Good evening, everyone, and welcome to the Jefferies Global Healthcare Conference. My name is Arjun with the Jefferies Investment Banking Team, and it is my great pleasure to introduce Richard Stewart, CEO of Achieve Life Sciences.
Thank you very much, and thank you for staying late today. It's my great pleasure to introduce you to Achieve Life Sciences, and we're at a pivotal point in our development. We have several catalysts coming up in the very near future. Without further ado, we have our standard forward-looking statements. I'm sure you've heard this recited many times today, so I won't go into the detail. I think the key here with Achieve is that we're addressing a major public health crisis in the U.S. We're poised to be the solution to the problem of nicotine dependence, and we're building a drug called Cytisinicline into a potential blockbuster for the treatment of nicotine dependence and other comorbidities.
The scale of the addressable market, or addressable patients, is around about 46 million people in the U.S., of which 29 million are current smokers and around about 17 million are vapers. Now, if I'd had this conversation with you last week, that number would have been 11 million vapers. It just shows you how quickly there is an increase in the number of vapers, so an increase of 6 million vapers in the last 24 months. Our intention is to have cytisinicline as best in class for smoking cessation and first in class for vaping cessation. The importance of our pivotal catalyst is that we are filing an NDA for cytisinicline in nicotine dependence for smoking cessation this month. At the end of this month, the intention is that the NDA will be filed with the FDA.
Our expectation is that we'll have NDA approval mid-2026 and a product launch towards the end of 2026 in anticipation of the New Year's resolutions to stop smoking at the beginning of 2027. Now, this is an important drug because it's the first potential new treatment for nicotine dependence in nearly 20 years, and both physicians and patients currently lack the tools, adequate tools, to be successful in the quitting journey. The drug has conducted two large-scale phase three clinical trials in over 1,600 patients, and it has shown a very differentiated efficacy profile and tolerability profile, with the idea that as part of our launch, we will have a highly targeted, precision-focused launch strategy, predominantly digital, focused on primary care physicians and on the patient. We believe this really has the potential to be the new solution for this nicotine dependence crisis.
Allied to that, of course, is that the comorbidities associated with nicotine dependence include COPD, asthma, and so on. I will address that in a minute. Our goal here is to reframe nicotine dependence as a medical condition. It's currently viewed primarily as a lack of willpower, but in fact, nicotine is the most addictive drug currently out there. Previously, I would have said that nicotine is the third most addictive drug after heroin and cocaine, but I was recently corrected by one of our key opinion leaders who told me that it was the most addictive. It kind of frames that as a medical condition. We also have conducted a phase two clinical trial in vaping cessation, which was highly successful using exactly the same treatment. We'll go on to that in a minute. We have a strong IP estate to support the product going forward.
As we look at this situation in terms of the overall public health crisis, we look at this and we say, okay, in terms of COPD and asthma, 80% of COPD patients have the disease because they either were or are smokers. Out of the 16 million diagnosed COPD patients in the U.S., 6 million are current smokers. Out of the 25 million asthma patients in the U.S., 5 million are current smokers. Cardiovascular, 5 million current smokers out of 32 million. This is an ongoing crisis, and particularly you'll find that in that area of respiratory disease, the standard of care treatments are impaired in the smoking population. We believe that by getting those patients to stop smoking, we'll improve both the efficacy of standard of care and we'll actually slow the overall disease progression.
You can see from the scope of this that combined in those two categories, you've got 11 million smokers out of 29 million. In cardiovascular, you've got 5 million smokers. If you draw a Venn diagram, you'll see that some of these comorbidities are actually combined. We really strongly believe that of the $300 billion annually in cost, we can actually have a major impact, not just on patient welfare, but also in cost reduction. Returning now to vaping, the emerging crisis in vaping is only just becoming evident. Vaping was originally intended to be a smoking cessation tool, and there is validity behind that. However, with the advent of flavors and colorings, the actual underlying role of it has changed fairly dramatically. We're now starting to see the health risk and impact of vaping. You know, 17 million people in the U.S. are currently vaping.
