Cytisinicline

SEATTLE and VANCOUVER, British Columbia, March 26, 2026 (GLOBE NEWSWIRE) -- Achieve Life Sciences, Inc. (Nasdaq: ACHV), a late-stage specialty pharmaceutical company focused on the global development and commercialization of cytisinicline as a treatment of nicotine dependence, today announced the publication of a manuscript in Nicotine & Tobacco Research describing the receptor selectivity profile of cytisinicline. This study provides mechanistic characterization of cytisinicline’s receptor selectivity profile, which informs understanding of its favorable tolerability. There have been no new FDA-approved treatments for smoking cessation in 20 years, and there are currently no FDA-approved treatments for vaping cessation. Of the approximately 25 million U.S. adults who smoke and the nearly 18 million U.S. adults who vape, more than half want to quit.1 Research shows only 10% of people who try to quit smoking each year are successful, signaling the need for more treatment options.2 The Nicotine & Tobacco Research publication, entitled “Receptor Selectivity of Cytisinicline: Minimal 5-HT3 Binding May Explain Lower Incidence of Nausea in Smoking Cessation Therapy,” demonstrates that cytisinicline binds to the nicotinic receptor, which is believed to reduce nicotine cravings and support smoking cessation, while showing it has minimal interaction with the serotonin receptor known to trigger nausea. This may be appealing for people who are trying to quit smoking but have struggled with tolerability in past quit attempts.3-5 Key Findings: Strong binding: Cytisinicline demonstrated strong binding at the α4β2 nicotinic receptor, displacing nearly all (99%) of the comparison compound in laboratory testing. This high level of receptor engagement suggests cytisinicline effectively targets the mechanism associated with smoking cessation. Minimal 5-HT3 receptor displacement: At the same concentration, cytisinicline showed minimal displacement (-8%) at the 5-HT3 receptor, indicating negligible binding under assay conditions. This minimal interaction is significant as activation of the 5-HT3 receptor is known to induce nausea, which helps explain cytisinicline's tolerability profile observed in clinical trials. “These findings from our preclinical program provide additional insights regarding cytisinicline’s pharmacologic profile and support observations from clinical studies,” said Mark Rubinstein, MD, Chief Medical Officer of Achieve Life Sciences. "Namely, these results may lend further biological basis for why cytisinicline has such low rates of adverse events like nausea, which is thought to be linked to binding at the 5-HT3 receptor.” The data in this publication complement late-breaking voluntary survey data from ORCA-OL that were recently presented at the Society for Research on Nicotine & Tobacco (SRNT) 2026 Annual Meeting. The open-label, long-term exposure safety study of cytisinicline followed participants for up to one year of treatment. In the voluntary post-trial survey of cytisinicline use, participants self-reported high quit and reduction rates of nicotine use, driven by fewer cravings, and few or manageable side effects. Together, these data contribute to a more complete understanding of cytisinicline’s potential impact on the lives of people who smoke as they strive to quit nicotine. Nicotine dependence remains a leading cause of preventable death, claiming nearly half a million lives annually in the United States alone.6-7 Despite the availability of smoking cessation pharmacotherapies, poor tolerability and side effects remain significant barriers to effective treatment. About Achieve Life Sciences, Inc.  Achieve Life Sciences, Inc. is a late-stage specialty pharmaceutical company focused on the global development and commercialization of cytisinicline as a treatment of nicotine dependence. In September 2025, the company announced that its New Drug Application, submitted to the U.S. Food and Drug Administration (FDA) in June 2025, had been accepted for review. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) date of June 20, 2026. The NDA is for cytisinicline to be used as a treatment of nicotine dependence for smoking cessation in adults, based on two successfully completed Phase 3 studies and its open-label safety study. Additionally, the company has completed a Phase 2 study with cytisinicline in vaping cessation and conducted a successful end-of-Phase 2 meeting with the FDA for a future vaping indication.  About Cytisinicline There are approximately 25 million adults in the United States who smoke combustible cigarettes.1 Tobacco use is currently the leading cause of preventable death that is responsible for more than eight million deaths worldwide and nearly half a million deaths in the United States annually. 