Enliven Therapeutics, Inc. · NASDAQ:ELVN
Enliven Therapeutics — SOHO 2025
16 slides from Enliven Therapeutics's conference presentation, September 2025
Slide 1: ENABLE: A Phase 1a/1b Study of ELVN-001 in previously treated CML
• […] ENABLE: A Phase 1a/1b Study of ELVN-001, a selective active site inhibitor of BCR::ABL1, in patients with previously treated CML Michael Mauro1, Fabian Lang2, Dong-Wook Kim3, Dennis Kim4, Sebastian Kreil5, Philipp le Coutre6, Michael C. Heinrich7, Sarah Altmeyer8, Naranie Shanmuganathan9, Elv
Slide 2: Disclosures
Disclosures Dr. Michael Mauro • […] • Employment or leading position: n/a • Advisory role: Bristol Myers Squibb, Enliven, Novartis, Pfizer, Takeda, Terns • Share ownership: n/a • Honoraria: n/a • Research funding: Enliven, Novartis, Terns • Other financial relationship: n/a 2 SOHO 2025: September 3-
Slide 3: Why is There Still an Unmet Need in CML?
Why is There Still an Unmet Need in CML? Off-Target Toxicity imatinib • Available ATP-competitive TKIs have poor kinase nilotinib selectivity, resulting in off-target toxicity via KIT, FLT3, dasatinib PDGFRB, VEGFR2 and/or SRC1 bosutinib ponatinib Administration Limitations • Concomitant medication
Slide 4: ELVN-001: Highly Selective ATP-competitive Inhibitor of BCR::ABL1
ELVN-001: Highly Selective ATP-competitive Inhibitor of BCR::ABL1 • ELVN-001 binds to a unique P-loop “folded-in” active conformation in the ATP-binding pocket: • Provides greater selectivity than available ATP inhibitors, with potential for better tolerability • Creates a narrow tunnel allowing bin
Slide 5: ELVN-001: Broad Activity Against BCR::ABL1 Mutations
ELVN-001: Broad Activity Against BCR::ABL1 Mutations • ELVN-001 maintains activity against T315I and emerging BCR::ABL1 mutations known to confer resistance to asciminib • Emerging BCR::ABL1 mutations are predicted to require concentrations in a similar range to native BCR::ABL1 T315I M244V A337T E3
Slide 6: ELVN-001: Phase 1 Trial Design
ELVN-001: Phase 1 Trial Design Phase 1a Dose Escalationa: 3+3 Phase 1b Dose Expansion n = 20 each Total N ≈ 80 Key eligibility criteria: 80 mg BID 80 mg QD Completed Non-T315I Enrollment • Chronic phase CML 60 mg BID • Failed, intolerant to, or Phase 1b doses 120 mg QD 60 mg QD not a candidate for s
Slide 7: Patient Demographics and Baseline Characteristics
Patient Demographics and Baseline Characteristics All Patientsa All Patientsa Parameter Parameter (N = 90) (N = 90) Age, years, median (range) 58 (19–79) Median number of prior unique TKIs, n (range)e 3 (1–7) Male / female 58%/42% 1–2 prior 32% White / Asian / Black or African American / 70%/18%/1%/
Slide 8: Patient Disposition
Patient Disposition Total • 80% of patients remain on study with a Disposition (N = 90) median duration of exposure of 29 weeks Median duration of exposure, weeks (range) 29 (0.1–126) • 4 patients discontinued due to AEs: Ongoing, n (%) 72 (80.0%) • Alcoholic pancreatitis (10 mg QD) Discontinued, to
Slide 9: Duration on Study Treatment
Duration on Study Treatment Initial Dose Time on Study (weeks) 10mg QD 20mg QD • The majority of patients remain on study 40mg QD • 56% of patients have been on study 60mg QD > 24 weeks, with the longest ongoing at 126 weeks (~2.5 years) 80mg QD 120mg QD T315I Atypical transcript Re-enrolled 60mg BI
Slide 10: ELVN-001 had Favorable Safety and Tolerability Across Dose Levels
ELVN-001 had Favorable Safety and Tolerability Across Dose Levels Treatment Emergent Adverse Events (TEAEs) in ≥ 10% of Patients Total (N = 87) Preferred term n (%) Any Grade 3/4 • No Maximum Tolerated Dose identified Lipase increased 16 (18.4%) 1 (1.1%) • No dose-toxicity relationship observed Diar
Slide 11: Grade 3/4 TEAEs Were Uncommon and Not Dose-Dependent
Grade 3/4 TEAEs Were Uncommon and Not Dose-Dependent Grade 3/4 TEAEs Reported in ≥ 5% of Patients by Dose Level Preferred term 10−40 mg QD 60 mg QD 80 mg QD 120 mg QD 60−80 mg BID Total n (%) (n = 23) (n = 6) (n = 33) (n = 20) (n = 8) (N = 87a) Any Grade 3/4 event 5 (21.7%) 1 (16.7%) 8 (24.2%) 4 (20
Slide 12: ELVN-001 Pharmacokinetic Profile
ELVN-001 Pharmacokinetic Profile • ELVN-001 PK profile showed a fast absorption followed by a monophasic decline • ELVN-001 has linear PK, with both AUC and Cmax increasing approximately dose-proportionally from 10−120 mg • Half Life (t1/2 range 10−20 hours) in patients supports the QD regimen PK/PD
Slide 13: Encouraging Efficacy by 24 Weeks
Encouraging Efficacy by 24 Weeks BCR::ABL1 ≤ 0.1% (MMR) by 24 weeks BCR::ABL1 ≤ 1% by 24 weeks Overall MMR by 24 weeks 25/53 (47%) Overall ≤ 1% by 24 weeks 43/56 (77%) Achieved (not in MMR at baseline) 13/41 (32%) Achieved (not ≤ 1% at baseline) 14/27 (52%) Maintained (in MMR at baseline) 12/12 (100
Slide 14: BCR::ABL1 transcript by 24-weeks
98% (52/53) Patients with Improved or Stable MR Category Change in BCR::ABL1 Transcript in Patients Evaluable for MMR by 24 Weeks (n=53) Improvement in MR Category Baseline BCR::ABL1 transcript No Category change >MR4.5 MR4.5 MR4 MR3 Worsening in MR > 0.1 to 1 > 1 to 10 > 10 ≤ 0.0016 > 0.0016 to 0.0
Slide 15: Conclusions
Conclusions • ELVN-001, a novel active-site inhibitor of BCR::ABL1, had a favorable safety and tolerability profile in this phase 1 study − No MTD identified and no dose-toxicity relationship observed − Most TEAEs were low grade, with low rates of dose reductions and discontinuations due to TEAEs −
Slide 16: Acknowledgments
Acknowledgments Thank you to all investigators and site staff, to the patients and their families for their participation in the study, to the Enliven medical team and to Ingrid Koo, PhD, who provided editorial support. This study was funded by Enliven Therapeutics, Inc. 16 SOHO 2025: September 3-6,