REGN9933 / Regeneron - LARVOL DELTA

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

TOLERABILITY AND PHARMACODYNAMIC EFFECT OF REGN9933, A MONOCLONAL ANTIBODY DIRECTED AGAINST THE FACTOR XI APPLE 2 DOMAIN: RESULTS FROM A FIRST-IN-HUMAN STUDY (THSNA 2024) - P1 | "These first-in-human data suggest that REGN9933 has a dose-dependent inhibitory effect on the intrinsic coagulation pathway without affecting extrinsic pathway activity. These findings, allied with the tolerability profile of REGN9933, support its continued development as an anticoagulant that may carry less risk of bleeding than existing therapies."

P1 data • PK/PD data • Cardiovascular • Fatigue • Hematological Disorders • Pain • 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 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Surgery • Cardiovascular • Musculoskeletal Diseases • Orthopedics • Pain • Thrombosis • 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 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P2 trial • Cardiovascular • Thrombosis • Venous Thromboembolism

A Trial to Learn How Well REGN9933 Works for Preventing Blood Clots After Knee Replacement Surgery in Adult Participants (clinicaltrials.gov) - P2 | N=360 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Surgery • Cardiovascular • Musculoskeletal Diseases • Orthopedics • Pain • Thrombosis • Venous Thromboembolism

Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN9933 in Adult Healthy Volunteers (clinicaltrials.gov) - P1 | N=56 | Completed | Sponsor: Regeneron Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion

Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN9933 in Adult Healthy Volunteers (clinicaltrials.gov) - P1 | N=56 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2023 ➔ Apr 2023 | Trial primary completion date: Jul 2023 ➔ Apr 2023

Enrollment closed • Trial completion date • Trial primary completion date

A Trial to Learn How Well REGN9933 Works for Preventing Blood Clots After Knee Replacement Surgery in Adult Participants (clinicaltrials.gov) - P2 | N=360 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Jun 2024 ➔ Oct 2024 | Trial primary completion date: Jun 2024 ➔ Oct 2024

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

A Trial to Learn How Well REGN9933 Works for Preventing Blood Clots After Knee Replacement Surgery in Adult Participants (clinicaltrials.gov) - P2 | N=360 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P2 trial • Cardiovascular • Musculoskeletal Diseases • Orthopedics • Pain • Thrombosis • Venous Thromboembolism

Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN9933 in Adult Healthy Volunteers (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Nov 2022 ➔ Jul 2023 | Trial primary completion date: Nov 2022 ➔ Jul 2023

Trial completion date • Trial primary completion date