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Carrie Wade: I'm Carrie Wade. I'm the Senior Manager of Global Scientific Engagement at PMI, but I cannot stress enough right now that due to the last-minute change in hosting a panel, which is my first panel I've ever chaired, my views today do not necessarily represent those of PMI. So please, please keep that in mind. Today we're focusing on on 10 years of science and what we've learned, and I will change it a little bit with my questions of what do we need to learn in the next 10 years. On our panel today is Summer Hanna from BAT, who is the head of scientific regulatory engagement, focusing on product categories, and today she'll be talking about oral and heated. And then we will move to Jaz Alawalia. To me, he's the most well-known for investigating how tobacco harm reduction affects minority populations in the U.S., and he's published over 375 papers, many that are focused on tobacco-related health disparities, and he was the chair of the study section on health disparities in equity promotion. And then Dr. Amalia from Indonesia, and she studies oral health and is the principal researcher for the SMILE study, which investigates the oral health implications from switching from cigarettes to non-combustible products. About a week and a half ago, I was in Hong Kong at the Asia-Pacific Dental Conference where one of my colleagues, Yvonne, presented on some oral studies, and so I learned a lot, so I think this is very interesting to learn about. And then we'll move to Bernd Maier, who does a lot of work on nicotine toxicity, and he's spent a lot of time evaluating the actual estimate of nicotine toxicity. His background is in pharmacology and toxicity, focusing on cardiovascular pharmacology. So, thank you, and I will move to you.

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Summer Hanna: Thanks, Carrie, and really appreciate you stepping in at the last minute like this. Thank you all for joining us this morning. So, when I was asked to give a summary of the science on heated tobacco products and oral nicotine pouches seven minutes or less, I felt a bit intimidated because it feels a bit insurmountable and like boiling the ocean to consolidate all of that information in such a short period of time. But one of the things that really struck me about both of those product categories was while the scope of today is the last 10 years, really the origins of the story here go back 40 and 50 years for both of them. And starting with heated tobacco products, having grown up in the Reynolds world, I can't help but start with Premier and Eclipse. And if you've ever seen the volume of science that really began the foundations of learning for the heated tobacco product category and the Premier monograph that if you've not seen, makes a great doorstop because it's about this big. And thinking that 40 years ago, we were already considering what the last 10 years today would look like for the heated tobacco products. And then in 2014, with the introduction of ICOS, and fun fact, in 2015, there was a small resurrection of Eclipse known as Revo, which if you were ever in the great state of Wisconsin, you'd be familiar with. But then in 2016, the introduction of GLOW, and that really just changing the landscape of what heated tobacco products would look like and understanding and creating so much scientific evidence that really substantiates that 95% reduction in toxicants through our chemistry studies, the breadth of preclinical evidence that's out there. Most recently looking at studies around the 360 day study for tobacco heated products where you're looking at over 500 subjects and you're seeing, you know, almost 80% product compliance when you get people to switch to a tobacco heated product, and that translating into a 94% reduction in toxic exposure, and that's amazing. And then you can combine that even further with the great work that's happened in Japan, where you can track the introduction of heated tobacco products, then you can look at hospitalization rates, and you can see that correlation, that reduction in hospitalization associated with the introduction of the heated tobacco products in Japan, And it's the contribution, the positive impact to public health that that has. And it's really hard to argue such a compelling story that's really just over that last decade been built into something that's come to life for so many people in so many different ways. Switching over to oral nicotine pouches, and forgive me if I slip into some very, like, industry-specific terminology. I'll try to keep, to avoid that. But thinking about the Swedish experience, and, you know, yesterday, if you were at Eisentech, the great work that was shared by colleagues at PMI, Swedish Match, and Altria, I certainly won't do the hours that they had justice in the next two to three minutes to talk about it, but they shared so much insightful data and thinking about how oral nicotine pouches build on that great foundation that you see in Sweden with the introduction of snus. And then even this week, taking that a step further in the release of the Smoke-Free Sweden that says, you know, when you think about the Swedish experience, that story, the introduction of all of, you know, not just snus, but oral nicotine pouches, a wide variety of other reduced risk products, and that in Europe you would have had, you know, 3 million fewer deaths and 103 million additional life years if you had seen that same kind of adoption of reduced risk policies. Thinking, you know, again recently with oral nicotine and I think Carrie you touched on this. It's not just where we've been in the last decade but where we're really going and I think you see for oral nicotine a good example of where we're going next is the science really working. I think we have set the foundation for the story associated with reduced risk products and what they can deliver. But now it's about the Thinking about what the questions that we receive associated with those are from regulators, from people who are skeptical of novel product categories, and how we respond to those. And so I think about the BFR report that was released in Germany and thinking about nicotine ceilings, that 16 milligrams pouch limit, and how we start to think about those kinds of scientific questions and preparing for that journey. And for me, that becomes really important, not just with the insights that we've already generated, but really where we go next. So I think I'll pass it to you, Jez.

