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

Greetings, and welcome to the Achieve Life Sciences ORCA-V1 Top Line Clinical Trial Results Conference Call. [Operator Instructions] As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Jaime Xinos, Executive Vice President of Achieve. Please go ahead.

Thank you, operator, and thank you to everyone for joining the call. Today from achieve, we have John Bencich, Chief Executive Officer; Dr. Cindy Jacobs, President and Chief Medical Officer; and Rick Stewart, Achieve Co-Founder and Chairman of the Board of Directors. 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 will now turn the call over to John.

Thank you, Jaime, and thanks, everyone, for joining us today. Earlier today, we announced positive top line results from our groundbreaking Phase II ORCA-V1 clinical trial, the first-ever randomized placebo-controlled trial for vaping cessation. Cytisinicline treatment resulted in a statistically significant benefit for nicotine e-cigarette cessations compared to placebo. Results for the primary endpoint showed that study participants who received cytisinicline were approximately 3x more likely to quit vaping compared to those who received placebo. The exceptional safety and tolerability profile of cytisinicline was again seen in this trial. Cytisinicline was very well tolerated with no serious adverse events reported. We are extremely encouraged by these results as this study confirms our belief that cytisinicline has the potential for broad utilization in the treatment of nicotine dependence. The majority of participants in ORCA-V1 were former smokers who utilized e-cigarettes as the tool for smoking cessation and now wanted to quit their nicotine/vaping dependence altogether. ORCA-V1 was conducted at 5 clinical trial locations in the U.S. Dr. Nancy Rigotti, Professor of Medicine at Harvard Medical School and the Director of the Tobacco Research and Treatment Center at Massachusetts General Hospital, served as the primary investigator for the study. The trial was initiated in June 2022 and completed enrollment in roughly 4 months, with 160 participants randomized to the study. The final subject received their last dose in February of this year, and today, we are sharing the top line findings. With that, I will turn the call over to Cindy to provide an overview of the results.

Thanks, John. The ORCA-V1 study was designed to evaluate the safety and efficacy of 3 milligram cytisinicline dosed 3 times daily for 12 weeks. The dosing and administration is identical to that being used in the 2 Phase III registrational trials for smoking cessation. ORCA-V1 randomized subjects in a 2:1 ratio, such that a total of 160 subjects were randomized, with 107 receiving cytisinicline for 12 weeks and 53 receiving placebo. The average age of ORCA-V1 subjects was 34, and approximately half of the participants had previously tried to quit vaping by self-attempt methods. Subjects were stratified based on past smoking history, with 72% identifying as former or past smokers. To be included in the study, subjects were required to be daily users of nicotine e-cigarettes only and could not be currently smoking cigarettes. This was intentional in order to closely monitor that past smokers do not revert back to smoking combustible cigarettes while reducing or stopping their vaping. Smoking combustible cigarettes was considered a safety issue for increasing harm despite having stopped vaping. As such, we utilized both expired carbon monoxide levels and cotinine, a metabolite of nicotine, as methods of biochemical verification for any nicotine use. Carbon monoxide monitored for smoking, and cotinine monitored for any vaping or other nicotine use. For the 12 weeks treatment duration, participants were required to attend weekly clinic visits where they received behavioral support counseling to help quit vaping and were tested for both smoking and vaping [indiscernible]. The primary endpoint of the study was e-cigarette or vaping cessation, which was measured as biochemically verified vaping absence during the last 4 weeks of treatment. The primary endpoint results for vaping cessation showed subjects who received cytisinicline had 2.6x higher odds or likelihood to quit vaping during the last 4 weeks of treatment compared to subjects who received placebo. This endpoint was statistically significant with a p-value of 0.035. Four-week continuous vaping cessation rate during weeks 9 through 12 was 31.8% for cytisinicline-treated subjects compared to 15.1% for those who received placebo. Additionally, a benefit of -- in favor of cytisinicline was consistently seen -- observed across the various secondary endpoints. Importantly, cytisinicline benefit was also observed across clinical trial sites and demographics, such as participant age, gender, race or whether they had been past smokers or not. We also did not see increased carbon monoxide, indicating subjects did not regress to smoking behavior. Overall, cytisinicline was very well tolerated, and no serious adverse events were reported. Similar rates of adverse events or AEs were observed between treatment arms. The placebo arm had a slightly higher rate with 54.7% of subjects reporting at least 1 AE compared to 50.9% of subjects treated with cytisinicline reporting an AE. Cytisinicline-treated subjects had slightly more sleep disturbances than placebo subjects in this trial. Similar to previous studies, we saw higher rates of headache and nausea in the placebo arm compared to cytisinicline arm. Overall, we are very pleased with the safety and efficacy results observed in this pilot study, and to have achieved statistical significance in this pilot Phase II study is truly remarkable. The results of ORCA-V1 provided us with the data needed to plan for future clinical development of cytisinicline for e-cigarette cessation. We will continue to analyze the results and look forward to providing additional details on our findings as we learn more and have an opportunity to share additional data points. I will now turn the call back over to John.

