amrecibart (REGN9933) / Regeneron - LARVOL DELTA

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

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-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

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

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

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-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 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Thrombosis • Venous Thromboembolism

ROXI-PALISADE: Reducing Adverse Vascular Outcomes With Factor XI Inhibition in Adult Participants With Peripheral Artery Disease (clinicaltrials.gov) - P3 | N=7050 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

Adverse events • New P3 trial • Cardiovascular • Peripheral Arterial Disease

ROXI-ATLAS: Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation (clinicaltrials.gov) - P2 | N=1200 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Atrial Fibrillation • Cardiovascular

ROXI-ATLAS: Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation (clinicaltrials.gov) - P2 | N=1200 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P2 trial • Atrial Fibrillation • Cardiovascular

Assessment of Gastrointestinal Blood Loss After Receiving Aspirin or Aspirin Plus Rivaroxaban, or Aspirin Plus REGN9933, or Aspirin Plus REGN7508 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=224 | Completed | Sponsor: Regeneron Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion

Assessment of Gastrointestinal Blood Loss After Receiving Aspirin or Aspirin Plus Rivaroxaban, or Aspirin Plus REGN9933, or Aspirin Plus REGN7508 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=224 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2025 ➔ Jul 2025 | Trial primary completion date: Aug 2025 ➔ Apr 2025

Enrollment closed • Trial completion date • Trial primary completion date

Assessment of Gastrointestinal Blood Loss After Receiving Aspirin or Aspirin Plus Rivaroxaban, or Aspirin Plus REGN9933, or Aspirin Plus REGN7508 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=224 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Jul 2025 ➔ Nov 2025 | Trial primary completion date: Apr 2025 ➔ Aug 2025

Trial completion date • Trial primary completion date

Regeneron to Advance Two Factor XI Antibodies into a Broad Phase 3 Program Following Positive Phase 2 Proof-of-concept Results (GlobeNewswire) - P2 | N=373 | ROXI-VTE-I (NCT05618808) | P2 | N=179 | ROXI-VTE II (NCT06454630) | Sponsor: Regeneron Pharmaceuticals | "'We are eager to advance REGN7508 and REGN9933 into a broad Phase 3 program beginning in 2025.'...a pooled analysis across both trials showed REGN7508 was superior to enoxaparin and non-inferior to apixaban, and REGN9933 was non-inferior to enoxaparin. All VTE events were asymptomatic, except for one symptomatic case of pulmonary embolism in the apixaban arm...There was no major bleeding (including surgical site bleeding) or clinically relevant non-major bleeding in any arm; the only treatment-related adverse events (AE) in any arm was one case of minimal bleeding (contusion) reported in the enoxaparin arm of ROXI-VTE-I. There were no treatment-related serious AEs (SAEs) in any arm. There were also no AEs in any arm leading to trial discontinuation or dose interruption/modification, and no AEs of special interest or deaths in these trials."

New P3 trial • P2 data • Venous Thromboembolism

Assessment of Gastrointestinal Blood Loss After Receiving Aspirin or Aspirin Plus Rivaroxaban, or Aspirin Plus REGN9933, or Aspirin Plus REGN7508 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=224 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Disorder

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 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Thrombosis • Venous Thromboembolism

Preclinical characterisation and first-in-human results on the tolerability and pharmacodynamic effect of REGN9933, a monoclonal antibody targeting the factor XI/activated factor XI apple 2 domain (ESC 2024) - "REGN9933 was found to bind the FXI apple 2 domain, with subnanomolar binding affinities for FXI and FXIa at 37°C, resulting in reduced thrombin generation from the intrinsic (not extrinsic) pathway. REGN9933 competed with HMWK for FXI binding in a dose-related manner. In the Ph 1 study, 56 pts received REGN9933 (IV, n=30; SC, n=12) or PBO (n=14); 42.9% and 21.4% had ≥1 TEAE, respectively (most common with REGN9933: headache, 12%; oropharyngeal pain, 5%)."

P1 data • PK/PD data • Preclinical • Cardiovascular • Thrombosis

Assessment of Gastrointestinal Blood Loss After Receiving Aspirin or Aspirin Plus Rivaroxaban, or Aspirin Plus REGN9933, or Aspirin Plus REGN7508 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=224 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

Combination therapy • New P1 trial • Gastrointestinal Disorder

A novel method for measuring ex vivo intrinsic pathway-triggered thrombin generation in the development of REGN9933, a monoclonal antibody targeting factor XI (ISTH 2024) - "In normal pooled plasma, ellagic acid induced rapid and robust increases in thrombin generation. Incubation with REGN9933 at 16–250 nM for 30 minutes inhibited intrinsic pathway-triggered thrombin generation in a dose-dependent manner at Regeneron laboratories (Figure 1A); isotype control had no effect. Results were replicated in normal pooled plasma at MLM Medical Labs (Figure 1B)."

Preclinical • Cardiovascular • Hematological Disorders • Thrombosis

A Trial to Learn How Well REGN9933 Works for Preventing Blood Clots After Knee Replacement Surgery in Adult Participants (clinicaltrials.gov) - P2 | N=373 | Completed | Sponsor: Regeneron Pharmaceuticals | Active, not recruiting ➔ Completed

Surgery • Trial completion • Cardiovascular • Musculoskeletal Diseases • Orthopedics • Pain • Thrombosis • Venous Thromboembolism