Enliven Therapeutics, Inc. announced positive proof of concept data from the Phase 1 clinical trial evaluating ELVN-001 in patients with chronic myeloid leukemia (CML) who are relapsed, refractory, or intolerant to available tyrosine kinase inhibitors (TKIs) (NCT05304377). ELVN-001 is a potent, highly selective, potentially best-in-class small molecule kinase inhibitor designed to specifically target the BCR-ABL gene fusion, the oncogenic driver for patients with CML. Patient Demographics: As of the cutoff date, March 18, 2024, 27 patients had enrolled in the ongoing Phase 1 clinical trial across five dose levels of ELVN-001, ranging from 10mg once daily (QD) to 120mg QD.

Of the enrolled patients, 16 were evaluable for molecular response by 12 weeks. Patients enrolled were heavily pretreated: 70% of patients had = 3 prior TKIs. 70% of patients had received prior ponatinib and/or prior asciminib.

67% of patients had discontinued their last prior TKI due to lack of efficacy. Preliminary Efficacy: ELVN-001 achieved a cumulative major molecular response (MMR) rate of 44% (7/16) 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% (4/9) by 12 weeks. Among TKI-resistant patients, ELVN-001 achieved a cumulative MMR rate of 40% (4/10) 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 = Grade 3 non-hematologic treatment-related adverse events (TRAE) and no specific non-hematologic TRAE of any grade occurred in >11% of patients. Hematologic adverse events observed are consistent with the approved BCR::ABL1 TKIs.

Pharmacokinetics (PK) & Target Coverage: ELVN-001?s PK profile supports once daily dosing with flexible administration requirements (no significant food effect and minimal risk of drug-drug interactions). 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. ELVN-001, at 80mg QD, achieved similar target coverage compared to asciminib.