ORCA-3 Demonstrated a Significant Increase in Quitting and Reduction in Nicotine Cravings for Cytisinicline-Treated Participants Compared to Placebo Cytisinicline New Drug Application (NDA) Submission to FDA Planned for June 2025 SEATTLE and VANCOUVER, British Columbia, April 21, 2025 (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 for sm ...

Financial Data and Key Metrics Changes - As of December 31, 2024, the company's cash, cash equivalents, and marketable securities were $34.4 million, up from $15.6 million on December 31, 2023, indicating a significant increase in liquidity [34] - Total operating expenses for Q4 2024 were $12.2 million, and for the year ended December 31, 2024, they were $39.1 million, reflecting the company's ongoing investment in its strategic initiatives [35] - The net loss for Q4 2024 was $12.4 million, and for the year, it was $39.8 million, showing a consistent financial performance as the company transitions towards commercialization [35] Business Line Data and Key Metrics Changes - The company is focused on the NDA submission for cytisinicline, a treatment for nicotine dependence, with a planned submission by the end of Q2 2025 [7][43] - The ORCA Open Label Long-Term Safety Exposure clinical trial has completed enrollment with 479 participants, meeting FDA requirements for the NDA submission [11][18] Market Data and Key Metrics Changes - The company aims to address the nicotine dependence crisis, which affects approximately 29 million Americans, with 15 million attempting to quit each year [14] - The health risks associated with smoking and vaping are becoming increasingly recognized, emphasizing the need for effective treatment options like cytisinicline [9] Company Strategy and Development Direction - Achieve Life Sciences is transitioning from a clinical to a commercial company, with a focus on launching cytisinicline as a first-in-class treatment for nicotine dependence [12][23] - The company is also preparing for a Phase 3 trial for vaping cessation, with plans to initiate it in the first half of 2026, depending on financing [21][23] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the NDA submission process and the potential of cytisinicline to become a best-in-class treatment for nicotine dependence [23][43] - The company is committed to effective cash management to support its strategic goals and maximize shareholder value [36][44] Other Important Information - The company received Breakthrough Therapy designation for cytisinicline as a treatment for vaping cessation, highlighting its potential impact in the market [11][22] - The management team has been strengthened with new appointments, including a CFO to oversee financial strategy [12] Q&A Session Summary Question: Clarification on NDA submission requirements - Management confirmed that the NDA submission is on track, with all necessary documents being finalized and external consultants assisting in the process [48][50] Question: Commercial access and distribution strategy - The company is considering a specialty pharmacy model to track prescriptions and mitigate access barriers, while also preparing for payer discussions [54][56] Question: Potential partnerships for comorbid indications - Management indicated that while there is interest in partnerships, the primary focus remains on the NDA submission and the U.S. market opportunity [62][90] Question: Future DSMC reviews and CMC readiness - Management confirmed that additional DSMC reviews are expected, and external consultants are being utilized to ensure the NDA's quality [70][72] Question: Sales ramp and market segmentation - The company anticipates a slow sales ramp post-launch, focusing on high-volume prescribers and motivated patients for cytisinicline [80][84] Question: Patient satisfaction with current treatments - Research indicates low satisfaction rates with existing treatments like varenicline, suggesting a strong opportunity for cytisinicline [113][115] Question: Vaping study expectations - The company is preparing for higher placebo rates in future studies and has designed the Phase 3 trial accordingly [144]

