Achieve Life Sciences, Inc.

Greetings and welcome to the Achieve Life Sciences fourth quarter and year-end 2024 earnings 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 conference over to your host, 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 Oke, Chief Financial Officer, Jamie Zenos, Chief Commercial Officer, and Jerry Wan, Vice President of Finance and Principal Accounting Officer. Management will be available for a Q&A session following our 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 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 reply. 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 FCC. Achieve undertakes no obligation to update or revise any of these forward-looking statements. Please refer to Achieve documents available on our website and files with the FCC concerning factors that could affect the company. I'll now turn the call over to Rick.

Thank you, Nicole, and good morning. It's great to be with you today at this exciting time for Achieve. Achieve expects to submit the NDA for cytosinicline as a treatment for nicotine dependence for smoking cessation with the FDA at the end of next quarter. Cytosinicline will be the first new drug for nicotine dependence in nearly 20 years and will provide patients and doctors with a desperately needed new tool to combat the impact of nicotine dependence for cigarette smoking and vaping. All of our resources are now dedicated to a successful NDA submission, acceptance, and approval. Execution of the successful submission is critical. There's an increasing urgency for new nicotine dependence treatments. because existing treatments are either less effective or have side effects that deter compliance. This, combined with the rapid expansion of vaping and nicotine pouches, puts greater emphasis on the importance of Achieve's mission and the role of cytosinicline to become the only nicotine-dependent product being promoted to healthcare providers. The health risks of smoking are well established, and vaping perils are are only now starting to become evidence with lung injury and disease being seen in a much younger population. We're extremely proud of the progress we have made in 2024 toward bringing cytosinicline to patients and doctors with a planned commercial launch in the third quarter of 2026. With each milestone met, Our confidence and momentum grow as we work to solve this challenging public health crisis while creating long-term shareholder value. Looking back at 2024, we've hit some key milestones that are driving us toward the next stages of development and commercial launch. Here's a quick recap of those accomplishments. We completed enrollment in the ORCA Open Label Long-Term Safety Exposure Clinical Trial and reached the requirement of at least 300 participants receiving six months of cumulative cytosinicline treatment, which was a necessary step required by the FDA for submission of the NDA. We also received breakthrough therapy designation to cytosinicline as a treatment for vaping cessation. We completed the end of phase two meeting with the FDA for vaping cessation as a future indication which included agreement on the design of a phase three trial. We strengthened our leadership team with the hire of our CFO, Mark Oakey, to oversee our financial strategy and operational initiatives. We appointed Dr. Kristin Slaoui and Nancy Thielen to the board of directors, bringing extensive leadership experience in corporate strategy and commercialization. And finally, we advanced our commercial readiness efforts. The steps we've been taking all year bring us to where we are today, transitioning from a clinical company towards a commercial one. As a reminder of our mission, nicotine dependence is one of the most pressing yet underserved public health crises of our time, claiming lives, driving severe comorbidities, and burdening the US healthcare system with over $300 billion in costs annually. By some reports, nicotine is the third most addictive drug, trailing only heroin and cocaine. Let that sink in for a moment. Right now, 29 million Americans are battling nicotine dependence, with 15 million attempting to quit each and every year. Yet, most fail, not for a lack of willpower, but because available treatment options are inadequate. There have been no new FDA-approved products for the treatment of nicotine dependence in nearly 20 years. Instead, multiple new nicotine delivery systems have been put on the market, all effectively enhancing nicotine dependence rather than decreasing or stopping it. It is time to recognize nicotine dependence for what it truly is, a medical condition, not a moral failing. Millions are being left behind to deal with their nicotine dependence without the effective tools they need to quit, and that must change in the same way that the GLP-1s changed the treatment for obesity. We're excited about the milestones we've accomplished and have reached a pivotal moment for the company. To provide more details on our next steps, including updates on the ORCA-OL trial and the NDA submission timing, I'll turn over to Cindy.

