Sumitomo -Â Model TP-0184 - ALK2 and ALK5 Investigational Inhibitor
TP-0184 is an investigational inhibitor of activin receptor-like kinase 2 (ALK2) and ALK5 (also known as TGFβR1). This bimodal inhibitor is believed to downregulate multiple TGF-β superfamily signaling pathways and has shown antitumor activity in several cancers.
Understanding our target
ALK2 and ALK5 are 2 members of the TGF-β superfamily signaling pathways.23 ALK2 binds with members of the TGF-β family of ligands, such as BMPs and GDFs, to initiate a signaling cascade.24 When mutated or upregulated, ALK2 pathway signaling has been associated with several types of solid tumors, including DIPG, and anemia.21,25-28
ALK5 is part of the canonical TGF-β pathway, which, when dysregulated, may be involved in the hematopoietic aberrations observed in MDS.22,23 ALK5/TGF-β signaling has also been known to enable cancer progression through multiple avenues, including invasion and metastasis, angiogenesis, immune escape, and inflammation.23
Preclinical evidence
TP-0184 has shown the ability to decrease hepcidin expression, increase bioavailable iron, and restore normal levels of hemoglobin in preclinical models of anemia caused by acute and chronic inflammation and by cancer.20,21 Additionally, TP-0184 has shown activity against ALK5 signaling, which improved hematopoiesis in a separate in vitro study in MDS.22
Clinical development
TP-0184 is currently being investigated in a phase I trial in patients with advanced solid tumors and in a phase I/II trial for treatment of anemia associated with MDS.
