Achieve Life Sciences, Inc.

Greetings and welcome to the Achieve Life Sciences third 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's Vice President, Strategic Communications and Stakeholder 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. Mark Rubenstein, Interim Chief Medical Officer, Jamie Zenos, Chief Commercial Officer, and Mark Oakey, Chief Financial Officer. The management team will be available for Q&A following the prepared remarks. A replay will be available later today using the information in the earnings press release or by visiting the Achieve Life Sciences 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 risk, uncertainties, and other factors including, but not limited to, the 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, everyone. This has been another truly significant quarter for Achieve in our mission to get a new treatment for nicotine dependence into the hands of patients. Our priorities of NDA submission, NDA acceptance, and ultimately NDA approval for cytosinicline as a treatment for nicotine dependence in smoking cessation have advanced significantly this quarter. These priorities have now been reinforced by the recent announcement that the FDA has awarded Achieve a Commissioner's National Priority Voucher, or CNPV, for the e-cigarette or vaping indication. This is a significant recognition of the importance of cytosinicline in addressing the emerging public health crisis caused by vaping. The CNPB is designed to provide enhanced FDA communications and an expedited NDA review timeline, reducing the potential NDA approval to one to two months from the standard 10 to 12 months. The implications are enormous for patients and physicians and are significantly value-enhancing for our stockholders. A rapid approval of a vaping indication means cytosinicline could be launched eight months earlier than expected. This would allow Achieve to potentially pioneer the first and only FDA-approved treatment for the 60% of people who want to quit vaping. During the quarter, we hit several regulatory milestones related to our smoking cessation indication. Most notably, the FDA acceptance of our new drug application for cytosinicline for review and set a producer or approval date of the 20th of June, 2026. Additionally, we submitted the 120-day safety review to the FDA on time. All interactions with the FDA remain normal and timely. To put our progress into perspective, nearly 29 million adults in the United States smoke cigarettes. and more than 15 million people attempt to quit every year. Smoking remains the leading cause of preventable death in the U.S. Approximately half a million deaths annually are attributable directly to smoking, costing over $600 billion each year in smoking-related U.S. healthcare costs and lost productivity. Numerous comorbidities including respiratory, cardiovascular and metabolic disease and of course cancer result from cigarette smoking and countless lives are impaired. This is the urgent need Achieve is focused on and cytosinicline is designed to address. Smoking cessation is an immense addressable market that has no new FDA-approved treatment options for nearly 20 years. Patients and physicians are frustrated by the lack of adequate tools to help drive success in their quit journey. The message is clear. Achieve is not quitting on you. With cytosinicline, Achieve is on the threshold of delivering a potential game changer for the millions hoping to quit. Fundamentally, it is clear that the narrative surrounding smoking and vaping has to change. Nicotine dependence has to be acknowledged as a medical condition in much the same way as obesity is now recognized with the advent of GLP-1s. There are clear similarities between the obesity and nicotine dependence market dynamics. Nicotine dependence is a neurobiological condition resulting from an overabundance and the number of nicotinic receptors in the brain and needs to be treated as such. As I mentioned in the introduction, comorbidities are a significant life impairment as a result of smoking, anything from COPD, asthma, cardiovascular disease, cancer, type 2 diabetes. The list is long. We decided to specifically investigate the impact of cytosinicline in smokers with COPD and achieves two phase three clinical trials. Our recent publication in Thorax highlighted cytosinicline's potential to help individuals with COPD who remain smokers. As a reminder, approximately six million of the 16 million Americans diagnosed with COPD continue to smoke today. In our two phase three trials, we saw the smokers with COPD had higher quit rates on cytosinicline compared to placebo. COPD smokers on placebo did not quit at all. We were thrilled to see this outcome within this subgroup as these patients are often amongst the most difficult to treat due to the severity of their progressive illness. We know that quitting smoking improves the effectiveness of COPD treatments and helps reduce exacerbations and hospitalizations. since smoking worsens symptoms and increases disease progression. These findings underscore cytosinicline's potential impact in offering meaningful benefits to one of the most vulnerable patient populations. Dr. Mark Rubenstein will discuss the findings in more detail in a minute. Jamie Zenos will also discuss Achieve's data-driven digital commercialization strategy and provide an update. I'd like to set the stage by noting that many large and specialty pharmaceutical companies have embraced AI as a powerful tool to advance precision targeting of both physicians and patients. What differentiates Achieve's commercial strategy is the integrated nature of our ecosystem and platform. Achieve leverages AI and machine learning to drive next best action orchestration, omnichannel marketing, and audience activation across healthcare professionals, patients, and payers. By utilizing a unified, HIPAA-compliant data warehouse and generative AI, Achieve is able to optimize campaigns, enhance engagement, and measure ROI across all channels. For Achieve Life Sciences, this represents a scalable model for deploying AI-powered commercialization at launch. while minimizing infrastructure investment. Without getting into too much technical jargon, the benefits of an AI or data-driven approach include channel sequencing, determining the next best action email, social ad, webinar invite, or rep visit for each audience. Message optimization, using AI-driven models to tailor messaging to behavioral and conceptual data. dynamic measurement, real-time KPI or performance monitoring, and tracking, allowing optimization mid-campaign. These powerful AI-driven tools allow integrated payer, HCP, and patient activation through a single HIPAA-compliant environment. The integrated platform is cost-efficient, ensuring resources are applied with targeted precision, providing improved revenue outcomes. I'm sure you will share Achieve's excitement with the commercial build-up prior to launch in the third or fourth quarter next year. Turning to updates on our team, we had two promotions and one new hire. Dr. Mark Rubenstein became our interim chief medical officer, and Craig Donnelly was promoted to chief operations officer. Eric Atkinson joined us recently as chief legal officer. Dr. Rubenstein joined is a seasoned physician and executive with deep experience in patient care, clinical development, scientific research, and medical affairs leadership, with a strong focus on nicotine cessation and preventative medicine. Having served as our head of medical affairs since 2024, he brings a strong understanding of our programs, pipeline, and strategic objectives, along with real-world experience treating patients who are eager to quit nicotine. Dr. Rubenstein is steeped in the world of smoking cessation and nicotine dependence. In his academic career, he led a clinical and translational research program focused on nicotine addiction and smoking cessation as a professor at UCSF. Prior to joining Achieve, Dr. Rubenstein served as the head of medical affairs at Blip, where he spearheaded the company's strategy to help smokers and vapers quit through FDA approved medications and digital support tools. His deep understanding of the nicotine dependence landscape positions him to seamlessly lead our clinical and medical efforts as we move toward potential approval and commercialization. It's been great to work with Dr. Rubenstein in his new role. We promoted Craig Donnelly to Chief Operations Officer since joining Achieve in 2022 Craig has shown outstanding leadership in manufacturing and regulatory. In his new role, he will align our supply chain and commercial strategy as we prepare to launch CytoCineClean. With over 25 years in biopharma, his expertise will be key as we build the infrastructure to deliver CytoCineClean to patients and move Achieve into a commercial stage company. Lastly, in October, we welcomed Eric Atkison, as our new chief legal officer who will oversee our legal strategy, corporate governments, compliance, and risk management. With over 25 years' experience in the pharmaceutical and biotech industries, specifically in legal, regulatory, and M&A, ERIC's already been a tremendous asset as we move cytosinicline through regulatory review and get ready for a potential launch. Thanks to our world-class team and relentless focus on execution, we continue to deliver on our milestones and move confidently toward bringing a much-needed new treatment to market. With that, I'll now turn it over to Dr. Rubenstein.

Thank you, Rick, and good morning, everyone. As a clinician who has spent much of my career helping people overcome nicotine dependence, I'm honored to serve as interim chief medical officer during this pivotal time for the company. I'm also excited to continue to build on the solid foundation we have established thus far. Since last quarter, we have met several important milestones, and our regulatory process remains on track. Most notably, the FDA has accepted our NDA for cytosinicline, initiating the review process, and setting a PDUFA action date of June 20, 2026. All interactions with FDA remain normal and on track. We submitted our 120-day safety update, ensuring that the most current and comprehensive long-term safety data are available for review from the ORCA-OL trial. In this submission, we included data on 411 individuals with at least six months of cumulative cytosinicline exposure and 214 with at least one year of cumulative cytosinicline through the submission cutoff date of June 4, 2025. Our ORCA-OL long-term exposure study received its fourth and final comprehensive safety review from the Data Safety Monitoring Committee. The DSMC found that adverse events were mostly mild in severity and no serious adverse events were deemed to be treatment-related. Additionally, there were no safety concerns with the drugs. Furthermore, we were pleased to report that our last ORCA-OL participant completed the study in October, marking 334 participants who completed one full year of the trial. The final site closeout visit took place at the end of October, representing an important milestone in our long-term development program. We are thrilled with the outcomes from ORCA-OL. Long-term studies can be challenging 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 well in excess of what the FDA requested. As someone who's treated countless patients struggling with nicotine dependence, I know firsthand how difficult it is for people to remain engaged in any quit attempt. Seeing participants stay committed for a full year truly underscores the tolerability and appeal of cytosinicline. We believe their willingness to remain on cytosinicline speaks to its favorable side effect profile and possible efficacy benefit and is a strong signal of the potential impact cytosinicline could have in clinical practice. In terms of patient experience in the OL trial, We collected exit survey responses from participants and are encouraged by their feedback. Over 97% of respondents believe cytosinicline helped them quit or reduce their nicotine use. In addition to reduced cravings, our respondents reported that they believe the lack of side effects and withdrawal symptoms helped them quit. Many described the treatment as the added push they needed, and something that gave them the confidence to quit. Nearly all respondents indicated they would recommend cytosinicline to a friend or family member trying to quit. We remain on track to lock the ORCA-OL database by year end and are preparing for presentations and further publications in 2026. Our entire team is energized by the progress and the real-world impact we are poised to deliver. As Rick mentioned, new post-hoc data from an analysis of the ORCA2 and ORCA3 trials were published in Thorax, demonstrating that cytosinicline significantly improved quit rates compared to placebo in adults with COPD. Despite having more severe tobacco use histories and greater prior prescription treatment exposure, participants with COPD achieve quit rates with cytosinicline comparable to those without COPD. These findings support cytosinicline as a potential new pharmacologic option for people with COPD who continue to smoke despite their progressive disease. Lastly, we are thrilled to have received the Commissioner's National Priority Voucher for Cytosinicline and Vaping Cessation. This is a significant recognition of the public health importance of our work and positions us well to advance cytosinicline as the potential first FDA-approved treatment for nicotine vaping dependence. We are now preparing to initiate our ORCA V2 Phase III trial for vaping cessation, including finalizing the study protocol, selecting trial sites, and identifying the principal investigator. The CNPV allows us to have enhanced engagement with FDA to shorten the timeframe for NDA submission and approval. That concludes my remarks. And I'll now turn the call over to Jamie to provide updates on our commercial strategy.

