RB042 / Atisama Therapeutics - LARVOL DELTA

Inhaled mRB042 reduces lung inflammation and fibrosis due to bronchoscopic instillation of bleomycin or silica dust in mice. (ERS 2026) - "RB042 is an inhaled antisense oligonucleotide that switches the splicing of RAGE mRNA in the lung, to increase beneficial esRAGE and reduce pathogenic mRAGE; mRB042 is its mouse-specific homolog.This study aimed to explore the activities of mRB042 following exposure to bleomycin or silica dust, mechanistically distinct models of lung injury and fibrosis in c57bl6 mice.Mice were pre-treated with mRB042 (10mg/kg) or saline by bronchoscopic intralobar instillation. In the bleomycin model, this was associated with a reduction in fibrotic remodelling and lower Ashcroft scores (Figure A). In the silicosis model, mRB042 also reduced silicotic pulmonary nodules and reduced King's fibrosis score (Figure B).These data support further investigation into the antifibrotic potential of our splice-switching strategy, currently in clinical development for chronic respiratory disorders."

Preclinical • Fibrosis • Immunology • Inflammation • Pneumonia

Redirecting RAGE mRNA splicing with inhaled mRB042 reduces lung inflammation and attenuates emphysema in LPS challenged Serpina1a-e null "AATD" mice (ERS 2026) - "RB042 is an inhaled antisense oligonucleotide that switches the splicing of RAGE mRNA in the lung to increase beneficial esRAGE and reduce pathogenic mRAGE; mRB042 is its mouse-specific homolog... These data support further investigation into the disease-modifying potential of our splice-switching strategy currently in clinical development for chronic respiratory disorders."

Preclinical • Alpha-1 Antitrypsin Deficiency • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Fibrosis • Hepatology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • SERPINA1

Redirecting RAGE mRNA splicing with inhaled mRB042 suppresses long term cigarette smoke-induced emphysema and inflammation in mice. (ERS 2026) - "RB042 is an inhaled antisense oligonucleotide that switches the splicing of RAGE mRNA in the lung to increase beneficial esRAGE and reduce pathogenic mRAGE; mRB042 is its mouse-specific homolog...In the smoking cessation cohort, mRB042 administration was associated with normalisation of body weight when compared to air controls. These data support further investigation into the therapeutic potential of our splice-switching strategy currently in clinical development for chronic respiratory disease."

Preclinical • Chronic Obstructive Pulmonary Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • Tobacco Cessation • CXCL8 • IL1B • IL6 • PTPRC • TNFA

The discovery of RB042, a novel inhaled antisense oligonucleotide that harnesses the alternative splicing of the Receptor for Advanced Glycation End-products in the lungs (ERS 2026) - "10 days after the last dose, ~90% of all RAGE mRNA in the lungs was RAGE_v1 mRNA, encoding esRAGE, and less than 10% retained exon 10, encoding mRAGE. As a biomarker of mRB042 splice-switching activity in the lungs, plasma RAGE was also increased.RB042-directed splice-switching of RAGE may offer a novel therapeutic strategy for chronic respiratory disorders."

Metastases • Inflammation • Respiratory Diseases

A FIRST-IN-HUMAN STUDY OF INHALED RB042 EVALUATING SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS IN HEALTHY ADULTS AND PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (CHEST 2026) - No abstract available

Clinical • First-in-human • Late-breaking abstract • P1 data • PK/PD data • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Inhaled RB042 in Healthy Adult Volunteers, Healthy Adult Smokers and Patients With Chronic Obstructive Pulmonary Disease (clinicaltrials.gov) - P1 | N=105 | Recruiting | Sponsor: Atisama Therapeutics | Trial completion date: Feb 2027 ➔ Oct 2027 | Trial primary completion date: Feb 2027 ➔ Oct 2027

First-in-human • Trial completion date • Trial primary completion date • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

The Phase 1 study of RB042, which evaluates the drug candidate in healthy volunteers and healthy smokers, has advanced to multiple ascending dose cohorts (Investing.com) - "Three of four single ascending dose cohorts have been completed, and the first multiple ascending dose cohort has been initiated. The company stated the drug has demonstrated safety and tolerability to date. Higher-dose cohorts are expected to report results in the second half of 2026"

P1 data • Trial status • Chronic Obstructive Pulmonary Disease

Inhaled RB042 in Healthy Adult Volunteers and Healthy Adult Smokers (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: RAGE Bio | Not yet recruiting ➔ Recruiting

Enrollment open • First-in-human

Phase 1 Dose-escalation Study of Inhaled RB042 in Healthy Adult Volunteers and Healthy Adult Smokers (clinicaltrials.gov) - P1 | N=90 | Not yet recruiting | Sponsor: RAGE Bio

New P1 trial