6-7 More than 87% of lung cancer deaths, 61% of all pulmonary disease deaths, and 32% of all deaths from coronary heart disease are attributable to smoking and exposure to secondhand smoke.7 In addition, there are nearly 18 million adults in the United States who use e-cigarettes, also known as vaping.1 In 2024, approximately 1.6 million middle and high school students in the United States reported using e-cigarettes.8 There are no FDA-approved treatments indicated specifically as an aid to nicotine e-cigarette cessation. FDA has awarded the Commissioner’s National Priority Voucher for e-cigarette or vaping cessation and granted Breakthrough Therapy designation to address this critical need. Cytisinicline is a plant-based alkaloid with a high binding affinity to the nicotinic acetylcholine receptor. It is believed to aid in treating nicotine addiction for smoking and e-cigarette cessation by interacting with nicotine receptors in the brain, reducing the severity of nicotine craving symptoms, and reducing the reward and satisfaction associated with nicotine products. Cytisinicline is an investigational product candidate being developed as a treatment of nicotine dependence for smoking cessation and has not been approved by the FDA for any indication in the United States. Forward Looking Statements This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements Achieve makes 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 development and effectiveness of new treatments, and the successful commercialization of cytisinicline. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Achieve may not actually achieve its plans or product development goals in a timely manner, if at all, or otherwise carry out its intentions or meet its 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 Achieve’s Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q. Achieve 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. Achieve Contact Nicole Jones VP, Strategic Communications and Stakeholder Relations ir@achievelifesciences.com 425-686-1510 References Released March 26, 2026

Achieve also Announces Partnership with U.S.-based Adare Pharma Solutions for Cytisinicline Manufacturing Conference Call Scheduled for 8:30 AM EDT Today, March 24, 2026 SEATTLE and VANCOUVER, British Columbia, March 24, 2026 (GLOBE NEWSWIRE) -- Achieve Life Sciences, Inc. (Achieve) (Nasdaq: ACHV), a late-stage specialty pharmaceutical company focused on the global development and commercialization of cytisinicline as a treatment of nicotine dependence, today announced financial results for the fourth quarter and full year 2025 and provided updates on the cytisinicline development program, including the announcement of its partnership with Adare Pharma Solutions (Adare). “Achieve is fully committed to bringing cytisinicline to the millions of people who continue to struggle with nicotine dependence and need a new solution to help them quit. Much like GLP-1 therapies have transformed the way obesity is treated, shifting it from a lifestyle issue to a recognized medical condition, smoking cessation deserves the same evolution,” said Rick Stewart, President and Chief Executive Officer of Achieve. “Achieve is not quitting on smokers or people who want to quit vaping. We are relentlessly working towards the potential approval of cytisinicline, the initiation of the Phase 3 vaping trial, and a data-driven, highly targeted commercial launch approach.” Achieve has selected Adare, based in the U.S., to manufacture cytisinicline drug product for potential commercial launch and beyond. Achieve expects this partnership will help decrease risks related to international importation of pharmaceuticals and reduce costs, including potential tariffs. Achieve has commenced the technology transfer to Adare. In addition to potential cost-savings, the Adare partnership provides supply chain redundancy and U.S.-based contingency capacity. One manufacturer named in the cytisinicline NDA recently underwent an FDA current Good Manufacturing Practices inspection, where two observations related to solid oral dose manufacturing were identified, which are being addressed through an ongoing communication with FDA of its remedial action plan. The company anticipates U.S. commercial launch in the first half of 2027. Mr. Stewart commented further, “Establishing U.S. manufacturing with Adare increases our confidence in our supply chain and continues our strong progress towards launch.” Key Highlights Made meaningful progress toward regulatory approval in smoking and vaping: FDA accepted the cytisinicline NDA for treatment of nicotine dependence for smoking cessation in adults, assigning a PDUFA targeted action