Achieve Life Sciences Inc

NASDAQ:ACHV

Earnings Call Transcript

[Operator]

Greetings, and welcome to the Achieve Life Sciences Fourth Quarter and Year-End 2024 Earnings Call and Webcast. [Operator Instructions]. 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.

[Nicole Jones, executive]

Thank you, operator. Good morning, everyone, and thank you for joining us today. From Achieve Life Sciences, we are joined by Rich Stewart, Chief Executive Officer; Dr. Cindy Jacobs, President and Chief Medical Officer; Mark Oki, Chief Financial Officer; Jaime Xinos, 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 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 Rich.

[Richard A. Stewart, executive]

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 cytisinicline as a treatment for nicotine dependence for smoking cessation with the FDA at the end of next quarter.



Cytisinicline 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 cytisinicline to become the only nicotine dependence product being promoted to health care providers. The health risks of smoking are well established and vaping perils 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 cytisinicline 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 6 months of cumulative cytisinicline treatment, which was a necessary step required by the FDA for submission of the NDA. We also received breakthrough therapy designation for cytisinicline as a treatment for vaping cessation. We completed the end of Phase II meeting with the FDA for vaping cessation as a future indication, which included agreement on the design of a Phase III trial.



We strengthened our leadership team with the hire of our CFO, Mark Oki, to oversee our financial strategy and operational initiatives. We appointed Dr. Kristen Slaoui and Nancy Pheland 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 U.S. health care 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 will power, 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 change 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 it over to Cindy.

[Cindy Jacobs, executive]

Thank you, Rich. 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 cytisinicline 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 5 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 cytisinicline for a cumulative 6 months, meeting one of the FDA's requirements for the submission. Additionally, we continue to collect for the long-term cumulative 1-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 cytisinicline 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 3-month process of finalizing the safety database for the cumulative 6-month exposure data and we'll 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 II meeting to discuss advancing cytisinicline's indication 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 cytisinicline as a treatment for vaping cessation. Specifically, FDA agreed that one well-controlled Phase III trial, ORCA-V2, in addition to Achieve completed Phase II ORCA-V1 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 III ORCA-V2 clinical trial for vaping cessation within the first half of 2026, dependent on financing.



We're confident that cytisinicline 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 Jaime for a commercialization update.

[Jaime Xinos, executive]

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 cytisinicline. 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 3 key priorities: awareness, access and availability, all built on a foundation of measurability to ensure impact and effectiveness of spend. We have established partnerships with leading strategic health care agencies with deep expertise in our areas of focus.



Over the past quarter, we have been onboarding our agency partners, refining our launch road map 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 cytisinicline and providing the necessary evidence to support that value. Our goal is to initiate formal discussions with payers well in advance of launch through preapproval 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 health care providers who are actively prescribing high volumes of smoking cessation treatments and to patients who are motivated to quit.



In recent months, we have further refined our patient segmentation and have deeper insight 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 cytisinicline'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.

[Mark Oki, executive]

Thank you, Jaime. I'm excited to join my first earnings call 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 cytisinicline to market, drive sustainable growth and maximize value for our shareholders. Thank you, and I'll now turn the call back over to Rick for closing remarks.

[Richard A. Stewart, executive]

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, cytisinicline's efficacy and safety profile has demonstrated superiority over other nicotine dependence treatments. In fact, cytisinicline has shown up to 2.5x better efficacy than the previous market-leading prescription product with a far more benign side effect profile.



As you've heard, commercial planning is in an advanced stage. We are 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 cytisinicline 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 cytisinicline 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. Cytisinicline can be used for COPD patients who are smokers as it reduces the number of exacerbations and hospitalizations. Data from our 2 large-scale Phase III clinical trials show a higher abstinence rate in COPD smokers than non-COPD patients. Cytisinicline 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 US attempt to quit each year. Fewer than 10% do so successfully, highlighting the critical need for a new treatment option. Cytisinicline 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 cytisinicline NDA submission as a treatment for nicotine dependence for 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 cytisinicline 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.

[Operator]

[Operator Instructions] Our first question comes from the line of Gary Nachman with Raymond James.

[Gary Nachman, analyst]

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 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.

[Richard A. Stewart, executive]

Right. I'll kick off, Gary. 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 the resources and efforts to making sure that's the case. But I'm going to hand over to Cindy.

[Cindy Jacobs, executive]

Yes. 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 regimen of 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.

[Gary Nachman, analyst]

Okay. Great. That color is helpful. And then on the commercial side, as you prepare to have good access cytisinicline. Do you expect there'll 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 the specialty pharmacy just to help also ensure that patients get their refills so they have the full 3 months of treatment?

[Jaime Xinos, executive]

Yes. Gary, it's Jamie. I'll take that question. So first of all, 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 of 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 specialty light type of channel will help us to mitigate some of those barriers to access. But the reality is with varenicline is 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?

[Cindy Jacobs, executive]

Ever in their journey to try to smoke.

[Jaime Xinos, executive]

And these are heavily experienced quitters, if you will, that have made multiple quit attempts in the past, and they still refuse to utilize varenicline, 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.

[Gary Nachman, analyst]

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 cytisinicline and running that study? And are there any other potential partnerships that 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 III. 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?

[Richard A. Stewart, executive]

Gary, multiple questions in there. I think I'll start at the beginning. The impact of cytisinicline 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 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 we are driving towards the launch of cytisinicline 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 something comes along, we have to evaluate whatever the transaction is on its merits.

[Operator]

Our next question comes from the line of Thomas Flaten with Lake Street Capital Markets.

[Thomas Flaten, analyst]

Cindy, are there future DSMC reviews coming? And if so, when might we expect to see the results of those?

[Cindy Jacobs, executive]

You're talking about for the open-label safety.

[Thomas Flaten, analyst]

Yes.

[Cindy Jacobs, executive]

Yes. We'll probably have one more to be scheduled, and that would probably be reviewing, obviously, the longer-term 1-year safety data. And I think that would probably be about the last one.

[Thomas Flaten, analyst]

Excellent. And then following up on the question around CMC. How are the kind of mock reviews going with Sopharma? 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?

[Richard A. Stewart, executive]

Yes. No, as we look across the board, frankly, the whole NDA activity, 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 we're using all the resources that we need to ensure the quality of that NDA.

[Thomas Flaten, analyst]

Got it. And then a quick one for Mark. 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 million to be kind of a good starting place going into 2025? Or is there something onetime in nature in that?

[Mark Oki, executive]

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.

[Operator]

Our next question comes from the line of François Brisebois with Oppenheimer & Company.

[François Brisebois, analyst]

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 -- 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? I have a follow-up.

[Jaime Xinos, executive]

Sure. 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 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? There were 3... The ramp was...

[François Brisebois, analyst]

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

[Jaime Xinos, executive]

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 deciles. 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 look 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 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 that -- who are convinced that they need help and are willing to talk to their physicians and engaging actively in quit 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.

[Richard A. Stewart, executive]

Right, Frank, I think the key to all of this is -- and I know we said it right away 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. I think that the market has generally thought that this is a lack of willpower on behalf of patients. But it isn't. 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 nicotine dependence is a medical condition.



And we do look quite closely at the change in attitude to obesity that the GLP-1s actually created. So that's really a long-winded way of saying that as is, we're focused on getting the NDA submitted. We have a commercialization plan, which is extremely well thought out. But alongside that, we are looking for somebody, a strategic partner who can actually exploit perhaps an optimized revenue potential in the U.S. and also globally. And I think 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.

[François Brisebois, analyst]

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?

[Mark Oki, executive]

Yes. We'll get that over to you. I'll give you a firm number with -- it's broken down kind of options and warrants. So that way you can have a fuller picture rather than just one number.

[François Brisebois, analyst]

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

[Mark Oki, executive]

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

[Operator]

Our next question comes from the line of Justin Walsh with Jones Trading.

[Justin Walsh, analyst]

You mentioned that the initial launch will target converting high-volume providers from the varenicline to cystisinicline. 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.

[Jaime Xinos, executive]

Yes. 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 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 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 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. And Rick, would you like to add something?

[Richard A. Stewart, executive]

Yes. No, if I can add this, the experience from the 2 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 a kind of exemplar who she's been smoking for 30-odd years. She was smoking at least a pack of cigarettes a today and tried to quit more than 20x. And yet, even today, cytisinicline is the only treatment that she's ever successfully quick. So I think what you find is that the patients actually really like cytisinicline. And 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 2 Phase IIIs, and we can build on that going forward.

[Justin Walsh, analyst]

Great. One more question for me. You guys have noted your anticipated exclusivity period for cytisinicline 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 a plant extraction would make it easier or harder for others to manufacture.

[Richard A. Stewart, executive]

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, we've had the discussion around the source of it. It takes a while to -- 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 as you say, it takes it out beyond 2040. I think that combination of factors really does play very strongly in our favor.

[Operator]

Our next question comes from the line of Brandon Folkes with Rodman [indiscernible]

[Unknown Analyst]

: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. Just given the high usage, is that just because there 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?

[Jaime Xinos, executive]

Yes. 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 2/3 of their patients ultimately failed 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, 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 bupropion patients over to cytisinicline as well. So I think we've baked kind of some of those numbers on a much more conservative basis into our forecast. But there's a great likelihood of an interest in having something new and having something that works in the marketplace.

[Richard A. Stewart, executive]

If I can add, Brandon, 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 for success. And I think already, we're starting to see the awareness of the benefits of cytisinicline certainly in the quitter community. And I think there's clearly -- should 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.

[Unknown Analyst]

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

[Jaime Xinos, executive]

So I think from a physician perspective, the commercial approach is very similar to 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 even 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 activities, 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.

[Operator]

Our next question comes from the line of John Vandermosten with Zacks SCR.

[John Vandermosten, analyst]

There were a couple of relevant Jamal articles that came out in the last week or so. One was 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 are really interesting coming out now as you are developing your commercialization strategy and wondered if you had any thoughts on how these 2 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. I'd love to hear your thoughts on that.

[Cindy Jacobs, executive]

As far as pregnancy, we don't have any actual human data as far as cytisinicline with pregnancy. We do certainly have animal [tox] 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 patients, the pregnant patients to consider it and so that obviously is a natural kind of option in that regard.

[Jaime Xinos, executive]

One interesting point on that. Thanks for the question, John, as 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 pregnancy. 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 effective 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 working, they're vaping. So 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. And 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. But they're really interested in unburdening themselves from this dependence as Rick commented during our call.

[Richard A. Stewart, executive]

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 another -- 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. So I think that we're aware on all fronts that the opportunity is expanding, and we have a drug that can actually help these patients with their nicotine dependence.

[John Vandermosten, analyst]

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. Second question is on just the 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 preparing or 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?

[Richard A. Stewart, executive]

Yes. 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 is exactly the same. We brought in consultants, and we're prioritizing the resources that we need to make sure that we've got products available at launch.

[John Vandermosten, analyst]

Okay. Okay. And then just one last thing. You kind of gave us a clue that it will not be -- the brand name will not be not Chantix. But any clue on what it might be to -- when you roll it out? Is that in progress determining that name?

[Cindy Jacobs, executive]

Yes. We actually have pre-conditional approval or conditional approval on a name from FDA. We are not sharing that at this time because in true FDA's fashion, that's subject to change upon final approval. So -- but no, we've moved forward with a brand name that has been researched and cleared through various analyses of eligibility 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.

[Operator]

Our final question this morning comes from the line of Boris Tolkachev with Freedom Broker.

[Boris Tolkachev, analyst]

I have a quick one regarding the future vaping study. Given the relatively high placebo effect observed in ORCA-V1 trial, could you briefly share, if possible, your views and expectations for the effect size in the future Phase III study? And I was also wondering whether such questions were raised by the FDA during the end of the Phase II meeting.

[Cindy Jacobs, executive]

Sure. 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 higher placebo rates were seen when the smoking cessation trials were being conducted 20 years ago. So we didn't -- we kind of expected that it would be slightly higher. So the arms are a little higher in number to be able then as the sample size to accommodate that.



Certainly, as a company, you do not run a Phase III study that's underpowered. So we still have power at greater than 90% for a trial that's right 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 for each of those arms is definitely powered to accommodate that higher placebo rate.

[Operator]

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

[Richard A. Stewart, executive]

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.

[Operator]

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