Moderna's Co-Founder on the Drive for a Covid-19 Vaccine

24:05Noubar Afeyan:That's one of the key considerations. But as well, the nature of the science that we're pursuing in the technology is intrinsically modular, is intrinsically a kind of design-based, as opposed to hit or miss trying to find a small molecule that might have an effect. So I can get into it in more detail, but suffice it to say, those of you who are interested should really look up the underlying technology. This is the closest thing to software. If you liken the human body to the hardware equivalent of a computer. Hey, it's Kelly Rowland. You may not know this, but I have eczema, so I get how it can steal your time.

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25:39Noubar Afeyan:Software that allows you to run a program that is injected into a patient a piece of code, nothing more than code, the same exact code, different letter arrangement, would make any protein you want. In this case, we called it to make the spike protein. And the rest, the human body takes care of. How? Well, because if you can make cells in the body make this spike protein that the virus uses to do a lot of damage, and which is immunogenic, we know that, then the body's immune system will go after the spike protein without having been exposed to the virus, and you have an immune response. So there are some kind of things that have advantaged our ability to go quickly and build on what we have learned for the last decade.

26:22Noubar Afeyan:I should say that wild messenger RNA has not been the basis of any approved vaccine. It has been in human trial for 10 different vaccines before COVID-19 came along. And we definitely built upon that background, as well as the NIH, I should also say, who had been researching these class of viruses, these coronaviruses, and with us had been developing a MERS vaccine, which was getting close to getting into human trials. And it's the same team and the same knowledge that we repurposed for this. So we were lucky in many ways that all these precedent conditions were there. You have to be good to get lucky, I guess.

27:05Noubar Afeyan:And I think we were in a pretty good position to be able to get. Now, again, luck for us is even being able to go this far. To be honest with you, I mean, we keep reminding each other that what we've done so far is highly unlikely and anything could stop us from getting to the next step. But even getting this far, I think, was built on a lot of prior work. Yeah, definitely. So I just want to remind everyone watching that we'll be answering some of your questions. So please do keep posting them in the comments. And Nubar, thank you for everything you've shared. As you know, ethnic minority communities have been disproportionately affected by COVID-19.

27:46And as you just outlined, there are currently 30 ,000 participants enrolled in your phase three study. Can you tell us what steps were taken during enrollment to ensure adequate representation of minority groups? Sure.

28:00Noubar Afeyan:Happy to have them. And look, this was an important issue for us, maybe even more important, given that this was our first, very first large trial or even phase three trial. We've never been in a phase three trial as an organization before. And we initially kind of went about doing it the way trials are generally run in the biopharmaceutical industry. And what we found early in our enrollment in phase three was actually not only was there not a representative of a population that is representative of the U.S. population, but that there was a particular kind of lack of enrollment, particularly from the black population, that we felt alarmed by.

28:40Noubar Afeyan:and then went and asked what happens in other trials. And we found that in general, five to 7 % of trial enrollments often will be representative of that minority. And in general, there's a problem there. So we had a choice to make. We could either say, you know what, that's not our problem. Let's move on and let's get this trial done. Or we could do a rather painful decision that the management team put forward with its own initiative and then with the board to say, should we actually slow down enrollment in order to increase the representation of minorities? And should we further tell our shareholders that we're doing that at the expense of what might seem to them as delays, but what seemed to us as the responsible thing to do?

29:24Noubar Afeyan:And I'm pleased to say that several weeks ago, we did do that. We slowed down enrollment from the mainly white population that had been volunteering for these trials. Of course, these trials were being done in many, many different locations where the virus was in a hot zone because we wanted to be able to maximize the chance of having affected people in the trial. Otherwise, we couldn't read as to the effect of the vaccine and the placebo. And I'm glad to say that by the time we concluded the trial, the numbers of broadly minorities and diversity represented were over 35%, at least 37%. There was over 10 percent represented from the black population.

30:05Noubar Afeyan:That was a doubling almost of where we were in the beginning. And the Hispanic population ended up being quite a large population as well. So we took steps we could take responsibly. And I know that others are doing. Likewise, some of the large pharma companies, for example, Pfizer, have increased the size of its trial to achieve a similar goal. So I think we're all cognizant of this. and we want to make this as representative as possible. And I think we have a lot of work to do as a country and the healthcare system to develop the enrollment procedures that will make these trials as representative as possible.

