REGN5381 / Regeneron - LARVOL DELTA

NATRIX-SBP: REGN5381 in Adult Participants With Uncontrolled Hypertension (clinicaltrials.gov) - P2 | N=34 | Terminated | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Feb 2026 ➔ Oct 2025 | Active, not recruiting ➔ Terminated; Sponsor decision

Trial completion date • Trial termination • Cardiovascular • Hypertension

Agonist Antibody to Natriuretic Peptide Receptor 1 for CKD (KIDNEY WEEK 2025) - "The addition of empagliflozin to REGN5381 plus enalapril further improved survival and reduced albuminuria. In the RKM model of CKD, REGN5381 reduced albuminuria, and improved kidney histopathology and cardiac ejection fraction, indicating that the benefits of REGN5381 are not limited to AS. Conclusion NPR1 agonism with REGN5381 benefited the kidney and heart in multiple CKD models, presenting a potential novel therapeutic strategy to treat CKD."

Chronic Kidney Disease • Fibrosis • Genetic Disorders • Immunology • Inflammation • Nephrology • Renal Disease

NATRIX-BNP: REGN5381 in Adult Participants With Heart Failure With Reduced Ejection Fraction (clinicaltrials.gov) - P2 | N=89 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=394 ➔ 89 | Trial completion date: Feb 2027 ➔ Dec 2025 | Trial primary completion date: Nov 2026 ➔ Sep 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure

Impact of REGN5381, a Monoclonal Antibody Agonist to Natriuretic Peptide Receptor 1, on Pulmonary Capillary Wedge Pressure in Patients With Heart Failure With Preserved Ejection Fraction (AHA 2025) - "Available on Sunday, November 09, 2025 at 03:36pm CDT."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure

Safety and Tolerability of REGN5381, a Monoclonal Antibody Agonist of NPR1 in Patients With Heart Failure With Reduced Ejection Fraction (AHA 2025) - "Available on Saturday, November 08, 2025 at 10:59am CDT."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure

NATRIX-SBP: REGN5381 in Adult Participants With Uncontrolled Hypertension (clinicaltrials.gov) - P2 | N=34 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=732 ➔ 34 | Trial completion date: Jul 2026 ➔ Feb 2026 | Trial primary completion date: May 2026 ➔ Dec 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Cardiovascular • Hypertension

NATRIX-BNP: REGN5381 in Adult Participants With Heart Failure With Reduced Ejection Fraction (clinicaltrials.gov) - P2 | N=394 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Apr 2026 ➔ Feb 2027 | Trial primary completion date: Jan 2026 ➔ Nov 2026

Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure

REGN5381 in Heart Failure Adult Participants With Elevated Pulmonary Capillary Wedge Pressure (clinicaltrials.gov) - P2 | N=59 | Completed | Sponsor: Regeneron Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

NATRIX-SBP: REGN5381 in Adult Participants With Uncontrolled Hypertension (clinicaltrials.gov) - P2 | N=732 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Hypertension

REGN5381 in Heart Failure Adult Participants With Elevated Pulmonary Capillary Wedge Pressure (clinicaltrials.gov) - P2 | N=59 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=122 ➔ 59

Enrollment change • Enrollment closed • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

NATRIX-SBP: REGN5381 in Adult Participants With Uncontrolled Hypertension (clinicaltrials.gov) - P2 | N=732 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P2 trial • Cardiovascular • Hypertension

Agonist antibody to guanylate cyclase receptor NPR1 regulates vascular tone. (PubMed, Nature) - "In healthy human volunteers, REGN5381 produced the expected haemodynamic effects, reflecting reductions in venous pressures, without obvious changes in diuresis and natriuresis. These data support the development of REGN5381 for long-lasting and selective lowering of venous pressures that drive symptomatology in patients with heart failure."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