Respiratory disease is one of the emerging risks. Some of you may remember prior to COVID, there was the EVALI crisis with vitamin E acetate that caused some very significant injury to lungs in a much younger population. Beyond that, you've got the impact of CVD. Because this is a much younger population that we're dealing with, there are neurological and cognitive impairments that are becoming in the adolescent and early 20s population, where the brain doesn't reach full maturity until roughly 25 years old. Of course, some vapes actually have toxic substances in them, anything from arsenic to tin to lead. The propellants were never intended to be superheated. Overall, we're just starting to see the impact of health risk in the vaping population. Because they're much younger, in our phase 3 clinical trials, the average age was roughly 55 years.
In our phase two study in vapers, the average age was 33- 35. That's a kind of prime time of life. These patients are now starting to experience wheeziness when they did not have it before, and get kind of allied to this impact on respiratory disease. Just introducing cytisinicline in a bit more detail, we've got the opportunity here to address a high unmet medical need. As I said, current treatments are inadequate. We have a highly differentiated product profile, and we have the flexibility of both a six-week and a 12-week treatment period dosed with 3 milligrams three times daily. It's shown evidence also in relapse prevention in the phase three trials. This is a very large target market, and again, we have a differentiated digital approach to that.
The patient and physician segments are highly defined, and we'll address that in a minute in terms of how is a small company like ours going to approach the market, and were there opportunities for life cycle extension in terms of once-daily oral dosing, other forms of patches, lozenges, et cetera. Again, we view that there's huge opportunity here. Now, just kind of looking forward, the mechanism of action is well defined. What happens with smokers is they have a proliferation of alpha-4 beta-2 receptors, and that is to do with addictive levels of dopamine that are actually produced. What cytisinicline does is to partially block the receptors to the uptake of nicotine, whilst at the same time stimulating the receptors. The dopamine levels slowly start to normalize, typically over a period of between 6 and 12 weeks.
Over a period of time, the dopamine is actually normalized, but along with that is the gene expression starts to be normalized as well. We start to see an impact in terms of IL-5 reduction, IL-6 reduction, and IL-33. There is a whole cascade of genes that are actually normalized over the period of time of quitting. If we compare cytisinicline to other treatments that are currently available, as you'll see here, in the two phase 3 clinical trials, combined total of 1,602 patients, the ORCA-2 and ORCA-3 studies, the measure of success is called an odds ratio, and that is what's the probability of you quitting smoking versus placebo. As you can see here, the odds ratio in the ORCA-2 clinical trial was 5.3. You're 5.3 times more likely to quit on Cytisinicline than placebo. In the ORCA-3, it was 5.8.
Now, on the right-hand side, you'll see here a comparison. This was not a head-to-head trial, but we used the Cochrane database review, and Chantix had an odds ratio of 2.3, bupropion or Zyban at 1.4, and nicotine replacement at 1.4 as well. We're twice as effective as Chantix at quitting, but without the side effect profile that impaired it. More importantly, on this slide, we're looking at the excellent safety profile of cytisinicline, and particularly in the area of nausea and headache. Here you'll see that in fact, cytisinicline was pretty much the same as placebo. The nausea and vomiting was one of the major barriers to Chantix or varenicline. This just demonstrates that Cytisinicline has got an advantage over that drug.
If we expand that side effect profile, on the nausea and vomiting, you'll see that we're roughly five times less in terms of nausea and vomiting. All the other side effects, insomnia, abnormal dreams and nightmares, headache, were half the level of side effects experienced. The question is, why is that? It's really because Cytisinicline is highly specific of the alpha-4 beta-2 receptor versus varenicline, which has got a less specific activity and is actually hitting the 5-HT3 receptor, which is causing the nausea and vomiting, and the alpha-7 receptor causing the sleep disturbances. Let's just look briefly at the journey, the regulatory journey. As I said, we're filing the NDA at the end of this month. We're on the left-hand side there. NDA acceptance is expected within 74 days of submission, standard FDA approval period.
