Financial Data and Key Metrics Changes - As of December 31, 2025, cash equivalents and marketable securities totaled $36.4 million [25] - Total operating expenses for Q4 2025 were $14.7 million, and for the full year, they were $54.9 million, reflecting ongoing investments in regulatory, clinical, and commercial activities [25] - The total net loss for Q4 2025 was $14.7 million, and for the full year, it was $54.7 million [25] Business Line Data and Key Metrics Changes - Achieve Life Sciences is transitioning from a clinical development company to a commercially focused enterprise, with a primary objective to make cytisinicline available to 25 million smokers and nearly 18 million vapers [5][6] - The NDA submission for smoking cessation was accepted by the FDA, marking a significant step towards becoming the first new FDA-approved treatment in 20 years [6][7] - The ORCA-OL long-term exposure trial demonstrated cytisinicline's safety profile, showing strong tolerability and excellent patient satisfaction [8] Market Data and Key Metrics Changes - Approximately 25 million adults in the U.S. smoke cigarettes, with over 15 million attempting to quit each year [12] - The CDC estimates that smoking causes around 500,000 deaths annually and incurs over $600 billion in healthcare costs and lost productivity [12] - There are 6 million COPD smokers in the U.S. with limited options for cessation, highlighting the potential market for cytisinicline [8] Company Strategy and Development Direction - The company aims to launch cytisinicline for smoking cessation in the first half of 2027, focusing on ensuring supply chain readiness and building a scalable commercial model [9][10][19] - Achieve is leveraging AI and advanced analytics to enhance decision-making and customer engagement, positioning itself for an efficient launch [10][23] - The company has initiated a "Willpower" awareness campaign to reframe the conversation around nicotine dependence as a medical condition [14][22] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the regulatory progress and the potential for cytisinicline to deliver the first FDA-approved treatment for nicotine dependence in two decades [18] - The company is focused on addressing the unmet medical needs in nicotine dependence, emphasizing the importance of a controlled and successful product launch [26][27] - Management highlighted the urgency of the public health need for vaping cessation treatments, with the potential to be first to market [27] Other Important Information - Achieve has partnered with Adare Pharma Solutions for U.S. manufacturing, which is expected to enhance supply chain security and reduce risks associated with international imports [10][11] - The company is actively engaging with payers to secure coverage and affordability for cytisinicline, with ongoing discussions showing positive feedback [21][53] Q&A Session Summary Question: What is the critical path between NDA approval and launch? - The company needs to ensure drug availability in the supply chain and is working on additional data and partnerships during the lead-up to launch [30][31] Question: Will the manufacturer in the NDA supply commercial product? - The company plans to transfer manufacturing to Adare, ensuring contingency supply and addressing observations from the FDA inspection [36][37] Question: What is the current awareness level among healthcare providers? - Awareness has not been a priority pre-approval, but the company plans to ramp up educational efforts as the launch approaches [40][42] Question: What is the status of FDA dialogue on the vaping indication? - Discussions with the FDA have focused on protocol approval, with site selection for the ORCA-V2 trial already underway [44][45] Question: How robust is the raw plant material supply chain? - The company has stockpiled sufficient starting material for over three years of supply, ensuring readiness for market demand [58] Question: What are the pricing considerations for cytisinicline? - The company is not ready to comment on pricing but acknowledges the substantial unmet need highlighted in the ICER report [66][68]

