idrevloride (P-1037) / Vertex, Parion Sciences, Gilead - LARVOL DELTA

Involvement of PG1037 in the repair of 8-oxo-7,8-dihydroguanine caused by oxidative stress in Porphyromonas gingivalis. (PubMed, Mol Oral Microbiol) - "Taken together, the results show that PG1037 is an important member of a novel mechanism that recognizes and repairs oxidative stress-induced DNA damage in P. gingivalis."

Journal

ETD001: A novel inhaled ENaC blocker with an extended duration of action in vivo. (PubMed, J Cyst Fibros) - "These data support that the ENaC blocker hypothesis is yet to be appropriately tested in pwCF. ETD001 has a profile that enables dosing at a level sufficient to provide a long duration of action in a Phase 2 clinical study in pwCF scheduled for 2024."

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

RCT Abstract - Safety and efficacy of idrevloride in people with primary ciliary dyskinesia: a double-blind, randomized, placebo-controlled crossover trial (CLEAN-PCD) (ERS 2023) - No abstract available

Clinical • Otorhinolaryngology • Respiratory Diseases

Safety and efficacy of the epithelial sodium channel blocker idrevloride in people with primary ciliary dyskinesia (CLEAN-PCD): a multinational, phase 2, randomised, double-blind, placebo-controlled crossover trial. (PubMed, Lancet Respir Med) - P2a | "In this phase 2 crossover study, idrevloride in hypertonic saline was safe and associated with improved lung function over a 28-day period in people with primary ciliary dyskinesia compared with hypertonic saline alone. Larger, longer clinical studies are warranted to explore the potential benefits of idrevloride in combination with hypertonic saline in people with primary ciliary dyskinesia."

Journal • P2 data • Cough • Otorhinolaryngology • Pain • Pediatrics • Respiratory Diseases

Executing precision longitudinal flow to differentiate natural variation of immune populations from treatment response (P1037) (IMMUNOLOGY 2023) - "Furthermore, we calculated CVs for each population over time in each individual and averaged those CVs within their cohorts to quickly identify populations of interest with treatment—in this case, modulation of follicular helper cells. Employing this streamlined process produces clean data that can be analyzed confidently and allows for quick discernment of biological changes in subjects with or without immune perturbation across time."

Clinical • Late-breaking abstract • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Mesenchymal stem cell therapy to promote functional recovery in a limb transplant model (P1037) (IMMUNOLOGY 2023) - "MSC administration following limb Tx appears to promote limb function recovery and is attributed to enhanced nerve regeneration/myelination/innervation."

Mood Disorders • Transplantation • CD31 • CD34 • GFAP • ITGB1 • PECAM1 • THY1

C-terminally phosphorylated p27 drives cancer-promoting inflammation (P1037) (IMMUNOLOGY 2023) - "Notably, both p27 knockdown and STAT3 inhibition decreased p27pTpT-driven CCL2 secretion. Together, these data indicate that when p27 is C-terminally phosphorylated, it acquires a novel oncogenic role to promote STAT3-driven CSC expansion and cancer inflammation."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CCL2 • IL6 • JAG1 • KLF4 • NANOG • NF-κβ • POU5F1 • RELA

[VIRTUAL] In Vitro Validation Study for HER2 Mutations Identified in Secondary Analysis of the LUX-Lung 8 Randomized Clinical Trial (IASLC-WCLC 2020) - "Methods We have introduced ten HER2 mutations (Q57R, G152A, S250C, E265K, E395K, P489L, R683L, G815R, R929W and P1037L) into mouse pro-B cell line (Ba/F3)...For Ba/F3 cells which acquired IL-3 independent growth, we analyzed the efficacy of six EGFR or pan-ERBB tyrosine kinase inhibitors (TKIs) including afatinib, erlotinib, dacomitinib, neratinib, poziotinib, and osimertinib using growth inhibitory assay...Conclusion HER2 E395K, G815R and R929W mutations had transforming ability, and 2nd/3rd generation TKIs, including afatinib, showed higher efficacy compared with erlotinib. These results may support the search of HER2 mutation in lung squamous cell carcinoma patients."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • EGFR • HER-2