Core Insights - Achieve Life Sciences has reached a significant milestone in its ORCA-OL clinical trial, with over 300 participants completing six months of cumulative treatment with cytisinicline, which is essential for the New Drug Application (NDA) submission [2][3][4] - The FDA has requested six-month safety exposure data for the NDA, and no safety concerns have been identified during the ongoing review [2][3] - The planned NDA submission for cytisinicline is on track for Q2 2025, aiming to address nicotine dependence and smoking cessation [2][4] Company Overview - Achieve Life Sciences is focused on the global development and commercialization of cytisinicline as a treatment for nicotine dependence, having completed two Phase 3 trials involving over 1,600 subjects [6][4] - The company has received Breakthrough Therapy designation for cytisinicline, highlighting its potential to meet an urgent public health need [8][9] - Cytisinicline is a plant-based alkaloid that interacts with nicotinic acetylcholine receptors to help reduce nicotine cravings and dependence [9] Clinical Trial Details - The ORCA-OL trial is an open-label study evaluating the long-term safety of a 3 mg cytisinicline regimen taken three times daily, conducted at 29 clinical sites across the U.S. [5][4] - The trial aims to provide safety data from at least 300 participants for the NDA submission, with additional data from at least 100 subjects treated for a cumulative one-year period to be submitted prior to potential product approval [5][4] Market Context - Approximately 29 million adults in the U.S. smoke combustible cigarettes, with tobacco use being the leading cause of preventable death globally [7][8] - There are over 11 million adults in the U.S. who use e-cigarettes, and currently, there are no FDA-approved treatments specifically for nicotine e-cigarette cessation [8][9]

Core Insights - Achieve Life Sciences, Inc. is focused on developing and commercializing cytisinicline for nicotine dependence, with significant milestones expected in 2025 [1][5]. Company Overview - Achieve Life Sciences is a late-stage pharmaceutical company dedicated to addressing nicotine addiction through cytisinicline [5]. - The company has completed two Phase 3 clinical trials involving over 1,600 subjects for smoking cessation and one Phase 2 trial for vaping cessation [3][5]. Clinical Development - Achieve plans to submit a New Drug Application (NDA) for cytisinicline as a smoking cessation aid in Q2 2025 [3][5]. - A single Phase 3 clinical trial for vaping cessation is expected to commence in Q3 2025 [3][5]. Market Context - Approximately 29 million adults smoke combustible cigarettes, with tobacco use being the leading cause of preventable death globally, accounting for over 8 million deaths 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]. Product Mechanism - Cytisinicline is a plant-based alkaloid that interacts with nicotinic acetylcholine receptors in the brain, aiming to reduce nicotine cravings and the satisfaction derived from nicotine products [8].

Core Insights - Achieve Life Sciences has successfully completed its End-of-Phase 2 meeting with the FDA, marking a significant milestone for the development of cytisinicline as a potential first-in-class treatment for nicotine e-cigarette cessation [1][4][6] - The FDA has agreed on the proposed Phase 3 study design for cytisinicline, which includes a well-controlled trial (ORCA-V2) and the use of safety data from an ongoing study for label expansion [2][4] Company Overview - Achieve Life Sciences is focused on developing and commercializing cytisinicline to address nicotine dependence, particularly in the context of e-cigarette and vaping cessation [1][8] - The company has received Breakthrough Therapy designation from the FDA, which has facilitated expedited interactions and feedback during the clinical development process [4][8] Clinical Development - The Phase 3 ORCA-V2 trial is set to evaluate the efficacy and safety of 3 mg cytisinicline administered three times daily for 12 weeks in approximately 800 adults who use e-cigarettes [5][6] - The primary objective of the ORCA-V2 trial is to measure weekly vaping abstinence with biochemical confirmation during the last four weeks of treatment [5] Market Context - There are approximately 11 million adults in the U.S. who use e-cigarettes, with about 60% expressing a desire to quit, highlighting a significant unmet need for effective cessation treatments [3][8] - Currently, there are no FDA-approved treatments specifically for nicotine e-cigarette cessation, positioning cytisinicline as a potential solution in a growing public health challenge [3][8]