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Jasjit Ahluwalia: Thanks. So I was asked to cover e-cigarettes and that technology with regards to the past 10 years. But I think, as Kerry said, the next 10 years are probably more important. I look to the future rather than the past. And I think about other industries, and I think that innovation is going to become key, right? When you think about, I remember when I bought my first 30-inch LCD TV many years ago, I paid $3,000 for it. Now you can buy a 30-inch TV for $129, I think. And if you think about hybrid cars or electric cars, the same thing. The first cars, I don't know who they were, Toyota, something, it went from zero to 60 in like 10 hours, you know. You're pressing the gas pedal, and I'm sort of a heavy-leaded, fast driver. And now you have Teslas that can go zero to 60 faster than a Porsche. And then you have autonomous driving, and so on and so forth. And it wasn't safe. There were some accidents. There were battery fires. But, you know, this is the wave of the future in the automotive industry. And the very companies that sort of put out tons of carbon emissions for, you know, and so on and so forth, they are all on the bandwagon. And likewise, I think we see the industry, the tobacco industry, of switching, whether it's PMI or Altria, with their tagline smoke-free future or X number of revenue dollars from smokeless non-combustible products. As a physician, to me, these are all very, very good things. And I think that we're going to see more. I personally think, obviously, that a fourth generation e-cigarette is both safer and better way to deliver nicotine than the first generation e-cigarettes, the cig-a-likes, or whatever the case may be. And I think we're going to see more innovation. For example, I know that Juul 2 is available, I think, in the UK, not in the US. And there's some technology, which I'm not an engineer, which makes the delivery of the nicotine better, whatever that case might be, so that you have less inhalation but more nicotine, which is, of course, from a physiological standpoint, the goal. My conflict of interest, you know, we all have them, is that while I'm an academic and I do research funded by the government, I'm also an equity owner and chair of the Scientific Advisory Board of a startup company called Qunovia. So Qunovia is working on a delivery device. Some of you saw it on Tuesday when Brian Quigley was there. Brian used to be at Altria. And we are working to develop a device to deliver nicotine through a medication route. So through the FDA, it will be a prescription product. So it won't go through the center of tobacco products. It won't be a vape. And it doesn't use a battery, so there's theoretically no thermal degradation products. It uses what's called a vibrating mesh nebulizer. No idea how it works. But I think it's breath actuated. But it vibrates at such a rapid speed that it then aerosolizes the liquid with nicotine into these five micron drops, which is invisible to the eye, just like an e-cigarette. And then it goes down to the alveoli and works. I mean, the lung and the nose are the two best vehicles to take a nicotine if you want to emulate the pharmacokinetics of the cigarette. So I think there's going to be innovation in the medicinal route. And by the way, just the fact that there is a medicinal route doesn't mean I, or speaking for myself, doesn't, don't, don't feel that there is a space for recreational e-cigarettes, if that's what we want to call them, that go through the Center for Tobacco Products in the United States and that are available to consumers at shops wherever they may be. So that there's much choice. I'm a big fan of choice. I like different coffees. I like different flavored candies. I like different, different kinds of cereals. And I think, so therefore I'm a fan of flavors of e-cigarettes. I don't know that we need 75,000 flavors, but I think some flavors are very reasonable. So I think there's going to be a lot more innovation, and the products will only get safer. We'll better understand the science of PG and VG. We'll better understand the science of battery, the metal coils, and the leaching of metals, and so on and so forth. And I think the products will just get safer. They will always have nicotine in it. So I think, as Neil Bennewitt says, one has to decide, is there a role for recreational nicotine in society? I know that the audience here probably feels the answer is a strong yes. And I think, in my case, I think it's also yes. I think, I mean, some people like to compare nicotine to caffeine. I don't know if that's the best comparison. But I think, you know, it's a legal product. It's a product that people enjoy. It's relatively not dangerous, if that's the way to say it. Surely doesn't cause cancer, even though 80% of American physicians think it causes heart disease, COPD, and cancer, which it doesn't do any of the above. I think that with regards to, you know, often you'll hear from people, we have no long-term data, we have no long-term data. And I think, you know, as each year goes by, we have more data. And I think the snus example in Sweden is an amazing sort of real-world example of what has happened over 30 years. Hannah, is that your first name is Summer? I always do that, sorry. And we've met a number of times. Summer, sorry. Summer talked about the Japanese data with heat not burn and the hospitalizations. And we'll do that hospitalizations and then we'll know more about incidents. That takes longer and prevalence and so on and so forth. of COPD, I think we're going to see the same thing with e-cigarettes. We don't have that kind of epi data, but I think we're going to get it from New Zealand, and we're going to get it from the United Kingdom, where there's a high acceptance usage of these products. And, you know, we need that kind of data. The Cochrane Review, which in the world of science comes out of Oxford University in the U.K., is sort of an unbiased, non-industry funded clean scientific organization that does meta-analyses and reviews. And they have said there is very strong evidence that e-cigarettes help people quit smoking, if that's what someone wants to use it for. The United States can't decide what it wants to say to the federal government, but the National Academy of Sciences issued a report in 2018, about five years ago, I think 2018. saying that there appears to be evidence for it. It's a cautionary statement, but that's old data. And now if it's updated, there are a number of clinical trials that are done. We published the first one using a fourth generation pod. It happened to be Juul about two and a half years ago, which showed strong evidence that it helped people quit. There was significant reduction in biomarkers of exposure and harm. And interestingly enough, that with dual users, people who smoked and used e-cigarettes. This is always a big concern. People go, oh my god, they're going to be using e-cigarettes and smoking cigarettes. It's more dangerous than smoking cigarettes. Well, it turns out that's not true early on. So early on, what happens is that when people are dual users, let's say they're using vapes to get off cigarettes to substitute, and they're using both, Early on, they tend to be high e-cig users and low-cig users. So in our study, at the end of our measurement time period, which is short-term, six weeks, people were only smoking two cigarettes a day down from about 15. Now, if you follow them over another year or two, what naturally happens is either they completely quit their combustible cigarettes, which is not very common spontaneously, or they actually end up, unfortunately, going back to more combustibles and rarely using the e-cigarettes. And there's been some papers, Mohammadi in the audience published a nice paper from the PATH dataset looking at dual users. Ricardo might be here in the audience. Ricardo Palosa, Chris Russell, myself, and some others have two papers. One has been accepted. One I think is in review, which used varenicline versus placebo for dual users. So people dual use, and you give them varenicline versus placebo to get off the combustibles, but encourage them to stay on the e-cigarette. And it worked very well. So that's one important thing to remember about dual users. So people think dual users is like, you know, the never bad land and so on and so forth. I view it as for someone who wants to get off combustibles is not a great place, but not a bad place. And then you can do something about it. And then for people who want to quit vaping, there are people who want to quit vaping. This study showed that in fact, Vereniclein helps people quit vaping as well. So I think there's going to be more innovation in the field. There'll be more choice. Pouches are an incredibly safe product. They're basically nicotine gum. I would love to see the industries take the pouch through Cedar as a medicinal route. They're not going to do it, of course. But I think they should. And it doesn't prevent them from marketing it both as a product for consumers and as a medicinal product. But I'll leave that for the corporate people to figure out. So I look forward to the Q&A.

