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1 Corporate Presentation November 2025 Transforming public health and delivering shareholder value
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2 Forward Looking Statements This presentation contains forward-looking statements, including, but not limited to, statements regarding the timing and nature of cytisinicline clinical development and regulatory review and approval; data results and commercialization activities; the potential market size for cytisinicline; the potential benefits, efficacy, safety and tolerability of cytisinicline; the ability to discover and develop new uses for cytisinicline, including but not limited to as an e-cigarette cessation product; the development and effectiveness of new treatments; the successful commercialization of cytisinicline; and expectations regarding cash forecasts. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Achieve Life Sciences, Inc. (“we,” “us,” “our,” or “the Company”) may not actually achieve its plans or product development goals in a timely manner, if at all, or otherwise carry out the intentions or meet the expectations or projections disclosed in these forward-looking statements. These statements are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements, including, among others, the risk that cytisinicline may not demonstrate the hypothesized or expected benefits; the risk that we may not be able to obtain additional financing to fund the development and commercialization of cytisinicline; the risk that cytisinicline will not receive regulatory approval in a timely manner or at all, or be successfully commercialized; the risk that new developments in the smoking and vaping cessation landscapes require changes in business strategy or clinical development plans; the risk that our intellectual property may not be adequately protected; general business and economic conditions; risks related to the impact on our business of macroeconomic and geopolitical conditions, including fluctuating inflation, interest and tariff rates, volatility in the debt and equity markets, actual or perceived instability in the global banking system, global health crises and pandemics and geopolitical conflict; and the other factors described in the risk factors set forth in the Company's filings with the Securities and Exchange Commission from time to time, including its Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q. The Company undertakes no obligation to update the forward-looking statements contained herein or to reflect events or circumstances occurring after the date hereof, other than as may be required by applicable law. These slides also contain 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. Certain data in this presentation are based on cross-study comparisons and are not based on any head-to-head clinical trials. Cross-study comparisons are inherently limited and may suggest misleading similarities and differences. The values shown in the cross-study comparisons are directional and may not be directly comparable.
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3 Cytisinicline, as a first potential new nicotine dependent treatment in nearly 20 years, gives Achieve Life Sciences a unique opportunity to treat an addressable market of up to 50 million Americans who use tobacco1 1 2 3 4 Focused launch strategy leveraging innovative, data-driven solutions to drive adoption and future growth. Competitive advantage with a highly differentiated and well- tolerated product profile and favorable payor environment with anticipated Affordable Care Act coverage. Cytisinicline PDUFA for treatment of nicotine dependence for smoking cessation expected June 20, 2026. Addressing nicotine dependence, an underserved public health crisis costing billions of dollars and impacting lives. 1. Cornelius ME, Loretan CG, Jamal A, et al. Tobacco Product Use Among Adults —United States, 2021. MMWR Morb Mortal Wkly Rep 2023;72:475–483. DOI: http://dx.doi.org/10.15585/mmwr.mm7218a1. 5 Vaping cessation indication, awarded Commissioner's National Priority Voucher (CNPV) and under FDA Breakthrough Therapy designation
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4 Introducing… Cytisinicline: Innovation, overdue. High Unmet Need Differentiated Product Profile Targeted Launch Strategy Lifecycle Expansion Opportunities • First potential new FDA-approved treatment 20 years • Limited competition in market or development • Strong demand anticipated from dissatisfied HCPs & patients • Highly selective MOA • Excellent efficacy & tolerability in 6- or 12-week treatment durations • Effective in treatment-resistant smokers • Relapse prevention • Once-daily oral dosing • Alternate admin routes (patch, spray, lozenge) • Expanded indications: long-term maintenance/relapse prevention, cutting down to quit • Synthetic cytisinicline manufacture • Large and clearly defined customer segments • Scalable for market share and/or market growth strategies • Ideal for leveraging AI & omnichannel communications cytisinicline
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5 Driving toward regulatory approval and launch Anticipated timeline and key milestones 1H’25 2H’25 1H’26 1H’26 2H’26 Smoking Cessation Expected Cytisinicline Milestones 6-month Completed Phase 3 Trial Preparation* NDA Submission Completed NDA Acceptance Phase 3 Trial Initiation* FDA Review Period FDA Approval PDUFA June 20, 2026 E-cigarette Cessation Product launch Timeline are estimates based on management current expectations that have no guarantee and may vary. *E-cigarette cessation program timeline is finance dependent.