Thanks, Cindy. In the U.S. alone, there are more than 9 million adults and over 2 million high school students who use e-cigarettes to vape nicotine. We believe the swift enrollment of this trial and the lower age of participants supports the need and interest of a younger audience to take control of their nicotine dependence. There are currently no medications specifically approved for the treatment of e-cigarette cessation, representing a unique opportunity for cytisinicline to make a meaningful impact in the lives of millions. We would like to extend our appreciation to the ORCA-V1 participants, our clinical sites and to NIDA and the NIH for providing grant support to fund this important trial. This study provides a road map to future clinical development and paves the way for cytisinicline to potentially become the first product available for vaping cessation. As we look ahead, we expect to report top line results from the second Phase III trial of cytisinicline for smoking cessation in the coming months. The ORCA-3 trial randomized 792 subjects across 20 clinical trial locations in the U.S. and mirrors our previous Phase III ORCA-2 study in evaluating efficacy and tolerability of 3 milligram cytisinicline dosed 3 times daily for either 6 or 12 weeks compared with placebo. The ORCA-3 trial aims to replicate the positive results observed in the ORCA-2 trial, which continue to be well received and have been submitted for publication. Like many of you, we have faith in the potential of our product to make a significant impact in the lives of those who are struggling with nicotine dependence and searching for alternative solutions to help them quit cigarettes and now vapes. With the potential to positively transform the lives of millions, we remain committed to advancing our mission. Thank you for joining us today, and we'd now like to open the line for questions.

[Operator Instructions] Our first question today is from Thomas Flaten of Lake Street.

Congrats, everyone, on the data. Cindy, I don't want to read too much between the lines, but you mentioned pilot study and achieving statistical significance. Is it fair to assume that this exceeded your expectations from an efficacy perspective?

Well, yes, because in a pilot Phase II study, it's really not a large enough study that you expect to see statistical significance. So we were really pleased that with the primary endpoint, we actually did see statistical significance.

Excellent. John, I was wondering if you could comment maybe or Cindy, for that matter, on how you plan based on having the data on -- or in hand now, what you might be thinking about from an FDA discussion perspective when you do submit the NDA for cytisinicline for smoking cessation. Are you planning on bringing it up with them? Or could you give us some color on your thoughts there?

So we planned on incorporating the V1 data, especially the safety data in the NDA. The NDA is going to be focused on approval for smoking cessation. So although we will present it as supportive data, it will not really be part of the efficacy for this NDA submission and approval. But yes, we will have further discussions independently on having smoking -- after having smoking cessation market approval that we would go for a label expansion for vaping cessation. So it will be in the discussions but not specifically part of the NDA. We need to get approval for smoking cessation first.

Great. And then just one final one for me. Obviously, vaping, e-cigarette use kind of dominates the media narrative relative to traditional smoking. I was curious if you have any plans for more mass media outreach with this data or how you plan on communicating that to the -- to a much broader audience than perhaps the investors that are gathered here today.

Yes. We are doing a broader outreach in terms of media. This is obviously probably a more topical category than smoking has been as of late. So we do think this is important news that should be more broadly disseminated.

The next question is from François Brisebois of Oppenheimer.

I was just wondering if you can put the odds ratio -- the 2.6 odds ratio a little more into context. And just as you answer, maybe discuss a little bit the placebo rate that was seen here versus what you had seen with smoking cessation and like ORCA-2.

