Enliven Therapeutics Announces Positive Phase 1 Data and FDA Alignment for ELVN-001 in Chronic Myeloid Leukemia (CML)
Key Highlights from the ENABLE Phase 1 Clinical Trial
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Robust Clinical Results:
- 61% overall major molecular response (MMR) and 48% MMR achievement by 24 weeks in the 80 mg once daily cohort.
- 67% overall MMR and 55% MMR achievement by 24 weeks in all Phase 1b patients who had previously received 1 or 2 prior unique tyrosine kinase inhibitors (TKIs).
- Deep Molecular Response (DMR) rates were also encouraging, with 22% in overall Phase 1b and 30% in the 80 mg QD cohort achieving DMR by 24 weeks.
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Favorable Safety and Tolerability Profile:
- 161 patients enrolled, with a median treatment duration of 35 weeks.
- Most patients (76%) remain on study.
- ELVN-001 was generally well-tolerated, with 6% discontinuation due to adverse events.
- The majority of treatment-emergent adverse events (TEAEs) were Grade 1 or 2.
- At the biologically optimal dose of 80 mg QD, Grade ≥ 3 TEAEs were reported in 24% of patients, with thrombocytopenia (6%) being the only Grade ≥ 3 AE in more than 5% of patients.
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Heavily Pretreated Patient Population:
- 70% received three or more prior unique TKIs; 23% received five or more unique TKIs.
- 62% of patients had prior asciminib exposure, with these patients being more heavily pretreated.
- 8% of patients had mutations associated with resistance to allosteric inhibitors.
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FDA Alignment on Phase 3 Trial Design:
- 80 mg QD selected as the recommended dose for the ENABLE-2 pivotal Phase 3 trial.
- ENABLE-2 will enroll patients with CML previously treated with one or more TKIs and will be randomized to receive either ELVN-001 or physician’s choice of an ATP-competitive TKI.
- Further design details to be finalized after additional discussions with the FDA, including a planned End-of-Phase 2 meeting in Q3 2026.
- ENABLE-2 is expected to initiate in the second half of 2026.
Clinical and Regulatory Commentary
“Despite recent advances in CML treatment, there remains a need for highly effective therapies with excellent safety and tolerability profiles optimized for long-term treatment and capable of deep and durable molecular responses,” said Dennis Kim, M.D., Professor of Medicine at the Princess Margaret Cancer Centre, Canada. “The updated data from the ENABLE trial are very promising and encouraging, demonstrating meaningful responses across lines of therapy in heavily pretreated patients, including those refractory to the most effective approved therapies. ELVN-001’s favorable safety and tolerability profile, reflecting its high selectivity, could make it an important new treatment option for patients with previously treated CML.”
Helen Collins, M.D., Chief Medical Officer of Enliven, added: “These promising results continue to showcase ELVN-001’s consistent profile and reinforce its potential to be a best-in-class ATP-competitive inhibitor with differentiated activity relative to allosteric inhibitors. We observed higher response rates in earlier lines of therapy and comparable response rates regardless of prior asciminib exposure. The FDA alignment on our Phase 3 design is a major milestone as we advance towards initiating ENABLE-2 later this year.”
About ELVN-001 and the ENABLE Clinical Trial
- ELVN-001 is a potent, highly selective, and potentially best-in-class small molecule kinase inhibitor specifically targeting the BCR::ABL1 gene fusion — the oncogenic driver in CML.
- ELVN-001 has complementary activity to allosteric BCR::ABL1 inhibitors and was designed to have activity against the T315I mutation, which confers resistance to nearly all approved TKIs.
- The ENABLE study (NCT05304377) is a Phase 1 dose escalation and expansion trial evaluating safety, tolerability, and determining the recommended dose for further clinical evaluation in patients with CML, with and without T315I mutations, who are relapsed, refractory, or intolerant to TKIs.
- Secondary endpoints include pharmacokinetics, MMR by central quantitative reverse transcriptase polymerase chain reaction, duration of MMR, BCR::ABL1 transcript levels, and complete hematologic response.
Potential Price-Sensitive Information for Investors
- Positive Clinical Data: The updated Phase 1 results demonstrate robust efficacy and safety in a heavily pretreated population, including those refractory to other approved therapies. This strengthens ELVN-001’s potential as a future best-in-class therapy for CML.
- FDA Alignment: The FDA’s agreement on the recommended Phase 3 dose and patient population, and the anticipated initiation of the ENABLE-2 pivotal trial in the second half of 2026, are significant regulatory milestones that could accelerate clinical development and eventual commercialization.
- Market Opportunity: ELVN-001’s activity against the T315I mutation and mutations resistant to allosteric inhibitors positions it favorably in addressing unmet needs in the CML market.
- Risks: Investors should note risks including potential changes in interim clinical results, regulatory uncertainties, the possibility of adverse events, delays in trial enrollment or completion, and the lack of head-to-head data versus other therapies. The company has not performed any head-to-head trials for ELVN-001, so cross-trial comparisons are not valid.
- Next Steps: The company expects to finalize Phase 3 trial details with the FDA in Q3 2026, and will provide further updates as ENABLE-2 is initiated.
Investor Information
Enliven Therapeutics will host a webcast and conference call today at 8:30 a.m. ET / 2:30 p.m. CEST. Further details and the presentation slides will be available on the company’s investor relations website.
Contact:
Investors: [email protected]
Media: [email protected]
Disclaimer
This article contains forward-looking statements based on current information and management assumptions. These statements are subject to substantial risks and uncertainties, including those described in Enliven’s filings with the SEC under “Risk Factors”. Actual results may differ materially from those expressed or implied. Investors should not rely solely on this article for investment decisions and are encouraged to review official company filings and disclosures.
