Enliven announces proof of concept data from Phase 1 trial of ELVN-001

Enliven Therapeutics announced positive proof of concept data from the Phase 1 clinical trial evaluating ELVN-001 in patients with chronic myeloid leukemia who are relapsed, refractory, or intolerant to available tyrosine kinase inhibitors. Preliminary Efficacy: ELVN-001 achieved a cumulative major molecular response rate of 44% by 12 weeks and demonstrated responses in patients with prior exposure to asciminib and/or who were TKI-resistant: Among post-asciminib patients, ELVN-001 achieved a cumulative MMR rate of 44% by 12 weeks. Among TKI-resistant patients, ELVN-001 achieved a cumulative MMR rate of 40% by 12 weeks. Among response-evaluable patients, all had improved or stable BCR::ABL1 transcript levels by 12 weeks. These data compare favorably to precedent Phase 1 cumulative MMR rates for approved BCR::ABL1 TKIs, particularly given the shorter time frame for response assessment and a more heavily pre-treated patient population. Preliminary Safety: ELVN-001 has been well tolerated, consistent with its selective kinase profile. A maximum tolerated dose has not been identified, and there have been no dose reductions. No greater than or equal to Grade 3 non-hematologic treatment-related adverse events and no specific non-hematologic TRAE of any grade occurred in greater than11% of patients. Hematologic adverse events observed are consistent with the approved BCR::ABL1 TKIs. Pharmacokinetics & Target Coverage: ELVN-001’s PK profile supports once daily dosing with flexible administration requirements. Importantly, given the strong correlation between target coverage and 1L efficacy for the approved BCR::ABL1 TKIs, ELVN-001, at doses equal to or greater than 40mg QD, achieved superior target coverage compared to 2nd Generation, active-site TKIs.