Nuvisertib (TP-3654): A Comprehensive Profile of a Selective PIM1 Kinase Inhibitor Poised to Address Unmet Needs in Myelofibrosis

I. Executive Summary

Nuvisertib, also known as TP-3654, is an orally available, second-generation small molecule inhibitor of Proviral Integration site for Moloney murine leukemia virus (PIM) kinases, currently under clinical investigation by Sumitomo Pharma America.[1] As a highly selective inhibitor of the PIM1 isoform, Nuvisertib represents a novel therapeutic approach for hematological malignancies, with its most advanced development program focused on myelofibrosis (MF), a rare and debilitating blood cancer.[3] The drug is emerging as a promising agent for patients with intermediate or high-risk MF who are relapsed, refractory, or intolerant to current standard-of-care Janus-associated kinase (JAK) inhibitors.

The strategic value of Nuvisertib is anchored in its distinct mechanism of action, which confers a unique and highly advantageous clinical profile. Unlike existing therapies that are often limited by myelosuppressive toxicities, Nuvisertib has demonstrated a favorable and manageable safety profile, characterized primarily by low-grade, transient gastrointestinal side effects. This benign hematological profile is a direct consequence of its high selectivity for the PIM1 kinase, a pharmacological feature that differentiates it from less selective pan-PIM inhibitors and enables its use in patients with pre-existing cytopenias.