Yes. So the placebo rate for this pilot Phase II was a little higher. It was not totally unexpected. But we believe it's due to the subjects in ORCA-V1. They really haven't -- half of them hadn't tried to quit before, and half of them had. This is a very different population than what is in the smoking cessation trials, where those subjects had tried a median of like 5, 6x, had failed. So they're more refractory to their attempts in quitting. So this population is less refractory, younger. So the placebo effect is going to be a little higher. This is also similar to what was seen 2 decades ago when the smoking cessation trial started. Those placebo rates were about 11% to 15% as well.

Understood. And then in terms of the read-through to ORCA-3 that's still expected to read out here very soon, is it fair to say this is mostly probably a read-through on the safety side?

The readthrough for ORCA-V1 you're talking about? Sorry.

Sorry, for ORCA-3, just the read-through to smoking cessation. Obviously, it's quite different. But on the safety side, if you're thinking of showing this as part of the NDA, I assume this is just incremental data that they can have a read-through for the safety side.

Yes. So any -- the more we have as far as our safety population that have received 3 milligrams cytisinicline 3 times a day for 12 weeks, we then gather all of what we have so that FDA has a larger safety database that we can supply to them.

Great. And then just a last -- maybe 2-part question. In terms of the secondary endpoints, when will you -- do you intend to give more granularity and details around what those were and the efficacy seen? And then finally, if you wanted to go with a label expansion into vaping, would that maybe require more trials? Or is it too early to tell at this point?

So for your first question, Dr. Nancy Rigotti will be looking at when to present these results at -- as soon, next conference as well as publicly presenting the data and in publication. So she'll be looking to submit a manuscript. So time line for that will be given at a later time frame for more detailed data. For label expansion, this pilot study definitely supports our view that in discussions with FDA that we would only need to do one Phase III study to look at vaping cessation for a label expansion.

Excellent. Congrats again.

The next question is from Michael Higgins of Ladenburg Thalmann.

Congrats on the great data, really impressive. Question for you on what we may be able to find here this morning. I realize you have to dig through the secondaries. But you posted data here, obviously, at the end of the study ended 12 weeks. Just curious if there's any statistical benefit seen earlier than that.

Yes. I think on the secondary endpoints, Michael, we did see a benefit in favor of cytisinicline across the secondary endpoints. I think if you go to ClinicalTrials.gov, you can see that there was quite an extensive list of secondary endpoints unlike a Phase III trial where you may have one critical secondary endpoint like we had in ORCA-2 and have an ORCA-3. So there's a number of data points, and we look forward to sharing those additional data with everyone at a future medical conference.

Okay. Fair enough. Cindy, can you help us on the cytisinicline-specific adverse events here in V1 versus prior ORCA studies, anything unique about the adverse events that are related more so to the patients here versus prior patients?

So it was a younger population in the V1 study. So that's probably why we had absolutely no serious adverse events. That's one difference obviously in this. ORCA-2, you have a population that's meeting ages in the mid-50s. So although they had serious adverse events, none were related to the study treatment. This population had absolutely no serious adverse events reported at all. Otherwise, the rates were pretty similar and no surprises. Again, we're seeing a little more of sleep disturbances of cytisinicline-treated subjects and more nausea and headache in the placebo group. So a lot of it was very similarly what we have seen and others have seen in the trials with cytisinicline.

Okay. That's helpful. And then lastly, going forward, you mentioned one Phase III required. I would assume it'd be very similar to this. Would the plan B postlabel expansion to then go test in dual users, is that anything that you ever look to study in?

Well, the Phase III would be similar to the Phase II. That's why we did it in looking at people who are vaping only just so we can again monitor and make sure that you're not pushing somebody and reducing the nicotine/vaping in back into smoking combustible cigarettes. So that -- our Phase III trial would be similar in that population. Obviously, if you have a product that helps in smoking cessation and vaping cessation, then that's where then the market covers the dual users for helping dual users stop their nicotine dependence.

I see. So the longer-term plan would not be to test the combination of dual users but to have the indication and keep separately. Is that what I'm hearing?

Right, the indication would be more for a broader nicotine dependence. Being nicotine dependent, so whether you're dependent on nicotine with smoking or vaping or both, we would be covering all the population.

Makes sense. Appreciate it. Congrats again guys.

There are no additional questions at this time. I'd like to turn the call back to John Bencich for closing remarks.

Great. Thanks, operator, and thanks, everyone, for joining us today. Absolutely thrilled to be presenting positive ORCA-V1 trial results this morning, the first ever trial to read out in this setting. We really appreciate the continued support and look forward to providing additional details as we move ahead.

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