Greetings, and welcome to the Achieve Life Sciences Fourth Quarter and Full Year 2025 Earnings Conference Call and Webcast. As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to Nicole Jones, Vice President, Strategic Communications. Nicole, please go ahead.

Thank you, Operator. Good morning, everyone, and thank you for joining us today. From Achieve Life Sciences, we are joined by Rick Stewart, President and Chief Executive Officer; Dr. Mark Rubinstein, Chief Medical Officer; Jaime Xinos, Chief Commercial Officer; and Mark Oki, 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 risks, 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. The NDA submission in June 2025 started the transformation of Achieve from a pure-play clinical development company into a commercially focused enterprise. Our primary objective now is to make cytisinicline available to the 25 million patients who smoke and nearly 18 million who vape. The need for a new nicotine dependence treatment like cytisinicline has never been greater. Achieve is committed to providing the new therapeutic tool to patients seeking to break free from the cycle of nicotine dependence. I'm incredibly impressed by the commitment and resilience of the entire Achieve team and their dedication to addressing the nicotine dependence public health crisis in the U.S. Key highlights in 2025 include: firstly, the submission of the New Drug Application or NDA for the smoking cessation indication and its acceptance by the FDA, moving us one important step closer to becoming the first new FDA-approved treatment in 20 years. Secondly, Achieve's vaping cessation indication was one of the first recipients of the Commissioner's National Priority Voucher. Recognition of cytisinicline as a national priority is an incredible achievement of the work conducted by Achieve and the importance of cytisinicline in tackling the previously intractable problem of nicotine dependence. The Commissioner's voucher gives us an accelerated pathway to be the first and only FDA-approved vaping cessation treatment. Thirdly, our clinical team delivered on all planned regulatory milestones and generated encouraging clinical data across our program during the year. This includes concluding the ORCA-OL long-term exposure trial, which underlined cytisinicline's safety profile, demonstrating strong tolerability and excellent patient satisfaction data. We should not underestimate the importance of the findings from the ORCA-OL safety study, which demonstrated the tolerability of cytisinicline over long-term, 52-week exposure to treatment. Dr. Mark Rubinstein will elaborate in a minute. Lastly, post-hoc data published in Thorax, a leading peer-reviewed medical journal, demonstrated that cytisinicline significantly improved smoking quit rates compared to placebo in adults with chronic obstructive pulmonary disease. There are 6 million COPD smokers in the U.S. today with few options to help them quit. Their level of nicotine dependence must be high, as continued smoking exacerbates COPD symptoms and impairs the efficacy of COPD drugs. The positive data on COPD patients highlights the expansive scope of opportunities for cytisinicline in terms of the range of comorbidities that could potentially benefit from treatment and the broad range of health care providers who would be interested in its benefits. Our commercial team has moved forward decisively towards building a scalable, data-driven commercial model that will position us to launch successfully. Our model is built to address the rapidly evolving health care environment, where approximately 75% of primary care physicians will no longer meet with medical reps. Achieve's omnichannel digital platform provides precision targeting of physicians and patients, which will allow us to identify high-volume prescribers and the patients motivated to quit, deploying resources efficiently and maximizing impact per dollar spent. AI is a critical enabler in this evolution. We'll be using advanced analytics and machine learning to enhance decision-making, automate customer engagement, and generate predictive insights about which messages will resonate most with target audiences, positioning us to continue building an efficient commercial organization that punches well above its weight. We just announced that we have selected Adare Pharma Solutions, a U.S.-based manufacturing organization that will produce cytisinicline drug product as we prepare for potential commercial launch and future demand. We believe this partnership will secure our supply chain, reduce risks associated with international pharmaceutical importation, and may lower overall costs, including the risk and uncertainty for tariffs on international imports of the drug product. I'm pleased to report that work has commenced and our technology transfer to Adare is already underway. The Adare partnership provides redundancy in our supply chain, allowing contingency capacity in the U.S. The manufacturer named in the cytisinicline NDA recently had an FDA Good Manufacturing Practices inspection with two observations related to solid oral dose manufacture, which are being addressed through an ongoing communication of its remedial action plan with the FDA. By establishing U.S. manufacturing with Adare, we increase confidence in our supply-chain security as we advance towards a planned commercial launch of cytisinicline expected in the first half of 2027. We remain focused on bringing cytisinicline to patients as quickly as possible, and our decision to work with Adare positions us to launch with the manufacturing reliability and the operational readiness our patients and stakeholders expect. Now, let me take a moment to remind you why our team is so passionate about bringing cytisinicline to market. Recent data issued by CDC estimated that in 2024, approximately 25 million adults in the United States smoked cigarettes. It's estimated that more than 15 million attempt to quit every year. Smoking remains the leading cause of preventable death in the U.S., claiming approximately 500,000 lives annually and costing over $600 billion each year in health care cost and lost productivity. The comorbidities are devastating. To name a few, respiratory disease, cardiovascular disease, metabolic disease, and cancer. We also know that 60% of the nearly 18 million adult e-cigarette users in the U.S. want to quit, and adult nicotine e-cigarette use is on the rise. However, there is no FDA-approved treatment for e-cigarette cessation. Patients are frustrated, physicians are frustrated. The narrative around nicotine dependence needs to change. We've seen this transformation happen with obesity. When GLP-1s emerged, they helped society recognize obesity for what it truly is—a medical condition, not a personal failure. Nicotine dependence deserves the same recognition. It's a neurobiological condition rooted in how nicotine alters brain chemistry and creates physical dependence. It's a medical condition and it demands medical treatment. That's why we launched our Will Power awareness campaign in January. This is the beginning of us reframing the conversation to help people understand that quitting takes more than Will Power alone and that an effective treatment exists. The bottom line is that Achieve is not quitting on people who smoke. The parallels between obesity and nicotine dependence are not lost on many investors: unmet medical needs, same physician call points, same cost to society. In summary, our science is strong. We're advancing through the regulatory review process with the FDA, working constructively towards approval. Our commercial infrastructure is taking shape with real progress in 2025, and we're actively building for launch. With that, let me turn it over to Dr. Mark Rubinstein, who will detail our regulatory progress and the data that continue to reinforce cytisinicline across patient populations.

