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EHA Data Presentation June 13, 2025 Company Presentation
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2 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 forward-looking statements include, among other things, statements regarding our future financial condition, business strategy and plans, objectives of management for future operations, statements regarding industry trends, the potential of, potential market opportunities for, and expectations regarding, ELVN-001, including expectations regarding the positioning of ELVN-001 with respect to other therapies; the expected milestones and timing of such milestones for ELVN-001, including the timing of the Phase 1 trial, the timing of the initiation of, and expectations regarding the design of and enrollment for, a Phase 3 head-to-head trial of ELVN-001; and statements regarding Enliven’s financial position, including its liquidity, cash runway and the sufficiency of its cash resources. In some cases, you can identify forward-looking statements by terminology such as “estimate,” “intend,” “may,” “plan,” “potentially” “will” or the negative of these terms or other similar expressions. We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things: the limited operating history of Enliven; the ability to advance product candidates through preclinical and clinical development; the ability to obtain regulatory approval for, and ultimately commercialize or license, or identify and complete strategic alternatives for product candidates; the outcome of preclinical testing and early clinical trials for product candidates and the potential that the outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, including extrapolations or predictions regarding the safety and efficacy of ELVN-001 based on comparisons to published results of trials of other products, which may be different when evaluated in head-to-head studies; Enliven’s limited resources; the risk of failing to demonstrate safety and efficacy of product candidates; Enliven’s limited experience as a company in designing and conducting clinical trials; the potential for interim, topline and preliminary data from Enliven’s preclinical studies and clinical trials to materially change from the final data; potential delays or difficulties in the enrollment or maintenance of patients in clinical trials; developments relating to Enliven’s competitors and its industry, including competing product candidates and therapies; the potential market opportunity for any of Enliven's programs; the decision to develop or seek strategic collaborations to develop Enliven’s current or future product candidates in combination with other therapies and the cost of combination therapies; the ability to attract, hire, and retain highly skilled executive officers and employees; the ability of Enliven to protect its intellectual property and proprietary technologies; the scope of any patent protection Enliven obtains or the loss of any of Enliven’s patent protection; reliance on third parties, including medical institutions, contract manufacturing organizations, contract research organizations and strategic partners; geopolitical developments, general market or macroeconomic conditions; and Enliven’s ability to obtain additional capital to fund Enliven’s general corporate activities and to fund Enliven’s research and development. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in documents that Enliven files from time to time with the Securities and Exchange Commission. These risks are not exhaustive. New risk factors emerge from time to time, and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, we undertake no obligation to update publicly any forward-looking statements for any reason after the date of this presentation. ELVN-001 is investigational only and has not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of ELVN-001 for the use for which it is being studied. Data presented for ELVN-001 and other agents are not based on head-to-head trials and are based on publicly available data, which include cross-trial and/or cross- phase data and information. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions, and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk.
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3 Q&A5 Today’s Agenda Introduction The Evolving Chronic Myeloid Leukemia (CML) Landscape & ELVN -001 Introduction ELVN-001 Phase 1a/b Data Presented at EHA Congress Next Steps for ELVN-001 1 2 3 4
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4 On Today’s Call Sam Kintz, M.B.A. Co-founder, Chief Executive Officer of Enliven Therapeutics Helen Collins, M.D. Chief Medical Officer of Enliven Therapeutics Damiette Smit, M.D. VP of Clinical Development of Enliven Therapeutics
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5 Large CML Market Opportunity Unique and Complementary Design Differentiated Efficacy & Safety Profile BCR::ABL1 TKIs have historically generated ~$6B of combined annual sales, despite generic options Potential $9B opportunity for differentiated TKIs in the U.S. alone, validated by successful Scemblix launch ELVN-001 is the only selective ATP-competitive BCR::ABL1 TKI and has activity against asciminib- resistant mutations PK supports QD dosing with or without food, and has low risk of DDIs ELVN-001 efficacy, safety and tolerability profile in late line CML compare favorably to approved BCR::ABL1 inhibitors despite a more heavily pretreated patient population Phase 1 data predicted performance in precedent registrational trials; biomarker endpoints allow for smaller , faster studies Expected to initiate first ELVN-001 head-to-head pivotal trial in 2026 Enliven has a strong balance sheet expected to provide cash runway into late 2027 ELVN-001: Well-positioned to Compete in a Large CML Market ATP = Adenosine triphosphate. BCR::ABL = Breakpoint cluster region-Abelson leukemia virus. CML = Chronic myeloid leukemia. DDI = Drug-drug interactions. QD = once daily. PK = Pharmacokinetics. TKI = Tyrosine kinase inhibitor. Note: U.S. CML market assumes branded pricing and is calculated based on historical sales while adjusting for current prevalence and pricing. References: public company filings and announcements. Conclusions from cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. ELVN-001 data reportedon June 13th, 2025. Defined Regulatory Path
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CML Landscape & ELVN-001 Introduction
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7 Maintain or improve quality of life CML is Now a Long-Term Condition As patients live longer on treatment, quality of life and tolerability have become important treatment goals Prior to imatinib, the annual CML survival rate was <20% 10-year survival rate improved from <20% to >80% CML 10-Year Survival Rate Over Time Estimated Prevalence of CML in the U.S. Over Time CML = Chronic myeloid leukemia. FIH = First-in-human. k = Thousands. TKI = Tyrosine kinase inhibitors. *For patients who have received two prior therapies. References: Huang X et al. Cancer. 2012;118:3213-3127. Kantarjian et al. Chronic Myeloid Leukemia, In: Harrison’s Principles of Internal Medicine, 2014. Lang et al, EHA 2023; Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring. Am J Hematol. 2024 Nov;99(11):2191-2212 • Prevalence is increasing globallywith expected overall survival approaching age-matched controls • CML has become a chronic disease that can require life-long TKI-treatment Top Treatment Goals for Physicians and Patients* Manageable side effects 1st 2nd ~110K ~450K 2020 2050 Number of CML Patients (k) >4x