Drug Development and Efficacy - Cytisinicline is expected to be the first new prescription medicine for smoking cessation in nearly two decades, with a New Drug Application (NDA) filing anticipated at the end of Q2 2025[21]. - The FDA granted Breakthrough Therapy Designation for cytisinicline for nicotine e-cigarette cessation, indicating substantial improvement over existing therapies[20][39]. - Cytisinicline has demonstrated robust efficacy with minimal adverse events in two randomized placebo-controlled Phase 3 studies[24][29]. - The ORCA-OL trial has enrolled 479 subjects across 29 clinical trial sites, with safety data from at least 300 subjects completing six months of treatment to be included in the NDA submission[46][48]. - Cytisinicline is a plant-based alkaloid that acts as both a receptor agonist and antagonist, targeting nicotine dependence by reducing withdrawal symptoms and the reward associated with nicotine[23][25]. - The company plans to initiate Phase 3 clinical development for nicotine dependence related to e-cigarettes in H1 2026, with completion expected approximately 12 months after initiation[21]. - In the Phase 2b ORCA-1 trial, cytisinicline treatment arms demonstrated a 74-80% median reduction in cigarettes smoked, compared to a 62% reduction in placebo arms[60]. - The 3 mg TID cytisinicline arm achieved a 50% abstinence rate at week 4, compared to 10% for placebo (p<0.0001)[61]. - In the Phase 3 ORCA-2 trial, the continuous abstinence rate from week 9 to 24 was 21.1% for the 12-week cytisinicline arm compared to 4.8% for placebo (OR of 5.3, p<0.0001)[73]. - The ORCA-V1 trial showed a vaping cessation rate of 31.8% for cytisinicline compared to 15.1% for placebo (p=0.04)[69]. - Cytisinicline was well tolerated across trials, with no serious adverse events reported[63][70]. - The renal impairment study indicated that cytisinicline pharmacokinetics are dependent on renal function, and it was well tolerated in subjects with varying degrees of renal impairment[57]. - The cardiac safety study demonstrated that cytisinicline has no clinically relevant effect on QT interval prolongation[58]. - Cytisinicline treatment resulted in a 32.6% smoking abstinence rate during weeks 9-12 compared to 7.0% for placebo, with an odds ratio of 6.3 (p<0.0001) for the 12-week treatment group[75]. - In the 6-week cytisinicline treatment group, the smoking cessation rate was 25.3% during weeks 3-6 compared to 4.4% for placebo, with an odds ratio of 8.0 (p<0.0001)[75]. - The continuous smoking cessation rate from week 9 to week 24 was 20.5% for the 12-week cytisinicline arm compared to 4.2% for placebo, with an odds ratio of 5.79 (p<0.0001)[79]. - The average age of ORCA-3 trial subjects was 53 years, with a median smoking history of 36 years and 4 prior quit attempts[79]. Market Potential and Commercialization - The market for a new, safe, and effective smoking cessation treatment is substantial in the U.S., EU, and globally, with cytisinicline positioned to address unmet needs[29]. - The global revenues for prescription smoking cessation therapies are estimated to reach $5.6 billion by 2030, with approximately 8 million prescriptions written in the U.S. in 2023[87]. - The company aims to explore additional indications for cytisinicline in the future, expanding its potential market impact[21]. - The company expects to stockpile cytisinicline to meet projected demand upon commercial launch[124]. - The FDA may grant up to seven and a half years of data exclusivity for cytisinicline tablets under the Hatch-Waxman Act[106]. - The company has an exclusive license and supply agreement with Sopharma for the development and commercialization of cytisinicline outside of Central and Eastern Europe[27]. - The company has a license agreement with Sopharma, which includes a mid-single digit royalty on net sales of Tabex branded products[95]. - The company acquired 75% of Extab Corporation for $2.0 million in cash and a deferred payment contingent on regulatory approval of cytisinicline[98]. - The company has entered into a license agreement with the University of Bristol, with potential payments up to $4.8375 million tied to specific milestones[103]. - The company is responsible for royalty payments in the low-single digits and mid-teens percentage of sublicense income based on net sales of licensed products[100]. - Sopharma plans to evaluate commercial partnerships and direct-to-consumer marketing strategies in ex-U.S. territories[128]. Financial and Operational Challenges - The company currently does not generate cash flow from operations, raising concerns about its ability to service its debt obligations[154]. - The financing environment for biotechnology companies is challenging, impacting the company's ability to raise additional capital on favorable terms[150]. - The company has incurred losses since inception and anticipates continuing to incur losses for the foreseeable future[159]. - The company has never generated any revenue from product sales and does not expect to do so in the near future[162]. - The principal amounts due under the company's debt instruments totaled $10.0 million as of December 31, 2024[153]. - The company’s existing and future indebtedness may limit cash resources available for business operations and investments[157]. - The company is dependent on a single supplier, Sopharma AD, for the manufacture and supply of cytisinicline, with the current supply agreement expiring on July 28, 2037[169]. - The company is required to keep substantially all cash and investments with Silicon Valley Bank (SVB), which faced closure in March 2023 but regained access to funds shortly thereafter[167]. - The company anticipates regulatory challenges similar to those faced in the U.S. in other countries where it seeks to commercialize cytisinicline[117]. Regulatory and Compliance Risks - The FDA has expressed support for the NDA submission based on adequate efficacy data from completed Phase 3 trials, with additional long-term safety data required[37]. - The FDA may require additional studies before granting marketing approval for cytisinicline, which could delay commercialization[176]. - Regulatory approvals are essential for commercialization; failure to obtain them would leave the company without saleable products and revenue sources[195]. - The FDA's authority to require post-marketing studies and compliance with risk evaluation strategies could lead to increased costs and restrictions on sales[195]. - Conducting clinical trials internationally introduces additional regulatory risks that could delay approval and commercialization of cytisinicline[192]. - The company is subject to various federal and state healthcare laws aimed at preventing fraud and abuse in the healthcare industry[109]. - Compliance with ongoing regulatory requirements for cytisinicline will likely incur substantial costs, and failure to comply could result in penalties or loss of approvals[208]. - The company is subject to continuous review and inspections to ensure compliance with cGMP regulations, with potential severe harm to business if compliance is not maintained[209]. - Any government investigation of alleged violations could require significant resources and generate adverse publicity, impacting the company's ability to commercialize products[212]. - The company may face challenges in obtaining adequate product liability insurance, which could adversely affect financial condition[187]. Supply Chain and Manufacturing - Sopharma's API manufacturing process for cytisinicline includes techniques such as solvent extraction, recrystallization, filtration, and purification[125]. - The new API facility for cytisinicline was built in 2022 within Sopharma's tableting plant in Sofia, Bulgaria, which complies with EU cGMP requirements[126]. - The therapeutic component of cytisinicline is derived from limited natural sources, raising concerns about supply sustainability[172]. - Weather conditions and natural disasters could disrupt the supply chain for cytisinicline, impacting production and business operations[190]. - The company has significant uncertainties regarding raw material supply chains, which could materially impact financial results[127]. Competitive Landscape - The company faces competition from major pharmaceutical and biotechnology companies in the smoking cessation market, which may impact its market share[133]. - The company has established contract research agreements to outsource certain product development activities[121]. - The company has significant uncertainties regarding raw material supply chains, which could materially impact financial results[127]. Future Outlook - The company anticipates that future healthcare measures could limit government payments for healthcare products, potentially reducing demand or pricing pressures[203]. - Legislative reforms, including the Inflation Reduction Act, may impose price negotiation on certain drugs, affecting revenue potential starting in 2026[203]. - Automatic cuts to Medicare payments of up to 2% per fiscal year are in effect through 2025, which could impact the company's financial condition[204]. - The company faces potential material adverse effects on its business due to future government shutdowns or delays impacting access to public markets and necessary capital[200]. - Ongoing uncertainty in the FDA-regulated industry may lead to delays in obtaining guidance and regulatory approvals for product candidates[201]. - Undesirable side effects from cytisinicline could delay or prevent regulatory approval, limit commercial viability, or result in significant negative consequences post-marketing[181]. - The discovery of impurities, such as nitrosamines, above regulatory thresholds could delay product development and adversely impact business[182]. - The ORCA-OL trial's long-term safety results may not align with earlier trials, and positive past results do not guarantee future success, potentially leading to abandonment of cytisinicline[180]. - Misconduct by employees or contractors could lead to regulatory sanctions and significant harm to the company's reputation and financial condition[218].