Thank you, Rick, and good morning, everyone. We have made tremendous progress in 2025 for cytisinicline from a clinical and regulatory standpoint. Since our last earnings call, we've continued to validate cytisinicline's clinical profile through peer-reviewed publications and scientific conference presentations. We were pleased to present findings from a pooled analysis of over 1,600 participants from our Phase III trials at the Society for Research on Nicotine and Tobacco or SRNT conference a few weeks ago. This analysis examines cytisinicline's efficacy across participants with different prior treatment histories and quit-attempt patterns. Regardless of whether the participants had previously tried varenicline, bupropion, or nicotine replacement therapy, or whether they had made four or fewer quit attempts versus many more, we saw consistent efficacy. These data show that if approved, cytisinicline will offer a new quit option for patients, including those for whom medications have failed. This consistent efficacy across patient subgroups shows that past setbacks should not discourage people from trying again. For millions of people who have tried and failed, cytisinicline offers real hope. We also presented late-breaking survey data from our year-long ORCA-OL study that demonstrated voluntary, self-reported patient experiences with extended cytisinicline use up to 52 weeks. This survey of data from people who chose to continue treatment beyond the 6- or 12-week standard courses offers insight into long-term tolerability and impact. Patient experience is hugely important for those trying to quit smoking, and it's encouraging to see trial participants describing meaningful benefits, including successful quitting and improvements in physical health. We have also been accepted to present research at the 2026 American Thoracic Society Conference in May and look forward to updating you in the coming months. On the e-cigarette front, we received the FDA Commissioner's National Priority Voucher for cytisinicline in e-cigarette or vaping cessation, a significant recognition of the public health urgency. The CNPV is designed to provide enhanced FDA communications and an expedited NDA review timeline of 1 to 2 months compared to a typical 10 to 12 months. We are now laying the groundwork for our ORCA-V2 Phase III trial for vaping cessation, including selecting trial sites and identifying principal investigators. In summary, 2025 has strengthened our clinical and regulatory position significantly. We're advancing through the FDA's review process with an active dialogue with the agency. We remain confident that cytisinicline has the potential to deliver the first FDA-approved treatment for nicotine dependence in 2 decades.