Thank you, Dr. Mark. This quarter, our team continued to make great progress in preparation for the U.S. commercial launch of cytosine and clean. Our mission is to deliver this transformative therapy to the millions of Americans who want to overcome their nicotine dependence using the most advanced tools and strategies available. Our team remains focused on three strategic imperatives, availability, access, and awareness. each underpinned by a rigorous data-driven approach and a commitment to maximizing efficiency and measurable impact. Starting with availability, our first priority is ensuring cytosinicline will be available to patients nationwide. To this end, we have made progress on several key fronts. We've selected our third-party logistics provider and will begin the implementation process in Q4 well ahead of potential approval. I'm pleased to report that our home state licensing application was accepted in Washington State We are now in the process of working on licenses for states that will allow us to submit prior to product approval. Additionally, we have further evaluated specialty distribution options and have selected our specialty light hub partner. Administrative and logistical initiatives will begin this quarter and continue through launch. We believe these foundational steps will be critical to ensure patients can access cytosinicline and that prescriptions written are prescriptions filled. On the access front, our focus remains on securing rapid, broad, and affordable coverage for cytosine and clean. Our pricing and payer research accelerated significantly in Q3, culminating in a comprehensive segmentation of payer organizations. The work identified distinct payer profiles, which will guide the alignment of our target list and inform tailored engagement strategies. We've also completed both the quantitative and qualitative phases of our pricing and contracting research. This effort provides critical insights into market access dynamics, optimal price positioning, and payer expectations, laying out the foundation for a strategy designed to maximize reimbursement potential at launch. Importantly, payers continue to recognize Cytosynaclean's differentiated profile and the importance of having a new treatment to help people overcome nicotine dependence. Beginning in Q1, we will start proactive engagement with prioritized payers to deliver pre-approval information exchange communications. Feedback from these interactions will be critical in finalizing our access and contracting strategy as we move closer to launch. Turning to awareness. Building product-specific awareness and establishing Achieve's reputation as a trusted, science-driven partner continues to be a cornerstone of our strategy. In Q3, we significantly advanced our patient and HCP targeting initiatives. We have finalized patient journey mapping, communications frameworks, and decile segmentation to prioritize HCPs on a series of key treatment, prescribing, and engagement behaviors, allowing us to deeply understand and motivate our key targets. Our partnership with Omnicom remains highly productive. The MarTech and data work streams have now an established foundation infrastructure, and we are progressing towards a unified data ecosystem to power our AI-enabled commercial platform. This will allow us to continuously optimize targeting, messaging, and performance across all channels. Turning to our team, we have continued to build out our internal commercial organization, which includes new talent leading commercial development, market access, supply chain, and communications. While we have added key new hires, we are maintaining a lean, efficient internal team. Our collaborative approach with partners ensures we benefit from their deep expertise and scalable resources across every critical function. In summary, I want to emphasize that our progress is guided by a clear and focused commercial strategy centered on precisely targeting the highest impact audiences, both patients and providers, ensuring our efforts are concentrated where they will make the greatest difference. Reaching the right audiences at the right time with the right message to deliver adoption and successful quitting. and leveraging our partnership with Omnicom and deploying advanced AI-powered tools that will enable us to optimize segmentation, personalized messaging, and measure engagement in real time. As we look ahead to our potential launch in 2026, our path is clear. We are committed to delivering cytosine and clean to the millions of Americans seeking a better path to quit nicotine. We remain confident in our ability to execute efficiently scale effectively, and deliver long-term value for patients, providers, and shareholders. I look forward to updating you on our continued progress as we move closer to launch. And I will now turn the call over to Mark.

Thank you, Jamie. And good morning, everyone. We ended the third quarter with a strong balance sheet supported by our recent capital raise and continued financial discipline. As of September 30th, 2025, Cash, cash equivalents, and marketable securities totaled $48.1 million. As we noted last quarter, our current cash runway is expected to fund operations into the second half of 2026. Total operating expenses for the three and nine months ended September 30th, 2025, were $14.7 million and $40.1 million, respectively, reflecting our ongoing investment in regulatory, clinical, and pre-commercial activities. With respect to net loss, for the three and nine months ended September 30th, 2025, it was $14.4 million and $40 million, respectively. We remain focused on disciplined capital allocation as we advance toward key regulatory and commercial milestones. With that, I'll turn the call back to Rick for closing remarks.

Thanks, Mark.

The progress discussed today underscores the momentum behind Achieve, and our unwavering commitment to addressing the critical unmet needs of nicotine dependence. A recent receipt of the FDA Commissioner's National Priority Voucher for cytosinicline for vaping cessation is truly a landmark event. Being selected as one of only nine therapies in the program's inaugural year demonstrates the urgent national need for effective treatments and the FDA's recognition and nicotine dependence is a public health crisis. Cytosinicline is uniquely positioned to address both of these significant public health challenges. For smokers who want to quit, it represents a potential new standard in smoking cessation at a time when it's been nearly two decades since the neutral trials have shown compelling results with cytosinicline's potential efficacy and safety profile continuing to generate excitement among both patients and clinicians. For those who vape and want to quit, cytosinicline could become the first ever FDA-approved treatment, opening a nicotine-free path to quitting for the 17 million adult e-cigarette users in the U.S., about 60% of whom want to quit but currently have no approved options. The CMPV designation means we can accelerate our efforts to bring this life-changing therapy to those who bathe. As we look at the three key value drivers for the company, we're focused on, firstly, executing on the NDA approval and product launch with a PDUFA date set for the 20th of June, 2026, and a launch in the third or fourth quarter of 2026. Secondly, driving the progress on our innovative data-driven commercial platform to enable a successful launch, allowing us to precisely target both patients and physicians. And finally, the growing recognition of value in our second indication, vaping, where we recently were awarded the CMBB by the FDA. This highlights the urgency of the public health crisis in the U.S., and enables a shortened review process of just one to two months. At Achieve, our message is simple. We are not quitting on you. We remain committed to providing evidence-based solutions to help you succeed. I'm grateful to our patients, partners, investors, and the entire Achieve team for their ongoing support and dedication. We are energized and excited about the opportunities that are ahead. and confident that our efforts will deliver meaningful benefits for patients and long-term value for our stockholders. I also want to thank Cindy Jacobs again for her many contributions, and I'm pleased to have her as an ongoing consultant. Thank you for joining us today, and we look forward to sharing more updates in the courses ahead. With that, operator, we're now ready for Q&A.

Thank you. Ladies and gentlemen, we will now conduct the question and answer session. If you have a question, please press star followed by the number one on your touchtone phone. You will hear a three-tone prompt acknowledging your request. If you would like to cancel your request, please press star two. Please ensure you lift the handset if you are using a speakerphone before pressing any keys. One moment, please, for your first question. Your first question comes from the line of Thomas Flatton from Lake Street. Your line is now open.

Hey, good morning. I appreciate you taking the questions. A couple of quick follow-ups from the call itself. Jamie, I know you mentioned a specialty distributor. Should I presume that you're going to go specialty only or is there a retail strategy in place as well?

Hey, Thomas, it's Rick here. Jamie has actually had to step away to address an urgent matter that and she's not going to be available for the Q&A. But the rest of our executive team are here, and we're happy to take your questions. I'll fill in for Jamie on any questions you might have on the commercial front. Okay, so could you just repeat your question, Thomas?

Yeah, so in the prepared remarks, there was a comment made that you've selected a specialty distributor. I was wondering if there was also a complementary retail strategy in place, or are you going specialty only?

No, no, there's going to be a complementary retail strategy in place as well. But, you know, the specialty route is, you know, one of the quickest and I think the optimal route, at least in the initial stages, and then we'll build out from there.

Got it. And then a follow-up from Mark. The cash runway into the second half of next year, just to confirm, that does not contemplate funding the vaping study. Is that correct, that we need separate funding? Yes.

Yeah, to complete the vaping study, we'll need to raise additional capital. That's correct.

Got it. And then, Rick, anything that you can share with respect to the protocol you anticipate having for the vaping study? I don't know what conversations you've had with FDA or how far along that is, but any insight there would be great.

Yeah, it's a very similar protocol to the ones that we use for the smoking cessation trials. So it is a two-arm study, placebo for three milligrams three times daily for 12 weeks, and then it is active. It's cytosinicline, three milligrams three times daily for 12 weeks. Roughly 400 patients in each arm. There is a difference between the smoking cessation trials and the vaping trials. And we believe that the vapors are actually more nicotine-dependent than necessarily the smoking population was, so they are only treated for 12 weeks, whereas in the smoking cessation trial, we had the flexibility of 6 or 12 weeks. But other than that, they're very similar.

And the end point will be what? Because you can't do any kind of objective breath analysis, right? Correct.

It's simple. It's going to be the overall quit rates at end of 12 weeks of treatment and then with a 24-week follow-up.

Got it. I appreciate you taking the question.

Thank you. Thanks, Thomas.

Your next question comes from the line of Gary Nachman from Raymond James. Your line is now open.

Okay, good morning and congrats on all the progress. So first with the priority voucher for vaping, you said you're preparing to initiate that phase three. How are you looking for ways to accelerate it and maybe start it on the earlier side of the first half of next year? Could you clarify that? And you mentioned the phase three design. That's just going to be the same as what you've talked about previously? Just wanted to confirm that.

I'll take the first part of it, Gary, and then I'll hand over for a bit more detail to Dr. Mark Rubenstein. Yeah, I mean, the CMPV allows us a once-to-month of approval. So the MPV or ROI on that eight months that we're potentially benefiting from accelerating the product launch That's substantial, whereas the CMPV doesn't allow the transfer of the actual voucher itself. We strongly believe that the acceleration, both in the launch period, but you've also got to look at the acceleration of peak revenues by eight or nine months. So, yeah, it's extremely valuable. And, yes, we are going to go back to the agency because I think we need to take advantage of of the benefits under the CMBV to see where we could streamline the agreed clinical trial design. You remember that we got breakthrough designation originally. Now that is reinforced by the CMBV. So we do see that there's potential for some kind of streamlining of it. I'll hand it over to Dr. Mark. Are you there?

Yes. So just to clarify, you wanted to hear a little bit more about the study design. And so as Rick has said, it will be a 12-week trial of cytosinicline with behavior versus placebo with behavioral treatment with follow-up at 12 weeks and 24 weeks. We will be biochemically confirming that. I understand the prior caller's question about confirmation with just breath CO, and he is correct. That is only to detect cigarette smoke. However, we will also be employing blood analyses and or saliva. We're looking to see which we can do more rapidly to look for cotinine. which is a biomarker of nicotine exposure so that we can confirm self-report. Does that answer your question?

Yeah. And I guess, you know, just in terms of size, it sounds like you're going to try and streamline that the way that Rick described and will it be the same dosing as what you currently have for smoking?

Exactly. Same dosing.

Okay. And then, you know, I guess it's a heavy mark, maybe just, you know, regarding the benefits for cytosinicline and COPD patients that you just published. And, you know, this is also for Rick, but, you know, maybe just talk about, you know, a little bit more just about what you saw in those patients, like how much of a benefit there was. And then, Rick, are you still having conversations about with potential partners to do a study in that patient group? So, you know, what's the status there?

Again, I'll kind of flip that one as well, because Dr. Mark can answer part of it. Look, I think the key is that, you know, the effect that we saw, the benefit that we saw in COPD smokers was quite remarkable. we'd always suspected that those were potentially the highest beneficiaries because to be a COPD smoker, you have to be highly nicotine dependent when you have a progressive disease like COPD. And our belief was that they could well be the real beneficiaries. By being COPD smokers, they are impairing the efficacy of their standard corticosteroid treatments and the anti-IL-33s simply don't work in the smoking population. So we see that there are 6 million COPD smokers in the U.S. today, and we believe strongly that cytosinicline can have a significant impact on making sure that their current treatment actually works more effectively. So there's a kind of unique characteristic to this in terms of a 6 million population of patients with COPD who actually have, you know, the ability to benefit from cytosinicline. And that kind of parallels with, you know, other respiratory companies because we believe there should be an interest in ensuring that they can target that 6 million population. So over to you, Dr. Mark.

Sure. Thank you, Rick. So one of the things that we saw were that these patients with COPD were older, they were heavier smokers, they had higher levels of dependence and higher levels of depression, all of which we know are associated with poorer outcomes. However, despite that, with cytosinicline, their quit rates were roughly the same as what we saw in smokers without COPD. For example, the odds ratio without COPD was 5.2 and with COPD was 5.3, so basically the same. And interestingly, and I think Rick had mentioned this earlier, patients on placebo had a tremendously difficult time quitting. Really, when you had COPD, given probably those other factors, that you were heavier, smoker, and older, you couldn't really quit unless you use cytosinicline.

Okay, that's really helpful. And then just last one, Rick. Pfizer, I think, is bringing Chantix back to the market. So what are your thoughts on how that impacts the overall smoking cessation market? You know, will that potentially help it grow again? And I'm not sure... if you've seen how Pfizer is pricing Chantix with generics available. So if you have any color on that, thanks.

Well, I mean, I can take a kind of strategic view on it. You know, why reintroduce Chantix when the generics have basically taken over the market? You know, there's no value in the promotional activity because it really drives them towards the generic rather than the brand. So if they're going to promote it, then it's going to be an interesting kind of ROI on that investment. And regardless of whether Chantix varenicline is in the market, I think the differentiation between cytosinicline in terms of not just its efficacy but also the superior overall side effect profile and particularly focusing on that nausea and vomiting profile experienced in the first few days of taking varenicline or chantix, we clearly believe we've got a much superior product. I mean, cytosinicline has five times less incidence of nausea and vomiting than varenicline does, and less than half of the other side effects, be they sleep disturbances, abnormal dreams and nightmares, headache, et cetera. You know, it's a huge market. There are about 8 million scripts for smoking cessation annually. You know, at peak, Chantix had about 2.8 million scripts written. 75% of those were in the U.S. So, you know, regardless, I think that, you know, we have the benefits and the advantage over, you know, generic varenicline, and we see that as not being a necessary stumbling block.

Okay, great. Thank you very much.

Your next question comes from the line of Brandon Fox from HC Wainwright. Your line is now open.

Hi, thanks for taking my questions, and congratulations on all the progress. Maybe for me, can you just elaborate on the commercial infrastructure overlap you expect between smoking cessation and vaping? And then given that vaping could now come to the market earlier in the launch of the smoking cessation, you know, which is probably not going to be at peak, does that change your commercial infrastructure outlook or how you're looking at sort of launching these two products in tandem, or I guess not launching them in tandem, but I guess maximizing their potential in tandem? Just any changes to the go-to-market strategy there? And then along the same lines, you know, just with the priority voucher, how are you viewing manufacturing just, you know, that vaping may be earlier in the process and perhaps yet planned for?

Thank you. Brandon, thanks for the question. We are anticipating or estimating that the vaping indication will be launched around about 12 to 14 months after the smoking cessation date. indication. I think that is a really beneficial time because it allows us to effectively knock out any of the wrinkles that might be as a result and we've got some learning to be done from the launch of the smoking cessation. Are we targeting different markets or different patients? The answer is yes. We're targeting a much younger patient population. The typical age of smokers is in our clinical trials, is around about 55 years old. They've been smoking for somewhere up to 30 years. Our key strategy here is the highly motivated quitters. So of the 29 million smokers currently in the U.S., we're estimating that approximately 7 million are highly motivated quitters. On the vaping target population, it's different. They're a much younger population. Again, average age in our Phase II trial was 33 to 35. On average, they've been vaping between five and eight years, and we're already starting to experience some of the comorbidities associated with vaping. So I think that the fundamental approach to targeting the patients will remain the same. But I think that the younger population of vapers are more digitally inclined than the perhaps slightly older population to smoking cessation. Again, we think that gives us kind of an advantage because the ability to communicate directly to the patients digitally is a fundamental part of our overall strategy. From a physician standpoint, it won't make any difference. The physicians, all we've got to do is make them aware of the benefits of cytosinicline in vapors because they will already be aware of the benefits in the smoking population. So I think that's the slight nuance between the two populations. In terms of manufacturing, it'll be the same. It's three milligrams three times daily. But as far as vaping is concerned, it's three milligrams three times daily over 12 weeks only. It won't have the flexibility that we've seen in the smoking cessation at six or 12 weeks.

Great. Thank you very much, and congrats on all the progress. Thank you.

As a reminder, if you wish to ask a question, please press star 1 on your telephone keypad. There are no further questions at this time. I will now turn the call back to Mr. Ricks to work. Please continue.

Well, I'd just like to thank you for your time and attention. We are progressing rapidly with both the smoking cessation indication. We're excited about the prospect of the PDUFA date in June and actually launching the product for smokers who have few treatment options at the current time. From a vaping standpoint, obviously, the CMPV is a real recognition of the value of cytosinicline in treating vapers who want to quit, and we look forward to updating you on our next quarterly call. Thank you very much.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.