Greetings. Welcome to Achieve Life Sciences First Quarter 2025 Earnings Conference Call and Webcast. At this time all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. As a reminder, this conference is being recorded. I would now like to turn the call over to Nicole Jones, Achieve Investor Relations. Thank you. You may begin.

Thank you, operator. Good morning, everyone, and thank you for joining us today. From Achieve Life Sciences, we are joined by Rick Stewart, Chief Executive Officer; Dr. Cindy Jacobs, President and Chief Medical Officer; Mark Oki, Chief Financial Officer. The management team will be available for Q&A following the prepared remarks. As a reminder, a replay will be available later today by using the information provided in the earnings press release issued prior to this call or visiting the Achieve website. Today's conference call will contain certain forward-looking statements including statements regarding the goals, strategies, beliefs, expectations and future potential operating results of Achieve. Although management believes these statements are reasonable based on estimates, assumptions and projections, as of today, these statements are not guarantees of future performance. Time sensitive information may no longer be accurate at the time of any telephonic or webcast replay. Actual results may differ materially as a result of risks, uncertainties and other factors, including, but not limited to factors set forth in the company's filings with the SEC. Achieve undertakes no obligation to update or revise any of these forward-looking statements. Please refer to Achieve documents available on our website and filed with the SEC concerning factors that could affect the company. I'll now turn the call over to Rick.

Thank you, Nicole, and good morning to everyone and thank you for joining us on today's call. It's good to be able to say that Achieve is on track to submit the NDA for cytisinicline next month. It's been a long road to get us here and all internal resources are now focused on a successful NDA submission, acceptance and approval. Today's focus is primarily on the NDA submission. The role that cytisinicline can play as a treatment for nicotine dependence is immense. In the U.S. alone, over 29 million adults smoke cigarettes and 11 million adults vape. More than half want to quit, but fewer than 10% succeed because they have inadequate tools to help them overcome nicotine dependence successfully. Cytisinicline can change that and improve the probability and the opportunity to quit smoking and vaping with excellent efficacy and tolerability. If approved, cytisinicline will be the first new nicotine dependence drug in nearly 20 years, providing Achieve the opportunity to offer new hope to patients and their healthcare providers. We want to change the conversation, reminding the patient and medical community that nicotine dependence is a serious medical condition and needs to be treated as such. It's not about willpower, it's about science. Nicotine is the third most addictive drug after heroin and cocaine. We believe that cytisinicline can be a part of the solution that helps reframe this medical condition much like GLP-1s did for obesity. As Cindy will review shortly, we conducted a Scientific Advisory Board Meeting in March with experts in nicotine and tobacco cessation research to discuss cytisinicline. And in April, we were pleased to have our ORCA-3 clinical trial results published in JAMA Internal Medicine. Since our call in March, further progress has been made and Achieve now has over 100 patients with the FDA's required one year exposure to cytisinicline in the ORCA-OL open-label study. The fact that so many patients remain on the study and continue on the drug is a testimony to cytisinicline's tolerability. Additionally, the Data Safety and Monitoring Committee completed another successful review of the ORCA-OL safety data and the trial is continuing as planned. With that, I'll turn the call over to Cindy to provide more details on the ORCA-OL trial and the overall clinical development and regulatory process.