Thank you, Mark. When I look back at where we started at the beginning of 2025 and where we stand today, I'm struck by the incredible progress our commercial team has made in just over a year. We've built the foundation for a launch-ready infrastructure from the ground up while remaining lean and right-sized for our current stage requirements. We've established partnerships, deployed advanced analytics, created an AI-powered asset factory, and are positioning ourselves to execute at scale. I'm deeply grateful to the entire team who have been instrumental in bringing this vision to life. As a reminder, our commercial execution rests on three critical priorities: availability, or ensuring supply-chain readiness so that cytisinicline can reach the patients who need it; access to secure coverage and affordability; and awareness, which is educating the right patients and healthcare professionals at the right time about this transformative new option. Every initiative is data-driven, and every decision is tied to measurable impact with the goal of making cytisinicline accessible to the millions of Americans struggling with nicotine dependence. Now, I'll provide updates on each of our three priorities. First, let's look at availability. Implementation with our third-party logistics provider is well underway. We are on track with our state licensing and have secured more than half of the required licenses to date. Additionally, we have now completed the administrative and logistical setup with our specialty pharmacy hub partner. We believe these foundational steps will be critical to ensure patients can obtain cytisinicline and that prescriptions written are prescriptions filled. On the access front, our focus remains on securing rapid, broad, and affordable coverage for cytisinicline. In Q1, we continued discussions with prioritized payers to share our clinical data. Feedback from these ongoing discussions will be critical in finalizing our pricing, access, and contracting strategy as we move closer to launch. On awareness, our focus is establishing Achieve's reputation as a trusted, science-driven partner and shifting how patients and providers think about nicotine dependence. As Rick mentioned, we launched our Will Power campaign, which directly challenges the outdated narrative that quitting smoking is simply a matter of personal determination. The campaign featured visuals that reimagine vintage cigarette advertising, but instead of selling cigarettes, they're selling Will Power as a miracle product. It is deliberately provocative because the message is clear: Will Power alone is not enough. We will continue to strategically deploy this campaign throughout 2026 to drive ongoing conversation and awareness around nicotine dependence as a medical condition requiring a medical solution. Beyond this, we are leveraging technology and AI tools to generate rapid, evidence-based and regulatory-compliant content that will fuel our launch. To use a bit less marketing jargon, this means we are able to build things faster using fewer resources. Through our partnership with Omnicom, we developed a marketing engine designed to shave weeks off the development, review, and approval of brand messaging, promotional, and educational materials. This is just one example of how modern tech and data are improving our ways of working at Achieve. We've also established our unified data ecosystem and our custom-built marketing technology foundation to support hyper-targeted, personalized customer engagement and measurement. Finally, we've completed detailed customer segmentation to better understand how to reach and meet the needs of our future patients and prescribers. As we look ahead, we are building plans for optimizing sales deployment and non-personal promotion to key audiences at launch and beyond. We will look to deploy the Will Power campaign in select audiences, complete our data and performance-measurement capabilities, and finalize media channels and plans. We are confident in our ability to execute and scale effectively and deliver long-term value for patients, providers, and shareholders.

Thank you, Jaime. Let me walk through our financial position and results. As of December 31, 2025, cash, cash equivalents, and marketable securities totaled $36.4 million. Total operating expenses for the three and twelve months ended December 31, 2025, were $14.7 million and $54.9 million, respectively, reflecting our ongoing investment in regulatory, clinical, pre-commercial, and commercial infrastructure activities. Our total net loss for the three and twelve months ended December 31, 2025, was $14.7 million and $54.7 million, respectively. As always, we continue to evaluate financing options and cash management strategies, and we will provide updates if and when appropriate. I'll turn it back to Rick for closing remarks.