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6 Over $600B in smoking- related U.S. health care costs annually 1 2-4x increased risk of CVD from smoking3 80% of deaths from lung cancer &COPD from smoking3 30-40% increased risk of Type 2 Diabetes from smoking3 9x increased risk of stroke from heavy smoking4 1. Centers for Disease Control and Prevention. (2024, September 17). Economic trends in tobacco. https://www.cdc.gov/tobacco/php/data-statistics/economic-trends/index.html. 2. VanFrank B, Malarcher A, Cornelius ME, Schecter A, Jamal A, Tynan M. Adult Smoking Cessation — United States, 2022. MMWR Morb Mortal Wkly Rep 2024;73:633–641; 3. USDHHS-The Health Consequences of Smoking-2014; 4. Bhat VM,-2008. Respiratory disease COPD and asthma Immune system diseases Infections, autoimmune diseases Neurodegenerative disease Dementia Cardiovascular disease Hypertension, heart attack and stroke Cancer Lung and multiple other cancers Type-2 Diabetes Nicotine dependency is a medical issue, requiring a medical solution 29M U.S. smokers with few treatment options2 Profound co-morbidity health harms from smoking
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7 ~60% of adult e-cigarette users want to quit 1 • Majority of people who vape are 18-24 and have never smoked3,4 • Instead of harm reduction, this is possible harm creation for this group • Many popular vapes used by young adults contain the nicotine equivalent of 13 packs of cigarettes5 • The cumulative exposure to vape aerosols over time in these young vapers could lead to severe nicotine dependence and the emergence of previously unknown lung diseases 1. Palmer AM, Smith TT, Nahhas GJ, et al. Interest in quitting e-cigarettes among adult e-cigarette users with and without cigarette smoking history. JAMA Netw Open. 2021;4(4):e214146. 2. Vahratian A, Briones EM, Jamal A, Marynak KL. Electronic cigarette use among adults in the United States, 2019–2023. NCHS Data Brief, no 524. Hyattsville, MD: National Center for Health Statistics. 2025. DOI: https://dx.doi.org/ 10.15620/cdc/174583 3. Cornelius ME, Loretan CG, Jamal A, Davis Lynn BC, Mayer M, Alcantara IC, Neff L. Tobacco Product Use Among Adults - United States, 2021. MMWR Morb Mortal Wkly Rep. 2023 May 5;72(18):475-483. 4. Centers for Disease Control and Prevention.QuickStats: Percentage distribution of cigarette smoking status among current adult e-cigarette users, by age group—National Health Interview Survey, United States, 2021. MMWR Morb Mortal Wkly Rep. 2023;72:270. 5. Leigh, N. J., Page, M. K., Jamil, H., & Goniewicz, M. L. (2024). Characteristics and ingredients of disposable ‘Elfbar’e‐cigarettes sold in the United States and the United Kingdom. Addiction. 6. National Center for Health Statistics. Percentage of current electronic cigarette use for adults aged 18 and over, United States, 2019—2024. National Health Interview Survey. Generated interactively: Jul 18 2025 from https://wwwn.cdc.gov/NHISDataQueryTool/SHS_adult/index.html ~17M U.S. adults reported use of e-cigarettes2 Source: National Center for Health Statistics, National Health Survey6
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8 Cytisinicline: The first new potential treatment option for nicotine dependence in 20 years
