Discovery and development of INNA-051, a TLR2/6 agonist for the prevention of complications resulting from viral respiratory infections.

Viral respiratory infection is associated with significant morbidity and mortality. The diversity of viruses implicated, coupled with their propensity for mutation, ignited an interest in host-directed antiviral therapies effective across a wide range of viral variants. Toll-like receptors (TLRs) are potential targets for the development of broad-spectrum antivirals given their central role in host immune defenses.

Evaluation of intranasal TLR2/6 agonist INNA-051: safety, tolerability and proof of pharmacology.

Background: Local priming of the innate immune system with a Toll-like receptor (TLR)2/6 agonist may reduce morbidity and mortality associated with viral respiratory tract infections, particularly for the elderly and those with chronic diseases. The objectives of the present study were to understand the potential of prophylactic treatment with a TLR2/6 agonist as an enhancer of innate immunity pathways leading to accelerated respiratory virus clearance from the upper airways.

Methods: Two randomised, double-blind, placebo-controlled clinical trials were conducted in healthy adult participants.

Perspectives on Treatment Decisions, Preferences, and Adherence and Long-Term Management in Asthma and COPD: A Qualitative Analysis of Patient, Caregiver, and Healthcare Provider Insights.

Purpose: Asthma and chronic obstructive pulmonary disease (COPD) are associated with substantial morbidity and mortality. This analysis assessed patient, caregiver, and healthcare provider (HCP) opinions regarding asthma and COPD diagnosis and treatment, including inhaler device preferences.

Patients And Methods: Insights were from: (1) face-to-face/telephone patient/HCP communications with GSK Global Medical Teams; (2) social media listening; (3) a self-completed online patient/caregiver survey.

Polygenic and transcriptional risk scores identify chronic obstructive pulmonary disease subtypes in the COPDGene and ECLIPSE cohort studies.

Background: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics.

Methods: We defined high-risk groups based on PRS and TRS quantiles by maximising differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets.

The Responsiveness of Exercise Tests in COPD: A Randomized Controlled Trial.

Background: COPD is characterized by reduced exercise tolerance, and improving physical performance is an important therapeutic goal. A variety of exercise tests are commonly used to assess exercise tolerance, including laboratory and field-based tests. The responsiveness of these various tests to common COPD interventions is yet to be compared, but the results may inform test selection in clinical and research settings.