Thank you, Mark. In closing, I'm pleased with our regulatory, clinical, and go-to-market efforts, which underscore the momentum behind Achieve Life Sciences and our unwavering commitment to addressing the critical unmet needs of nicotine dependence. As we look ahead, I want to highlight three critical value drivers for our Company. First, receiving NDA approval and successfully launching cytisinicline for smoking cessation. This is our near-term priority, and the team is executing with discipline and purpose. Discipline is important to ensure there is a controlled and successful launch. Second, the growing recognition of the significant opportunity represented by our vaping indication. With the Commissioner's National Priority Voucher and the urgent public health need around e-cigarette cessation, we have the opportunity to be first to market with a treatment for an indication where no approved options currently exist. Finally, both of these are underpinned by our digital commercial platform, the AI-powered data-driven infrastructure we built that positions us to launch efficiently and scale rapidly with precision targeting and measurable impact. To the millions of Americans who are ready to break free from nicotine dependence, Achieve Life Sciences is not quitting on you. We are dedicated to this urgent need. The standard of care in smoking cessation has not evolved in two decades, and we are about to change that. I'm grateful to our patients, clinical investigators, regulatory partners, investors, and our incredible Achieve team for their unwavering dedication to this mission. Together, we're building something meaningful. We're not quitting on you. We will not quit until we deliver a treatment that changes the standard of care for nicotine dependence and helps people live free of nicotine. Lastly, we're limited in what we can say about our interactions with the FDA while the NDA is under review. And as I said earlier, the communications are normal for this stage of the review process. I look forward to updating you on our progress. Thank you for your time, attention, and continued confidence in Achieve Life Sciences.

Our first question is coming from Thomas Flaten from Lake Street.

Perhaps for Jaime, the launch timing for the first half of '27, can you talk a little bit about the critical path between a late June NDA approval and the first-half launch? Is this primarily scale-up on the commercial side? Is it potentially product supply? Can you just talk a little bit about that gap that's created there?

Sure. Thanks for the question, Thomas. So obviously, we need drug in order to be able to go to market. And so that is our first consideration is when can we get drug into the supply chain to get it out into the hands of patients. Everything that we need to do on the trade and distribution side will be ready to go as soon as we have the drug. So we have our 3PL setup, as I mentioned during the call, serialization, our specialty-pharmacy vendor, all of those requirements for copay and access; all of those will be aligned and ready to go at launch. The rest of the time that we'll be spending over the next six months gives us an opportunity to get some additional data into the marketplace and to the scientific community and also work towards additional partnerships with advocacy and potentially policymakers. So it does afford us a bit more time to get a few other operational things activated as well.

If I can add to that, if you look at it from a strategic standpoint, given the scale of the market that we're actually addressing, we made the decision that we need to ensure that we have all of the processes in place to maximize or optimize the product launch. I think Jaime and the team are doing a terrific job on that front, and Craig on the manufacturing side is doing an excellent job. So I think taking time to get it right is critically important for the success of the launch.

And then with respect to manufacturing, you did mention the observations during the GMP inspection. Did you imply—maybe perhaps I'm reading too much into it—that the manufacturer in the NDA will not be supplying commercial product; rather Adare will? And then, what implications does that have for folding Adare into the process now during the NDA review?

Yes. I think the critical part of this is that the PDUFA date remains the 20th of June of this year. That is what the FDA has set, and that's what we're working toward. But of course, any time that there are any observations, we've already made the decision to transfer manufacturing to the U.S. given the geopolitical situation. So, we basically just accelerated that. At the moment, the PDUFA date remains exactly the same. I think given the scale of this opportunity, it's prudent to ensure that we have contingency supply. It's prudent to ensure that we've got onshored manufacturers here in the U.S.

Our next question today is coming from Jason Butler from Citizens Bank.

On all the progress in 2025. Two from me. Can you just talk a little bit more about where you believe awareness currently is with healthcare providers and what additional work you'll be doing in 2026 to continue to build awareness of cytisinicline and the data? And then second, is there anything you can say about FDA dialogue on the vaping indication since you got the CNPV?

Jaime, do you want to address the commercialization?

