Bonus: Vaccines for dummies with Moderna President Dr. Stephen Hoge

good news. Remember what that's like. Fisser has sought emergency use authorization for its vaccine after a study showed it was effective. Asked. Resenica has seemed very promising results as well, although they're still figuring out the dosing. And then there's Maderna, a tiny biotech firm compared to these giants, which has also cracked the code on a vaccine using a novel approach. Stephen Hoague is a doctor, a scientist, and the president

of Maderna. I had a wide ranging conversation with him about his company, the pandemic, and the vaccines and the pipeline, who gets them and when call this vaccines for dummies. I started by asking him how excited he was when he first heard the news that Maderna was making it happen, doctor Hope. Last week, Maderna announced it had developed a

vaccine that was ninety four point five effective. What went through your head when you heard the news, Well, I had the privilege of actually hearing it live from the Independent Data and Safety Monitoring Board. It's called it dsmb UM. So you're called into a virtual room with eight or nine senior academics, real leaders in their field, and they

start reading out the results to you. And the first bit was a little bit of the procedure, and the second they started calling out the case numbers, and they said that of the cases cases were on placebo. And I'll have to admit I went ear to ear with a grin and almost didn't hear anything else for the next two minutes. Um. It was this feeling of incredible relief. We've been working really hard for a year, but for many years on this technology, and it's just this feeling of, oh,

my goodness, it hasn't all been for nothing. There is going to be a vaccine. It's available. It quickly passed within within about a minute or two, it turned into this dread of the work we have ahead to manufacture and distribute hundreds of millions of doses in the vaccine. But but it was a really wonderful day lessunday. Tell me what that means when you say without getting too and the weeds. Uh, ninety of the patients were on placebo. I mean, can you just boil down the news you heard?

And so somebody at home without any kind of medical background might understand. Sure. Yeah. Let me let me start by described being the study that we were that we were running. So the clinical trial involved thirty tho participants and the value of these clinical trials is that their placebo control. And so you randomize people one to want to either receive a placebo or the vaccine. And so there's fifteen thousand people that received placebo and fifteen thousand

people that receive vaccine. And for the last two to three months, those people have been going about their daily lives, hopefully practicing social distance and other things, but ultimately going to work and doing things that might give them a risk of infection. And what we've been doing is an independent data and Safety Monitoring board has been counting out every time somebody becomes infected with COVID where you confirm its COVID and they've become ill, maybe severe COVID or mild,

it doesn't really matter. They're they're just trying to see where their cases happen, and those cases are counted up until there's overwhelming statistical evidence that there were more cases on the placebo arm than the vaccine arm. And as that happened over the last three months, what eventually came transpire, what we and about last Sunday was that they had reached nine cases. Ninety out of the fifteen thousand people on the placebo had developed COVID, and that contrasted with

in the fifteen received vaccine only five cases. Only five people had contracted CODE, which meant that the relative protection was about ninety four point five the difference between the ninety out of fifteen thousand and five. You described the moments before the call revealing these results as the most nerve wracking hour of nerves, of a nerve wracking week, of a nerve racking year. Yes, it's been really long.

I think we've all lived it, uh and so our experience that during our my experience have been no different in some ways than what we've all gone through in our lives. Everything feels disrupted, everything feels like it's on pause. The difference for us is that we have been working nearly seven for about about nine ten months now, never a day off, trying to advance this vaccine. You know, on the belief that it was going to make a difference, but until you have proof, it's just belief. And so, uh,

it was. It was a nerve right that final hour, that final weekend when you knew the results were in. But it's a bit like it's at the OSCARS and it's an infin in an envelope. You're not allowed to open the envelope. Only the Independent Data Safety Monitoring Board is allowed to open it. And they've got a scheduled meeting two days from now, and so for those forty eight hours, you're just tossing and turning. Um, my wife said,

I was. I didn't sleep the entire time. I thought I did, but apparently I tossed and turned all mine both right, And I know everybody else that was involved in the study, even outside of the company, probably felt the same way. Uh. And then of course you get

news that they've gone into the room. Um, and so they've the virtual room, they started their meeting, and you're just waiting, just waiting for them to call you in, and an hour goes by, and a second hour goes by, and you're you're you're biting your finger, and I was going, Wow, what's going on? How could it be so difficult? Uh? And it was finally at that last moment that we were let in about noon on Sunday, UH and heard

the results live. Operation warp Speed basically encouraged a lot of companies to come up with vaccines, and in fact, Viser and now astro Zeneca are coming up with vaccines. How do you feel about these other companies that are coming forward with their own vaccines? Is that good news? I think it's great news. Um. I think if you everybody sort of accepts that the only way we're really going to stop this pandemic is a vaccine. We have

to beat the virus everywhere. And since there's billions of us on the planets and you know us, we need many billions of doses. And so from the beginning, even from earliest part of this year, we said the most vaccine we'd probably be able to make in one is about a billion doses, and we're still on track for that. But one billion doses will only cover half a billion people, five and a million people. There two doses per person exactly,

that's right. So since our vaccine requires two doses per person, it would only cover five or million. So there are literally billions of doses more that need to be created by other persons. So as a group of companies, we've actually been rooting for each other because if we only end up with five million people covered, the pandemic doesn't end.

