Sumitomo -Â Model TP-3654 -Investigational Oral PIM Inhibitor
TP-3654 is an oral investigational inhibitor of PIM kinases, which has potential antitumor and anti-fibrotic effects through multiple pathways, including induction of apoptosis.41,42
Understanding our target
PIM kinases are overexpressed in solid tumors and hematologic malignancies.41 PIM kinase expression correlates with increased cell survival and reduced apoptosis in tumors, implicating PIM kinases as novel therapeutic targets.41 PIM-1 expression is also significantly elevated in myelofibrosis hematopoietic cells and is a potential therapeutic target for myelofibrosis.42
Clinical evidence
TP-3654 has shown clinical activity and modulation of downstream biomarkers in a first-in-human, phase I study in patients with advanced solid tumors.43
Preclinical evidence
Additionally, TP-3654 has shown tumor growth inhibition in bladder cancer and androgen-independent prostate cancer xenograft models in mice.41 TP-3654 inhibited proliferation and increased apoptosis in murine and human hematopoietic cells expressing clinically relevant JAK2V617F mutation.42 TP-3654 alone and in combination with ruxolitinib normalized WBC and neutrophil counts, and reduced spleen size and bone marrow fibrosis in JAK2V617F and MPLW515L murine models of myelofibrosis.42
Clinical development
TP-3654 is currently being evaluated in phase I clinical trials in patients with advanced solid tumors and in patients with intermediate and high-risk myelofibrosis.