Thank you, Rick. We continue to make tremendous progress and have kept the momentum toward our goals into the start of this year. We are fast approaching a major milestone, filing our cytosinicline NDA. We're in the final stages of preparing our NDA submission with accomplishing a last key requirement, the additional long-term safety exposure data from the open-label ORCA-OL safety trial. In under five months, this trial enrolled 479 participants across 29 trial sites in the United States, underscoring our team's efficiency and commitment. In January, we successfully reached the critical milestone of treating 300 subjects with cytosinicline for a cumulative six months, meeting one of the FDA's requirements for the submissions. Additionally, we continue to collect for the long-term cumulative one-year exposure safety data on at least 100 subjects during the open-label trial, which we expect to reach in the second quarter of 2025. And we'll submit that safety data with the standard 120-day safety update to be submitted during the NDA review period. Both the first and second data safety monitoring committee's review of the open label safety data reaffirmed excellent cytosiniclin adherence with no safety concerns reported and no modifications required in the conduct of the study. With these various milestones completed, we have now begun the rigorous three-month process of finalizing the safety database for the cumulative six-month exposure data and will be integrating the safety data into our NDA documents. As the documents have finalized, we have been conducting quality audits on them and placing them into the NDA backbone structure. For example, all Phase I, Phase II, and Phase III clinical study reports have been audited, finalized, and are already in the backbone structure. We are now in the process of finalizing the various summary of efficacy documents. And we will then turn our attention on finalizing the summary of safety documents. We remain fully confident in our ability to file as planned and bring this important smoking cessation treatment to market. Regarding bringing an important vaping cessation treatment to the market, last December in 2024, we had our end of phase two meeting to discuss advancing cytosinicline syndication as a potential first-in-class treatment for e-cigarette or vaping cessation. Based on this meeting, FDA has agreed on our proposed Phase III study design for the treatment of vaping cessation and on the requirements for submitting a supplemental NDA to expand cytosinicline as a treatment for vaping cessation. Specifically, FDA agreed that one well-controlled Phase III trial, ORCAv2, in addition to achieve completed phase two ORCAV1 trial would be acceptable for a vaping cessation indication. Additionally, we received agreement that the overall safety exposure data being currently collected in the ongoing ORCA-OL study would be adequate for the label expansion. As a reminder, in July 2024, the FDA granted breakthrough therapy designation for this indication. In looking ahead and ensuring that our focus and cash resources are directed towards the NDA for smoking cessation, we will be looking to initiate the Phase 3 ORCA V2 clinical trial for vaping cessation within the first half of 2026, dependent on financing. We're confident that cytosiniclin is on track to be the best in class treatment for nicotine dependence and smoking cessation. where there hasn't been a new FDA-approved treatment in nearly 20 years. We will continue to work diligently to get this product to the market for the millions of people who want to end their dependence on nicotine. I'll now pass it over to Jamie for a commercialization update.

Thank you, Cindy, and good morning, everyone. We continue to make great progress advancing critical commercial activities required both for the NDA and for launch readiness. Beginning with the commercial NDA requirements, we've worked closely with Cindy and her team to develop a draft product label that effectively highlights the differentiated efficacy and safety profile of cytosinicline. This cross-functional effort, including commercial team engagement, is critical as the label will serve as the foundation for future promotional and educational messaging. We have also finalized the details for packaging to be included in the submission and have completed the review and request for proposal process for selection of our third party logistics or 3PL partner. We expect to make our final decision and sign our letter of intent in the coming weeks. So to summarize, we remain on schedule for the commercial activities required for the NDA submission. Our current launch readiness efforts are centered on three key priorities, awareness, access, and availability. all built on a foundation of measurability to ensure impact and effectiveness of spend. We've established partnerships with leading strategic healthcare agencies with deep expertise in our areas of focus. Over the past quarter, we've been onboarding our agency partners, refining our launch roadmap, and initiating high priority projects that require immediate action due to long lead times. Aligned with our key priorities, particularly availability and access, As we are advancing our 3PL selection process, we are simultaneously evaluating our distribution channel strategy. Our objective is to ensure that every script written translates into a script filled, ensuring tools are in place to mitigate any potential barriers to access. We will begin engaging with payers to assess future pricing and contracting requirements. This includes shaping how we communicate the value proposition of cytosinicline and providing the necessary evidence to support that value. Our goal is to initiate formal discussions with payers well in advance of launch through pre-approval information exchange, ensuring a smooth market entry. Finally, regarding our third pillar, ensuring appropriate awareness as we approach launch is crucial. As I mentioned on our last call, our plan will rely heavily on data-driven insights to precisely target and deliver messaging to healthcare providers who are actively prescribing high volumes of smoking cessation treatment and to patients who are motivated to quit. In recent months, we have further refined our patient segmentation and have deeper insights on where to focus our patient awareness launch initiatives. Likewise, with prescribers, our awareness efforts will initially be dedicated on high-volume varenicline prescribers. We believe cytosinicline's profile will resonate well with these providers and be a compelling alternative to currently available treatments. Narrowing our focus at launch will enable meaningful and measurable engagements to activate prescribing before we expand awareness activities to a broader audience. We have an exciting and incredibly busy year ahead as we approach launch and this epic opportunity to change the face of public health. I look forward to sharing further details on our progress in the coming months. I will now turn the call over to Mark to review the financials.

