Slide 1: Company Presentation: EHA Data Presentation
Company Presentation EHA Data Presentation June 13, 2025
Slide 2: Disclaimer
Disclaimer This presentation contains forward-looking statements that involve substantial risks and uncertainties of Enliven Therapeutics, Inc. (“Enliven” or the “Company”). All statements other than statements of historical facts contained in this presentation are forward-looking statements. Such f
Slide 3: Today’s Agenda
Today’s Agenda 1 Introduction 2 The Evolving Chronic Myeloid Leukemia (CML) Landscape & ELVN-001 Introduction 3 ELVN-001 Phase 1a/b Data Presented at EHA Congress 4 Next Steps for ELVN-001 5 Q&A 3
Slide 4: On Today’s Call
On Today’s Call Sam Kintz, M.B.A. Helen Collins, M.D. Damiette Smit, M.D. Co-founder, Chief Executive Officer Chief Medical Officer VP of Clinical Development of Enliven Therapeutics of Enliven Therapeutics of Enliven Therapeutics 4
Slide 5: ELVN-001: Well-positioned to Compete in a Large CML Market
ELVN-001: Well-positioned to Compete in a Large CML Market Large CML Market Unique and Differentiated Efficacy & Defined Opportunity Complementary Design Safety Profile Regulatory Path BCR::ABL1 TKIs have ELVN-001 is the only ELVN-001 efficacy, safety Phase 1 data predicted historically generated ~$
Slide 6: CML Landscape & ELVN-001 Introduction
CML Landscape & ELVN-001 Introduction
Slide 7: CML is Now a Long-Term Condition
CML is Now a Long-Term Condition As patients live longer on treatment, quality of life and tolerability have become important treatment goals CML 10-Year Survival Rate Over Time Estimated Prevalence of CML in the U.S. Over Time Number of CML Patients (k) 10-year survival rate >4x improved from Prior
Slide 8: Significant Need Remains for Better Treatment Options for CML
Significant Need Remains for Better Treatment Options for CML Challenges with Current Standard of Care Switching Dynamics Demonstrate Unmet Need • Growing 3L+ patient population (>25% of CP-CML) with limited Rationale for Switching Treatment Need for Better Options treatment options • All of the app
Slide 9: The CML Market is Large and Open to New Entrants
The CML Market is Large and Open to New Entrants as Demonstrated by the Strong Launch of Scemblix U.S. Branded CML Market has the Q4 2024 1L+ Approval Expanded Scemblix’s Addressable Potential to be ~$9B Based on Historical Sales Market by 4-5x and is Expected to Drive Significant Growth Majority of
Slide 10: ELVN-001 Well Positioned to Follow Scemblix in Future CML Paradigm
ELVN-001 is Well Positioned to Follow Scemblix in the Future CML Treatment Paradigm and Has Potential to Compete in 1L+ Limitations of Prior Generation TKIs Future Treatment Paradigm Market Insights & Assumptions (if data supports) (if data supports) • Asciminib (allosteric TKI) was recently approve
Slide 11: ELVN-001 is a Selective Active Site, Active Form Inhibitor of BCR::ABL1
ELVN-001 is a Selective Active Site, Active Form Inhibitor of BCR::ABL1 ATP-BINDING SITE BINDING Key Attributes of ELVN-001: DRUG CONFORMATION • Type 1 small molecule inhibitor of BCR::ABL1 ELVN-001 Active targeting the ATP-binding site of the ABL1 kinase domain that binds to a unique P-loop BOSUTIN
Slide 12: ELVN-001 is Highly Selective and Active Against Asciminib Emergent Mutations
ELVN-001 is Highly Selective and Active Against Asciminib Emergent Mutations ELVN-001 selectively inhibits ABL with low off-target activity ELVN-001 maintains activity against T315I and other BCR::ABL1 mutations against other kinases known to confer resistance to asciminib Cellular Phosphorylation I