Financial Performance - Achieve Life Sciences reported a total net loss of $12.4 million for Q4 2024 and $39.8 million for the full year 2024, compared to a net loss of $5.5 million and $29.8 million for the same periods in 2023, respectively[10][21]. - Operating expenses for Q4 2024 were $12.2 million, compared to $4.4 million in Q4 2023, while total operating expenses for the year were $39.1 million, up from $27.3 million in 2023[10][21]. - The company's cash, cash equivalents, and marketable securities as of December 31, 2024, were $34.4 million, an increase from $15.5 million at the end of 2023[10][23]. Clinical Trials and Drug Development - Achieve successfully completed enrollment in the ORCA-OL clinical trial with 479 participants across 29 U.S. sites, meeting the requirement of 300 participants receiving six months of cumulative cytisinicline treatment[4][5]. - The company announced two positive data safety monitoring committee (DSMC) reviews for the ORCA-OL trial, with no safety concerns identified[6]. - Achieve plans to submit its New Drug Application (NDA) for cytisinicline at the end of Q2 2025, marking it as the first new FDA-approved nicotine dependence treatment in nearly 20 years[1][3]. - The FDA granted Breakthrough Therapy designation for cytisinicline for vaping cessation, aimed at accelerating development and review processes[9]. - The company has conducted a successful end-of-Phase 2 meeting with the FDA for a future vaping indication, confirming alignment on the proposed Phase 3 study design[9]. Leadership and Management - Achieve appointed Mark Oki as Chief Financial Officer in December 2024 to oversee financial strategy and operational initiatives[8]. Share Information - Achieve's weighted average number of basic and diluted common shares outstanding as of March 11, 2025, was 34,685,072[10].

