Enliven Therapeutics’ ELVN-001 shows strong Phase 1 results in CML, with Phase 3 plans in 2026

Enliven Therapeutics Inc. (NASDAQ: ELVN), a clinical-stage American biotech company developing targeted oncology therapies, has reported updated Phase 1 data for its lead candidate ELVN-001 in patients with chronic myeloid leukemia (CML). The latest results were presented at the European Hematology Association (EHA) 2025 Congress in Milan on June 13 and underscore the therapy’s favorable efficacy and safety profile, even in a heavily pretreated population.

ELVN-001, a selective small molecule inhibitor targeting the BCR::ABL1 fusion gene, demonstrated a cumulative major molecular response (MMR) rate of 47% by 24 weeks. Of the 53 evaluable patients with typical BCR::ABL1 transcripts and without the T315I mutation, 25 achieved MMR, with all remaining in MMR at the data cutoff. The achieved MMR rate of 32% compares favorably with early clinical results of existing therapies like asciminib, positioning ELVN-001 as a potential next-generation therapy for CML.

ELVN-001 shows efficacy even in heavily pretreated patient cohorts

The ENABLE Phase 1 study (NCT05304377) enrolled 90 patients as of the April 28, 2025 data cutoff, evaluating ELVN-001 across a range of dose levels from 10 mg once daily to 80 mg twice daily. Approximately 67% of patients had been exposed to three or more prior TKIs, and 72% had discontinued previous treatment due to lack of efficacy. Despite this challenging baseline, ELVN-001 continued to deliver positive MMR outcomes. Among patients resistant to their last TKI, 41% achieved MMR by 24 weeks. Additionally, 35% of patients previously treated with asciminib or ponatinib also responded.

All patients who achieved or maintained MMR remained in MMR at the time of cutoff. These outcomes are especially significant given that previous Phase 1 trials for other BCR::ABL1 TKIs have reported lower MMR rates in less pretreated populations. The data presented at EHA 2025 indicate a potentially differentiated profile for ELVN-001, which could drive both clinical interest and future regulatory traction.

Safety and tolerability profile supports long-term use in CML

Given the chronic nature of CML treatment, long-term safety and patient adherence are critical considerations. According to Enliven Therapeutics’ Chief Medical Officer Dr. Helen Collins, ELVN-001 has been well-tolerated across all evaluated doses. Only 3.4% of patients required dose reductions due to treatment-emergent adverse events (TEAEs), and 4.6% discontinued due to AEs. Hematologic adverse events were consistent with or better than approved TKIs, and only two patients experienced ≥ Grade 3 non-hematologic treatment-related AEs.

Importantly, no arterial occlusive events or evidence of cardiovascular toxicity were observed, distinguishing ELVN-001 from prior-generation BCR::ABL1 inhibitors. The trial also did not reach a maximum tolerated dose, and no exposure-toxicity relationship was seen. This safety profile may enable greater dosing flexibility and improve long-term treatment adherence in clinical practice.

Expert sentiment highlights the therapy’s value proposition

Speaking at EHA 2025, Professor Andreas Hochhaus of Jena University Hospital emphasized that despite improved survival outcomes in CML, resistance and intolerance remain major clinical hurdles. He described the ELVN-001 results as “encouraging,” especially given the depth of response in patients who had exhausted multiple prior treatment lines. He also pointed to the compound’s tolerability and consistent MMR maintenance as potentially practice-changing attributes.

According to Enliven’s CEO Sam Kintz, ELVN-001 could offer best-in-class performance across all lines of therapy. Kintz noted that Phase 1 MMR data from other BCR::ABL1 inhibitors has historically been predictive of success in registrational trials, and expressed confidence in using molecular response as a regulatory endpoint for faster clinical development. The biotech firm expects to initiate a head-to-head Phase 3 pivotal trial in 2026.

Pharmacokinetics and drug interaction profile support ease of administration

ELVN-001’s pharmacokinetic profile supports once-daily oral dosing with no requirement for food co-administration, making it a convenient option for patients. The drug also exhibits low potential for interactions with other medications—a key benefit in CML, where patients are typically on multiple therapies. This favorable drug metabolism profile further enhances ELVN-001’s suitability for chronic use.

The investigational drug is also engineered to retain activity against the T315I mutation, a particularly problematic variant that confers resistance to nearly all current BCR::ABL1 inhibitors. This feature may broaden the therapy’s utility and support its inclusion in future combination regimens or sequencing strategies.

Investor sentiment and stock market response to clinical update

Following the EHA 2025 presentation, Enliven Therapeutics stock (NASDAQ: ELVN) showed moderate upside, closing at $22.46 on June 13, 2025, with an intraday high of $23.47 and a low of $18.75. This follows recent dilution concerns after a $200 million stock offering, which had temporarily pressured the share price. However, sentiment remains bullish as investors refocus on the clinical potential of ELVN-001.

Analyst consensus has trended positive, with multiple firms assigning Buy ratings and a mean price target in the range of $38–$40, representing a potential upside of 70–90%. GuruFocus reports an average 12-month target of $37.71, and TipRanks shows strong institutional interest. Over 52.7 million shares are currently held by institutional investors, including OrbiMed, BlackRock, Vanguard, and Polar Capital, with institutional holdings increasing slightly in the last quarter.

Short interest remains relatively high at ~24%, suggesting potential for a short squeeze if additional positive catalysts emerge. Enliven Therapeutics’ 1-year beta of 0.92 and weekly price volatility around 12% highlight ongoing investor sensitivity to trial updates and financing events.

Strategic outlook and trial roadmap through 2026

Looking forward, Enliven Therapeutics aims to finalize the recommended Phase 2 dose and complete patient enrollment across dose expansion cohorts. The company also plans to initiate a registrational Phase 3 trial by 2026, potentially targeting accelerated approval using MMR as a biomarker-driven endpoint.

Given the consistent efficacy seen in difficult-to-treat CML patients, and a favorable safety profile across dosing levels, ELVN-001 could enter late-stage development with a strong competitive narrative. Analysts expect that if upcoming trials confirm early results, Enliven may attract larger pharmaceutical interest, or consider strategic partnerships to support global development and commercialization.

Institutionally, sentiment remains positive but cautiously optimistic, as investors weigh the upcoming Phase 3 trial timeline against broader biotech volatility and capital market conditions. The company’s ability to navigate future financing needs while maintaining momentum on ELVN-001 will be critical to sustaining long-term shareholder confidence.

For retail and institutional investors, Enliven Therapeutics offers a compelling Buy-to-Hold opportunity. The Phase 1 data for ELVN-001 compares favorably to existing therapies and sets the stage for potential breakout success in late-line CML. With a clear regulatory pathway, growing institutional support, and upcoming pivotal trials, the oncology-focused biotech firm remains well-positioned for long-term upside.