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Hi, everyone. Thank you so much for being with us here today. My name is Courtney Breen. I am the farmer analyst here at Bernstein. And I have the privilege of sharing this stage today with Stefan Bansal, CEO of Moderna, as well as David Berman, recently joined chief development officer at Moderna as well. I'm looking forward to a fun conversation. There's lots going on with the company at the moment. stock price is moving a huge amount at the moment as well so there's lots of news ahead and and kind of we're certainly excited for ESMO perhaps just to start really big and broad for those who haven't been following the company as closely although I don't imagine that's many some may know Moderna as kind of a COVID or vaccines company in a couple of minutes what's Moderna today and what's what what is the most material things that have changed in the last 12 months well good morning it's great question actually Modana has never been a COVID-19 vaccine company exactly I know most people think of a company like this one has been since day one an MRN platform company as you know and we've always built the company in terms of how do we maximize the value of a Company by developing the most exciting medicine for patients doing things that cannot be done with other technologies across many, many therapeutic areas. That was our revision since the beginning. And I would say people who know us well, I think in the IPO S1, anybody who is interested in doing research, go read the IPO S1 the intro, I mean, 10 pages or whatever. It described what we set as a company strategy since the beginning. We reinforced it during the IPO process. And then COVID happened. Of course, we never planned for COVID. We thought it was the company's responsibility because we had done nine vaccines in the clinic before to try to get the COVID vaccine in case this was going to become a pandemic to help as many people as we could. And we are very thankful for what the team has achieved with all of our partners to help protect so many people during the pandemic. But that was an off plan. It was off strategy. It was not the strategy. It was a huge distraction, But it was the right thing to do for the world. So what we've been doing since there was enough vaccine available, kind of end of 2021 in the world, is to kind of go back on strategy. But because it takes a long time in this industry to get moving, we're now starting to get to a place where I think people were doing the work, because it's a platform company, so it's complicated. It's not a one product company. But people that are doing the working, I think, are starting to realize more and more in the last 12 months since our Analyst Day in November of last year, where people I think started to say, okay, this is not a COVID-19 company, it's really a platform company. And what's actually just so interesting is that we're actually the only mRNA platform company left. Because if you think about it, CureVac was the first mRNA company. Their vaccine failed in phase three during the pandemic in the spring of 2021. I think because they made a big scientific mistake of an insight we had because of all the research we did and all the investment we did in science, We took a very different scientific route, which I think paid off nicely. They are gone. BioNTech just announced the splitting of the company, keeping the late stage assets in the company and starting a new company. Translate Bio was built by Sanofi, who recently announced stopping the mRNA vaccine programs. So we are de facto because of what happened. The only mRNA company is standing up and the breadth of a company is very exciting because basically today we have a vaccine business. We have five approved products, and launch is happening as we speak. We're launching two products this year, so think about the growth of the next few years. We have an oncology business, and we talk a lot about Intismaran, but that's only our first oncology product. As Dr. David will tell you, there's many more coming that are as exciting as Intismaram, and we own all of these because Intismarat, of course, is a 50-50. We have a great partner, Merck. We have already this business that we should know by the end of the year, Pivotal Data, but those kids have been on study and disease for years, and we've already shared the data many times, the drug is working. And because it's a genetic disease, there's no genetic biology risk, and because it is time-bound phase three, we're not going to have data this year. And then if you look at what we presented at Science Day in June in liquid tumor multiple myeloma, you know, shared antigen cancer vaccine, autoimmune diseases, what, at least three programs, including CAR-T in autoimmune disease, the company is actually becoming a very broad M&A platform, and it's called, from a therapeutic standpoint today, a very, very important, I think, if you look at the next 20 years, immunology company, infectious disease, oncology, autoimmune business. So I think what the team has really done an amazing job in the science and the labs is figure out how can you exclusively use mRNA technology and lipid delivery technology to interact with the immune system of humans. And that I think if you think about the number of disease in an aging world, this is very, very powerful. So I think people who are doing the work over the last years are starting to realize that COVID was just our first product, not the company. Absolutely. No, I think this platform