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9 Nicotine dependence alters brain chemistry Cytisinicline helps restore it Sources: 1. Perry D-1999; 2. Picciotto M-1998; 3. Coe, J.W. -2005; 4. Radchenko, E. V.-2015 Dual-acting mechanism of action SMOKER Increased Nicotine Receptors TREATMENT INITIATION Receptors Partially Blocked TREATMENT COMPLETION Receptors Normalized Addictive levels of Dopamine Dopamine levels start to normalize Normal Dopamine Cytisinicline blocks some of the receptors so that nicotine can't get in Cytisinicline is designed to provide just enough reinforcement to reduce craving Nicotine Dependence is a neurobiological cycle of craving and withdrawal
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10 Smoking cessation trials demonstrated clear benefits Efficacy, tolerability, craving reduction, broad patient response Key insights from smoking cessation trials (N=1602) Odds ratios exceeding all available treatment options in both 6- and 12-week dosing options Robust efficacy Excellent tolerability Nearly all single-digit rates of adverse events and excellent treatment adherence Broad patient response Cytisinicline benefited heavily pre-treated and hardened smokers regardless of gender, age, prior quit attempts (# and methods), and other concomitant medical conditions Clear and significant reductions in overall urges and cravings occurred within 6 weeks of cytisinicline treatment Reduction in cravings and urges
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11 Strong results from smoking cessation trials ORCA-2 and ORCA-3: Efficacy, tolerability, craving reduction, broad patient response Cytisinicline Placebo 32.6% 30.3% 7.0% 9.4% 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 35.0% Quit Rates Odds Ratio: 6.3 (p<0.0001) Odds Ratio: 4.4 (p<0.0001) 12-week Cytisinicline Treatment Primary Endpoint (Weeks 9-12) 25.3% 14.8% 4.4% 6.0% 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 6-week Cytisinicline Treatment Primary Endpoint (Weeks 3-6) Odds Ratio: 8.0 (p<0.0001) Odds Ratio: 2.85 (p=0.0008) Quit Rates Source: ORCA-2: Rigotti NA, Benowitz NL, Prochaska JJ, et al. Cytisinicline for Smoking Cessation: A Randomized Clinical Trial. JAMA. 2023;330(2):152–160. ORCA-3: Rigotti NA, Benowitz NL, Prochaska JJ, et al. Cytisinicline for Smoking Cessation: The ORCA Phase 3 Replication Randomized Clinical Trial. JAMA Intern Med. Published online April 21, 2025. doi:10.1001/jamainternmed.2025.0628
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12 Overall effectiveness: Pooled Phase 3 studies Cytisinicline demonstrates higher abstinence rates vs placebo Abstinence by self-report of not smoking and verified by carbon monoxide < 10ppm Source: ORCA-2 and ORCA-3 Pooled Phase 3 Results - Data on File; Achieve Life Sciences, Inc. 6-week Cytisinicline Treatment 12-week Cytisinicline Treatment Point prevalence abstinence rates by week for placebo vs 6-weeks or 12-weeks cytisinicline