We don't get our lives back. Um. And so what's really been happening between the companies coordinated by Operation warp Speed, But frankly, I think between the companies organically is an unprecedented level of coordination because everybody recognizes that we all have to deliver. When when any one of us achieves a result like we did last week, we often email each other and I emailed congratulations to ask Prozonica just

this week, because we're counting on each other. We're counting on them to come through, just like they were counting on us to come through to feed back to ours. Why is it so difficult to produce huge amounts of these vaccines. No, it's the numbers. If you think about it, the absolute numbers of vaccines there's not many things that we create as in this world, and drugs have to

be made to a very high standard quality UM. That have that to be a complexity that we make billions of, right, we make lots of things that are smaller UM, but it's the it's the complexity of making a medicine making sure it's done to the highest quality standards and the highest degree of control. That adds the additional challenge. It's not just like trying to create something else that we might create billions of every year as a society. And

so you have to invest in manufacturing. You have to invest in purpose built manufacturing lines, you have to train people. They have to get extremely good. You can't get it right of the time. It has to be multiple sigma here to be nine UM. And you have to establish quality systems around that that allow you to measure it and control it and make sure that when somebody takes your vaccine, whether it's madonnas or astrosenacers or visors, they can be sure it's a high quality vaccine. It's gonna

work for them. That process just takes time and money and effort from people, and even with the incredible financial resources that the US government has brought to their UM and many of the companies are brought to their it's still a huge lift, UM, and there's still lots of potholes along the way that you have to plan for and get act. Let's talk about the technique that you and Fizer use, something called messenger RNA. Tell me about tried to explain it to me. I think I got it,

but I'm going to give you a chance. Can you explain for people who have an eighth grade understanding of science, how this actually works? Right? This is one Katie, I might have to take a couple of stabs at because I'm still working on explaining this to some of my family after after ten years in the field. It's it's there's something a little bit counterintuitive about it. But but let me try so. Messenger RNA is a molecule that

exists in all of ourselves. UM. That is the instructions for making every protein in your body, every protein in life, UM. And so it's just a set of instructions. It literally tells us all what protein to make, it how much of it to make. It's a very natural molecule. In fact, if it's one of the oldest molecules in life, and what we do as a message company is rather than giving you the protein, which is what most vaccines do. If you think about a flu vaccine, you'll grow up

the protein and eggs or something like that. You'll purify it. You'll then administer it in the body will have an immune response to that protein, so learn how to fight against the virus that protein. What messenger ARNA is is it's just the instructions for the body to make that protein itself. It sort of works with your body, not on your body. It provides the instructions to yournune system so they can make copies of the protein as if they'd encounter the virus, as if Stars Kobe two had

snuck in, but actually it hadn't. They just got one piece of instructions, one part of the virus that they then make copies of that protein and then learn how to defend against it. In this case the spike protein, so it probably I am getting it, so it triggers the immune response in both cases, but in this case you're not You're you're not injecting the body with a version of the virus. You're simply instructing the cells how to deal with the virus. If in fact it happens,

that's right, that's exactly right. And the big differences do you inject the virus or a broken piece of the virus or do you just inject the instructions for what the virus looks like? If you will all wanted toister that, then the immune system gets to learn on and train on and when it encounters the virus, it's not naive. Your immune system knows what it's looking for, says, oh, I've seen this, I've seen this wanted tister before, and

I'm now going to be able to protect this. So this is the method that Maderna and Visor used, But astro Zenicas is more old school. It is UM, it's more UM, it's more the traditional way. There are there are six big efforts in vaccines under the rubric of operation work, speed, and so there's two Messenger Arny companies, and there's two companies working on viral vectors is what they're called. And so astra Zeneca and Johnson and Johnson are both working on viral vectors. What this means is

you take another virus. In the case of astrosenneca, it's a twopen ze virus. And you cause that virus to make a copy of one of the proteins on the stars copy two virus, and so it kind of makes a mimic and you inject that You grow up that virus, and then you inject that virus into people and it sneaks into their immune system, infects them because it's a virus and makes copies of that protein. That technology using

using engineered viruses has been around a bit longer. The longest in the tooth technology is actually something called we're combinant proteins um and the last couple of companies, so Sena Fee and a company called Novavax, are working on

a combinant protein appropaches. That's where similar to what you're used to do with your flu vaccine, you grow up the protein in a culture or in the case of fluids and eggs, and you purify that protein now from the surface of the virus, and then you inject that piece of the virus into the body. Knowing that you may have a best at interest. Dr Hope Um, is there any approach that is preferable over the others. I'll confess I'm I'm ten years into a story. Believing messenger

RNA is going to be the best approach. So I'm not a d percent objective, but I am a scientist as well, and I think they all have pluses and minuses. One of the advantages of messenger RNA that we've always thought uh is, frankly is being brought to bear right now is the fact that it's so versatile. The fact

that it's really just information. It's more of a digital technology where we can use our systems are manufacturing systems for any vaccine has allowed us to go incredibly fast, and I think that proof is in the pudding in the sense that both Fiser and Maderna to Messenger RNA approaches have been first to be able to produce phase three results despite these being new technologies, and hopefully you're going to be able to distribute millions of doses this year.

