Achieve Life Sciences, Inc. (ACHV) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by, and welcome to the Achieve Life Sciences ORCA-2 Clinical Data Results Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. [Operator Instructions] I would now like to hand the conference over to your speaker, Ms. Jaime Xinos. Please go ahead.

Thank you, Sheri, and thanks, everyone, for joining us. On the call today from Achieve, we have John Bencich, Chief Executive Officer; Dr. Cindy Jacobs, President and Chief Medical Officer; Rick Stewart, Executive Chairman of the Board of Directors; and Dr. Anthony Clarke, Chief Scientific Officer. Dr. Nancy Rigotti, Professor of Medicine at Harvard Medical School and Principal Investigator of the ORCA-2 trial is also joining for Q&A. 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 filed with the SEC concerning factors that could affect the company, copies of which are available on our website. I will now turn the call over to John.

Thank you, Jaime, and thank you, everyone, for joining us. Today, we reached a major milestone, reporting the highly successful results from our ORCA-2 Phase III clinical trial of cytisinicline for smoking cessation. We are excited to report that cytisinicline demonstrated a positive efficacy benefit across the primary and secondary endpoints for both the 6- and 12-week cytisinicline treatment arms. Results for the primary endpoint of the study shows 6x to 8x higher odds or increased likelihood of smoking abstinence with cytosinicline treatment compared to placebo. Importantly, and as expected, cytisinicline continues to be very well tolerated with single-digit rates of side effects reported across both active treatment arms. This compares very favorably to what has been historically reported for the approved oral therapeutics currently on the market. We are encouraged by these positive results and believe cytisinicline, if approved, has the potential to become the new gold standard for the treatment of smoking cessation and nicotine addiction. I'd now like to turn the call over to Cindy to review the ORCA-2 results in more detail.

Thanks, John. We are pleased to report clinically robust and statistically significant results for both primary and secondary endpoints for 6 weeks and 12 weeks of cytisinicline treatment compared to placebo in this trial. As a reminder, ORCA-2 is the first of 2 multicenter, randomized, Phase III trials evaluating cytisinicline for smoking cessation in adult smokers in the U.S. The trial is designed to evaluate the safety and smoking cessation effectiveness of 3 milligrams cytisinicline taken 3 times daily for either 6 or 12 weeks compared with placebo. Study participants were randomized to 1 of 3 arms, and received either 6 weeks of cytisinicline followed by 6 weeks of placebo, or 12 weeks of cytisinicline or 12 weeks of placebo. All subjects also received standard behavioral support for the duration of the study. The ORCA-2 study had 2 independent primary endpoints that evaluated the success of smoking abstinence for both 6-week and 12-week duration of cytisinicline treatment compared to placebo. For both primary endpoint comparisons, smoking abstinence was defined as abstinence during the last 4 weeks of treatment. Meaning for the 6-week treatment arm, biochemically verified abstinence was required at weeks 3, 4, 5 and 6. For the 12-week arm, abstinence was required at the assessments conducted at weeks 9, 10, 11 and 12. This 4-week biochemically verified abstinence measure remains the FDA's approvable endpoint for smoking cessation medications. The corresponding secondary endpoints evaluated for continuous abstinence and those who successfully quit smoking by week 3 through to week 24 or by week 9 through to week 24, depending on the treatment duration. ORCA-2 completed enrollment of 810 smokers at 17 clinical trial locations in June of last year. The study population represented 55% female, 45% males, and were primarily Caucasian with 16% African-Americans. On average, the study population was 54 years old, had been smoking for 38 years, had 4 prior quit attempts, but were still smoking about a pack of cigarettes a day. This first slide represents the primary and secondary endpoint results for 12 weeks of cytisinicline treatment compared to placebo treatment. After 12 weeks of cytisinicline, 32.6% of smokers had quit smoking compared to only 7% of smokers treated with placebo. This resulted in an odds ratio of 6.3%, meaning that those smokers treated with cytisinicline had 6x the odd or likelihood of quitting smoking compared to smokers treated with placebo. For the secondary endpoint at 24 weeks, 21.1% treated with cytisinicline were nonsmokers compared to only 4.8% treated with placebo. This gave an odds ratio of 5.3, for remaining a nonsmoker at 12 weeks after -- at 24 weeks after 12 weeks cytisinicline treatment. Both the primary and secondary endpoints were highly statistically significant in favor of cytisinicline treatment for smoking cessation. This next slide represents the primary and secondary endpoint results for 6 weeks of cytisinicline compared to placebo. After 6 weeks of cytisinicline, 25.3% of smokers had quit smoking, compared to only 4.4% of smokers treated with placebo. This resulted in an odd ratio of 8, meaning that those smokers treated with cytisinicline had 8x the odds or likelihood of quitting smoking, compared to smokers treated with placebo. For the secondary endpoint at 24 weeks, 8.9% treated with cytisinicline or nonsmokers, compared to only 2.6% treated with placebo. This gave an odds ratio of 3.7 for remaining a nonsmoker at 24 weeks after 6 weeks' cytisinicline treatment. Both the primary and secondary endpoints were highly statistically significant in favor of cytisinicline treatment for smoking cessation. Turning to the top line safety and adverse events reported in ORCA-2, the frequency of treatment emergent adverse events was similar in all 3 arms. We continue to see that cytisinicline is very well tolerated with the incidents of specific adverse events in the single digits. The most common adverse events occurring in 5% or more of study participants were insomnia, abnormal dreams, headaches and nausea. However, the frequency of nausea and headaches were higher in the placebo arm than in the cytisinicline treated arms. And the frequency of insomnia or abnormal dreams was only slightly higher in the cytisinicline treated arms compared to placebo. We expect that tolerability will remain a critical point of differentiation from currently available treatments. We would like to thank the investigators, healthcare providers and subjects, whose commitment and efforts to ORCA-2 made this trial a success even during the pandemic. That concludes the overall view of the ORCA-2 top line results. We look forward to submitting these data for publication, and we'll keep you posted on further updates in that regard.

