Core Insights - Achieve Life Sciences is presenting additional analyses from its Phase 3 ORCA-3 study on cytisinicline at the 2025 ATS International Conference, emphasizing its dual mechanism of action in treating nicotine dependence [1][8] - Cytisinicline has shown significant efficacy in reducing nicotine cravings and intake, even among smokers who do not completely quit, indicating its potential as a therapeutic option for smoking cessation [3][4] Company Overview - Achieve Life Sciences is a late-stage specialty pharmaceutical company focused on developing cytisinicline for nicotine dependence and smoking cessation, having completed two Phase 3 studies and one Phase 2 study for vaping cessation [7] - The company plans to submit a New Drug Application for cytisinicline in June 2025, aiming to address the smoking health epidemic affecting millions [6][7] Clinical Findings - The ORCA-3 study demonstrated a significant reduction in craving scores (p=0.0001) and serum cotinine levels among participants treated with cytisinicline compared to placebo, with a reduction equivalent to nearly four times more in cotinine levels [4][5] - Cytisinicline's dual action as a selective partial agonist and antagonist at the nicotinic acetylcholine receptor may help smokers reduce their nicotine intake while on the path to quitting [3][5] Market Context - There are approximately 29 million adult smokers in the U.S., with smoking being the leading cause of preventable death, highlighting the critical need for effective cessation treatments [9] - Cytisinicline has received Breakthrough Therapy designation from the FDA, indicating its potential to address the urgent need for effective nicotine cessation therapies [10][11]

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]

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 is positioned to 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 primary focus is on treating nicotine dependence and addressing comorbidities associated with smoking, such as COPD [21][22] - The company aims to build a foundation for long-term growth and create lasting value for stockholders through prudent cash management and resource allocation [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 [6][66] - The company anticipates a 12-month timeline for NDA approval following submission, with a potential commercial launch in 2026 [20][66] Other Important Information - The ORCA-three clinical trial results were published in JAMA Internal Medicine, reaffirming cytisinicline's efficacy and tolerability [15][16] - The company convened a Scientific Advisory Board meeting with experts in nicotine and tobacco cessation research, highlighting the excitement surrounding cytisinicline [15][31] Q&A Session Summary Question: How long before we see the full safety data from the long-term study? - The full safety data will be compiled after the NDA submission and presented at a conference later this year or next year [27] Question: What were some key takeaways from the SAB meeting? - The SAB meeting discussed the applications of cytisinicline treatment and the enthusiasm of key opinion leaders regarding its efficacy and tolerability [29][31] Question: What are the 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 [35][36] Question: What is the status of any partnership discussions for non-dilutive capital? - The company is specifying what it wants from potential partnerships, particularly in the COPD space, and is in discussions with several candidates [41][43] Question: Have there been any changes in interactions with the FDA? - There have been no significant changes; interactions have remained responsive as the NDA submission approaches [47] Question: How are pricing discussions with payers going? - Initial conversations have occurred, but strong perspectives will emerge once pricing is set and further exchanges take place [52] Question: Will the company rely on external partners for commercialization? - The company will heavily rely on agency partners to implement its strategy and build a digital launch roadmap [59]

Financial Data and Key Metrics Changes - As of March 31, 2025, the company's cash, cash equivalents, and marketable securities totaled $23.2 million [16] - Total operating expenses for Q1 2025 were $12.9 million, resulting in a net loss of $12.8 million [16] 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 [5][10] - The ORCA-OL open label study has over 100 patients with one year of exposure to cytisinicline, demonstrating strong tolerability [8][12] 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 [6] - Cytisinicline is positioned to be the first new nicotine dependence drug in nearly 20 years, addressing a significant unmet need in the market [7][15] 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 [7] - Achieve Life Sciences is preparing for a potential commercial launch in 2026, focusing on managing resources wisely to support this goal [16][17] 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 [19][60] - The company is optimistic about cytisinicline's ability to address comorbidities associated with smoking, particularly in COPD patients [18][19] Other Important Information - The ORCA-three clinical trial results were published in JAMA Internal Medicine, reaffirming cytisinicline's efficacy and tolerability [14] - The company is actively engaging with key opinion leaders to gather insights and support for the NDA filing and commercial plans [13][29] Q&A Session Summary Question: When will the full safety data from the long-term study be available? - The company plans to compile and present the safety data after the NDA submission and the 120-day safety update in October [24] Question: What were the key takeaways from the SAB meeting? - The SAB meeting highlighted the enthusiasm for cytisinicline and discussed its potential applications in various settings, including hospital environments [27][29] Question: What are the plans for pre-commercial efforts to increase awareness of cytisinicline? - The company is focusing on awareness, availability, and access, ensuring that physicians are informed about the new treatment option [33][34] Question: What is the status of partnership discussions for non-dilutive capital? - The company is specifying its needs for partnerships related to COPD and is in discussions with potential candidates [39] 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 [43] Question: How are pricing discussions with payers progressing? - Initial conversations with payers have occurred, but strong perspectives will emerge after pricing is set [48] Question: Will the company rely on external partners for commercialization? - The company plans to leverage agency partners for implementing its digital launch strategy [53] Question: When can the market expect first sales post-approval? - The company anticipates needing some time to establish the drug in the market following approval, aiming for a strong launch as soon as feasible [55]

