplasty: A Network Meta-analysis of Randomized Controlled Trials. (ISTH 2026) - "The NMA compared the following Factor XI inhibitor regimens: oral milvexian (25, 50, or 200 mg once daily; 25, 50, 100, or 200 mg twice daily), intravenous abelacimab (30, 75, or 150 mg single dose), intravenous osocimab (0.3, 0.6, 1.2, or 1.8 mg/kg postoperative; 0.3 or 1.8 mg/kg preoperative), subcutaneous FXI-ASO (200 or 300 mg preoperative), and intravenous REGN7508 (250 mg) or REGN9933 (300 mg), against enoxaparin (40 mg once daily). However, the lack of a significant reduction in symptomatic events warrants confirmation in larger phase 3 trials. Table or Figure Upload (1) Figure1 Page 2 Table or Figure Upload (2) Figure 2 DOI*10.1016/j.rpth.2026.103764"

Retrospective data • Cardiovascular • Hematological Disorders • Orthopedics • Venous Thromboembolism

ROXI-PEAK: Venous Thromboembolism (VTE) Prophylaxis With REGN7508 and REGN9933 in Adult and Adolescent Participants With a Peripherally Inserted Central Catheter (PICC) (clinicaltrials.gov) - P3 | N=1908 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P3 trial • Cardiovascular • Venous Thromboembolism

Mechanistic population pharmacokinetic/pharmacodynamic and time-to-event modelling support sustained Factor XI inhibition and superior post-operative venous thromboembolism prevention with REGN7508CAT (ISTH 2026) - P1, P2 | "Table or Figure Upload (1) Figure. Sustained FXI suppression following REGN7508 CAT is associated with delayed post-operative VTE events compared with enoxaparin Page 2 DOI*10.1016/j.rpth.2026.105551"

Clinical • First-in-human • PK/PD data • Cardiovascular • Hematological Disorders • Venous Thromboembolism

A Novel Monoclonal Antibody (REGN7508) Targeting FXI Reduces Clotting During Hemodialysis Ex vivo (ISTH 2026) - "Aims To investigate whether two novel factor XI-directed monoclonal antibodies, REGN7508 and REGN9933, prolong circuit patency and preserve platelet function compared to an inert control antibody alone or to apixaban (only REGN7508) in an ex vivo hemodialysis model. These findings support further clinical investigation of FXI-directed strategies, particularly agents capable of inhibiting FXIa, as a potential anticoagulation approach in hemodialysis and other extracorporeal procedures. Table or Figure Upload (1) Page 2 Table or Figure Upload (2) DOI*10.1016/j.rpth.2026.105545"

Preclinical • Hematological Disorders

Bleeding risk associated with Factor XI (FXI) monoclonal antibodies (mAbs) in combination with aspirin (ASA) in healthy volunteers and post-orthopaedic surgery patients: Analysis from recent Phase 1 and 2 studies (ISTH 2026) - P1, P2 | "In the Phase 1 study (NCT06444178), healthy volunteers received a single intravenous (IV) REGN9933 A2 300 mg or REGN7508 CAT 250 mg dose + oral ASA 75 mg once daily (QD), oral rivaroxaban 20 mg QD + ASA 75 mg QD, or oral ASA 75 mg QD alone...In Phase 2 studies (ROXI-VTE-I, NCT05618808; ROXI-VTE-II, NCT06454630), patients post-total knee arthroplasty received a single REGN9933 A2 300 mg IV dose, enoxaparin 40 mg subcutaneous QD or oral apixaban 2.5 mg twice daily (ROXI-VTE-I); or a single REGN7508 CAT 250 mg IV dose or enoxaparin 40 mg subcutaneous QD (ROXI-VTE-II); adjunctive ASA ≤100 mg/day was permitted...Table or Figure Upload (1) Figure. Bleeding rates (Phase 1) Page 2 DOI*10.1016/j.rpth.2026.105548"

Clinical • Combination therapy • P1 data • Surgery • Atherosclerosis • Cardiovascular • Orthopedics • Venous Thromboembolism

Mechanistic population pharmacokinetic/pharmacodynamic (PK/PD) modelling of Factor XI (FXI)-targeting monoclonal antibodies (Abs) supports durable anticoagulant coverage and translational dose and regimen selection (ISTH 2026) - P1 | "Observed versus predicted aPTT following single-dose administration of REGN7508 CAT and REGN9933 A2 in HVs Page 2 Table or Figure Upload (2) Figure 2. Simulated dose–aPTT response comparison between HV model parameters and disease state parameters (100% increased clearance for REGN7508 CAT and REGN9933 A2 ) DOI*10.1016/j.rpth.2026.105550"

Clinical • First-in-human • PK/PD data

ROXI-EVEREST: Stroke and Systemic Embolism Prevention in Adult Participants With Atrial Fibrillation (clinicaltrials.gov) - P3 | N=15364 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P3 trial • Atrial Fibrillation • Cardiovascular

ROXI-CAT-II: Treatment and Secondary Prevention of Venous Thromboembolism (VTE) in Adult Participants With Solid and Hematologic Cancers (clinicaltrials.gov) - P3 | N=1600 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Hematological Malignancies • Oncology • Venous Thromboembolism

ROXI-CAT-I: REGN7508 in Adult Participants for Prevention of Cancer-Associated Thrombosis (clinicaltrials.gov) - P3 | N=1120 | Recruiting | Sponsor: Regeneron Pharmaceuticals | N=860 ➔ 1120