basis is an incredibly important part of the the story and I'm sure we'll continue to discuss it as well as spending a decent amount of time on antismoran which is incredibly exciting David you you joined the company and in March there has been a bit going on there was a kind of some late-stage disappointments with CMV norovirus is being pushed out some really exciting data with within tismor and and some challenges with the FDA in in terms of some of the filing strategies as well. Can you tell us a little bit about your background, first of all, and kind of why kind of this was the right opportunity for you to come into and kind the critical things on your to-do list at Moderna? Courtney, thank you. Thank you for that. So I began my industry experience about 20 years ago at Bristol Myers Squibb right when it was starting to work on ipilimumab, and I helped to develop ipilimuab. And that launched, of course, the Checkpoint Revolution. After about 10 years at BMS, I moved to AstraZeneca, where I led the immuno-oncology franchise and helped to launch Infinzi there. And then three years after that, I joined a small biotech called Immunocore to launch the world's first TCR therapeutic called Chemtrak. So I've always been attracted to innovative immunotherapy programs. And if you look at the arc of my career, and, in fact, it mirrors the arc of the excitement of immunotherapy. It has really been an arc. It's almost been a bell-shaped curve, unfortunately, because there was a lot of enthusiasm for the PD-1 field, a lot of investment, and then it sort of seemed to plateau when the field came to believe PD-2s were the ceiling, that there was nothing really you could maneuver on the immune system to really improve above PD-3s, and so enthusiasm has tailed up. the phase two data that was presented by moderna and mark a few years ago to me radically rearranged that belief and when i saw that data and i tore apart that phase two trial backwards and forwards to try to find the the flaws in it um and i've and actually when i joined and stefan remembers i said this will be a landmark phase two trail because it is the it's the most rigorous beautiful phase two immunotherapy cancer trial that i've seen most times people go straight to phase three And so that's why I joined, because I believed at the time that if Entismorant is positive, it will herald a new wave of enthusiasm, and it's been borne out, in my opinion. And we can talk more about Entismarant and my enthusiasm for it. In terms of what I'm doing here or what I'M doing in the first couple months, it's really threefold. The first is to build a therapeutics development group. There's a superb infectious disease development group, obviously, from COVID and beyond, five products. We need to equal that on the development side. So developing expertise in development therapeutics, number one. Number two is Entismaran. It was to help bring it over the finish line and help it get launched. And then what else do we need to do with Entismalan? And then number three was what we are calling MRED, Moderna Research and Early Development, which is to rapidly move forward those early stage therapeutics programs that should be moved forward and rapidly stop those that shouldn't, to make rapid decisions. And I think that's where maybe my effect might initially be seen is making rigorous decisions on phase one and two trials. Fantastic. Really, really helpful. And maybe just to spend a couple of moments on Tiz Moran, purely from the perspective of we're going to get some new data presented soon. You already have it in hand. It seems like it. and we've got a big conference coming up without kind of giving numbers ahead of that medical meeting how should we be thinking about what clinically meaningful means how should we be be thinking of this phase three relative to the phase two and that path to getting this drug approved especially given there was a potential with the phase 2 and kind of it wasn't able to be delivered against right so I'll I'll take the first step and So if you remember, the initial approvals of pembrolizumab and nivolumab in adjuvant melanoma were against placebo, first initially in stage three, and then eventually also moving earlier to stage two. Those are both fantastic drugs. They beat placebo, and they are widely used and standard of care. This trial adds on to Keytruda versus Keytrude. So it's not a very easy control arm to beat. And the fact that it hit its primary endpoint at the first interim analysis I think tells you one thing. Secondly, it also hit distant metastases-free survival at the endpoint. That was the secondary endpoint. It's the first adjuvant trial to hit both primary and secondary endpoints at the interim. It's the first phase three adjuvant trial to beat a PD-1 monotherapy as an add-on. And then, you know, I think the fact that it combined both stage two and stage three into a single population, because stage two is even harder to beat than stage three, and the fact it still had a statistically significant endpoint tells you about the strength of this data. think this you know the phase two was a phase two trial and phase two adjuvant trials of course are not controlled well enough usually for FDA approval this is an 1100 patient trial rigorously controlled blinded phase three trial so I'm very confident that we have a strong case for approval fantastic and maybe just one of the big questions and debates around in Tismoran at the moment is where else might it work? You've obviously got a development plan that