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Bernd Mayer: Is it me now, or? Okay. Ladies and gentlemen, it's a pleasure to be here. First of all, I apologize, I cannot impress you with a fancy car. I'm driving a VW Tiguan with a diesel engine, so I really appreciate your car. And I cannot... I don't have a Tesla, just for the record.

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Jasjit Ahluwalia: I have a combustible

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Bernd Mayer: Okay, and the second thing is I cannot impress you with any clinical studies. I'm not doing this. I'm not from the tobacco field. I'm an outsider. As has been mentioned, I'm in cardiovascular pharmacology. I'm a pure scientist and just stumbled into the field of tobacco control. So why I'm invited here, the basis is one paper that I published a couple of years ago. where I corrected a little dose of nicotine. I corrected it by a factor of 10 or 20 upwards, after 150 years of misinformation. And I think this is the basis why I get invited to these kind of conferences. It's a good, fine paper. I won't talk about this. I provided a PDF file if you're interested, and you can download this. And I explained the history of the discovery of this little dose, how everything started. I don't talk about this. So what should I talk about? I don't know. I accepted this invitation under the conditions that I don't have to give a talk.

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Carrie Wade: But to be clear, you do have to talk.

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Bernd Mayer: I have to talk, but not to give a talk. But then suddenly I saw in the program, burnt seven minutes nicotine. And I complained, Jessica noted, I complained, come on. But this is the trick of the girls, the trick of the organizing girls. Anyway, what could I talk about? I thought, I'm really not prepared. I think we all agree that the war on tobacco has shifted to a war on nicotine. That's where we all agree about. The wording is different as we yesterday heard. First it was just smoking, then it was tobacco use, now it's nicotine use. Everything goes against nicotine. But we probably not agree about the time frame Most of you may have the impression that it just started in the last five, ten years. And I can tell you my experience. When I was presented the first e-cigarette, this was in the spring 2006, I think most of you didn't know about e-cigarettes at that time, yeah? I got this Chinese stuff in my hands, yeah? I was impressed, I was a heavy smoker, I tried it, and I predicted that within 15 years nobody's gonna going to smoke anymore, because you don't need tobacco cigarettes when you have, even though this was a poor performance, this Ruan stuff. Okay, so what I did immediately, because I was so enthusiastic, I wrote to different non-smoking organizations, you know, anti-tobacco and so on. And I was enthusiastic, because now we have the problem solved. You are fighting for 30 years against smoking. Now you have it. You just have to promote this and we're getting rid of smoking. Yeah, I was not in the tobacco control field. And the replies that I got, this was amazing. It was inciting emails. This was apparently a network of anti-tobacco people. It was inciting emails, probably hundreds of emails that I got from different areas where they said, oh, you are crazy. And this is the same arguments that we hear today. 2006, I heard exactly the same. They continue with the ritual, with the behavior, and you're going to normalize smoking, and so on. It's all these arguments. And then the other mistake I made was, as an outsider again, because I didn't know what smoking cessation means, I wrote a report on this and recommended these e-cigarettes for smoking cessation. And of course, this was the key word for the government and for the authorities. Smoking cessation is a medicinal thing, and it has to go to a pharmacy. And they started to ban all these products in Austria, not officially, but practically. Nobody dared to sell it anymore. So this is the story. And what they also did already at that time, and we see it again now, is that they blamed nicotine for whatever they had in mind what it could do. And in the same paragraph, they wrote me, the only thing we recommend is commercial, is medicinal nicotine replacement therapy. It's the gums, it's the inhalers, it's the batches. So suddenly, and that's why I always say, nicotine is converted somehow. This is a mysterious conversion. It's converted from a helpful remedy sold in pharmacies to a neurotoxic, highly addictive neurotoxin as soon as it leaves the pharmacy and enters the liquid of an e-cigarette. And they are not ashamed about that. They do it regularly. I just recently read an article in Nature Outlook. very famous journal, and this was a series of articles on tobacco control, and they had a nicotine article there, and with all this bullshit, even in nature, and they started to argue in this article that the medicinal products are safe because they are FDA approved. So the stem from the FDA converts nicotine from a potent neurotoxin, and highly addictive as heroin, from this kind of compound to a very helpful and recommended drug. And the final point that I want to make in Austria, I don't know if the regulations are different in different countries. In Austria, these medicinal nicotine products are approved for children above 12 if they are smoking. So this is tobacco harm reduction for teenagers and for kids. And this makes sense, of course. If they are smoking, they should take a nicotine replacement product. But they are flavored. And they're sold to kids, legally sold to kids. If I promote an e-cigarette, even nicotine-free e-cigarette for kids, They say, I'm a child abuser. I'm a monster. Nobody would tell this. And this is a really crazy thing. Maybe you can do the best you can is to really expose this hypocrisy, this discrepancy between public views and public perception of nicotine. That would be really helpful. Because you don't need a PhD and you don't need to be a professor to understand this extreme discrepancy between the good and the bad nicotine, the two nicotines. There's a pink and a black. OK, I think I'm ready.