Being objective, I think the other approach that is the most established is there comminant protein approaches. So the approach being taken by Santa Fia Nova vacs where you make the protein, you purify it using pretty traditional approaches, and then you injected into the arm directly. And that's a situation as an approach that's got many decades of experience UM and ultimately works well within the infrastructure for vaccine distribution UM that already exists out there because it's you know,

decades old. And so if you were to sort of pick on the extremes, the fast and new UM and hopefully in the long term, I believe quite quite positively disruptive would be Messenger RNA and the more established UM and precedented or common protein are probably the most known. The adamovol vector approaches being taken by Astra, Zeneca and

and Johnson and Johnson are all equally valid. There's there's not really the same history as our common protein and they're not quite as fast and simple as Messenger our name, but will be very grateful if they're able to deliver billions of doses and help self the pandemic. And so you're rooting for all of them, and frankly, I would take any of them. I hope to get a Maderna vaccine personally selfishly, but I would I would feel comfortable based on the data that I'm seeing on phase three

receiving union. When we come back more with Maderna President Dr Stephen Hogue once again, Dr Stephen Hogue president of MADERNA. Let's talk about Messenger RNA. Does it portend a lot of exciting breakthroughs for other diseases? You know, I'm thinking, why can't we come up with a cure for cancer if we can get operation warp speed to develop all these different vaccines and record time. It's a great question.

And we at Maderna had been working on this for about a decade um and so we actually have five programs in clinical trials against cancer right now using message our including at least two programs that are vaccine approaches and three programs that are therapeutic approaches. Those are in earlier stages of development and so their phase one in phase two studies, and we're still proving the potential of the technology there. But we have approaches in other therapeutic

carriers as well, rare diseases and autommune diseases. And we do think ultimately this technology will change the way people

make medicine in the future. We think about it, we move away from creating drugs that work on your body they kind of come from the outside and do something to it, and actually try and move to a world where we're just providing information to yourselves to your body in the way that's used to processing it um and the instructions for for how to either treate a disease like cancer or prevent a disease like stars Kobe and I think that's the exciting part of messenger urity that's

generated a lot of enthusiasm for us over the last decade. We never intended to be a COVID nineteen company. We still don't think of ourselves as a COVID nineteen company. We've certainly got an allot of attention to become a bit of a household team because of it, and so in that sense we have to recognize it. But I think the potential of the technology is is just starting to be discovered, and I'm really excited about the work we're doing exactly in cancer right now, because I think

that that potential could impact our allives as well. Other than cancer. Do you see promise and other diseases like I don't know, Parkinson's for example, and some of these neuromuscular disorders at Alzheimer's. I mean, do you think that that you can can sort of help the body respond to some of these things when it goes haywire? I think so the question is when, all right, if you if you ask somebody like me, an entrepreneur, UM, it's

just a question of time. And I do think some of those diseases, well, we will get there and I absolutely believe will make a difference, but it will probably take a decade. And the reason I say that is there's a lot of complexity in some of the diseases you're listing out Alzheimer's and Parkinson's. UM there's a huge inflammatory component of the immune system there, but there's also other things happening, and so it will take some time to figure out how to use a new technology like

this to try and address those diseases. Whereas some of the things like infectious disease, metabolic diseases, heart diseases, where we're actually working right now in clinical trials, UM, you have a better understanding what's going to be required when you use a new technology of this. So I view it over the twenty thirty year time horizon as absolutely and that's what we're committed to trying to do. And obviously cancer, as you mentioned, is a huge area of

rethink you can have an impact. Absolutely, yeah, we've made In fact, if you look at our pipeline. The second largest area of clinical work we're doing clinical trials is in cancer, any particular cancer. I'm just curious. So we have our most advanced programs. There's three of them. UM. One is in skin cancer and so melanoma. There's a it's a randomized phase to traveling. We have a program in head and neck cancer SCREAM and cell carcinoma in the head and neck UM that's in an expansion covert.

And then we have a no variant cancer phase to study that's up and running as well. There's other cancers we're looking in, but those are the three most advanced. So exciting I think to hear about this and hopefully calling cancer that's my particular area of interest and concerned,

so hopefully you guys can work on that too. Let me move back to the back vaccine sort of in general, let's talk about distribution, if we could, Doctor Hoag, how involved are you in distribution and how concerned are you about rapid distribution to the populations who need it the most? So I think we're all deeply focused on making sure the vaccine rapidly becomes available as many people as possible. Selfishly,

we want our lives back. But truly it's been about all the what we've done is all for not if we can't get the vaccine in the arms of people who needn't want it UM. So we've worked with the US government and particularly the folks at the Department of Defense under operational warp speed. It's a general Tarnis team pretty intensely over the summer and fall in anticipation of

