Core Viewpoint - Achieve Life Sciences plans to submit a New Drug Application (NDA) for cytisinicline to the FDA in June 2025, marking a significant milestone in the development of a new treatment for smoking cessation [1][2]. Company Developments - The company reported financial results for Q1 2025, with cash and equivalents totaling $23.2 million and a net loss of $12.8 million for the quarter [10][20]. - Achieve has successfully completed the FDA's long-term exposure requirements for cytisinicline, demonstrating safety data on over 300 participants completing six months and 100 participants completing one year of treatment [6][8]. - The company conducted a Science Advisory Board (SAB) meeting with leading experts to discuss clinical progress and NDA preparations [9]. Clinical Trial Results - The Phase 3 ORCA-3 trial results published in JAMA Internal Medicine confirmed cytisinicline's efficacy and tolerability, showing reduced nicotine cravings and extended quit rates through 24 weeks [5][8]. - In the ORCA-OL long-term exposure trial, 75% of the 479 enrolled participants remained on treatment, indicating the potential for cytisinicline to shift the treatment paradigm for smoking cessation [4][6]. Market Context - There are approximately 29 million adults in the U.S. who smoke combustible cigarettes, with tobacco use being the leading cause of preventable death [13]. - Cytisinicline has been granted Breakthrough Therapy designation by the FDA, addressing the critical need for effective treatments for nicotine dependence, including e-cigarette cessation [14][15].

Core Insights - Achieve Life Sciences announced significant results from the ORCA-3 trial, demonstrating that cytisinicline effectively aids in smoking cessation by increasing quitting rates and reducing nicotine cravings compared to placebo [1][2][4] Company Overview - Achieve Life Sciences is a late-stage specialty pharmaceutical company focused on developing cytisinicline for nicotine dependence and smoking cessation [7][8] - The company plans to submit a New Drug Application (NDA) for cytisinicline to the FDA in June 2025 [1][5] Clinical Trial Details - The ORCA-3 trial involved 792 U.S. adults, assessing the efficacy of cytisinicline over 6 and 12 weeks, with results published in JAMA Internal Medicine [1][6] - Participants had an average age of 53 years, smoked a median of 20 cigarettes per day, and had a median smoking history of 36 years [3][6] - Cytisinicline was administered at a dosage of 3mg three times daily, with behavioral support provided throughout the trial [6] Efficacy and Tolerability - Cytisinicline showed a significant increase in the odds of smoking cessation and a reduction in nicotine cravings, leading to decreased nicotine intake among participants [4][5] - The drug was well tolerated, attributed to its selective binding to nicotine receptors with limited off-target effects [2][4] Market Context - Tobacco use is the leading cause of preventable death, with over 8 million deaths globally and nearly half a million in the U.S. annually [9] - There is a critical need for effective smoking cessation treatments, as current options are limited [5][9]

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 plans to submit 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 evident, highlighting 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 planned commercial launch of cytisinicline in Q3 2026 [9][13] - The company has received Breakthrough Therapy designation for cytisinicline as a treatment for vaping cessation, indicating strong regulatory support for its development [11][22] - The strategic focus includes enhancing awareness, access, and availability of cytisinicline, with a digital-first approach to engage both healthcare providers and patients [27][117] Management's Comments on Operating Environment and Future Outlook - Management emphasized the urgency for new nicotine dependence treatments due to the ineffectiveness of existing options and the rising prevalence of vaping [8][9] - The company is confident in its ability to file the NDA as planned and is focused on bringing cytisinicline to market to help millions of individuals seeking to quit nicotine [23][43] Other Important Information - The company has strengthened its leadership team with the appointment of a new CFO and board members with extensive experience in corporate strategy and commercialization [12] - The company is conducting quality audits on NDA documents to ensure high standards for submission [20] Q&A Session Summary Question: Clarification on NDA submission requirements - Management confirmed that the focus is on ensuring the quality of the NDA, with external consultants assisting in the preparation process [48][51] Question: Commercial access and potential barriers - 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 immediate focus remains on the NDA submission [62][90] Question: Future DSMC reviews and CMC status - Management confirmed that one more DSMC review is expected, focusing on long-term safety data, and that CMC sections are nearly complete [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 [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 a Phase 3 study with a sample size that accommodates higher placebo rates, ensuring robust statistical power [145]

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]