Thanks, Cindy. We are very excited about the strength of the ORCA-2 results and the magnitude of effect seen with cytisinicline throughout the ORCA program. We continue to see strong efficacy, particularly when we consider the odds ratios that have been reported for available cessation treatments. Both the 6-week and 12-week treatment arms of ORCA-2 exceeded what was previously reported for cytisinicline in the Cochrane Review, proving our hypothesis that a higher dose given for a longer duration has improved outcomes for smokers. As we look to the path ahead, our primary focus will be on enrollment and execution of the confirmatory Phase III ORCA-3 trial, while in parallel, initiating the Phase II ORCA-V1 trial in e-cigarette users, pending final NIH grant approval. Similar in design to the ORCA-2 trial, ORCA-3 participants will be randomized to 1 of 3 study arms to evaluate 3-milligram cytisinicline, dosed 3 times daily over a period of either 6 or 12 weeks compared to placebo. ORCA-3, which we initiated in January of this year, aims to enroll 750 smokers at 15 clinical sites in the U.S. We look forward to providing you additional updates on the ORCA-3 and ORCA-V1 trials as we progress through this year. We continue to believe in the strong potential of cytisinicline to be an important new treatment option to help smokers and possibly electronic cigarette users achieve their cessation goals. There is still more than 34 million smokers in the U.S. alone, who have not been offered a new FDA-approved treatment in nearly 2 decades, and there remains more than 1 billion smokers globally. Additionally, the growing number of e-cigarette users exceeds a 11 million adults in the U.S., and there are no currently approved treatment options specifically indicated for this population. The nicotine addiction market continues to be significantly underserved and in need of new, safe and effective treatment alternatives. We believe that cytisinicline's differentiated safety profile, shorter course of treatment, and compelling efficacy, positions us well to make a significant impact in this large market. Closing out, we are pleased to announce that in connection with the positive ORCA-2 results, we have received approval from Silicon Valley Bank to access the remaining capital under our $25 million debt facility put in place in December 2021. Under the agreement, we now have access to an incremental $10 million of capital that can be drawn down at our discretion over the course of the next 12 months. We are thrilled to continue to have the support of SVB, as we continue to drive forward the cytisinicline program. Additional details of the facility can be found in the 8-K filed today. That concludes our prepared remarks. We will now open the line for questions. Sheri?

[Operator Instructions] Our first question comes from Thomas Flaten with Lake Street.

Congrats guys on the excellent data. I don't know if Dr. Rigotti has joined, but I would be curious just to hear from her, if you take into account the totality of the data that you've generated to date with cytisinicline, just what would be the clinical pitch for cytisinicline versus CHANTIX given what we know with the data that you guys released today?

