Enliven Therapeutics Reports Positive Phase 1 Trial Data for ELVN-001 in Chronic Myeloid Leukemia

Enliven Therapeutics, Inc., a clinical-stage biopharmaceutical company based in Boulder, Colorado, recently shared promising updates from their Phase 1 clinical trial of ELVN-001, a selective small molecule kinase inhibitor designed to treat chronic myeloid leukemia (CML). The announcement was made at the European Society of Hematology International Chronic Myeloid Leukemia Foundation (ESH-iCMLf) 26th Annual John Goldman Conference.

ELVN-001 specifically targets the BCR-ABL gene fusion, the primary oncogenic driver in CML patients, and aims to be a best-in-class therapy. The updated data presented includes results from 39 patients who participated in the trial, with a median treatment duration of 20 weeks. Among these, 18 patients were evaluable for molecular response by 24 weeks, with notable results showing a 44.4% cumulative major molecular response (MMR) rate. This outcome is favorable when compared to precedent Phase 1 trials of approved BCR::ABL1 tyrosine kinase inhibitors (TKIs).

Fabian Lang, M.D., from Goethe University Hospital Frankfurt, expressed optimism about the results, highlighting the drug’s ability to provide clinical benefits to heavily pretreated CML patients. Lang emphasized the ongoing need for more effective and better-tolerated TKIs, particularly for patients who have not responded to allosteric inhibitors.

The trial data revealed a promising safety profile for ELVN-001. No dose reductions were reported, and the drug was well-tolerated across various dosage levels ranging from 10 mg to 120 mg once daily. Additionally, no significant non-hematologic treatment-related adverse events were observed, further supporting the drug's potential as a safe treatment option.

Helen Collins, M.D., the Chief Medical Officer of Enliven, echoed these sentiments, underscoring the drug’s potential to address the limitations of current TKIs. She noted that the increasing number of enrolled patients and extended follow-up periods continue to show anti-CML activity, even in a heavily pre-treated patient population. Collins also highlighted the consistency of ELVN-001’s safety profile with its high selectivity, which remains unchanged even with higher doses and longer treatment durations.

The patient demographics in the trial were diverse, with the majority having received multiple prior therapies. Specifically, 69.2% of the patients had been treated with at least three prior TKIs, and 53.8% had previously received asciminib. The trial also included patients who had discontinued their last TKI due to lack of efficacy, emphasizing the challenging nature of this patient group.

Efficacy data showed that among TKI-resistant patients, ELVN-001 achieved a 41.7% cumulative MMR rate by 24 weeks, and among post-asciminib patients, the rate was 40.0%. These results are particularly impressive given the heavily pre-treated nature of the patient population in the trial.

The Phase 1 trial of ELVN-001 focuses on evaluating the safety, tolerability, and optimal dosing for further clinical development. Secondary endpoints include pharmacokinetics and various measures of molecular response. The promising results from this trial indicate that ELVN-001 could be a valuable addition to the treatment options for CML, complementing existing therapies and addressing unmet medical needs.

Enliven Therapeutics remains focused on developing small molecule therapeutics to improve the quality of life and survival rates for cancer patients. Their precision oncology approach aims to create first-in-class or best-in-class therapies by leveraging deep insights into validated biological targets and differentiated chemistry.