an approval or an emergency use authorization. It's such that you know, we now know down to the hour what's happening post approval, post authorization to try and get the truck's rolling, if you will, to the States so they have access to the vaccine. We've been working to make sure they understand all of the characteristics of the vaccine,

how it has to be stored and distributed. We've been working with companies that they brought in, like McKesson uh to to start deepoting and stockpiling some of the vaccine UM and we're going to continue to work around the Clockett it seems we're literally two seven as an operation right now. UM to make sure that we're manufacturing on a regular schedule, delivering those are getting filled, and then

ultimately move into the distribution supply chain. It's important to note that as a company, our limits we we have, we're only about people, mostly in Massachusetts, and so where we will hand off to the government and rely on the government for distribution is after filling at the factory and ultimately from a depot. Distributing to the states is something that really only the United States government and the

states can can manage effectively. So that will be the primary mendisum by which people will get their vaccines through their state departments out. Have you guys applied for emergency authorization already? If not, what we've said is sometime in the next week or so, we expect we will, but we've got work to do. We just got access to the data last week and as you can imagine, there's a tremendous amount to pour over and to prepare UH appropriate and high quality filing for the d So we're

working on that now. Expect that to happen um in the next week or so and then UH and then we're hoping for an emergencies authorization sometimes a second half to set. When do you think your vaccine can get out there? Do you have any timetable, yet it's entirely dependent upon the FDA, So you know, I always want to make clear that they have a solemn and important responsibility to decide that it's appropriate distribute that we think the data is compelling, and we're going to ask for

permission to do that. But it's it's a very important part of our society that we have an entrepreneurship on one hand, and then we have strong civil service that actually provides a check on that and a review on that, and that is a key part of our industry. So the FDA are the only people that can decide when this happens. But on the assumption that they decide uh within the next two to three weeks, let's say, is in the middle of December, which is where we are

we're aiming ourselves. We want to make sure that we have as much vaccine available as possible for the second half of December to start that distribution process, and we've been working towards about twenty million doses by the end of December that we'd be able to hand off to the folks at operation work speed, so that they can actually literally get it into vaccine centers as fast as possible, and that would vaccinate ten million people because doses are required,

that's right, So twenty million doses by the end of December would vaccinate ten million people. But we'll continue manufacturing and so almost every week or every other week from then forward, we will keep making deliveries. We've committed to deliver the first one million doses to the United States government, and frankly, there are options for them to buy up

to five million more UH. And so that first one million doses will be delivering, you know, on a straight schedule through January and February, and then perhaps continuing through March a point and may, depending upon whether there's a need. Who will get the vaccine first? Do you know, Dr oge I don't. It really is up to the c d C UM and their Advisory Committee on Immunization Practices UM.

At the end of the day, the federal government is as deluted to them, the responsibility figure out who gets it first. It's fair to say, though that the CDC will just issue guidelines. UH. What will really happen is Operation morps Speed will distribute our twenty million doses in December to the States in proportion to their jurisdictions, and then the individual states will look at the CDC guidelines, look at what's happening in their communities, and decide the

best place to deploy. I think if everything goes to the CDC guidelines, it's pretty clear that the healthcare providers, those frontline healthcare workers that we need to keep safe during the pandemic so that we can keep caring for people when they come out, they're going to be the first folks vaccinated, and there maybe up to twenty million

of them across the country. Does include people who need to work in nursing homes and hospitals and primary care clinics, and that's not just to make sure that they're protected from COVID for COVID sake, but to make sure that they're able to do all the other important things to protect people who are having heart attacks or pneumonia or all the other things that happened in our day to day lives, UM, and that they're not outstick during this

important time. UM. Then I think you moved to critical infrastructure, so frontline workers, people who work in food security, people who work in UM, in government, and firefighters, police first responders, and then ultimately to those that are the highest risk of severe COVID nineteen, so those over the age of sixty five or those who have co morbid conditions. And I think that's where the CDCs recommendation will come out. Certainly based on the conversations, that's what it seems like

will be the guy that's what about children? School aged children? Will school aged children be vaccinated? I hope. So. I gotta tell you, as a parent who's been doing virtual school for for most of the fall and expect to do it for a good part of the next year, UM, I feel deeply to need to get our kids back in school, make sure the teachers are saving and get our kids back in school. And so, as a company, Maderna, just like some of the other companies, have begun the

work of showing the vaccine is safe and effective in children. UM. That starts with adolescence, so those twelve one up and then you move into the five to twelve year old school age kids, and those studies are actually starting in

the coming weeks with us and others. The goal of those will be that by let's say the end of this school year, there will be data show the vaccine is safe and effective you know the right dose to give to children, and ultimately we all want to make sure that everybody who's a schools child could receive a vaccine before next school year, so that we could we could start in September of two one the normal school year, Soccer games on Saturdays and everything that we've come to

miss so well can't be part of another clinical trial because they weren't part of the initial ones. Correct, that's correct. They weren't part of the initial ones UM, and that's appropriate. You want to make sure a vaccine is safe and

effective in adults before you enroll a kid. There's there's there's obviously a whole bunch of extra considerations, including the fact that a child, um you know, is immunologically can be different, and so you can you want to make sure that there's a potential, clear, potential benefit of the vaccine before you give it to a job. So children were not initially involved in the Phase three trials, but they are rapidly getting UM tested in them right now,

and those are much smaller trials. You do not need thirty thousand people. It's more like a couple of thousand children, because really all you're looking for there is to make sure that there's nothing surprising in terms of safety or the dose level that you need in a trial, and that's not you're not looking for infections as a measure of efficacy. I know diversity in clinical trials is critically important and there hasn't been nearly enough in the past.