date of June 20, 2026. Completed the ORCA-OL long-term exposure trial with 334 participants finishing the one-year study, providing comprehensive long-term safety data for cytisinicline and significantly exceeding the number of patients required for FDA review. Cytisinicline was selected as one of the first nine therapies chosen for the inaugural FDA Commissioner’s National Priority Voucher for e-cigarette or vaping cessation. The voucher is designed to provide enhanced FDA communications and expedited review, once complete materials are submitted to the FDA. Preparation for commercial readiness in anticipation of launch: Completed supply chain and market access readiness activities, including beginning implementation of third-party logistics provider and specialty pharmacy partner selection. Announced partnership with Omnicom across multiple, cross-functional agencies to create a data-driven commercial model designed to execute with precision, scale efficiently and accelerate meaningful engagement for patients and providers. Advanced scientific exchange surrounding nicotine dependence, including: Complete results from its ORCA-3 trial were published in the Journal of the American Medical Association (JAMA) Internal Medicine . The authors concluded that ORCA-3 reaffirms cytisinicline’s efficacy and tolerability for smoking cessation in adult smokers at both 6- and 12-week treatment durations, including reduction in nicotine cravings and extended cessation benefits through 24 weeks. Publication of new data in Thorax demonstrated that cytisinicline significantly increased continuous smoking abstinence versus placebo in both chronic obstructive pulmonary disease (COPD) and non-COPD subgroups. Despite more severe tobacco use histories and greater prior treatment exposure, participants with COPD achieved quit rates comparable to those without COPD. Presented new data at the Society for Research on Nicotine and Tobacco (SRNT) 2026 Annual Meeting indicating that cytisinicline delivers meaningful quitting success, regardless of participants' prior use of smoking cessation medications or number of previous quit attempts. Presented late-breaking survey data from ORCA-OL at SRNT , which followed participants for up to one year of treatment. The voluntary post-trial survey offered insights into patient-reported experiences with the extended use of cytisinicline beyond the 6- and 12-week courses previously studied. “Our comprehensive clinical program demonstrates cytisinicline's potential to address a persistent, public health challenge,” said Mark Rubinstein, MD, Chief Medical Officer of Achieve. “The SRNT findings are particularly encouraging because they indicate that cytisinicline helps people quit smoking regardless of their prior treatment history or number of prior attempts, and, if approved, could offer hope to those who have struggled to quit. Combined with our published research on cytisinicline's tolerability profile, we have a comprehensive body of evidence that could represent a potential new standard of care in nicotine dependence treatment.” Financial Results As of December 31, 2025, the company’s cash, cash equivalents, and marketable securities were $36.4 million. Total operating expenses for the three and twelve months ended December 31, 2025, were $14.7 million and $54.9 million, respectively. Total net loss for the three and twelve months ended December 31, 2025, was $14.7 million and $54.7 million, respectively. Conference Call Details Achieve will host a conference call at 8:30 AM EDT today, Tuesday, March 24, 2026. To access the webcast, please use the following link: 4Q25 Earnings Webcast . Alternatively, you may join the live conference call by dialing 877-269-7756 (U.S. & Canada) or 201-689-7817 (International) and referencing conference ID 13758715. A webcast replay will be available approximately three hours after the call and archived on the website for 90 days. About Achieve Life Sciences, Inc. Achieve Life Sciences, Inc. is a late-stage specialty pharmaceutical company focused on the global development and commercialization of cytisinicline as a treatment of nicotine dependence. In September 2025, the company announced that its New Drug Application, submitted to the U.S. Food and Drug Administration (FDA) in June 2025, had been accepted for review. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) date of June 20, 2026. The NDA is for cytisinicline to be used as a treatment of nicotine dependence for smoking cessation in adults, based on two successfully completed Phase 3 studies and its open-label safety study. Additionally, the company has completed a Phase 2 study with cytisinicline in vaping cessation and conducted a successful end-of-Phase 2 meeting with the FDA for a future vaping indication. About Cytisinicline There are approximately 25 million adults in the United States who smoke combustible cigarettes. 