Entrectinib – Targeting NTRK, ROS1, ALK fusions
Currently undergoing STARTRK-2, a global, potentially registration enabling Phase 2 clinical trial, entrectinib is a potent, CNS-active, orally available, selective tyrosine kinase inhibitor of the TRKA, TRKB, TRKC, ROS1, and ALK proteins. This product candidate was designed to target cancers harboring activating molecular alterations to the corresponding subset of oncogenes. Learn more about gene fusions in cancer, data from the entrectinib ongoing Phase I and Phase II trials, and clinical responses. Click here to Learn more about Entrectinib (RXDX-101), and NTRK, ROS1, and ALK Fusions, as well as data from the entrectinib ongoing Phase I and Phase II trials, and clinical responses.
RXDX-105 – Targeting RET and Other Kinase Targets
An orally available, VEGF-sparing, potent RET inhibitor. A Phase Ib basket study of RXDX-105 is currently underway.
Learn more about RET fusions.
Taladegib – Targeting Hh/SMO
A small molecule hedgehog/smoothened inhibitor. In normal cells, the hedgehog molecule acts as a ligand that can bind the smoothened transmembrane receptor and set off a signaling cascade that can influence early development and replication of adult stem cell populations. Stem cells that acquire molecular changes activating the hedgehog/smoothened pathway can transform into tumor precursors; this process has been implicated in some forms of brain cancer, skin cancer, and pancreatic cancer. Targeting these stem cells in combination with other therapeutics could potentially help eradicate residual disease.
RXDX-106 – Targeting TYRO3, AXL, MER
RXDX-106 is a small molecule, pseudo-irreversible inhibitor of the TAM (TYRO3, AXL, and MER) family of receptor tyrosine kinases. This product candidate is currently in late-stage preclinical development. RXDX-106 binds to each of its targets – for example, as a TYRO3 inhibitor – and forms non-covalent bonds with a slow off-rate that ensure continued signaling attenuation long after the molecule becomes undetectable in the patient’s serum. This could translate into a short half-life followed by a longer period of potential tumor-suppressing activity. It also appears to potentiate the immune system, particularly in combination with other agents.
Learn more about Pan-TAM Inhibitors.