So I'm not a marketer, I'm an academic, but I would say that if I were to evaluate the 2, it is that cytisine has -- looks to be similar in efficacy and has a better side effect profile. And in addition to the issue of side effect profile, the other problem with varenicline, which is otherwise our best single agent available, and I'm no way meaning to disrespect it, is that the name is called CHANTIX, and an awful lot of people just don't want to use a medicine called CHANTIX. So having another medicine that has a similar efficacy and even better tolerability will be positive. The other issue that we've had with varenicline in the last 6 months or so is that there was a recall of the product, and it became difficult to get. And so I know that clinicians were frustrated, because they weren't -- they didn't have availability of the drug that they often wanted to use. The bottom line is what we need is more medication, more options for our patients. And I'm extremely excited that the trial has turned out so well, because this could be an option for the future, but obviously, it has to be FDA approved.

Great. I appreciate that. And then, John, from a regulatory strategy perspective, do you think the data that you have in hand now is sufficient to have a chat with FDA about maybe circumventing the need to finish the second Phase III before you submit an NDA to FDA? Or how are you thinking about regulatory strategy at this point?

Yes. Let me hand that one over to Cindy to talk a little bit about the regulatory strategies.

Yes. We've had a number of conversations with FDA. And the reason that they are insisting on 2 phase III trials is really more for gaining safe enough numbers of subjects that have been treated with 3 milligrams 3 times a day for a safety profile. So it's not only showing efficacy in 2 well-controlled Phase III trials, but it's also having enough safety information in the profile for approval. So yes, we'll definitely use this good data to maybe look at how we can get submitted faster, rolling submission in those type of benefits in an NDA, but we're still committed to completing the ORCA-3 trial.

Our next question will come from Francois Brisebois with Oppenheimer.

Just to touch on the prior question. In terms of the efficacy being similar to CHANTIX with better safety, can you just remind us maybe what's the most reasonable cross comparison, although dangerous, but the most reasonable cross comparison in terms of odds ratios, and doesn't it seem that this could potentially be seen as superior in terms of efficacy?

Yes. Good question, Frank. And I think this is one that's always a bit dangerous to compare across trials. I think typically, how we look at that is looking at odds ratios that really just looks at the effect over baseline or placebo to get a handle on how the drugs can compare to each other, knowing that there's differences in demographics, times the trials were run, things like that. So I think that when we look across the board, you look at nicotine replacement therapy and Bupropion, those both have odds ratios a bit less than 2%. CHANTIX, what we've seen historically and again reported from the Cochrane Group has been just under 3 over the course of its life cycle. I think what we're seeing here in the ORCA program so far, I think, does have a trend line that it could have more compelling efficacy. Obviously, something that we would have to tease out over time, but I think it's very encouraging in terms of the efficacy. And I think when you look at, at least the most recent CHANTIX trial, the EAGLE study that they ran to remove the black box warning, even looking at quit rates there, for the U.S. patients that was reported, they had a quit rate at 6 months of 16%. And then in the comparable arm in ORCA-2, the 12-week arm, we saw 21% abstinence at the end of 6 months. So again, we feel pretty good that efficacy is in the right zone for this market.

Okay. Great. And is this something that maybe down the road, maybe post approval, this data today give you confidence that maybe a -- basically a AURORA that actually goes to completion, head-to-head with CHANTIX might be a good call on the marketing side? Or is this still more of a question of, look, maybe just based on the safety that in the real world, compliance to a medication could actually just lead to better efficacy?

Yes. I think commercially, we don't think a head-to-head trial is required. And I think, obviously, having data showing that we were better than all other agents would be supportive for sure. But I think when you look at the market today, actually, the most utilized product is nicotine replacement therapy, which happens to have lower efficacy than what we see with CHANTIX. So it's a little bit counterintuitive. And again, Nancy walked through some of the reasons why CHANTIX isn't used more. But we think, again, another treatment option really will drive additional usage and we think the product profile we have with cytisinicline will resonate here.

Okay. Great. And then just -- sorry, if I could sneak in a last one. In terms of the thoughts for -- now that the market is going generic, thoughts about potential step edits here or should you not -- maybe not expect step edits if the safety seems better?