Sure. Thanks for the question. Regarding HCP awareness, I would say it's not been a priority to date to do broad-spread awareness about the product. A lot of that has to do with what you are allowed to say in a pre-approval environment. Disease state education is one channel that we can provide information in a regulatory-compliant way, but one of the decisions that we've made is that we understand that everyone knows that smoking is bad for you, and there's really not a huge need to go out and spread that message. So what we've been doing is conserving our resources so that when we get closer to launch, we can do a stronger push from an educational perspective that is specific to data about the product and when the product is going to be in the hands of physicians so they can use it with their patients. So we're scaling it adequately based on the need to do disease-awareness education, or lack thereof, in a smoking-cessation indication. I think as we get closer to launch, we will be ramping up more opportunities, and you're already seeing us do that around some of the conferences where we will be presenting data and where we have. So, ATS is a huge opportunity that Mark mentioned, where we're going to have some new data that we want to get out into the medical community and into the hands of physicians. So, it's something that we are scaling up as we get closer to launch, but we've been very conservative in our efforts so far in how we spend money prior to them having the solution in their hands to give to their patients. And then, Rick or Mark, I'll turn it back over to you to discuss FDA dialogue on vaping.

Sure. So right now, to date, our discussions with the FDA around vaping have largely been around approval for the protocol itself. We hope to continue engagement as the study progresses.

I think if I can add to that, we're already in site-selection. So, it is progressing at a pace. The key is that we're anticipating commencement in the first half of this year. It's moving along at the pace. I noted also the public forum that the FDA is putting together—coming up on the 14th of June. There's some debate around the validity of the CNPV. For us, we think that the opportunity is huge as being the first in-market for a vaping cessation product. That's clearly an underserved market, as there are no treatments there. I think that's going to be a real area of focus and interest.

Our next question is coming from Brandon Folkes from H.C. Wainwright.

Congrats on all the progress. So, just coming back to the manufacturing, does your U.S. commercial launch timeline of 1H 2027 assume a June 2026 approval or potential later approval? What level of flexibility should we think about in terms of when in 1H '27 you may launch? Anything to read into in that broad timeline? And then, maybe on a similar vein, are you looking to add Adare to the NDA before the June approval? Or is this potentially something to qualify them post-approval?

I'll take the answer in reverse order. Yes, it's going to be post the June approval. The key now is to focus in on the approval and also to ensure that we put a stake in the ground, frankly, in terms of the first half of '27 for the product launch quite simply because of all of the activities that need to go into it to ensure that we've got product to go into channel to make sure that all of the commercial operations have completed their activities. I think there's nothing to read into it other than we got a couple of observations that our third-party manufacturer is currently addressing with the FDA. There's a little bit of opacity around that, of course, because it's a discussion between the FDA and the manufacturer. But as far as we're concerned, on the flip side, we're always in favor of transparency. We'll keep you in the picture with respect to that as things move along.

That's very helpful. Maybe lastly from me, just given the lead time between a potential June approval and a 1H 2027 launch, how should we think about insurance coverage at launch? Should we think about this similarly to normal launches? Or could we have better than normal insurance coverage at launch, obviously, given the indication, but also given that lead time to have those discussions?

Thanks. I'll take that question, Rick. So regarding payers, yes, we have been out actively having conversations in the regulatory compliant pre-approval information exchange opportunities that we do have. We've had about 40 touchpoints with payers in the first quarter. We've attended PCMA. We've actually had inbounds from payers who want to have conversations with us. We are obviously on the radar. They are very interested. They recognize the differentiated profile of cytisinicline and the clear unmet need. We know there are still 25 million people who smoke in this country who need treatments that will help them stop. The ongoing conversations are very encouraging. We also know that the Affordable Care Act requires coverage of smoking-cessation treatments. That certainly helps in our favor at launch and beyond. Regarding timing, the actual clock really starts building for the demand when the drug is in channel. We will have more time to have more conversations, but we won't start building demand. Any initial restrictions to access, such as new-to-market blocks, will still require a ramp period from time of drug being distributed and in hands of patients to the timing of the bleed out that it takes in order to get on formulary for some of those plans. We're still tracking a slow ramp for the initial six months of launch.

Our next question is coming from Justin Walsh from JonesTrading.

I'm wondering if you can provide additional color on the robustness of the raw plant material supply chain. Are third-party suppliers able to meet expected demand if Sopharma is unable to do so?

