ACHV Achieve Life Sciences Inc

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 for smoking cessation, today announced that additional analyses from its Phase 3 ORCA-3 study will be presented during an oral presentation at the 2025 American Thoracic Society (ATS) International Conference in San Francisco, CA.

Presentation Details:

• Title: Cytisinicline Reduces Cravings and Nicotine Intake in People Who Smoke and Don’t Quit Completely
• Session: C95 – Public Health and Policy Relevant Research
• Format: Mini Symposium Oral Presentation
• Date & Time: Tuesday, May 20, 2025; 2:15 PM – 4:15 PM EDT
• Location: 2025 ATS International Conference

The oral presentation will highlight the unique benefit of cytisinicline treatment in clinical trials in reducing nicotine cravings which led to reduced nicotine intake, even in individuals who did not achieve complete smoking cessation. These analyses reinforce the importance of the dual mechanism of action for cytisinicline as a highly selective partial agonist and antagonist at the nicotinic acetylcholine receptor.

Data from the ORCA-3 Phase 3 study showed a significant reduction in craving scores for smoking as well as a corresponding and significant decrease in serum cotinine levels, a biomarker of nicotine exposure, among participants who received cytisinicline compared to placebo. In participants who did not quit smoking entirely, mean craving scores were significantly lowered compared with placebo (p=0.0001), which led to decreased cotinine levels of nearly four times more with cytisinicline treatment than with placebo.

“The observed reductions in nicotine exposure among participants who continued to smoke during cytisinicline treatment were roughly equivalent to a pack of cigarettes a week, and further reinforce cytisinicline’s potential to decrease tobacco dependence,” said Mark Rubinstein, MD, Head of Medical Affairs at Achieve. “By acting both as a highly selective partial agonist to reduce nicotine cravings and as an antagonist to blunt nicotine’s reward effects, cytisinicline may offer a valuable option for smokers, who are not yet ready to quit entirely. It may help them begin reducing their smoking while on a path to quitting with greater ease and confidence.”

The cessation outcomes recently published in JAMA Internal Medicine, along with these findings, underscore cytisinicline’s potential as a novel therapeutic option for smoking cessation. If approved, cytisinicline could play a critical role in alleviating the burden of smoking-related diseases, such as chronic conditions like Chronic Obstructive Pulmonary Disease (COPD), where quitting smoking remains the most effective intervention. Smoking is the leading cause of COPD, and cessation has been shown to not only slow disease progression but also improve the effectiveness of existing COPD treatments.

“As we approach submission of our New Drug Application next month, these clinical data continue to build a compelling case for cytisinicline’s therapeutic benefit and have the potential to redefine treatment of nicotine dependence as a serious medical condition, bringing real hope to the nearly 29 million adults in the U.S. alone who continue to smoke,” said Rick Stewart, Chief Executive Officer at Achieve. “Beyond treating the broader population of smokers, cytisinicline has also showed high quit rates among a subset of smokers with COPD in our Phase 3 trials, suggesting important benefits for cytisinicline in this high-risk population.”

About Achieve Life Sciences, Inc.  Achieve Life Sciences is a late-stage specialty pharmaceutical company committed to addressing the global smoking health and nicotine dependence epidemic through the development and commercialization of cytisinicline. The company has successfully completed two Phase 3 studies with cytisinicline for smoking cessation and one Phase 2 study with cytisinicline in vaping cessation. The company has fully enrolled its ongoing open-label safety study with cytisinicline and plans to submit its new drug application for smoking cessation in June 2025. Achieve has also conducted a successful end-of-Phase 2 meeting with the FDA for a future vaping indication. 

About Cytisinicline There are approximately 29 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 over 11 million adults in the United States who use e-cigarettes, also known as vaping.4 In 2024, approximately 1.6 million middle and high school students in the United States reported using e-cigarettes.5 There are no FDA-approved treatments indicated specifically as an aid to nicotine e-cigarette cessation. Cytisinicline has been granted Breakthrough Therapy designation by the FDA 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 for the treatment of nicotine addiction and has not been approved by the Food and Drug Administration 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 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, among others, the risk that cytisinicline may not demonstrate the hypothesized or expected benefits; the risk that Achieve 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 Achieve’s 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 Achieve’s filings with the Securities and Exchange Commission from time to time, 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.

Achieve Contact Nicole Jones ir@achievelifesciences.com 425-686-1510 

References 1VanFrank 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. 2World Health Organization. WHO Report on the Global Tobacco Epidemic, 2019. Geneva: World Health Organization, 2017. 3U.S. Department of Health and Human Services. The Health Consequences of Smoking – 50 Years of Progress. A Report of the Surgeon General, 2014. 4Cornelius ME, Loretan CG, Jamal A, et al. Tobacco Product Use Among Adults – United States, 2021. MMWR Morb Mortal Wkly Rep 2023;72:475–483. 5Jamal 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.