30:44Yes. So let's talk a bit about the distribution process of a vaccine. Who gets it first and why? And who makes those tough decisions?

30:55Noubar Afeyan:Well, look, this is a bit unprecedented, but there have been prior pandemics and prior situations, not as large as this, that at least guide the way. This is something that in the current situation will be conducted through the Operation Warp Speed, this OWS entity that's been created, which is largely using the military's logistics capabilities to ensure distribution to a network of the providers and further distributors. and all of this has been laid out. The decision as to who gets it will be largely a decision that's made by the HHS, CDC. The government will put forward their list of priorities and the order in which they expect under emergency use that the vaccine will be distributed.

31:45Noubar Afeyan:And our responsibility will be manufacturing, filling vials, and handing over to OWS, our supply. After that, and I'll say parenthetically, thankfully, we're not in that loop because we wouldn't know how to adjudicate who's getting it. And I'm happy that the government is playing its proper role, as it is in other countries.

32:11So, Nubar, I'm also wondering if you can speak to the difference between emergency use that we've talked about, which is what most of the companies seem to be going for, versus what the FDA might be as signaling around expanded use and what that might mean and what is that discussion really all about?

32:35Noubar Afeyan:There is an ongoing discussion, which I think is still kind of early in its progress, as to whether there's alternatives to emergency use that could be used. And this is a kind of, those of your aficionados can follow this because there's been a lot posted on Twitter and other places about these things by experts and also lots of non-experts, but to talk about what an emergency use authorization may do to the treatment of placebo subjects. Because once you have a vaccine available, is it ethically appropriate to keep the placebo group not knowing whether it received vaccine or not? And if you were actually to break that placebo, then what effect will it have on the ultimate assessment of the trial when it comes time to a final biological license application?

33:32Noubar Afeyan:So these are technicalities that are being discussed. They tread on ethical issues. And the FDA certainly has been soliciting input from different folks about what else could be done, how else everybody understands that telling this country with a thousand in debt every day that it should wait another few weeks so that we can do kind of keep placebo in its place and not issue emergency use authorization if a vaccine or more than one are efficacious and safe. That's a pretty difficult thing to accept. On the other hand, we should do everything we can to make sure that such emergency use does not corrupt or delay or affect the ultimate availability of the vaccine to everybody.

34:12Noubar Afeyan:And it's there that people are looking for potential alternative routes. The good news for us is that we will do what the regulators advise us to do. Our goal is to be ready to do what they allow us to do. Sure. So let me, we're getting a lot of questions from our viewers and let me turn to the first one. This is from Mohammed in Pittsburgh. And it's, you know, how does Moderna think about vaccine hesitancy and what can you do to address it? And the viewer says that he's not just talking about the anti-vaxxers, but talking about reasonable people who have concerns about topics ranging from this being novel technology to accelerated development timelines that maybe they're suspicious about.

34:56So what role can Moderna and the rest of us play in addressing this hesitancy?

35:05Noubar Afeyan:So, Adi, it's a very appropriate question because it reveals the degree to which product development, innovation in this type of endeavor does not allow you as a technologist or scientist to hide behind kind of saying, well, I'm just taking the product and the market will determine it because ultimately the market needs information from you and you can't stop your involvement involvement in that information flow by just providing. It's a way of saying we all have the responsibility to be transparent with how we do these trials, provide as much data as possible about what they mean, make sure that people at least know that there's no data that's missing or that there's other thing about shortcuts being taken.

35:55Noubar Afeyan:I think people have every right to question whether a shortcut's taken, but not the right to believe they're taken just because we're going fast. I think there are ways to go fast and there's been evidence without taking shortcuts. And so I think people have to kind of look at the evidence, look at what people are reporting. And then I think ultimately it's going to depend on the data, because the data will indicate what level of protection we can expect. There'll be some adoption, the concept of early adopters common to your audience. In this case, it's not the consumer trust issue, but it'll be emergency availability.

36:30Noubar Afeyan:But guess what? People who don't want to take it will effectively be doing what non-earned adopters do in other technologies. Some people who will consider this a wise will take it, they themselves will become part of the data. And the hope is that based on the level of threat, based on the level of explanation And leaders meeting by example and explaining to people, not just shooting themselves up with vaccines, but explaining to people what the risk and reward calculus is on this. I think the FDA and the other NIH, there's just a lot of different voices that will be heard. And if people often ask me, what are the sequence of steps that will take to contract vaccine And I can't tell you that because what's happening, unfortunately, in my mind, is also inseparable from the politics that's been happening in the background.