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8 Significant Need Remains for Better Treatment Options for CML Challenges with Current Standard of Care Rationale for Switching Treatment Switching Dynamics Demonstrate Unmet Need • Growing 3L+ patient population (>25% of CP-CML) with limited treatment options • All of the approved ATP-competitive TKIs have poor kinase selectivity, resulting in tolerability issues that can impact efficacy • Long-term use of 2nd generation TKIs is associated with adverse events such as pleural effusions, GI and cardiovascular events • Adverse events, comorbidities, restrictions with concomitant medications, and specific administration requirements may impede long-term patient adherence ATP = Adenosine triphosphate. 1L = First line. 2L = Second line. 3L+ = Third line or later. 2nd generation TKIs = Nilotinib, Dasatinib, Bosutinib. CML = Chronic myeloid leukemia. CP-CML = Chronic phase CML. GI = Gastrointestinal. TFR = Treatment-free reemission. TKI = Tyrosine kinase inhibitor. HCP = Healthcare professional. EU3 = France, UK, Germany. References: HCP Qualitative & Quantitative Interviews (ClearView); Hochhaus A et al. ASH 2015; Hochhaus A et al. Leukemia. 2017; Kota V, et al. Presented at: ASH 2023; 31(7):1525-1531; Osorio S et al. Ann Hematol. 2018; 97(11):2089-2098; Rea et al. Blood. 2021; blood.2020009984; Baccarani M and Gale RP. Leukemia. 2021; 35:2199-2204; Iclusig® (ponatinib) USPI; Sprycel® (dasatinib) USPI; Tasigna® (nilotinib) USPI.; Bosulif® (bosutinib) USPI. ~30% of 2L patients switch therapy within 1st year of 2nd treatment Lack of Response Loss of response Intolerance Other 30% 30% 30% 35% 5% ~25% of 1L patients switch therapy within 1st year ~60% switch due to lack of response or intolerance in U.S. and EU3 Switching Rates Need for Better Options 77% of HCPs indicated need for more effective, safe, and tolerable agents <10% of patients achieve sustained treatment-free remission (TFR)
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9 $149 $413 $689 $952 2022 2023 2024 1Q25 Annualized Majority of Scemblix revenue generated to-date is from initial 3L+ approval The CML Market is Large and Open to New Entrants as Demonstrated by the Strong Launch of Scemblix 1L = First line. 2L = Second line. 3L+ = Third line and later. B = Billion. CML = Chronic myeloid leukemia. K = Thousand. WAC = Wholesale acquisition cost. Notes: Percent of patient breakdown by line of therapy is based on HCP Qualitative & Quantitative Interviews (ClearView) and extrapolated from the November 2023 Novartis R&D Investor Event; U.S. branded CML market calculated using total U.S. 2015 branded sales and adjusting those figures for the pricing of CML drugs today and today’s increased prevalence. $ in millions. The Scemblix launch may not be indicative of the potential success of any launch of ELVN-001. References: : Public company filings, announcements and research reports; Huang X et al. Cancer. 2012;118:3213-3127 1L: ~$4.3B-5.3B (55-65K patients) 2L: ~$2.4-3.5B (33-30K patients) 3L+: ~$1.3-1.8B (15-22K patients) U.S. Patient Population: ~110K U.S. Branded CML Market has the Potential to be ~$9B Based on Historical Sales Q4 2024 1L+ Approval Expanded Scemblix’s Addressable Market by 4-5x and is Expected to Drive Significant Growth U.S. Weighted Average WAC for Branded CML Drugs: ~$240K
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10 (if data supports) (if data supports) 1L Generic ATP- competitive TKI Allosteric TKI • Asciminib (allosteric TKI) was recently approved in 1L+ based on improved efficacy/tolerability • Opportunity for EL VN-001 to compete for 1L share based on potentially differentiated efficacy, tolerability or convenience 2L Allosteric TKI Allosteric TKI • ELVN-001 is potentially well positioned to follow asciminib given its unique binding mode and complementary MoA (ATP-site/active form vs. allosteric/inactive form) 3L+ ATP-competitive or Allosteric, based on patient need • Launch of asciminib has recently demonstrated the multi-billion-dollar opportunity in 3L+ for a a drug with improved efficacy & tolerability in late line CML ELVN-001 is Well Positioned to Follow Scemblix in the Future CML Treatment Paradigm and Has Potential to Compete in 1L+ 1L = First line. 2L = Second line. 2L+ = Second line or later. 3L+ = Third line or later. 2nd Gen TKIs = Nilotinib, Dasatinib, Bosutinib.ATP = Adenosine triphosphate. CML = Chronic myeloid leukemia. Gen = Generation. NBRx = New to brand prescription. MoA = Mechanism of action. TKI = Tyrosine kinase inhibitor. Note: Illustrative current and future treatment paradigm. Conclusions from cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. References: HCP Qualitative & Quantitative Interviews (ClearView). Public company filings and announcements. Future Treatment Paradigm Limitations of Prior Generation TKIs Safety / Tolerability Market Insights & Assumptions ELVN-001 ELVN-001 ELVN-001 3L+ 1L 2L Potential for Improved Efficacy & Safety/Tolerability Efficacy LOW HIGH LOW HIGH 2nd Gen TKIs Imatinib Selective TKIs EL VN-001 Asciminib In 1Q 2025 Novartis reported Scemblix NBRx of 40% in 2L and 10% in 1L in the U.S., further highlighting the need for improved treatment options across all lines of therapy
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11 • Type 1 small molecule inhibitor of BCR::ABL1 targeting the ATP-binding site of the ABL1 kinase domain that binds to a unique P-loop “folded-in” active conformation of ABL1 creating a narrow selectivity tunnel • Broad activity against multiple clinically important BCR::ABL1 mutations, including T315I, and those that confer resistance to asciminib • Unlike all the approved TKIs, ELVN-001 is not a substrate for the common drug efflux transporters, P-gp and BCRP, which may play a role in resistance to TKIs in CML • PK supports once daily dosing with or without food, and has low risk of DDIs ELVN-001 is a Selective Active Site, Active Form Inhibitor of BCR::ABL1 DRUG BINDING CONFORMATION ELVN-001 Active BOSUTINIB Active DASATINIB Active IMATINIB Inactive NILOTINIB Inactive PONATINIB Inactive ATP-BINDING SITE DRUG BINDING CONFORMATION ASCIMINIB Inactive MYRISTOYL POCKET Key Attributes of ELVN-001: ATP = Adenosine triphosphate. BCR::ABL1 = Breakpoint cluster region-Abelson leukemia virus 1. BCRP = Breast cancer resistance protein. CML = Chronic myeloid leukemia. DDI = Drug-drug interaction. P-gp = P-glycoprotein. PK = Pharmacokinetics. TKI = Tyrosine kinase inhibitor. References: Braun T. et al. Cancer Cell 2020 2020 Apr 13;37(4):530-542; Qiang W et al., Mechanisms of Resistance to the BCR-ABL1 Allosteric Inhibitor Asciminib; Leukemia 2017.