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13 Highly selective targeting improves tolerability profile Adverse event profile compared to Chantix® Cytisinicline3 Varenicline (Chantix®)2 Adverse Events Selective Receptor Targeting3Comparative Analysis of Safety Events* Cytisinicline1 Varenicline (Chantix®)2 Treatment Time Adverse Events 12 weeks 12 weeks Chantix® is a registered trademark of Pfizer, Inc. 1. Data on file; Achieve Life Sciences ORCA-2 & ORCA-3 pooled data. 2. Chantix Prescribing Information, 6/2018 Pfizer, Inc. 3. Coe J et al. J. Med. Chem. 2005, 48:3474-3477; Papke RL et al. JPET. 2011, 337:367–379; Slater YE et al. Neuropharm. 2003, 44:503–515; Lummis SCR et al. JPET. 2011, 339:125–131. 4. Lummis, SCR, Price,KL, Clarke A, SRNT-E 2020. *Not a head-to-head comparison trial evaluation. α4β2 5-HT3 α7 Nausea Sleep Disturbances Headache, GI Upsetα4β2 Cytisinicline is >2000 fold less potent at the human 5-HT3 receptor4 6.2%Nausea 30% 10.8%Insomnia 18% 7.7%Abnormal Dreams 13% Headache 8.1% 15%
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14 Comparable quit rates in COPD and non-COPD smokers 5.8 5.3 6.3 19.3% 17.3% 32.6% 19.1% 5.5% 2.1% 8.6% 4.3% 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 35.0%Quit Rates Cytisinicline Placebo No-COPD No-COPDCOPD COPD Primary Endpoint (Weeks 3-6) Primary Endpoint (Weeks 9-12) Odds Ratio: 4.1 Odds Ratio: 9.7 Odds Ratio: 5.2 Odds Ratio: 5.3 Prochaska, J., Rubinstein, M., Perdok, R., Blumenstein, B., & Jacobs, C. (2025). Cytisinicline for smoking cessation in individuals with self-reported COPD: a post hoc analysis of the ORCA-2 and ORCA-3 trials. Thorax. Quitting smoking remains the most impactful intervention for COPD, and cytisinicline is being explored as a potential therapy to help address this critical need. Aligns with Achieve’s broader strategy to expand indications to vaping cessation and beyond Efficacy and tolerability extend to heavier, more treatment-experienced smokers
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15 Commissioner’s National Priority Voucher for vaping Cytisinicline one of nine treatments awarded CNPV • CNPV program accelerates the review of products that align with national priorities • Selected products must address large emerging public health needs such as crises, provide innovative cures, address unmet medical needs or enhance national security through drug development and manufacturing to advance the health interests of the U.S. • Rapid approval in 1-2 months compared to standard 10-12 months • Enhanced communication with FDA reviewers to streamline development and approval processes • Non-transferable designation
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16 Vaping trial expands nicotine dependence opportunity Efficacy, tolerability, compliance, Phase 3 warranted Phase 2 ORCA-V1 trial design Key insights from vaping cessation trial (N=160) Arm A (N=53) Randomize Follow- up Placebo TID 12 weeks + Behavioral support Arm B (N=107) 3.0 mg Cytisinicline TID 12 weeks + Behavioral support Nicotine E-Cigarette Cessation Trial Greater compliance observed in cytisinicline-treated arm compared to placebo Statistically significant quit rates despite small sample size showing 2.6x (p=0.035) increased likelihood of quitting Robust efficacy Excellent tolerability Favorable adverse event profile demonstrated, no serious adverse events reported Phase 3 warranted Strong evidence supporting use of cytisinicline for vaping cessation to be further evaluated in Phase 3 ORCA-V2 trial High-level compliance Source: Rigotti NA, Benowitz NL, Prochaska JJ, et al. Cytisinicline for Vaping Cessation in Adults Using Nicotine E-Cigarettes: The ORCA-V1 Randomized Clinical Trial. JAMA Intern Med. 2024;184(8):922–930.