Slide 13: ELVN-001 Clinical Focus and Target Product Profile
ELVN-001 Clinical Focus and Target Product Profile Our Opportunity Phase 1a/b: Dose Escalation in Late Line Status • Patients with CML who have exhausted all available • Currently treatment options enrolling Drive Deeper Improve Enhance Safety • Seek to demonstrate improved therapeutic window Phase
Slide 14: ELVN-001 Phase 1 Trial: April 2025 Data Snapshot
ELVN-001 Phase 1 Trial 28 April 2025 Data Snapshot
Slide 15: ENABLE (ELVN-001 Phase 1) Trial Design
ENABLE (ELVN-001 Phase 1) Trial Design Phase 1a: Dose Escalationb Phase 1b: Dose Expansion 60 mg QD Primary endpoints Non-T315I Enrolling n=20 • Incidence of dose limiting toxicities, adverse events, Key eligibility criteria: clinically significant • Chronic Phase 80 mg QD Completed laboratory and E
Slide 16: Baseline Characteristics: Heavily Pre-treated Patient Population Enrolled
Baseline Characteristics: Heavily Pre-treated Patient Population Enrolled Patient Demographics and Baseline Characteristics All Patientsa Parameter All Patients Parameter (N = 90) (N = 90) Age, years, median (range) 58 (19–79) Median number of prior unique TKIs e, n (range) 3 (1–7) Male / female, n
Slide 17: Patient Disposition: Majority of Patients Remain on Study
Patient Disposition: Majority of Patients Remain on Study Total • 80% of patients remain on study with a median Disposition (N = 90) duration of exposure of 29 weeks Median Duration of Exposure, weeks (range) 29 (0.1–126) • Four patients discontinued due to adverse events: Ongoing, n (%) 72 (80.0%)
Slide 18: ELVN-001 Median Duration of Exposure 29 Weeks
ELVN-001 Median Duration of Exposure 29 Weeks Initial Dose Time on Study (weeks) 10mg QD 20mg QD 40mg QD • Majority of patients remain on study • 56% of patients have been on study > 24 weeks 60mg QD with the longest 126 weeks (~2.5 years) ongoing • ≥ 40mg QD anticipated to have improved anti- 10 mg
Slide 19: Molecular Response Milestones
Molecular Response Milestones BCR::ABL1 Molecular Relevance Transcript Level Response ≤ 10% MR1 • Even in 3L+ setting insufficient for optimal survival • Equivalent to complete cytogenetic remission (absence of ≤ 1% MR2 Philadelphia chromosome) by bone marrow biopsy > 1 log reduction • ≥ MR3 is also
Slide 20: ELVN-001 24-Week Efficacy Data Continue to be Highly Encouraging
ELVN-001 24-Week Efficacy Data Continue to be Highly Encouraging Overall MMR (BCR::ABL1 ≤ 0.1%) by 24 weeks Overall MR2 (BCR::ABL1 ≤ 1%) by 24 weeks Overall MMR by 24 weeks 25/53 (47%) Overall MR2 by 24 weeks 43/56 (77%) Achieved (not in MMR at baseline) 13/41 (32%) Achieved (not in MR2 at baseline)
Slide 21: ELVN-001 Data Compares Favorably to Precedent Phase 1 Trials
ELVN-001 Data Compares Favorably to Precedent Phase 1 Trials Asciminib Phase 1 Bosutinib Phase 1 ELVN-001 Phase 1a (2019)1 (2012)2 2 30 (27%) 115 (97%) 22 (24%) Demographics 3 41 (36%) 3 (3%)b 16 (18%) (Prior TKIs) 4 32 (28%) 21 (23%) More heavily pre-treated patients ≥5 9 (8%) 23 (26%) Cumulative M
Slide 22: 98% of Patients with Improved or Stable MR Category by 24 Weeks
98% (52/53) Patients with Improved or Stable MR Category by 24 Weeks 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
Slide 23: MMR in Patient with Resistant CML with F359V Mutation
