gremubamab (MEDI3902) / AstraZeneca - LARVOL DELTA

A Bispecific Monoclonal Antibody Targeting Psl and PcrV for Chronic Pseudomonas Aeruginosa Infection in Patients With Bronchiectasis: Results From a Randomized, Double-Blind Placebo-Controlled Trial (GREAT-2) (ATS 2025) - "Gremubamab treatment significantly reduced P. aeruginosa airway bacterial load and improved patient-reported quality of life in patients with bronchiectasis, providing proof-of-concept for specific anti-microbial monoclonal antibody therapy."

Clinical • Late-breaking abstract • Bronchiectasis • Infectious Disease • Pulmonary Disease • Respiratory Diseases

AstraZeneca showcases innovation in infectious disease protection at ESCMID Global 2025 (AstraZeneca Press Release) - "AstraZeneca will share new data across its Vaccines & Immune Therapies portfolio at the 2025 Congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Global 2025) in Vienna, Austria, from 11-15 April 2025. With 13 abstracts, including two oral presentations and two late-breaking poster presentations, the Company will highlight progress in advancing novel immunisations against bacterial and viral infectious diseases and share real-world evidence showing the burden of respiratory viral infections and the continued need for protection."

Clinical data • Preclinical • Bronchiectasis • Infectious Disease • Influenza • Respiratory Diseases

Anti-Psl/PcrV bispecific monoclonal antibody potentiates in vitro and in vivo bacterial clearance of Pseudomonas aeruginosa from children with cystic fibrosis who failed tobramycin eradication therapy (NACFC 2024) - "Background: New-onset Pseudomonas aeruginosa infections in people with cystic fibrosis (PwCF) are routinely treated with antibiotics such as inhaled tobramycin (Tob)...In this study, we examined a new bispecific monoclonal antibody (mAb) (gremubamab) that targets Psl and the type III secretion system protein PcrV as a novel therapy to enhance neutrophil-mediated OPK in vitro and improve P. aeruginosa clearance in vivo... The bispecific anti-Psl/PcrV mAb potentiates in vitro neutrophil OPK of persistent isolates 505P and 565P. A single prophylactic dose of the mAb significantly improved bacterial clearance of 565P and 505P in vivo. Preliminary studies of the bispecific mAb in combination with Tob suggest that combination therapy may promote bacterial clearance more than single-modality therapy."

Preclinical • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Respiratory Diseases

Population pharmacokinetics of Gremubamab to inform evaluation in patients with NCFBE (WBC 2024) - No abstract available

Clinical • PK/PD data • Non‐Cystic Fibrosis Bronchiectasis

A Bispecific Monoclonal Antibody Targeting Psl and PcrV Enhances Neutrophil-Mediated Killing of Pseudomonas aeruginosa in Patients with Bronchiectasis. (PubMed, Am J Respir Crit Care Med) - "Gremubamab enhanced bronchiectasis patient neutrophil phagocytosis and killing of P.aeruginosa and reduced virulence."

Journal • Bronchiectasis • Infectious Disease • Pulmonary Disease • Respiratory Diseases

AAV-vectored expression of monospecific or bispecific monoclonal antibodies protects mice from lethal Pseudomonas aeruginosa pneumonia. (PubMed, Gene Ther) - "Serum concentrations of MEDI3902 were ~10× lower than that of αPcrV, but mice treated with this vector showed a greater reduction in bacterial dissemination to the liver, lung, spleen, and blood compared to other AAV-mAbs. These results support further investigation into the use of AAV vectored immunoprophylaxis to prevent and treat P. aeruginosa infections and other bacterial pathogens of public health concern for which current treatment strategies are limited."

Journal • Preclinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

AAV-Mediated Monoclonal Antibody Expression for the Prevention and Treatment of Pseudomonas aeruginosa Infections (ASGCT 2023) - P2 | "Bispecific hIgG antibody (MEDI3902) which combines single-chain variable fragments of both anti-Psl and anti-PcrV mAbs has been found to provide protection in prevention and treatment of P. aeruginosa infections in vivo and was evaluated in a Phase II clinical trial (NCT02696902)...All vectors provided significant protection, although notably the bispecific vector provided significantly greater protection against bacterial dissemination to the liver, lung, spleen, and blood compared to the monospecific vectors. Together, these results support further investigation of utilizing AAV-mediated mAb expression for the prevention and treatment of P. aeruginosa infections and other bacterial pathogens of public health concern, in which current treatment strategies are limited."

Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial. (PubMed, Crit Care) - P2 | "The bivalent, bispecific monoclonal antibody MEDI3902 (gremubamab) did not reduce PA nosocomial pneumonia incidence in PA-colonised mechanically ventilated subjects. Trial registration Registered on Clinicaltrials.gov ( NCT02696902 ) on 11th February 2016 and on EudraCT ( 2015-001706-34 ) on 7th March 2016."

Clinical • Journal • P2 data • PK/PD data • Critical care • Infectious Disease • Pneumonia • Respiratory Diseases

Monoclonal antibodies targeting Psl and PcrV potentiate bacterial clearance of Pseudomonas aeruginosa from cystic fibrosis children who failed eradication therapy (NACFC 2022) - "Background:Antibiotics such as inhaled tobramycin (TOB) are routinelyused to treat new-onsetPseudomonas aeruginosainfections in people with cystic fibrosis (CF) to prevent progression to chronic infection, but up to40% fail eradication therapy. Targeting Psl and PcrV with mAb potentiates neutrophil-mediated OPK of persistentP. aeruginosaisolates. Preliminary results suggest that MEDI3902 treatment may also enhance in vivo bacterialclearance of persistent isolates, raising the possibility that such therapiesmay improve the outcome ofP ."

Clinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Anti-virulence Bispecific Monoclonal Antibody Mediated Protection Against Pseudomonas aeruginosa Ventilator-Associated Pneumonia in a Rabbit Model. (PubMed, Antimicrob Agents Chemother) - "Cytokines and chemokines associated with ARDS were significantly downregulated in lungs from rabbits pretreated with MEDI3902 compared with c-IgG. These results suggest that MEDI3902 prophylaxis could have potential clinical utility for decreasing severity of P. aeruginosa ventilator-associated pneumonia."

Journal • Preclinical • Acute Respiratory Distress Syndrome • Hematological Disorders • Infectious Disease • Leukopenia • Metabolic Disorders • Neutropenia • Pneumonia • Pulmonary Disease • Respiratory Diseases

Multifunctional Monoclonal Antibody Targeting Pseudomonas aeruginosa Keratitis in Mice. (PubMed, Vaccines (Basel)) - "MEDI3902 is a multifunctional antibody that targets the P. aeruginosa persistence factor Psl exopolysaccharide, and the type 3 secretion protein PcrV...They reduce infection in mice treated concurrently at inoculation and reduced the signs of cornea pathology in mice with established infection. Taken together, these data indicate treatment with monoclonal antibodies directed against Psl and PcrV may be clinically effective in the treatment of P. aeruginosa keratitis and suggest that the design of further antibodies to be an additional tool in the treatment of bacterial keratitis."

Journal • Infectious Disease • Keratitis • Ocular Inflammation • Ophthalmology • Pneumonia • Respiratory Diseases

[VIRTUAL] Efficacy, Pharmacokinetics (PK), and Safety Profile of MEDI3902, an Anti-Pseudomonas aeruginosa Bispecific Human Monoclonal Antibody in Mechanically Ventilated Intensive Care Unit Patients; Results of the Phase 2 EVADE Study Conducted by the Public-Private COMBACTE-MAGNET Consortium in the Innovative Medicines Initiative (IMI) Program. (IDWeek 2020) - P2 | "A single IV dose of MEDI3902 provided PK exposure above the target level but did not achieve primary efficacy endpoint of reduction in PA pneumonia. Efficacy trends were observed in subjects with lower levels of baseline inflammatory biomarkers. MEDI3902 may have a path forward in certain patient populations such as ICU patients with lower baseline inflammation."

Clinical • P2 data • PK/PD data • Infectious Disease

Treatment Efficacy of MEDI3902 in Pseudomonas aeruginosa blood stream infection and acute pneumonia rabbit models. (PubMed, Antimicrob Agents Chemother) - "MEDI3902 prophylaxis or treatment was protective in both acute models and exhibited enhanced activity when combined with a subtherapeutic dose of meropenem. These findings further support MEDI3902 for prevention or treatment of serious P. aeruginosa infections."

Clinical • Journal • Preclinical • Infectious Disease • Pneumonia • Respiratory Diseases

EVADE: Effort to Prevent Nosocomial Pneumonia Caused by Pseudomonas Aeruginosa in Mechanically Ventilated Subjects (clinicaltrials.gov) - P2; N=188; Completed; Sponsor: MedImmune LLC; Active, not recruiting ➔ Completed

Clinical • Trial completion

EVADE: Effort to Prevent Nosocomial Pneumonia Caused by Pseudomonas Aeruginosa in Mechanically Ventilated Subjects (clinicaltrials.gov) - P2; N=190; Active, not recruiting; Sponsor: MedImmune LLC; Recruiting ➔ Active, not recruiting

Enrollment closed

Pseudomonas aeruginosa PcrV and Psl, the molecular targets of bispecific antibody MEDI3902, are conserved among diverse global clinical isolates. (PubMed, J Infect Dis) - "MEDI3902 maintained potent in vivo activity against various strains, including strains expressing only a single target. Psl and PcrV are highly prevalent in global clinical isolates, suggesting MEDI3902 can mediate broad coverage against P. aeruginosa."

Clinical • Journal

A Phase 1 Study of MEDI3902, an Investigational Anti-Pseudomonas aeruginosa PcrV and Psl Bispecific Human Monoclonal Antibody, in Healthy Adults. (PubMed, Clin Microbiol Infect) - P1; "Phase 1 study results of MEDI3902 in healthy subjects support further evaluation of its safety and efficacy in subjects at risk for P. aeruginosa pneumonia."

Clinical • Journal • P1 data

MEDI3902 correlates of protection against severepneumonia in a rabbit acute pneumonia model. (PubMed, Antimicrob Agents Chemother) - "In addition, MEDI3902-treated animals exhibited a profound reduction inorgan burden and a marked reduction in expression of proinflammatory mediators from lung tissue, which correlated with reduced lung histopathology. These results confirm that targeting PcrV and Psl via MEDI3902 is a promising candidate for immunotherapy againstpneumonia."

Biomarker • Journal

Adeno-Associated Virus-Mediated Expression of Monoclonal Antibodies against Healthcare-Acquired Bacterial Infections (ASGCT 2019) - "...Additionally, AAV6.2FF was re-engineered to express hIgG mAbs with variable heavy and light domains of MEDI3902 to target the type 3 secretion system (PcrV) and exopolysaccharide (Psl) of Pseudomonas aeruginosa...Intramuscular injection of 5x1010vg of both AAV6.2FF-Actoxumab and AAV6.2FF-Bezlotoxumab resulted in serum concentrations of human IgG over 250µg/ml by 28 days post-injection. This method of AAV-mediated gene delivery and vectored immunoprophylaxis offers advantages prophylactically or post-infection and shows promise in prolonging the therapeutic effect of recombinant mAb administration."