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12 ELVN-001 is Highly Selective and Active Against Asciminib Emergent Mutations 12 Fold-Shift from Native BCR::ABL1 T315I M244V A337T E355G F359C F359V P465S Asciminib 96 611 173 >2380 >2380 >2380 >2380 ELVN-001 4 2 1 4 3 2 2 Dasatinib 2935 2 1 3 4 2 2 Bosutinib 113 3 1 4 5 5 4 Ponatinib 3 2 1 3 5 5 2 Imatinib >20 3 1 8 18 10 4 Nilotinib >341 2 1 5 33 21 3 Antiproliferative activity of ELVN -001 vs. approved ABL TKIs in Ba/F3 cells harboring various BCR::ABL1 mutations BCR::ABL1 = Breakpoint cluster region-Abelson leukemia virus 1.IC50 = Half-maximal inhibitory concentration.nM = Nanomolar. TKI = Tyrosine kinase inhibitor. WT = Wildtype. Cell viability measured with CellTiter-Glo luminescent assay. Values expressed as fold-shift in IC50 from BCR::ABL1WT. References: Réa D and Hughes TP. Crit Rev Oncol Hematol. 2022;171:103580.; Qiang W et al. Leukemia. 2017;31(12):2844-2847.; Réa D et al. Blood. 2021;138:2031-2041. Cellular Phosphorylation IC50 (nM) cKIT FLT3wt PDGFRb VEGFR2 cSRC ELVN-001 >10,000 >10,000 >10,000 >10,000 >10,000 Ponatinib 30 3.8 89 4.8 630 Nilotinib 200 >10,000 720 2,900 >10,000 Dasatinib 0.6 >1,000 7.1 >1,000 10 Bosutinib 1,000 4,700 7,900 >10,000 16 Imatinib 82 >10,000 230 9,600 >10,000 Asciminib >10,000 >10,000 >10,000 >10,000 >10,000 Off-target kinase inhibition (IC 50) by ELVN-001 vs. approved ABL TKIs in cell -based assays ELVN-001 selectively inhibits ABL with low off-target activity against other kinases ELVN-001 maintains activity against T315I and other BCR::ABL1 mutations known to confer resistance to asciminib A337T and M244V were the most frequent emergent mutations to asciminib and F359C/V were the most frequent mutations at baseline in patients resistant to asciminib in ASCEMBL
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13 Target Product Profile ELVN-001 Clinical Focus and Target Product Profile • Patients with CML who have exhausted all available treatment options • Seek to demonstrate improved therapeutic window & efficacy (BCR::ABL1 transcript level reductions) in highly resistant/intolerant disease • Superiority to imatinib / 2G TKIs based on MMR at 48 weeks • Better overall tolerability, fewer dose reductions & discontinuations vs. approved agents • Superiority based on MMR at 24 weeks • Better overall tolerability, fewer dose reductions & discontinuations vs. approved agents Phase 1a/b: Dose Escalation in Late Line Future: 1L Pivotal Trial Initial Pivotal Trial (3L+ or 2L+) • Activity against native BCR::ABL1, T315I and asciminib-resistant mutations • Highly selective: No/minimal clinically relevant off-target toxicity • Efficacy: MMR greater than approved TKIs driven by an enhanced therapeutic window • Tolerability: Fewer dose reductions & discontinuations • Safety: No black box warnings; no edema, effusions, reduced GI toxicity • No restrictions with concomitant medications BCR::ABL1 = Breakpoint cluster region-Abelson leukemia virus 1. CCyR = Complete cytogenetic response. CML = Chronic myeloid leukemia. CP-CML = Chronic phase CML. GI = Gastronintestinal. H2H = Head-to-head. MMR = Major molecular response. mo = Month.MR = Molecular response. MR2 = BCR::ABL1 transcripts ≤ 1%. TKI = Tyrosine kinase inhibitor. Conclusions from cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. Our Opportunity Drive Deeper Responses Improve Tolerability Enhance Safety & Convenience Status • Currently enrolling Phase 1b • Phase 3 estimated 2026 start Status Status • After initial pivotal trial, potential to accelerate
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ELVN-001 Phase 1 Trial 28 April 2025 Data Snapshot
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15 ENABLE (ELVN-001 Phase 1) Trial Design BID = Twice daily. CML = Chronic myeloid leukemia. CP = Chronic phase. ECG = Electrocardiogram. MR = Molecular response. n = Number of patients. PK = Pharmacokinetics. QD = Once daily. qPCR =Quantitative reverse transcriptase polymerase chain reaction. Notes: Clinicaltrials.gov Identifier: NCT05304377. a. In the United States, S. Korea, Australia, EU; at least 2 prior therapies known to be active for treatment of their CML are required in Canada. b. Re-enrollment and intra-subject dose escalation allowed if meeting specific criteria. Dose TBD CP-CML with T315I mutations n=20 120 mg QD Non-T315I n=20 10 mg – 120 mg QD 60 mg – 80 mg BID n = up to ~80 Key eligibility criteria: • Chronic Phase CML (CP-CML) • Failed, intolerant to, or not a candidate for, available therapies known to be active for treatment of their CMLa Primary endpoints • Incidence of dose limiting toxicities, adverse events, clinically significant laboratory and ECG abnormalities Key Secondary endpoints • Molecular response (MR) by central qPCR • PK parameters 80 mg QD Non-T315I n=20 60 mg QD Non-T315I n=20 Completed enrollment Enrolling Enrolling Phase 1a: Dose Escalationb Phase 1b: Dose Expansion
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16 Baseline Characteristics: Heavily Pre-treated Patient Population Enrolled 16 Parameter All Patientsa (N = 90) Age, years, median (range) 58 (19–79) Male / female, n (%) 52/38 (57.8%/42.2%) Race White 63 (70.0%) Asian 16 (17.8%) Black or African American 1 (1.1%) Other or not reported 10 (11.1%) ECOG performance status 0/1 (%) 74%/26% Median time since diagnosis, months (range) 58.1 (2.6–281.9) Typical BCR::ABL1 transcript (e13a2 and e14a2) 84 (93.3%) Baseline BCR::ABL1 Transcript Levelb <=0.1% 15 (17.9%) >0.1% 63 (75.0%) BCR::ABL1 mutation at baseline (central)c , n (%) No mutation 49 (54.4%) T315I mutation 8 (8.9%)d Other mutation 6 (6.7%) Not available 27 (30.0%) 16 Parameter All Patients (N = 90) Median number of prior unique TKIse, n (range) 3 (1–7) 1 prior TKI, n (%) 7 (7.8%) 2 prior TKIs, n (%) 22 (24.4%) 3 prior TKIs, n (%) 16 (17.8%) 4 prior TKIs, n (%) 21 (23.3%) ≥ 5 prior TKIs, n (%) 23 (25.6%) Prior TKI, n (%) Dasatinib 66 (73.3%) Imatinib 60 (66.7%) Asciminib 52 (57.8%) Nilotinib 49 (54.4%) Ponatinib 39 (43.3%) Bosutinib 34 (37.8%) Reason for discontinuation of last TKI, n (%) Lack of efficacy 65 (72.2%) Lack of tolerability 21 (23.3%) Other 3 (3.3%) a Includes 3 re-enrolled patients (87 individual patients). b Percentages based on 84 patients with typical transcript. c Only available for patients with typical transcripts. Other mutations include: E255V, F359V, H375Y, M244V, P465L, L387M/M244V. d Includes 2 re-enrolled patients (6 individual patients with T315I). e Median lines of prior TKIs is 4 (range 1 -9). Patient Demographics and Baseline Characteristics BCR::ABL1 = Breakpoint cluster region-Abelson leukemia virus 1. TKI = Tyrosine kinase inhibitor. Data cutoff: 28 Apr 2025. Notes: Patients who had gone through intra-patient dose escalation as per protocol were counted under their initial treatment group only. 3 patients who were re-enrolled were counted under their initial treatment group and their re-enrolled treatment group.
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17 Patient Disposition: Majority of Patients Remain on Study Disposition Total (N = 90) Median Duration of Exposure, weeks (range) 29 (0.1–126) Ongoing, n (%) 72 (80.0%) Discontinued, T otal n (%) 18 (20.0%) Lack of efficacy 11 (12.2%)* Adverse Event 4 (4.4%) Death 1 (1.1%) Protocol violation 1 (1.1%) Withdrawal of consent 1 (1.1%) *3 of 11 patientsdiscontinued at lower doses, subsequently re-enrolled at higher dose levels; no patients progressed to blast crisis or acute leukemia • 80% of patients remain on study with a median duration of exposure of 29 weeks • Four patients discontinued due to adverse events: − Alcoholic pancreatitis (10 mg QD) − Thrombocytopenia (20 mg QD and 80 mg QD) − Dyspnea (80 mg QD; confounded by pulmonary comorbidities) • One patient died of a post-operative complication (after hip surgery; not related to study drug) QD = Once daily. Data cutoff: 28 Apr 2025. Notes: Patients who had gone through intra-patient dose escalation as per protocol were counted under their initial treatment group only. 3 patients who were re-enrolled were counted under their initial treatment group and their re-enrolled treatment group.