Thank you, Jamie. I'm excited to join my first earning calls as CFO of Achieve. Since joining the team, I've been impressed with the incredible progress the company has made, particularly as we prepare for the NDA filing and the transition to a commercial stage company. I look forward to working with our talented team to continue executing on our strategic goals and driving long-term shareholder value. With that, I'll turn to the financial update. As of December 31, 2024, the company's cash, cash equivalents, and marketable securities were $34.4 million, up from $15.6 million on December 31, 2023. We believe our current cash balance is sufficient to provide us runway into the third quarter of 2025. Turning to our statement of operations, total operating expenses for the fourth quarter and year-ended December 31, 2024 were $12.2 million and $39.1 million, respectively. Net loss for the fourth quarter and year-ended December 31, 2024 was $12.4 million and $39.8 million, respectively. As we maintain our focus on executing our strategy towards NDA submission at the end of the second quarter and advance our plans for commercial readiness in 2025, we are dedicated to upholding strict cash management practices. This ensures that our resources are allocated effectively to continue to accomplish our objectives. Specifically, bringing Cytosynaclean to market drives sustainable growth and maximizes value for our shareholders. Thank you, and I'll now turn the call back over to Rick for closing remarks.

Thank you, Mark, and thanks to all of the Achieve team for your continued commitment and energy. I want to emphasize that although not head-to-head comparisons, Cytosynaclean's efficacy and safety profile has demonstrated superiority over other nicotine-dependent treatments. In fact, cytosinicline has shown up to two and a half times better efficacy than the previous market-leading prescription product with a far more benign side effect profile. As you've heard, commercial planning is an advanced stage. We're confident in the product, and we need to get it into patients' hands as soon as possible and give physicians the tools to help their patients who most want to quit. Millions of people are suffering, and they need a new tool to help them quit. Over half of all smokers make a quit attempt every year. They want to save or improve their own lives, but they don't have effective tools. I'd also like to highlight that cytosinicline has a greater role than the treatment of nicotine dependence disease. It will be crucial in reducing the disease burden caused by smoking in related conditions. There is evidence that cytosinicline can have near-term benefit on comorbidities such as COPD and other respiratory diseases. About 80% of all diagnosed COPD patients have this progressive disease as a direct result of smoking. Furthermore, approximately 6 million Americans out of the 16 million diagnosed with COPD currently continue to smoke. Cytosinicline can be used for COPD patients who are smokers as it reduces the number of exacerbations and hospitalizations. Data from our two large-scale phase three clinical trials show a higher abstinence rate in COPD smokers than non-COPD patients. Cytosinicline itself may well be a potent treatment to deter COPD progression and alleviate the symptoms experienced by COPD smokers. More than half of the 29 million American people who smoke in the U.S. attempt to quit each year. Fewer than 10% do so successfully, highlighting the critical need for a new treatment option. Cytosinicline offers a breakthrough opportunity with blockbuster potential, and we're excited to be at the forefront of this market. Looking ahead to 2025, we remain focused, energized, and on track to file our first cytosinicline NDA submission as a treatment for nicotine dependence to smoking cessation at the end of next quarter. Following submission, we anticipate acceptance and look forward to securing marketing authorization. While launch readiness moves forward, I'm proud of the extremely dedicated and focused team that want nothing more than to get cytosinicline into the hands of those patients that are ready to quit. Bringing this product to market will ultimately deliver long-term value to our shareholders and help patients who desperately want to improve their health and unburden themselves from this addiction. As Mark commented, effective cash management is a priority. for the company and I am also grateful for our leading shareholders who have expressed their strong support for the company. They believe in our goal of addressing the nicotine dependence public health crisis with or without a strategic partner. We appreciate your time today and we look forward to updating you on our progress in the coming months. I'll now turn you over to the operator for questions.