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Amaliya Amaliya: Thank you. As mentioned, I'm Amalia from Indonesia. Maybe a few of you know Indonesia, where it's located. Well, Indonesia has one of the largest or greatest smoking rates in the world. So after China and India, we have very, very greatest rates of our prevalence of smokers, and it's about 65 million smokers in Indonesia, so it's really big. And as a researcher, and I'm a dentist, I am deeply concerned that this is happening to our country without any measure or preventive program that successfully decline the rates or the prevalence of smokers. And as a dentist, I frequently see how the smoking deteriorates the condition in the oral health. So from the very mild condition, from tooth staining, gum staining, tooth decay, bad odor or halitosis, or maybe when you talk and somebody can smell bad odor from your mouth, and then to the life-threatening disease like oral cancer. And then as a dentist, I also see that smokers have a sign of really mild inflammation, despite the oral health condition that is severely deteriorated. So it's like smoking has some masking effect. on the gum or other tissue in oral health. So when you have plaque or bacteria attached to your tooth surface, the gum has to be respond to the plaque or to the bacteria. It will be redness or inflamed or maybe painful or bleeds. But in the condition of smokers, I cannot see any clinical sign of inflammation nor bleeding. So it is well known that smoking has, as I said, masking effect or we call it hiding the factual or the true condition of a smoker's condition. And so let me tell you interesting finding of my recent studies that we invite three groups in our dental faculty, and it is non-smokers, smokers, and smoker who switch to vape. And we instruct them not to brush for 21 days. So only in the lower jaw. only in the lower jaw, because if we instruct them not to brushing in the upper jaw, they will be rejected, because they have to see colleagues, maybe a relation and relate on something like that. So I only instruct them not to brush for the lower jaw for 21 days to see how the gum will respond to the bacteria. because they say that in smokers, the inflammation or the response of the gum is masking by nicotine. Nicotine will constrict or narrowing the blood vessel of the gum, so when bacteria came, nothing will happen because the vascular or the blood vessel is narrowing. So this is the key point of our body response, the blood vessel or the wall of the blood vessel. It could be narrowing or widening. depends on the response that we need. So it's flexible. But in smokers, I could see that nothing, even if we have a plug accumulation. So I would like to see in this experimental gingivitis or artificial gingivitis, what is the response of smokers versus vapors versus non-smokers. taken into consideration that vapors also use a liquid containing nicotine. So nicotine is something to be blamed. Then I see this interesting finding that after 21 days of abstaining from toothbrushing or other tooth cleaning measures, I can see that smokers fail to respond to the bacterial invasion or plaque accumulation in their tooth surface. No bleeding, no inflammation, no reddish coloring, just fine. But it is alarming because they don't respond to the invasion of the bacteria. For 21 days, you can imagine. And I can see that it is not expected at first that vapors respond similar as non-smokers did. they blitz, they have inflammation, they have body response to this plaque accumulation. So instead of the abundant and similar plaque accumulation, smokers fail to appear or to show or to demonstrate the normal body response while vapors with nicotine-containing liquid they use, they still respond well to this plaque accumulation or bacterial invasion. And non-smokers have the same or similar response as vapors. So I think that we conclude from this experimental gingivitis that instead of nicotine, there is something else to be blamed. Because we already confirmed from the saliva that smokers have higher cotinine levels in the saliva. It's confirming that they take nicotine. Vapors as well, they also show elevated cotinine level in the saliva, so it is also confirming that they use a liquid containing nicotine. And non-smoker have no cotinine level or only a small amount of cotinine levels in the saliva, confirming that they don't take any nicotine. And we concluded maybe there is something else to be blamed, not nicotine, that constrict or narrowing the blood vessel and masking or hiding the clinical sign of inflammation, which is normal. So it is not nicotine itself, but instead of maybe tar or maybe something else.

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Carrie Wade: Thank you all, very interesting. Something that I want to think about, and I'd like to bring more conversation to, not just here, but in general, is what do we need to know in the next 10 years? And what more do we need to be focusing on risk perceptions? Do we need to continue focusing on toxicity and individual risk reduction? Or is it case closed on that one? I don't know. Should society invest more in exploring the benefits of nicotine? These are some of the questions I have. I will ask each of you if you can just keep it to a minute because I do want to be able to give the audience lots of time to ask their questions. But for instance, Jazz, we know a lot of what you do. I know a lot of what you do in other populations and focusing on African-American populations. What do we know about other populations? What should we know about other populations? What's important to them with regard to switching? And what should the next 10 years look like?

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Jasjit Ahluwalia: That's a lot. Yes, it is. I mean, I think we do know about other populations. Like, for example, just in the United States, those who are Hispanic or Latino, Latina, they smoke fewer number of cigarettes per day. They're more likely to be non-daily users of combustible cigarettes. In fact, the vast majority, almost 60%, 70% in the United States. We know very little about older smokers, It's almost like they're invisible. People seem to forget about them. So that is sort of like an unknown group. I think that we also know that, for example, that different groups of populations, it gets a little touchy because we're talking about genetics, metabolize nicotine differently. Like Asians, Japanese metabolize differently than whites, which metabolize differently than African Americans. And that has ramifications for the consumption of the number of combustible cigarettes, or the ability to quit smoking, or whatever the case might be. I think for the next 10 years, was the other part of your question, I would say that, you know, we need to continue to innovate these products, need to keep making them, I'm all about safety, make them safer, make them safer. I think societies have to decide, is there a role for nicotine in society? I mean, that's the bottom line. I mean, the 80s, 90s, 2000s, it was all about the endgame, as most people know. The endgame was combustible cigarettes, or tobacco fuel, if you want. But it was always that. Then all of a sudden, we were making progress in that. Then certain groups, I won't name them, sort of dominate the noise level of the media, and it's converted to the endgame is now nicotine. And that's like, whoa, how did that happen? And by the way, that leads to the confusion amongst people, and even our intelligent doctors who apparently don't know the role of nicotine in disease.

