KYM-001 / Kymera Therap, Vertex - LARVOL DELTA

Targeted Proteasomal Degradation of IRAK4 Ameliorates Kidney Fibrosis Caused by AKI (KIDNEY WEEK 2022) - "Methods We tested the IRAK4 degrader molecule KYM-001/IRW-1080 in vitro , on isolated kidney stroma PDGFRb + pericyte/fibroblasts cells and on hPSC-derivedkidney organoids incubated with interleukin 1b,(IL1b) and in vivo in a mouse model of unilateral ischemia/reperfusion injury...After unilateral IRI, IRW-1080 delivered by gavage at a dose of 50mg/Kg, every 48h starting on the day of IRI surgery and over a period of 14 days, showed superior anti-inflammatory and anti-fibrotic activity compared to the IRAK4 kinase activity inhibitor small molecule CA-4948 delivered at a 75mg/Kg dose. In addition, animals that received IRW-1080 showed reduced levels of tubule injury and expression of the tubule injury marker KIM1. Conclusion Collectively, our findings validate the role myddosome signaling and particularly of IRAK4 in the process of kidney fibrosis, and indicated that targeted degradation of IRAK4 is an efficacious therapy for acute kidney injury."

Acute Kidney Injury • Cardiovascular • Fibrosis • Immunology • Inflammation • Nephrology • Renal Disease • Reperfusion Injury • Targeted Protein Degradation • IL1B • IRAK4 • KIM1 • PDGFRB

Kymera Therapeutics to present preclinical data on its first-in-class IRAK4 degraders demonstrating robust inhibition of inflammatory responses and superiority to IRAK4 kinase inhibitors (BioSpace) - "Kymera Therapeutics...announced the company will present new preclinical data showing its first-in-class selective and potent oral IRAK4 degraders demonstrate broad and robust in vitro and in vivo inhibition of the toll-like receptor (TLR) and Interleukin-1 receptor (IL-1R) pathways underlying the pathogenesis of many inflammatory and autoimmune diseases. Data will be shared during an oral presentation (Abstract #1768) at the American College of Rheumatology Annual Meeting in Atlanta on Monday, November 11 at 3:30 PM EST."

Preclinical

Kymera Therapeutics to present new preclinical data for its first-in-class oral IRAK4 degrader in MYD88-mutant B cell lymphoma at the 15th International Conference on Malignant Lymphoma (PRNewswire) - "'We look forward to sharing our findings and engaging with an international group of lymphoma experts at this year's ICML meeting to define the path forward into the clinic in 2020.'...Orally dosed KYM-001 caused in vivo tumor regression in a dual MYD88/CD79 mutant OCI-LY10 mouse xenograft model of ABC-DLBCL associated with ≥75% IRAK4 knockdown in tumors. Subtherapeutic doses of KYM-001 in combination with the BTK inhibitor ibrutinib increased OCI-LY10 apoptosis in vitro and drove tumor regression in vivo in the OCI-LY10 mouse xenograft model."

Clinical • Preclinical

Newly added product (PRNewswire) - Preclinical, Diffuse Large B Cell Lymphoma, Inflammation

Pipeline update