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17 Granted CNPV and Breakthrough Therapy designation for cytisinicline in vaping cessation Phase 3 ORCA-V2 trial design for vaping cessation Phase 3 ORCA-V2 trial design Arm A (N=53) Randomize Follow- up Arm B (N=107) 3.0 mg Cytisinicline TID 12weeks + Behavioral support Nicotine E-cigarette cessation trial Source: Rigotti NA, Benowitz NL, Prochaska JJ, et al. Cytisinicline for Vaping Cessation in Adults Using Nicotine E-Cigarettes: The ORCA-V1 Randomized Clinical Trial. JAMA Intern Med. 2024;184(8):922–930. Randomize Placebo TID 12 weeks + Behavioral support Placebo TID 12 weeks + behavioral support Arm A (N=400) 3 mg cytisinicline TID 12 weeks + behavioral support Arm B (N=400)
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18 Innovative and Focused... a data-driven commercialization strategy for maximum impact
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19 Attractive market conditions to launch the first smoking cessation treatment in 20 years Clearly defined customer segments with high unmet need Well-established therapeutic category Ease of market entry and prescribing Quiet promotional landscape Limited treatment options with nothing new since 2006 – most have tried and failed Harms of smoking are known – education to focus on optimal patient selection ACA coverage expected Favorable tolerability profile reduces HCP burden No branded products to battle for share of voice and customer headspace – nothing new on the horizon
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20 Unlocking value by addressing a critical unmet public health need ~15.4M adults who smoke attempt to quit annually1 ~29M1 adult smokers Estimated 60% want to quit4 ~17M3 adult vape users $11 Billion Estimated Rx Opportunity2 ~53% attempt to quit smoking annually1 ~50% who saw an HCP received advice about quitting5 <10% successfully quit1 No new FDA-approved options in nearly 20 years CDC estimates 36% of people who smoke utilize Rx and OTC cessation treatments annually5 Lack of options for people who want to quit & for HCPs 1. VanFrank B, Malarcher A, Cornelius ME, et al. Adult Smoking Cessation United States, 2022. MMWR Morb Mortal Wkly Rep 2024;73:633-641 2. Estimate of $500/mo. Chantix pricing – 1 mo.. Rx/patient 3. Vahratian A, Briones EM, Jamal A, Marynak KL. Electronic cigarette use among adults in the United States, 2019–2023. NCHS Data Brief, no 524. Hyattsville, MD: National Center for Health Statistics. 2025. DOI: https://dx.doi.org/ 10.15620/cdc/174583 4. Palmer AM, Smith TT, Nahhas GJ, et al. Interest in quitting e-cigarettes among adult e-cigarette users with and without cigarette smoking history. JAMA Netw Open. 2021;4(4):e214146. 5. Centers for Disease Control Smoking Cessation Fast Facts, accessed 2/8/25.
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21 Precise targeting of high-volume prescribers and engaged quitters Focus at Launch on Audiences Most Likely to Take Action: High-Volume Prescribers & Engaged Quitters Cessation Rx Enthusiasts Highly Motivated Quitters • High prescribing volume of varenicline • Sizeable smoking population in practice • Actively initiates in cessation discussions and follows up • Prefers Rx to natural treatments • Favorable impression of cytisinicline • Heavy, long-term smoker embarrassed of habit and concerned about its health impact • Consider quitting a top priority • Confident in healthcare system and utilize it regularly • Proactively pursue Rx from doctor • Willing to take oral medication for 6 -12 weeks Changing the Narrative about Nicotine Dependence Medical Issue vs. Moral Issue Drive Awareness & Education of Cytisinicline First New Treatment in 20 Years Source: ACHV Data on File; HCP & Patient Segmentation, S ymphony Nicotine Dependence Claims Analysis 2023
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22 Focused Health Care Provider (HCP) launch strategy Built for growth: initial target on varenicline market share • Chantix peaked at ~2.8M Rx (75% in U.S. market - $800M)1,2 • Launch focus on priority, primary care HCP targets to convert varenicline market share to cytisinicline • Designed to establish foothold and direct future expansion efforts on additional targets, other product conversion, and/or market growth initiatives. Varenicline Universe Varenicline Market Launch target: High volume HCPs Expansion to include all varenicline HCPs All prescribers of any Rx Cessation Treatment Smoking Cessation Total Market SmokingCessation Rx Total Market 1 2 3 Market share launch strategy: Phased digital + F2F/virtual promotion to high-decile prescribers 1. Symphony Nicotine Dependence Claims Analysis 2023 2. PFE 10k 2019 2nd wave expansion option: Extend promotion efforts to additional targets 3rd wave expansion option: Conversion of buproprion, NRT, and market growth HCP = Health Care Provider