MMR in Patient with Resistant CML with F359V Mutation MMR by Day 90 @ 80 mg QD ELVN-001 Patient Background Relevant past None medical history Prior TKI therapy Nilotinib (discontinued due to lack of efficacy) (reason for switch) Mutations F359V Safety No adverse events reported Efficacy Major Molecu
Slide 24: ELVN-001 Well Tolerated with No Observed Dose-Toxicity Relationship
ELVN-001 Well Tolerated with No Observed Dose-Toxicity Relationship • Well-tolerated across all evaluated doses (10 mg QD to 80 mg BID) TEAEs (regardless of attribution) in ≥ 10% of patients • The majority of treatment emergent adverse events (TEAEs) Total (N = 87) were low grade Preferred term − He
Slide 25: Grade 3/4 TEAEs are Uncommon and Not Dose-Dependent
Grade 3/4 TEAEs are Uncommon and Not Dose-Dependent Grade 3/4 TEAEs (regardless of attribution) by Dose Level reported in ≥ 5% of patients 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) Subjects with any G3/4 5 (21
Slide 26: Summary of ELVN-001 Phase 1 Data
Summary of ELVN-001 Phase 1 Data • ELVN-001 has encouraging anti-CML activity in a heavily pre-treated patient population − 47% MMR rate by 24 weeks, with 32% achieving MMR (not in MMR at baseline) − 52% of those with a transcript >1% at baseline, achieved MR2 by 24 weeks − Efficacy observed in pati
Slide 27: Next Steps for ELVN-001
SS gZ Next Steps for ELVN-001 —_ a —_ ——— SO ee —_ Sy Ya
Slide 28: Phase 1 Data in Late Line CML Has Historically Predicted Regulatory Success
Phase 1 Data in Late Line CML has Historically Predicted Regulatory Success In precedent Phase 1 trials, achieved MMR rates have predicted performance in late-line pivotal trials Clear Translation from Phase 1 to Pivotal Trials (Cumulative Achieved MMR Rates by 24 weeks) • Achieved MMR rates in late
Slide 29: Precedent CML Pivotal Trials Establish Potential Path for ELVN-001
Precedent CML Pivotal Trials Establish Potential Path for ELVN-001 ASCEMBL: Resulted in 3L+ Approval ASC4FIRST: Resulted in 1L+ Approval MMR evaluation R 1:1 MMR evaluation R 2:1 Key Enrollment Criteria • Primary endpoint: n = 402 Asciminib Key Enrollment Criteria n = 233 Asciminib 40 mg • Primary e
Slide 30: Initial Pivotal Trial Options Provide Roadmap for ELVN-001
Initial Pivotal Trial Options Provide Roadmap for ELVN-001 Initial Pivotal Trial in either 3L+ or 2L+ Initiate 1L Pivotal Trial if ELVN-001 data continue to be supportive 3L+ Trial ELVN-001 vs. bosutinib • ASCEMBL precedent provides regulatory roadmap 1L Trial • Addresses large unmet need (this labe
Slide 31: ELVN-001 has Potential to Become Preferred TKI for Patients with CML
ELVN-001 has Potential to Become Preferred TKI for Patients with CML Large Market Opportunity Potential ~$9B opportunity for differentiated TKIs in the U.S. alone Recent successful Scemblix launch validates the need for better treatment options and with Evolving SoC its adoption in earlier lines of
Slide 32: Appendix
Appendix
Slide 33: ELVN-001 Safety Profile Consistent with High Selectivity for ABL1
ELVN-001 Safety Profile Consistent with High Selectivity for ABL1 Treatment Related Adverse Events in ≥ 5% of patients ELVN-001 Dose Group Total 10 mg to 40 mg QD 60 mg QD 80 mg QD 120 mg QD 60 and 80 mg BID (N = 87) (n = 23) (n = 6) (n = 33) (n = 20) (n=8) Preferred term n (%) Any Gr Gr 3+ Any Gr G
Slide 34: ELVN-001 Enrolled More Heavily Pretreated Patients than ASCEMBL
ELVN-001 Enrolled More Heavily Pretreated Patients than ASCEMBL ELVN-001 Asciminib Prior TKIs (N=90) (N=157) Median number of prior unique TKIs, n (range) 3 (1–7) 1 prior TKI, n (%) 7 (7.8%) 2 prior TKIs, n (%) 22 (24.4%) 89 (56.7%) 3 prior TKIs, n (%) 16 (17.8%) 53 (33.8%) ≥ 4 prior TKIs, n (%) 44