Thank you. At this time, we'll be conducting a question and answer session. If you'd like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question comes from the line of Gary Nachman with Raymond James. Please proceed with your question.

Thanks. Good morning and congrats on all the progress. So first, regarding the NDA for smoking cessation that should be filed at the end of 2Q, just clarify a bit more what still needs to be done prior to the submission. And, you know, given the way the product is made, is there anything specific that the FDA is requiring from a manufacturing standpoint? So do you feel buttoned up on the CMC side? And have you hired any external help to help you prep with the NDA? And then I have a couple of follow-ups.

Right. I'll kick off, Gary. Good morning. I think the key here is the absolute focus on getting this NDA submitted. It's the execution that really counts in terms of ensuring that the quality of the NDA is as good as it possibly can. And Cindy and her team are doing an absolutely fantastic job in devoting their resources and efforts to making sure that's the case. But I'm going to hand over to Cindy.

Yeah, and as I stated, we're actually finalizing the summary documents for efficacy, and then we will be turning our attention to all the summary documents for safety. The CMC sections are almost done. There's nothing unusual in this NDA. It's the standard routine NDA. It's pretty much regimented what FDA wants, and so it's all coming together. It's just a lot of work, a lot of documents, And our focus has always been on accuracy and quality. And that's where then a lot of the quality checking at the end is very, very important. Have we had other outside assistance with experts, consultants, vendors? Yes. This is something that... We actually try to pick the best of the best as far as consultants that have done this before. They've been successful at it, and they've been helping us as well with all of this for the last year.

Okay, great. That color is helpful. And then on the commercial side, you know, as you prepare to have good access for cytosinicline, do you expect there will be – a PA or step edits in place for generics? Or will you have a chance to be first line? That might be something that you're sorting through, but what are your initial thoughts on that? And also, will you be using a specialty pharmacy, you know, just to help also ensure that patients get their refills so they have the full three months of treatment?

Hi, Gary. It's Jamie. I'll take that question. So first of all, I'll work backwards. We are looking at our distribution channel strategy now, as I mentioned in the remarks. We will have further color on that in the future, but we are definitely considering at launch a specialty pharmacy because we obviously want to be able to track and monitor the scripts that are being written and those that are being filled and any barriers to access that may be imposed and make sure that we have plans in place to mitigate those. And I think specialty pharmacy is well poised, what we're kind of calling specialty light pharmacy now instead of a full specialty pharmacy because the price of the product wouldn't consider itself in a specialty tier. Regarding your other question, it's hard to know, and it's going to come down to contracting and strategy, where eventually payers put us on their formulary. So we are preparing, and we put pretty conservative estimates in for where we may come out on rebates when we're doing our forecasting. Again, as I mentioned, using a social light type of channel will help us to mitigate some of those barriers to access. But the reality is with and it's that a number of patients have either tried it and failed or they simply don't want to use it. And we saw that in our trials, and Cindy can correct me if I'm wrong, but I think it was around 40% of the people had only previously used.

Yes, antics ever in their journey to try to quit smoking.

And these are heavily experienced quitters, if you will, that have made multiple quit attempts in the past, and they still refuse to utilize antics. And we're seeing an even higher resistance when we look at the claims data. So I think you can implement step edits that require patients to use products, but there's ways to get around those through medical exceptions and look-back periods and also just patients' refusal to use the medication. So we're certainly looking at all those as we're developing our access strategy.

Okay, great. And then just last question for you, Rick. Are you getting closer to a potential partner for looking at a comorbid indication with cytosine queen and running that study? And are there any other potential partnerships that, you know, we could think about that you might put in place that could help with non-dilutive funding and then maybe accelerate the start of the vaping phase three? you know, now that's scheduled for the first half of next year. Is there any way you think that that could be moved forward potentially if you find a source of funding? Thank you.