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23 Traditional pharma promotional model is evolving HCP access and engagement preferences have changed Traditional approach: Activity based & siloed Over-indexing on F2F sales rep-to-doctor interactions and rep-provided content Field Sales Calls HCP Rep-provided “Nonpersonal” Promotion Speaker Programs/ Conferences Ignores HCP reality 1. Veeva Pulse Field Trend Report, Jan.-Dec. 2023. 2. P360 “Maximizing Pharma Sales Call Effectiveness in Today's Industry” Dec. 2023. 3. Prescriber Point Maximizing HCP engagement with your mobile & social media channels, July 2024. 75% IM HCPs do not meet with pharma reps1 1 to 3 minutes Time HCPs give rep for in-person discussion2 73 minutes Average time HCP spends daily engaging with non- branded affiliated digital and social channels3
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24 Integrated ecosystem is required HCP access and engagement preferences have changed Leverages AI and ML to orchestrate fully integrated services with more agility and efficiency AI/ML Data Engine HCP Patient FORMULARY COVERAGE CO-PAY CARDS/ PATIENT SUPPORT Selective F2F Rep HCP Digital Campaign Virtual Rep DTC Digital Campaign Telehealth Prevalence & distribution dataAI/ML Data Warehouse
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25 AI as a strategic enabler Unified Data Ecosystem Customer Journey & Insights Marketing Resource Management CX Orchestration & Omnichannel Activation Marketing Measurement & Analytics Personalization & Content Management Data Integration & Intelligence: Unify marketing, sales, and medical data 1 AI-Driven Personalization: Dynamic engagement with HCPs & Patients 2 Predictive & Prescriptive Analytics: Forecast trends, optimize outreach, and maximize engagement 3 Marketing / Workflow Automation: Streamline campaign planning & execution, ensuring compliance 4 AI Enablement FocusMarTech Capabilities Content Production: Streamline content creation, ensuring compliance 5 AI is a critical enabler in our marketing evolution: enhancing data-driven decision- making, customer engagement, automation, and predictive insights
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26 I N G E S T I N T O A N D A C T I V AT E F R O M A U N I F I E D D ATA E C O S Y S T E M Enable targeting precision through enriched profiles Drive activation success with actionable insights Ensure compliance with data privacy standards D A T A N E E D S D A T A G O A L S HCP Decile-based prescribing behavior and openness to prescribing Channel Performance metrics across digital, social, and offline channels Public Health & Regulatory Market and competitor trends, legislation and insurance changes, and research outcomes Patient Designed Enriched behavioral and demographic data (e.g., search behavior, smoking cessation intent) Role of data in Achieve’s marketing strategy Achieve’s data requirements are anchored in strategic marketing imperatives
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27 Launch focus on data-driven omnichannel approach Right message, right time, right channel - to optimize reach and impact Data Warehouse Data Engine HCP Toolkit Examples Patient Toolkit Example F2F Reps Email Virtual Sales Reps Social KOL Content Banner Ads Social Paid Search Earned Media Professional Networks ADVOCACYFREEDOM ADHERENCE EVALUATION ENGAGEMENT Path To Prescription Path To Advocacy INTEREST AWARENESS POST-PRESCRIPTION Rx
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28 Transforming public health while delivering shareholder value
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29 ACHV: Poised to disrupt and drive value Executive summary Public health priority Smoking is the leading cause of preventable death and disease.1 Covered by the Affordable Care Act.2 Strong IP position Broad IP portfolio and patent protection to 2040. Synthetic cytisinicline IP pending. Clear commercial vision Large and underserved market opportunity and patient need for new and effective treatment for nicotine dependence. Near-term solution With a compelling data package and differentiated product profile, we believe cytisinicline is well- positioned to become the new standard of care for nicotine dependence. Cash position Cash runway into the second half of 2026. Proven leadership Executive team and board of directors with track record of successful value creation. 1. US Department of Health and Human Services. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. Centers for Disease Control and Prevention; 2014. https://www.cdc.gov/tobacco/sgr/50th -anniversary/index.htm. 2. US Department of Health and Human Services. Patient Protection and Affordable Care Act Health-Related Portions of Health Care and Education Reconciliation Act; 20210. https://www.hhs.gov/healthcare/about-the-aca/index.html.
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