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Overview Line Alvocidib (CDK9, R/R AML) Line TP-1287 (Oral CDK9 Inhibitor) Line TP-0903 (AXL Kinase Inhibitor) Line TP-0184 (BMPR Signaling Inhibitor)

TP-0903 (AXL Kinase Inhibitor)

TP-0903 is a potent anti-cancer agent targeting the AXL receptor tyrosine kinase that has demonstrated profound activity in several cell-based and animal models of cancer. Therefore, TP-0903 has multiple paths of development that are being explored by Tolero.

AXL and other TAM family members are known to be involved in maintaining a mesenchymal phenotype in cancer cells. Mesenchymal cells have increased invasion and migratory properties, enhanced cell survival in stressed environments, and increased resistance to targeted therapies. In fact, AXL overexpression is a reoccurring theme observed in multiple tumor types that have acquired resistance to various agents.

Treatment of cancer cells with TP-0903 reverses the mesenchymal phenotype in multiple models and sensitizes cancer cells to treatment with other targeted agents. AXL-induced resistance to erlotinib in EGFR mutant lung cancer and cetuximab resistance in head and neck cancer exemplify this phenomenon. TP-0903 restores sensitivity to erlotinib in cell-based and preclinical animal models of cancer by reversing the mesenchymal phenotype driving resistance. Additionally, Tolero is exploring parallel clinical development paths in ibrutinib-progressing patients with B-cell malignancies and FLT3 inhibitor resistance in acute leukemias.

TP-0903; AXL Inhibitor

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