US-based Loxo Oncology has announced that its lead clinical program is a potent and selective inhibitor of the Trk family of receptor tyrosine kinases.
Loxo Oncology acquired rights to this program from Array Biopharma, which had pursued a multi-year discovery effort to design purpose-built compounds that spare structurally similar kinase targets, such as ALK, JAK and VEGF.
Loxo Oncology scientific advisory board chairman Dr Keith Flaherty noted after years of debate, it seems clear that highly specific kinase inhibitors have won the day in oncology.
"We have learned that maximal target inhibition leads to measurably better clinical outcomes. Limitations of dose, because of off-target mediated toxicity, prevent us from realizing the full therapeutic potential of a target. We were fortunate to have access to chemical matter rationally designed to inhibit Trk to maximal effect in patients," Flaherty added.
Loxo Oncology's lead candidate has been optimized to preserve low nanomolar potency in both enzymatic and cell based assays, while demonstrating compelling pharmacology through oral dosing. The company remains on track to launch its Phase I study in 2014.
Research suggests that Trk has therapeutic potential in many tumor types.
In a recent article, 'Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer', published online in Nature Medicine, Doebele and colleagues describe new findings implicating Trk in lung cancer.
The work includes results showing potent growth inhibition with one of the many Trk inhibitors licensed to Loxo Oncology in cell lines harboring a translocation, or rearrangement, of Trk.
Several other translocations, including ALK, ROS1 and RET, have been studied as oncogenic drivers in lung cancer and have been associated with robust objective response rates in the clinic.