Excellent question, Justin. Yes, as I mentioned before, we have been stockpiling the starting material for some considerable time. By the time we get to launch, we believe we'll have more than three years' supply of starting material for the amounts required for in-market sales. We will continue to add to that stockpile. We don't really see the inventory going much below three years for the foreseeable future. We've been buying in for quite a few years now. The starting material has a three-year shelf life, but we will reprocess it as required to be used.

And one more for me. I'm wondering if you can comment on the cytisinicline dosing schedule and if there's any concern that a potential pill burden could limit real-world compliance or commercial uptake.

That's a great question. We actually have found, just after completing our ORCA-OL, where people actually use the pill three times a day for up to a year, that not only did people not find it excessively burdensome, but our completion rate and the number of people who adhered to the protocol was incredibly high. A lot of participants reported that they felt that their highest cravings were around mealtime. Even though you don't have to take cytisinicline with meals because it's TID, it can be perfectly timed around meals. They found that it was reassuring to take something to address their cravings right around the time periods that they would have their highest cravings. Again, our adherence rates in all of our trials and our OL trial, which was 52 weeks, was incredibly high, over 75%.

Next question is coming from John Vandermosten from Zacks.

In December, there was an ICER report that came out that calculated some prices for cytisinicline. I was wondering if you've seen that. And then wondering how that compares with your internal calculations and what prices you're thinking about when that comes about next year.

Jaime?

We have definitely seen the report—thanks for the question. Yes, we have seen the ICER report. We were involved in the process, providing information when requested that was appropriate for their consideration. I think, importantly, what it did highlight is that they have affirmed there is a substantial unmet need despite currently available treatments, and that payers should make cytisinicline immediately available. As far as pricing goes, we're not going to comment on our pricing because we've obviously not set that yet, and we're not ready to have those conversations with payers on an exact price. We'll leave it at that, but we are pleased with the recommendation that ICER made.

And then a few questions on manufacturing. I guess I wanted to frame it first. Where does it stand with a synthetic manufacturer of API? And then I believe there are three different entities, perhaps, that you're working with. There's Adare. I believe there's a European manufacturer and then there's Sopharma. How does that all fit together?

Right. So, some pieces of a jigsaw puzzle. The synthetic is an end process, put it that way. It's not an easy process, and I've stressed this before; we're making substantial progress on that front. In terms of the three manufacturers, we start off with Sopharma. Sopharma was not included in the NDA because we had concerns over their FDA inspection-readiness. I was down in Sofia about three weeks ago, and Sopharma has made substantial progress with respect to their inspection-readiness. We intend to add them to the NDA once it's approved. The third-party manufacturer, the key there is that, as I mentioned, we've got these observations that we're monitoring very carefully, and they're collaborating with the FDA to rectify any observations and the remedial action associated with it. Ultimately, the transfer of manufacturing to the U.S. has largely been driven by a desire to have contingency and redundancy in our overall supply chain. Given the uncertainty around tariffs in particular, we decided some time ago to move manufacturing into the U.S. Timing-wise, we're anticipating that Adare should be available to be added to the NDA in the third quarter, that kind of timeframe. So does that answer the question?

Yes. We've reached the end of our question-and-answer session. I'd like to turn the floor back over for any further or closing comments.

Well, I'd just like to thank you all for your continued interest in Achieve Life Sciences. We've made terrific progress this year. I want to put it into context: 15 years ago, Tony Clarke, who is the Co-Founder of Achieve, and I had this idea that cytisinicline could do immense societal benefit with a desperate need for a new treatment for nicotine dependence for smoking cessation. At that point, vaping didn't even exist. Over the years, we've worked tremendously hard. The initial eight years was Tony Clarke and I actually funding the company ourselves. Over the last seven years, we've made fantastic progress to address this huge unmet medical need. We really do believe that we're on the brink of great success and having the ability to treat patients who have very few options to quit. Thank you for your continued interest in the company, and we look forward to updating you.

Thank you. That does conclude today's teleconference and webcast. You may disconnect your lines at this time, and have a wonderful day. We thank you for your participation today.