Financial Data and Key Metrics Changes - As of December 31, 2025, cash equivalents and marketable securities totaled $36.4 million, with total operating expenses for Q4 2025 at $14.7 million and for the full year at $54.9 million, reflecting ongoing investments in regulatory, clinical, and commercial activities [25] - The total net loss for Q4 2025 was $14.7 million and for the full year was $54.7 million, indicating a consistent investment strategy despite losses [25] Business Line Data and Key Metrics Changes - Achieve Life Sciences is transitioning from a clinical development company to a commercially focused enterprise, with a primary objective to make cytisinicline available to 25 million smokers and nearly 18 million vapers in the U.S. [5][6] - The NDA submission for smoking cessation was accepted by the FDA, marking a significant milestone towards becoming the first new FDA-approved treatment in 20 years [6][7] Market Data and Key Metrics Changes - The company highlighted the urgent public health need for nicotine dependence treatment, with approximately 25 million adults in the U.S. smoking and over 15 million attempting to quit annually [12] - The recognition of cytisinicline as a national priority by the FDA enhances its market potential, particularly for vaping cessation, where no approved treatments currently exist [6][18] Company Strategy and Development Direction - Achieve is building a scalable, data-driven commercial model to launch cytisinicline, utilizing an omni-channel digital platform for precision targeting of physicians and patients [9][10] - The partnership with Adare Pharma Solutions aims to secure the supply chain and reduce risks associated with international pharmaceutical importation, enhancing operational readiness for the planned commercial launch in the first half of 2027 [10][11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the regulatory progress and the potential of cytisinicline to deliver the first FDA-approved treatment for nicotine dependence in two decades, emphasizing the importance of addressing the unmet medical needs in this area [26][27] - The company is focused on ensuring a controlled and successful launch, with ongoing discussions with payers to secure coverage and affordability for cytisinicline [19][53] Other Important Information - The ORCA-OL long-term exposure trial demonstrated cytisinicline's safety profile and strong tolerability, with high patient satisfaction reported [8][17] - The company is leveraging advanced analytics and machine learning to enhance decision-making and customer engagement, positioning itself for an efficient launch [9][23] Q&A Session Summary Question: Can you talk about the critical path between a late June NDA approval and a first half launch? - The primary consideration is ensuring drug availability in the supply chain, with all trade and distribution processes ready to go once the drug is available [30][31] Question: Did you imply that the manufacturer in the NDA will not be supplying commercial product, rather Adare will? - The PDUFA date remains June 20, and the decision to transfer manufacturing to the U.S. was made to ensure contingency supply and address geopolitical concerns [36][37] Question: Can you discuss the current awareness level with healthcare providers and plans for 2026? - Awareness has not been a priority yet, but as the launch approaches, the company plans to ramp up educational efforts specific to cytisinicline [40][42] Question: What is the status of the raw plant material supply chain? - The company has been stockpiling starting material and expects to have more than three years' supply by the time of launch [58] Question: Can you comment on the cytisinicline dosing schedule and potential compliance issues? - High adherence rates were reported in trials, with participants finding the dosing schedule manageable and effective in addressing cravings [60][61] Question: What are the pricing considerations for cytisinicline? - The company is not ready to comment on pricing but acknowledges the substantial unmet need highlighted in the ICER report [66][68]

Cytisinicline Overview - Cytisinicline represents a potential new treatment for nicotine dependence in nearly 20 years, targeting an addressable market of up to 50 million Americans who use tobacco[7] - The FDA's PDUFA date for cytisinicline for smoking cessation is expected on June 20, 2026[9] - Nicotine dependence is a significant public health crisis, costing billions of dollars[7] Clinical Trial Results - Smoking cessation trials (ORCA-2 and ORCA-3) demonstrated robust efficacy, excellent tolerability, and significant craving reduction[30] - In 12-week cytisinicline treatment trials, quit rates reached 32.6% compared to 7% with placebo, yielding an odds ratio of 6.3 (p<0.0001)[31] - In 6-week cytisinicline treatment trials, quit rates reached 25.3% compared to 4.4% with placebo, yielding an odds ratio of 8.0 (p<0.0001)[31] - Cytisinicline shows a more favorable adverse event profile compared to Varenicline (Chantix®), with lower rates of nausea (6.2% vs 30%), insomnia (10.8% vs 18%), abnormal dreams (7.7% vs 13%), and headache (8.1% vs 15%)[37] Market and Commercial Strategy - Over $600 billion is spent annually in the U S on smoking-related health care costs[14] - Approximately 29 million U S smokers have few treatment options[15] - The company estimates an $11 billion Rx opportunity in the smoking cessation market[57]

Core Insights - Achieve Life Sciences has made significant progress in the regulatory process for cytisinicline, a treatment for nicotine dependence, with the completion of the ORCA-OL long-term safety trial and submission of a 120-day safety update to the FDA [1][2][7] Company Developments - The ORCA-OL trial successfully concluded with 334 participants completing one year of treatment, surpassing FDA requirements for safety data [3][7] - The Data Safety Monitoring Committee (DSMC) conducted its final review and found no safety concerns related to cytisinicline, indicating a favorable safety profile [2][7] - The company submitted a New Drug Application (NDA) to the FDA in June 2025, which has been accepted for review, with a Prescription Drug User Fee Act (PDUFA) date set for June 20, 2026 [5] Industry Context - Approximately 29 million adults in the U.S. smoke combustible cigarettes, and tobacco use is the leading cause of preventable death, highlighting the critical need for effective smoking cessation treatments [6] - There are currently no FDA-approved treatments specifically for e-cigarette cessation, indicating a significant market opportunity for cytisinicline [8][9]