A Trial to Learn How REGN5381 Works and How Safe it is in Adults With Heart Failure With Reduced Ejection Fraction (HFrEF) (clinicaltrials.gov) - P2 | N=391 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Jul 2026 ➔ Apr 2026 | Trial primary completion date: Apr 2026 ➔ Jan 2026

Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

A Trial to Learn How REGN5381 Works and How Safe it is in Adults With Heart Failure With Reduced Ejection Fraction (HFrEF) (clinicaltrials.gov) - P2 | N=391 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN9035 in Healthy Adult Volunteers and Mildly Hypertensive Participants (clinicaltrials.gov) - P1 | N=93 | Completed | Sponsor: Regeneron Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion

EFFECTS OF REGN5381, A NATRIURETIC PEPTIDE RECEPTOR 1 AGONIST ANTIBODY, IN HYPERTENSIVE MOUSE MODELS AND MILDLY HYPERTENSIVE BUT OTHERWISE HEALTHY ADULTS IN A PHASE 1 FIRST-IN-HUMAN STUDY (ACC 2024) - P1 | "Consistent with the preclinical data, a single-dose REGN5381 showed sustained hemodynamic effects up to day 4 with an acceptable safety profile in mildly hypertensive adults."

P1 data • Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Hypotension

REGN5381 in Heart Failure Adult Participants With Elevated Pulmonary Capillary Wedge Pressure (clinicaltrials.gov) - P2 | N=122 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Aug 2025 ➔ Apr 2025 | Trial primary completion date: Aug 2025 ➔ Apr 2025

Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

A Trial to Learn How REGN5381 Works and How Safe it is in Adults With Heart Failure With Reduced Ejection Fraction (HFrEF) (clinicaltrials.gov) - P2 | N=391 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P2 trial • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

Safety and Tolerability of Single Ascending Intravenous (IV) Doses of REGN5381 in Adult Heart Failure Patients With Elevated Pulmonary Capillary Wedge Pressure (clinicaltrials.gov) - P2 | N=122 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Suspended ➔ Recruiting | Trial completion date: Dec 2023 ➔ Aug 2025 | Trial primary completion date: Dec 2023 ➔ Aug 2025

Enrollment open • Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN9035 in Healthy Adult Volunteers and Mildly Hypertensive Participants (clinicaltrials.gov) - P1 | N=93 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed

Safety Outcomes From a First-in-Human Study of a Novel Investigational Monoclonal Antibody, REGN5381, an Agonist to the Natriuretic Peptide Receptor 1 (AHA 2023) - P1 | "A single dose of REGN5381 is generally well-tolerated and provides sustained hemodynamic effects."

Clinical • P1 data • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypotension • Pain

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN9035 in Healthy Adult Volunteers and Mildly Hypertensive Participants (clinicaltrials.gov) - P1 | N=107 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Suspended ➔ Recruiting | Trial completion date: Jan 2024 ➔ Jul 2024 | Trial primary completion date: Jan 2024 ➔ Jul 2024

Enrollment open • Trial completion date • Trial primary completion date

Safety and Tolerability of Single Ascending Intravenous (IV) Doses of REGN5381 in Adult Heart Failure Patients With Elevated Pulmonary Capillary Wedge Pressure (clinicaltrials.gov) - P2 | N=149 | Suspended | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Suspended

Trial suspension • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN9035 in Healthy Adult Volunteers and Mildly Hypertensive Participants (clinicaltrials.gov) - P1 | N=107 | Suspended | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Oct 2023 ➔ Jan 2024 | Recruiting ➔ Suspended | Trial primary completion date: Oct 2023 ➔ Jan 2024

Trial completion date • Trial primary completion date • Trial suspension

Safety and Tolerability of Single Ascending Intravenous (IV) Doses of REGN5381 in Adult Heart Failure Patients With Elevated Pulmonary Capillary Wedge Pressure (clinicaltrials.gov) - P2 | N=149 | Recruiting | Sponsor: Regeneron Pharmaceuticals | N=80 ➔ 149

Enrollment change • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB