Enliven Therapeutics, Inc. · NASDAQ:ELVN
Enliven Therapeutics — IMARA — Merger or Acquisition (October 2022)
45 slides from Enliven Therapeutics's merger presentation, Oct 13, 2022
Slide 1: Merger Announcement
Merger Announcement October 13, 2022 Exhibit 99.2
Slide 2: Disclaimer
Disclaimer About this Presentation For the purposes of this notice, the “presentation” that follows shall mean and include the slides that follow, the oral presentation of the slides by members of management of Imara Inc. (“Imara”) or Enliven Therapeutics, Inc. (“Enliven”) or any person on their beh
Slide 3: Merger with Imara Has the Potential to be Transformative for Enliven
Transition into a clinical-stage, precision oncology company with multiple shots on goal Merger with Imara Has the Potential to be Transformative for Enliven Enliven Therapeutics opportunity Provides Imara shareholders with opportunity to participate in the Enliven growth story, at a pivotal time fo
Slide 4: Merger of Enliven and Imara
Merger of Enliven and Imara Merger with Enliven, a privately held precision oncology company Strong balance sheet of approximately $300 million of cash and cash equivalents expected to provide funding for operations into early 2026 Upon close, company expected to be renamed “Enliven Therapeutics, In
Slide 5: The Enliven Story
The Enliven Story Supported by top tier healthcare investors and a strong balance sheet expected to provide cash runway into early 2026 Discovery process rooted in validated biology, differentiated chemistry, and disciplined trial design Capital-efficient approach on high potential programs aiming t
Slide 6: Leadership Team
Leadership Team Highly Distinguished & Industry-Leading Team with Top-Tier Advisors and Investors Joe Lyssikatos, PhD Co-founder and CSO Anish Patel, PharmD Co-founder and COO Helen Collins, MD CMO Sam Kintz, MBA Co-founder and CEO Board of the Directors Sam Kintz, MBA Enliven Therapeutics Joe Lyssi
Slide 7: Leadership Team with Broad Range of Experience and Success
Leadership Team with Broad Range of Experience and Success FDA-Approved Drugs Co-Invented by Enliven Chemists Primarily or co-invented over 20 product candidates that have advanced to clinical trials Led or been involved with the discovery, development, or commercialization of over 60 kinase inhibit
Slide 8: Pipeline & Discovery Programs
Pipeline & Discovery Programs Program Target Disease Differentiation Lead Optimization IND-Enabling Phase 1 Phase 2 Phase 3 Next Milestone Milestone Expected ELVN-001 BCR-ABL CML Highly selective w/T315I activity Early Phase 1 Data YE 2023 ELVN-002 HER2 & mutants NSCLC, other solid tumors EGFR spari
Slide 9: ELVN-001: Significant Need Remains for Better CML Treatment Options
ELVN-001: Despite Great Advances, a Significant Need Remains for Better Treatment Options for Chronic Myeloid Leukemia TKI = Tyrosine kinase inhibitors, HCP = Healthcare professional References: HCP Qualitative & Quantitative Interviews (ClearView); Hochhaus A et al. ASH 2015; Hochhaus A et al. Leuk
Slide 10: Evolving Chronic Myeloid Leukemia Market Dynamics
Evolving Chronic Myeloid Leukemia Market Dynamics Current Market Our Vision New drugs with better tolerability and efficacy profiles further drive increased switching rates and gain rapid adoption (similar to the HIV market) Additional focus from patients and doctors on deeper molecular responses (T
Slide 11: ELVN-001 Potentially Affords an Improved Therapeutic Index
ELVN-001 Potentially Affords an Improved Therapeutic Index MMR = Major molecular response. MTD = Maximum tolerated dose. NHP = Non-human primate 1Dasatinib was excluded from our analysis due to its short half-life in humans (3-5 hours), however early clinical responses correlated with dasatinib conc
Slide 12: Target Product Profile ELVN-001
Target Product Profile ELVN-001 Clinical Focus and Target Product Profile Progressed/Intolerant CP-CML Explore early LoT & combinations Seek to demonstrate improved efficacy (CCyR, MMR, MR4.5) and tolerability Single-arm study; precedent for approval in last line based on CCyR/MMR by 12m T315I mutat
Slide 13: ELVN-002: Opportunity for a Selective Irreversible Pan-Mutant HER2 TKI
ELVN-002: Opportunity for a Selective Irreversible Pan-Mutant HER2 TKI Current HER2 TKI Landscape Designed to irreversibly inhibit HER2 and multiple key HER2 mutations, including HER2 YVMA and L755, and Selectively inhibit HER2 while sparing EGFR to prevent EGFR-related toxicities, with the potentia
Slide 14: HER2 Mutant NSCLC May Provide More Rapid Market Entrance
HER2 Mutant NSCLC May Provide More Rapid Market Entrance Opportunity with Expansion into Other HER2-Driven Cancers to Follow *Other cancers include prostate, endometrial, gastric, stomach, hepatobiliary, etc. BRC = Breast cancer. GI = Gastrointestinal. NSCLC = Non-small cell lung cancer. MBC = Metas
Slide 15: ELVN-002 More Selective for HER2 YVMA Than Dual EGFR/HER2 Competitors
Current investigational dual EGFR/HER2 TKIs are roughly equipotent against EGFR and HER2 YVMA ELVN-002 was >100x More Selective for HER2 YVMA Relative to EGFR Than Dual EGFR/HER2 Competitors Lack of Differentiation Across Next Generation TKIs Neratinib Pyrotinib BDTX-189 Poor efficacy & tolerability
Slide 16: Target Product Profile ELVN-002
Target Product Profile ELVN-002 Clinical Focus and Target Product Profile Monotherapy in HER2-driven solid tumors Evaluate the safety in the combination with ADCs in HER2+ breast cancer and HER2 mutant NSCLC Single-arm study with potential to support accelerated approval 1L HER2 mutant NSCLC +/- SOC
Slide 17: ELVN-001 Potential Pivotal Studies and Near-term Clinical Milestones
ELVN-001 Potential Pivotal Studies Late line single arm T315I single arm ponatinib or asciminib intolerant / ineligible Early line H2H vs. Physician’s Choice 2H22 2022 ELVN-001 Ph1a initiation (completed) ELVN-002 IND filing ELVN-002 Ph1a initiation 1H23 2023 ELVN-001 Ph1 early clinical data 2H23 EL
Slide 18: ELVN-001 (BCR-ABL)
\. ELVN-001 (BCR-ABL) << oS SS
Slide 19: CML: A big success story for precision oncology, but needs remain
1985 BCR-ABL protein identified 1998 Imatinib FIH study initiated 1987 HTS yielded the discovery of STI-571 (imatinib) 2001 Imatinib approved 2006 Dasatinib approved 2007 Nilotinib approved 2012 Ponatinib and Bosutinib approved 2017 Emerging Treatment Goals (MR4.5, TFR) 2021 Asciminib 3L approval Ch
Slide 20: Significant Need Remains for More Treatment Options for CML
Significant Need Remains for More Treatment Options for CML Majority of HCPs (77%) indicated need for more effective, safe, and tolerable agents in CML Challenges with Current Standard of Care Rationale for Treatment Switching Intolerance ~30% Lack of response ~30% Loss of response (eg, >2 years pos
Slide 21: Poor Selectivity Limits Tolerability & Efficacy of 1st, 2nd & 3rd Gen Agents
Poor Selectivity Limits Tolerability & Efficacy of 1st, 2nd & 3rd Gen Agents Compound Company T315I Coverage Off Target(s) & Treatment-Related AEs BCR-ABL Coverage 1L Efficacy Drug & Administration Requirements 2021 FY Sales (USD) Imatinib (Gleevec®) Novartis X c-KIT, CSFR-1, PDGFR Myelosuppression:
Slide 22: Review of Asciminib (Scemblix), 4th Generation Allosteric TKI
Observations Review of Asciminib (Scemblix®), 4th Generation Allosteric TKI Approved in US based on 3L+ ASCEMBL Trial Strong launch & blockbuster sales projections in 3L+ alone demonstrate the size of the market (1L Ph3 readout 2024) ~30% discontinued due to lack of efficacy/AE by 48 wk ~50% discont