Core Viewpoint - Achieve Life Sciences is on track to submit its new drug application (NDA) for cytisinicline, a treatment for nicotine dependence, by the end of Q2 2025, following significant progress in clinical trials and corporate governance [1][3][4]. Company Developments - The company has completed enrollment in the ORCA-OL clinical trial with 479 participants across 29 U.S. sites, focusing on the long-term safety of a 3 mg cytisinicline regimen for smoking and vaping cessation [4]. - Achieve received two positive reviews from the Data Safety Monitoring Committee (DSMC) for the ORCA-OL trial, confirming no unexpected treatment-related adverse events and excellent participant adherence [5]. - The company appointed Dr. Kristen Slaoui and Nancy Phelan to its Board of Directors, enhancing its expertise in corporate strategy and commercialization [6]. - Mark Oki was appointed as Chief Financial Officer in December 2024, bringing over 25 years of experience in financial leadership within the biotechnology and pharmaceutical sectors [7]. Clinical Trial Progress - The ORCA-OL trial met the requirement of at least 300 participants completing six months of treatment, which is essential for the NDA submission [4][8]. - An End-of-Phase 2 meeting with the FDA confirmed that one well-controlled Phase 3 trial (ORCA-V2) would be sufficient for a vaping cessation indication, with plans to initiate this trial in the first half of 2026, depending on funding availability [9]. Financial Overview - As of December 31, 2024, Achieve reported cash, cash equivalents, and marketable securities totaling $34.4 million, with total operating expenses of $39.1 million for the year [10][20]. - The net loss for the fourth quarter and the year ended December 31, 2024, was $12.4 million and $39.8 million, respectively, with a basic and diluted net loss per share of $0.36 and $1.24 [10][20]. Market Context - There are approximately 29 million adults who smoke combustible cigarettes in the U.S., with tobacco use being the leading cause of preventable death [13]. - Over 11 million adults in the U.S. use e-cigarettes, highlighting a significant market opportunity for cytisinicline, which has received Breakthrough Therapy designation from the FDA for vaping cessation [14][15].

Company Overview - Achieve Life Sciences, Inc. is a late-stage specialty pharmaceutical company focused on the global development and commercialization of cytisinicline as a treatment for nicotine dependence and smoking cessation [3] - The company has successfully completed two Phase 3 studies for smoking cessation and one Phase 2 study for vaping cessation, with plans to submit a new drug application in Q2 2025 [3][6] Product Information - Cytisinicline is a plant-based alkaloid that interacts with nicotinic acetylcholine receptors in the brain, aimed at reducing nicotine cravings and the satisfaction associated with nicotine products [6] - Approximately 29 million adults smoke combustible cigarettes in the U.S., with tobacco use being the leading cause of preventable death, responsible for over 8 million deaths globally and nearly half a million in the U.S. annually [4] - There are over 11 million adults in the U.S. who use e-cigarettes, with no FDA-approved treatments specifically for nicotine e-cigarette cessation, highlighting a critical need that cytisinicline aims to address [5] Upcoming Events - Achieve Life Sciences will present at the Barclays 27th Annual Global Healthcare Conference from March 11-13, 2025, with CEO Rick Stewart scheduled to present on March 12, 2025 [1][2]

Company Overview - Achieve Life Sciences, Inc. is a late-stage specialty pharmaceutical company focused on developing and commercializing cytisinicline for nicotine dependence and smoking cessation [3] - The company has completed two Phase 3 studies for smoking cessation and one Phase 2 study for vaping cessation, with plans to submit a new drug application in Q2 2025 [3] Product Information - Cytisinicline is a plant-based alkaloid that interacts with nicotinic acetylcholine receptors in the brain, aimed at reducing nicotine cravings and the satisfaction associated with nicotine products [6] - Approximately 29 million adults smoke combustible cigarettes, with tobacco use being the leading cause of preventable death, resulting in over 8 million deaths globally and nearly 500,000 deaths annually in the U.S. [4] - There are over 11 million adults in the U.S. who use e-cigarettes, with no FDA-approved treatments specifically for nicotine e-cigarette cessation, highlighting a critical need for cytisinicline [5] Upcoming Events - Achieve Life Sciences will report its fourth quarter and year-end 2024 financial results and provide an update on the cytisinicline development program on March 11, 2025, at 8:30 AM EDT [1]

