Nanoromidepsin, a Polymer Nanoparticle of the HDAC Inhibitor, Improves Safety and Efficacy in Models of T-cell Lymphoma Available to Purchase

• The treatment options for patients with relapsed or refractory PTCL are dwindling, given the paucity of drugs available for these patients.

• Leveraging a novel polymer nanochemistry platform we synthesized a new epigenetic modulator with superior features in T-Cell malignancies.

Histone deacetylase inhibitors (HDACi) are valued treatment options for patients with T-cell malignancies. Romidepsin is a selective Class I HDACi initially approved for patients with relapsed or refractory (R/R) CTCL and PTCL. Romidepsin was withdrawn from its PTCL indication following a negative randomized Phase IV study (Ro-CHOP) that showed no benefit over CHOP alone, further diminishing options for patients. Herein, we describe the development of a first-in-class polymer nanoparticle (PNP) of romidepsin using an innovative amphiphilic di-block copolymer-based nanochemistry platform. Nanoromidepsin exhibited superior pharmacologic properties with improved tolerability and safety in murine models of T-cell lymphoma (TCL). The PNP also exhibited superior anti-tumor efficacy in multiple models including in vitro -TCL cell lines, ex vivo LGL leukemia patient samples, and murine TCL xenografts. Nanoromidepsin demonstrated greater accumulation in tumors and a statistically significant improvement in overall survival compared to romidepsin in murine xenograft models. These findings justify the clinical development of Nanoromidepsin in patients with T-cell malignancies.