Yes. So right now, what we've seen in the current market is very limited, if at all, step edits with respect to existing treatments. And CHANTIX before went generic last year was up to 10x more expensive than some of the other agents. Based on our discussions with payers, as long as we're not pricing this excessively high, we believe there would be minimal step edits put in place, and that's exactly what we want. We want this product to be widely accessible at the time of launch.

Our next question will come from John Vandermosten with Zacks.

Nice results there. When we look at the 2 different durations of treatment, the 6 weeks and the 12 weeks, is one of them indisputably better than the other? I mean I know one has a higher odds ratio, but how would that be examined by payers and by physicians when they're trying to decide between the two.

I think actually, we are pleased that both are so well tolerated and also give such good efficacy results. Because it's that flexibility of treatment that we're after. So a smoker and their physician can look at, well, let me try 6 weeks. And if I have stopped smoking by that 6-week treatment, then I don't need to have another 6 weeks. If however, I'm still having difficulty from quitting smoking, then I may need that additional 6 weeks then to quit smoking. So it's really that flexibility that can be fine-tuned for the smoker with their physician on how long it takes them to quit smoking on treatment.

And keep in mind, John, that the rates are not apples-to-apples here. When you look at the 6-week treatment arm out at the 6-month time point, that's a 5.5-month continuous abstinence rate, compared to the 12-week arm that's only 4 months. So they're not exactly calculating the same levels there.

I think one other things to appreciate is just how rigid the successful quitter had to be, because you started treatment, and you had to commit to trying to stop smoking after 7 days of treatment. And then for the 6-week treatment, basically, you only had one week of grace. And then you were counted as you had to be nonsmoking in during week 3, 4, 5 and 6, and you couldn't even have one cigarette to be a successful quitter in these analyses. So it was pretty rigid. So you were really looking at those smokers, who are very committed and successful at immediately quitting smoking, basically only after 2 weeks of treatment.

Okay. And then we're going to see, I guess, at a later time, the 6-month quit rate as we follow up with everyone?

That was included.

That was included.

That's the secondary endpoints. Yes.

Okay. Right, right. And then on the AEs, it looked like generally, the treatment arm was better. But I think with CHANTIX, it was a little bit worse for the treatment arm. I just can't remember that data. Can you recall it for me?

Yes. And I think the big differentiator with CHANTIX is about a 28% rate in the label of nausea and vomiting that's been reported. There are other double-digit rates that include insomnia, abnormal dreams and nightmares and headaches. So...

And those were materially above the placebo group?

They were above, yes, in the double digits compared to placebo, which didn't see those...

Yes. Great. Great. Okay. And then just last one for me. Great data here. If you were running an adaptive trial, what would you modify to make it a little bit better if you could, based on the data that we got today?

Well, I think seeing statistical significance like we did with so many zeros. I think we probably wouldn't change anything. I think we're pretty happy with the results of the trial for ORCA-2.

Our next question comes from Michael Higgins with Ladenburg Thalmann.

Congrats guys, really impressive data. I think you're right to be pleased with it. A couple of questions here, if I could. Just a follow-up on the last one as well on ORCA-3. Any conduct or design differences between ORCA-2 and ORCA-3, site differences? And can you give us an update on the enrollment?

Sure for ORCA-3, we are using U.S. sites only, but different sites. So they are different sites from the ORCA-2 sites. And we've opened up the inclusion exclusion criteria a bit, loosened the criteria as far as past psychiatric history. And it will be interesting, because, frankly, ORCA-3 as we are hoping is being run not in a pandemic, where ORCA-2 was really run in the midst of a pandemic. So we hopefully will find that ORCA-3 will be at a time that it won't be so stressful to maybe quit smoking or to remain a non-smoker, once you quit.

That's helpful. Just to follow up on the past psych history. How would it be a different year in the ORCA-3 trial?

Can you repeat that?

Sure. In ORCA-3, it sounds like there are past psychiatric history is a bit different in the inclusion exclusion criteria. How is it different than ORCA-2?

So ORCA-2, we were pretty restrictive as far as any past psychiatric history. We've loosened that up in ORCA-3 that you can have a past history. You obviously can't have a current bipolar or psychiatric symptoms at the time of the study, but just loosening that up that you could have a past medical history of that.

Okay. That's super helpful. John, a question or 2 for you. the results here impact your plans and execution on partnering. These are really impressive, I really like the odds ratio slides, especially compared to CHANTIX and others. Does that do anything for you here in partnering?

