Achieve Life Sciences, Inc. (NASDAQ:ACHV) is a clinical-stage pharmaceutical company committed to the global development and commercialization of cytisinicline, a plant-based alkaloid with a high binding affinity to the nicotinic acetylcholine receptor. Cytisinicline is being developed as a treatment for smoking cessation and nicotine addiction, with the potential to address the considerable unmet need among millions of smokers and e-cigarette users.

Market Opportunity

The company's focus on cytisinicline comes at a critical time, as smoking remains the leading cause of preventable death globally, responsible for over 8 million deaths worldwide and nearly 500,000 deaths annually in the United States alone. Smoking and exposure to secondhand smoke contribute to various cancers, as well as other pulmonary and cardiovascular diseases, creating devastating consequences for patients and their families. Additionally, the prevalence of e-cigarette use, particularly among youth, has become a growing public health concern, with an estimated 11 million adults and 2 million middle and high school students using e-cigarettes in the U.S.

Product Differentiation

Cytisinicline's unique mechanism of action, which involves interacting with nicotine receptors in the brain to reduce the severity of withdrawal symptoms and the reward and satisfaction associated with nicotine, positions it as a potentially differentiated treatment option compared to existing smoking cessation therapies. The company's clinical development program has demonstrated robust efficacy and a favorable safety profile for cytisinicline in both smoking and e-cigarette cessation.

Recent Developments

In the first quarter of 2024, Achieve Life Sciences made significant progress in advancing cytisinicline's development. The company reached an agreement with the U.S. Food and Drug Administration (FDA) on the long-term exposure data required for the submission of a New Drug Application (NDA) for cytisinicline as a treatment for smoking cessation. Specifically, the FDA agreed that a single, open-label study (ORCA-OL) evaluating the long-term safety effects of cytisinicline will be sufficient to complete the requirement and enable an NDA submission anticipated in the first half of 2025.

Concurrently, Achieve Life Sciences secured financing of up to $124.2 million, which includes a $60 million registered direct offering and a concurrent private placement of warrants. This financing provides the necessary resources to execute the ORCA-OL trial and support the company's operations through the NDA submission, potential approval, and beyond.

Financials

The company's financial performance in the first quarter of 2024 reflects its focus on advancing cytisinicline's development. Total operating expenses for the quarter decreased to $6.0 million, compared to $8.6 million in the same period of 2023, as the company completed its Phase 3 ORCA-3 trial and Phase 2 ORCA-V1 trial in the second quarter of 2023. The net loss for the quarter was $6.5 million, compared to a net loss of $9.0 million in the first quarter of 2023.

Achieve Life Sciences' cash, cash equivalents, and restricted cash as of March 31, 2024, were $66.4 million. The company expects the initial net proceeds from the recent financing to sustain its operations well into the second half of 2025, and if the milestone-driven warrants are fully exercised, the financing could extend the company's financial runway into 2026 and through potential approval of cytisinicline in the U.S.

Outlook

The company's focus for the remainder of 2024 is clear: initiate and complete enrollment of the ORCA-OL study, continue preparations for the NDA submission for smoking cessation, and obtain further guidance from the FDA for a potential expansion into the e-cigarette cessation indication.

Clinical Trial Results

The positive results from the Phase 2 ORCA-V1 trial, published in JAMA Internal Medicine, have further highlighted the potential of cytisinicline as a treatment for nicotine addiction. The study showed that cytisinicline more than doubled the odds of quitting e-cigarettes compared to placebo, with 31.8% of cytisinicline-treated participants achieving continuous vaping abstinence, compared to just 15.1% of those receiving placebo. Cytisinicline was also well-tolerated, with no serious adverse events reported.

The company's Phase 3 ORCA-2 and ORCA-3 trials have consistently demonstrated cytisinicline's efficacy in achieving smoking cessation, with favorable safety and tolerability profiles. Notably, survey results from participants in these trials showed that over 80% of those treated with cytisinicline had successfully quit smoking, and of those who did not quit completely, approximately one-quarter cut their smoking in half. Additionally, nearly all participants were willing to recommend cytisinicline to others, and 86% of participants, including those who did not quit completely, showed interest in using cytisinicline again if needed.

Conclusion

Achieve Life Sciences' focus on addressing the global smoking health and nicotine addiction epidemic through the development and commercialization of cytisinicline is well-aligned with the significant unmet need in this area. With no new approved smoking cessation agents in nearly 20 years and no FDA-approved treatment for e-cigarette cessation, the company's progress in advancing cytisinicline's development could have a meaningful impact on public health.

The company's financial position has been strengthened by the recent financing, providing the necessary resources to execute the ORCA-OL trial and support the NDA submission and potential approval process. Achieve Life Sciences' net loss for the first quarter of 2024 was $6.5 million, compared to a net loss of $9.0 million in the same period of 2023. The company's annual net income for the fiscal year 2023 was -$29,815,000, and it did not generate any revenue during the year. The annual operating cash flow and free cash flow for 2023 were -$24,479,000 and -$24,500,000, respectively.

As Achieve Life Sciences continues to advance cytisinicline's development and prepare for a potential NDA submission, the company's progress will be closely watched by the investment community and the broader healthcare industry. The successful commercialization of cytisinicline could provide a much-needed new treatment option for the millions of individuals struggling with nicotine addiction, both from traditional cigarettes and the growing e-cigarette epidemic.