Eilean Therapeutics has announced that the US Food and Drug Administration (FDA) has cleared the IND for lomonitinib (ZE46-0134), allowing the company to proceed with a Phase 1 clinical trial in FLT3 mutated relapsed/refractory (R/R) AML. 

While the Phase 1 study has already been initiated in Australia, clearance from the FDA will allow the trial to be initiated in the US. Lomonitinib is a highly potent and selective pan-FLT3/IRAK4 inhibitor that targets clinically relevant FLT3 mutations and putative escape pathways.

"This is a major milestone for Eilean Therapeutics and validates our rational drug discovery approach with our collaborator Expert Systems," commented Iain Dukes, Chief Executive Officer of Eilean Therapeutics.

"We are looking forward to getting our clinical trial underway in the US and further expanding our global trial testing a targeted approach to treating FLT3 mutated AML,"Dukes added.

Lomonitinib is a highly potent and selective inhibitor of FLT3 ITD, TKD and other clinically relevant FLT3 mutations, as well as IRAK4. FLT3 mutations are the most frequently identified mutations in AML. There are two main mechanisms of resistance to FLT3 inhibitors: the FLT3-ITD-F691L mutation deemed the 'gatekeeper' mutation that confers resistance to all currently approved FLT3 inhibitors and the activation of the IRAK4 escape pathway. Lomonitinib inhibits both resistance mechanisms. 

Given the excellent safety profile (with no cytological changes) and ability to rapidly reach a steady state, target engagement exposures in a healthy volunteer study, it is anticipated that lomonitinib will have a deeper response (i.e. more CR/CRh) and longer duration of response in R/R AML patients, and eventually expand to be the best-in-class FLT3 inhibitor.