Greetings, and welcome to the Achieve Life Sciences Third Quarter 2024 Earnings Conference Call and Webcast. [Operator Instructions] And as a reminder, this conference is being recorded. I would now like to turn the call over to Nicole Jones, Achieve Investor Relations. Thank you, Nicole. You may begin.

Thank you, operator. Good afternoon, 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; Jerry Wan, Principal Accounting Officer; and Jaime Xinos, Chief Commercial Officer. Management will be available for a Q&A session following today's prepared remarks. Before we begin, I'd like to remind everyone that today's conference call contains forward-looking statements based on current expectations. These statements are only predictions, and actual results may vary materially from those projected. Please refer to Achieve documents available on our website and filed with the SEC concerning factors that could affect the company. I'll now turn the call over to Rick.

Thanks, Nicole. The third quarter was yet again eventful and productive for Achieve with the change of management, new hires in key roles, the FDA granting breakthrough therapy designation for e-cigarette or vaping cessation and refinancing our SVB loan. Much of this activity reflects the rapidly maturing Achieve and reflects the increasing value to patients, physicians and shareholders as the company transitions from a pure-play clinical development company towards a more commercially focused company. As a result, the Board decided that as Achieve swiftly approaches NDA submission, acceptance and approval, the company needed to strengthen executive management with greater commercial and M&A expertise to enhance the future value of the company. The value proposition continues to increase. A target population of more than 40 million Americans with nicotine dependence is awe-inspiring to big pharma, let alone a micro biotech. To continue value enhancement, we have carefully and thoughtfully assessed the future strategy of Achieve and cannot rely solely on a third-party exit or strategic partnering to commercialize cytisinicline. In fact, to do so would hold Achieve to ransom for unpalatable terms. We have to move forward from a position of strength with strong conviction about our ability to provide patients with a best-in-class smoking cessation therapy and a first-in-class vaping cessation treatment. As you will hear a little later, smoking does not only affect the health and life expectancy of the people who smoke, it has a profound impact on family, friends and the wider community. The proliferation of smoking-related diseases, including respiratory, cardiovascular, cancer, diabetes, dementia and so on, reverberates through society. For far too long, we've ignored the medical nature of nicotine dependence and solely focused on the $300 billion a year cost of the consequences of smoking-related diseases. Nicotine dependence is a disease, and it needs to…

Thanks, Rick. We began the open-label ORCA-OL safety trial for long-term cytisinicline exposure in May 2024 and recently completed enrollment in early October, ahead of expectations with 479 participants across 29 trial sites in the United States. All participants were part of our previous Phase 2 and Phase 3 smoking and e-cigarette cessation studies, allowing for swift enrollment in just over four months. This trial is designed to meet the FDA requirements in providing safety data for at least 300 subjects treated with cytisinicline for a cumulative period of six months to support our NDA submission. In addition, data on at least 100 subjects treated for a cumulative period of one year will also be submitted as an NDA clinical safety update before product approval. Additionally, the Data Safety Monitoring Committee for the ORCA-OL trial recently completed their first safety data review and found no safety concerns. They reported an excellent overall safety profile, allowing the study to continue as planned without any modifications. I now want to give more detailed timing on the cytisinicline NDA submission, which remains on track to occur in quarter 2, 2025, subject to completion of data collection, safety analysis of the ORCA-OL and on manufactured cytisinicline product stability data. We expect that at least 300 subjects in the open-label study will have reached their six months of cytisinicline exposure by late January, early February. It will then take approximately three months to collect the data, monitor it, lock the safety database and incorporate the safety data into the integrated safety summary document for the NDA. Once complete, the NDA will undergo final quality assurance checks before submission. We expect the NDA submission acceptance subject to FDA's review within 74 days of NDA submission and then product approval approximately 12 months after that. As Rick mentioned, we recently participated in a joint public meeting with the FDA and NIH on priorities for advancing smoking cessation innovation. I had the opportunity to share and present our Achieve Life Sciences' journey regarding cytisinicline to representatives from FDA, NIH, NIDA and other smoking cessation experts. During this meeting, I spoke about the urgent need for new FDA-approved treatments for smoking cessation. I appreciated the opportunity to speak on the issue and to be a part of this important meeting. Comments from my presentation are available on the FDA website as noted in our press release. Finally, we were pleased to announce this quarter that FDA granted breakthrough therapy designation to cytisinicline for the vaping cessation indication. Breakthrough therapy designation is important because it offers access to an FDA cross-disciplinary project management team for interactive communications with senior managers and reviewers at FDA. This will be beneficial in completing the regulatory requirements necessary for expanding cytisinicline treatment as the first approved pharmacotherapy in treating nicotine dependence for e-cigarette cessation, not only in adults, but also potentially for an adolescent vaping population. I will now turn the call over to Jaime.

