Enliven Therapeutics (ELVN) Study update summary

Program overview and rationale

• ELVN-001 is a highly selective, ATP-competitive BCR-ABL1 TKI designed for chronic myeloid leukemia (CML), aiming to minimize off-target adverse events and maximize efficacy with once-daily dosing, low drug-drug interaction potential, and no food restrictions.

• The drug addresses unmet needs in CML, including poor tolerability, suboptimal efficacy, and treatment burden associated with current TKIs, and is engineered for broad mutational coverage, including resistance mutations to other ATP inhibitors and allosteric TKIs such as T315I.

• ELVN-001 is positioned as complementary to allosteric TKIs and is anticipated for use across all lines of therapy.

• The U.S. branded CML market is estimated at $10 billion, with ELVN-001 targeting both second-line-plus and frontline settings.

Clinical study design and patient population

• The ENABLE Phase 1 study enrolled chronic phase CML patients who had failed, were intolerant to, or were not candidates for available therapies, with most being heavily pretreated and high rates of prior asciminib or ponatinib exposure.

• Dose escalation and expansion included 60 mg, 80 mg, and 120 mg once daily; 80 mg QD was selected as the optimal biological and Phase 3 dose.

• At data cutoff, 49 patients were enrolled at 80 mg QD, with 70% having received at least three prior TKIs and over half with prior asciminib exposure; 82% of patients in the 80 mg QD cohort remained on study.

• Median exposure was 35 weeks, with over one-third on therapy for more than a year; no patients progressed to blast phase.

• 161 patients were enrolled overall, with a median treatment duration of 35 weeks and 76% remaining on study.

Safety and tolerability results

• ELVN-001 demonstrated a favorable safety profile, with most adverse events being low grade or Grade 1/2, and only 6% discontinuing due to adverse events.

• The incidence of arterial occlusive events and grade 3–4 hematologic toxicities was low, with thrombocytopenia as the only Grade ≥3 TEAE reported in more than 5% of patients at 80 mg QD.

• Hematologic and vascular toxicities were lower compared to historical data for other TKIs, potentially due to ELVN-001’s high selectivity for ABL1 over ABL2.

• Rates of hypertension and off-target toxicities such as GI events and rash were low, and patients reported minimal subjective side effects.

• Grade ≥3 TEAEs occurred in 34% overall, but only 24% at the 80 mg QD dose.