Yes. I think what we've been saying here recently is that the ORCA-2 results are going to help further the discussions that have been ongoing. Now we have one of the 2 Phase III trials in hand, I think it will help read on likelihood of outcomes on ORCA-3, especially given the statistical significance we saw in ORCA-2. So yes, we'll be pounding the pavement with this and reengaging with folks on the partnering front.

Just a follow-up to that, remind us again on the European outlook from both the regulatory, the conduct of the study. Eastern Europe is never a real big market opportunity for us, but to Western Europe, I would think you would have that, but if you can just get into that before?

Yes. So our focus, first and foremost, is on the U.S. market. If we look historically at CHANTIX sales, about 75% of their global sales were coming from the U.S. So this is where we want to start. But once we move forward with the U.S., we clearly want to take this drug rest of world, Europe being one of those key markets. We have had interactions with regulators in the EU that are supportive of our current development plan, that it would be sufficient for registration in Europe. And so we feel pretty good again about the package that we're developing to take that rest of world.

Just a very brief follow-up to that. It sounds like you're saying, you would need to run a European study or patients and sites and so forth to be able to file. You think with ORCA-2 and 3 and on and so forth, you could file?

That's our belief, correct.

Okay. And then just one last brief one here. Timing and venue for additional details you gave us quite a bit today, but maybe SRNT in September?

Yes. We will be looking at presenting at that meeting and Dr. Rigotti is on the phone, and I'm sure she is going to be taking up and drafting that publication as soon as we're off the phone.

Yes. This has already begun. So I'm waiting to see the full analysis as well. These are top line results. So we -- it's not that I think there's going to be a problem, but -- there's more -- a little more analysis to be done and discussed, but we're eager to get this out.

Our next question will come from Chen Lin with Lin Asset Management.

Congratulations for the results. And most of my question actually have been answered. I'm just curious on what's -- can you repeat to us what's the timing for ORCA-3, when will you [indiscernible] expect you get the final Phase III results out? And also you think about potential FDA approval time line.

Sure. Thanks, Chen. Yes. So as we mentioned, we are in the midst of enrollment on ORCA-3. That -- we'll have further updates in terms of the timing of enrollment there. But I think early second half of the year, Q3, something in that neighborhood. We feel pretty good about getting enrollment wrapped up, which should put us in a position to have top line results sometime in the first half of next year. And once we have that in hand, that should be the final piece, at least clinically, to move things forward to an NDA here in the U.S. in the back half of '23.

Our next question will come from Jim Molloy with Alliance Global.

Congrats on the outstanding results. Just a quick question for Dr. Rigotti. I know it's early yet and just look at the top line data. Anything jump out at you on the data that you found sort of surprise or even the positive or negative side?

I was surprised at how positive it was, not surprised, but I was pleasantly surprised, I guess. Otherwise, no, I mean, it's -- you couldn't imagine something better than this, really.

Certainly, yes, it looks outstanding. What are your thoughts on the AEs, those sort of in line with your expectations?

Well, we were one of the sites, and so we enrolled 45 of these subjects. And our experience anecdotally was that this was very well-tolerated medication. Nobody had much trouble and especially nobody had much nausea, which has been the main issue that has troubled varenicline. We also didn't see much in the way of people being troubled by having abnormal dreams that troubled them. And so it was extremely well tolerated by our patients. So that's very positive, I think. And I can say that, I've had conversations with colleagues, who work in the smoking cessation area as well as other colleagues, who are primary care docs like myself. And people are really looking for another -- a new option, because there hasn't been one. And most of our patients have tried what's out there. And so I think that the idea of having something new will be -- that's well tolerated will be very well received. I think the 2 things that -- the thing that was most satisfying to me was that, this was a new -- a new dosage administration or a new way of giving the medication. Because the previous trials that have been done with this drug have been done with that kind of crazy 25 days downward titration, which is not how every other smoking cessation medicine is given. And the fact that it did so well and it was very encouraging, because the actual quit rates in some of the earlier trials with cytisinicline were not as high as what we're seeing here.

Outstanding. Thank you for that. The new dosing certainly seems superior to the old titration. Maybe a quick question for John then. I know we touched on -- it was touched on briefly earlier. How would you characterize potential partnership discussions given this data? I know you just got it. I'd be even very clear that before a U.S. partner to launch this. Would there be a way to characterize how this data helps that effort?