Thanks, Cindy. Commercial planning is moving forward as we begin to set the stage for a successful launch of cytisinicline in the U.S. For over two years, we've been working closely with agencies and partners to create a launch strategy that ensures we're ready to go upon FDA approval, regardless of partnering status. We've conducted extensive customer research diving into patient, prescriber and payer perceptions about smoking and vaping, the challenges of quitting, experiences with currently available treatments and opinions about cytisinicline. This invaluable feedback is guiding our approach, particularly as we position cytisinicline as a promising new treatment option. Over the next several months, our focus will be on key activities essential for NDA filing and foundational projects that typically require 18-plus months to execute prior to FDA approval. These include, but are not limited to, packaging design, label and promotional claims drafting, third-party logistics selection, channel and distribution strategy, state licensure, compendia listings and health outcomes research to enhance our value messaging, which is essential groundwork for effective pre-approval communications with payers. Achieve has always operated with a lean, efficient team since our inception in 2017. We remain dedicated to this approach and we'll continue outsourcing where feasible. As we begin key commercial activities, we're strategically building our in-house team, focusing on experts with deep relevant experience. A great example of this approach is our recent hire, Dr. Mark Rubinstein, a nicotine addiction specialist with rich cross-functional experience. Mark's expertise in direct patient treatment, clinical research and his experience across medical affairs in both small and large companies brings an immediate valuable impact to our team. Our next key commercial hire will be a lead for trade and market access with extensive experience managing the complexities of a small biotech preparing for its first launch. We are currently…

Thank you, Jaime. Good afternoon, everyone. I'd like to provide an update on our financial activities this quarter and then review our current financial status and forward outlook. Beyond our clinical progress this quarter, we are also pleased to have successfully completed a debt refinancing agreement with SVB that provides for up to $20 million in availability. Under the terms of this new agreement, the $20 million term loan is divided into three tranches. The first tranche of $10 million was received at closing. The second tranche of $5 million will be available upon FDA acceptance of the NDA for cytisinicline and the final $5 million tranche will be available subject to SVB's discretion and credit committee approval. Let's now take a look at our third quarter financials. As of September 30, 2024, the company's cash, cash equivalents, restricted cash and short-term investments were $42.9 million as compared to $61.3 million for the prior quarter. We believe our current cash balance is sufficient to provide us runway into the second half of 2025, including through potential NDA submission. Turning to our statement of operations. The company incurred a net loss of $12.5 million for the quarter ended September 30, 2024, as compared to a net loss of $7.1 million for the same quarter in the prior year. Net loss for the nine months ended September 30, 2024, increased to $27.5 million as compared to $24.3 million for the same period in 2023. In line with expectations, operating expenses increased in the third quarter with the achievement of the targeted enrollment in our ORCA-OL trial. We expect our quarterly operating expenses will remain elevated as we continue to progress forward with ORCA-OL. With our continued focus to execute on our strategy towards NDA submission and plans to expand our M&A and commercial preparation activities, we remain committed to maintaining rigorous expense controls to ensure resources are applied efficiently and effectively to achieve our goals, fuel our growth and create shareholder value. I will now turn the call back over to Rick.