Thank you, Rick. We continue to keep up the momentum in driving toward the completion of the NDA and we're in the final stages of submission preparation. We are taking the necessary steps and focus on ensuring that we will file a high quality NDA in June. So let's now turn to some recent highlights. In January, we hit a key milestone of having 300 participants in ORCA-OL with cumulative cytisinicline safety exposure data for a total of six months. This was the gatekeeping requirement to be completed to move toward the NDA submission and we're proud to have checked that box. Furthermore, in April, we reached the second requirement of having at least 100 participants with cumulative cytisinicline safety exposure data for a total of one year. Safety data for one year exposure is being monitored and will be finalized to include it in the standard 120 day safety update that we will be submitting during the NDA review process as agreed upon with FDA. As Rick mentioned earlier, just last week we had our third Data Safety Monitoring Committee review of the open-label study safety data. The committee once again reaffirmed excellent adherence to cytisinicline treatment, reported no safety concerns and required no modifications to the trial conduct. We are thrilled with how quickly the ORCA-OL has progressed. Long-term studies are often difficult when it comes to retention of participants for one year treatment requirements, so it is encouraging to see so many participants choosing to stay on treatment. Of the 479 participants who enrolled by the end of September last year, approximately 75% remain on cytisinicline in the study to date. We believe their willingness to remain on cytisinicline speaks to its favorable side effect profile and possibly efficacy benefit and is a strong signal of the potential impact cytisinicline could have in clinical practice. Also during the quarter, we convened our Scientific Advisory Board with a roundtable of 10 leading experts in nicotine and tobacco cessation research. The discussion focused on updating these key opinion leaders on our research progress and NDA filing preparations while gathering invaluable insights from this esteemed group. The presence of such respected experts from Harvard, Yale, Stanford and UCSF among them underscores the excitement surrounding cytisinicline and its potential to treat nicotine dependence. This excitement continues as we recently had our Phase 3 ORCA-3 trial results published in the Journal of the American Medical Association, JAMA, Internal Medicine. The authors concluded that ORCA-3 reaffirmed cytisinicline's efficacy and tolerability for helping adult smokers quit at both the 6 and 12 week treatment durations. The data showed not only higher quit rates compared to placebo, but also a meaningful reduction in nicotine cravings and sustained benefits out to 24 weeks. Even among participants who didn't fully quit, cytisinicline helped reduce their cigarette smoking as verified by a reduction in nicotine intake. This was demonstrated by decreased levels of cotinine, a key nicotine metabolite, as well as by overall lower craving scores. In fact, Achieve's Dr. Mark Rubinstein will present data on the participants who didn't fully quit at the American Thoracic Society 2025 International Conference next week, highlighting the importance of cytisinicline's mechanism of action in helping to lower cravings and reduce nicotine intake. As we look to the future, our enthusiasm continues to grow around cytisinicline's potential to set a new standard in treating nicotine dependence for smoking cessation. It's been nearly two decades since a new prescription treatment has been approved by FDA and we believe cytisinicline is well positioned to fill this high unmet need for patients and providers. I will now turn the call over to Mark to review the financials.

Thank you, Cindy, and good morning. As we work toward our NDA submission in June and continue laying the groundwork for a potential commercial launch in 2026, we're staying laser focused on managing our resources wisely and will continue doing so. As of March 31, 2025, the company's cash, cash equivalents and marketable securities were $23.2 million. Now turning to our statement of operations, our total operating expenses for the first quarter of 2025 were $12.9 million and the corresponding net loss was $12.8 million. We remain committed to strong financial discipline, making sure our spending directly supports our key priorities getting cytisinicline to market, building a foundation for our long-term growth and creating lasting value for our stockholders. With that, I'll turn it back to Rick for his closing remarks.

Thank you Mark and thanks to the entire Achieve team for their support and tremendous efforts in pushing the NDA over the goal line. We are on track and weeks away from reaching this milestone. Adding to Mark's remarks, cash management remains a priority for the company and we're being prudent with expenditures to ensure Achieve's cash runway is extended and the NDA remains the focus. Once the NDA is submitted, we anticipate receiving a 74 day letter from the FDA acknowledging the acceptance of our submission and from there we expect the NDA approval to take approximately 12 months from the date of submission. Treating nicotine dependence is our primary focus. And as I have mentioned before, cytisinicline can also help reduce the comorbidities and broader disease burden caused by smoking, particularly in conditions like COPD and asthma. Smoking is a major driver of multiple chronic conditions. For example, around 80% of people diagnosed with COPD develop the disease due to smoking and about 6 million of the 16 million Americans diagnosed with COPD currently smoke today. In our two Phase 3 trials, it was notable that smokers with COPD had higher quit rates on cytisinicline than those without the disease, a promising signal for COPD patients. Quitting can improve COPD treatment effectiveness plus reduce exacerbations and hospitalizations in COPD patients where smoking worsens symptoms and increases severity. These findings highlight cytisinicline's potential impact beyond just treating nicotine dependence alone. Achieve's mission driven team, together with support from key opinion leaders and patients in our clinical program, has built a strong foundation for success. By meeting both patients and physician needs, we are ultimately positioned to deliver long lasting value to stockholders. Thanks again for spending time with us this morning. We look forward to keeping you updated as we continue making progress in the months ahead. With that, I'll hand you back over to the operator to begin the Q&A.

Thank you. Our first question is from Gary Nachman with Raymond James. Please proceed.

Thanks and congrats on the progress. So a couple of questions. First, how long before we see the full safety data from the long-term study? How will you present that? What will it be after you update the NDA with the one year data? And when you say 75% of the enrolled patients remain on treatment in the long-term study, what's the average duration for patients getting cytisinicline? And is that reflective of how it will be used in a real world setting? And then what were some of the key takeaways from the SAB meeting and how did that inform you for your filing and also for your commercial plans?