How were you able to ensure that you did have a diverse population. Well, the first thing is we had to recognize that initially it wasn't very diverse, and so we started our clinical trial at the very end of July, and by the end of August, about one month in, we'd recruited about half the trial, about fifteen thousand and thirty thousand people. But the population was was unfortunately not

very diverse. Um there was only four five percent African American, there was around ten percent of those of Hispanic or Latino descent, and it was it was clear that we were not going to have While that might be okay by historical standards, it was not going to be enough to generate real confidence in the vaccine in those communities, and so we took a very difficult choice. M the first week in September, we came up publicly and said

we're failing to meet our expectations. We need to look more like the country in terms of the ethnic makeup of our of our trial, and therefore we're going to slow down our quote unquot trial in the middle of the pandemic in a bit of a race against the virus and maybe a friendly race against other companies. That was a pretty tough choice to me, but it was one that we thought was the right thing to do.

The reason we slowed down is that we we thought we need to go work with the one hundred investigator

sites across the country that we were working with. These are doctor's offices and local communities UM and help them figure out how to reach out to those communities that are underrepresentative, particularly the black and hispact communities UM who were massively underrepresented our study, and do everything we can to help, you know, work with them, build trust with those You have to leave the door open, you have

to work three times. Is hard in places where there is not trust, and there's a huge trust deficit in those communities. We had to bring in new materials, we had to do training on bias, we had to do we did a whole range of things. We even engaged Dr Fauci and and the Surgeon General in outreach, we brought in other experts and it was all focused on let's do everything we can to try and invite those

communities with the trial. We're really pleased to say that six or eight weeks later, when we completed enrollment, we'd actually increased the ethnic and racial makeup of study to be almost bang onto the United States. Um there was only sixty folks of white non Hispanic origin over over spending her Latin X, which is obviously higher than you see in the country, and over ten percent Black African American, which is a little bit lower than you see in

the country, but substantially. It gives us great pleasure m to have accomplished that. But that's just the first step. We know that the data therefore will be sufficiently representative that people from those communities to have confidence the vaccine was evaluated and if it's effective, it's effective in them,

and in fact we announced that it looks terrific. The results look equally good in those populations, but that still requires us to work the next step to build trust with those communities to receive the vaccine, and there's a lot of vaccine have with hesitancy across the country, including in those communities, and we've got work to do there.

The one source of optimism that I'll take from it is it it did show that in the middle of a very difficult year on those sorts of issues on race relations in particular, if you're willing to take the time, slow down and work can build trust. It's hard work, but you can do it. Um. And I I think we were proudest of all of those one sites and those investigators, they're the real heroes there. And actually they went back into communities that had not wanted to participate,

tried harder and build those relationships. So I take optimism from it. I always I'm optimistic by nature. Um. But it does show that it requires more work. Um, That if you're gonna correct an inequity or and imbalance, you're going to have to do it with additional effort. It's

not going to come just from equity your valance. And as you say, you still have a lot of work to do to convince the population writ large that people of color can trust the medical establishment, given the the very uh checkered history with Tuskegee and operating on enslaved people. I mean, it's it's going to be a bit of a health to climb, isn't it. It is? And the history here is horrible, and so this mistrust or this

distrust is well placed based on a lot of that history. Uh, there's and we were coming at this partner with the federal government through Operation War Speed through NIH uh coming forward and saying hey, we're an exciting new biotechnology company partnered with federal government here to help. Don't start in

a place of immediate trust. Uh. The thing that we discovered was most important is that you have to work with those those voices that are already trusted in the community, whether those are faith, faith leaders or people that are

just present in the community offering healthcare advice. Um, there are there are voices there who can actually carry that message, and you have to make sure they understand and they have access to information, they make their own judgments about whether whether to recommend this or not, and those that

do can then become powerful advocates to their communities. But you're not going to do it just by coming in and saying, hey, we're here to help, because frankly, the history on that as you just point to a Tuskegee UM and other instances has been quite quite horth We'll be right back after this short break. Let's talk about

the storage requirements. MADERNA and five or vaccines dr Hope require special treatment if you will cold temperatures from madernast sub arctic temperatures for fiser and outside those conditions, they have a limited shelf life. Does this give astro Zeneca's vaccine and edge because it doesn't have those requirements, It can be produced in mass quantities and can be shipped and uh, and it's and it's quite inexpensive. Are all those things pointing to a better situation for astra Zeneca?