spans different tumor types, predominantly, to your point, adding on to IO where it exists today. However, it's not just early stage indications. You've got some metastatic indications. You've also got some indications that are perhaps not traditionally as immunogenic as others. How should we think about kind of that repeatability of this melanoma data in less hot tumors but also in patients where their immune systems might not necessarily be as as intact and I know you've got some phase one pancreatic data anticipated later this year as well kind of how informative will that be for helping to unlock and answer those questions so there's a couple of ways that I think about it one is if you look at the phase two trial and you look look at the subset analysis by tumor mutational burden, high TMB and low TMB, it's very interesting to see that the efficacy was the same, whether the patients had high or low TMD. So what you can do then is you can take that famous TMB figure plot, which plots every tumor by the distribution of tumor mutation burden, and you can put a line or a bar where low TMG cutaneous melanoma is, and can roughly assume that that bar is going to cover tumors where Entismoran is going to work, because at the end of the day, we need 34 neoantigens in a cassette. We don't need 1,000 neoantigen. We need 34 good neoantigans, and we know usually only one-third of those are going to be immunogenic. So if you create that bar, essentially RCC, which is one of the next readouts that we're going to have, covers that lower TMB and cutaneous melanoma. So in essence, I believe that everywhere checkpoints work, Entismouran should be able to work. It acts upstream of PD-1s. It's actually the first step. It's alerting the immune system. So our initial approach has been in adjuvant melanoma, which is the right place, and then looking in adjudant lung cancer. And by the way, we've stopped screening on our leading Phase III adjuvant trial in patients who had no prior neoadjuvant therapy. We should expect to have randomization complete later this year. That was posted on ct.gov. We have three phase three trials in lung cancer, and then what we want to do is look in earlier stage disease also. This is something both Stefan and I believe. Entismoran does not need, I believe, a PD-1 to be active. You can combine it. There's strategic reasons. Can you say that's a good story? Yes. does not need a PD-1 to be active. I'll pause there for a second because this is a really important point. There was a belief in immunotherapy that everything had to be added on it onto a PD one and I don't believe that's the case. And if you take that to be the belief, which I do, in Tiz Moran should be able to work in very early stages of disease where PD ones don't or aren't used. So we have a a stage one lung cancer trial ongoing at phase three. We have a non-muscle invasive bladder cancer, essentially stage one, in Tismoran trial with BCG that's ongoing, randomized phase two. And so there is our belief that in Timoran can go into very, very early stages and the risk-benefit profile is very favorable also. After lung cancer, of course we have RCC, we have kidney cancer and bladder cancer, which should read out hopefully over the next 12 months or so and then we are studying metastatic disease and now that's a higher risk because in this case you are getting a sample of the tumor from one lesion the patient may have multiple lesions so there is a higher risk there but it deserves to be studied and then finally we're moving into tumors where either the TMB is very low pancreatic cancer exploring or we're looking at tumors where PD-1s haven't been as successful, although some are, and that's gastric cancer. So we are studying the entire spectrum of opportunities for intesmorin. And just to add a couple of things and to step back, if you think about intescorin, we're basically coding in one mRNA molecule, as David said, 34 mutations specific to the patient's cancer. And we know for a fact now we should ask at ASCO in the spring, the translational medicine in data was presented by the MGH group and our team, showing that we know for sure now, we believed it for the last 10 years, now we know full fact, that when you inject OMRNA with Orlipid in somebody's arm, I cannot talk about any other MRNA approach, I don't know, with OMRMA algorithm, because we need to talk about data as well, that's very important for selection. We know full a fact now, we can create de novo T cell in the patients, and we can expand T cells. So based on that mechanism, as David is saying, I think our strategy is pretty simple, and it is one, we believe, we have to prove it in the clinic obviously, that everywhere a checkpoint works, we should add value to patients. We have to do a clinical experiment to know is it, like we saw the hazard ratio of 0.5 in the phase two study on melanoma, or more or less, we're gonna have to that work, and we are doing. One thing we're going to do now with our colleagues at Merck is to look at how do we accelerate new studies? Because we have nine studies ongoing right now, But the plan cannot be the same from when you believe something to when you know something. And now we know, in this man working for X-Ray, I think people will get a good sense of the data soon. And we know the mechanism. And we've always been a very mechanistic company. We don't believe in black magic. We believe in science. And so based on that, what we want to do is to add to I.O. very quickly. And we have a lot of tumors where we know KTDR works, for the great work Merck has done over the years. We want to test that in the clinic with intismoron. The second piece, which is also very important, as David mentioned, is going early. Because in early disease, checkpoints have so long-term side effects, autoimmune disease, as we all know, that they're not used in stage 1 disease. But if you think about where the world is going, and again, I'm talking about the next 5, 10 years or the next 2 weeks, where the word is going is better and better diagnostic, earlier and earlier diagnostic. Think about a world where you could have potentially intismuron as a monotherapy. on a stage one lung cancer that is in phase three study right now or any other cancer and you can get your vaccine at your local CVS because it's an IM. You have to go to a hospital. You can go on your way to work for nine doors every three weeks. How big that would be a deal for cancer patients? And we think lung is a great place to start because former smoker and x-ray, very easy diagnostic, you can catch stage one patient. So we're going to investigate that as strategy number two pillar for Intesmoron. And the third one is to combine it with other agents that are helping patients, because Intesmoron is an orthogonal mechanism. We believe that adding an orthogonal mechanism will help patients. That's why we're gonna go so aggressively, look at that. Fantastic. It's very, very exciting. And obviously, there's a personalized element to this that you've both highlighted that is critically important. And I have two questions kind of on that personalized element. The first is kind of there are partners that are involved in terms of sequencing and all the steps that occur here. I would love to understand first kind of how much of the proprietary work is within Moderna versus relying on any of those other players. And then the second is that when you think about personalization, scale up is also really important. And so can you just help us understand where will be the most likely bottlenecks as we think about the scale up? Is it going to be in the healthcare systems themselves? Is it gonna be in manufacturing? How do we think about kind of the path to expansion for this product? So that's a lot of questions. I'm gonna try to give you the shot, and if I miss anything, I'm sure you'll keep me honest. The first one is very easy. All the proprietary information is within Moderna. What we get from our partners, we are doing great work and very important partners, is sequence of a healthy DNA of a patient, healthy cells, and the cancer cell. That's what we get from them, the raw data. Then everything that happened after in terms of selection of 34 is ours. And we keep it in a very tight wrap, because I believe another piece that most investors do not appreciate yet is the tail that Inti Smaran is going to have. How do you copy Inti's Smaran? How do you go to FD and say, probably this has to generate, it's the same. How can you do that if you don't know what's in the product and every product is individualized? So manufacturing. So manufacturing, a few observations. First, this is a product where we only use from the patient the information of their genes, right? We don't use any biological sample from a patient. So it's very different from other technology are individualized that people can think about. The other piece is it's a liquid manufacturing process with enzyme. So it's not like making your cells or whatever in biotech. This is actually a process you can compress. And I speak as a chemical engineer by training. You can squeeze things down, make things very, very tiny, which is what we have to do because we have to make product for one human. And so it's on the scale up like you have in traditional medicine. it's a scale out, which is the key of a game. How you scale this is make machines that are smaller and smaller in footprint. Why? Because our biggest cost is depreciation of a clean room. So if I can do a thousand machines versus 10 machines in this room, you can do the math on my cost, right? And the second piece is cycle time. Because if I take five weeks or if I take a week to make the products, you do the basic math, my output has a massive impact in terms of what happens economically so on manufacturing i think we're in a very good place because it's all synthetic uh cell-free manufacturing process and by the way it's the team who did covid and just as an important little piece we scaled by ourselves as a startup company we had never done a phase three never launched a commercial product in 2019 we made less than 100 000 doses across all our clinical trial studies And we got a billion dollars out of the system 18 months after. And we had to build everything. Everything. And that team, when we got the phase two data in Tismoran, I told Scott, who was the site head of Norwood, Scott, go take a month or two off. In the meantime, I'm going to look for a site to buy to build in Tismoraan. Because when you come back, I need to do the same thing on COVID for in Tismeran and and go to what you did to help some people with COVID, with cancer. So, I think the biggest bottleneck is gonna be the hospital. I think payers and so on, Merck is an amazing commercial machine. They have great relationships in order to do this in their sleep. It's gonna be, the hospital, and we saw it in clinical trial in a phase two, which in the phase three we did a much better job, is you have to help the hospital move their hands off and getting the muscles of how do you get the biopsy very quickly from the lab, all the data, the patient, all the piece we need to be able to do our work as fast as we can with high integrity in terms of data and quality. And so we have now teams that Merck and us are setting up as we speak, to go and basically to set up hospital by hospital. We're ranking the hospitals across the country in terms very importance. And we're just going hospital after hospital with that team going around and making sure everything works well in the system. We built a great digital platform behind So we can track everything, of course, anonymous, respecting all the patient privacy, obviously. So all this is a thing we didn't even have in a phase three. We didn't dream of having in a Phase 2. So we're just getting stronger, going faster, reducing cycle time. So is there a lot of work ahead of us in manufacturing? For sure. Do I worry about manufacturing? Not a minute. Got it. Super, super helpful. You mentioned, obviously, the scale is very different to the vaccine scale. The cost and the pricing is likely also gonna be very different relative to the vaccines. Can you just help us think through the economics of this and particularly with the collaboration with Merck? How does this commercial structure work? Sure, the commercial structure, you want to think about it as a JV, as virtual JV. Like there's no legal JV but basically we are 50-50 cost in for everything. The sales rep, the clinical study, manufacturing, capex, opex, just cash, 50-50 costing. And at the end, 50% of profit left goes to each company. We wanted to align the two companies, to be totally aligned that there's no funny games or whatever, and that's working extremely well. I have to give a lot of credit to the Merck leadership and to all our colleagues at Merck that are working with our teams. I think at this stage, we want to focus on the data and there's more, because it's tough to talk about anything with value without talking about data, right? So let's work through the data, talk about pricing and other things, and then we're focusing extremely on filing the BLA as fast as we can. Fantastic. Intismarin is not the only oncology product, and I think you've both touched on that. David, can you kind of help us think through some of the next legs of innovation and kind of where the opportunity lies in the application of this platform beyond the personalized cancer vaccine or INT? Yeah, so I think, Courtney, with Intusmoran demonstrating that cancer vaccines or cancer antigen therapies do work, the next logical question for us is, can you have a cancer antigen therapy, cancer vaccine that's off the shelf? And that's where our Lynch syndrome first comes in. So this is a fascinating, it's a terrible disease to have. It's a high risk of developing cancer. but one of the fascinating aspects is patients share neo antigen mutations these frame shifts so it actually lends itself perfectly to developing an off-the-shelf vaccine for neo antigens and we have an ongoing phase 1 2 trial in the UK with the ultimate goal of being cancer interception this is Stefan's vision he kind of articulates which is can you in patients or people there are people they're not patients who are high risk for developing cancer or can you prevent them from getting cancer, which is an incredible vision. So that's number one. Can I just add one or two things on this? Because I'm excited as this doctor on Lynch. So Lynch is basically a genetic disease. It's one in 300 people. Think about the math again. One in 300 of people have Lynch syndrome. As soon as I learn about it, I want to get tested. It increased for some tumors by up to 10x, chance of having cancer when you see a lot of time a 35 year old having colon cancer most probably you have lynch syndrome they might have added a lot of factors like the food and lack of sport and other things that we all know if you look at the data and i had so many emails from friends i had no idea lynch syndrome we know that all this parts of it or employees so it's a big big issue and it's literally myriad as a test you can go do it for a couple hundred bucks it's once in a lifetime because genetics and the idea here is a prevention vaccine So if you're positive, you go to the pharmacy. We don't know if it's once a year, once every two years. David and his team and Oxford would have to figure this in the clinic. But the idea, you get this regularly so that you don't develop cancer. So think about it. One in front of people. And it's exactly, and David, it would be good to have your thoughts, actually the most de-risk application, based on Ninti Smaran, as a wither cross, is Lynch. DAVID GLAZER- Yeah, that's exactly right. neoantigens that the body has not that the thymus hasn't eliminated T cells that are reactive to so to me it's a high probability of success of course we have to do the clinical experiment but that's one that we're very enthusiastic about and by the way we own this hundred percent and think how it could help our vaccine business with retail pharmacies you could make such a product into a retail pharmaces so that's that's our Lynch syndrome program then we have a series of off-the-shelf cancer vaccines cancer antigen therapies which are targeting antigens that are proteins that are expressed and shared broadly across major cancers these are in phase one testing and part of what we're trying to do now is to accelerate these to try and determine do these work there's a higher scientific risk because these are proteins that in theory the thymus may try to eliminate T cells that are reactive to although we do see, interestingly, T-cells being activated when we give the vaccine. So there's hope and reason to believe it can work. But those are the ones that I think are next on the horizon for us. Behind that, one of the benefits of our platform is multiplexing. And although there are T-cel engagers being studied in myeloma targeting single targets, and now there are P-cel engages targeting two targets, We are the first company ever to multiplex three T-cell engagers into one single drug. And we have this ongoing phase one in multiple myeloma in heavily pretreated patients, many of them who've received multiple T-cel engagers or multiple different CAR-Ts, so a completely unmet need population. And that trial is progressing well, and we'll share that data later this year. And this is a sentinel program for us, this multiplexing T-sel engagers, Because like in Tosmoran, Sentinel program, if that works, it de-risks potentially other cancer antigen vaccines. If this multiplexing T-cell engager works, it leads us to further invest in other programs for solid tumors in that case. And then we have what I'd like to highlight also is our autoimmune program. Because in essence, this started as an mRNA company platform, But it's an immunology company with viruses, immunotherapy for cancer, and now for autoimmune diseases. And at our science day in June, we talked about our in vivo CAR-T program, which is heading to the clinic. And then we have several other programs for autoimmune diseases as well. So I think over the next maybe 12 to 18 months, we'll be able to share additional progress on where we're going with these other exciting programs. Fantastic. I have perhaps a quick question on PA, which is one of your rare disease indications that will read out in Q4, and you've got MMA as well. What does a good result look like, and does this unlock a broader rare disease platform, or is this a two-program franchise? It's a great question. So like everything we do at Moderna, we don't like onesies. I'm not interested in onesies, too much risk, too many risks. Too much money. we like broad platforms within the big mRNA platform and so the way we've always thought about where this is in the liver is if we get into the liver given the liver it's most probably the organ in our body that makes the most protein and what we do with mRNA is to give instructions to your liver to make a protein to give gain of function that if you look at just a list of disease that unfortunately many people have around the world that it was going to be very, very large opportunity, even to the point that at some stage, not for today, for some disease, because we are end of 10 or 20, do you do an like approach and go deal with that tail, but that's more of a public health standpoint and bring the right thing for patients and the world. The financial opportunity is going to be on the front of a curve, obviously, and PA being one of them. And so, PA for us is just with the risking, like we've always done with capital, being very disciplined because we have to manage technology risk. It was the first of another family of lipid, injected IV, not IM, like in T-Smeran and so on. So we have a lot of new things that we wanted to carefully manage and understand in the clinic to then have a load of assets going forward. For anybody who does work, as I said, to understand modern AI, you have to do work, I'm sorry. But if you do work and you can use AI to help you do the work faster, you can see we have published more than 12 different models of rare genetic disease in the liver. They're all published. Some of them have been out there for five or six years. They are ready to go into the clinic. It's just a financial discipline. We use the same lipid as PA. It's the same as PA, same manufacturing. Think about the manufacturing leverage in terms of PNL because we can do all of these off-season. Because today, of course, the goods don't look great. Why? Because for half of a year, we do nothing. Because we're in a seasonal business with vaccines. But what if you can start loading the factory in a month where you do nothing? We're making a rare disease product, and just use your fixed cost, and you can do the math yourself. So, rare disease is going to be important for the patient first, important for us. In terms of outcome, look, I'm a pretty pragmatic guy. Look at the Phase I-II data and how you looked at one year, two year, three year. We've showed those swim lanes, and I don't expect anything different. Those swim lanes include the kids that were at the lowest dose because it was a Phase I, II study. Despite the kids at the lowest dose, of course, we think being under-treated therapeutically, if you take the kids that the dose as is in a pivotal study, like the data is wow. So I expect great data when we get, because again it's not black magic, it's a rare disease. So that's going to be really interesting for us. It will help of course in terms of top line growth. Again, talking about long, long runways. As an owner, entrepreneur, you know, I've been here since being at this company. I don't care about the EPS next quarter. We manage EPS for next quarter, and the team has shown great discipline. I care about how do I create a 10x return over the next five, 10 years for all of the decisions that we do. I've done it since day one. I'm still doing it now 15 years after. And so the way we think about this opportunity for us is we can help patients. We can have very long duration. Because