Achieve Life Sciences, Inc.

Good day and thank you for standing by. Welcome to the Achieve Life Sciences fourth quarter and year end 2021 earnings conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star 0. I would now like to hand the conference over to your speaker today, Nicole Jones. Please go ahead.

Thank you, operator, and thanks, everyone, for joining us. On the call today from Achieve, we have John Binsitch, Chief Executive Officer, Dr. Cindy Jacobs, President and Chief Medical Officer, and Jerry Wan, Principal Accounting Officer. Achieve management will be available for Q&A after the prepared remarks. I'd like to remind everyone that today's conference call contains forward-looking statements based on current expectations. These statements are only predictions, and actual results may vary materially from those projected. Please refer to a chief documents filed with the SEC concerning factors that could affect the company, copies of which are available on our website. I'll now turn the call over to John.

Thank you, Nicole, and thanks, everyone, for joining us today. During today's call, we will discuss updates on the cytosinicline development program for smoking cessation and nicotine addiction, including the status of the ORCA-2, ORCA-3, and ORCA-V1 studies. Additionally, Jerry will provide an overview of our Q4 and year-end 2021 financial results. We are off to a great start in 2022 with the kickoff of our second phase three trial, evaluating cytosinicline for smoking cessation. We announced initiation of the ORCA III trial in January and are now enrolling adult smokers at 15 clinical trial locations across the United States. ORCA III will serve as the confirmatory phase III trial required for registrational approval and marketing of cytosinicline in the U.S. Given our confidence in the safety and efficacy we have seen with cytosinicline to date, our ability to quickly hire and onboard additional clinical operations personnel, and importantly, our successful securement of capital from Silicon Valley Bank in December, we were able to initiate this trial sooner than expected. By expediting ORCA III, we are not only reducing the overall capital requirements of the development program, but also accelerating the overall timelines for cytosinicline and FDA submission for market approval. This is of critical importance to help the millions of smokers looking for additional treatment options. Similar in design to the ongoing ORCA-2 trial, ORCA-3 participants will be randomized to one of three study arms to evaluate three milligrams cytosinicline dosed three times daily over a period of either six or 12 weeks compared to placebo. All subjects will receive standard behavioral support throughout the duration of the trial and will be assigned to receive either 12 weeks of placebo, six weeks of cytosinicline followed by six weeks of placebo, or 12 weeks of cytosinicline. The primary outcome measure of success in ORCA3 will be biochemically verified continuous abstinence during the last four weeks of treatment in the six and 12-week cytosinicline treatment arms compared with placebo. Each treatment arm will be compared independently to the placebo arm, and the trial will be determined to be successful if either or both of the cytosinicline treatment arms show a statistical benefit compared to placebo. Secondary outcome measures will be conducted to assess continued abstinence rates through six months from the start of study treatment. All clinical sites are now enrolling subjects, and we have just recently launched a number of recruitment activities in the cities surrounding the trial locations. We are seeing great interest from smokers who are seeking more information on the trial and who hope to kick the habit. We look forward to sharing additional details on the trial as we progress throughout this year. Moving on to the highly anticipated ORCA2 trial, like you, we are eagerly awaiting the results from the first Phase III cytosinicline trial in adult U.S. smokers. To recap, ORCA2 enrolled 810 smokers at 17 clinical trial locations. This trial completed enrollment in the summer of last year, and in December, the last subject, last visit, was completed, in line with the six-month follow-up requirements. As part of ORCA II, an independent data safety monitoring committee conducted five preplanned study conduct reviews, which also included safety. They concluded there were no concerns regarding the study conduct and the safety and adverse event profile remained favorable. Additionally, the DSMC members commented that compliance with study medication was excellent and the study had progressed well despite the challenges of the COVID-19 pandemic. With regards to efficacy, ORCA2 has two independent primary endpoints that will evaluate the rate of smoking abstinence for both six-week and 12-week durations of cytosinicline treatment compared to placebo treatment. Beginning at the second week of treatment, assessments for smoking abstinence were performed via weekly self-reporting of abstinence with biochemical verification of abstinence by exhaled carbon monoxide levels. These weekly assessments occurred through the 12 weeks of blinded study treatment. Then, similar monthly follow-up assessments occurred for smoking abstinence at weeks 16, 20, and finally week 24. For both primary endpoint comparisons, smoking abstinence is defined as continuous abstinence during the last four weeks of treatment, meaning for the six-week treatment arm, Biochemically verified abstinence is required at weeks 3, 4, 5, and 6. And for the 12-week arm, abstinence is required at the assessments conducted at weeks 9, 10, 11, and 12. This four-week continuous abstinence measure is the FDA-approvable endpoint for smoking cessation medications. Secondary endpoint outcome measures will assess continued smoking abstinence from the end of cytosinicline treatment in both arms out to week 24 compared to placebo, as well as reduction in risk of relapse at week 24 for subjects treated with 12 weeks of cytosinicline versus six weeks of cytosinicline. ORCA2 was designed with over 95% power to be able to demonstrate a continued abstinence benefit compared to placebo at the long-term follow-up comparison at 24 weeks. Finally, on ORCA-2, we continue to expect top-line results to be announced in the second quarter of this year, and until then, we remain blinded to the outcome. Concluding our updates on the development program is the status of ORCA-V1, which is the Phase II trial evaluating cytosinicline as a cessation treatment for nicotine e-cigarette users. Following the smoking cessation approval, our ultimate goal is to later expand the cytosinicline label indication to help nicotine vapors to quit. With more than 11 million adult users of e-cigarettes in the United States and no currently approved treatment options available specifically for this population, there is a growing unmet need for a cessation therapy to help the significant numbers of vapors who want to quit. Based on survey data that we have collected in partnership with IQVIA, approximately 73% of e-cigarette users expressed an interest in quitting. We announced last year that Achieve was awarded a grant from the National Institutes of Health, or NIH, to support the execution of the ORCA V1 trial. In addition to the preparation of trial-related operational activities, the first phase of the grant funding enabled submission to the FDA of a new IND specific to e-cigarette cessation, which was accepted by the agency in November. We have recently submitted documentation to the NIH outlining our completion of activities associated with the first phase of the grant. Pending their review, we expect the second stage of the grant award of approximately $2.5 million to be released and to enable the initiation of the ORCA V1 trial in the second quarter of this year. As a reminder, ORCAv1 is designed to enroll approximately 150 subjects and will be led by Dr. Nancy Rigotti, Professor of Medicine at Harvard Medical School and Director of the Tobacco Research and Treatment Center at Massachusetts General Hospital. I'd now like to turn the call over to Jerry to discuss our financial results and our strong cash position that we ended with in 2021.