REGN13335 / Regeneron - LARVOL DELTA

REGN13335, a novel PDGF-B antagonist monoclonal antibody, for the treatment of pulmonary hypertension: Preclinical efficacy and a first-in-human phase 1 study (ERS 2026) - P1 | "In a secondary PH mouse model, C57bl mice received bleomycin (Bleo) for 21 d to induce LF followed by tx with human IgG or REGN13335 (25 mg/kg) for 21 d. Single-cell sequencing of lung tissue from Bleo-treated mice and pts with IPF assessed PDGF expression and pathway activation. PDGF signalling is activated in lung MFBs and SMCs in Bleo-induced LF mice and pts with IPF. REGN13335 mitigated PH in mice and was generally well-tolerated in healthy adults up to 40 mg/kg IV and 600 mg SC supporting further investigation in pulmonary hypertension."

First-in-human • P1 data • Preclinical • Cardiovascular • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

ILLUMINATE: Study of REGN13335 in Adult Participants With Pulmonary Arterial Hypertension (PAH) (clinicaltrials.gov) - P2 | N=99 | Recruiting | Sponsor: Regeneron Pharmaceuticals

Trial initiation date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

ILLUMINATE: Phase 2 Study of REGN13335 in Adult Participants With Pulmonary Arterial Hypertension (PAH) (clinicaltrials.gov) - P2 | N=99 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting | N=47 ➔ 99

Enrollment change • Enrollment open • Trial initiation date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

ILLUMINATE: Phase 2 Study of REGN13335 in Adult Participants With Pulmonary Arterial Hypertension (PAH) (clinicaltrials.gov) - P2 | N=47 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals | N=19 ➔ 47

Enrollment change • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

ILLUMINATE: Phase 2 Study of REGN13335 in Adult Participants With Pulmonary Arterial Hypertension (PAH) (clinicaltrials.gov) - P2 | N=19 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals | N=14 ➔ 19

Enrollment change • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

R13335-PAH-2365: Phase 2 Study of REGN13335 in Adult Participants with Pulmonary Arterial Hypertension (PAH) (clinicaltrialsregister.eu) - P1/2 | N=5 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals Inc.

New P1/2 trial • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

ILLUMINATE: Phase 2 Study of REGN13335 in Adult Participants With Pulmonary Arterial Hypertension (PAH) (clinicaltrials.gov) - P2 | N=99 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P2 trial • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Platelet-derived growth factor antagonist antibody attenuates pulmonary arterial hypertension and prevents right heart dysfunction in the Sugen-Hypoxia rat model (AHA 2025) - "Sildenafil, a standard of care (SOC) treatment in PAH, attenuated RV dysfunction in this model suggesting its translatability to study RV function in PAH. Longitudinal cardiac imaging revealed RV dysfunction in the SuHx rat model of PAH. Treatment with SOC or REGN13335 improved RV hypertrophy, systolic function and output. REGN13335 may represent a novel therapeutic approach to address RV remodeling and dysfunction in patients with PAH."

Preclinical • Cardiovascular • Pulmonary Arterial Hypertension • Respiratory Diseases • GDF15 • MYH7 • PDGFRB

THE IMPACT OF THE HUMAN MONOCLONAL ANTIBODY REGN13335 ON PDGF-B: A POTENTIAL, NOVEL THERAPEUTIC STRATEGY FOR PULMONARY ARTERIAL HYPERTENSION (CHEST 2025) - "Combining REGN13335 with the endothelin receptor antagonist macitentan improved survival compared to vehicle control treatment and macitentan monotherapy in MCT rats. In the bleomycin-induced lung fibrosis model, REGN13335 mitigated RVSP elevation... Neutralizing PDGF-B with REGN13335 reduces PDGF-BB/AB signaling through PDGFR-α and PDGFR-β on vascular support cells and fibroblasts, contributing to remodeling and pulmonary resistance. REGN13335 demonstrated efficacy in mitigating PAH-related endpoints across preclinical models of primary and secondary PAH. CLINICAL IMPLICATIONS: These findings suggest that the PDGF-B antagonist monoclonal antibody REGN13335 may represent a promising therapeutic strategy for PAH treatment, potentially reducing the risk of right heart failure and improving survival in patients with PAH."

Anemia • Cardiovascular • Congestive Heart Failure • Fibrosis • Genetic Disorders • Heart Failure • Hematological Disorders • Immunology • Pulmonary Arterial Hypertension • Respiratory Diseases • Sickle Cell Disease • PDGFRA • PDGFRB

THE IMPACT OF PLATELET-DERIVED GROWTH FACTOR-BB ANTAGONIST ANTIBODY ON RIGHT HEART FAILURE IN PULMONARY HYPERTENSION IN PRECLINICAL ANIMAL STUDIES (CHEST 2025) - "We employed an investigational fully human monoclonal antibody, REGN13335, which is designed to bind and neutralize PDGF-B with high affinity, to evaluate its therapeutic potential in mitigating RV remodeling and dysfunction using echocardiography and cardiac magnetic resonance imaging (MRI) in the SU5416/hypoxia (SuHx) PAH rat model. Longitudinal RV imaging by echocardiography and MRI effectively detected RV remodeling and dysfunction in the SuHx rat model of PAH. REGN13335 treatment mitigated RV remodeling, preserved RV function, and improved oxygen saturation. CLINICAL IMPLICATIONS: Targeting the PDGF-BB pathway with REGN13335 may offer a novel therapeutic strategy to prevent or reverse RV remodeling and dysfunction in PAH patients."

Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • GDF15 • MYH7 • PDGFRB

A Study to See How Safe and Tolerable Different Doses of REGN13335 Are When Administered Intravenously (IV) or Subcutaneously (SC) to Healthy Adult Participants (clinicaltrials.gov) - P1 | N=56 | Completed | Sponsor: Regeneron Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion