#1Merger Announcement October 13, 2022 Enliven THERAPEUTICS www 7 imara#2Disclaimer 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 behalf, any question and answer session that follows that oral presentation, hard copies of this document and any materials distributed at, or in connection with, that presentation. This presentation does not purport to contain all information that may be required or relevant to an evaluation of the proposed transaction between Imara and Enliven and the concurrent financing (together, the proposed transaction"), and each recipient will be responsible for conducting any investigations and analysis that it deems appropriate and for seeking independent advice as to the legal, tax, accounting, financial, credit and other related advice with respect to the proposed transaction. No Representations or Warranties No representations or warranties, express or implied are given in, or in respect of, this presentation or as to the accuracy, reasonableness or completeness of the information contained in or incorporated by reference herein, or as to the value that may be realized in connection with the proposed transaction, or the legal, regulatory, tax, financial, accounting or other effects of the proposed transaction. To the fullest extent permitted by law, in no circumstances will Imara, Enliven or any of their respective affiliates, directors, officers, employees, members, partners, shareholders, advisors or agents have any liability arising from the use of this presentation, its contents (including the internal economic models), its omissions, reliance on the information contained within it, or on opinions communicated in relation thereto or otherwise arising in connection therewith, and they expressly disclaim any responsibility or liability for direct, indirect, incidental, exemplary, compensatory, punitive, special, or consequential damages, costs, expenses, legal fees, or losses (including lost income or profits and opportunity costs) in connection with the use of the information herein. Certain information contained herein has been derived from sources prepared by third parties. 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Recipients of this presentation should each make their own evaluation of Imara, Enliven or the proposed transaction and of the relevance and adequacy of the information and should make such other investigations as they deem necessary. Recipients are not entitled to rely on the accuracy or completeness of this presentation and are entitled to rely solely on those particular representations and warranties, if any, which may be made by Imara or Enliven to a recipient of this presentation or other third party in a definitive written agreement, when, and if executed, and subject to the limitations and restrictions as may be specified therein. The information contained herein and the parties involved in the proposed transaction, any representations, warranties, agreements or covenants between the recipient and any parties involved in the proposed transaction will be set forth in definitive agreements by and among such persons. Imara and Enliven disclaim any duty to update the information contained in this presentation. Industry and Market Data This presentation contains estimates and other statistical data made by independent parties and by Imara and Enliven relating to market size and growth and other data about Imara's and Enliven's industries. 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 Imara's, Enliven's, and the combined company's future performance and the future performance of the markets in which Imara and Enliven operate are necessarily subject to a high degree of uncertainty and risk. Drugs under Clinical Investigation This presentation concerns drugs that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration (FDA). Such drugs are currently limited by federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated. Cautionary Note Regarding Forward-Looking Statements This presentation contains forward-looking statements (including within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended (Securities Act)) concerning Enliven, Imara, the proposed transactions and other matters. These statements may discuss goals, intentions and expectations as to future plans, trends, events, results of operations or financial condition, or otherwise, based on current beliefs of the management of Imara and Enliven, as well as assumptions made by, and information currently available to, management of Imara and Enliven. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as "may," "will," "should," "would," "expect," "anticipate," "plan," "likely," "believe," "estimate," "project," "intend," and other similar expressions or the negative or plural of these words, or other similar expressions that are predictions or indicate future events or prospects, although not all forward-looking statements contain these words. Statements that are not historical facts are forward-looking statements. Forward-looking statements in this presentation include, but are not limited to, expectations regarding the proposed merger and financing transactions; the potential benefits and results of such transactions; the sufficiency of the combined company's capital resources; the combined company's cash runway; the expected timing of the closing of the proposed transactions; statements regarding the potential of, and expectations regarding, Enliven's programs, including ELVN-001, ELVN-002 and its research stage opportunities; the expected timing of Enliven's Phase 1 data for ELVN-001; the expected timing of Enliven's filing of an IND, Phase 1 clinical trial initiation and Phase 1 data for ELVN-002; and the expected timing to make a product candidate nomination for Enliven's third program. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation: the limited operating history of each company; the significant net losses incurred since inception; the ability to raise additional capital to finance operations; the ability to advance product candidates through preclinical and clinical development; the ability to obtain regulatory approval for, and ultimately commercialize, Enliven's product candidates; the outcome of preclinical testing and early clinical trials for Enliven's product candidates, including the ability of those trials to satisfy relevant governmental or regulatory requirements; Enliven's limited experience in designing clinical trials and lack of experience in conducting clinical trials; the ability to identify and pivot to other programs, product candidates, or indications that may be more profitable or successful than Enliven's current product candidates; the substantial competition Enliven faces in discovering, developing, or commercializing products; the negative impacts of the COVID-19 pandemic on operations, including ongoing and planned clinical trials and ongoing and planned preclinical studies; the ability to attract, hire, and retain skilled executive officers and employees; the ability of Imara or Enliven to protect their respective intellectual property and proprietary technologies; reliance on third parties, contract manufacturers, and contract research organizations; the risk that the conditions to the closing of the proposed transactions are not satisfied, including the failure to obtain stockholder approval for the proposed transactions from both Imara's and Enliven's stockholders or to complete the transactions in a timely manner or at all; uncertainties as to the timing of the consummation of the proposed transactions and the ability of each of the parties to consummate the proposed transactions; risks related to Imara's continued listing on the Nasdaq Stock Market until closing of the proposed transactions; risks related to Imara's and Enliven's ability to correctly estimate their respective operating expenses and expenses associated with the proposed transactions, as well as uncertainties regarding the impact any delay in the closing would have on the anticipated cash resources of the combined company upon closing and other events and unanticipated spending and costs that could reduce the combined company's cash resources; the occurrence of any event, change or other circumstance or condition that could give rise to the termination of the merger agreement or the financing transaction; competitive responses to the proposed transactions; unexpected costs, charges or expenses resulting from the proposed transactions; the outcome of any legal proceedings that may be instituted against Imara, Enliven or any of their respective directors or officers related to the merger agreement, the financing transaction, or the proposed transactions contemplated thereby; the effect of the announcement or pendency of the transactions on Imara's or Enliven's business relationships, operating results and business generally; and legislative, regulatory, political and economic developments and general market conditions. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors included in Imara's most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K filed with the SEC as well as the registration statement on Form S-4 to be filed with the SEC by Imara. Imara and Enliven can give no assurance that the conditions to the proposed transactions will be satisfied. Except as required by applicable law, Imara and Enliven undertake no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. No Offer or Solicitation This presentation is not intended to and does not constitute an offer to sell or the solicitation of an offer to subscribe for or buy or an invitation to purchase or subscribe for any securities or the solicitation of any vote in any jurisdiction pursuant to the proposed transaction or otherwise, nor shall there be any sale, issuance or transfer of securities in any jurisdiction in contravention of applicable law. No offer of securities shall be made except by means of a prospectus meeting the requirements of the Securities Act. Subject to certain exceptions to be approved by the relevant regulators or certain facts to be ascertained, the public offer will not be made directly or indirectly, in or into any jurisdiction where to do so would constitute a violation of the laws of such jurisdiction, or by use of the mails or by any means or instrumentality (including without limitation, telephone and the internet) of interstate or foreign commerce, or any facility of a national securities exchange, of any such jurisdiction. Important Additional Information Will be Filed with the SEC In connection with the proposed transaction between Imara and Enliven, Imara intends to file relevant materials with the SEC, including a registration statement on Form S-4 that will contain a proxy statement/prospectus of Imara and information statement of Enliven. IMARA AND ENLIVEN URGE INVESTORS AND STOCKHOLDERS TO READ THESE MATERIALS CAREFULLY AND IN THEIR ENTIRETY WHEN THEY BECOME AVAILABLE BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION ABOUT IMARA, ENLIVEN, THE PROPOSED TRANSACTION AND RELATED MATTERS. Investors and stockholders will be able to obtain free copies of the proxy statement/prospectus/information statement and other documents filed by Imara with the SEC (when they become available) through the website maintained by the SEC at www.sec.gov. In addition, investors and stockholders will be able to obtain free copies of the proxy statement/prospectus/information statement and other documents filed by Imara with the SEC by contacting Imara Inc. at 116 Huntington Ave., 6th Floor, Boston, MA 02116. Investors and stockholders are urged to read the proxy statement/prospectus/information statement and the other relevant materials when they become available before making any voting or investment decision with respect to the proposed transaction. Participants in the Solicitation Imara, Enliven and their respective directors and executive officers may be considered participants in the solicitation of proxies in connection with the proposed transaction. Information about Imara's directors and executive officers is included in Imara's most recent Annual Report on Form 10-K, including any information incorporated therein by reference, as filed with the SEC, and the proxy statement for Imara's 2022 annual meeting of stockholders, filed with the SEC on April 22, 2022. Additional information regarding the persons who may be deemed participants in the solicitation of proxies will be included in the proxy statement/prospectus/information statement relating to the proposed transaction when it is filed with the SEC. These documents can be obtained free of charge from the sources indicated above. 2#3Merger with Imara Has the Potential to be Transformative for Enliven Transition into a clinical-stage, precision oncology company with multiple shots on goal imara Enliven THERAPEUTICS Enliven Therapeutics opportunity Provides Imara shareholders with opportunity to participate in the Enliven growth story, at a pivotal time for Enliven Diversified and clinical-stage portfolio Two parallel lead programs currently in development, ELVN-001, a highly selective BCR-ABL inhibitor for Chronic Myeloid Leukemia, and ELVN-002, a highly selective HER2 and pan-HER2 mutant irreversible inhibitor for HER2-driven cancers, as well as additional programs in the research pipeline Multiple near-term milestones Planned steady stream of company milestones, including early Phase 1 data for ELVN-001 expected by the end of 2023 Strong balance sheet supports runway into 2026 Combined company expected to have approximately $300 million in cash and cash equivalents upon closing; resources expected to fund operations into early 2026 3#4Merger of Enliven and Imara Transaction Summary Overview Management & Programs . ● ● 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, Inc." trading as Nasdaq: ELVN Supported by the Board of Directors of both companies and is subject to shareholder approval and other customary closing conditions Expected ownership is approximately 84% Enliven (including those purchasing Enliven shares in the private financing), 16% Imara, subject to adjustment based on Imara's net cash at closing Projected $82.3 million net cash and cash equivalents from Imara and an additional $164.5 million of cash from concurrent financing CVR agreement to provide additional consideration to Imara stockholders if milestone payments are received from the previously announced pending sale of tovinontrine (IMR-687) or a potential sale or license involving IMR-261 Merger and concurrent financing expected to close in 1Q 2023 Existing Enliven management to lead the combined company New Board of Directors will include 9 members (8 existing Enliven, 1 existing Imara) Combined company will focus on advancing the development of Enliven programs 4#5The Enliven Story 過 Discovery process rooted in validated biology, differentiated chemistry, and disciplined trial design Capital-efficient approach on high potential programs aiming to develop first-in-class or best- in-class candidates a ELVN-001 and ELVN-002 supported by preclinical evidence of an improved therapeutic index Multiple near-term milestones in lead programs targeting large and attractive markets Bo 8-8 Experienced team with a track record of inventing and developing multiple FDA-approved cancer therapies Supported by top tier healthcare investors and a strong balance sheet expected to provide cash runway into early 2026 LO 5#6Highly Distinguished & Industry-Leading Team with Top-Tier Advisors and Investors Sam Kintz, MBA Co-founder and CEO abbvie Genentech A Member of the Roche Group Joe Lyssikatos, PhD Co-founder and CSO ARRAY Genentech A Member of the Roche Group BIOPHARMA Stefan Gross, PhD VP, Biology blueprint ARRAY BOPHARMA Anne Thomas VP, Clinical Operations Five Príme GILEAD Leadership Team Anish Patel, PharmD Co-founder and COO abbvie pharmacyclics Wei Deng, PhD VP, Biometrics Five Príme GILEAD lan Scott, PhD VP, CMC zentalis ARRAY BIOPHARMA * To be added to the Board of Directors at the close of the proposed transaction Helen Collins, MD CMO Five Príme GILEAD Andy Ren, PhD VP, Chemistry ARRAY BIOPHARMA Qi Wang, PhD VP, Clinical Pharmacology Bristol Myers Squibb Jazz Pharmaceuticals Ben Hohl CFO Goldman Sachs Board of the Directors Sam Kintz, MBA Enliven Therapeutics Joe Lyssikatos, PhD Enliven Therapeutics Rishi Gupta, JD OrbiMed Andy Schwab 5AM Ventures Andy Phillips, PhD Cormorant Asset Management Mika Kakefuda Derynck, MD Amunix Genentech Jake Bauer, MBA Myokardia Rich A. Heyman, PhD Aragon Pharmaceuticals, Seragon Pharmaceuticals Rahul Ballal* Current CEO of Imara Scientific Advisors Brian Druker, MD Oregon Health & Science University Rich A. Heyman, PhD Aragon Pharmaceuticals, Seragon Pharmaceuticals Lori Kunkel, MD Loxo Oncology, Pharmacyclics Kevin Koch, PhD Array Biopharma, Edgewise Therapeutics Current Investors OrbiMed Healthcare Fund Management SURVEYOR Roche Venture Fund Connecting Innovation to Value BOXER CAPITAL AM VENTURES 5 INVESTORS Cormorant Asset Management SHEATREE CAPITAL LOGOS CAPITAL Janus Henderson CO 6#7Leadership Team with Broad Range of Experience and Success World-Renowned Chemists ● Primarily or co-invented over 20 product candidates that have advanced to clinical trials Precision Oncology and Kinase Inhibitor Experts Led or been involved with the discovery, development, or commercialization of over 60 kinase inhibitor programs Leaders with a Track Record of Success ● Significant experience building and/or leading research, development, and commercial operations FDA-Approved Drugs Co-Invented by Enliven Chemists ●OOD MEKTOVI (binimetinib) 15 mg tablets Ⓡ "TUKYSA tucatinib 50 mg 150 mg tablets Koselugo (selumetinib) 10 mg & 25 mg capsules ✔ Retevmo™ selpercatinib capsules 40 mg-80 mg 7#8Pipeline & Discovery Programs Parallel lead product candidates: Program ELVN-001 ELVN-002 Target Target 1 Target 2 Target 3 Target Target 4 BCR-ABL HER2 & mutants The following table highlights discovery programs that we are prioritizing: Target ID / Validation Disease Solid tumors Solid tumors Solid tumors Disease Solid tumors CML NSCLC, other solid tumors Differentiation Highly selective w/T3151 activity EGFR sparing, pan-mutant Differentiation No approved therapies CNS penetration No approved therapies No approved therapies Lead Optimization CML = Chronic myeloid leukemia. CNS = Central nervous system. IND = Investigational new drug. NSCLC = Non-small cell lung cancer IND-Enabling Lead Identification Phase 1 Lead Optimization Phase 2 IND-Enabling Phase 3 Phase 1 Next Milestone Early Phase 1 Data IND Filing Phase 2 Milestone Expected YE 2023 4Q 2022 Phase 3 Expected to make a product candidate nomination for our 3rd program by 1H 2023 8#9● ● ELVN-001: Despite Great Advances, a Significant Need Remains for Better Treatment Options for Chronic Myeloid Leukemia Challenges with Current Standard of Care Approximately 1 in 5 patients switch therapy within the first year and ~40% of patients switch in the first 5 years (1L & 2L) Growing 3L+ patient population (>25% of CP-CML) with limited treatment options Except for asciminib, approved TKIs have poor kinase selectivity, resulting in tolerability issues that impact efficacy • Comorbidities, restrictions with concomitant medications, and specific administration requirements impede long-term patient adherence • Fewer than 10% of patients successfully achieve sustained treatment-free remission (TFR) Majority of HCPs (77%) indicated need for more effective, safe, and tolerable agents in CML Switching Dynamics Demonstrate Unmet Need Rationale for Treatment Switching Intolerance ~30% Other ~5% Lack of response ~30% Loss of response (eg, >2 years post-initiation) ~35% In the US and EU3, majority of treatment switches across lines of therapy and TKIs are driven by intolerance or initial lack of molecular response (~60% combined) TKI = Tyrosine kinase inhibitors, HCP= Healthcare professional References: HCP Qualitative & Quantitative Interviews (ClearView); Hochhaus A et al. ASH 2015; Hochhaus A et al. Leukemia. 2017; 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; Icsluig® (ponatinib) USPI; Sprycel® (dasatinib) USPI; Tasigna (nilotinib) USPI.; Bosulife (bosutinib) USPI 9#10Evolving Chronic Myeloid Leukemia Market Dynamics Current Market Growing patient population due to improved survival, requiring some patients to be on TKIs for decades Existing approved drugs have liabilities as chronic therapy, including poor tolerability due to off-target effects and inability to dose to maximal efficacy resulting in high switch rates Nevertheless, the five approved drugs (including generics) drive annual sales of >$6B, with every drug achieving ~$500M in sales and multiple drugs achieving sales of >$2B Treatment Duration for SOC by Line of Therapy % Patients Still on Therapy 100% 80% 60% 40% 20% 0% 0 1 2L median: 2-3y 3L median: 1y 2 3 Years on Therapy 1L median: ~7y 4 5 6 7 CML is a chronic disease requiring many years (even decades) of treatment *Develop BCR/ABL Mutations Develop other molecular abnormalities. † Assumes current branded pricing CML = Chronic Myeloid Leukemia. SOC Standard of care. TFR = Treatment free remission. TKI = Tyrosine kinase inhibitor Reference: Baccarani M and Gale RP. Leukemia. 2021; 35:2199-2204. 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 (TFR) as well as tolerability and convenience factors for long-term treatment Chronic nature of CML allows doctors to freely switch between therapies, with limited consequences, thereby blurring lines of therapy Current Outcomes in CML Treatment decisions are guided by mutation status, etc. in only 15- 20% of patients who develop BCR-ABL mutations or other molecular abnormalities Normal Survival on Contin. TKI 10% Progress to Acute Phase and Death*** 5-10% Sustained TFR 5-10% Normal Survival on Continuous TKI 70% Treatment decisions guided holistically based on individual patient (co-meds, co-morbidities, tolerability, etc.) for >70% patients 10% overall share (by patients) equates to >$1 billion market opportunity in the U.S. alone* 10#11ELVN-001 Potentially Affords an Improved Therapeutic Index ● ● Target Coverage at Cmin vs. 1L MMR Fold above PCRKL IC50 at Cmin 2.5 2.0- 1.5- 1.0- 0.5- 0 Nilotinib Bosutinib Imatinib Ponatinib 20 40 60 80 100 MMR (%) at 12 Months Clear correlation between target coverage of the approved agents and major molecular response rate (MMR) at 12 months¹ Phosphorylated CRKL or PCRKL IC50 represents a robust pharmacodynamic marker for BCR-ABL inhibition Fold above pCRKL IC50 at Cmin 13- 12 11 10 ● 32109 BTCF43210 Therapeutic Index vs. NHP Safety Margin Ponatinib Nilotinib ELVN-001 Toxicology studies with other ABL TKIs show that the maximum tolerated drug exposure is similar between non-human primates and humans • Data suggests ELVN-001 has the potential for significantly greater therapeutic index than existing TKIs Human (approved dose) Non human primate (MTD) 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 concentrations above its pCRKL IC50 for more than 13 hours. *NHP data for ponatinib, nilotinib, and dasatinib were obtained from the data reported for the maximum tolerated dose (MTD) in their respective NDAS (Cmin was estimated). NHP data from 28-day GLP tox study for ELVN-001 at 5 mg/kg, a well-tolerated, no adverse event dose (NOAEL) y-axis: mean Cmin plasma concentration at the human approved dose (or NHP MTD) divided by K562 pCRKL ICso in 100% human serum Reference: Ishida et al. Eur J Clin Pharmacol. 2016;72(2):185-93. 11#12ELVN-001 Clinical Focus and Target Product Profile Our Opportunity ● Target Product Profile Drive Deeper Responses ● Improve Tolerability ● Enhance Safety & Convenience High selectivity vs. clinically relevant off-targets Efficacy: MMR (& MR4.5) greater than approved TKIs driven by an enhanced therapeutic window Tolerability: fewer dose reductions & discontinuations Safety: No black box warnings; no edema, effusions, or rash • No restrictions with concomitant medications Activity against native BCR-ABL and T3151 mutation (& known asciminib resistant mutations) CCYR Complete cytogenetic response. CP-CML = Chronic phase CML. H2H = Head-to-head. LoT = Line of therapy. MMR = Major molecular response. MR4.5 = Deep molecular response. TKI = Tyrosine kinase inhibitors Dose Escalation in 3L+ and Expansion Progressed/Intolerant CP-CML Explore early LOT & combinations Seek to demonstrate improved efficacy (CCYR, MMR, MR4.5) and tolerability ● ● ● 4L+ and T3151 mutation ● Single-arm study; precedent for approval in last line based on CCYR/MMR by 12m T3151 mutation in ponatinib or asciminib progressed/intolerant/ineligible Early Line H2H vs Physician's Choice Superiority based on 12m MMR in CP-CML • Fewer dose reductions/discontinuations vs. approved agents ● 12#13ELVN-002: Opportunity for a Selective Irreversible Pan-Mutant HER2 TKI Current HER2 TKI Landscape • The high degree of structural homology between EGFR and HER2 makes it difficult to design HER2-selective inhibitors • Most approved and investigational agents are dual EGFR/HER2 inhibitors that are dose-limited by EGFR-driven toxicity ● ● Tucatinib is the only approved HER2-selective TKI, but lacks potency against key mutants, including HER2 YVMA, the most common Exon 20 insertion mutation (E201M) in NSCLC, and L755, the most common HER2 breast cancer mutation Current HER2 TKIs do not achieve sufficient CNS free drug levels to address brain metastases, leading to disease progression in patients with lung and breast cancer Our HER2 Candidate: ELVN-002 CNS = Central nervous. IM Insertion mutation. NSCLC = Non-small cell lung caner. TKI = Tyrosine kinase inhibitor. NHP = non-human primate. ● 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 potential for improved efficacy in NSCLC and other cancers Demonstrated superior pre-clinical activity in HER2- amplified subcutaneous and intracranial models, and an improved safety margin in NHPs compared to tucatinib We believe that our product candidate, if it achieves the target profile, will be able to achieve an improved therapeutic index compared to current approved and investigational TKIs as well as provide a meaningful therapeutic option to patients with brain metastases 13#14HER2 Mutant NSCLC May Provide More Rapid Market Entrance Opportunity with Expansion into Other HER2-Driven Cancers to Follow Initial Focus: HER2 Mutant NSCLC ● • ~70% of all HER2 mutations in lung cancer are HER2 YVMA High unmet need in this indication may provide a fast to market opportunity ● ● ● Approximately 3% of NSCLC patients harbor HER2 mutations, for which there are no approved TKIs Secondary Focus: Other HER2 Mutant Cancers Represents a larger market with limited treatment options ● Indication Expansion: HER2 Amplified Cancers Largest potential market opportunity, with nearly 30K metastatic patients across breast, colorectal, and gastric cancers Despite the advances in therapeutic options for HER2+ breast cancer, ~25% of patients experience primary or acquired resistance, and up to 50% of patients develop brain metastasis Despite limitations, Tukysa (tucatinib) is on a ~$335mm revenue run rate with only a 2L+ HER2+ MBC label *Other cancers include prostate, endometrial, gastric, stomach, hepatobiliary, etc. BRC = Breast cancer. Gl= Gastrointestinal. NSCLC = Non-small cell lung cancer. MBC = Metastatic breast cancer Reference: Robichaux et al. Cancer Cell. 2019;36(4):444-457.e7; SGEN 2Q22 Investor Presentation (28July2022) HER2 Mutant NSCLC Any HER2 Mutation HER2 Overexpressing 0 US Market Size Estimates BRC ~3K ~5K Other Solid Tumors* ~5K Metastatic Breast Cancer ~22K 10 5 US Incidence (1,000's) || GI Cancers ~7K 30 14#15Selectivity over EGFR ELVN-002 was >100x More Selective for HER2 YVMA Relative to EGFR Than Dual EGFR/HER2 Competitors 1000 100 10 1 0.1 Mobocertinib Poziotinib >100x Pyrotinib Investigational dual inhibitors ORR = Overall response rate. NSCLC = Non-small cell lung cancer. TKI = Tyrosine kinase inhibitor. BDTX-189 ELVN-002 } Our selective product candidate A431/ Beas2b HER2 YVMA H2073/Beas2b HER2 YVMA Current investigational dual EGFR/HER2 TKIs are roughly equipotent against EGFR and HER2 YVMA Lack of Differentiation Across Next Generation TKIs HN HN. HN 'N HN. Neratinib HN CN Pyrotinib HN CN BDTX-189 Poor efficacy & tolerability in HER2 mutant setting Phase 1b/2 30% ORR in HER2 mutant NSCLC, poor tolerability Poor efficacy & tolerability in HER2 mutant setting 15#16ELVN-002 Clinical Focus and Target Product Profile Our Opportunity ● Target Product Profile ● ● ● Drive Durable Responses ● Well Tolerated CNS activity Activity against: HER2 mutant NSCLC (e.g., Exon 20 IM) and Breast Cancer (e.g., L775) HER2 amplified and/or overexpressed tumors (breast, CRC, etc.) Brain metastases Selective: vs. wild-type EGFR Safety/tolerability: minimal Gl and skin toxicity (avoid EGFR-tox) Combinable: with SOC including ADCs across HER2-driven tumors Convenient: oral QD or BID | Dose Escalation in solid tumors with HER2 alterations ● ● Monotherapy in HER2-driven solid tumors Evaluate the safety in the combination with ADCs in HER2+ breast cancer and HER2 mutant NSCLC Expansion: 2L+ HER2 mutant NSCLC Single-arm study with potential to support accelerated approval Multiple Indication Opportunities • 1L HER2 mutant NSCLC +/- SOC Evaluate HER2+ CRC and HER2+ Breast in combination with SOC ● ADC = Antibody drug conjugate. BID = twice daily. CNS = Central nervous system. CRC = Colorectal cancer. Gl= Gastrointestinal. NSCLC = non-small cell lung cancer. SOC = Standard of care. TKI = Tyrosine kinase inhibitors. QD = once daily Explore other HER2 mutant solid tumors with "basket study" 16#17Expected Near-term Clinical Milestones for Parallel Lead Product Candidates 2022 2H22 ● ● ELVN-001 Phla initiation (completed) ELVN-002 IND filing ● 2023 ELVN-001 ELVN-001 Potential Pivotal Studies Late line single arm T3151 single arm ponatinib or asciminib intolerant / ineligible Early line H2H vs. Physician's Choice 1H23 ELVN-002 Ph1a initiation CRC = Colorectal cancer. IND = Investigational new drug. NSCLC = non-small cell lung cancer. MBC = metastatic breast cancer. 2H23 ELVN-001 Ph1 early clinical data 2024 1H24 ELVN-002 Phla data ELVN-002 ELVN-002 Potential Pivotal Studies • 2L+ NSCLC HER2 mutant monotherapy ● HER2 amplified MBC monotherapy & combinations HER2 mutant basket, HER2-amp CRC, etc. 17#18ELVN-001 (BCR-ABL)#19Chronic Myeloid Leukemia A big success story for precision oncology, but needs remain as treatment goals have evolved Prior to imatinib the annual CML mortality rate: <20% 1985 BCR-ABL protein identified Survival Probability 1.0 0.8 0.6 0.4 0.2 0.0 0 1987 HTS yielded the discovery of STI-571 (imatinib) CML 10-Year Survival Rate Over Time TK 2001-day (CML-related deaths) 445 17 Ti 2001-40day (all deaths) 1996-2000 581 178 367 220 415 308 227 220 1983-1990 1982 1 2 3 4 1998 Imatinib FIH study initiated 5 6 7 Years 8 9 92% 83% 43% 35% 8% 10 11 2001 Imatinib approved 10-year survival rate improved from <20% to over >80% 12 13 14 2006 Dasatinib approved CML = Chronic myeloid leukemia. FIH = First-in-human. MMR = Major molecular response. TFR = Treatment-free reemission References: Huang X et al. Cancer. 2012;118:3213-3127. DOI: 10.1002/cncr.26679; Kantarjian et al. Chronic Myeloid Leukemia, In: Harrison's Principles of Internal Medicine. 2014. 2007 Nilotinib approved Estimated Prevalence of CML in the US Over Time Number of CML Patients 200000 180000 160000 140000 120000 100000 80000 60000 40000 20000 Number of patients living with CML has more than doubled since introduction of TKIs 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050 Year 2012 Ponatinib and Bosutinib approved 2013 NCCN Update (MMR) 2016 Generic imatinib becomes available 2021 Asciminib 3L approval 2017 Emerging Treatment Goals (MR4.5, TFR) 19#20● ● ● Significant Need Remains for More Treatment Options for CML Challenges with Current Standard of Care Approximately 1 in 5 patients switch therapy within the first year and ~40% of patients switch in the first 5 years (1L & 2L) Growing 3L+ patient population (>25% of CP-CML) with limited treatment options Except for asciminib, the approved TKIs have poor kinase selectivity resulting in tolerability issues that impact efficacy Comorbidities, restrictions with concomitant medications, and specific administration requirements impede long-term patient adherence • Fewer than 10% of patients successfully achieve sustained treatment-free remission (TFR) Majority of HCPs (77%) indicated need for more effective, safe, and tolerable agents in CML Switching Dynamics Demonstrate Unmet Need Rationale for Treatment Switching Intolerance ~30% Other ~5% Lack of response ~30% Loss of response (eg, >2 years post-initiation) ~35% In the US and EU3, majority of treatment switches across lines of therapy and TKIs are driven by intolerance or initial lack of molecular response (~60% combined) TKI = Tyrosine kinase inhibitors, HCP= Healthcare professional References: HCP Qualitative & Quantitative Interviews (ClearView); Hochhaus A et al. ASH 2015; Hochhaus A et al. Leukemia. 2017; 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; Icsluig® (ponatinib) USPI; Sprycel® (dasatinib) USPI; Tasigna® (nilotinib) USPI.; Bosulife (bosutinib) USPI 20#21Poor Selectivity Limits Tolerability & Efficacy of 1st, 2nd & 3rd Gen Agents BCR-ABL Coverage Drug & Administration Requirements Compound Company Imatinib (Gleevec®) Dasatinib (Spyrcel®) Nilotinib (TasignaⓇ) Bosutinib (Bosulif®) Ponatinib (IclusigⓇ) Novartis BMS Novartis Pfizer Takeda T3151 Coverage X X X X Off Target(s) & Treatment-Related AEs Myelosuppression: 20-25% Gr 3+ Fluid Retention/Edema: 68% Myalgia/Arthralgia: 50% Gl-related: 50% C-KIT, CSFR-1, PDGFR SRC family, C-KIT, PDGFR-aß C-KIT, PDGFR, CSFR-1, DDR-1 (hERG Channel) SRC family KDR, FGFR, C-KIT, RET, FLT3, PDGFR Myelosuppression: 10-20% Gr 3+ Edema/Effusions: 15-30% FY = Fiscal year. MMR = Major molecular response. MR4.5 = Deep molecular response. PPI = Proton pump inhibitors MMR and MR 4.5 at 12m; 2020 FY Sales (USD) are approximate figures Myelosuppression: 10-20% Gr 3+ Hypertension: 10% Black Box: QT Prolongation, Sudden Deaths Diarrhea: 82% Nausea: 39% Vomiting: 32% Increased LFTs: 20% Myelosuppression: 50% Gr 3+ Hypertension: 70% Black Box: Arterial Occlusive Events, Heart Failure, VTE, Hepatoxicity N/A ++ ++ +++ 1L Efficacy 28% MMR 3% MR4.5 46% MMR 5% MR4.5 44% MMR 11% MR4.5 41% MMR 7.5% MR4.5 82% MMR* 56% MR4.5 Avoid strong CYP3A inhibitors or inducers Avoid strong CYP3A inhibitors or inducers, PPIs, antacids, and H2 blockers Avoid strong CYP3A inhibitors or inducers and PPIs; avoid food 2 hours before and 1 hour after each dose Avoid strong CYP3A inhibitors or inducers, PPIs, antacids, and H2 blockers Avoid strong CYP3A inhibitors or inducers A selective BCR-ABL inhibitor could yield enhanced target coverage, leading to greater efficacy and better long-term tolerability 2021 FY Sales (USD) $1.0B $2.1B $2.0B $500M $500M *Based on the discontinued Ponatinib's 1L CML study; not an approved line of therapy References: Cortes JE et al. J Clin Oncol, 2012; 30(28):3486-92; Kantarjian H et al. NEJM, 2010; 362(24):2260-70; Saglio G et al. NEJM 2010; 362 (24):2251-9; Jain P et al. Lancet Haematol, 2015; 2(3):e118-28; Cortes JE et al. J Clin Oncol. 2016; 34(20):2333-40; Hochhaus A et al. Leukemia. 2016; 30(5):1044-54; Gleevec® (imatinib) USPI; Ilclusig (ponatinib) USPI; Sprycel® (dasatinib) USPI; Tasigna® (nilotinib) USPI; Bosulife (bosutinib) USPI. 21#22Review of Asciminib (Scemblix®), 4th Generation Allosteric TKI Observations ● • ~30% discontinued due to lack of efficacy/AE by 48 wk • ~50% discontinued by 96 wk, but only 1.2% due to PD/death T3151 dosed 5x higher resulting in more dose reductions, enhanced pancreatic toxicity (25%) & elevated liver enzymes Drug-drug interactions: CYP3A4, CYP2C9 Potential off-target resistance liabilities: PgP & BCRP Requires fasting 2 hours before and 1 hour after each dose ● ● . 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) ● PD Progressive disease. TKI = Tyrosine kinase inhibitor References: Hochhaus et al. ASH 2020; Cortes et al. ASH 2020; ASH 2021; Novartis Q2 2021 IR; Scemblix (Asciminib) USPI; ASCO 2022; Eadie et al Oncotarget 2018 Emerging BCR-ABL mutations upon discontinuation due to lack of efficacy or progressive disease No mutations ATP Binding Site Myristol Binding Pocket Asciminib (n=39) 22 (56%) M244V (n=3), E355G, F359V, T3151 ATP Binding Site A337T (n=3), P465 Mutations at baseline & end of treatment F359C/V (n=3), F317L (n=2), Y253H Bosutinib (n=30) 20 (67%) T3151, V299L None M244V (n=2), E255V, F317L, Q252H 22#23Evolving Chronic Myeloid Leukemia Market Dynamics Current Market Growing patient population due to improved survival, requiring some patients to be on TKIs for decades Existing approved drugs have liabilities as chronic therapy, including poor tolerability due to off-target effects and inability to dose to maximal efficacy resulting in high switch rates Nevertheless, the five approved drugs (including generics) drive annual sales of >$6B, with every drug achieving ~$500M in sales and multiple drugs achieving sales of >$2B Treatment Duration for SOC by Line of Therapy % Patients Still on Therapy 100% 80% 60% 40% 20% 0% 0 1 2L median: 2-3y 3L median: 1y 2 3 Years on Therapy 1L median: ~7y 4 5 6 7 CML is a chronic disease requiring many years (even decades) of treatment *Develop BCR/ABL Mutations "Develop other molecular abnormalities. † Assumes current branded pricing CML = Chronic Myeloid Leukemia. SOC Standard of care. TFR = Treatment free remission. TKI = Tyrosine kinase inhibitor Reference: Baccarani M and Gale RP. Leukemia. 2021; 35:2199-2204. 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 (TFR) as well as tolerability and convenience factors for long-term treatment Chronic nature of CML allows doctors to freely switch between therapies, with limited consequences, thereby blurring lines of therapy Current Outcomes in CML Treatment decisions are guided by mutation status, etc. in only 15- 20% of patients who develop BCR-ABL mutations or other molecular abnormalities Normal Survival on Contin. TKI 10% Progress to Acute Phase and Death*** 5-10% Sustained TFR 5-10% Normal Survival on Continuous TKI 70% Treatment decisions guided holistically based on individual patient (co-meds, co-morbidities, tolerability, etc.) for >70% patients 10% overall share (by patients) equates to >$1 billion market opportunity in the U.S. alone* 23#24Our Strategy and Initial Positioning in an Evolving CML Market Treatment Paradigm 1L (50%) 2L (30%) 3L+ (20%) T3151 1st Gen TKI Imatinib 28% MMR 2nd Gen TKIS ~35% MMR 2nd Gen TKIS Nilotinib, Dasatinib, Bosutinib ~45% MMR 3rd Gen TKI Ponatinib 58% MMR 2nd Gen TKIs ~20-25% MMR 2nd 3rd & 4th Gen TKIs Bosutinib Ponatinib Asciminib ~20% MMR 35% MMR ~33% MMR 4th Gen TKI High Dose Asciminib 58% MMR** 2nd Gen TKIs = Nilotinib, Dasatinib, Bosutinib. MMR = Major Molecular Response at ~12 months. *Depending on patient population ELVN-001 30-40%+ MMR Target* ELVN-001 >50% MMR Target Market Insights ~50% of patients start on 2nd Gen TKIS, driven by faster & deeper molecular responses Further improvement in efficacy may still allow for new entrants in 1L setting HCPs consistently express high interest in prescribing novel agents with improved safety/tolerability and efficacy in 2L+ Asciminib has the potential to become the preferred option in earlier lines of therapy HCPs report up to ~25% of patients end up back on imatinib in 3L+ setting Potentially more tolerable choice for T3151 patients and has the potential to displace ponatinib High dose asciminib is now an option in the US, but risks remain **Ponatinib-naïve patients (n = 21). References HCP Qualitative & Quantitative Interviews (ClearView); Gleevec® (imatinib) USPI; Icsluig (ponatinib) USPI; Sprycel® (dasatinib) USPI; Tasigna® (nilotinib) USPI; Bosulif® (bosutinib) USPI; Cortes JE et al. Blood. 2020;136(Supplement1):47-50; Hochhaus et al. ASH 2020. Market Size (US) ~30K+ O ~18K+ O ~12K+ < $500M USD оо ~2K+ > $2B USD 24#25ELVN-001 Clinical Focus and Target Product Profile Our Opportunity ● Target Product Profile Drive Deeper Responses ● Improve Tolerability ● Enhance Safety & Convenience High selectivity vs. clinically relevant off-targets Efficacy: MMR (& MR4.5) greater than approved TKIs driven by an enhanced therapeutic window Tolerability: fewer dose reductions & discontinuations Safety: No black box warnings; no edema, effusions, or rash • No restrictions with concomitant medications Activity against native BCR-ABL and T3151 mutation (& known asciminib resistant mutations) CCYR Complete cytogenetic response. CP-CML = Chronic phase CML. H2H = Head-to-head. LoT = Line of therapy. MMR = Major molecular response. MR4.5 = Deep molecular response. TKI = Tyrosine kinase inhibitors Dose Escalation in 3L+ and Expansion Progressed/Intolerant CP-CML Explore early LoT & combinations Seek to demonstrate improved efficacy (CCYR, MMR, MR4.5) and tolerability ● ● ● 4L+ and T3151 mutation ● Single-arm study; precedent for approval in last line based on CCYR/MMR by 12m T3151 mutation in ponatinib or asciminib progressed/intolerant/ineligible Early Line H2H vs Physician's Choice Superiority based on 12m MMR in CP-CML • Fewer dose reductions/discontinuations vs. approved agents ● 25#26ELVN-001 is a Selective Active Site, Active Form Inhibitor of BCR-ABL 1 I SH3 SH2 BCR Kinase Domain Drug Drug Asciminib ATP-Binding Site ELVN-001 Bosutinib Dasatinib Imatinib Nilotinib Ponatinib Binding Conformation Myristoyl Pocket BCR-ABL Active / Inactive Inactive Active Active Inactive Binding Conformation Inactive Inactive Y BCR SH3 SH2 ATP Y SH1 ATP Competitive BCR-ABL Inhibitors Bosutinib Dasatinib Nilotinib Ponatinib NLS Y=Tyrosine; NLS-Nuclear Localization Signal; SH1-Src Homology 1 Domain; SH2=Src Homology 2 Domain; SH3-Src Homology 3 Domain; DB-DNA-Binding Region; AB=Actin-Binding Region; BCR=Breakpoint cluster region Proline Rich Imatinib ELVN-001 DB AB 26#27ELVN-001 Has a Differentiated and Attractive Profile for CML KCL-22 (BCR-ABLwt) cytotox IC50 (50% human serum) KCL-22 (BCR-ABLT3151) cytotox IC50 (50% human serum) K-562 (BCR-ABLwt) cytotox IC50 (50% human serum) K-562 pCRKL IC50 (100% human serum) HL-60 cytotox IC50 (10% FBS) Human Hepatocyte stability, extraction ratio Plasma Protein Binding (% unbound) CYPS (% inhibition @ 10 μM) hERG IC50 BCRP Substrate ● Asciminib 7 nM >1,150 nM 101 nM ΝΑ 12,200 nM ● 60 ~2 All < 50% 25 μΜ Yes Ponatinib 1 nM 14 nM 4 nM 36 nM 366 nM 62 <1 All < 50% 2.3 μM Yes Nilotinib 90 nM > 10,000 nM 228 nM 1,080 nM 5,050 nM 62 < 1 2C8, 2C9, 3A4, 2C19 > 50% 0.13 μΜ Yes ELVN-001 19 nM 131 nM 65 nM 112 nM 3,550 nM 0 40 All < 50% > 30 μη No Good potency in the presence of human serum against native BCR-ABL and T3151 (smaller potency shift compared to ponatinib & asciminib) Designed for safe and flexible use including reduced risk of DDIs, appropriate for a chronic disease setting • Good predicted human PK will enable maximal target coverage through the full dosing window Strong correlation to MMR in humans DDI = Drug-drug interaction Note: IC values represent an average derived from multiple runs internally with a minimum of two independent experiments. ADMET data were generated internally or obtained from literature including NDAs. Results of a head-to-head comparison may differ from those set forth herein. BCRP may play a role in off-target resistance 27#28ELVN-001 is Selective for ABL1 • ELVN-001 has a very selective kinase profile Clean vs. key off-targets in cells 372 kinases screened at 1 µM compound (100 μM ATP) ● ● ● ● ● ELVN-001 is also very clean (>10 µM) in an in vitro safety panel of >130 receptors ELVN-001 Ponatinib Nilotinib Dasatinib Kinases with >50% inhibition selected for IC50 determination >100x window vs. all but 2 kinases profiled Bosutinib CKIT >10,000 30 200 0.6 1,000 Cellular Phosphorylation IC50 (nM) FLT3wt >10,000 3.8 >10,000 >1,000 4,700 PDGFRb >10,000 89 720 7.1 7,900 VEGFR2 >10,000 4.8 2,900 >1,000 >10,000 CSRC >10,000 Reference: Abl kinases are required for vascular function, Tie2, and angiopoietin-1-mediated survival. Pendergast et al. PNAS. 2013;110(30):12432-7. 630 >10,000 10 16 ELVN-001 (100 μM ATP) Kinase ABL1 ABL2/ARG TRKC TNIK LOK/STK10 LRRK2 FGR ACK1 FYN HGK/MAP4K4 LCK IC50 (NM) 1 31 41 110 183 486 550 698 725 973 >1,000 Large window for ABL2/ARG may result in a favorable safety profile 28#29ELVN-001 Potentially Affords an Improved Therapeutic Index ● ● Target Coverage at Cmin vs. 1L MMR Fold above PCRKL IC50 at Cmin 2.5 2.0- 1.5- 1.0- 0.5- 0 Nilotinib Bosutinib Imatinib Ponatinib 20 40 60 80 100 MMR (%) at 12 Months Clear correlation between target coverage of the approved agents and major molecular response rate (MMR) at 12 months¹ Phosphorylated CRKL or PCRKL IC50 represents a robust pharmacodynamic marker for BCR-ABL inhibition Fold above pCRKL IC50 at Cmin 13- 12 11 10 ● 32109 BTCF43210 Therapeutic Index vs. NHP Safety Margin Ponatinib Nilotinib ELVN-001 Toxicology studies with other ABL TKIs show that the maximum tolerated drug exposure is similar between non-human primates and humans • Data suggests ELVN-001 has the potential for significantly greater therapeutic index than existing TKIs Human (approved dose) Non human primate (MTD) 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 concentrations above its pCRKL IC50 for more than 13 hours. *NHP data for ponatinib, nilotinib, and dasatinib were obtained from the data reported for the maximum tolerated dose (MTD) in their respective NDAS (Cmin was estimated). NHP data from 28-day GLP tox study for ELVN-001 at 5 mg/kg, a well-tolerated, no adverse event dose (NOAEL) y-axis: mean Cmin plasma concentration at the human approved dose (or NHP MTD) divided by K562 pCRKL ICso in 100% human serum Reference: Ishida et al. Eur J Clin Pharmacol. 2016;72(2):185-93. 29#30ELVN-001 Clinical Development Strategy Phase 1 TRIAL ● ● CP-CML intolerant / resistant T3151 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 GOALS ● Late line single arm & T3151 single arm Explore based on data (MMR/MR4.5) Earlier lines of therapy Combinations with approved TKIs (e.g., asciminib) ● Establish PoC for deep and durable responses in early line CML Demonstrate efficacy and safety profile suitable for initiating early line H2H CP-CML = Chronic-phase CML. H2H = Head-to-head. MMR = Major molecular response. MR4.5 = Deep molecular response. PoC = Proof of concept Registrational / Phase 3 TRIAL GOALS ● File on 4L+ and T3151 single arm data Initiate early line H2H vs. Physician's Choice ● Accelerated Approval in late line CP- CML Initiate early line H2H for broad label accelerated approval in CP-CML 30#31ELVN-002 (HER2)#32ELVN-002: Opportunity for a Selective Irreversible Pan-Mutant HER2 TKI Current HER2 TKI Landscape • The high degree of structural homology between EGFR and HER2 makes it difficult to design HER2-selective inhibitors • Most approved and investigational agents are dual EGFR/HER2 inhibitors that are dose-limited by EGFR-driven toxicity ● ● Tucatinib is the only approved HER2-selective TKI, but lacks potency against key mutants, including HER2 YVMA, the most common Exon 20 insertion mutation (E201M) in NSCLC, and L755, the most common HER2 breast cancer mutation Current HER2 TKIs do not achieve sufficient CNS free drug levels to address brain metastases, leading to disease progression in patients with lung and breast cancer Our HER2 Candidate: ELVN-002 CNS = Central nervous. IM= Insertion mutation. NSCLC = Non-small cell lung caner. TKI = Tyrosine kinase inhibitor. NHP = non-human primate. ● 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 potential for improved efficacy in NSCLC and other cancers Demonstrated superior pre-clinical activity in HER2- amplified subcutaneous and intracranial models, and an improved safety margin in NHPs compared to tucatinib We believe that our product candidate, if it achieves the target profile, will be able to achieve an improved therapeutic index compared to current approved and investigational TKIs as well as provide a meaningful therapeutic option to patients with brain metastases 32#33HER2 Mutant NSCLC May Provide More Rapid Market Entrance Opportunity with Expansion into Other HER2-Driven Cancers to Follow Initial Focus: HER2 Mutant NSCLC ● • ~70% of all HER2 mutations in lung cancer are HER2 YVMA High unmet need in this indication may provide a fast to market opportunity ● ● ● Approximately 3% of NSCLC patients harbor HER2 mutations, for which there are no approved TKIs Secondary Focus: Other HER2 Mutant Cancers Represents a larger market with limited treatment options ● Indication Expansion: HER2 Amplified Cancers Largest potential market opportunity, with nearly 30K metastatic patients across breast, colorectal, and gastric cancers Despite the advances in therapeutic options for HER2+ breast cancer, ~25% of patients experience primary or acquired resistance, and up to 50% of patients develop brain metastasis Despite limitations, Tukysa (tucatinib) is on a ~$335mm revenue run rate with only a 2L+ HER2+ MBC label *Other cancers include prostate, endometrial, gastric, stomach, hepatobiliary, etc. BRC = Breast cancer. GI = Gastrointestinal. NSCLC = Non-small cell lung cancer. MBC = Metastatic breast cancer Reference: Robichaux et al. Cancer Cell. 2019;36(4):444-457.e7; SGEN 2Q22 Investor Presentation (28July2022) HER2 Mutant NSCLC Any HER2 Mutation HER2 Overexpressing 0 US Market Size Estimates BRC ~3K ~5K Other Solid Tumors* ~5K Metastatic Breast Cancer ~22K 10 5 US Incidence (1,000's) || GI Cancers ~7K 30 33#34HER2 Mutant NSCLC Landscape: No Approved Selective TKIs Selectivity vs. EGFRWT HER2mut NSCLC Efficacy Compound Platinum- doublet CURRENT & POTENTIAL FUTURE STANDARD OF CARE Poziotinib Company Trastuzumab deruxtecan Daiichi Sankyo (Enhertu®) INVESTIGATIONAL TKIS Pyrotinib BI-1810631 N/A Spectrum Jiangsu HengRui Medicine Stage Boehringer Ingelheim N/A FDA Approved (2L+) PDUFA Nov 2022 (ODAC 09/22) Phase 3 Phase 1a MoA Chemo HER2-ADC topoisomerase payload Irreversible, EGFR/HER2 Irreversible, EGFR/HER2 Irreversible, HER2 N/A HER2-specific < 1x ≤1x > 100x ORR: ~25-35% mPFS: 4-7m ORR: 58% DOR: 8.7m ORR: ~28% mPFS: 5.5m ORR: 19% mPFS: 5.6m ΝΑ Gr 3+ Neutropenia: 19% Nausea: 52% Constipation, diarrhea, vomiting, cough, dyspnea, decreased appetite (20-30% each) Gr 3+ Neutropenia: 16%; Black Box Warning: 12% ILD/pneumonitis (all grades) All Grade Nausea (61%), Anemia (34%), Fatigue (32%) Dose discontinuation due to AE: 8% Safety / Tolerability Gr 3+: Rash (49%) ; Diarrhea (26%) ; Stomatitis (25%) All Grade Rash (91%); Diarrhea (82%); Stomatitis (69%) ; Paronychia (38%) Dose modifications due to AEs: 91% | Dose discontinuations due to AEs: 13% Gr 3+: Diarrhea (17%) All Grade Diarrhea (86%); Fatigue (58%) ; Anemia (36%); Dizziness (33%); Decreased appetite (32%, Hand-foot syndrome (32%) ; Nausea (32%) Dose modification due to AEs: 8% Phase 1 in progress at 6 sites (US, Japan, China Netherlands) - As of April 2022, 11 pts dosed (QD and BID arm). Additional clinical pharmacology studies underway to bridge to a new formulation and assess food / PPI effect. Poor TKI selectivity of dual inhibitors resulting in EGFR-driven toxicities limits efficacy AE = Adverse event. BID = Twice a day. DOR = Duration of response. ILD = Interstitial lung disease. NSCLC = Non-small cell lung cancer. ORR = Overall response rate. PFS = Progression free survival. PPI = Proton pump inhibitor. TKI = Tyrosine kinase inhibitor References: Enhertu® (fam-trastuxumab deruxtecan) USPI; Le, et al. J. Clin Oncol 2021, 40:710-718; Song et al, BMC Medicine (2022) 20:42; NCT04886804, NCT05380947, ASCO TIP 2022 34#35HER2 Breast Landscape: No Irreversible, Highly Selective TKI Option Clinical Usage HER2+ BRC Efficacy Compound ANTIBODY DRUG CONJUGATES Enhertu (fam- trastuzumab deruxtecan) Kadcyla (ado- trastuzumab emtansine) trastuzumab + capecitabine) Tucatinib (single agent) Company TYROSINE KINASE INHIBITORS Tukysa (tucatinib + CHEMOTHERAPY Xeloda (capecitabine) Daiichi Sankyo Roche Seagen Seagen Roche MoA HER2-ADC topoisomerase payload HER2-ADC DM1 toxin payload Reversible, HER2 TKI Reversible, HER2 TKI Chemo 2L 2L 3L+ (CNS mets) N/A 3L+ mPFS: NR (18.5-NE) ORR: 80% mPFS: 6.8m ORR: 35% mPFS: 7.8m ORR: 40.6% mOS: 21.9m ORR: 11% CBR: 22% (med prior tx: 6) ORR: 25% DoR: 5m Safety / Tolerability Gr 3+: Neutropenia: 20% All Grade: ILD (11%); Nausea (72%); Alopecia, Anemia, Vomiting (30-40% each) Discontinuation due to AE: 13% (median txt duration: 14m) Gr 3+: Thrombocytopenia: 25% All Grade: Nausea, Fatigue, AST/ALT increase (20-30% each) Discontinuation due to AE: 5% (median txt duration 7m) Gr 3+: PPE / Diarrhea (12-13% each) All Grade: Diarrhea (80%) ; PPE (63%) ; Fatigue, Nausea (~50% each) Discontinuation due to AE: 6% (median txt duration 7m) Gr 3+: ALT increase (4%) ; Rash (4%) ; Diarrhea (0%) All Grade: Diarrhea (26-33%); Nausea (33%); Fatigue (18%) Gr 3+: Diarrhea (15%); PPE (11%); Nausea, Vomiting (4% each) All Grade: PPE / Diarrhea (57% each); Nausea (53%); Vomiting (37%) Discontinuation due to AE: 8% (median txt duration 3.8m) No selective, irreversible TKI to meaningfully address brain metastases AE = Adverse event. ADC = Antibody drug conjugate. AST= Aspartate aminotransferase. ALT= Alanine transaminase. ILD = Interstitial lung disease. NE = Not evaluable. NR = Not reached. ORR = Overall response rate. PFS = Progression free survival. PPE = Palmar-plantar erythrodysesthesia. OS = Overall survival. TKI = Tyrosine kinase inhibitor. References: Cortes J et al, Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer, NEJM 2022; Murthy RK et al, Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. NEJM 2020; Moulder S et al., Phase I Study of ONT-380, a HER2 Inhibitor, in Patients with HER2-Advanced Solid Tumors,. Clin Cancer Res; 23(14); 35 Stricker et al, A phase II study of tucatinib and trastuzumab for HER2-positive mCRC (ESMO 2022); Xeloda USPI, 2015#36ELVN-002 Clinical Focus and Target Product Profile Our Opportunity ● Target Product Profile ● ● ● Drive Durable Responses ● Well Tolerated CNS activity Activity against: HER2 mutant NSCLC (e.g., Exon 20 IM) and Breast Cancer (e.g., L775) HER2 amplified and/or overexpressed tumors (breast, CRC, etc.) Brain metastases Selective: vs. wild-type EGFR Safety/tolerability: minimal Gl and skin toxicity (avoid EGFR-tox) Combinable: with SOC including ADCs across HER2-driven tumors Convenient: oral QD or BID | Dose Escalation in solid tumors with HER2 alterations ● ● Monotherapy in HER2-driven solid tumors Evaluate the safety in the combination with ADCs in HER2+ breast cancer and HER2 mutant NSCLC Expansion: 2L+ HER2 mutant NSCLC Single-arm study with potential to support accelerated approval Multiple Indication Opportunities • 1L HER2 mutant NSCLC +/- SOC Evaluate HER2+ CRC and HER2+ Breast in combination with SOC ● ADC = Antibody drug conjugate. BID = twice daily. CNS = Central nervous system. CRC = Colorectal cancer. Gl= Gastrointestinal. NSCLC = non-small cell lung cancer. SOC = Standard of care. TKI = Tyrosine kinase inhibitors. QD = once daily Explore other HER2 mutant solid tumors with "basket study" 36#37ELVN-002 Had Favorable Mutant Coverage Compared to Tucatinib Proliferation IC50 [nm] Tucatinib ELVN-002 29 6 Proliferation IC50 Fold over Tucatinib ELVN-002 1 1 33 11 1 2 24 2 1 0.2 11 8 2 225 510 15 18 2 157 6 5 1 294 12 10 2 287 7 10 642 14 22 17 17 499 1104 88 41 38 13 3 34 43 1239 209 13 7 438 14 20 5 29 11 12 29 418 1284 7 64 11 3412 148 2524 21 >10000 >10000 HER2 Exon20 Insertion Mutations Common HER2 Point Mutations Ba/F3 HER2 Mutation A775-G776-ins-C A775-G776-ins-YVMA A775-G776-ins-YVMS A775-G776-ins-SVMA A775-G776-ins-VVMA A775-G776-ins-MMAY A775-G776-ins-YVMA-R678Q G776VC wild-type P95 G776-del-ins-IC G776-del-ins-LC G776-del-ins-VV S310F S310Y R678Q L755S L755P D769N V773M V777L T798M L869R G776-V777-del-ins-CVC G776-Del-ins-AVGC V777-G778-ins-GC P780-Y781-ins-GSP L869R/T7981 V8421 BaF3 parental cell line EGFR 3 3 ∞ w w 3 21 2 4 3 194 2 43 4 >10000 >10000 ∞ 15 1 1 0.4 0.4 1 14 44 0.3 2 0.4 118 5 87 1 >10000 >10000 1 2 3 7 2 5 2 2 1 1 0.5 0.5 1 1 3 0.3 1 1 32 0.4 7 1 >10000 >10000 } YVMA: 71% E20IM NSCLC VC: 11% E20IM NSCLC 22% HER2mut BRC 37#38ELVN-002 Potently Inhibited HER2 & HER2 Mutants While Sparing EGFR BT474 HER2WT pHER2 IC50 Beas2b HER2S310F PHER2 IC50 Beas2b HER2¹755S pHER2 IC50 Beas2b HER2YVMA PHER2 IC50 Beas2b HER2YVMA PHER2 IC50 in 100% human serum (fold shift) BT474 (HER2wt) cytotox IC50 NCI-N87 (HER2wt) cytotox IC50 Ba/F3 HER2YVMA Cytotox IC50 H2073 (EGFRwt) pEGFR IC50 A431 (EGFRwt) pEGFR IC50 A431 (EGFRwt) cytotox IC50 Human Hepatocyte stability, extraction ratio GSH in human liver cytosol, (% remaining @ 1h) Kinetic Solubility pH 7.4 (UM) Poziotinib 3.5 1.9 4 2.1 69 (33x) 0.9 0.4 1.5 1.4 1.3 0.6 68 80% 5.6 Pyrotinib 13 2 3.5 324 (65x) 2.3 2.6 3.2 6.4 10 75 74 34% < 0.1 Tucatinib 12 16 99 127 >1000 (~10x) 22 44 119 >10000 >10000 >10000 76 9.3 ELVN-002 13 2.8 4.7 4.2 33 (8x) 3.9 3.3 5.1 2160 2290 3530 22 70% 260 In contrast to tucatinib, potent pharmacodynamic activity for HER2 YVMA (71% of E20IM NSCLC) & HER2 L755 (22% HERmut BRC) In contrast to dual inhibitors, our candidates spare EGFR ELVN-002 has exceptional drug like properties and PK profile for a covalent TKI 38#39Selectivity over EGFR ELVN-002 was >100x More Selective for HER2 YVMA Relative to EGFR Than Dual EGFR/HER2 Competitors 1000 100 10 1 0.1 Mobocertinib Poziotinib >100x Pyrotinib Investigational dual inhibitors ORR = Overall response rate. NSCLC = Non-small cell lung cancer. TKI = Tyrosine kinase inhibitor. BDTX-189 ELVN-002 } Our selective product candidate A431/ Beas2b HER2 YVMA H2073/Beas2b HER2 YVMA Current investigational dual EGFR/HER2 TKIs are roughly equipotent against EGFR and HER2 YVMA Lack of Differentiation Across Next Generation TKIs HN HN. HN 'N HN. Neratinib HN CN Pyrotinib HN CN BDTX-189 Poor efficacy & tolerability in HER2 mutant setting Phase 1b/2 30% ORR in HER2 mutant NSCLC, poor tolerability Poor efficacy & tolerability in HER2 mutant setting 39#40Tumor Volume (mm³) ELVN-002 Demonstrated Robust Anti-Tumor Activity in Beas2b HER2 YVMA Xenograft Model at Well-Tolerated Doses 4000- 3000- 2000- 1000- 0 ● ● Beas2b HER2 YVMA Xenograft TGI 5 10 Days post treatment 15 20 Vehicle 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 ng*hr/mL (internal data) Pozi 16 mg human AUC ~450 ng*hr/mL (Spectrum website); mouse 1 mg/kg AUC ~3,500 ng*hr/mL (internal data) Tucatinib 100 mg/kg QD Poziotinib 1 mg/kg QD ENLV-002 5 mg/kg QD ENLV-002 10 mg/kg QD ENLV-002 20 mg/kg QD Beas2b HER2 YVMA Xenograft Body Weight Change Body Weight (% of starting weight) 120 110- 100- 90 80- 70- 0 JOK 3/8 mice required dose holiday(s) starting day 11 5 10 Days post treatment 15 Poziotinib's MTD in this model was 1 mg/kg, and this dose yielded an exposure ~8x its human exposure at 16 mg QD ELVN-002 yielded deep tumor regressions, and all doses tested were well-tolerated Minimal TGI vs. YVMA observed with tucatinib treatment up to ~14x its human exposure at 300 mg BID 20 Vehicle ELVN-002 20 mg/kg QD Tucatinib 100 mg/kg QD Poziotinib 1 mg/kg QD 40#41BLI (photons/sx106) ELVN-002 Demonstrated Robust CNS Anti-Tumor Activity in NCI-N87 HER2 amp Intracranial Model at Well-Tolerated Doses 200- 150- 100- 50- ● ● 0 NCI-N87 HER2wt Intracranial (CNS) Model H HOCHIL 10 Days post treatment 20 HH100 Vehicle Tucatinib 50 mg/kg BID Tucatinib 75 mg/kg BID ELVN-002 10 mg/kg QD ELVN-002 20 mg/kg QD ELVN-002 50 mg/kg QD Concentration (ng/mL) 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 ng*hr/mL (combined) (internal data) ELVN-002 10 mg/kg nude mouse AUC ~1,260 ng*hr/mL 10000- 1000- 100- 10- 0 Tucatinib vs. ELVN-002 Nude Mouse PK 10 hours 20 ELVN-002 yielded sustained tumor regressions in the NCI-N87 intracranial model, and all doses tested were well-tolerated Tucatinib treatment of 50 & 75 mg/kg BID results in ~4.5x & ~12x its human exposure at 300 mg BID ELVN-002 exhibited superior CNS anti-tumor activity at ~40-100x lower exposures compared to tucatinib in this model Tucatinib 75 mg/kg BID Tucatinib 50 mg/kg BID ELVN-002 10 mg/kg QD Tucatinib pHER2 WT IC90 (100% human serum) Tucatinib pHER2 WT IC50 (100% human serum) 41#42Tumor Volume ELVN-002 Demonstrated Robust Anti-Tumor Activity & Additive Activity in Combination with Enhertu at Well-Tolerated Doses (mm3) 1500- LE 10 Days post treatment 1000- 500- 0- 0 NCI-N87 HER2wt Xenograft TGI: ELVN-002 Mono ● ● 5 15 References: Li et al. Cancer Disc 2020; Abraham et al. J Clin Oncol 2019 20 Vehicle ELVN-002 1 mg/kg QD ELVN-002 2.5 mg/kg QD ELVN-002 5 mg/kg QD ELVN-002 10 mg/kg QD ELVN-002 20 mg/kg QD Tumor Volume (mm3) 1500- 1000- 500- 0 NCI-N87 HER2wt Xenograft TGI: Enhertu Combo 15 10 15 Days post treatment + 20 25 Vehicle 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 activity and deep tumor regressions in the same model In contrast to reversible inhibitors like tucatinib, irreversible inhibitors have been shown mechanistically to drive increased receptor internalization, and there is both preclinical and clinical precedent for additive activity upon combining irreversible TKIs with ADCs in HER2-driven settings ELVN-002 3.5 mg/kg QD T-DXd 1.5 mg/kg Q3W x 1 ELVN-002 3.5 mg/kg QD + T-DXd 1.5 mg/kg Q3W x1 42#43Concentration (ng/mL) 10000 1000 100- 10 0.1- 0 ELVN-002 Achieved a Wide Safety Margin in Preclinical Species = CHI • ELVN-002 28-day GLP Tox NHP TK ● 10 hours 20 pEGFR IC 50 (A431, 50% human serum) HER2 YVMA GI90 (Ba/F3, protien adj.) pHER2 YVMA IC 50 (Beas2B, 100% human serum) 15 mg/kg 10 mg/kg 5 mg/kg 5 mg/kg NOD-SCID mouse (highly efficacious dose) Dose (mg/kg) 5 10 15 ELVN-002 Safety Margin at NHP NOAEL Fold vs. Highly Fold vs. Tucatinib Efficacious Exposure TGI-matched exposure 2 5 8 5 12 22 Based on preclinical exposures (AUC), ELVN-002 had a >10x larger safety margin compared to tucatinib in NHPs (HER2 amp setting) At its 28-day NOAEL, ELVN-002 had a wide safety margin in non-human primates (NHPs) and even wider safety margin in rats NHP = Non-human primate. NOAEL = No observed adverse event level. Highly Efficacious Exposure equals the total AUC of ELVN-002 at 5 mg/kg in NOD-SCID mouse (836 ng*hr/mL), which yielded robust tumor regression in a HER YVMA xenograft To determine Fold vs. Tucatinib TGI-matched exposure, we use the linearly extrapolated AUC of ELVN-002 at 2.5 mg/kg in Nude mouse, which roughly matches the TGI of Tucatinib at 20 mg/kg BID measured in an NCI-N87 xenograft model ELVN-002 NHP data shown are measured averages from Day 1 TK male animals in a 28-day GLP tox study References: Tucatinib NDA; Moulder, SL; et al. Data from a Completed Phase 1 Study to Assess the Safety, Tolerability and PK of ARRY-380-an Oral Inhibitor of HER2. SABCS, December 8-12, 2010, San Antonio, TX. NHP NOAEL At its approved dose, tucatinib only achieves IC., all day in ~40% of patients • Due to its larger safety margin, irreversible inhibition and improved PK profile, we believe ELVN-002 has the potential to achieve better target inhibition and improved efficacy compared to tucatinib 43#44ELVN-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 GOALS ● Earlier lines of therapy Combinations with approved ADCs (e.g., trastuzumab deruxtecan) Establish PoC for HER2-mutant NSCLC Evaluate intracranial activity and combinability with approved ADCs Explore potential beyond NSCLC in other HER2-driven solid tumors (i.e., MBC, CRC, etc.) ADC = Antibody drug conjugate. CRC = Colorectal cancer. MBC = Metastatic breast cancer. NSCLC = Non-small cell lung cancer. PoC = Proof of concept Registrational / Phase 3 TRIAL GOALS ● File on Late line HER2-mutant NSCLC Initial registrational studies HTH against standard of care as mono or combination with HER2 ADC in NSCLC and breast ● Accelerated Approval in late line HER2-mutant NSCLC Initiate registrational studies in early line MBC and HER2-mutant NSCLC 44#45Thank You