Yes. I mean I think we're excited about the strength of the data. And I mean I think there is -- could have been a lot of nuance perhaps, just in different scenarios of how the trial could have read out. But frankly, we hit it on all cylinders. We've got both a 6-week and a 12-week treatment arm that both are working quite well and a clean safety profile. So yes, I think we're encouraged to take this back out and start to actively engage with potential partners with the data in hand.

Our next question will come from John Fichthorn with Dialectic Capital.

Great results. So let me just make sure I've got this right. So ORCA-3 timing is, it will be completed kind of end of this year, early next year, read out kind of a year from today, and then NDA and hopefully, FDA approval before the end of next year. Is that -- did I hear that right?

NDA submission by the end of next year. Obviously, FDA will have to review all the results and the information. So we are hoping that FDA approval would be in 2024.

Okay. And are you fully financed to get through that -- the ORCA-3 and that submission?

Yes. I think what we have on hand, we announced we had $43 million of cash on the balance sheet at the end of last year. We now have access to another $10 million today based on the positive trial results through Silicon Valley Bank. We think that combination gets us through the remaining development. Obviously, more runway on the back end would be helpful. But at the moment, we've got multiple data events still in front of us with our runway.

Great. And if the FDA is so hung up on safety, which is why they wouldn't consider some kind of early approval, and I guess that's because of the disaster they suffered with CHANTIX, which seems like an odd reaction function of, I've got a drug that's not safe in the market. So let's not approve one that is safe to go on the market. But is there any indication anywhere that shows that this doesn't achieve safety either from European data or any of the studies that have been done anywhere that would lead them to have that fear?

No, no, not at all. And I think it's just more of a numbers game, because remember, we did increase the dose and changed the regimen. So for these Phase III studies, there will be about 500 subjects that will have been given 3 milligrams 3 times a day for 12 weeks, which is not a lot of safety data, but certainly enough that FDA is looking for an approval. So they really have given us some leeway here on safety. But having both Phase III trials completed does nail it as far as their criteria and what they want. We will be having discussions with them, because of how well and how positive the data are. I think there are ways that FDA might be able to help us like a rolling NDA submission, various things like that, that will help make that NDA submission and review time smoother. And so we're hopeful that with this excellent data, that's kind of the helpful playing cards that maybe we'll ask for.

Right. You think they'd want to stop people from killing themselves of cigarettes with the cure since that seems to be the alternative. So what about timing and financing for the Vaping trial now that you've got these results. What does that look like?

Yes. So we'll have further updates on that. We're in the midst of logistics with the NIH to get the additional funding to run the trial. We were awarded the full grant, but it's broken up into pieces. So we'll have further updates as we work our way through that process. Ideally, we'd like to get that trial up and running by the end of this quarter, but we need the NIH to cooperate to hit that.

Great. And so, I don't know, maybe that starts, assuming they cooperate, what does the timing look like? Like just give me a best case scenario just for the sake of throwing it out there.

Sure. Yes. So if we're able to get the trial up and running here by the end of the second quarter, this is a shorter duration trial compared to ORCA-2. So it should put us in a position to have top line results first half of next year again.

Great. Great. That would be great. And I don't know, I guess, my last question is your stock doesn't, shockingly, although it's premarket, seem to care that much, right, which is a little bit of a shock to anybody, who is sitting here owning and hoping that we get results that were not even as good as the results you actually posted. It seems to me like it would create a situation where you might get approached by a strategic or someone to come in and try and scoop up the company, given the results are so positive and how much data there is around this, and it looks like an inevitability now that you guys, knock on wood, would get to the finish line. I mean, what are your thoughts in terms of how you view the opportunity here? Would you take unsolicited bids? Would you enter into discussions with strategics at this point? Just kind of curious what your thoughts are if the stock price stays so low.

Yes. I mean, I think we'll have to take everything into consideration. I think we'll do what's in the best interest of shareholders and push this forward in good stead. I think we need to take the results that we have, get back out in front of kind of the likely suspects that we think this would be a good product in their pipeline and further those discussions. Yes. I think it's still early days. I think hopefully, we see a little bit more cooperation in the market to drive the valuation up, because we think a sub-$100 million market cap with a potential $1 billion indication here, there's quite a bit of a mismatch still in the market.

One would think. Thank you very much. Good luck. Great results.

We have a follow-up question from Thomas Flaten with Lake Street.