Slide 23: Evolving Chronic Myeloid Leukemia Market Dynamics
Evolving Chronic Myeloid Leukemia Market Dynamics Current Market Our Vision New drugs with better tolerability and efficacy profiles further drive increased switching rates and gain rapid adoption (similar to the HIV market) Additional focus from patients and doctors on deeper molecular responses (T
Slide 24: CML Treatment Paradigm and Market Insights
1st Gen TKI Imatinib 28% MMR 2nd Gen TKIs Nilotinib, Dasatinib, Bosutinib ~45% MMR 2nd Gen TKIs ~35% MMR 2nd Gen TKIs ~20-25% MMR Treatment Paradigm Market Insights Market Size (US) 2nd Gen TKIs = Nilotinib, Dasatinib, Bosutinib. MMR = Major Molecular Response at ~12 months. *Depending on patient po
Slide 25: Target Product Profile ELVN-001
Target Product Profile ELVN-001 Clinical Focus and Target Product Profile Progressed/Intolerant CP-CML Explore early LoT & combinations Seek to demonstrate improved efficacy (CCyR, MMR, MR4.5) and tolerability Single-arm study; precedent for approval in last line based on CCyR/MMR by 12m T315I mutat
Slide 26: ELVN-001 is a Selective Active Site, Active Form Inhibitor of BCR-ABL
ELVN-001 is a Selective Active Site, Active Form Inhibitor of BCR-ABL
Slide 27: ELVN-001 Has a Differentiated and Attractive Profile for CML
ELVN-001 Has a Differentiated and Attractive Profile for CML Asciminib Ponatinib Nilotinib ELVN-001 KCL-22 (BCR-ABLwt) cytotox IC50 (50% human serum) 7 nM 1 nM 90 nM 19 nM KCL-22 (BCR-ABLT315I) cytotox IC50 (50% human serum) >1,150 nM 14 nM > 10,000 nM 131 nM K-562 (BCR-ABLwt) cytotox IC50 (50% huma
Slide 28: ELVN-001 is Selective for ABL1
ELVN-001 is Selective for ABL1 Reference: Abl kinases are required for vascular function, Tie2, and angiopoietin-1-mediated survival. Pendergast et al. PNAS. 2013;110(30):12432-7. Cellular Phosphorylation IC50 (nM) Cellular Phosphorylation IC50 (nM) cKIT FLT3wt PDGFRb VEGFR2 cSRC ELVN-001 >10,000 >1
Slide 29: ELVN-001 Potentially Affords an Improved Therapeutic Index
ELVN-001 Potentially Affords an Improved Therapeutic Index MMR = Major molecular response. MTD = Maximum tolerated dose. NHP = Non-human primate 1Dasatinib was excluded from our analysis due to its short half-life in humans (3-5 hours), however early clinical responses correlated with dasatinib conc
Slide 30: ELVN-001 Clinical Development Strategy
ELVN-001 Clinical Development Strategy Phase 1 TRIAL CP-CML intolerant / resistant T315I mutation GOALS Demonstrate potential for efficacy superior to 2nd Gen TKIs (at least as good as asciminib & ponatinib) at well tolerated dose(s) Identify dose(s) for Phase 1b and beyond Phase 1b / 2 TRIAL Late l
Slide 31: ELVN-002 (HER2)
— LD \ ELVN-002 (HER2) —s = = < 2 Za <>
Slide 32: ELVN-002: Opportunity for a Selective Irreversible Pan-Mutant HER2 TKI
ELVN-002: Opportunity for a Selective Irreversible Pan-Mutant HER2 TKI Current HER2 TKI Landscape Designed to irreversibly inhibit HER2 and multiple key HER2 mutations, including HER2 YVMA and L755, and Selectively inhibit HER2 while sparing EGFR to prevent EGFR-related toxicities, with the potentia
Slide 33: HER2 Mutant NSCLC May Provide More Rapid Market Entrance
HER2 Mutant NSCLC May Provide More Rapid Market Entrance Opportunity with Expansion into Other HER2-Driven Cancers to Follow *Other cancers include prostate, endometrial, gastric, stomach, hepatobiliary, etc. BRC = Breast cancer. GI = Gastrointestinal. NSCLC = Non-small cell lung cancer. MBC = Metas
Slide 34: HER2 Mutant NSCLC Landscape: No Approved Selective TKIs
HER2 Mutant NSCLC Landscape: No Approved Selective TKIs Compound Company Stage MoA Selectivity vs. EGFRWT HER2mut NSCLC Efficacy Safety / Tolerability CURRENT & POTENTIAL FUTURE STANDARD OF CARE Platinum-doublet N/A N/A Chemo N/A ORR: ~25-35% mPFS: 4-7m Gr 3+ Neutropenia: 19% Nausea: 52% Constipatio
Slide 35: HER2 Breast Landscape: No Irreversible, Highly Selective TKI Option
HER2 Breast Landscape: No Irreversible, Highly Selective TKI Option Compound Company MoA Clinical Usage HER2+ BRC Efficacy Safety / Tolerability ANTIBODY DRUG CONJUGATES Enhertu (fam-trastuzumab deruxtecan) Daiichi Sankyo HER2-ADC topoisomerase payload 2L mPFS: NR (18.5-NE) ORR: 80% Gr 3+: Neutropen
Slide 36: Target Product Profile ELVN-002
Target Product Profile ELVN-002 Clinical Focus and Target Product Profile Monotherapy in HER2-driven solid tumors Evaluate the safety in the combination with ADCs in HER2+ breast cancer and HER2 mutant NSCLC Single-arm study with potential to support accelerated approval 1L HER2 mutant NSCLC +/- SOC
Slide 37: ELVN-002 Had Favorable Mutant Coverage Compared to Tucatinib
ELVN-002 Had Favorable Mutant Coverage Compared to Tucatinib Common HER2 Point Mutations HER2 Exon20 Insertion Mutations YVMA: 71% E20IM NSCLC 22% HER2mut BRC VC: 11% E20IM NSCLC Ba/F3HER2 Mutation Proliferation IC50 Fold over HER2 wt Ba/F3HER2 Mutation Proliferation IC50 [nM] Proliferation IC50 Fol
Slide 38: ELVN-002 Potently Inhibited HER2 & HER2 Mutants While Sparing EGFR
ELVN-002 Potently Inhibited HER2 & HER2 Mutants While Sparing EGFR Poziotinib Pyrotinib Tucatinib ELVN-002 BT474 HER2WT pHER2 IC50 3.5 13 12 13 Beas2b HER2S310F pHER2 IC50 1.9 2 16 2.8 Beas2b HER2L755S pHER2 IC50 4 3.5 99 4.7 Beas2b HER2YVMA pHER2 IC50 2.1 5 127 4.2 Beas2b HER2YVMA pHER2 IC50 in 100
Slide 39: ELVN-002 >100x More Selective for HER2 YVMA Relative to EGFR
Current investigational dual EGFR/HER2 TKIs are roughly equipotent against EGFR and HER2 YVMA ELVN-002 was >100x More Selective for HER2 YVMA Relative to EGFR Than Dual EGFR/HER2 Competitors Lack of Differentiation Across Next Generation TKIs Neratinib Pyrotinib BDTX-189 Poor efficacy & tolerability
Slide 40: ELVN-002 Robust Anti-Tumor Activity in Beas2b HER2 YVMA Xenograft Model
ELVN-002 Demonstrated Robust Anti-Tumor Activity in Beas2b HER2 YVMA Xenograft Model at Well-Tolerated Doses BID = Twice a day. MTD = Maximum tolerated dose. TGI = Tumor growth inhibition. QD = Once a day Tucatinib 300 mg BID (tablet) human AUCtau ~5,234 ng*hr/mL (NDA); mouse 100 mg/kg AUC ~143,600
Slide 41: ELVN-002 Robust CNS Anti-Tumor Activity in NCI-N87 Intracranial Model
ELVN-002 Demonstrated Robust CNS Anti-Tumor Activity in NCI-N87 HER2 amp Intracranial Model at Well-Tolerated Doses BID = Twice a day. QD = Once a day Tucatinib 300 mg BID (tablet) human AUCtau ~5,234 ng*hr/mL (NDA); mouse 50 mg/kg BID AUC ~47,300 ng*hr/mL (combined), mouse 75 mg/kg BID AUC ~123,000
Slide 42: ELVN-002 Anti-Tumor Activity & Additive Activity with Enhertu
ELVN-002 Demonstrated Robust Anti-Tumor Activity & Additive Activity in Combination with Enhertu at Well-Tolerated Doses ELVN-002 yielded deep tumor regressions in the NCI-N87 xenograft model, and all doses tested were well-tolerated Low dose ELVN-002 combined with Enhertu resulted in additive activ
Slide 43: ELVN-002 Achieved a Wide Safety Margin in Preclinical Species
ELVN-002 Achieved a Wide Safety Margin in Preclinical Species ELVN-002 28-day GLP Tox NHP TK ELVN-002 Safety Margin at NHP NOAEL Dose (mg/kg) Fold vs. Highly Efficacious Exposure Fold vs. Tucatinib TGI-matched exposure 5 2 5 10 5 12 15 8 22 NHP NOAEL Based on preclinical exposures (AUC), ELVN-002 ha
Slide 44: ELVN-002 Clinical Development Strategy
ELVN-002 Clinical Development Strategy Phase 1 TRIAL HER2 mutant (e.g., Exon 20 IM) HER2 amplified or overexpressed GOALS Demonstrate potential for efficacy at well tolerated dose(s) Identify dose(s) for Phase 1b and beyond Phase 1b / 2 TRIAL Late line HER2-mutant NSCLC Explore based on data Earlier
Slide 45: Thank You
\ Thank You