We're looking at an FDA approval towards the middle of 2026. As I said, product launch in the second half of 2026 in anticipation of New Year's resolutions in 2027. On the vaping cessation indication, we'll start the phase three clinical trial in the first half of 2025. The expectation is we'll complete that in the second half of 2026. Looking at the results in a bit more detail of the phase three clinical trials, again, you can see here what we're looking at is the 12-week Cytisinicline treatment, looking at the primary endpoint of quit between weeks nine and 12. We had an odds ratio of 6.3 and 4.4 on the two trials. At the six-week treatment period, we had an odds ratio of eight versus 2.85. People have asked us, why is that 2.85 odds ratio lower than everything else?
The explanation to that is that the ORCA-3 clinical trial was actually conducted on the threshold of COVID. What we saw was there were patients experiencing higher levels of stress than they would otherwise. That is the explanation why that six-week result is somewhat lower. You will see that the ORCA-2 is a much clearer and more consistent approach. Summarizing, we have got robust efficacy at both six and 12 weeks, excellent tolerability. That is borne out by our ongoing open label safety study. FDA asked us to submit 300 patients with six months exposure to the drug and 100 patients with one year's exposure to the drug. We announced a couple of months ago we had hit the 100 patients at one year exposure. We have a large number of patients who are still involved in the clinical trial and are still taking the drug.
It demonstrates excellent tolerability. I think we benefit from the experience of having a longer-term exposure to the drug. Reduction in cravings and urges along with the quit, and that's really important. We have a broad patient response. It isn't just the heavy smokers, right? It is across the spectrum of smokers who experience a positive benefit from the drug. Very briefly, these are the results of the phase two vaping study. It was an odds ratio of 2.65 with a p-value of 0.035. It was a smaller study. We have actually been to FDA. We've got agreement on the design of the phase three. It is a two-arm study, 400 patients on drug, 400 patients on placebo. It is a 12-week only dosing period, primarily driven by the belief that there is a higher nicotine dependency in vapers because of the higher nicotine load.
We have also got breakthrough designation for the vaping indication. Moving on swiftly, how is a small company like Achieve intending to launch and commercialize the drug for maximum impact? I think going back to what we said at the beginning, this is a large and underserved patient population and physician population. They are frustrated that there are not better tools to help them quit. Since Chantix launched in 2006, there has been nothing indicated or prescribed for vaping cessation. There is high dissatisfaction with the current products. Because of the definition of these segments, it is very clear how we access them without deploying a significant sales force. Chantix is now generic. Varenicline is out there. Therefore, there is no share of voice in the physician community because the varenicline is not being supported on a promotional basis.
We believe that we have the opportunity as the single voice out there in promoting smoking cessation. You don't really need an awful lot of medical education to tell people that they shouldn't be smoking. There is a strong desire to quit, but because of that nicotine dependency, they're unable to do it. We strongly believe that limited medical education is going to get us to where we need to be. It's an easy product to take, 3 mg three times daily over six or 12 weeks, and it's well defined. Finally, smoking cessation is covered under the Affordable Care Act. We're going to get favorable access, and that's a real positive in terms of going forward. Let's frame the market here. As I said, 29 million smokers in the U.S. Annually, there are 15.4 million attempts to quit with inadequate tools.
Now, if you translated that into kind of Chantix pricing when it was in the market, that's roughly $11 billion market opportunity. I am not saying that we're going to access $11 billion. I wish I was, but it's just to give you an equivalency here. If you look at the 17 million vapers, roughly 60% of them actually want to quit as well. Going back to what we said before in terms of vaping as a quit tool, originally that was it. Roughly a third of the market are dual users who have got very heavy dependency on nicotine. Roughly a third of the market are people who are former smokers who are looking to quit entirely. The other third of the market are never smokers.
They're kind of the younger population who think that vaping is cool and is not going to have any health risk. There's a lack of option for people who really do want to quit. 53%, roughly half of them want to do something about it annually, but they simply aren't successful. The CDC estimates that 36% of people utilize RX and OTC cessation treatments annually. There's a big market there with inadequate tools. Now, going back to what I said before, it's a medical issue. This is a dependency. First new treatment in 20 years. We are going to start to develop the recognition and change the narrative that this is a medical issue and not one of willpower. There are two key targets that we are looking at. On the prescriber side, we're looking at the RX smoking cessation enthusiasts.