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Carrie Wade: Summer, question for you. What regulatory targets concern you from a scientific point of view and what should we be focusing on in industry?

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Summer Hanna: Thanks. I think one of the things that I've spent a lot of time thinking about most recently would be nicotine ceilings. So thinking about nicotine pouches, for example, how we navigate that. The BFR report was obviously incredibly helpful in giving some kind of guidance in terms of of a level to be seen in nicotine pouches. But when we think about the use of those products, the regulatory concerns that are becoming more present, this week in Finland, for example, they discuss, you know, the idea that small children might go and eat nicotine pouches, and then they have you know, they die of toxicity exposure and, you know, and on and on and on and on. And so you think about, you know, eventually it becomes a very easy place to contemplate nicotine pouches that are available, but no longer useful for the audience that they're intended to be used by. Um, so how you navigate those kinds of questions for me, I think is, is definitely a space that requires more scientific attention. I'm thinking about also the insights that are developed from a scientific standpoint to substantiate these kinds of positions and what you can do in terms of really just like very purist scientific experimental design. A lot of research that's generated that presents negative views around nicotine and products, once you start digging in, you find a lot of really just fundamental design flaws and how you can think about things like physiological relevance and actual use and building that into the scientific process really across the board to help respond to that as well.

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Carrie Wade: Thank you. Bern, I told you I was going to ask you this question, so I hope you've had time to prepare an answer. So what about regulating nicotine and what do we need to know more about regulating nicotine? Summer just talked, spoke on it a little bit, but your work on nicotine toxicity calls into question some of the current thoughts about nicotine toxicity and what the lethal dose is and that sort of thing. How do we extend that to abuse liability and does abuse liability need to be regulated? And should we question the idea that nicotine PK is a good metric and that parameter should not be exceeding that of cigarettes?

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Bernd Mayer: With BK, you mean the pharmacokinetic profile. Well, I mean, let me start maybe with the 20 milligram per ml limit that we have in the EU. So in the public perception, people think that this is fact-based somehow, that this is a scientific result. And whenever you have a liquid with 25 milligrams per ml, you're going to fall down. You will be killed immediately. That's simply not true. This is a purely political limit, this 20 mg per ml. It could be as well 5 or it could be 50. There's no reason to limit this to 20 mg. This was a compromise in the discussion before they implemented the TBD2. So this is the first thing. And I mean, when you say lethality, we don't want to have lethal doses of nicotine. I mean, it would be sufficient if you're pretty sick and you're in intensive care. You don't have necessarily to die, and it's still bad. But the positive thing about nicotine consumption is, and this was shown for smokers, and it was also shown for vapors, is the so-called self-titration with nicotine. Every smoker knows this. When you have the feeling it's too much, you get some headache, you become dizzy, then you automatically, unconsciously, you stop consumption. That's what the late Birch G. Langer said, that vapors will draw on the e-cigarette as long until they fall down unconsciously. This is just, this is a fairy tale. That won't happen. Everybody stops the consumption of nicotine if it's too much. So I'm really against, principally against regulation. Of course, there should be some kind of upper limits, just this clear. And because you mentioned the vouchers, yeah? The vouchers are different because the pharmacokinetics is so fast. So the e-cigarettes are a bit slower probably, cigarettes are at least comparable. But about the pharmacokinetics, the appearance of the nicotine in the plasma from pouches are very fast. This was shown by the BFR. I agree, this report is excellent. And they come up with a limit of 16 point something milligrams per gram pouch. And I think this is a reasonable limit. If you go higher and on the market are pouches with 40 milligrams or something, then you can imagine it takes about 30 minutes until this nicotine is in the plasma. So you have in 30 minutes, you have the amount of nicotine corresponding to two bags of cigarettes. You won't smoke this in 30 minutes. So I think it makes really sense to limit this. And as we heard, there's someone in the audience who needs a higher concentration, okay, then it takes two or three or whatever, yeah. If you really need them, you can put this up. You have a lot of space in your mouth to put these pouches in. Yeah, so principally, I think we shouldn't regulate, yeah, we should, and we should, the society should accept, and this is an important point, I think, society should expect, should I accept that there's a certain amount of people who wish to consume nicotine, who'd find some pleasure with nicotine consumption, who want to do that. And it applies to teenagers as well as to adults. We will always have a certain fraction of the population who want to consume nicotine for whatever reason. And that it won't help, you can ban as much as you want. It's like smoking. We have smoking bans all over the world and still we have 10, 15, 20% teenagers smoking. Where does it come from? Because they want it. And this has nothing to do with advertisement because advertisement was banned. And like the late George Carlin, which I really like, what he said in one of his appearances, he said, children don't smoke because they came here with sunglasses tells them to do so. They smoke for the same reason as adults do, because it decreases depression, it relieves anxiety and stuff like that. There are positive effects of nicotine, and it would be worth to emphasize this. This is always under the carpet from public health, doesn't talk about the positive cognitive effects and anti-inflammatory effects and so on of nicotine. And I think we should push this in the next 10 years.

00:42:02 --> 00:42:33

Carrie Wade: Thank you. And then finally, for you, Amalia, I have one question, and it's also a very similar question to a question from Ignacio Livia, who's watching online. My question is from the industry perspective, but he was asking more general. How do we reduce the skepticism of doctors and health officials about the lower risk nicotine delivery products? My question, which is very similar, is how do we as industry convince people that our science is reliable?