37:30Noubar Afeyan:I wish this pandemic hit us in a non-election year. I can't hear what would have been interesting if you were to get hit. Because we wouldn't be subjected to quite the level of rhetoric from both sides, by by the way, who have used the speculation, the uncertainty, the concern to people of health as an argument which now leaves behind the after effects of people having hesitancy. I think people are hesitant about a lot of things in this country. Inequality is a very important one. economic, everything has caused people to really feel as they are, the solutions that are being brought forward. So we're in a period of hesitancy, and I think that the only thing that can guide us is change of ideas, transparency, data, and then people will stop stored into when they feel the risk is worth taking.

38:34So, here's another one that I like, Alec from Tampa Bay Beach, Florida, who asks, is Moderna working with other pharmaceutical companies or is this a race to the top? And I like this question because I do think there is so much, we hear a lot about partnering in in very different ways in the pharmaceutical industry, sharing proprietary information, ingredients, different ways. I mean, really extraordinary collaboration. So I'm curious to hear you answer this question also to think about, is the industry really changing in a significant way, or is this just a moment in time?

39:15Noubar Afeyan:I think the people who are claiming the industry is changing fundamentally, however much I'd like to believe that, having been innovating in this space for the last 33 years. I think it's a little bit overstated. Indeed, people have found dense partners because they were lacking either manufacturing capacity. So strange bedfellows were made out of needing to collaborate to manufacture together, or distribution, or a lot of large companies basically gobbled up small company innovations in order to develop themselves. They didn't have anything in their own arsenal to throw at this. So there have been partnerships.

39:55Noubar Afeyan:But I don't think there, if you simply accelerate time, there are as many as would have happened in a longer period of time, because we would have all thought we had that long to develop a vaccine otherwise. I don't observe there to be highly unnatural things happening. I will say that the NIH has done a very good job of where appropriate insisting on harmonization across trials using similar assays or the same assays, the same way of actually adjudicating things so that the trials can be compared. And most of the participants who are developing vaccines have participated in that. As for Moderna, we have ended up having both the opportunity and the necessity to go it alone in the sense that we have not partnered with a larger pharmaceutical company, not out of an intent not to do so, but the opportunity didn't present itself.

40:48Noubar Afeyan:We were, I think, too far along in our own efforts by the time people started wanting to have their own vaccine developed. But I'll tell you, and this may sound surprising, ironically, there are several messenger RNA vaccines that are being developed. Pfizer's is one. There's another one being developed by another group in Germany called CureVac as well as Sanofi, each of those are effectively similar technologies to what Moderna pioneered and spent the last 10 years developing. None of those have been in vaccine trials ever before. So I would think that the 10 trials of vaccines that Moderna has already engaged in with the messenger RNA technology absolutely helped those who jumped on to this with a COVID vaccine.

41:38Noubar Afeyan:And that's another way. Sometimes people forget that a collaboration within our system happens by publications and by patents who teach others how it is you're doing what you're doing. Now, in the pandemic period, we are probably our most collaborative step in Moderna has been that we declared two weeks ago that we will not seek to enforce patents that we have across so many aspects of a COVID messenger RNA vaccine because of the situation we're in. So we've said publicly that we are not seeking to enforce that. And so others will be able to use the technologies that we've published on for many years to their vaccine development.

42:18Noubar Afeyan:And that's another form of indirect collaboration. Interesting. So I'm sorry to say we are out of time. I want to thank Nubar Afeyan for being our guest at this critical moment in his company's effort. So thank you very much, Nubar, for being our guest today. Thank you. And I want to thank our sponsor, Accenture. I want to thank all of our viewers, including the many who posed questions. I'm sorry we couldn't get to more of them today. Please join us next week. That is Election Day in the U.S. of A. We will be talking about the vote and what's at stake. So thanks for watching HBR Now.

43:15We're back. We're back. We're back. Pop, don't come running in and tell me to turn off the computer. We know we're back. We know we're back. We definitely could ask Nubar a zillion more questions. Well, so Nubar, let's get back to this. I mean, the potential for going from, as you said, no products, pretty much no revenue, no employees to, I don't know the numbers, billions, tens of billions in revenue, you know, overnight, practically. How do you ramp up for this possibility?