Company Overview - Achieve Life Sciences, Inc. is a late-stage pharmaceutical company focused on the global development and commercialization of cytisinicline for treating nicotine dependence [1][3] - The company is participating in two upcoming investor conferences: Jefferies London Healthcare Conference on November 19-21, 2024, and Piper Sandler 36th Annual Healthcare Conference on December 3-5, 2024 [2] Industry Context - Tobacco use is the leading cause of preventable death, responsible for over 8 million deaths globally and nearly 500,000 deaths annually in the United States [3] - Approximately 29 million adults smoke combustible cigarettes, and over 11 million adults in the U.S. use e-cigarettes [3][4] - In 2024, around 1.6 million middle and high school students in the U.S. reported using e-cigarettes [3] Product Information - Cytisinicline is a plant-based alkaloid with a high binding affinity to nicotinic acetylcholine receptors, aimed at treating nicotine addiction by reducing cravings and satisfaction associated with nicotine products [4] - Cytisinicline has received Breakthrough Therapy designation from the FDA to address the critical need for e-cigarette cessation treatments [3][4]

Financial Data and Key Metrics - The company's cash, cash equivalents, restricted cash, and short-term investments were $42.9 million as of September 30, 2024, compared to $61.3 million in the prior quarter [45] - Net loss for Q3 2024 was $12.5 million, compared to a net loss of $7.1 million in the same quarter of the prior year [46] - Net loss for the nine months ended September 30, 2024, increased to $27.5 million from $24.3 million in the same period in 2023 [46] - Operating expenses increased in Q3 due to the targeted enrollment in the ORCA-OL trial, with expectations of elevated expenses as the trial progresses [47] Business Line Data and Key Metrics - The ORCA-OL open-label safety trial for long-term cytisinicline exposure completed enrollment with 479 participants across 29 trial sites in the U.S. [19] - The trial aims to meet FDA requirements for safety data on at least 300 subjects treated with cytisinicline for six months and 100 subjects for one year [20] - The Data Safety Monitoring Committee reported no safety concerns, allowing the study to continue without modifications [21] Market Data and Key Metrics - The target population for nicotine dependence treatment includes over 40 million Americans and more than 1 billion people globally [10] - Approximately 29 million Americans smoke combustible cigarettes, and over 11 million adults in the U.S. vape nicotine [15] - 65% of smokers attempt to quit annually, with fewer than 10% succeeding [15] Company Strategy and Industry Competition - The company is transitioning from a clinical development focus to a more commercially focused strategy, with plans for NDA submission, acceptance, and approval [5][6] - Achieve is developing an innovative digital-first commercial strategy to target primary care physicians efficiently [11][12] - The company is exploring partnerships for COPD and asthma treatments, leveraging cytisinicline's potential in reducing smoking-related diseases [51] Management Commentary on Operating Environment and Future Outlook - Management emphasized the urgent need for new FDA-approved treatments for smoking cessation, highlighting the public health crisis caused by nicotine dependence [25][26] - The company is focused on executing its NDA submission plan, with a target submission date in Q2 2025 [22][23] - Achieve is optimistic about addressing future nicotine dependence crises, including tobacco pouches, after focusing on smoking and vaping cessation [52] Other Important Information - The FDA granted breakthrough therapy designation to cytisinicline for vaping cessation, providing access to FDA cross-disciplinary project management teams [26] - The company successfully refinanced its SVB loan, securing up to $20 million in availability, with tranches tied to NDA acceptance and FDA approval [43][44] Q&A Session Summary Question: Spike in G&A expenses in Q3 - The spike was due to one-time charges related to executive restructuring and severance costs [56] Question: ORCA-OL trial patient exposure - Approximately one-third of participants had prior exposure to cytisinicline for 12 weeks, one-third for 6 weeks, and one-third were in the placebo group [57] Question: ORCA-OL data disclosure - Data will not be presented before NDA submission; focus remains on safety data and NDA preparation [61] Question: Vaping cessation label expansion - Efforts are focused on smoking cessation first, with plans to expand into vaping cessation after establishing the commercial structure [63] Question: ORCA-OL enrollment reduction - Enrollment was capped at 479 due to low discontinuation rates, with retention programs in place to maintain participant engagement [83][84] Question: NDA review timeline - The NDA review process is expected to take 12 months from submission, with FDA acceptance within 74 days [86] Question: Non-dilutive financing for vaping study - The company is still considering leveraging NIH funding for the vaping study [87] Question: Synthetic cytisinicline development - Progress is ongoing, with updates to be provided as significant developments occur [78]