Slide 35: The Standard Clinical Endpoint in CML is Molecular Response
The Standard Clinical Endpoint in CML is Molecular Response • Measured by blood test and physical examination Hematologic • Normalization of white blood cell and platelet count without immature cells, 1 Response such as blasts, in peripheral blood • No signs or symptoms of disease, including resolut
Slide 36: Switching TKIs is Usually Due to Lack of Efficacy or Intolerance
Switching TKIs is Usually Due to Lack of Efficacy or Intolerance • Often used interchangeably with resistance or loss of efficacy, is assessed based on molecular parameters Lack of − 1L/2L: switching is recommended after failure to meet specific molecular milestones at 3, 6 and 12 Efficacy months, l
Slide 37: ELVN-001 in Patient with Asciminib-resistant CML with A337T Mutation
ELVN-001 in Patient with asciminib-resistant CML with A337T mutation MR5 post-Asciminib @ 40mg QD ELVN-001 Patient Background Relevant past Hyperlipidemia medical history Prior therapy Asciminib (LOE), ponatinib (LOE) (reason for switch) Mutations A337T and V506M (mutation detected locally) Safety G
Slide 38: Patient with BCR::ABL1 T315I (post-Ponatinib): Deep Response
Patient with BCR::ABL1 (atypical, e19a2), T315I (post-Ponatinib): Deep Response Achieved Deep Response in T315I 80 mg → 120 mg QD ELVN-001 Patient Background nilotinib Prior therapy nilotinib (LOE), dasatinib (LOE), ponatinib (LOE), asciminib (T315I) asciminib +/- ponatinib ponatinib (reason for swi
Slide 39: ELVN-001 Achieved Superior Target Coverage Compared to 2nd Gen TKIs
ELVN-001 Achieved Superior Target Coverage Compared to 2 nd Gen TKIs Cave Target Coverage vs. 1L MMR at 12 mo. Cave Target Coverage vs. Active Site TKIs (1L) Cave / K562 pCRKL IC50 100% human serum 10 8 Target Coverage at Cave 6 4 2 ~3x 0 D ID D D D D D Q B Q Q Q Q Q g g g g g g g 0m 0m 0m 0m 40 m 8
Slide 40: Superior Target Coverage vs 2nd Gen TKIs and Similar to Asciminib
ELVN-001 Achieved Superior Target Coverage Compared to 2 nd Gen TKIs and Similar Target Coverage Compared to Asciminib Cave Target Coverage vs. All TKIs (Late Line) Cave Target Coverage vs. Asciminib (Phase 1) Cave / K562 pSTAT5 IC90 PPB adjusted Cave / K562 GI50 PPB adjusted 8 Cave / K562 pSTAT5 IC
Slide 41: ELVN-001’s PK Profile Supports Once Daily Dosing
ELVN-001’s PK Profile Supports Once Daily Dosing with Flexible Administration Requirements 120 mg ELVN-001 (single dose) • Linear PK observed in healthy volunteers (HV) and patients 1000 − No time-dependent PK observed in either HVs or cancer Fasted patients Fed Plasma (ng/mL) − Both Cmax and AUC in
Slide 42: Poor Selectivity Limits Tolerability & Efficacy of 1st, 2nd & 3rd Gen Agents
Poor Selectivity Limits Tolerability & Efficacy of 1st, 2nd & 3rd Gen Agents Off Target(s) & Treatment-Emergent, Drug & Administration Peak Sales (USD) Compound 1L Efficacy Non-Hematologic Adverse Events (All Gr / Gr 3+) Requirements (US WAC in Peak Sales Year) 1st Gen c-KIT, Imatinib Peripheral Ede
Slide 43: The U.S. CML Market Has Historically Been Large and Has Potential to be Larger
The U.S. CML Market has Historically Been Large and has the Potential to be Larger In 2015, Global CML sales were $8B, with $4B from the U.S. alone $9B $9 $7B $7 $4B $4 2015 U.S. CML Sales WAC Adjusted Prevalence Adjusted Since 2015, the U.S. CML sales have on Since 2015, the weighted average WAC Si