43:52Noubar Afeyan:Carefully? Just kidding. You know, look, it's hard to describe what we are trying to kind of learn how to do. Look, the team, I want to describe the team that we have with Stefan Banzel and David Moline most recently was the CFO of Amgen who's now joined us with CFO of Moderna. The head of manufacturing CNC at Novartis is the head of manufacturing at Moderna. So the way we've gone about doing this is that we've brought on board people with 20, 30 years of experience in their corresponding roles, some early on, some very recently, in order to meet the challenge of scaling up. Unlike a traditional kind of product where we have to actually do the detailing and take television ads and create coal, this is one where because the intermediary is government, we think it's a little bit easier to do this.

44:54Noubar Afeyan:And look, we have obviously agreed upon some supply contracts that we need to fulfill with the U.S. government, increasingly with some foreign governments as well. And that will occupy, or let's say, pre-occupy us for the next six to nine months. Going into the second half of next year, I think there will be more supply available. And then it might become more of a competitive, also private sector kind of oriented activity, as opposed to only to governments. And so we'll see. We're hoping. One of the things, by the way, I should have responded, Josh, to your question, which I omitted to do so, is this notion of a race.

45:38Noubar Afeyan:I mean, we from day one, if you look at everything we've said, we from day one have said, we need to think of what we're doing as basically being within our own swim lane. We are basically racing against the virus. We are not racing against other people. And however kind of nice business talk that might seem to people, we really, really are not. And the reason is because somebody who finishes earlier than later by a bid isn't going to have any more sales. This is not a market-based demand equation. This is basically the government having pre-ordered and having the ability to order even more from all of us.

46:19Noubar Afeyan:So I think that getting it wrong is so much more hurtful than getting it right a little bit sooner. that for all the talk about race, race, race, look, I think this is a media-related thing. This is a sensationalist thing. It is not. We are moving as fast as we can reasonably go, but no faster. And we are within our – so that's why – just think about it. We announced, as I mentioned earlier, we're slowing down our trials in order to add diversity to it. If we were matching the finish line, nobody made us do it. We have made further announcements along the way that have clearly caused us to go slower than we could have.

47:01Noubar Afeyan:And even now, we're not trying to hit a particular date because we just want to make sure that the data is credible. But those are the things that we've been doing. But as to revenue growth, et cetera, we're going to have to – I'm sure it can have been done better by others, Adi, would be my answer to your question. I'm sure we will not do it well. And the good news is, if we have societal impact and our shareholders are rewarded, they'll never know how much more they would have been rewarded if we were even more effective at it, because that control experiment, unlike our placebo, will not be wrong.

47:40So, Nubar, one of the audience questions we'd received was from Christian in Las Vegas, who's an eighth grader. And he asked, if it takes so long to create one vaccine, how will you account for mutations that would require a new one? Basically, you ready to do this?

48:01Noubar Afeyan:It's a very good question. And it has actually a couple of different answers to it. One is that for Christians to know that a mutation in one part of a virus is not the same as a mutation in another. That is that there could be mutations that do not escape the immune system's visibility, because it will be somewhere other than the spike protein. And then there's mutations that could be in the spike protein. So first think that the entire virus can be mutating as long as the spike protein or the part of the spike protein that we're using to cause an immune response, it will not affect us. That's point one.

48:38Noubar Afeyan:Point two, there's reasons to believe that the spike protein's ability to mutate is a bit tamed by just how important it is to the virus doing what it's doing. Because when you think about mutations, mutations that help you, if you're a virus, become more infective or become able to reproduce more, etc., those are the ones that survive selection and evolution. The ones that hurt you in your ability to get yourself are basically lost through evolution. So you're looking for things. So a lot of mutations will not give the virus an advantage. And therefore, the spike protein has been actually relatively not the place where people have seen a lot of mutations.

49:21Noubar Afeyan:And then finally, yes, our platform, quite unlike any other platform, it's an integral part of RNA, hey, we could develop from scratch another vaccine at least as fast as we've done this one and probably much faster because we wouldn't have to do the manufacturing setup and the scale-up and the qualification runs because we've done all those. So us changing the sequence and then showing it's safe and trying it on a few hundred people is probably a few months of work at most compared to the years and years it would take with protein vaccines or attenuated killed virus vaccines or DNA vaccines. And these are much, much slower technologies.