I well, I'm grateful for the fact that astro and it can make many more doses, and so yes, I think, I think in some ways it is UM. There are differences. So you know, if you look at our storage conditions, our our vaccine can be stored in a standard freezer or refrigerator. It doesn't require any dry ice or special equipment. Most refrigeration comes with freezing and the temperatures are the same as you have in your home fridge. It's the kind of thing that exists in almost every pharmacy in

this country almost every doctor's off office. We do need to be stored in the freezer part for up to six months, and we only last about a month thirty days in the refrigerator. UM. And that contrast with AstraZeneca as where you pointed to, I think they're they're currently the most amenable distribution where they last six months in the refrigerator. Now they still require refrigeration, uh. And so you still need a piece of equipment that exists again

much more broadly available. But there are not vaccines right now that are stable at justist room temperature that can

go into those non cold chain logistics. So I think the reality of the AstraZeneca vaccine, the reason why I was so excited about the announcement this week is that although the efficacy wasn't as strong, uh, you know, the average efficacy was sev versus the potential for many more doses and for being the ability to distribute them into areas and maybe don't have freezers but do have refrigerators.

UM provides a real opportunity here. UM. The cost of the vaccines, I mean, I I think in general cost does matter for sure, UM, and the Astrogenica vaccine can be made more cheaply, which is good, but it's important to know that the costs of these vaccines, whether you're talking about five dollars or twenty dollars, is a PRODCE is a is a fraction of the costs that are being incurred just with things like testing UM you know, which we all seem to do on a on a

regular basis, or any of the other interventions. And so they're they're quite they're quite reasonably inexpensive. One of the things that I think um is exciting about vaccines is and it's often said that next to clean water, nothing has done more for human health than vaccines economically and

socially in terms of value. But there is a focus on the difference between the three pounds or the five dollars and twenty dollars of the prices, and in that sense, I do think it's it's it's good that there's a lower cost option in the Aftrizonica vaccines. So how much will the majournal vaccine cost. So we've entered into agreements with governments, the government of the United States agreements of

its average price about twenty dollars per dose. UM is so the first doses are fifteen to sixteen dollars uh, and that's you know, where we're selling it to. Almost all of the sales has have been to governments, to be fair, because governments are the best positions to distribute this. This is not something in the first half of next year during the pandemic phase that many of us are going to go to CBS and get or rite at of a wall. Grief kid, it's it's really going to

come through your public health departments. So at twenty dollars a dose, that's that's forty dollars per two doses roughly. Um. It's you know, it's hopefully uh not a big barrier to broad adoption. In fact that we we priced it that way with the U. S. Government and sold to USE government on the principle that it would be given free to every American regardless of their ability to pay. So we didn't we didn't try and maximize price or anything.

We said, we want to make sure this is given away, and the US government has agreed that they will not charge anybody for those doses, regardless of your ability, and so essentially the vaccine is going to be free to Americans every vaccine that's being created, Every vaccine purchased by works operational work speed, including the Materurna vaccine and the astros in A vaccine and Fiser vaccine, all of that will be free to Americans through the worst speed and ship.

So well, I get to pick which vaccine I want, I don't think so I don't know. UM, it's it's that is that is one of the the The reality is that the the Department of Health in your state UM may or may not want to engage in that kind of you know, letting people choose which one they'd like. I laugh only because every family member I have will be really upset if they don't receive the Materna vaccine. But the truth is, like a family all over the country,

and I don't think it's going to be possible. UM, and so uh you will get You will receive a vaccine UM that's approved from the FDA, that's safe, and that's going to provide a benefit. UM. The Department of Health in your state might make a determination to say that certain high risk populations we want to get a vaccine. It's got a higher faccine like the madern of vaccine UM. And if you're healthier, maybe we're gonna give you one that has a lower efficacy because you don't need it

as much. And some of those choices UM may happen in terms of how they allocate, but it really did fall to the departments of health in the states UM to determine how to distribute it. I don't think it will be a situation where consumers will get to decide until until everybody has had a chance to get a vaccine from the federal government, and that maybe next summer, at which point maybe people will have the ability to go to CBS and make their own line. Let me

go through quickly the questions from social media. How long will the immunity provided by the vaccines last. I'm optimistic that we're gonna see immunity last more than a year. UM. I think a year seems pretty safe at this point. We don't have a year's where the follow up, but we've got six months in some of our studies, and it looks like the early data shows that we're achieving levels of immunity and the blood that we think will

be protective for at least a year. So you're gonna have to get a shot like this or two shots every year, potentially like a flu shot. In the worst case scenario, you need a booster once a year like a flu shot. I think it's unlikely that that's going to be necessary. And the reason I say that is when you see vaccines that are this effective in our case um and it's really the Fiser and Maderna vaccines that I'm talking about that are dis effective. I think

for estras, I think it's a little lower. But when you see vaccines are effective, that's kind of like your measles vaccine or some of the other tetanus vaccines that we used to You don't need to get those every year. You can go every five years, every ten years, maybe

even once in your life. And so when you see this kind of efficacy, yeah, you know protection if I think it allgurs well, it bodes well for the fact that maybe you won't need one ever year, maybe every five year, or maybe only when you end up you know, with waning immunity, you get a test to show that you have lower immunity in your blood, and you just get a booster and maybe once every vidouty Well, the vaccine prevents spreading of the virus, so we don't know

for sure yet, but there are hints that it will, and so we're optimistic that the vaccine will prevent infections. We know from the studies we've run that it prevents disease, and so that's probably the most important thing. If you never get sick, you never have symptoms, you never get hospitalized, it kind of moved through you and you never knew it was there. Um, then maybe it doesn't matter as much.

