DEC has been closely following LOXO since the beginning of the year. Although an assessment of the company's drug, LOXO-101, can only be preliminary at this stage of development, a growing body of data supports investing in the company. LOXO is a cancer focussed company that has a similar focus to Blueprint Medicines (BPMC) in deciding which drugs to develop in the cancer space. Both companies develop drugs known as kinase inhibitors that are exquisitely selective for blocking the activity of enzymes that are driving tumor growth.
LOXO-101 targets the kinases encoded by the genes NTRK1, NTRK2, and NTRK3, with greater than 100-fold selectivity versus other proteins. This degree of selectivity allows for increasing the dose of the drug while mitigating off target toxicities. NTRK gene fusion events have been found in various types of cancers, and several lines of data have demonstrated that these fusions are most likely cancer driving genetic events. Inhibition of NTRK in in vitro and in vivo mouse models with these cell lines demonstrate potent control of tumor growth.
In the dose escalation stage of a Phase I trial, LOXO-101 was demonstrated to be well tolerated at doses predicted to achieve almost complete TRK kinase inhibition. The safety profile was acceptable at these doses. Yesterday, the company published data on the first NTRK mutated patient to be treated, and significant tumor regression was observed. More data in NTRK mutated patients will be needed to determine if the drug truly works, but this is a very good start.
Regression of lung metastases in a patient harboring an LMNA-TRKA driven soft tissue sarcoma dosed with LOXO-101.
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