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18 x 10 mg QD 20 mg QD 40 mg QD 60 mg QD 80 mg QD 120 mg QD 60 mg BID 80 mg BID T315I Atypical Re-enrolled Discontinued 24w ELVN-001 Median Duration of Exposure 29 Weeks BID = Twice daily. CML = Chronic myeloid leukemia. QD = Once daily. TKI = Tyrosine kinase inhibitor. W = Weeks. Data cutoff: 28 Apr 2025. Notes: The protocol allows re-enrollment and intrasubject dose escalation, as shown by color. The swimmer plot does not include 2 patients that received their first ELVN-001 dose in June (these patients were included in the safety analysis as it was confirmed they received at least one dose of ELVN-001, but daily dosing information had yet to be provided at cutoff date). • Majority of patients remain on study • 56% of patients have been on study > 24 weeks with the longest 126 weeks (~2.5 years) ongoing • ≥ 40mg QD anticipated to have improved anti- CML activity compared to second generation TKIs based on target coverage Time on Study (weeks) 10mg QD 20mg QD 40mg QD 60mg QD 80mg QD 120mg QD 60mg BID 80mg BID Initial Dose 24w 48w 72w 96w 120w
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19 Molecular Response Milestones BCR::ABL1 Transcript Level Molecular Response Relevance ≤ 10% MR1 • Even in 3L+ setting insufficient for optimal survival ≤ 1% MR2 • Equivalent to complete cytogenetic remission (absence of Philadelphia chromosome) by bone marrow biopsy ≤ 0.1% MR3 • ≥ MR3 is also known as a major molecular response (MMR) • Has become a key regulatory endpoint as this predicts close to 100% CML-specific survival ≤ 0.01% MR4 • MR4/4.5 lasting ≥ 2 years has been used as a benchmark to stop treatment (typically in earlier line treatment), which is the ultimate goal ≤ 0.0032% MR4.5 ≤ 0.001% MR5 > 1 log reduction in BCR::ABL1 transcript levels is a meaningful indication of efficacy There is no standard definition of an acceptable response to third, fourth or fifth -line treatment 3L+ = Third line or later. CML = Chronic myeloid leukemia.Molecular response in CML is measured by the ratio ofBCR::ABL1/ABL1. References: Hochhaus, et al. Leukemia 2020; NCCN Guidelines 2.2024.
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20 ELVN-001 24-Week Efficacy Data Continue to be Highly Encouraging Data cutoff: 28 Apr 2025. Notes: Subjects who had gone through intra-subject dose escalation as per protocol were counted under their initial treatment group only. Subjects who were re-enrolled were summarized under the treatment groups they enrolled to with the corresponding data collected during the treatment episode, respectively. Subjects are included if they had baseline BCR::ABL1 transcript, and postbaseline assessment of BCR::ABL1 transcript at 24 weeks or achieved MMR/≤1% within 24 weeks or discontinued treatment before 24 weeks without achieving MMR /≤1%. For subjects with MMR /≤1% at baseline, only postbaseline assessments beyond 70 days will be included in the analysis. Overall MMR (BCR::ABL1 ≤ 0.1%) by 24 weeks Overall MMR by 24 weeks 25/53 (47%) Achieved (not in MMR at baseline) 13/41 (32%) Maintained (in MMR at baseline) 12/12 (100%) Key subgroups Post asciminib 9/28 (32%) Post ponatinib 7/20 (35%) Lack of efficacy to last TKI 14/34 (41%) Intolerant to last TKI 9/17 (53%) Overall MR2 (BCR::ABL1 ≤ 1%) by 24 weeks Overall MR2 by 24 weeks 43/56 (77%) Achieved (not in MR2 at baseline) 14/27 (52%) Maintained (in MR2 at baseline) 29/29 (100%) Robust efficacy profile despite heavily pretreated patient population, including in patients exposed to prior asciminib or ponatinib
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21 ELVN-001 Data Compares Favorably to Precedent Phase 1 Trials Asciminib Phase 1 (2019)1 Bosutinib Phase 1 (2012)2 2 30 (27%) 115 (97%) 22 (24%) 3 41 (36%) 3 (3%)b 16 (18%) 4 32 (28%) 21 (23%) ≥ 5 9 (8%) 23 (26%) Cumulative MMR 37/99 (37%) 16/105 (15%) 25/53 (47%) MMR Achievedc 19/80 (24%) 13/41 (32%) MMR Maintained d 18/19 (95%) 12/12 (100%) MMR in TKI-resistant patients 3/32 (9%) 3/54 (6%) 14/34 (41%) Time Frame by 24 weeks median follow-up 28.5 mo. by 24 weeks Demographics (Prior TKIs) Efficacy (Non-T315I) CML = Chronic myeloid leukemia. MMR = Major molecular response. Mo. = Month. TKI = Tyrosine kinase inhibitor. Data cutoff: 28 Apr 2025 Notes: MMR is defined as BCR::ABL1 ≤ 0.1%. a. MMR rates includes all evaluable patients treated who had typical BCR::ABL1 transcripts without T315I mutation b. Refers to ≥ 3 prior TKIs. c. MMR in patients with BCR::ABL1 transcript > 0.1% at baseline. d. MMR in patients with BCR::ABL1 transcript ≤ 0.1% at baseline. These data are derived from different clinical trials at different points in time, with differences in trial design and patient populations. As a result, conclusions from cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. References: 1. Hughes et al., NEJM 2019. 2. Khoury HJ et al. Blood. 2012. 3. Asciminib USPI. ELVN-001 Phase 1a Asciminib’s Phase 1 rate of MMR Achieved by 24 weeks (24%) predicted successful Phase 3 approval endpoint (25%)3 More heavily pre-treated patients 12/34 (35%) who had prior asciminib or ponatinib were in MMR by 24 weeks
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22 Baseline BCR::ABL1 transcript >MR4.5 ≤ 0.0016 (n = 1) MR4.5 > 0.0016 to 0.0032 (n = 0) MR4 > 0.0032 to 0.01 (n = 3) MR3 > 0.01 to 0.1 (n = 8) > 0.1 to 1 (n = 16) > 1 to 10 (n = 9) > 10 (n = 16) BCR::ABL1 transcript by 24-weeks >MR4.5 ≤ 0.0016 1 1 2 MR4.5 > 0.0016 to 0.0032 MR4 > 0.0032 to 0.01 2 1 1 MR3 > 0.01 to 0.1 6 5 4 2 > 0.1 to 1 10 3 2 > 1 to 10 1 > 10 1a 11 BCR::ABL1 = Breakpoint cluster region-Abelson leukemia virus 1. CML = Chronic myeloid leukemia. MR = Molecular response. Data cutoff: 28 Apr 2025. a. Worsening of transcript level from 6.3% at baseline to 13% after 4 weeks in patient with E255V mutation who previously discontinued asciminib and ponatinib due to lack of efficacy. Notes: >MR4.5 category assigned based on transcript level < limit of quantitation. Evaluable patients had baseline typical BCR::ABL1 transcript without T315I mutation and post-baseline assessment of BCR::ABL1 transcript at 24 weeks or achieved MMR within 24 weeks or discontinued treatment before 24 weeks without achieving MMR. For patients with MMR at baseline, only post-baseline assessments beyond 70 days were included in the analysis. • Improvement in transcript category was observed in patients independent of baseline transcript Worsening in MR category No Category change Improvement in MR Category Change in BCR::ABL1 Transcript in Patients Evaluable for MMR by 24 Weeks (n=53) 98% (52/53) Patients with Improved or Stable MR Category by 24 Weeks
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23 MMR in Patient with Resistant CML with F359V Mutation AE = Adverse event. LOE = Lack of efficacy. MMR = Major molecular response. MR = Molecular response. NA = Not applicable. QD = Once daily. Data cutoff: 28 Apr 2025. References: Rea et al., Blood(2021) 138 (21): 2031–2041. Patient Background Relevant past medical history None Prior TKI therapy (reason for switch) Nilotinib (discontinued due to lack of efficacy) Mutations F359V Safety No adverse events reported Efficacy Major Molecular Response F359C/V were the most frequent mutations at baseline in patients resistant to asciminib in ASCEMBL MMR by Day 90 @ 80 mg QD ELVN-001
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24 ELVN-001 Well Tolerated with No Observed Dose-Toxicity Relationship • Well-tolerated across all evaluated doses (10 mg QD to 80 mg BID) • The majority of treatment emergent adverse events (TEAEs) were low grade − Hematologic TEAE profile similar or better than other TKIs − Low frequency of non-hematologic TEAEs • Low number of dose adjustments due to TEAEs − 14 patients (16.1%) with dose interruptions − 3 patients (3.4%) with dose reductionsb − 4 patients (4.6%) with discontinuationsc • Maximum tolerated dose has not been identified • No exposure-toxicity relationship observed AE = Adverse event. BID = Twice daily. G = Grade. QD = Once daily. TEAE = Treatment-emergent adverse event. TKI = Tyrosine kinase inhibitor. Data cutoff: 28 Apr 2025. Notes: a. Combined term: platelet count decreased/thrombocytopenia. b. Dose reductions due to AE were: G3 Musculoskeletal pain in patient who discontinued 6 prior TKIs due to musculoskeletal or neuropathic pain (80 mg QD); G3 Arthralgia in patient who discontinued 2 prior TKIs due to intolerance (60 mg QD), G2 lumbar radicular pain in patient who discontinued 2 prior TKIs due to intolerance, including arthralgia and myalgia (60 mg QD). c. G2 alcoholic pancreatitis (10 mg QD), G3/4 platelet count decreased/thrombocytopenia (20 mg QD and 80 mg QD; both in patients who discontinued prior TKIs due to hematologic toxicities), dyspnea (80 mg QD; confounded by pulmonary comorbidities including sleep apnea, diffuse interstitial pneumonitis, pulmonary hypertension and obesity). Preferred term n (%) Total (N = 87) Any Grade 3-4 Lipase increased 16 (18.4%) 1 (1.1%) Diarrhea 13 (14.9%) 0 Thrombocytopeniaa 12 (13.8%) 6 (6.9%) Arthralgia 11 (12.6%) 1 (1.1%) Headache 11 (12.6%) 0 Fatigue 9 (10.3%) 0 Myalgia 9 (10.3%) 0 TEAEs (regardless of attribution) in ≥ 10% of patients
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25 Grade 3/4 TEAEs are Uncommon and Not Dose -Dependent 25 Preferred term n (%) 10 - 40 mg QD (n = 23) 60 mg QD (n = 6) 80 mg QD (n = 33) 120 mg QD (n = 20) 60 - 80 mg BID (n=8) Total (n=87a) Subjects with any G3/4 5 (21.7%) 1 (16.7%) 8 (24.2%) 4 (20.0%) 2 (25.0%) 20 (23.0%) Thrombocytopenia 2 (8.7%) 0 3 (9.1%) 0 1 (12.5%) 6 (6.9%) Neutropenia 4 (17.4%) 0 0 0 1 (12.5%) 5 (5.7%) • Only 2 patients (2.3%) reported Grade 3 AOEsb (no Grade 4 AOEs were reported); both patients had prior ponatinib and nilotinib and both events were considered unrelated to ELVN-001 per investigator. In addition, both patients remain on study. − One patient with a history of pericarditis, transient ischemic attacks, and cardiac chest pain reported angina pectoris; of note, the patient also discontinued prior nilotinib, ponatinib and asciminib due to persistent cardiovascular events (80 mg QD) − One patient with a history of high blood pressure and high cholesterol reported coronary artery disease (120 mg QD) AOE = Arterialocclusion event. BID = Twice daily. CPK = Creatinephosphokinase. G = Grade. SMQ = StandardizedMeDRA queries. TEAE = Treatment-emergentadverse event. QD = Once daily. Data cutoff: 28 Apr 2025 Notes: a. Patients with intra-subject dose escalation were counted under their initial treatment group only. Re-enrolled subjects were summarized at both dose levels with the corresponding data collected during each period, and once in the total column. b. AOEs were defined by SMQ search terms. Grade 3/4 TEAEs (regardless of attribution) by Dose Levelreported in ≥ 5% of patients
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26 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 patients exposed to prior asciminib or ponatinib, and with asciminib-emergent mutations • ELVN-001 was well tolerated across dose levels − No Maximum ToleratedDose identified and no dose-toxicity relationship observed − Most TEAEs were low grade, with low rates of dose reductions and discontinuations due to TEAEs − No evidence to date of increased cardiovascular toxicity • The ELVN-001 pharmacokinetic profile supports once daily dosing with or without food, which, in addition to low potential for drug-drug interactions, addresses key challenges with currently available TKIs
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Next Steps for ELVN-001
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28 15%* 24% 32% 12% 25% Bosutinib* Asciminib ELVN-001 Phase 1 ASCEMBL (Phase 3) (Cumulative Achieved MMR Rates by 24 weeks) CML = Chronic myeloid leukemia. MMR = Major molecular response. *Phase 1 bosutinib reported overall MMR with a median follow up of 28.5 months. MMR at 24 weeks in ASCEMBL was 25% and 13% for asciminib and bosutinib, respectively. Conclusions from cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. References: Rea et al. Blood. 2021; blood.2020009984; Khoury HJ et al. Blood. 2012;119(15):3403-3412. Asciminib USPI. Phase 1 Data in Late Line CML has Historically Predicted Regulatory Success • Achieved MMR rates in late line CML Phase 1 trial for asciminib and bosutinib predicted MMR rates at 24 weeks, the primary endpoint in ASCEMBL • ELVN-001’s data in late line CML has consistently compared favorably to precedent Phase 1 trials, despite enrolling more heavily pretreated patients Clear Translation from Phase 1 to Pivotal Trials ELVN-001’s Phase 1 Data Highly Encouraging On Track to Initiate First Pivotal Trial in 2026 In precedent Phase 1 trials, achieved MMR rates have predicted performance in late-line pivotal trials
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29 Precedent CML Pivotal Trials Establish Potential Path for ELVN-001 2G = 2nd generation TKIs - bosutinib, dasatinib or nilotinib. 1L+ = First line and later. 3L+ = Third line and later. B = Billion. CML-CP = Chronic myeloid leukemia in chronic phase. ELTS = EUTOS long-term survival. EUTOS = European Treatment and Outcome Study. MCyR = Major and complete cytogenic response. MMR = Major molecular response (BCR::ABL1IS ≤ 0.1%). n = Number of patients.R = Randomized. TKI = Tyrosine kinase inhibitor. References: Publicly available filings, announcements and research reports; Percent of patient breakdown by line of therapy is based on HCP Qualitative & Quantitative Interviews (ClearView) and the November 2023 Novartis R&D Investor Event; Huang X et al. Cancer. 2012;118:3213-3127; PriceRx; Assumes 2024 weighted average U.S. WAC of ~$240,000. Assumes current U.S. prevalence of ~110,000 based on American Journal of Hematology: Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring. Key Enrollment Criteria • Adults with CML-CP previously treated with ≥ 2 TKIs • Stratified by MCyR vs no MCyR at baseline Asciminib 40 mg twice daily n = 157 Bosutinib 500 mg once daily n = 76 R 2:1 n = 233 MMR evaluation • Primary endpoint: MMR at 24 weeks • Key secondary endpoint: MMR at 96 weeks • Protocol allowed for a crossover if a patient experienced a lack of efficacy Enrollment start Enrollment ends Topline data Approval Nov 2017 Dec 2019 May 2020 Oct 2021 Key Enrollment Criteria • Newly diagnosed patients with CML- CP • Stratified by pre- randomization selection of TKI (imatinib/2G TKI) and ELTS (high/ intermediate/low) Asciminib 80 mg once daily n = 200 Investigator selected (IS) TKI: imatinib (n = 102) 2G TKI (n = 102) R 1:1 n = 402 MMR evaluation • Primary endpoint: MMR at 48 weeks vs imatinib • Primary endpoint: MMR at 48 weeks vs IS TKI • Key secondary endpoint: MMR at 96 weeks Enrollment start Enrollment ends Topline data Approval Nov 2021 Dec 2022 Nov 2023 Oct 2024 ASCEMBL: Resulted in 3L+ Approval ASC4FIRST: Resulted in 1L+ Approval ~$1.3-1.8B U.S. market size 14-20% of patients 3L+ Market Opportunity ~$9B total U.S. market size ~4-5x larger patient population than just 3L+ 1L+ Market Opportunity
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30 Initial Pivotal Trial Options Provide Roadmap for ELVN-001 Initial Pivotal Trial in either 3L+ or 2L+ Decision 3L+ Trial ELVN-001 vs. bosutinib • ASCEMBL precedent provides regulatory roadmap • Addresses large unmet need (this label is the driver of asciminib’s ~$1B annualized revenue) 2L+ Trial ELVN-001 vs. Physician’s Choice (2G TKI, imatinib) • 2.5x larger patient population, ~50% of patients with CML • Larger trial, but potentially faster enrollment due to attractive comparator and larger patient population 1L Trial Comparator: EL VN-001 vs. 2G TKI & imatinib • 1L trial could replicate ASC4FIRST • Broad label: access to growing ~110K U.S. patient population • Could be designed to demonstrate potential differentiation compared to asciminib Initiate 1L Pivotal Trial if ELVN-001 data continue to be supportive Both options could provide valuable post-asciminib data Expected predictable and attractive timelines Success of recent launches demonstrates need for improved treatments options 2G = 2nd generation TKIs - bosutinib, dasatinib or nilotinib. 1L = First line. 2L+ = Second line and later. 3L+ = Third line and later. B = Billion. CML = Chronic myeloid leukemia. MMR = Major molecular response. TKI = Tyrosine kinase inhibitor. Note: “Predictable timelines” refers to the length of the recent CML pivotal trials (ASCEMBL and ASC4FIRST). References: Publicly available filings, announcements and research reports. Huang X et al. Cancer. 2012;118:3213-3127
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31 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 1L = First line.ATP = Adenosine triphosphate. B = Billion. CML = Chronic myeloid leukemia. DDI – Drug-drug interactions. PK = Pharmacokinetic. QD = Once daily. SoC = Standard of care. TKI = Tyrosine kinase inhibitor. Potentially Best-in-Class ELVN-001 efficacy, safety and tolerability Phase 1 data compare favorably to approved inhibitors, and PK supports QD dosing with or without food, and has low risk of DDIs Defined Regulatory Path Phase 1 data predicted performance in precedent registrational trials; biomarker endpoints allow for smaller , faster studies Next Steps On track to initiate first ELVN-001 head-to-head pivotal trial in 2026; opportunity to move to 1L & compete across lines of therapy based on differentiated efficacy, tolerability or convenience Evolving SoC Recent successful Scemblix launch validates the need for better treatment options and with its adoption in earlier lines of therapy, creates a need for a selective ATP -competitive TKI
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Appendix
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33 ELVN-001 Safety Profile Consistent with High Selectivity for ABL1 33 Preferred term n (%) EL VN-001 Dose Group Total (N = 87)10 mg to 40 mg QD (n = 23) 60 mg QD (n = 6) 80 mg QD (n = 33) 120 mg QD (n = 20) 60 and 80 mg BID (n=8) Any Gr Gr 3+ Any Gr Gr 3+ Any Gr Gr 3+ Any Gr Gr 3+ Any Gr Gr 3+ Any Gr Gr 3+ Subjects with Any Treatment Related Adverse Event 14 (60.9%) 3 (13.0%) 3 (50.0%) 1 (16.7%) 21 (63.6%) 4 (12.1%) 12 (60.0%) 1 ( 5.0%) 6 (75.0%) 0 56 (64.4%) 9 (10.3%) Lipase increased 3 (13.0%) 0 0 0 7 (21.2%) 0 3 (15.0%) 1 ( 5.0%) 2 (25.0%) 0 15 (17.2%) 1 (1.1%) Arthralgia 1 (4.3%) 0 1 (16.7%) 1 ( 16.7%) 3 (9.1%) 0 3 (15.0%) 0 0 0 8 (9.2%) 1 ( 1.1%) Thrombocytopenia* 3 (13.0%) 2 (8.7%) 0 0 3 (9.1%) 2 (6.1%) 0 0 1 (12.5%) 0 7 (8.0%) 4 (4.6%) Amylase increased 1 (4.3%) 0 0 0 3 (9.1%) 0 1 (5.0%) 0 2 (25.0%) 0 7 (8.0%) 0 Fatigue 0 0 1 (16.7%) 0 2 (6.1%) 0 2 (10.0%) 0 2 (25.0%) 0 7 (8.0%) 0 Myalgia 1 (4.3%) 0 0 0 2 (6.1%) 0 3 (15.0%) 0 0 0 6 (6.9%) 0 Neutropenia* 3 (13.0%) 3 (13.0%) 0 0 1 (3.0%) 0 0 0 1 (12.5%) 0 5 (5.7%) 3 (3.4%) Headache 1 (4.3%) 0 0 0 3 (9.1%) 0 1 (5.0%) 0 0 0 5 (5.7%) 0 Treatment Related Adverse Events in ≥ 5% of patients AE = Adverse events. Gr = Grade. QD = Once daily. Data cutoff: 28 Apr 2025. *combined terms: platelet count decreased/thrombocytopenia, neutrophil count decreased/ neutropenia Notes: Subjects who had gone through intra-subject dose escalation as per protocol were counted under their initial treatment group only. Subjects who were re-enrolled were summarized under the treatment groups they enrolled to with the corresponding data collected during the treatment episode, and counted as one subject in total respectively
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34 ELVN-001 Enrolled More Heavily Pretreated Patients than ASCEMBL Prior TKIs ELVN-001 (N=90) Asciminib (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 (48.9%) 15 (9.6%) Prior Lines of TKI Therapy ELVN-001 (N=90) Asciminib (N=157) Median number of lines of TKI therapy, n (range) 4 (1–9) 1 prior line, n (%) 6 (6.7%) 2 prior lines, n (%) 21 (23.3%) 82 (52.2%) 3 prior lines, n (%) 13 (14.4%) 44 (28.0%) 4 prior lines, n (%) 18 (20.0%) 24 (15.3%) ≥ 5 prior lines, n (%) 31 (34.4%) 7 (4.5%) Notable Prior TKIs ELVN-001 (N = 90) ASCEMBL –asciminib (N=157) Asciminib 52 (57.8%) - Ponatinib 39 (43.3%) 23 (14.6) Reason for discontinuation of last TKI, n (%) Lack of efficacy 65 (72.2%) 95 (60.5) More heavily pretreated patient population in ENABLE vs. asciminib in ASCEMBL Data cutoff date: 28 Apr 2025 Conclusions from cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. References: Rea D et al., Blood. 2021. Hochhaus et al, Leukemia. 2023
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35 • Measured by blood test and physical examination • Normalization of white blood cell and platelet count without immature cells, such as blasts, in peripheral blood • No signs or symptoms of disease, including resolution of palpable splenomegaly The Standard Clinical Endpoint in CML is Molecular Response Hematologic Response Cytogenetic Response Molecular Response 1 2 3 • Best measured by bone marrow sample • Percent of bone marrow cells with Philadelphia chromosome by FISH/karyotype (cytogenetic test) • Measured by blood test • Number of copies of the BCR::ABL1 transcript in blood (qPCR) • Evolving into the standard of care in assessing treatment response in CML CML = Chronic myeloid leukemia. FISH = Fluorescence in situ hybridization. qPCR =Quantitative reverse transcriptase polymerase chain reaction. References: Hochhaus et al. Leukemia 2020.
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36 Switching TKIs is Usually Due to Lack of Efficacy or Intolerance 1L = First line. 2L= Second line. 3L+ = Third line or later. CML = Chronic myeloid leukemia. TKI = Tyrosine kinase inhibitor. MMR = Major molecular response. References: 1. Hochhaus, NEJM 2018; 2. Hochhaus Leukemia 2020; 3. Saxena 2021 J. of Heme Onc; 4. Ibrahim, 2011 Bood; 5. Hehlmann 2014 JCO. Treatment goal for late-line patients is often to achieve MMR and/or maintain MMR with a good quality of life Lack of Efficacy (LOE) Intolerance Disease Progression • Often used interchangeably with resistance or loss of efficacy, is assessed based on molecular parameters − 1L/2L: switching is recommended after failure to meet specific molecular milestones at 3, 6 and 12 months, loss of an already achieved milestone (e.g., loss of MMR), or development of resistance mutations or high-risk chromosomal abnormalities − 3L+: no standard recommendation of when to switch therapies • Inability to take TKI due to side effects that do not respond to dose reduction or medical management − Hematologic side effects, such as cytopenias (low blood cell counts), occur with all TKIs and are rarely a cause of treatment changes − Non-hematologic side effects are the most common reason to switch (due to medical necessity or reduction in quality of life) • Tolerability is an increasingly important consideration as therapy is often lifelong and multiple TKIs are available • Progression to blast crisis, which is rare in CML, and is associated with a change in the treatment paradigm
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37 ELVN-001 in Patient with asciminib-resistant CML with A337T mutation 1L = First line. G1 = Grade 1. QD = Once daily. LOE = Lack of efficacy. MR = Molecular response. R = Related to ELVN-001 per investigator. Notes: Mutation data not confirmed by central lab (transcript level too low at baseline). Data extracted as of18 March 2024; data from ongoing study-may change. References: Rea et al., Blood(2021) 138 (21): 2031–2041. Patient Background Relevant past medical history Hyperlipidemia Prior therapy (reason for switch) Asciminib (LOE), ponatinib (LOE) Mutations A337T and V506M (mutation detected locally) Safety G1 rash (R) resolved by day 28 on study Efficacy Molecular response = MR5 A337T was the most common clinically emergent mutation that conferred resistance to asciminib on ASCEMBL MR5 post-Asciminib @ 40mg QD ELVN-001
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38 BCR::ABL1 = Breakpoint cluster region-Abelson leukemia virus 1. G1 = Grade 1. LOE = Lack of efficacy. MR = Molecular response. QD = Once daily. TKI = Tyrosine kinase inhibitor. Notes: A deep response is defined as a 4-log-reduction. Data as of12 July 2024 (after latest data cutoff), based on a local laboratory (non-International System) as reported by the study investigator. Resistant to 4 prior TKIs, deep response on ELVN -001 Patient Background Prior therapy (reason for switch) nilotinib (LOE), dasatinib (LOE), ponatinib (LOE), asciminib (LOE) and ponatinib + asciminib combination (LOE) Mutations T315I Safety G1 dry skin Efficacy >1-log decrease Achieved Deep Response in T315I 80 mg → 120 mg QD EL VN-001 nilotinib dasatinib (T315I) ponatinib ELVN-001 80 mg 120 mg transcript levels on dasatinib not available Sensitivity asciminib +/- ponatinib Sensitivity Patient with BCR::ABL1 (atypical, e19a2), T315I (post -Ponatinib): Deep Response
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39 ELVN-001 Achieved Superior Target Coverage Compared to 2nd Gen TKIs At doses ≥ 40mg QD, ELVN-001 achieved better target coverage compared to 2nd Generation TKIs Cave Target Coverage vs. 1L MMR at 12 mo. Cave Target Coverage vs. Active Site TKIs (1L) 1L = First line. 2nd Gen TKIs = bosutinib, dasatinib, nilotinib. Cav e = Average concentration. CRKL = Crk-like protein. IC50 = Half-maximal inhibitory concentration.MMR = Major molecular response. QD = Once daily. TKI = Tyrosine kinase inhibitor. References: 1. Imatinib clin pharm in CML pts: Peng et al, Clin Pharmacokinet 2005. 2. Imatinib NDA. 3. Nilotinib USPI. 4. Dasatinib USPI. 5. Bosutinib USPI. MMR References: (Bosutinib) Cortes JE et al. J Clin Oncol. 2012; 30(28):3486-92; (Nilotinib and Imatinib) Saglio G et al. NEJM. 2010; 362(24):2251-9; (Dasatinib) Kantarjian H et al. NEJM, 2010; 362(24):226. Notes: Cav e = Area under the curve (AUC) divided by 24 hours. For the approved drugs, human pharmacokinetic (PK) values were obtained from population PK (popPK) simulation data reported in respective USPIs or from Ref 1 (imatinib). ELVN-001 human PK values are the mean values from a preliminary popPK simulation based on PK from 78 healthy volunteer subjects; to date, there has been no significant difference between ELVN-001 PK in cancer patients and healthy subjects. In vitro cell pharmacodynamic measurements were performed head-to-head and represent the average value from multiple experiments (n≥3). K562 cells were employed for these experiments. pCRKL IC50 measurements were performed in the presence of 100% human serum. Imatinib 400mg QD Nilotinib 300mg BID Dasatinib 100mg QD Bosutinib 400mg QD ELVN-001 40mg QD ELVN-001 80mg QD ELVN-001 120mg QD 0 2 4 6 8 10 Target Coverage at Cave Cave / K562 pCRKL IC50 100% human serum ~3x
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40 ELVN-001 Achieved Superior Target Coverage Compared to 2nd Gen TKIs and Similar Target Coverage Compared to Asciminib Cave Target Coverage vs. All TKIs (Late Line) Cave Target Coverage vs. Asciminib (Phase 1) 2nd Gen TKIs = bosutinib, dasatinib, nilotinib. BID = Twice daily. Cav e = Average concentration. GI50 = 50% growth inhibition. IC90 = 90% inhibitory concentration. QD = Once daily. CML = Chronic myeloid leukemia. CRKL = CRK-like protein. PPB = Plasma protein binding. STAT5 = Signal transducer and activator of transcription 5. TKI = Tyrosine kinase inhibitor. Notes: Cave = Area under the curve (AUC) divided by 24 hours. For the approved drugs, human pharmacokinetic (PK) values were obtained from population PK (popPK) simulation data reported in respective USPIs or from Ref 1 (imatinib) and Ref 6 (asciminib Phase 1). ELVN-001 human PK values are the mean values from a preliminary popPK simulation based on PK from 78 healthy volunteer subjects; to date, there has been no significant difference between ELVN-001 PK in cancer patients and healthy subjects. Human plasma protein binding values were obtained from the respective NDAs or measured in house (ELVN-001). In vitro cell pharmacodynamic measurements were performed head-to-head and represent the average value from multiple experiments (n≥3). K562 cells were employed for these experiments. pSTAT5 IC90 and GI50 measurements were performed in 10% FBS and the values were adjusted to account for human plasma protein binding by dividing by the unbound fraction for each drug. References: 1. Imatinib clin pharm in CML pts: Peng et al, Clin Pharmacokinet 2005. 