Financial Performance - The net loss for the nine months ended September 30, 2024, was $27.5 million, with an accumulated deficit of $193.2 million[119]. - The company has not generated any revenue from product sales to date and has incurred operating losses each year since inception[119]. - The company expects to incur significant expenses and increasing operating losses for at least the next several years as it continues clinical development[120]. - The accumulated deficit through September 30, 2024 was $193.2 million, with expectations of incurring substantial additional losses in the future[170]. - For the nine months ended September 30, 2024, net cash used in operations was $20.6 million[170]. - The company incurred a loss on extinguishment of debt of $0.3 million for each of the three and nine months ended September 30, 2024[169]. - Substantial doubt exists regarding the company's ability to continue as a going concern without additional financing[173]. Cash and Investments - As of September 30, 2024, the company had cash, cash equivalents, and short-term investments totaling $42.9 million, and a positive working capital balance of $38.8 million[119]. - Net cash provided by financing activities for the nine months ended September 30, 2024 was $47.8 million, significantly higher than $15.3 million in the same period of 2023, driven by proceeds from the February 2024 offering and other financing activities[199]. - Net cash used in investing activities increased to $33.3 million for the nine months ended September 30, 2024, compared to only $15,000 in the same period of 2023, attributed to transactions involving marketable securities[200]. - As of September 30, 2024, the company had $50.0 million available under an Open Market Sale Agreement with Jefferies LLC, although no shares were sold under this agreement during the three and nine months ended September 30, 2024[197]. Clinical Trials and Drug Development - The FDA granted Breakthrough Therapy designation for cytisinicline for nicotine e-cigarette cessation, which allows expedited development of the drug[125]. - The company initiated the ORCA-OL open label trial in May 2024, enrolling 479 subjects to provide long-term safety data for cytisinicline[127]. - In the Phase 2b ORCA-1 trial, cytisinicline treatment arms showed a 74-80% median reduction in the number of cigarettes smoked compared to a 62% reduction in placebo arms[133]. - The 3 mg TID cytisinicline arm demonstrated a 50% abstinence rate at week 4, compared to 10% for placebo (p<0.0001)[135]. - The ORCA-V1 trial showed a vaping cessation rate of 31.8% for cytisinicline compared to 15.1% for placebo during weeks 9 through 12 (p=0.04)[141]. - The Phase 3 ORCA-2 trial demonstrated that subjects receiving 12 weeks of cytisinicline had a 6.3 times higher likelihood of quitting smoking compared to placebo, with an abstinence rate of 32.6% versus 7.0%[144]. - The continuous abstinence rate from week 9 to 24 for the 12-week cytisinicline arm was 21.1%, compared to 4.8% for placebo, with an odds ratio of 5.3[145]. - The Phase 3 ORCA-3 trial showed that subjects receiving 12 weeks of cytisinicline had a 4.4 times higher likelihood of quitting smoking, with a cessation rate of 30.3% compared to 9.4% for placebo[150]. - Cytisinicline was well tolerated in both ORCA-2 and ORCA-3 trials, with no treatment-related serious adverse events reported[154]. Research and Development Expenses - R&D expenses for the three months ended September 30, 2024, increased to $7.6 million from $3.6 million in the same period in 2023, primarily due to the initiation of the ORCA-OL trial[162]. - The company initiated the ORCA-OL trial in May 2024, contributing to higher R&D expenses, while costs associated with completed trials (ORCA-3 and ORCA-V1) were reduced[198]. General and Administrative Expenses - General and administrative expenses for the three months ended September 30, 2024, rose to $4.9 million from $3.0 million in the same period in 2023, attributed to higher employee and consulting costs[164]. Financing Activities - In May 2023, the company sold 3,000,000 shares of common stock at $5.50 per share, raising approximately $15.3 million in net proceeds after fees and expenses[194]. - In February 2024, the company sold 13,086,151 shares of common stock at $4.585 per share, resulting in gross proceeds of approximately $60.0 million and net proceeds of about $56.1 million after deducting fees[197]. - The company issued unregistered warrants to purchase up to 13,086,151 shares at an exercise price of $4.906 per share, which are immediately exercisable and will expire under specific conditions[196]. Accounting Policies - There have been no material changes to the company's critical accounting policies since December 31, 2023, as disclosed in the Annual Report filed on March 28, 2024[202]. - The company has adopted new accounting standards in 2024, as detailed in the consolidated financial statements[203].

