Enliven Therapeutics Announces Positive Data Update from Phase 1 Clinical Trial of ELVN-001 in Chronic Myeloid Leukemia

Enliven Therapeutics, Inc. recently announced updated, positive data from the Phase 1 clinical trial evaluating ELVN-001 in patients with chronic myeloid leukemia (CML) that has failed, or the patient is intolerant to or not a candidate for, available therapies known to be active for treatment of their CML (NCT05304377) at the European Society of Hematology International Chronic Myeloid Leukemia Foundation (ESH-iCMLf) 26th Annual John Goldman Conference. 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.

“I am happy to present the updated ELVN-001 Phase 1 data today at ESH-iCMLf. ELVN-001 continues to show clinical benefit in heavily pretreated CML patients,” said presenting investigator Fabian Lang, MD, from Goethe University Hospital Frankfurt. “I am encouraged that the initial clinical profile presented in April continues to hold, even as patient numbers and the median duration of exposure increased. We continue to see categorical improvements in molecular response, and the drug remains well-tolerated with an encouraging safety profile. Despite recent advancements in the CML treatment paradigm, there continues to be a need for more efficacious and better tolerated active-site TKIs, especially for patients who have failed treatment with allosteric inhibitors. I remain excited to see the progress of ELVN-001 as the trial continues.”

The updated data presented today includes 39 patients across various dose levels, 18 of whom were evaluable for molecular response by 24 weeks. Consistent with the 12-week results the Company presented in April 2024, a cumulative major molecular response (MMR) rate of 44.4% (8/18) was observed by 24 weeks in response-evaluable CML patients. Additionally, ELVN-001 continues to be well-tolerated with no dose reductions and a median treatment duration of 20 weeks.

“We are excited by the continued advancement of the ELVN-001 Phase 1 trial, and we remain confident in ELVN-001’s potential to address the limitations of the available active-site TKIs,” said Helen Collins, MD, Chief Medical Officer of Enliven. “With more patients enrolled and longer follow up, we continue to see anti-CML activity in a heavily pre-treated patient population that includes patients previously treated with asciminib. Additionally, ELVN-001’s safety profile remains consistent with its high selectivity, even with longer duration and more patients enrolled at higher dose levels. We believe the data demonstrate the potential clinical utility of ELVN-001 for patients across the full spectrum of the CML treatment paradigm.”

Patient Demographics

As of the cutoff date, June 25, 2024, 39 patients have been enrolled in the ongoing Phase 1 clinical trial across five dose levels of ELVN-001, ranging from 10 mg once daily (QD) to 120 mg QD, and the vast majority remain on study with a median treatment duration of 20 weeks.

Patients enrolled were heavily pretreated:
-2% of patients had ≥ 3 prior tyrosine kinase inhibitors (TKIs) and 25.6% had ≥ 5 prior TKIs.|
-8% of patients had received prior asciminib.
-2% of patients had discontinued their last prior TKI due to lack of efficacy.

Updated Efficacy

Of the enrolled patients, 18 with typical transcripts and without T315I mutations were evaluable for molecular response by 24 weeks.

ELVN-001 achieved a cumulative MMR rate of 44.4% (8/18) by 24 weeks.
-Among the 16 patients previously evaluated for efficacy, all 16 had stable or deepening responses between weeks 12 and 24.
-Among TKI-resistant patients, ELVN-001 achieved a cumulative MMR rate of 41.7% (5/12) by 24 weeks.
-Among post-asciminib patients, ELVN-001 achieved a cumulative MMR rate of 40.0% (4/10) by 24 weeks.
-Among patients that were not in MMR at baseline, 23.1% (3/13) achieved MMR by 24 weeks.

These data continued to compare favorably to precedent Phase 1 cumulative MMRs for approved BCR::ABL1 TKIs, particularly given the more heavily pre-treated patient population in the ELVN-001 clinical trial.

Updated Safety

ELVN-001 remains well-tolerated, consistent with its selective kinase profile.

A maximum tolerated dose has not been identified.

There have been no dose reductions and at ≥ 40 mg, no discontinuations due to treatment-emergent adverse events (TEAE).

There have been no ≥ Grade 3 non-hematologic treatment-related adverse events (TRAE), no specific non-hematologic TEAE of any grade occurred in >14% of patients, and no TRAE of any grade occurred in >11% of patients.

Hematologic adverse events observed remain consistent with those observed with the approved BCR::ABL1 TKIs.

“We are very pleased with how the ELVN-001 Phase 1 data is maturing,” said Sam Kintz, Co-founder and Chief Executive Officer of Enliven. “We are encouraged to see stable and deepening responses between weeks 12 and 24 and clinical benefit for almost every patient we’ve enrolled. Most importantly, now with 39 patients enrolled at time of cutoff, we continue to see an impressive safety and tolerability profile, which is especially important given the chronic nature of this disease. We also continue to be encouraged by the Scemblix launch and the 1L data that was presented at ASCO. We believe that Scemblix, an allosteric inhibitor, will soon become an important part of the early-line standard of care in CML, thereby heightening the need for a well-tolerated, active site BCR::ABL1 TKI and creating a great opportunity for ELVN-001.”

The Phase 1 clinical trial of ELVN-001 is a dose escalation and expansion trial designed to evaluate the safety and tolerability, and to determine the recommended dose for further clinical evaluation of ELVN-001 in patients with CML with and without T315I mutations that is relapsed, refractory or intolerant to TKIs. The primary endpoint of the trial is safety. Secondary endpoints include pharmacokinetics, MMR by central quantitative reverse transcriptase polymerase chain reaction, duration of MMR, BCR::ABL1 transcript levels and complete hematologic response.

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 chronic myeloid leukemia. As a highly selective active site inhibitor, ELVN-001 has a mechanism of action that is complementary to allosteric BCR::ABL1 inhibitors, which may play an increasingly important role in the standard of care. ELVN-001 was also designed to have activity against the T315I mutation, the most common BCR::ABL1 mutation, which confers resistance to nearly all approved TKIs as well as activity against mutations known to confer resistance to allosteric BCR::ABL1 inhibitors.

Enliven is a clinical-stage biopharmaceutical company focused on the discovery and development of small molecule therapeutics to help people with cancer not only live longer, but live better. Enliven aims to address existing and emerging unmet needs with a precision oncology approach that improves survival and enhances overall well-being. Enliven’s discovery process combines deep insights in clinically validated biological targets and differentiated chemistry to design potentially first-in-class or best-in-class therapies. Enliven is based in Boulder, Colorado.