But the reason is that the studies that we're running, what we the endpoints that we were counting where when people got sick, because people could tell you they got sick. They could call you up and say I'm not feeling well, and you could test them, and that's how we knew

that those cases it happen. In order to figure out what somebody got sick but didn't have an infection what's called asymptomatic infection, you actually have to test them at regular intervals over time, and so we're gonna bring everybody back in on the study three months and six months and twelve months and figure out if they became infected asymptomatically. But that takes time, and so we won't really get that data until the early part of nature. What are

possible side effects from the vaccine. Well, fortunately there haven't been any safety issues in our vaccine, and I haven't seen any reporter for the others as well, so that's good news. Um, the kinds of side effects therefore the people are seeing are not really safety, but they're more tolerability. Think of them as the aches and pains that you

get when you get a vaccine. When when you go get a flu vaccine, people will say you may have some muscle aches and pains, joined as some pains, a headache. You may occasionally rarely have a fever. Those are the sorts of things that have been seeing mostly it's been a couple of days of duration mild to moderate aches and pains that you see with many other vaccines. The good news on that is those aren't really side effects.

With the side effects and the way people think about them, but actually that is your body's immune system getting turned on by the proteins in the back scene or the m morna instruction the vaccine so that it can protect you against ours code too. And so while people think of that maybe as an adverse event as not something they want, it's actually a sign that your immune system is kicked in and ready to protect you. That brings me to my next question. Um, r m RNA vaccines

problematic for people who have automnimmune disease. There's no evidence that m MORNA medicines are problematic for autimmune disease. If anything, I think they might be safer, although we have to see that over time. The reason I'd say that is that there there's no viral vector. There's no virus that's infecting you here, so there's a lot of other proteins, and a viral vector vaccine like the astrozennicer Johnston johnsons that that could do other things to your immune system.

And similarly, in there were common A protein vaccines, you usually give an adjument which you can kick off your immune system UM in a non specific way. In the case of the m MORNA vaccines, there's neither of those things. UM, it's really purely the information and so there's a reason for optimism it, but there's really no data yet. UM.

Certainly there's no evidence that it's it's less safe. I guess immunotherapy can sometimes put your immune system in and overdrive, so can m r NA put your immune system in overdrive for certain patients. So it really depends on what

you're making with the m morna. And the short answer for the vaccines is no, because the m morn a is just making the spike protein the coronavirus, and so your immune system isn't overdrive against the coronavirus, and only we'll get turned on if it sees the coronavirus in the future. We do, in the case of cancer vaccines or in the case of some of our cancer therapies, try and induce an immune response and ramp it up. And so there are definitely cases where will express things

that will try and kick off your immune system. But we do those very different types of things in cancer where we're trying to, as you just said, turn on the immune system so it starts attacking things. In that case, the cancer got it. Okay. What about pregnant women, Dr Hoag, So we do need to make sure thevaccine is safe and pregnant women. Were in discussions with the FDA right now, as are the other vaccine developers to figure out the best way to do that. There's a couple of ways

to do it. One is you run a small study. UM. The other is that you just follow people over time who incidentally get pregnant and make sure through like a registry that there's no there's no safety issues there. We have completed all of the necessary pre clinical work to show that there's no reproductive toxicity issues. We believe it's going to be safe. UM. But what remains to be done is just followed that more carefully and make sure

that there are no showstopper concerns. Do you feel that safety has been compromised because of the speed in which these vaccines have been developed? Do not? UM? I think actually this has got to be the gold standard for how you respond to pandemics in the future. UM. If you think about the size of the trials that have been run and the deliberate nature in which they run through it. We've run through a phase one study, a phase to studies six d people. In our Phase three

study thirty thou people. That's not commonly done for any drug that's approved infect It's a huge number. And if you add to that that we did that Advisor did that with thirty thousand, and Astra Zeneca has got there's going to be hundreds of thousands of people that have been tested across these vaccine platforms. That's just not precedented. There's not that kind of confidence that we've ever really been able to have around new technology, new new drugs,

new medicines, vaccines in these kings. UM. So I think people should take a huge degree of confidence from that. Now, we don't have long term follow up. To be fair, we do not have two years of history post that vaccine, UM, and, so we're gonna need to follow that very closely. But the overwhelming majority plus percent events that have been seen historically with drugs and vaccines happened in the first two

months after your vaccine, not two years later. UM. And when you say you've got that kind of confidence that you've looked really intensively for the first two months, and you've got hundreds of thousands of people you've looked in, I think you can take a lot of confidence. I certainly do, UM. And I don't think that there's been any sacrifices on safety. UM. We have moved quickly. I think the biggest risk taken were financial. All the way through.