Financial Data and Key Metrics Changes - Achieve Life Sciences closed the second quarter with a strengthened balance sheet following a successful $45 million public offering in June, which included common stock and warrants [29] - As of June 30, 2025, the company had cash, cash equivalents, and marketable securities totaling $55.4 million, expected to support operations into 2026 [29] - Total operating expenses for the three and six months ended June 30, 2025, were $12.6 million and $25.5 million respectively, consistent with expectations as the company increased investment in regulatory and pre-commercial planning [30] - The net loss for the same periods was $12.7 million and $25.5 million respectively [30] Business Line Data and Key Metrics Changes - The company achieved three transformative milestones: the submission of a new drug application (NDA) for cytisinicline, a strategic partnership with Omnicom, and a capital raise of $49 million [5][6] - The NDA submission is supported by data from over 2,000 clinical trial participants, including results from two Phase III studies and long-term safety data [12][13] Market Data and Key Metrics Changes - There are approximately 29 million smokers in the U.S., with over 15 million attempting to quit each year, highlighting a significant market opportunity for cytisinicline [7] - The annual cost of smoking-related health issues in the U.S. is over $600 billion, indicating a substantial public health burden [8] Company Strategy and Development Direction - The company aims to change the narrative around nicotine dependence, positioning it as a medical condition that requires effective treatment options [7][24] - Achieve is focused on a data-driven approach to its commercial launch strategy, leveraging a proprietary AI-enabled platform for decision-making and performance optimization [19][26] - The strategic partnership with Omnicom is intended to enhance brand development, market access, and stakeholder engagement ahead of the product launch [18][27] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the regulatory process and anticipates receiving the FDA's Day 74 NDA acceptance letter in mid-September [31] - The company is committed to executing its strategy with financial prudence while preparing for a potential product launch in late 2026 [31][32] - Management highlighted the importance of building relationships with payers to ensure rapid access to cytisinicline following approval [22][23] Other Important Information - The company plans to complete the ORCA-OL study database by the end of the year and aims to present the results in 2026 [15][68] - Achieve is actively engaging with the FDA and has requested a priority review for the NDA submission, although a standard review is currently anticipated [50] Q&A Session Summary Question: Will the 120-day safety update include only 100 patients or the full 290? - The company will submit all subjects available at the time of the database cut, which will be more than 100 but not the full 290 [34] Question: How will commercial spending ramp up ahead of launch? - The company will incrementally increase pre-commercial activities prior to approval, with a disciplined approach to commercial investment [35][36] Question: Will cytisinicline be priced at a premium compared to generic options? - The company views cytisinicline as a branded product at a premium price, supported by its differentiated profile [37] Question: What initial contact methods will be used to reach providers? - The company plans to identify individual needs of targeted physicians and engage through various channels, including social media and email [40][42] Question: What is the overall safety profile of cytisinicline? - The safety profile remains consistent with previous data, with no new safety signals identified [46][47] Question: Will there be any updates on future clinical development before the end of the year? - The company plans to complete the ORCA-OL study database quickly and aims to present data at conferences in 2026 [66][68]