Gary, multiple questions in there. I think I'll start over the beginning. You know, the impact of cytosine and ethylene in COPD patients is something that we will be saying more about perhaps later on in the year. but it's certainly got the attention of some interested parties. But the focus is purely right now, given we're resource-bound on getting that NDA submitted. So, you know, I wouldn't expect it to be announcing anything on that regard in the near future. But I think that the bigger picture is our preference is that, you know, we are driving towards the launch of sanctus iniqui in ourselves. And I think that as we gain increasing confidence in terms of the overall opportunity, that gives us a better leverage in terms of the discussions that we might have with a partner. But at the end of the day, we have to act in the interest of our shareholders. And if somebody comes along, we have to evaluate whatever the transaction is on its merits.

Okay, great. Thank you.

Thank you. Our next question comes from the line of Thomas Flatton with Lake Street Capital Markets. Please proceed with your question.

Hey, good morning. I appreciate you taking the questions. Cindy, are there future DSMC reviews coming? And if so, when might we expect to see the results of those?

Are you talking about for the open label safety?

Yes, correct.

Yes, we'll probably have one more. to be scheduled, and that would probably be reviewing, obviously, the longer-term one-year safety data. And I think that would probably be about the last one.

Excellent. And then following up on the question around CMC, how are the kind of mock reviews going with so far? Do you feel like they're in pretty good shape and would successfully pass an FDA inspection at this point, or do you think there's still work to be done there?

Yeah, no, as we look across the board, frankly, the whole NDA activity, you know, as Cindy said, we brought in external consultants to assist us with ensuring that the NDA is the highest possible quality there is. So I think the simple answer to the question, Thomas, is that we're using all the resources that we need to ensure the quality of that NDA.

Got it. And then a quick one for Mark. And last quarter, G&A was up pretty substantially, but I think there were some one-timers in there, but the number was the same this quarter or this past quarter, sorry. Do you expect that 4.9 to be kind of a good starting place going into 2025, or is there something one-time in nature in that?

No, we consider that the starting point. We obviously will manage our costs and hope to bring the number down a bit, but that's a good starting point.

Excellent. Thanks for taking the questions.

Thank you.

Thank you. Our next question comes from the line of Francois with Oppenheimer & Company. Please proceed with your question.

All right. Thanks for the questions. Just a couple here. In terms of the sales ramp, can you help us understand? I think you mentioned launch in third quarter 26. Is this, you know, can you just help us figure out a little bit how we should expect this ramp to go and just a little more color on the segmentation that you discussed? And any color on partnership or not, you talked about going either way. Is this kind of a 50-50, or should we expect this size of market to have a partner try to help out here? Thank you. I'll have a follow-up.

Sure. Hi. I will start with the first couple of questions regarding the ramp. So we're not really disclosing our forecasting assumptions at this point as far as revenue potential, but we do anticipate a slow ramp because it takes time to get access and awareness. And so, you know, we're not expecting this to move super quickly initially out of the gate. I think that was the first part of your question. Sorry, can you repeat the second or three? I know the ramp was the first one.

Yeah, I guess maybe any color on partnership availability. You talk about awareness and, you know, affecting the ramp. I know there's been discussions about going at it with a partner, without. If you can give any color on that preference and a little bit more on the segmentation of these doctors that you talked about.

Okay, I can take the segmentation, then I'll hand the partnership question over to Rick. But on the segmentation, a lot of the work that we've done is both on patients and the physician side. So we know that these varenicline scripts are really concentrated in those top decile. So there's about 460,000 physicians who are writing smoking cessation treatments in the U.S., but we've narrowed it down to about 10% of those that are writing about 60% of varenicline. And so really our initial efforts when we looked at the physician segmentation will be going after those high-volume prescribers who are most likely to adopt the product. And then on the patient side, again, I think as I've mentioned in the past, we're looking at these highly motivated quitters who are ready and willing to take prescription treatments to help them to quit. And so this is what we've seen through our market research and also when we've looked at the Chantix launch plans. It's really going after people who are convinced that they need help and are willing to talk to their physicians and engaging actively in quick conversations with them, and they just need another option. So that narrows it down to about 25% of that highly motivated. And then our segmentation work that we've recently completed looking at claims across medical and just general consumer behavior, we can narrow it down even further. So we'll have a very clear plan of how to engage with these patients at the time of launch. And I'll let Rick handle partnering.