Thank you, Jerry. There are 16 million people in the U.S. currently suffering from smoking-related diseases. For every one death that smoking is responsible for, 30 other people are living with diseases that have been caused as a result. That is a staggering number. As I mentioned earlier, cytisinicline has a greater role in the treatment of nicotine-dependent disease. It will be crucial in reducing the disease burden caused by smoking and related conditions such as respiratory diseases like COPD and asthma, cardiovascular disease, stroke, complications from diabetes, dementia and numerous forms of cancer. COPD is a particular focus for Achieve because 80% of all diagnosed COPD patients have this progressive disease as a result of smoking. Roughly 6 million Americans currently living with COPD continue to smoke. Abstinence from smoking reduces the number of exacerbations and hospitalizations, and there is increasing evidence that standard of care COPD drugs have greater efficacy in nonsmokers than current smokers. Our goal is to work with a COPD or asthma potential partner with greater resources and expertise than Achieve to exploit this potential. But for now, please do not misinterpret this statement as Achieve is losing focus. We are not. Nicotine dependence disease through smoking and vaping cessation is our core strategy. In time, we're also optimistic that Achieve will address the next potential nicotine dependence crisis in tobacco pouches. Our near-term focus is executing according to the plan with NDA submission, acceptance and approval the priority, closely followed by the ORCA-V2 Phase 3 clinical trial. Finally, commercial planning to fully optimize the cytisinicline opportunity in the U.S. The importance of nicotine dependence treatment and Achieve's role in this fight is gaining recognition, and this is just the beginning. Cytisinicline has been featured in many recent articles, including those in The New York Times and Time Magazine and I'd like to thank Emily Schmall and Jamie Ducharme for their interest in this global public health crisis and in Achieve. Thank you again for joining us today. I'll now turn the call over to the operator for questions.

[Operator Instructions] And the first question comes from the line of Thomas Flaten with Lake Street Capital. Please proceed with your question.

Good afternoon. I appreciate you taking my question. Congrats on all the progress. Just a quick one for Jerry. Jerry, there was a spike in G&A in the third quarter. Were there onetime or nonrecurring amounts in that $4.9 million?

Thanks for the question, Thomas. That's correct. There were onetime charges this quarter relating to the executive restructure and associated severance costs.

Got it. And then, Cindy, if I may, you mentioned that all the patients that were enrolled in ORCA-OL had come from prior studies. Would you be willing to share how many of those patients were -- had prior exposure to cytisinicline and how many of them might have had a full 12 weeks?

Yes. Actually, it's pretty much similar to what the ratios were in the Phase 3 trials. We basically have about one-third that have -- were on the 12-week arm and one-third on the 6-week arm and one-third in placebo.

Excellent. I appreciate you taking my questions. Thank you.

And the next question comes from the line of Justin Walsh with JonesTrading. Please proceed with your question.

Hi. Thanks for taking the questions. Sorry if I missed this. What are your expectations with respect to disclosing data from the ORCA-OL trial? Do you expect that we'll get to see a complete presentation of the results before the NDA submission moves forward?

I'll hand that one over to Cindy.

Yes, not at this time, actually, because it's an ongoing. We are not going to be presenting results at a meeting before submitting to the NDA. I think we'll probably be looking at what presentation or meeting that we could actually present after we submit the NDA. I mean at this point, focus on the Data Safety Monitoring Committee reviews that all the safety looks good and there are no safety concerns.

Got it. And one more quick question for me. Obviously, smoking cessation is the near-term focus in terms of commercial preparations. But I'm curious if any efforts have been made towards laying the groundwork for a potential vaping cessation label expansion down the line.

Yes. Justin, I think the key here is keep focused on the smoking cessation opportunity, and Jaime is doing a terrific job in terms of scoping that opportunity in terms of the market. But I think the vaping opportunity is increasing at a pretty dramatic rate as well. And I think trying to get a very firm grasp on the actual kind of the revenue potential for it is a dynamic situation. But once we've got the commercial structure in place for smoking cessation, we'll expand it into vaping cessation.

Great, thanks for taking the questions.

And the next question comes from the line of Francois Brisebois with Oppenheimer. Please proceed with your question.

Hi, thanks for taking our questions. This is Dan on for Frank. I guess, firstly, with regards to the ORCA-OL, once the data analysis is completed, are there any additional steps needed before submission? Do you need any more pre-submission meetings? Or does the positive feedback from the DSMC so far provide confidence that you are all set for the NDA submission? Basically, any additional steps needed before submission?

I think the key here is going to be the step process. Once the ORCA-OL 6-month data with 300 patients is complete, as Cindy said on the call, we're going to have to monitor the data, effectively put it into the ISS and then insert that into the NDA and then do a full quality control on the actual NDA itself. And hence, late January, early February for the completion of the 300 patients at six months and then step process through that to the NDA submission. In the meantime, obviously, the 100 patients at 12 months will be ongoing. So that is roughly the plan.

Great, thanks for taking questions

And the next question comes from the line of John Vandermosten with Zacks Small-Cap Research. Please proceed with your question.

Great, thank you and good afternoon everyone. Jaime, congratulations on your role as CCO. You hired Dr. Rubinstein about a little bit over a month ago. And I'm just wondering what he has been able to add to the strategy discussion so far and perhaps some of that was already discussed, but anyway I'd like to hear kind of what he's been able to bring to the table.

Yes, I'd be happy to answer that. Go ahead, Greg.

I was just going to say, if I can add, and then I'll hand it over to Jaime. I think he has been a terrific addition because his experience and insights as a practitioner and having been in the nicotine dependence space for many, many years has really allowed us to really hone in on some of the messaging. So I think he has been a great addition. So I'll now hand that one over to Jaime.

Yes. Sorry, Rick. Thanks, John. I absolutely agree with Rick. I mean, Mark's ability to go out and talk to his peers to get insights for us that will help inform future positioning and messaging as well as the medical education strategy and the need. So he's able to help us think about publication planning, where we need to be submitting data and how we need to be talking to potential prescribers. And again, like as Rick mentioned, he also has a different insight because he's treated patients. And so he knows what some of the hurdles and challenges are to getting them to consider taking medications and help us to understand how we need to be speaking to patients as well.

Okay. Great. And thank you for the refinement on the start of the vaping trial. Is there any idea how much that will cost and kind of the flow of cost as that -- as we move into mid-2025?

Yes. I think likely it's going to be similar to previous Phase 3 trials. But I think we can give better guidance on that after the FDA agreement is met on the protocol size, et cetera. But I think as a bellwether, I'd look at something similar to the previous Phase 3s.

Okay, great. Thank you.

And the next question comes from the line of Gary Nachman with Raymond James. Please proceed with your question.

So my first question is you mentioned vaping potentially setting that down to the adolescent population. What might a trial look like there? What kinds of special considerations are you going to have to take into account to get that adolescent teen population? Obviously, there's a big need there. And then also, you mentioned nicotine pouches as well. That's another use case that's growing. What would that look like? And could that be combined with vaping?

Yes. I'll hand that question over to Cindy in terms of the pediatrics.

Yes. We'll be focusing on getting the Phase 3 completed in adults 18 years and older. And one of the discussions we'll have with FDA as we proceed toward this clinical development is we will need to agree on what is called a pediatric study plan, and that will be when we'll have more discussions with FDA on a possible adolescent trial, what that would look like, the timing of that and the ability to do that. So that will be future discussions with FDA in regards to adolescents younger than 18.

I'll take the question about the tobacco pouches. I think the key here, Gary, is it almost seems that you have one nicotine dependence product after another, where initially, obviously, everything was focused on cigarette -- combustible cigarettes. Then we moved on to vaping and starting to understand some of the issues that are related to vaping. And then as soon as that is acknowledged, we're now looking at tobacco pouches. And I think for now, our focus is really on getting the ORCA-V2 vaping Phase 3 up and running, which -- during which time we'll be able to start to assess how you address the tobacco pouches. But it's certainly on our radar screen, but I think priority one is obviously the NDA submission for smoking cessation, then the vaping Phase 3, and then we'll move on to tobacco pouches.

And I just had one follow-up question as well. Do you have any updates you could share on the potential synthetic cytisinicline development process, where that timeline is, if there's anything you have to share? And then what would the regulatory process getting that approved look like at all?

Yes. I mean that's an ongoing process. As you know, we've tried on multiple occasions to crack the synthetic. We continue to make progress on that front. But I think the best thing to do is we'll keep you updated when we've got something more to say about that one, okay?

Okay. Thanks for taking my questions. Congrats on the quarter.

Thank you.

And the next question comes from the line of Boris Tolkachev with Freedom Broker. Please proceed with your question.

Good afternoon, everyone. Thanks for taking the question. Initially, you plan to include 650 patients, but actual enrollment was completed with 20% fewer participants. Could you give some clarification regarding the decision to decrease that number? And as the ORCA-OL study continues, is there a risk that the discontinuation rate will be higher as participants become more and more -- less and less motivated to stay on therapy? Are there any strategies employed to maintain engagement? Thank you.

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

Sure. We had put in 650 as the maximum, not sure that we actually needed it. When we started to get to 450 and the discontinuation -- early discontinuation rate was so low, that's where then we decided to go ahead and cap enrollment under 500. The early discontinuation rate remains very low. So we don't have concerns that we won't be able to achieve 300 subjects at cumulative six months and 100 for one year. Regarding the one year, we do have kind of retention programs at all the 29 sites for the subjects. And obviously, right now, we kind of view that they're working as far as the discontinuation rate continues to remain very low.

Okay. Thank you so much

And the next question comes from the line of Thomas Flaten with Lake Street Capital. Please proceed with your question.

Hi guys, thanks for letting me back in. Cindy, I was just looking at my notes, and I just want to confirm, you said that following the 74-day letter, you would have -- did you say 10- or 12-month review process? I wrote down 12, but I think you meant 10 or did I misunderstand that?

Yes, it's 12 months total from the time we submit. But in 74 days from submitting, that's when FDA accepts the NDA submission for review, yes. Sorry.

No, no problem. And then for Rick or Cindy, I know we talked previously about leveraging some non-dilutive financing from the NIH to fund the vaping study. Is that still on the cards? Or should we think about that coming out of internal cash?

That's definitely still on the cards. I mean I think once we've actually scoped out the size and the protocol related to the vaping study, we'll be able to engage more fully. So definitely still on the cards.

Great. Thanks again.

And at this time, there are no further questions. Now I'd like to turn the floor back over to Rick Stewart for any closing comments.

Well, thank you. We are in exciting times. As the NDA submission for smoking cessation approaches, we're making tremendous progress on a quarter-by-quarter basis. Obviously, the priority and the focus in the near term is that NDA submission. And as Cindy said, we're targeting the second quarter of 2025. But the role of cytisinicline in the public health crisis in the U.S. with nicotine dependence is significant. There are over 40 million Americans suffering from nicotine dependence. And as Jaime said, yes, we're privileged to be in a position to be able to actually do something about that. We can alter the lifespan of millions of Americans by getting them to cease nicotine dependence. And cytisinicline will be the first new product in nearly 20 years, offering hope to nicotine dependence patients, not just in the U.S. but up to 1 billion globally. So we'd like to thank you again for your continuing support of the company, and we look forward to updating you on the fourth quarter call. Thank you.

And ladies and gentlemen, that does conclude today's teleconference. You may disconnect your lines at this time. Thank you for your participation.