Financial Performance - The net loss for the three months ended March 31, 2025, was $12.8 million, with an accumulated deficit of $218.4 million as of the same date[121]. - The company incurred an accumulated deficit of $218.4 million through March 31, 2025, and expects to incur substantial additional losses in the future[149]. - For the three months ended March 31, 2025, net cash used in operations was $11.1 million, an increase from $5.3 million for the same period in 2024, primarily due to higher R&D expenses[170]. - The company has substantial doubt regarding its ability to continue as a going concern without additional financing, which may be impacted by macroeconomic conditions[152]. - The company expects to incur significant expenses and increasing operating losses for at least the next several years as it continues clinical development and seeks regulatory approval for its product candidate[154]. - The company has not generated any revenue from product sales to date and may not do so in the near future[149]. Research and Development - Research and development expenses increased to $7.1 million for the three months ended March 31, 2025, compared to $2.8 million for the same period in 2024, primarily due to costs from the ORCA-OL trial[141]. - The ORCA-OL trial completed enrollment of 479 subjects, with safety data from at least 300 subjects treated for six months to be included in the NDA submission[127][129]. - The FDA granted Breakthrough Therapy designation for cytisinicline for nicotine e-cigarette cessation in 2024, expediting its development[124]. - The company plans to submit the NDA for cytisinicline to the FDA in June 2025, following the completion of a long-term safety study initiated in May 2024[122]. Expenses and Income - General and administrative expenses rose to $5.8 million for the three months ended March 31, 2025, up from $3.2 million in the same period in 2024, driven by higher employee expenses and commercial launch preparation costs[142]. - Interest income decreased to $0.3 million for the three months ended March 31, 2025, compared to $0.4 million for the same period in 2024, due to lower average cash balances[143]. - Interest expense decreased to $0.2 million for the three months ended March 31, 2025, down from $0.8 million in the same period in 2024, attributed to a lower principal balance on the New Convertible Term Loan[144]. Cash and Financing - As of March 31, 2025, the company had a cash, cash equivalents, and marketable securities balance of $23.2 million, with a positive working capital balance of $17.9 million[149]. - The company raised approximately $60.0 million in gross proceeds from a registered direct offering in February 2024, receiving net proceeds of approximately $56.1 million after fees[168]. - The company entered into a New Debt Agreement on July 25, 2024, providing term loans with an aggregate original principal amount of $10.0 million, with additional loans available upon certain events[157]. - The New Convertible Term Loan matures on December 1, 2027, with an option to extend to June 1, 2028, and has an interest rate of at least 7.0%[158]. - For the three months ended March 31, 2025, net cash provided by investing activities was $11.4 million, attributed to transactions involving marketable securities[174]. Accounting Standards - New accounting standards will be adopted in 2025, as detailed in Note 2 of the unaudited consolidated financial statements[177].

Financial Performance - As of March 31, 2025, the company reported cash, cash equivalents, and marketable securities of $23.2 million, down from $34.4 million at the end of 2024[10][23] - Total operating expenses for Q1 2025 were $12.9 million, compared to $6.0 million in Q1 2024, reflecting a 115% increase year-over-year[21] - The net loss for Q1 2025 was $12.8 million, compared to a net loss of $6.5 million in the same quarter of the previous year, representing a 97% increase[21] - Achieve's stockholders' equity decreased to $10.3 million as of March 31, 2025, from $20.9 million at the end of 2024[23] Clinical Trials and Drug Development - Achieve Life Sciences plans to submit a New Drug Application (NDA) for cytisinicline to the FDA in June 2025[1] - Approximately 75% of the 479 participants in the ORCA-OL trial remain on treatment, indicating strong tolerability of cytisinicline[4] - The Phase 3 ORCA-3 trial involved 792 U.S. adult smokers and demonstrated efficacy in reducing nicotine cravings and improving quit rates[6] - Achieve has met FDA long-term exposure requirements with safety data from over 300 participants completing six months of treatment and 100 participants completing one year[7] - The company completed its third safety review of the ORCA-OL trial, with no unexpected treatment-related adverse events reported[8] - The company conducted a Science Advisory Board meeting with leading experts to discuss clinical progress and NDA preparations for cytisinicline[9]

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].

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 and one Phase 2 study related to cytisinicline, with plans to submit a new drug application in June 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 derived from nicotine products [5] - The product has received Breakthrough Therapy designation from the FDA, highlighting its potential to address the significant need for effective smoking and vaping cessation treatments [4][5] Market Context - Approximately 29 million adults in the U.S. smoke combustible cigarettes, with tobacco use being the leading cause of preventable death globally [4] - There are over 11 million adults in the U.S. who use e-cigarettes, and no FDA-approved treatments specifically for e-cigarette cessation currently exist [4] Upcoming Events - Achieve Life Sciences will report its first quarter 2025 financial results and provide updates on the cytisinicline development program on May 13, 2025, at 8:30 AM EDT [1]

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 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]