There were billions of dollars of risk taken financially, and in that sense, I think the American people and the federal government deserve a lot of credit. UM. Congress with the Cares Act and the administration on warp speed UM, I think underwrote, wrote UM. The American people underwrote the

development of vaccines for the entire world. If you look at the vaccines that are now getting bought by everybody else that's Japan or Europe or the rest of the world, including in low and middle income countries, it's really it's really the six made in the USA and in the USA.

And I think while we did it to protect ourselves, it's something that I have been proud of as I've watched unfold just as American because UM, we although we didn't participate in the w h O activities and many of the things that were multilateral, we did as a as a country underwrite the creation of of the solution of the six solutions UM that we think are going to get deployed most broadly across the world, and and did it in record time, and relied a lot on

American ingenuity and that you know, the high quality of American civil service UH and and workers to to make this happen. And I think it's something we will look back on and and be proud of. Someone asked, if I get the vaccine, am I protected against COVID even if of other people are vaccinated. Yes. So the vaccine that we're the studies that we're running are happening in

the middle of the pandemic, and so nobody else is vaccinated. UM. And so if we're offering protection against COVID in the middle of the pandemic, in very hot areas, UM, you can have confidence that even if the people are around you aren't vaccinated, that you will not be getting COVID. What we don't know, and I think what's oun denying My question is, UM, will the virus still be passing between us? And if you've got vaccinated, maybe you don't get sick? Or what about the other people who didn't

get baccinated? And in that case, I think the answer is yes, they will probably still be at risk until we cross a threshold of people that have been vaccinated or have immunity because they were sick, and that's just because the virus will circulate. Finally, can this virus mutate dr hoge and create a new strain of covid COVID one for example, where you're going to have to go back to square one and start all over again. How

possible is that? Not meaning to to rein on your well deserved parade, UM, I think it's the thing that should always concern us. UM. Pandemics do happen, and they happen at a regular interval. So this virus has evolved, it has mutated a little bit during the year of this year of UM. Fortunately, the mutations have have not been enough to move away from protection from our vaccines,

and I think they won't be UM. If I were to sort of conjecture, I'd say this virus would have to make a lot of changes to avoid the vaccines that are currently in development, not just the madernal one. That's because we're making the whole spike protein. There are you know, one thousand, seven hundred amino acids little pieces of protein on it, and evolution or mutation works one amino acid at a time. So if our immune system can recognize all one thousand, seven hundred, you can change

a few of those meno acids. You're really going to have to make whole scale changes hundreds of them before it's unrecognizable to the immune system. And the problem with that for a virus is the protein has a job to do. It's like a key fitting in a lock. You can't make that many changes from a mutation perspective before actually it just stops working, and maybe the virus stops being able to affect you. So I think starts

COVID too. I'm very optimistic that it's not going to mutate around found our vaccines and we're gonna We're gonna get through this. Your question that was about COVID twenty one,

will there be another coronavirus pandemic? And the answer there is almost certainly yes, Probably not this virus, but at some point in the decade or hundred years ahead of us, a different coronavirus will move out of animals and find its way into humans, and we will have no immunity to it, and then we'll be racing again and defeat it again. That is almost inevitable as well. But do you think the technology that you all have established will help create new vaccines in the future in a much

more expedited way. I hope. So, I really hope that becomes a long lasting benefit of what we've been through in is that governments around the world, including the US, look at the technologies that were most useful and say, well, we did something epic, heroic. We did in one year, the thing that nobody thought was possible. Now, let's figure out how to do it in six months. Now, let's figure out how we can respond more quickly in the

next pandemic. But I think it will be technologies like Messenger RNA that are going to be at the center of that because because at the end of the day, they're so flexible, and so I'm very optimistic that we will get better and better at being able to beat back pandemics with technology like mess and Journey and others, perhaps even the well Dr Hope, Stephen Hope, thank you so much. You were awesome. Um really, thank you. I understood probably nine d four percent of what. I don't

believe that for a second. I'm sure you got it. All. That does it for this bonus episode of Next Question, I'm Katie Couric. Thank you so much for listening, and have a very happy and safe holiday season. Next Question with Katie Couric is a production of I Heart Radio and Katie Kurrik Media. The executive producers are Katie Curic, Courtney Litz, and Tyler Klang. The supervising producer is Lauren Hansen. Our show producer is Bethan Macaluso. The associate producers are

Emily Pinto and Derek Clements. Editing by Derrek Clements, Dylan Fagin, and Lowell Berlante, Mixing by Dylan Fagin. Our researcher is Gabriel Loser. For more information on today's episode, go to Katie Curik dot com and follow us on Twitter and Instagram at Katie Currich. For more podcasts for my heart Radio, visit the i heart Radio app, Apple Podcasts, or wherever you listen to your favorite shows.