VCP/p97 inhibitors / Cleave Therap - LARVOL DELTA

Efficacy of Vcp/p97 Inhibitor, CB-5339, Alone and in Combinations Against High-Risk AML, Including Those with Genetic Lesion in TP53 (ASH 2022) - "Valosin-containing protein (VCP)/p97 or p97 is an AAA+ type ATPase involved in quality control of cellular proteins in normal and transformed cells, especially under cellular stress. Finally, in a tail-vein infused, luciferase transduced, aggressive xenograft model of MOLM13 cells, after AML engraftment, co-treatment for 3 weeks with CB-5339 (50 mg/kg/day, PO) and either venetoclax (30 mg/kg/day, PO) or OTX015 (30 mg/kg/day, PO), as compared to treatment with vehicle or each drug alone, significantly reduced the AML burden and improved median and overall survival of the NSG mice, without inducing significant toxicity. Taken together, these findings highlight that CB-5339 induces lethal ER stress in AML cells regardless of the TP53 status, and underscore the promise of CB-5339 treatment alone and in rational combinations in exerting efficacy against AML, including those with high-risk genetic alterations in TP53 or chromosome 3q26 lesions and EVI1 overexpression."

Clinical • Acute Myelogenous Leukemia • CNS Disorders • Oncology • Psychiatry • Targeted Protein Degradation • ATF3 • ATF4 • BBC3 • CD86 • CXCR4 • FBXO32 • FLT3 • FOXA1 • HSPA5 • IL7R • ITGAM • MDM2 • MDM4 • MECOM • TLR4 • TP53

VCP/p97 inhibitor CB-5083 modulates muscle pathology in a mouse model of VCP inclusion body myopathy. (PubMed, J Transl Med) - "Altogether, these findings suggest that long-term use of CB-5083 by moderate doses is safe and can improve VCP disease-associated muscle pathology. Our results provide translationally relevant evidence that VCP inhibitors could be beneficial in the treatment of VCP disease."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Immunology • Myositis • Oncology • Orthopedics • Proteinopathy • TARDBP

"$CASI Cleave Therapeutics Licenses First-in-Class VCP/P97 Inhibitor CB-5339 To CASI Pharmaceuticals For Greater China Region https://t.co/BBtXCNexhM" (@stock_titan)