Right, Frank. I think the key to all of this is, I know we said it right the way through, is the NDA preparation, getting the execution right, getting everything in place. And I think part of the message now to our strategic partnering thoughts is to really emphasize the fact that nicotine dependence is a medical condition. You know, I think that The market has generally thought that this is a lack of willpower on behalf of patients, but it isn't. You know, as I said in the call, nicotine is reported to be the third most addictive substance after heroin and cocaine, and therefore it needs to be treated as such. And I think you'll see that in our kind of discussion about the future strategy, we start to look at other areas, as we mentioned COPD, but it really is reinforcing that message that that negative independence is a medical condition. And we do look quite closely at the change in attitude to obesity that the GLP-1 has actually created. So that's really a long-winded way of saying that, you know, as is we're focused on getting the NDA submitted, we have a commercialization plan which is extremely well thought out. But alongside that, you know, we are looking for... Somebody, a strategic partner who can actually exploit, perhaps, and optimize revenue potential in the U.S. and also globally. And I think, you know, whilst we're absolutely laser-focused on the NDA submission, we're laser-focused on the U.S. market opportunity. But, of course, the rest of the world represents a pretty significant revenue opportunity for somebody else.

Okay, great. And then just lastly, in terms of the financial position, can you help us maybe, Mark, go through? So you have 34 million shares, but there's been a lot of warrants and stuff. And can you just remind us, are there pre-funded warrants? Just how do you get to the fully diluted share count and what is that? Thank you.

Yeah, we'll get that over to you. I'll get you a firm number with it broken down kind of, options and warrants, so that way you can have a fuller picture rather than just one number.

Understood. And that's mostly in the 10K already, right? So, I mean, are we talking like an extra $35 million, $40 million kind of ballpark to get to fully diluted?

No, it's closer to another $20 million.

Excellent. All right. Thank you.

Thank you. Our next question comes from the line of Justin Walsh with Jones Trading. Please proceed with your question.

Hi. Thanks for taking the question. You mentioned that the initial launch will target converting high-volume providers from the varinocline to cistacinicline. Can you provide any color on what narrative and or data you believe will be most effective in actually triggering conversion? Highlighting the nicotine dependence that you just mentioned, as a medical condition does make sense, but that would seem to apply to both drug options.

Yeah, I think one of the kind of anecdotally, thanks for the question, Justin. I think anecdotally one of the things that we've heard from our key opinion leaders that kind of gives us a laugh is that we could have named this product not Chantix, and it would be wildly successful. And so I think that, you know, the huge thing here is that there's been nothing new in 20 years, and physicians need new options to help them help their patients. And so, you know, when we're looking at the label and we're talking about how we're going to position this drug in the market, we've got such solid evidence from both our tolerability profile, the efficacy, the compliance of the product, and so it's really packaged very nicely and something that's going to be compelling and different. Rick, would you like to add something, too?

Yeah, if I can add this, you know, the experience from the two Phase III clinical trials And the response from the patients was pretty much uniformly positive. And, in fact, we've got one patient in particular who we use as our kind of exemplar who she'd been smoking for 30-odd years. She was smoking at least a pack of cigarettes a day and tried to quit more than 20 times. And yet, even today, cynicline is the only treatment that she's ever successfully quit. So I think what you find is that patients actually really like cytosinicline. And again, I think that that feedback stands in really good stead because it's reputational. And I think that we can benefit from the reputation that we got in the two phase threes, and we can build on that going forward.

Great. Thanks. One more question for me. You guys have noted your anticipated exclusivity period for cysticinicline is expected to extend into and through the 2040s. Acknowledging that we expect these to be in place, I'm wondering if you can comment on if there are potential barriers for generics that could enter the market down the line. I'm just curious if the drug being derived from plant extraction would make it easier or harder for others to manufacture.

I think that's a great question. The key in our mind is the actual starting material. And it isn't easy to extract the kind of volumes that we're going to be talking about. And I think over the years, and we've had the discussion around the source of it, it takes a while for these plants to actually reach maturity. And that is a barrier to entry in itself. But I think if you layer on top of that a pretty comprehensive IP estate, and as you say, it takes it out beyond 2040, I think that combination of factors really does play very strongly in our favor.

Great. Thanks for taking the question.

Thank you. Our next question comes from the line of Brandon Folks with Rodman and Renshaw. Please proceed with your question.

Hi, thanks for taking my questions, and congratulations on all the progress. I do just want to follow up on an earlier question. I think it may have been the prior question. Hearing your answer on sort of you could have named this drug, not Chantix, but any color in terms of how satisfied patients are at these high prescribers and the satisfaction of these high prescribers using varenicline? You know, just given the usage, is that just because they're Is nothing else? How much education do you think you will need for these high prescribers to understand the differentiation in your product and change that very ingrained prescribing habit, given there hasn't really been much change for so many years?

Yeah, so some of the work that – thanks for the question, Brandon. Some of the work that we've done on the physician side, they've reported a relatively low satisfaction rate with Chantix. In fact, if I recall from our data off the top of my head, I think it was about two-thirds of their patients ultimately fail the product, yet it's the most prescribed product that they utilize. And so it's a rather unique treatment landscape where you continue to use a product that doesn't work. But in light of not having any other options, that's just what they're using. So I think they are going to be very receptive to something that's got an excellent efficacy and safety profile. And as far as conversions, you know, we did some analysis with our prescribers in that initial research asking them of conversion rates of what they would transfer over their prescriptions, and a majority of them, based on our profile, converted not only varenicline, but from the NRT and the bupropion patients over to cytosinicline as well. So I think, you know, we've baked kind of some of those numbers on a much more conservative basis into our forecast. But, you know, there's a great likelihood of an interest in having something new and having something that works in the marketplace.

If I can add, Brian, this goes to the very heart of our commercialization strategy. So it's a question of how. The commercialization strategy is really founded on a digital-first strategy where increasing the awareness to both the physicians and the patients is absolutely vital to success. And I think already we're starting to see the awareness of the benefits of cytosinically certainly in the quicker community. And I think there's clearly... so we say pent-up interest and demand from that community. And as soon as we have a commercial launch, we can really capitalize on that level of interest.

Great. Thanks very much. And one follow-up, if I may. Just how different of a commercial approach is vaping, just given it's a much younger population? You know, I heard you mention digital first there. So I'd just love to sort of understand, you know, not jumping too far ahead here, but Just how different is the commercial approach in vaping or how similar is the commercial approach? Thank you.

So I think from a physician perspective, the commercial approach is very similar because the same doctors, primary care prescribers, or primary care physicians are the key prescriber in that audience. From the consumer, that's where we're going to have a lot more unique opportunities to engage in partnership conversations with those who have apps and perhaps wearables. So the digital tech space could be really interesting for that younger population, as you mentioned. And also they're engaging more, not to say that the smoking population isn't also engaging in social, but really when you see the younger audiences, you're expanding the utilization of social and how frequently and how the number of social channels that they're utilizing. So it's certainly nuanced.

Great, thanks for taking my questions, and congrats on all the progress.

Thank you.

Thank you. Our next question comes from the line of John Vandermosten with Zacks SCR. Please proceed with your question.

Great, thank you, and good morning, everyone. There were a couple of relevant JAMA articles that came out in the last week or so. One was on the high rate of smoking during pregnancy, or at least I thought it was high. They found a rate of about 7%. during pregnancy and almost 12% after. And then there was another article that was looking at vaping and how it was ineffective in really controlling smoking. And I thought these were really interesting coming out now as you are developing your commercialization strategy and wondered if you had any thoughts on how these two items might impact your move forward especially on the pregnancy side, because I don't think anyone's really pursued that. I mean, I guess we all assume that people just didn't smoke. Let me hear your thoughts on that.

You know, as far as pregnancy, we don't have any actually human data as far as cytosinicline with pregnancy. We do have certainly animal studies to show that it isn't a safety issue. So that is definitely an area that obviously physicians might actually view that it is important for the patient, the pregnant patient, to consider it. So that obviously is a natural kind of option in that regard.

One interesting point on that, thanks for the question, John, is we've talked about primary care prescribers as our key audience, but there are a lot of women visiting their OB-GYN who are planning And so that would be a unique market expansion opportunity for us to start tapping into that broader audience to help people with their family planning and why they should start cessation early in that process. So it certainly expands the opportunity over the longer horizon. And then I think regarding your question about vaping being ineffective for smoking cessation, to us that's not really surprising. I think this is a journey that people go on over many years, and most people, when we did our vaping research, they indicated they started vaping to quit smoking, and then what they ended up doing was both. So then you have dual users who are essentially consuming nicotine 24-7 because they're smoking when they're not vaping, and when they're indoors or working, they're vaping. I think we're looking at an audience of people who are looking to get off of nicotine altogether, and that's going to be our focus. We know they're out there and we know that they're ready to quit, whether it's financial or health or a combination of both. They're really interested in unburdening themselves from this dependence, as Rick commented during our call.

If I can add something, John. I've also commented in the past that this is like whack-a-mole. We started this journey with smoking cessation. It migrated to include vaping cessation. And now we've got the tobacco patches now presenting yet another method of nicotine dependency. So I think that this is expanding in front of our eyes. And each one of those interplays really reinforces that nicotine dependence. I think that we're aware on all fronts in terms of the opportunity is expanding, and we have a drug that can actually help these patients with their nicotine dependence.

Right. And that UCSD study that I referenced, they actually found the same thing that you said, Jamie, is that people who tried to stop with vaping actually ended up doing both and consuming more nicotine. The second question is on just to ramp up at SoPharma. I guess the product that they make will be exclusive to the U.S. market, I assume, because I think the dosing schedule that they're producing for now or manufacturing for now is different. How will that affect when they start manufacturing supply for the commercialization? Will they start that after the approval is given, or will they kind of prepare in anticipation of it?

Yeah, I think the key to the whole situation in terms of the NDA submission preparation is to ensure that we've got the right resources available to us at the right time. So we're actually planning to ensure that, as Cindy said, we're bringing in external consultants to assist us across the board. So I think as far as the manufacturing area is concerned, that's exactly the same. We brought in consultants, and we're prioritizing the resources that we need to make sure that we've got product available at launch.

Okay. Okay. And just one last thing. You kind of gave us a clue that it will not be – the brand name will not be NotChantic. Okay. But I was wondering if there's any clue on what it might be when you roll it out. Is that in progress, determining that name?

Yeah, we actually have preconditional approval or conditional approval on a name from FDA. We are not sharing that at this time because in true FDA fashion, that's subject to change upon final approval. But no, we've moved forward with a brand name that has been researched and cleared through various analyses of legibility and pronounceability and all of the things that are required by FDA. And we've started working on some of the brand identity aspects as well, including our logo. So we're definitely making progress, and this is a really exciting time for us.

Great. Thanks so much.

Thank you.

Thank you. Our final question this morning comes from the line of Boris Tolkachev with Freedom Broker. Please proceed with your question.

Good morning, everyone, and thanks for taking the question. I have a quick one for regarding the future vaping study. Given the relatively high placebo effect observed in ARCAV1 trial, could you briefly share, if possible, your views and expectations for the effect size in a future phase three study? And I was also wondering whether such questions were raised by FDA during the end of phase two meeting. Thank you.

And that's where the ORCA V1 trial was most valuable for being able to assess and look at the sample sizing. And that Phase III study is definitely powered for higher placebo rates. And, you know, higher placebo rates were seen when the smoking cessation trials were being conducted 20 years ago. We kind of expected that it would be slightly higher. The arms are a little higher in number to be able then as the sample size to accommodate that. As a company, you do not run a phase three study that's underpowered. So we still have power at greater than 90% for a trial that's now estimated at about 800 subjects. And looking at really because of that, what we view as maybe a little higher addiction with vaping. We're only going to be looking at the 12-week regimen with the placebo regimen, so that's where 400 subjects per each of those arms is definitely empowered to accommodate that higher placebo rate.

Okay, thank you so much.

Thank you. Ladies and gentlemen, that concludes our question and answer session. I'll turn the floor back to Mr. Stewart for any final comments.

Well, I'd just like to thank you all for your continuing interest in Achieve and our mission. The NDA submission next quarter is going to be a critical value creation event, and the opportunity is only getting bigger in terms of our ability to treat patients for nicotine dependence So we're across the board. The company is excited, and I just want to thank all the employees for their dedication and commitment to getting us to where we are today and where we're about to go. So thank you very much.

Thank you. This concludes today's conference call. You may disconnect your lines at this time. Thank you for your participation.