00:42:38 --> 00:44:13

Amaliya Amaliya: So maybe we have to conduct more research, especially clinical trials and also systematic review, because with the clinical trials you can also extrapolate what you have found in the lab and in the preclinical trial. and as well as systematic review and meta-analysis, which is already written by me and my colleagues in Indonesia, that this kind of alternative tobacco product has effectiveness in smoking reduction and smoking cessation as well as safe. So you can see it in a journal from Dove publisher that we already conducted systematic and meta-analysis. So, we can adopt this in our daily practice from the systematic and meta-analysis that this product is effective in reducing and as a stopping aid for smoking cessation, and also it is safe. So I think we have a long journey to keep on doing what we believe and keep on researching. That's why it's not search, but research. Yes? You already search, you find something, and again, you search, so it will be research.

00:44:13 --> 00:45:38

Carrie Wade: I absolutely love that, and I'm totally stealing it. So thank you. Does anybody have any questions from the audience? I'm happy to moderate that. Somebody has a question? Well, then I'll just continue to ask mine. What is I'm going to follow up on this. How do we convince people that our science is reliable? I mean, I come from industry, and we do so much science. And when I was at the think tank in Washington, DC, we focused our policy positions on the scientific basis. And a lot of what we used was industry-based science. I mean, now I work for industry, so I'm obviously pretty accepting of that. But I don't know how we can convince, how we in industry can actually convince people that what we're doing is in the right direction and is robust. And I would like to know anybody's thoughts or each of your thoughts on how we are, how we should be tasked with using science, using what we do, using what we produce to reach healthcare providers, to reach regulators, to reach consumers.

00:45:38 --> 00:45:43

Bernd Mayer: There's an opinion in the back.

00:45:47 --> 00:48:32

Jasjit Ahluwalia: I can attempt to answer that, and then we can take the question, I guess. But I think it's hard. I think some of my colleagues in the audience have told me, and I heard from before, and then new people I met told me that if they're from an industry, a big tobacco industry, that they have trouble getting their papers published. You know, I just, I feel sad by that a little bit, you know. I mean, either you accepted it at face value or you don't. And some journals, of course, have an absolute ban on publishing tobacco industry funded or from the industry itself papers. So that's black and white, so there's that. But then for those that don't have a ban, apparently they're treating you worse than they'll treat me, right? I mean, that's the bottom line, what you're getting at. And I think that's unfortunate. Today's world is very different than the 1980s. In the 1980s, You may not have been born, I don't know, but you people were lying. You were publishing misinformation. You were lying. You were hiding data. You were perjuring in front of Congress. It was an unbelievable field day for you guys, and you were making money hand over fist. In today's world, You still make money, but you are watched like a hawk. The FDA, I believe I'm not an expert on this type of stuff, but can subpoena, if that's the right word, any of your paperwork, any of your research, and look at it. So you're being watched carefully. They're breathing down your neck. Your science is monitored much more tightly than my science. I can actually get away. with fake science better than you can. I don't do that, by the way. But I probably could. And I think, you know, I tend to generally trust the science from the industry. I mean, I'll have a little bit more of a cautionary eye. But by the way, just as much as that, you have to remember that everyone has an agenda. I mean, you have an agenda. You want your science to look good, but you will be ethical, I'm sure, Carrie. I hope I'm ethical, but I maybe have an agenda, and I know some other colleagues without names who have had to retract papers sometimes have had agendas on the other side, too, as well. So agenda-driven science, in my opinion, You know, we're all driven by that to some extent. It's a little bit dangerous for all of us, whether it's me or for you. I think science should be science and should be of the highest quality. Yeah. There's some questions if you want to take.

00:48:32 --> 00:49:00

Kgosi Letlape: Great. Thank you. My question is about the TPD and setting the limit for nicotine liquids. Are you suggesting that that should be open-ended? Not open-ended. And the follow-up is, in the 10 years, has any science been done as to what the reasonable maximum should be and what the basis of that should be, just like you have in pouches?

00:49:00 --> 00:51:07

Bernd Mayer: I mean, the point is that the industry started to handle this 20 milligram per ml limit by developing devices that are with sufficient performance. But still, for the small devices, the 20 milligrams are probably not enough. And we see this from the Joule in the United States, where this is, I think, sold at 55 milligrams or 60 milligrams per ml. And this is successful, and with the 20 milligrams limit, It's not successful. I'm not suggesting that it's open-ended, but the initial suggestion from the Parliament in this discussion in the EU was 32 milligrams per ml, and this would probably be acceptable for most vapors. And then the Commission suggested 4 milligrams per ml. And at that time, this was homeopathic. Today, there are some vapors who have this direct-to-lung vaping. They have enough with four or two milligrams per ml. But at that time in 2013, this would have been a ban of nicotine, in fact, because the devices weren't good enough. And then there was this Trilog discussion, where they then found this compromise of 20 milligrams per ml. So what I'm just saying is that this number is just, this is an arbitrary number. This has nothing to do with science. And now even in the United States, they take Europe as a as an ideal country with this 20 milligram per ml limit and they say we should implement the same because they know what they are doing. No, they didn't know what they are doing. They were just dealing. This was a deal, nothing else. No scientific basis. I think it should just be sufficient for everybody even if a smoker switches to a low performance, a poor performance device should be able to get enough nicotine. That's the point. Satisfied? Is it sufficient or should I? I can continue for hours.