2. Imatinib NDA. 3. Nilotinib USPI. 4. Dasatinib USPI. 5. Bosutinib USPI. 6. Hughes TP et al. NEJM. 2019;381(24):2315-2326. 7. Asciminb NDA. Asciminib 40mg BID Phase 1 ELVN-001 80mg QD 0 2 4 6 Target Coverage at Cave Cave / K562 GI50 PPB adjusted Cave / K562 pSTAT5 IC90 PPB adjusted • Novartis referenced preclinical 90% inhibitory concentration for phosphorylated STAT5 or pSTAT5 IC90 and anti-proliferation GI50 as the key target coverage metrics supporting an optimal asciminib dose of 40 mg BID or 80 mg QD for CML patients without T315I mutations • ELVN-001 had better target coverage based on plasma protein binding adjusted pSTAT5 IC90 at ≥ 40 mg QD compared to 2nd Gen TKIs, and similar target coverage as asciminib at 80 mg QD Imatinib 400mg QD Nilotinib 400mg BID Dasatinib 100mg QD Bosutinib 500mg QD Asciminib 40mg BID (Ph 1) ELVN-001 40mg QD ELVN-001 80mg QD ELVN-001 120mg QD 0 2 4 6 8 Target Coverage at Cave Cave / K562 pSTAT5 IC90 PPB adjusted 2nd Gen TKIs
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41 ELVN-001’s PK Profile Supports Once Daily Dosing with Flexible Administration Requirements • Linear PK observed in healthy volunteers (HV) and patients − No time-dependent PK observed in either HVs or cancer patients − Both Cmax and AUC increased dose-proportionally − High concordance between HV and patient PK based on current data • Fast and complete absorption with no significant food effect • Mean terminal t1/2 is ~12 hours in healthy volunteers − Similar effective t1/2 observed in patients (10-20 hours) − Suitable for QD regimen • Minimal risk of drug-drug interactions (DDIs) − Not an inhibitor (competitive or time-dependent) or inducer of major CYP enzymes, or of UGT1A1 − Not a substrate for major CYP enzymes − Not a substrate of BCRP or P-gp • No correlation between AEs and PK parameters in patients • Food effect study at 120mg single dose in HVs showed that: − AUCinf under fasting conditions were similar to that under fed conditions, with a fed/fasted AUC ratio of 1.2. − Cmax under fasting conditions were similar to that under fed conditions, with a fed/fasted Cmax ratio of 0.8. AEs = Adverse events. AUC = Area under the curve. AUCinf = AUC extrapolated to infinity. BCRP = Breast cancer resistance protein. Cma x = Maximum serum concentration. CYP = Cytochromes P450. DDI = Drug-drug interactions. HV = Healthy volunteers. P-gp = P-glycoprotein. PK = Pharmacokinetics.QD = Once daily. t1/2 = Half life. UGT1A1 = UDP Glucuronosyltransferase Family 1 Member A1. 0 5 10 1 10 100 1000 Time (h) Plasma (ng/mL) Fasted Fed 120 mg ELVN-001 (single dose)
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42 Poor Selectivity Limits Tolerability & Efficacy of 1st, 2nd & 3rd Gen Agents A selective BCR-ABL inhibitor could yield enhanced target coverage, leading to greater efficacy and better long-term tolerability 1L = Front line. B = Billion. Gen = Generation. GI = Gastrointestinal. Gr = Grade. FY = Fiscal Year. K = Thousands. . M = Millions. MMR = Major Molecular Response. MR4.5 = Deep Molecular Response. PPI = Proton pump inhibitors. STAMP = Specifically targeting the ABL myristoyl pocket. MMR and MR4.5 at 12 months. VTE = Venous thromboembolism. WAC = Wholesale acquisition cost. Notes: Numbers in the billions have been rounded to the 1/10th of a billion and sales numbers in the millions have been rounded to the nearest $10 million increment from Company Investor Reports. Iclusig sales calculated using the latest available information by region for the 4 trialing quarters; Iclusig Japan sales reported by Otsuka are as of 2020. References: Publicly available filings, announcements and research reports; Gleevec® (imatinib) USPI; Sprycel® (dasatinib) USPI; Kantarjian H et al. NEJM, 2010; 362(24):2260-70; Cortes JE et al. J Clin Oncol. 2016; 34(20):2333-40; Tasigna® (nilotinib) USPI; Saglio G et al. NEJM 2010; 362(24):2251-9; Hochhaus A et al. Leukemia. 2016; 30(5):1044-54; Bosulif® (bosutinib) USPI. Cortes JE et al. J Clin Oncol, 2012; 30(28):3486-92; Iclusig® (ponatinib) USPI; Scemblix® (asciminib) USPI. Hochhaus A et al. NEJM, 2024; 391(10):885-898. Compound Off T arget(s) & Treatment-Emergent, Non-Hematologic Adverse Events (All Gr / Gr 3+) 1L Efficacy Drug & Administration Requirements Peak Sales (USD) (US WAC in Peak Sales Year) Imatinib (Gleevec®) c-KIT, CSFR-1, PDGFR Peripheral Edema (20% / 0%) Nausea (41% / 2%) 28% MMR 3% MR4.5 Avoid strong CYP3A inhibitors or inducers $4.7B $120K (2014) Dasatinib (Spyrcel®) SRC family, c-KIT, PDGFR-αβ Fluid Retention (38% / 5%) Pleural Effusions (28% / 3%) Diarrhea (22% / 1%) 46% MMR 5% MR4.5 Avoid strong CYP3A inhibitors or inducers, PPIs, antacids, and H2 blockers $2.2B $190K (2022) Nilotinib (Tasigna®) c-KIT, PDGFR, CSFR-1, DDR-1 (hERG Channel) Rash (38% / <1%) Headache (32% / 3%) Nausea (22% / 2%); Diarrhea (19% / 1%) Black Box: QT Prolongation/Sudden Deaths 44% MMR 11% MR4.5 Avoid strong CYP3A inhibitors or inducers and PPIs; avoid food 2 hours before and 1 hour after each dose $2.1B $203K (2021) Bosutinib (Bosulif®) SRC family Hepatic dysfunction (45% / 27%) Diarrhea (75% / 9%) Abdominal Pain (39% / 2%) 41% MMR 7.5% MR4.5 Avoid strong CYP3A inhibitors or inducers, PPIs, antacids, and H2 blockers $650M $241K (2024) Ponatinib (Iclusig®) KDR, FGFR, c-KIT, RET, FLT3, PDGFR Black Box: Arterial Occlusive Events, Heart Failure, VTE, Hepatoxicity N/A Avoid strong CYP3A inhibitors or inducers $640M $256K (2024) Asciminib (Scemblix®) N/A Hypersensitivity (32% / 2%) Hypertension (19% / 9%) Cardiovascular (13% / 3.4%) 68% MMR 17% MR4.5 Avoid CYP2C9 substrates and certain statins; avoid food 2 hours before and 1 hour after each dose $690M $261K (2024) 2nd Gen3rd Gen 1st GenST AMP
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43 $4 $7 $9 2015 U.S. CML Sales WAC Adjusted Prevalence Adjusted The U.S. CML Market has Historically Been Large and has the Potential to be Larger Since 2015, the weighted average WAC has increased by 78% Since 2015, prevalence has increased ~22% Since 2015, the U.S. CML sales have on average been ~50% of global sales B = Billion. CML = Chronic myeloid leukemia. WAC = Wholesale acquisition cost. References: Publicly available filings, announcements and research reports; Huang X et al. Cancer. 2012;118:3213-3127; PriceRx; Assumes 2024 weighted average U.S. WAC of ~$240,000. Assumes current U.S. prevalence of ~110,000 based on American Journal of Hematology: Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring. In 2015, Global CML sales were $8B, with $4B from the U.S. alone $4B $7B $9B