Thanks, Gary. I'll hand that one over to Cindy.

Sure. In the open label study, we are currently working to complete all patients by June, July, August, and a few in September. Most subjects will have received over six months of treatment in that study. We plan to compile this information and present it after the NDA is submitted and after we submit the 120-day safety data in October. We are considering opportunities to present that data at a conference towards the end of this year or next year, but we don't have anything scheduled at this time.

That's okay. That's helpful.

Yes, what was the next…

Yes, the SAB meeting.

Oh, the SAB meeting actually was really just interesting as far as discussing the applications that cytisinicline treatment could have from obviously individuals who want to stop smoking, but also in hospital situations where interactions with other medications this would be important since there are no nausea side effects. There were a lot of other avenues of interest on how cytisinicline and where cytisinicline could be used.

Okay, great.

If I can add something, I was…

Yes, please Rick.

Yes, Gary, I attended that meeting, and what stood out to me was the strong enthusiasm from the key opinion leaders for the drug. As we broaden our group of key opinion leaders, it becomes increasingly clear that this is the first new treatment for nicotine dependence in over 20 years. There is also a growing acknowledgment of both the drug's effectiveness and its tolerability. The consensus among the key opinion leaders is that this drug is poised to make a significant impact in the field of nicotine dependence.

Okay. So just to follow up, given that, what are some of your plans just in terms of pre-commercial efforts to continue to increase awareness and what cytisinicline could offer? And then just lastly, the status of any partnership discussions ongoing that could help provide some non-dilutive capital, whether looking at a comorbid COPD study like you talked about in the past, or maybe a commercial partner, U.S. or ex-U.S.? Thanks.

First part, I'll hand that one over to Jaime.

Sure, hi. Thanks for the question, Gary. Yes, so on the commercial readiness, what we're really doing at the moment is making sure we're focusing on our three key areas and one of those you mentioned is awareness. But availability and access are two of our priorities. The first one, making sure that we have drug in the channel. So we've made some great strides over the last several weeks to ensure that we are ready to actually sell the product. And then on the access side, we're continuing work on our pricing and payer strategy as well and beginning to start thinking about how our pre-information, our pre-approval information exchange conversations will go with those payers. On the awareness side, we're really again focused right now highly on the NDA and making sure that our PI and our label is what we will need to be able to support the claims that we hope to make to differentiate cytisinicline from current treatment options. Alongside that, we have some efforts to make with physicians to bring smoking cessation back to the conversation that they're having with their patients because for 20 years they've had no new options to offer them and so they're quite frustrated. And so, I think, it's really important that we get out prior to launch to make sure they know that there is going to be a new option and the same will apply when those patients are coming in to have conversations, they have something different to offer them. We spent a lot of time too on the awareness side just building out more of a marketing focus, but really how we're going to be communicating with physicians. So we're building out our digital roadmap, so that we have an omni-channel, very efficient platform that we can reach our customers and make sure that we're meeting them where they are and where they want to be finding information instead of trying to go to them in channels that they're not really receptive to hearing from pharma. So a lot of efforts on the commercial planning phase as well. And then Rick…

In response to the second part of your question, yes, we believe we can launch the nicotine dependence initiative in the U.S. independently. However, your question about strategic partnerships is relevant. Currently, we are defining our requirements for partnerships related to COPD, asthma, and other respiratory conditions. It's crucial to determine how cytisinicline can be integrated into COPD treatment plans. We have been closely examining anti-IL-33 drugs, some of which face challenges in demonstrating effectiveness in smokers. Our focus now is on clearly outlining the opportunities in this area, specifically how to design a clinical study that effectively measures improvements in efficacy. We are in discussions with several potential partners, but it's essential to establish a solid foundation for our goals before moving forward.

Okay, great. Thanks for all that color. Appreciate it.

Our next question is from Justin Walsh with Jones Trading. Please proceed.

Hi. Thanks for taking the question. I'd love to hear if you notice any changes in your interactions with the FDA.

Cindy, that one is for you.

At this point, we haven't seen any real changes. They're just as responsive as they have been. We have had some interactions obviously, as we get closer with the NDA submission and asking them over the last three to four months and their responses have been as normal. And so we have not seen any changes to date in the last few months.

Great. And maybe a quick follow-up on that. I'm just curious if you see potential opportunities with the shift in focus towards more chronic diseases. While your interactions with the FDA have remained consistent, I wonder from a broader philosophical standpoint if there's any alignment with the current administration regarding this type of product.

Well, I mean, obviously it's hard to speculate, but we would hope, because we are very proud of the efficacy and the safety data, that the ability to use cytisinicline to address chronic diseases like COPD and all of the cardiovascular diseases, smoking causes, will be a play as far as when they're reviewing and looking at all of our efficacy and safety data.

Great. Thanks for taking the questions.

Our next question is from John Vandermosten with Zacks Investment Research. Please proceed.

Great. Thank you and good morning, you guys. On the last call, you mentioned that you'd be discussing pricing with payers. I'm not sure if that happened yet. But if they have, have those conversations gone? And are there any products that they're using as comparison to determine pricing? And then also on that same topic, are there any pharmacoeconomic elements guiding the discussion?

Jaime, that's for you.

Good morning, John. Yes, we have had some discussions with payers and are currently analyzing the information we've received. The samples are small and the research is blinded, so while it provides some direction, we won't have a solid perspective until we conduct further exchanges and establish our pricing. From what we've heard historically, formulary placement and reimbursement will ultimately depend on our pricing, which will inform our contracting needs and potential rebate strategies. There is clear value demonstrated with our product, and they recognize that; however, its placement will be influenced by our price. Regarding comparators, payers will certainly consider available options in the market, but our product shows clear differentiation from generics. Additionally, the patient population we're targeting has typically tried multiple therapies that are currently available. It's worth noting that nothing new has emerged in 20 years, making it challenging to enforce a step-through protocol since many patients have either attempted these therapies unsuccessfully or are reluctant to try them. Therefore, barriers to access are less significant from that viewpoint. Did you have a third part of that question?

And then, yes, on the pharmacoeconomic economic studies, perhaps? I mean, obviously there's some long-term benefits that we all know intuitively. But are you going to do anything there that quantifies it for 2025?

Yes. I don't think there's a need to repeat studies that have already been conducted that show smoking causes these chronic diseases that are very expensive. There is so much literature out there that we can leverage. I think there is value in showing our biggest value proposition that we believe is that increased adherence is going to lead to compliance, which is going to improve outcomes. And I think that's what we need to be able to make a strong argument in a case for. So instead of spending any resources on showing that chronic diseases caused by smoking are expensive, as we know they're costing the U.S. healthcare system over $300 billion a year that data is strong and it exists. And we've done analysis and kind of a HuR gap analysis to show that that data is out there. We're going to spend our time and energy on specifically how cytisinicline can improve the results that they are seeing with current treatments or not seeing with current treatments.

Okay. And there are a number of, I don't know, I guess you call maybe digital first commercialization companies out there like CliniOps and Indegene. Can they take up part of what you were doing? Maybe focus on some of the areas where they're more generic and they have leverage and then you focus on the areas where you have a competitive advantage. Is that something you might take advantage of? Or can you just do it all internally without using something like one of those guys?

We will be heavily relying on and have been on our agency partners to help us implement our strategy. So we've been working with Omnicom primarily and they have a strong digital company called Credera that works across all industries and sectors and they have helped build out a highly strategic and advanced model of what a digital launch roadmap would look like, what our data requirements will be, and how AI will help to inform every stage of the process, from improving our targeting strategies to improving the time and the efficiencies gained with the development of content and the measurements of whether or not the content is resonating with our target audiences. So we are definitely partnering and leveraging external resources very heavily.

Okay, sounds like you get some real-time data there as you're doing the process. And last question for me is you should be assuming that the products approved on time. About a year from now you'll start commercialization or you'll be free to start it. Do you think you'll start right as soon as the approval is given? Or will you take a little time to kind of set things up? I just was wondering kind of the timing from a model perspective on how we should anticipate first sales to fall in next year.

Yes, I think it's fair to assume a company of our size is going to need a minute following approval to get drug in channel. So it's going to take us a little bit of time and I'm not sure we can speak right now exactly to how much time, but we certainly want to have a strong launch as close to the timing of approval as possible. But again, we'll probably be able to give some further instruction and direction on that as we get closer.

Great. All right, thanks, Jamie. Appreciate it.

You bet.

There are no further questions at this time. I would like to turn the call back over to Rick Stewart for closing remarks.

Thank you, operator. We'd once again like to thank you for joining Achieve's Q1 call. It's clear that cytisinicline and Achieve can have a significant impact on the public health narrative in the U.S. today by providing patients and physicians with new, improved tools to address the nicotine dependence crisis in the U.S. The near-term NDA submission is a major milestone for Achieve for patients, for physicians and for our stockholders. And we are confident of driving forward to a product launch in 2026. Thank you for joining the call.

Thank you. This will conclude today's conference. You may disconnect your lines at this time and thank you for your participation.