Achieve Life Sciences, Inc.

will be a key point of differentiation as smokers and their doctors consider using cytosinicline once available. Smoking cessation prescription therapies historically have had black box warnings and high rates of troublesome side effects such as abnormal dreams, insomnia, nausea, and vomiting, which increases treatment discontinuation and limits the overall utilization of current products. Quitting smoking is difficult enough due to withdrawal symptoms without the treatment making you feel even worse. We think offering a more tolerable product should help maintain strong treatment compliance, leading ultimately to better outcomes for smokers looking to quit. As we look ahead to the next milestone for the smoking cessation program, we continue to anticipate enrollment completion for our second confirmatory phase three trial to occur by the end of the third quarter this year. ORCA III aims to enroll 750 smokers across 20 clinical trial locations in the U.S. The design of the trial is similar to ORCA II in that it will evaluate six and 12 weeks of cytosine and clean treatment versus placebo in smokers using the same dosing schedule and endpoints for evaluation. This trial was initiated in the first quarter of this year and is currently enrolling smokers. We look forward to the next update on ORCA III, which we expect will be when enrollment has completed in the coming months. And we continue to anticipate top-line results to be available in the first half of next year. Moving on to the potential for cytosinicline in users of nicotine e-cigarettes or vapes. In June, we initiated our Phase 2 ORCAv1 trial, thanks to the continued funding from the NIH and NIDA, which awarded us the next $2.5 million in grant funding to conduct this trial. ORCAv1 aims to enroll approximately 150 adult nicotine e-cigarette users in the U.S. and is led by our ORCA2 PI, Dr. Nancy Rigotti, Professor of Medicine at Harvard Medical School and Director of the Tobacco Research and Treatment Center at Massachusetts General Hospital. ORCAv1 has two treatment arms evaluating the safety and efficacy of 3 mg cytosinicline dosed three times a day for 12 weeks compared to placebo. As with the other ORCA trials, all participants will receive behavioral support. The primary objective of the study will be to evaluate for successful nicotine vaping cessation. Vaping cessation is defined as weekly nicotine vaping abstinence for the last four weeks of treatment from weeks nine to 12. Other timing for weekly vaping abstinence will also be assessed as secondary outcomes. For example, between weeks three to six, as well as any reduction in nicotine vaping during the 12-week period. There's great enthusiasm and interest in ORCAv1, and we are encouraged by what we are seeing thus far in terms of patient recruitment for this trial. We expect enrollment to be completed in the fourth quarter of 2022 and top-line results in the first half of next year. There are currently no FDA-approved treatments indicated specifically for users of nicotine e-cigarettes or vapes. The CDC reported that there were nearly 11 million adult e-cigarette users in the U.S. alone in 2019. While it is believed that noncombustible forms of nicotine present lower health consequences than traditional cigarettes, complete abstinence from nicotine is ultimately the goal for many. In a survey conducted by Achieve of vape and e-cigarette users, approximately 73% of participants stated they intended to quit vaping in the next three to 12 months. And an overwhelming majority would be interested in trying a new natural prescription treatment to help them do so. We believe cytosine and clean has great potential to meet the needs of this population who are ready to quit nicotine for good. With that, I will now turn the call over to Jerry for our financial update.

Thank you, John. I would like to provide an update on our cash position as of June 30th, 2022. as well as review our operating expenses for the second quarter. As of June 30, 2022, the company's cash, cash equivalents, short-term investments, and restricted cash were $29.4 million, compared to $43 million as of December 31, 2021. We believe we have sufficient cash to bring us into 2023. Our cash forecast includes the recently awarded $2.5 million grant funding received from the NIH to initiate the Phase II ORCAv1 trial to evaluate the use of cytosinicrine as a treatment for cessation of nicotine e-cigarette use. As a reminder, approximately half of the costs from the ORCAv1 trial are funded through the grant from the NIH. With respect to our statement of operations, net loss decreased to 10.4 million for the quarter ended June 30th, 2022. compared to $11.3 million for the same quarter of 2021. Debt loss for the six months ended June 30, 2022, decreased to $18 million, compared to $19.3 million for the same period of 2021. Operating expenses decreased for the quarter ended June 30, 2022, due to lower costs associated with the completion of the ORCA-2 trial. This was partially offset with the initiation of the ORCA-3 trial in January 2022, and the initiation of the ORCAv1 trial in June 2022. We expect our quarterly operating expenses will increase as we progress forward with both the ORCA3 and ORCAv1 trials. I'll now turn the call back over to John.

Thanks, Jerry. We continue to make tremendous progress with the cytosinicline development program, especially with the announcement of positive Phase III ORCA2 results and the initiation of both our ORCA3 and ORCAv1 trials. We remain committed to moving these trials forward and ultimately bringing a new treatment option to the market for nicotine addiction. With a compelling efficacy and safety profile and a shortened treatment regimen, cytosinicline has the potential to make a strong impact in a market that has lacked innovation and new treatments in over 15 years. The most successful prescription smoking cessation product was Chantix, which had peak global sales of $1.1 billion before it was withdrawn in 2021 for safety concerns. There are currently only two non-nicotine prescription products available to the 30 million-plus smokers in the U.S., generic Chantix and generic Zyban. Despite being tainted with its historical black box warning and disruptive side effects, Generic Chantix is anticipated to reach approximately 300 million in U.S. sales over the coming year. We believe that cytosinicline's product profile, including robust efficacy, high tolerability, and shorter duration of treatment, has potential to resonate in this underserved market. We look forward to moving cytosinicline to market and providing smokers and their physicians a compelling new treatment option. We look forward to sharing with you our continued progress in the back end of this year, including completion of enrollment in our ORCA III and ORCA V1 studies, as well as potential for publication of the ORCA II results. At this time, I'd like to turn the call over to the operator and take any questions you might have. Operator?