Company Overview - Achieve Life Sciences, Inc. is a late-stage specialty pharmaceutical company focused on the global development and commercialization of cytisinicline for smoking cessation and nicotine dependence [3] - The company has successfully completed two Phase 3 studies for smoking cessation and one Phase 2 study for vaping cessation [3] - Achieve plans to submit its new drug application for smoking cessation in Q2 2025 and has conducted a successful end-of-Phase 2 meeting with the FDA for a future vaping indication [3] Product Information - Cytisinicline is a plant-based alkaloid with a high binding affinity to the nicotinic acetylcholine receptor, aimed at treating nicotine addiction for both smoking and e-cigarette cessation [6] - The product is believed to reduce the severity of nicotine craving symptoms and the reward associated with nicotine products [6] - Cytisinicline has been granted Breakthrough Therapy designation by the FDA to address the critical need for e-cigarette cessation treatments [5] Market Context - Approximately 29 million adults smoke combustible cigarettes in the U.S., with tobacco use being the leading cause of preventable death, responsible for over eight million deaths worldwide annually [4] - There are over 11 million adults in the U.S. who use e-cigarettes, with 1.6 million middle and high school students reporting e-cigarette use in 2024 [5] - Currently, there are no FDA-approved treatments specifically indicated for nicotine e-cigarette cessation [5]

Core Viewpoint - Achieve Life Sciences is progressing towards the submission of a New Drug Application (NDA) for cytisinicline, a treatment for nicotine dependence, following a positive safety review from the Data Safety Monitoring Committee (DSMC) [1][2][3] Company Overview - Achieve Life Sciences is a late-stage specialty pharmaceutical company focused on developing and commercializing cytisinicline for smoking cessation and nicotine dependence [7][8] - The company has completed two Phase 3 clinical trials involving over 1,600 subjects who smoke cigarettes and wish to quit [5] Clinical Trial Details - The ORCA-OL trial is an open-label study evaluating the long-term exposure of a 3 mg cytisinicline treatment regimen, dosed three times daily, in adults aged 18 and older who want to quit smoking or vaping [6] - The trial has enrolled 479 participants across 29 clinical sites in the United States, with a significant milestone achieved as at least 300 participants completed six months of treatment [3][4] Safety Review Findings - The DSMC's second independent review found no unexpected treatment-related adverse events, confirming the overall safety profile of cytisinicline consistent with previous trials [2][3] - The study can continue as planned without modifications, reinforcing confidence in the cytisinicline safety profile [2][3] Regulatory Pathway - Achieve plans to submit the NDA in Q2 2025, which will be the first new prescription treatment for nicotine dependence in nearly 20 years [4] - The FDA requires six-month safety exposure data from at least 300 participants and one-year cumulative exposure data from a minimum of 100 participants for NDA approval [4][6] Market Context - Approximately 29 million adults smoke combustible cigarettes, and tobacco use is the leading cause of preventable death globally [9][10] - There are over 11 million adults in the U.S. who use e-cigarettes, with no FDA-approved treatments specifically for nicotine e-cigarette cessation [10][11]

Core Insights - Achieve Life Sciences, Inc. has appointed Kristen Slaoui, Ph.D., and Nancy Phelan to its Board of Directors, bringing extensive experience in corporate strategy and commercialization to support the development of cytisinicline for smoking cessation [1][2][3] Company Overview - Achieve Life Sciences is focused on the global development and commercialization of cytisinicline, a treatment for smoking cessation and nicotine dependence [4] - The company has completed two Phase 3 studies for cytisinicline in smoking cessation and one Phase 2 study for vaping cessation, with plans to submit a new drug application in Q2 2025 [5] Industry Context - Approximately 29 million adults smoke combustible cigarettes, with tobacco use being the leading cause of preventable death, resulting in over 8 million deaths globally and nearly 500,000 in the U.S. annually [6] - There are over 11 million adults in the U.S. who use e-cigarettes, with no FDA-approved treatments specifically for nicotine e-cigarette cessation [7] - Cytisinicline has been granted Breakthrough Therapy designation to address the urgent need for effective treatments in this area [7][8]