if you look at our free business today, as we said, vaccine as massive long-term because the barrier to entry is so high. A billion dollar phase three is not for faint of heart, right? And so we have great franchise there for a long time and as we know for all the vaccine companies the sales keep on going for a really long time. We talk about intesmurine that maybe it's gonna be really hard to copy and then rare disease, same thing, how do you get a kid on another PA drug once, if it's approved, our PA drug is approved. How do you convince a KOL parent to take their kids off a drug that is working to try a new drug that might work? How do we do that? Which is why, as we all know, the rare disease business for those companies, the rare diseases business, as Henry showed us with Genzyme, have also a very long tail. And so that's how we think about PA. PA is just the first, a bit like COVID was the first product of the company, the first vaccine of the company, pH as the first release in the liver, they're going to be a lot. Fantastic. That's really, really helpful to understand the potential breadth of this opportunity. Perhaps just to pivot to, you mentioned a couple of things, one on kind of trade-offs you're making internally, and you also mentioned on that long-term direction. So I want to ask these two questions and then you can use the remainder of the time to answer. The first is you raised recently, you raised another $2.6 billion in convertible notes only a few weeks ago off the back of the INT excitement. What does this money do? What does it afford you in terms of the trade-offs that you otherwise would have been making or can make now? And then finally, long-term direction. You spoke about it's not about EPS next quarter, it's over the next 10 years. So So let's project 10 years into the future. What does Moderna look like to you? It's going to be much more of the same, but that's faster cycle time. As you know, Mike and I just talked before me about what Generate is doing. We are doing a lot of AI. We don't have time to even talk about AI so far. I could spend a day talking about AI because I'm so excited about what it's going to do to the field and to us as a company, not only in science, but also in our ability to process things much faster, to reduce costs, to have a much more agile company. As I've told when we, to our team, David was in the room and Lavina was in the room, when we announced our team that morning in August in this brand data, I told them, watch my lips, this is not our best product. And I believe it in every cell in my body, this not our best product, it's an amazing first oncology product. And I say that because we are living in this very exciting time in biology and AI is accelerating things so fast, which is we don't know how our body works. We know parts. But the next five, ten years are going to be an amazing time in human history to be able to learn that in the field. But then what we have is a platform that is an information molecule platform. And COVID was the best example for people who want to connect the dots. The virus was put online. Sorry, its sequence was put on line. My guys developed in 10 minutes a vaccine in silico in a computer It took two days to validate everything because I told them, you know, it's gonna be in the clinic in 60 days Are you sure and they look at me say what do you mean the clinic is 60 days? We don't do in 60 years when a clinic so are you sure so it took two Days to check and do models and 3d simulation and so on and they came back Yeah, we show and by the way that same sequence the design in 10 units on the computer and I'm not exaggerating It was a copy and paste of a sequence online literally and then on pull down menus in our system choosing which chemistry for the mRNA which manufacturing process which lipid but it was a copy and paste from a computer online that's how we develop medicine now think about people doing small molecule or large molecule in big pharma so think about that why do I use that example because if tomorrow is a paper from Harvard or China or Australia about a new gene doing XYZ my guys can get on a computer and in 10 minutes of a new medicine. Think about that tailwind we have on top of aging population with vaccines and cancer and autoimmune disease, which are all number one risk factor, age. So when you think about where Moderna is going, I don't know precisely, but I know it's going to be really fun. And I know we're just warming up. The last few years have been hard, and I'm so thankful for the team that have worked with so much headwind. You know, it's not fun when your sales go down 90%. We had a patent expiry on the company. Pharma always complains they lose one product. We had a patent expiry experience, minus 90%, on the entire company. And we restructured, the team worked really hard, and we kept our eyes on the long term, which is focus on patients, focus on science, focus on execute, collaborate together, because this platform is stronger than before the pandemic, because it has been proven, and we raised a lot of capital through supplying the vaccine. So now, we're just executing and the world doesn't understand yet where we're going. Because most people are not doing the work. If you do the work, if you look at all the data we have and Lavina and our team can help you connect the dots, if we do the the work where we are going is very exciting. Fantastic. Thank you so much, Stéphane. Thank you, David. I really appreciate your time. Thank you. Thanks, David