00:51:07 --> 00:52:28

Jasjit Ahluwalia: Just one very quick comment on that is that I would just say that the number of scientists, I think there's some truth to that, but I think there is some science. You can look at PK curves. I mean, there's some science. You can look at it. And the goal should be, in my opinion, to try to get, let's say, an e-cigarette to have a curve that emulates a cigarette and maybe just right below it so that theoretically it's dependent or abuse liability would be less than the cigarette or something like that. I will say that, you know, let's say a Juul 2% versus a Juul 5%, I vote for the 5% any day because for a variety of reasons. One is if you believe that vaping is not safe, which I think at least industry people, we all agree it's not safe. It's dramatically safer than combustibles. But it's probably not completely safe. So if that's the case, then the goal is, if the goal is to get the nicotine, get the pleasure, then why not get pleasure with using as little of this not-so-safe stuff possible? So then you get the 5%, you will use it less than if you use the 2%. It's not particularly rocket science. And if you want to switch off combustibles, then you want it to work, which is why something like the two milligram gum is like, excuse the American expression, pissing in the wind.

00:52:28 --> 00:53:35

Bernd Mayer: Let me get to this because the pharmacokinetics. I mean, the pharmacokinetics of nicotine delivery from e-cigarettes is pretty complex. And I don't think that anybody has ever looked for the pharmacokinetics or compared mouth-to-lung versus direct-to-lung. So my hypothesis is that when you vape direct-to-lung, it's much faster because you get this in the lungs where the uptake is faster. While when you do it mouth-to-lung, the vape has contact with your epithelial cells, and it goes much slower when you resorb it through the saliva. So I think that there are differences. There are documented differences. pretty high differences in the kinetics of nicotine uptake that are published. So some are very slow, some are steep, and then it depends on how you vape. That's the other thing. This is a matter of many, many factors, and I don't think that you can generalize this over all devices and all vapors.

00:53:35 --> 00:54:31

Kgosi Letlape: All I'm just raising is that if we're negotiating with policy makers and regulators, there needs to be a number that gets put out there. So let's do the work of making it based on science. And compromise will always occur when you negotiate. It's like speed limits. I mean, you go to some countries, it's 60 kilometers, and people will tell you, I drive a Lamborghini, it's more efficient with brakes, my limit should be 160. On the Escort, you can put a limit of 60. And we get into variable discussions. But with regulators, you're going to need a number, and all I'm just, pleading for is that there was an arbitrary number of 20 or a compromise of 20. Has the science been done to say actually it should be 18 or 25 or 30? Here's the evidence. When you review the TPD, take that into account so that you can adjust that upper limit appropriately.

00:54:31 --> 00:54:37

Carrie Wade: Thank you. I see a couple questions here and then one there, so since you're standing there, why don't you, and then we'll get to you.

00:54:39 --> 00:55:42

Joe Thompson: Thank you. Joe Thompson, Imperial Brands. I just wanted to share a little bit of some of the science that we've done that I think is relevant to this. So one of our clinical studies, a PK study on nicotine pouches and looking at low, medium and high levels of nicotine and we found two things. One we expected And when we didn't, what we expected was that effective delivery of nicotine satisfied craving. We expected that. What we didn't expect was that there was a lack of correlation between dose and satisfaction. And what it showed us was that the consumer is important, the adult smoker is important, And the level of nicotine, what they require from the product to be satisfied is different depending on the consumer. And I think that's important when we're thinking about levels. It's not necessarily higher is best. It's not necessarily about a limit. It's recognizing that consumer needs are different.

00:55:43 --> 00:56:04

Carrie Wade: No, I think that's very important. And I would also add that I think we have to do a better job at industry when we talk about what we're learning from, not just industry, everybody, what we're learning from animal models, what we're learning from talks, and that how it may or may not apply to actual human parameters. And I think we have to do a better job at explaining that. But yes.

00:56:10 --> 00:57:27

Norbert Schmidt: Your question, how could tobacco industry science better reach regular science, and I want to pass on a suggestion by science fiction author David Brin. He suggested you make a bet. You bet scientists that they can't do a replication of your study and come to different results, significantly different results. So if you're confident in your results, in your study, offer money to contradict you, if they can. This way, scientists from other, from the opposing, the anti-tobacco scientists will try to get this money from you. This would be replication studies that could be published.

00:57:27 --> 00:57:42

Carrie Wade: Thank you. Actually, I do know that there's a few studies or a few projects out there that actually investigate the repeatability of industry science. And so I'd like to see more of that for sure. Does anybody else have a comment on that?

00:57:47 --> 00:58:42

Amaliya Amaliya: Actually, in Indonesia, it started on 2021. We have a replica project, and it's funding from University of Catania or Cuihar with the spin-off. So my colleague in the medical faculty reproduce or have a replication. of studies conducted in epithelial cell of lungs and also in animal, so that will confirm the results that already conducted by CHOP-EQ company. We are from academician from university, prominent university in Indonesia. So I think that this replication or confirmation study will address your question.

00:58:44 --> 00:59:56

Bernd Mayer: May I just add one point? I want to make this clear. The best studies I've seen on toxicity, cell biology, and even clinical studies of vaping, it includes e-cigarettes and the tobacco heating systems. The best studies were published by the tobacco industry. Philip Morris, and this was British American to Baker in particular. They did excellent studies. Why is it? Because they have the money, they recruit good scientists. I wouldn't get a job there because then they need better scientists. They have the excellent, yeah, of course, they have the excellent people and they have the equipment that I, my tongue goes down to the stomach when I see all these equipments. I've seen such a lab. They had 10 machines where I was fighting for three years with our dean to get one. I mean, this is a huge difference. They did excellent studies, but the problem is that just nobody talks to them. When I argue with a study from the tobacco industry, then public health just pushes it away, says it's the tobacco industry. They don't even look at it. That's the problem. So if I were the editor of a medical journal, I would ban Bloomberg-funded studies.