Typically, these are high prescribing varenicline writers. Well defined, they fairly consistently are talking to their patients about smoking cessation, and they have a very favorable impression of cytisinicline to date. On the patient side, we're looking at highly motivated quitters. These are heavy long-term smokers. They're embarrassed about the habit. There is a stigma associated with smoking, but they are unable to quit. They really do consider quitting as their key priority. Our experience so far has been extremely favorable in the phase three trials, and we're getting really good feedback from patients who, even in the first phase three trial, which is three years ago, remain quit. That's important. How are we going to approach this? At stage one, these are the high prescribing HCPs. There's roughly 7,000 physicians who are actually writing the majority of the varenicline scripts.
We are going to progress beyond that into the next categories. In the near term, our focus is on the high prescribers. As we said before, Chantix generated $1 billion in revenues, of which about $800 million was actually in the U.S. There is an established market out there with an improved product, improved side effect profile. We really do believe that we can optimize this opportunity. How are we going to do it? It is a data-driven digital omnichannel approach. We have established a digital architecture whereby we can approach the physicians using digital means primarily. That may be as simple as actually sending them an email to say, "Look, here is the opportunity." We will be able to understand from their response exactly whether that message is actually carrying. Are we using the right channel? Are we using the right message?
We're able to, through data warehousing and data analysis, start to understand what is the right approach virtually on a physician-by-physician basis. The vertical approach is primarily for the primary care providers. Of course, if I go back to the comorbidities, it's equally possible that we can actually approach pulmonologists and cardiologists as well. On the patient side, it really is just building awareness that there are tools out there that they can be successful in their quit journey. You can start off from banner ads or KOL content to build that awareness. Right now, there really are very, very few alternatives in the market. Very briefly, this is a public health priority. We believe, obviously, that smoking is a leading cause of preventable death in the U.S. and globally. There is a global opportunity. We're covered by the Affordable Care Act.
This is near term. We're filing at the end of this month. We've got a compelling data package. We've been extremely careful with the compilation of the NDA. We believe this is going to be the standard of care for nicotine dependence. We've got a proven leadership team who've actually created value for shareholders. Clear commercial vision, and our IP position is strong. We've got the cash runway to get us to the end of the third quarter of 2025. Overall, it's a great opportunity. We're somewhat privileged to be in this position, even though it's not necessarily reflected in our share price. We strongly believe that as we drive forward, the value will be recognized. Thank you. Questions?
I saw on your website that Cytisinicline was marketed in Central and Eastern Europe for the past 20 years.
Yeah.
Have you guys—oh, sorry. Should I repeat that? Did everyone hear me?
Yeah.
Yeah. Since it was marketed in Central and Eastern Europe for the past 20 years, were you guys—were you part of that in any way, or is it another company that?
No, there's a company called Sofarma in Bulgaria. They are our partners, but what we've done is fundamentally redesigned the actual product. That was a titration dosing over 25 days. It was pretty complicated. We have simplified the entire dosing regimen.
Is it a pharmaceutical, like, is it a prescribed drug?
No, it's over the counter.
Over the counter. Do you eventually see this becoming over the counter in the U.S.?
Yeah, I think eventually, but it'll take time. The FDA is going to want evidence. I mean, yes, the safety profile is very, very strong. I think in the near term, even medium term, it'll remain as a prescription drug. We had long conversations with the FDA at the beginning, and they view this as a new chemical entity in the U.S. We've had to do the full gamut. We've done non-clinical, full clinical program.
I have another question, actually. Sorry. I noticed that a future indication might be for cannabis use.
Yeah.
The receptors are different, right, for cannabinoids and nicotine. So, would it be a redesigned version of the molecule?
Yeah, definitely. The dopamine production in cannabis addiction or dependence is pretty much the same. We do think there's an overlap in terms of the receptors. The question then is, is it a higher dose? Is it a different delivery?
Got it.
Yeah, that's in the distance. Let's focus on the near-term market opportunity. I think the good that we can do in nicotine dependence is the priority.
Got it. Thank you.
Any more questions? Look, thank you very much for being here. It's an exciting time for the company, the near-term catalysts. We look forward to keeping you updated. Thank you.