Enrollment change • Cardiovascular • Oncology • Solid Tumor • Thrombosis

ROXI-PALISADE: Reducing Adverse Vascular Outcomes With Factor XI Inhibition in Adult Participants With Peripheral Artery Disease (clinicaltrials.gov) - P3 | N=7050 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Aug 2029 ➔ Nov 2029 | Trial primary completion date: May 2029 ➔ Aug 2029 | Not yet recruiting ➔ Recruiting

Adverse events • Enrollment open • Trial completion date • Trial primary completion date • Cardiovascular • Peripheral Arterial Disease

ROXI-INCLINE: Stroke and Systemic Embolism Prevention in Adult Participants With Atrial Fibrillation for Whom Oral Anticoagulation is Unsuitable (clinicaltrials.gov) - P3 | N=2628 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Atrial Fibrillation • Cardiovascular

R7508-CAT-2392: REGN7508 in Adult Participants for Prevention of Cancer-Associated Thrombosis. (clinicaltrialsregister.eu) - P2/3 | N=97 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals Inc.

New P2/3 trial • Cardiovascular • Oncology • Solid Tumor • Thrombosis

ROXI-ASPEN: REGN7508 Versus Acetylsalicylic Acid (ASA) for Venous Thromboprophylaxis After Total Knee Arthroplasty in Adult Participants (clinicaltrials.gov) - P3 | N=2000 | Recruiting | Sponsor: Regeneron Pharmaceuticals | N=58 ➔ 2000

Enrollment change • Trial initiation date • Cardiovascular • Orthopedics • Pain • Venous Thromboembolism

ROXI-ASPEN: REGN7508 Versus Acetylsalicylic Acid (ASA) for Venous Thromboprophylaxis After Total Knee Arthroplasty in Adult Participants (clinicaltrials.gov) - P3 | N=58 | Recruiting | Sponsor: Regeneron Pharmaceuticals | N=40 ➔ 58

Enrollment change • Cardiovascular • Orthopedics • Pain • Venous Thromboembolism

ROXI-CATH: A Trial to Learn How Well REGN9933 and REGN7508 Work for Preventing Blood Clots, and How Safe They Are, in Adults Who Have a Peripherally Inserted Central Catheter (PICC) (clinicaltrials.gov) - P2 | N=195 | Completed | Sponsor: Regeneron Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Thrombosis • Venous Thromboembolism

R7508-DVT-24120: REGN7508 versus Acetylsalicylic Acid (ASA) for Venous Thromboprophylaxis after Total Knee Arthroplasty in Adult Participants (clinicaltrialsregister.eu) - P2/3 | N=40 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals Inc.

New P2/3 trial • Cardiovascular • Orthopedics • Pain • Venous Thromboembolism

ROXI-CAT-II: Treatment and Secondary Prevention of Venous Thromboembolism (VTE) in Adult Participants With Solid and Hematologic Cancers (clinicaltrials.gov) - P3 | N=1600 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P3 trial • Cardiovascular • Hematological Malignancies • Oncology • Venous Thromboembolism

ROXI-CAT-I: REGN7508 in Adult Participants for Prevention of Cancer-Associated Thrombosis (clinicaltrials.gov) - P3 | N=860 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Nov 2029 ➔ May 2030 | Trial primary completion date: Jul 2029 ➔ Jan 2030 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial completion date • Trial primary completion date • Cardiovascular • Oncology • Solid Tumor • Thrombosis

ASSESSMENT OF GASTROINTESTINAL (GI) BLEEDING VIA FECAL HEMOGLOBIN ANALYSIS AFTER TREATMENT WITH ANTIBODIES TARGETING FACTOR XI VERSUS RIVAROXABAN ON TOP OF BACKGROUND ASPIRIN: RESULTS FROM A PHASE 1 STUDY (ACC 2026) - P=N/A, P1 | "Background: Available anticoagulants effectively treat venous thromboembolism but carry a high bleeding risk, which further increases when combined with antiplatelet therapies (eg, aspirin [ASA]). Addition of Factor XI inhibitors did not increase subclinical GI bleeding vs ASA alone, whereas rivaroxaban + ASA increased bleeding vs ASA alone."

P1 data • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Venous Thromboembolism

TOLERABILITY AND PHARMACODYNAMIC EFFECT OF REGN7508, A MONOCLONAL ANTIBODY DIRECTED AGAINST THE FACTOR XI CATALYTIC DOMAIN: RESULTS FROM A FIRST-IN-HUMAN STUDY (ACC 2026) - P1 | "REGN7508 inhibits the intrinsic coagulation pathway without measurably affecting extrinsic or common pathway activity. REGN7508 was generally well tolerated and may prevent thrombosis without increasing the risk of bleeding."

First-in-human • P1 data • PK/PD data • Back Pain • Cardiovascular • Cough • Hematological Disorders • Inflammation • Musculoskeletal Pain • Respiratory Diseases

R7508-DVT-24116: REGN7508 versus Apixaban and Enoxaparin for Thromboprophylaxis After Total Knee Arthroplasty in Adults. (clinicaltrialsregister.eu) - P2/3 | N=1067 | Recruiting | Sponsor: Regeneron Pharmaceuticals Inc.

New P2/3 trial • Cardiovascular • Orthopedics • Pain • Venous Thromboembolism

ROXI-INCLINE: Stroke and Systemic Embolism Prevention in Adult Participants With Atrial Fibrillation for Whom Oral Anticoagulation is Unsuitable (clinicaltrials.gov) - P3 | N=2628 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P3 trial • Atrial Fibrillation • Cardiovascular

ROXI-CAT-I: REGN7508 in Adult Participants for Prevention of Cancer-Associated Thrombosis (clinicaltrials.gov) - P3 | N=860 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P3 trial • Cardiovascular • Oncology • Solid Tumor • Thrombosis