Achieve Life Sciences (ACHV) Conference Summary Company Overview - Achieve Life Sciences is focused on addressing nicotine dependence through its drug cytisinicline, which is positioned as a potential blockbuster treatment for smoking and vaping cessation [3][4][5] Industry Context - The U.S. faces a significant public health crisis with approximately 46 million individuals affected by nicotine dependence, including 29 million smokers and 17 million vapers [3][4] - The vaping population has increased by 6 million in the last 24 months, highlighting a growing concern [4] Key Points and Arguments 1. **Market Opportunity**: - The addressable market for nicotine dependence treatment is substantial, with an estimated annual market opportunity of $11 billion based on previous treatments like Chantix [33][35] - There are 15.4 million annual attempts to quit smoking, indicating a high demand for effective cessation tools [33] 2. **Product Development**: - Cytisinicline is expected to be the first new treatment for nicotine dependence in nearly 20 years, with an NDA filing planned for the end of June 2025 and anticipated FDA approval by mid-2026 [5][22] - The drug has shown a differentiated efficacy profile in clinical trials, with odds ratios of 5.3 and 5.8 in two phase three trials, indicating a significantly higher likelihood of quitting compared to existing treatments [19][20] 3. **Clinical Trials**: - Cytisinicline has undergone two large-scale phase three clinical trials involving over 1,600 patients, demonstrating robust efficacy and tolerability [5][25] - A phase two clinical trial for vaping cessation showed an odds ratio of 2.65, with plans for a phase three trial starting in early 2025 [27][23] 4. **Regulatory Pathway**: - The NDA submission is expected to be accepted within 74 days, with a clear regulatory pathway outlined by the FDA [22][43] 5. **Commercial Strategy**: - Achieve Life Sciences plans a targeted digital marketing strategy focusing on primary care physicians and patients, leveraging the lack of competition in the smoking cessation market since Chantix became generic [30][39] - The company aims to change the narrative around nicotine dependence from a lack of willpower to a medical condition, enhancing awareness and acceptance of cytisinicline [35][36] 6. **Safety and Tolerability**: - Cytisinicline has a favorable safety profile, with side effects significantly lower than those of existing treatments like Chantix, particularly in terms of nausea and vomiting [20][21] Additional Insights - The company has a strong intellectual property position and a proven leadership team, which is expected to drive shareholder value [43][44] - There is potential for future indications beyond nicotine dependence, including cannabis use, although the focus remains on the immediate market opportunity [50][52] Conclusion - Achieve Life Sciences is positioned to make a significant impact in the nicotine dependence treatment market with cytisinicline, addressing a critical public health issue while leveraging a well-defined commercial strategy and strong clinical data [44][54]

Financial Data and Key Metrics Changes - As of March 31, 2025, the company's cash, cash equivalents, and marketable securities totaled $23.2 million [19] - Total operating expenses for Q1 2025 were $12.9 million, resulting in a net loss of $12.8 million [19] Business Line Data and Key Metrics Changes - The company is focused on the NDA submission for cytisinicline, which is expected to be submitted in June 2025 [6][12] - The ORCA-OL open label study has over 100 patients with one year of exposure to cytisinicline, demonstrating strong tolerability [10][14] Market Data and Key Metrics Changes - In the U.S., over 29 million adults smoke cigarettes, and 11 million vape, with more than half wanting to quit but fewer than 10% succeeding due to inadequate tools [7] - Cytisinicline, if approved, will be the first new nicotine dependence drug in nearly 20 years, addressing a significant unmet need in the market [8][17] Company Strategy and Development Direction - The company aims to change the perception of nicotine dependence as a serious medical condition that requires treatment, similar to how GLP-1 medications have reframed obesity treatment [9] - The management is focused on ensuring a high-quality NDA submission and preparing for a potential commercial launch in 2026 [19][20] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the NDA submission process and the potential impact of cytisinicline on public health, particularly in treating nicotine dependence and related chronic conditions like COPD [21][66] - The company is committed to prudent cash management to extend its cash runway while focusing on the NDA submission [20] Other Important Information - The ORCA-three clinical trial results published in JAMA Internal Medicine reaffirm cytisinicline's efficacy and tolerability for helping adult smokers quit [16] - The company convened a Scientific Advisory Board meeting with leading experts to discuss cytisinicline and gather insights for the NDA filing and commercial plans [15] Q&A Session Summary Question: How long before we see the full safety data from the long-term study? - The company expects to complete the study by June to September 2025 and will present the data after the NDA submission [27] Question: What were some of the key takeaways from the SAB meeting? - The SAB meeting highlighted the enthusiasm of key opinion leaders for cytisinicline and discussed its potential applications in various settings [30][32] Question: What are your plans for pre-commercial efforts to increase awareness of cytisinicline? - The company is focusing on awareness, availability, and access, ensuring the drug is ready for sale and working on pricing and payer strategies [36][38] Question: What is the status of any partnership discussions for non-dilutive capital? - The company is specifying its needs for partnerships related to COPD and is in discussions with potential candidates [44] Question: Have there been any changes in interactions with the FDA? - There have been no significant changes; interactions have remained consistent as the company approaches the NDA submission [48] Question: How are pricing discussions with payers going? - Initial conversations have occurred, but strong perspectives will emerge once pricing is set [52] Question: Will the company rely on external partners for commercialization? - The company will heavily rely on agency partners to implement its strategy and digital launch roadmap [59] Question: When will commercialization begin after product approval? - The company anticipates needing some time post-approval to ensure a strong launch, but aims to start as close to approval as possible [61]

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]