50:04So before we let Nubar go, I kind of want to play the Armenian card. Nubar, you are an Armenian-American. I'm half Armenian. I'd love a quote that you said. Armenians have one thing in common. We're super survivors. So, you know, I know that you're, you know, the hottest hotspot in the world today might be Nagorno-Karabakh. And, you know, I won't go into all the details of what that is and who's fighting whom. But, you know, I know you wrote a piece, you contributed to the New York Times recently on the topic and you follow it closely. What's, you know, do you have a sense of the way out of that really brutal crisis?

50:45Noubar Afeyan:Well, thanks, Adi, for mentioning it. It is the case that going into 2020, I never thought that we'd be working on a pandemic that's afflicting people and killing lots of people. And that's bad enough, including in my case, close to my family. But to think that in this 2020 timeframe, governments put the side in that region to wage war, to take advantage of the world's inattention and distraction to COVID. in the middle of the pandemic, in the middle of the pandemic afflicting the population of the places that have been subjected to war is unimaginable. And yes, Armenians happen to be in an unfortunate part of geography.

51:30Noubar Afeyan:You know, we were there a long, long time ago, so we didn't choose the neighbors, but it has been an hostile environment. And I am well beyond my capabilities to imagine a solution that can be brought about if people don't have the tolerance that is needed to coexist. It is the case, Adi, as you know, since you're part of that broad community, that there are Armenians all around the world. of some 10 million of them. Only 3 million live in Armenia and Artof, the enclave that is the subject of this current war. And we found a way to survive historical episodes, including a genocide some hundred years ago, and to be living in a modern time, working on these kinds of problems, and seeing compatriots and people that I know quite well being sent off to to fight and die with inanimate objects, drones, missiles, airplanes, kind of all matched 100 to 1, is heartbreaking.

52:38Noubar Afeyan:And maybe it will increase my resolve to do good, wherever I can do good. But it really has been an incredibly painful situation. So switching back to Moderna for a second, because you did mention what you thought. You didn't think this would be in 2020. I'm curious because with any young company, nothing kind of happens the way founders necessarily think it will unfold. What was 2020? What was the game plan for Moderna? What did you think would be happening? It's a good question. In fact, anybody who really wants to see it live, you may know that in the healthcare field, there's an annual conference that J.P.

53:19Noubar Afeyan:Morgan puts on in January. It's been a mainstay. I've been to it for some 30 sequential years, presented many times. Nice to run public companies. And at that conference every year, including this year, Moderna has presented its outlook and its plans for the year, which is online, and it's worth watching. We had some 15 clinical programs, the most advanced one we expected to get through phase two trials, which is another vaccine for cytomegalovirus, a huge unmet need medically that there is no vaccine for today. And we have a very positive kind of early results on. And so that program coupled with a couple of other things in the cardiovascular space, our partnership with AstraZeneca, where we're testing that VEGF mRNA for VEGF in my conditions.

54:10Noubar Afeyan:So we have several programs that were advancing, would advance in 2020 through 2021 for us to be poised to have our own products coming out of clinical trials by 2022, beginning to start the commercial transition in 2022, 2023. That got moved up by three years, two and a half, three years, and we went from having messenger RNA in a thousand, two thousand people to now well over For 30 ,000 people, that's expanded our exposure base. So a lot of things happened that we're building on, but certainly challenging to the national course. And look, I could not be more proud. I cannot say this enough from the team and the leadership, in particular the CEO of Stefan Bansal, who was doing a heroic job leading this company for the last nine years, an HBS grad, by the way, and now is doing whatever a heroic job would have been to a non-heroic job, he's been doing to a heroic job in the middle of this pandemic, as have his colleagues that I mentioned earlier.

55:17Noubar Afeyan:And, you know, that's the best thing you can do. When people say, you know, people are the most important thing in these journeys, in this kind of storm, people have yet a different level of importance. Yeah, amazing. All right. Well, we have taken a lot of your time, Nubar, and we really appreciate it. This is what an amazing journey you were on. And thank you for giving us your time. Really great discussion. Thanks, everybody, for a great show. Thank you all. Thank you very much.