Financial Performance - As of September 30, 2024, the company's cash, cash equivalents, restricted cash, and short-term investments totaled $42.9 million[8] - Total operating expenses for the three months ended September 30, 2024 were $12.5 million, compared to $6.6 million for the same period in 2023, representing an increase of 90%[15] - The net loss for the three months ended September 30, 2024 was $12.5 million, compared to a net loss of $7.1 million for the same period in 2023, indicating an increase of 76%[15] - The total net loss for the nine months ended September 30, 2024 was $27.5 million, compared to $24.3 million for the same period in 2023[15] - Achieve's total assets as of September 30, 2024 were $47.9 million, significantly up from $19.4 million as of December 31, 2023[16] Clinical Development - Achieve completed enrollment in the Phase 3 ORCA-OL clinical trial with 479 participants across 29 U.S. sites, evaluating a 3 mg cytisinicline regimen for smoking and vaping cessation[3] - The FDA granted Breakthrough Therapy designation for cytisinicline for nicotine e-cigarette cessation, aimed at expediting development and review[6] - The company plans to submit a New Drug Application (NDA) in the second quarter of 2025[3] Leadership and Strategy - Achieve's leadership team has been enhanced with the appointment of Richard Stewart as CEO and Thomas King as Executive Chairman, focusing on strategic growth[7] - The company has initiated the formation of a dedicated U.S. product launch preparedness team to support the upcoming market entry of cytisinicline[3]

Core Points - Achieve Life Sciences, Inc. is focused on the development and commercialization of cytisinicline for nicotine dependence treatment, with recent presentations at a joint FDA and NIH meeting aimed at advancing smoking cessation treatments [1][2] - Cytisinicline is currently the only late-stage nicotine dependence treatment, having completed two Phase 3 clinical trials with over 1,600 subjects, demonstrating strong safety and efficacy [2] - The FDA has not approved a new prescription smoking cessation treatment in nearly two decades, highlighting the need for innovation in this area [2] Company Overview - Achieve Life Sciences aims to address the global smoking health crisis, with approximately 29 million adults and 2.25 million middle and high school students in the U.S. smoking combustible cigarettes [4] - Tobacco use is 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. using e-cigarettes, with no FDA-approved treatments specifically for e-cigarette cessation [4] Product Details - Cytisinicline is a plant-based alkaloid that interacts with nicotinic acetylcholine receptors, aiming to reduce nicotine cravings and satisfaction associated with nicotine products [5] - The drug has a revised formulation and dosing schedule compared to its predecessor, which had a complex 25-day titration regimen [2] - Achieve Life Sciences is preparing for a New Drug Application (NDA) filing and potential approval, following the completion of a long-term safety exposure study [2]

Core Insights - Achieve Life Sciences has promoted Ms. Jaime Xinos to Chief Commercial Officer to lead the commercial operations and strategic preparations for the anticipated U.S. launch of cytisinicline, a treatment for nicotine dependence [1][2][3] Company Overview - Achieve Life Sciences is focused on the global development and commercialization of cytisinicline, targeting the nicotine addiction epidemic, with approximately 29 million adults in the U.S. smoking combustible cigarettes [4] - The company aims to address the health impacts of tobacco use, which is responsible for over eight million deaths worldwide annually, including nearly half a million in the U.S. [4] Product Information - Cytisinicline is a plant-based alkaloid that interacts with nicotinic acetylcholine receptors in the brain, potentially aiding in smoking and e-cigarette cessation by reducing cravings and the satisfaction associated with nicotine [5] - Currently, there are no FDA-approved treatments specifically for e-cigarette cessation, highlighting a significant market opportunity for cytisinicline [4][5] Leadership and Strategy - Ms. Xinos brings nearly 25 years of experience in the biotechnology and pharmaceutical industries, having held leadership roles at major companies such as Pfizer and Novartis [3] - The company plans to forge strategic partnerships with commercialization experts to navigate the challenges faced by small biotech firms launching their first product [2][3]

SEATTLE and VANCOUVER, British Columbia, Oct. 01, 2024 (GLOBE NEWSWIRE) -- Achieve Life Sciences, Inc. (Nasdaq: ACHV), a late-stage pharmaceutical company dedicated to the global development and commercialization of cytisinicline for smoking cessation and nicotine dependence, is pleased to announce the appointment of Dr. Mark L. Rubinstein as its new Head of Medical Affairs. Dr. Rubinstein brings more than two decades of experience in clinical medicine, scientific research, and medical affairs leadership, w ...