1 Tobacco use is currently the leading cause of preventable death that is responsible for more than eight million deaths worldwide and nearly half a million deaths in the United States annually. 2,3 More than 87% of lung cancer deaths, 61% of all pulmonary disease deaths, and 32% of all deaths from coronary heart disease are attributable to smoking and exposure to secondhand smoke. 3 In addition, there are nearly 18 million adults in the United States who use e-cigarettes, also known as vaping. 1 In 2024, approximately 1.6 million middle and high school students in the United States reported using e-cigarettes. 4 There are no FDA-approved treatments indicated specifically as an aid to nicotine e-cigarette cessation. FDA has awarded the Commissioner’s National Priority Voucher for e-cigarette or vaping cessation and granted Breakthrough Therapy designation to address this critical need. Cytisinicline is a plant-based alkaloid with a high binding affinity to the nicotinic acetylcholine receptor. It is believed to aid in treating nicotine addiction for smoking and e-cigarette cessation by interacting with nicotine receptors in the brain, reducing the severity of nicotine craving symptoms, and reducing the reward and satisfaction associated with nicotine products. Cytisinicline is an investigational product candidate being developed as a treatment of nicotine dependence for smoking cessation and has not been approved by the FDA for any indication in the United States. Forward Looking Statements This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements Achieve makes regarding the timing, nature and outcome of cytisinicline clinical development and regulatory review and approval, data results, the timing, nature and success of Achieve’s commercialization activities, the potential market size for cytisinicline, the potential benefits, efficacy, safety and tolerability of cytisinicline, the development and effectiveness of new treatments, the performance of Achieve’s third-party manufacturing partners, and the successful launch and commercialization of cytisinicline. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Achieve may not actually achieve its plans or product development goals in a timely manner, if at all, or otherwise carry out its intentions or meet its 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 Achieve’s Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q. Achieve 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. Achieve Contact Nicole Jones VP, Strategic Communications and Stakeholder Relations ir@achievelifesciences.com 425-686-1510 References 1 National Center for Health Statistics. National Health Interview Survey, 2023 and 2024 . 2026 ( ). 2 World Health Organization. WHO Report on the Global Tobacco Epidemic, 2019. Geneva: World Health Organization, 2017. 3 U.S. Department of Health and Human Services. The Health Consequences of Smoking – 50 Years of Progress. A Report of the Surgeon General, 2014. 4 Jamal A, Park-Lee E, Birdsey J, et al. Tobacco Product Use Among Middle and High School Students — National Youth Tobacco Survey, United States, 2024. MMWR Morb Mortal Wkly Rep 2024;73:917–924. Consolidated Statements of Loss (In thousands, except per share and share data) Three months ended| December 31, Twelve months ended December 31, 2025 2024 2025 2024 Operating expenses: Research and development 3,874 7,296 22,998 22,817 General and administrative 10,857 4,894 31,882 16,252 Total operating expenses 14,731 12,190 54,880 39,069 Loss from operations (14,731 ) (12,190 ) (54,880 ) (39,069 ) Other income (expense) 69 (170 ) 232 (758 ) Net loss $ (14,662 ) $ (12,360 ) $ (54,648 ) $ (39,827 ) Basic and diluted net loss per share $ (0.28 ) $ (0.36 ) $ (1.25 ) $ (1.24 ) Weighted average number of basic and diluted common shares 53,276,361 34,510,786 43,594,652 32,071,146 Consolidated Balance Sheets (In thousands) December 31, December 31, 2025 2024 Assets: Cash, cash equivalents and marketable securities $ 36,404 $ 34,360 Prepaid expenses and other current assets 3,485 2,107 Other assets and restricted cash 52 39 Right-of-use assets 64 119 License agreement 751 974 Goodwill 1,034 1,034 Total assets $ 41,790 $ 38,633 Liabilities and stockholders' equity: Accounts payable and accrued liabilities $ 3,760 $ 6,627 Current portion of long-term obligations 61 55 Current portion of convertible debt 3,704 — Contingent consideration 1,557 1,149 Non-current portion of convertible debt 11,185 9,837 Other long-term obligations 5 66 Stockholders' equity 21,518 20,899 Total liabilities and stockholders' equity $ 41,790 $ 38,633