00:59:59 --> 01:02:08

Summer Hanna: And maybe one thing to also touch on in terms of acceptability of industry science, the points that Bern just made. One of the things that I think is already done as part of your question of how we create that dialogue, how we generate more buy-in on scientific concepts, how we increase our credibility as industry scientists, you and I, is also just the participation in many of the things that we're already doing, but we don't do a good job of talking about. So think about like the 21st century toxicity work that was done. So that was a collaborative piece of work with members of the tobacco industry, government officials, independent scientists, all coming together to really look at, say, you know, how do we reduce the use of animals in scientific testing for tobacco products? That was a giant piece of work. It was wildly impactful. It was innovative. It drives the points of things that we're trying to achieve broadly as scientists globally, not just as tobacco scientists. And it's a really well-respected piece of work. What we don't do a good job of is telling anybody about it. Those people who are involved in preclinical testing, maybe they have some experience with advocacy, moving away from animal models, they know about it. But how many people in this room outside of those communities have ever heard about anything like that? Those are the kinds of venues that I think when we talk about gaining more acceptance of science, we need to do a better job at not only participating in very intentionally, which I think is, you know, a PMI and a BAT employee, we'd argue we try to do a lot, but also talking about it in venues outside of our normal places. Going to meetings where people have not encountered us before and saying, you know, we've had a hand in this work, we've done this, these are the insights, this is how we behave, this is how we operate. And I think that that's really important because The feedback I got this week, which was always a helpful reminder, is you have a good message, you're a terrible messenger. So thinking about how to do that a little bit differently I think is also pretty critical.

01:02:08 --> 01:02:10

Carrie Wade: Thank you.

01:02:10 --> 01:05:07

Alex Wodak: Thank you, Alex Wodak, Australia. My question is really to any member of the panel, but especially to the two members of the panel from the tobacco industry. This is a difficult situation we're in where losing every year around the world the equivalent of the population of Switzerland from smoking related deaths. We're dealing also with the legacy of decades of behavior by the tobacco industry that was beyond reprehensible and I think It's good that that's now come out and accepted and acknowledged by people across this issue. But I'd suggest to you that in the next decade, there is one area of science that could make a huge difference, that is real data that exists already, that isn't released, and that would make a big difference. And that is data that the tobacco industry holds on cigarette sales and also of reduced risk product sales. We know that data exists, it's referred to frequently, and if that data was made available, and currently it almost isn't at all, and if it is released it's very, very sparing, but if more data was released, we know it's high quality data, We do two things. It would help drive the policy debate. and it would help improve the reputation of the tobacco companies. How could that happen when the tobacco companies are in, presumably, fierce competition with each other? And I think the answer to that is also fairly obvious. If all the tobacco companies got together and discussed this problem and worked out a way in which they could all release the data together, the same kind of data with the same kind of quality, That would help drive the policy debate, and the more the policy debate is driven, the more the sales of the reduced risk products would go up. So I'd suggest that if you think that's a reasonable suggestion, I'd hope you could take that back to your colleagues that you work with and make that suggestion. Now, I have to acknowledge that this is something David Sweenal from Ottawa has been banging on about frequently and regularly for years, and I think he's right. It's a difficult issue. It's stuck, and we need to have more things like this. And here's an advance that is really hiding in plain sight.

01:05:09 --> 01:08:09

Summer Hanna: So, oh, I feel like by default I'll pick that one up. I assume, having had the same conversation with David as well, part of the thought with this is that if you take the sales-weighted data of cigarettes, you take the sales-weighted data of reduced-risk products over a point of time, and correct me if I misstate this, that you could say, we've watched the sales of cigarettes do this in a specific geography. We've watched the sales of reducers products do this, and we see the inflection point, and we can say that here are the insights that you can gain from that, roughly. So we've talked a lot about this as a concept, because I think at that level, that's an amazing story. Why wouldn't we say that? What I can say as a person who has dug through this to try to tell that story is while our sales day can often look very flawless from the outside, it's only about 75 to 80 to 100 to numerous different inputs coming in to make a model. It's not necessarily as simple as it appears when you look at it in marketing presentations or when our senior leadership hits the street to talk about our numbers. So when we attempted to do this kind of thing, and you may ultimately walk away feeling like I'm trying to avoid the question for a thing that feels obvious, that when we start looking at the models, it's not as simple as that. And when we start trying to track over time, what we wind up seeing is if you start tracking in, you know, let's say a reducers products introduced in May of 2012, And in May of 2012, we had one mechanism that was tracking the sales data of that. And in August, we had 17. And in October, we had 74, and next year we have 378. Because you have so many moving inputs into that data over time, once you start trying to actually do the math, you have a bit of a garbage model. Because you've got such a good reporting mechanism up at FMC, just of how our factory made cigarettes, over how long it's just simply existed, as you look at the way that that sales data is captured for these other outlets, That's changing all the time. So you can never do a good one-to-one comparison on it. So while I appreciate David and probably now yourself after hearing me talk about it say, yeah, that's probably bullshit. But I will say that having looked at it, that becomes the problem in telling the story. That when we use this sort of proprietary company level data, there's just so many inputs into the model that it becomes really complicated complicated to tell what appears like should be a simple story. I don't know if you have anything to add to that.

01:08:09 --> 01:08:47

Carrie Wade: As the moderator, I think I get to bow out and not actually answer the question. So thank you. But no, I know that we've spoken with David Sweenor about this too, and expect that. Hopefully we can get to a place where those questions are answered. I know it's time to close the session. I'm going to leave us on one question to think about, which came from Ignacio again, who's online. And I think it's kind of an interesting question, and so we can all mull it over and discuss over the networking lunch. Is there any science which could be done which would satisfy the naysayers in tobacco control? I think we have a lot to think about. Thank you so much.