I just wanted to get ahead of a potential question that we might see here. The insomnia and abnormal dreams rates were consistent with ORCA-1. But I think one of the things that stood out in the AURORA study was the statistical significance relative to CHANTIX, but also just the numerical value. Is this just a case of mixing and matching data sets? Or do you have any thoughts on that? I'm just worried that, that might be a question that comes up, given how significant the results were in AURORA or with respect to those 2 AEs.

Yes. I mean I think overall, like we would trust the results here from ORCA-2 more than what we've seen in investigator-led trials. This had robust safety reporting across the board. So I think what we've seen here, we feel pretty comfortable with. Cindy?

Yes. Remember, the AURORA trial had the 25, the downward titration regimen, and then they had maintenance that was just out to 12 weeks. It also wasn't a double-blinded trial. So there's a lot of differences there to make it very hard to compare.

And we do have a follow-up question from Michael Higgins with Ladenburg Thalmann.

Just a follow-up from Jim's question earlier for a dialogue with Nancy. Dr. Rigotti, great to hear your voice again. Thanks for being on the call. Just trying to get your experience here before you go out and see patients this morning. If there's any 6-week data from CHANTIX and how this data here this morning compared to any early evidence, what I was looking for differences from NRTs and CHANTIX?

So are you -- let me make sure I understand your question. Are you asking how we would think about which drug to recommend to patients? Is that what you're asking?

Yes. I guess looking for early evidence of efficacy. If you look at any indication, you've got something that can work a little bit faster than otherwise. How impactful that may be from a marketing side will have -- will be determined in the future, but just curious, as I look at the CHANTIX data, I don't know that they have anything at 6 weeks, but looking through insights there.

Yes. I don't think that they have -- they did any trials that were only 6 weeks in length, although you could look at the point prevalence of each -- at each week and see how that would go. My sense about this is, if you look at the data that we have, the [indiscernible] better if you take it longer, you got higher quit rates in the 12-week group, even at 6 months, if you took it for a longer period of time. And my guess when we look at the point prevalence each week, which I haven't seen yet. I think that we'll see that the people continue to quit over time, so that it's not like some of the older drugs where the maximum effect is right after you start the medication and then people just start to relapse after that. But what we've seen with varenicline and since this has a similar mechanism of action, we would expect the same here is that probably over time, there will be more and more people who will be quitting up to a point. And then -- so I think that if I were -- if I had a patient in front of me and this was an FDA-approved drug, and I had a choice of 6 or 12 weeks, I would probably plan on 12 weeks, but see the patient sooner and see how they're doing. I'm not sure I would stop it prematurely. I don't think I'd necessarily go with 6 weeks, although certainly, patients and payers always like to have shorter courses and cheaper courses.

And we have a follow-up question from John Vandermosten with Zacks.

Might there be opportunity to use real-world evidence here for the safety side? I mean, I know that's been used. I don't know how much of a difference that's made in past submissions. But do you think that might be a possibility here, especially since there's all the real-world evidence for this compared to a lot of other drugs?

Well, I think the real world evidence is on that 25-day regimen. So in that regard, it's not helpful. However, when you have millions of individuals that have had cytisine, that gives you a feeling that there isn't a problem with like suicide, other kind of those -- the adverse events or the problems that you would see in a larger worldwide experience. So that gives you that feeling of comfort in that regard. So that's helpful. But for FDA, no, they really want to see the detailed laboratory, safety data, the vital signs, all of the very specific safety parameters that they look at for approval.

Okay. Yes, that's helpful. And then just one last thing. Does this qualify for expedited treatment in any way? I mean, because if you read the definitions of what should qualify, I think, life-threatening disease or something, where there's a material or better treatment. It seems if you looked at that in a certain way, you could actually qualify for some of those. And John, I think you mentioned, it will close your work with the FDA. I mean, is that something you've looked at, that might be possible?

We will explore all those options with FDA given this data.

Okay. Yes. I mean you can look at it in a way where it seems to qualify, because smoking kills you. So it's life-threatening.

I'm showing no further questions in the queue at this time. I will now turn the call back over to Mr. John Bencich for any further remarks.

Thanks, Sheri. I want to thank everyone again for joining us as we cleared the significant milestone for the company today with positive ORCA-2 results. We look forward to continuing to providing you additional updates as we move forward and appreciate all the continued support. Thank you all.

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