The Cancer Vaccine That Could Save Moderna

0:05The biotech company Moderna is best known for its COVID vaccine. The vaccine put the small startup on the map and made it billions of dollars. But in recent years, its business has been in deep trouble.

0:18Xavier Martinez:COVID starts to sort of wind down in terms of the urgency that we're treating it with. Sales start to drop in the U.S. because not as many people are getting vaccinated. That's our colleague Xavier Martinez, who covers biotech. And before you know it, their stock has really bottomed out. It's gone down more than 90 % from its peak. You know, the company is bleeding cash. You look at the stock chart, and it just looks like the tallest mountain in the world. But earlier this month, Moderna made a surprising announcement. I remember where I was. I was on a call with a different company, with a different pharmaceutical company.

0:57Xavier Martinez:earlier this month. And I was in the office in a little meeting room. And my editor comes over and starts waving her hands up and down. And clearly something is happening. Hang up the phone now. There's breaking news. Exactly, exactly. And she starts messaging me. And she starts saying like, okay, okay, I really need you to get on a call in five minutes. On the call, Xavier learned that a cancer vaccine that Moderna researchers had been working on showed real promise in clinical studies. That study met two goals in both preventing the growth of any cancer, but also preventing it spreading from other organs in the body or metastasizing.

1:40The vaccine is for people who've already had melanoma, a serious form of skin cancer. It's designed to prevent the cancer from returning or spreading to other parts of the body. How big of a deal potentially is this melanoma vaccine that Moderna has created?

1:56Xavier Martinez:It could be one of the biggest advancements in cancer that we've seen in the last 25 years. If Moderna continues down this path that they're going down, this could really just kind of totally change how we treat cancer. Not only that, but it's also breathed new life into a company that some thought was on death's door. This is really bringing Moderna back from the brink financially. They've been hemorrhaging cash for the last two and a half years. And so I think what it means is, and this is certainly a new chapter for them. Their cancer's in remission. Exactly, exactly. I think that's a good way to put it, right?

2:38Welcome to The Journal, our show about money, business, and power. I'm Ryan Knudsen. It's Friday, August 28th.

2:51Coming up on the show, the cancer vaccine could save lives and the company behind it.

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4:44A decade before the pandemic, Moderna was just another biotech startup outside of Boston.

4:52Xavier Martinez:Moderna was founded in 2010, and it was what we call in the biopharma industry a platform company. And so what that means is that it was designed with the goal that all of its drugs that it would make over the course of its whole lifetime would be all focused on mRNA. mRNA. mRNA, remind us what that is? mRNA is short for messenger RNA. It's sort of a sister to regular typical DNA. It's a natural molecule in your body that acts like a sort of a temporary instruction manual or a blueprint, and its job is just to shuttle directions from your DNA to different parts of your body. mRNA carries instructions that teach your body how to make proteins like antibodies to fight diseases.

5:36The idea Moderna was founded on was simple. What if scientists write that instruction manual? What if they could engineer mRNA to tell the body how to make antibodies? And so the idea with this is that you could manipulate the RNA in such a way that it can

5:51Xavier Martinez:create antibodies that can fight diseases. Yeah, I mean, the goal here is that you can actually encode like different sets of instructions to tell your immune system to say, hey, when you see a mutation like this on a cancer tumor, you should go fight it. But actually writing those instructions is easier said than done.

6:13In the early days, did Moderna focus its technology on cancer?

6:17Xavier Martinez:Not at all. Cancer, we still don't fully understand, right? I mean, we know that it definitionally is the uncontrolled growth of cells, but we're still learning every day what that actually means from a biological level, right? And so I think it was just a really unproven bet in terms of using mRNA to target any one component of the immune system, right? So early on, the company decided to focus on illnesses that seemed easier to target. Here's Moderna CEO Stéphane Boncel talking about this decision almost a decade ago. Because if we pick the wrong biology, we might, it might not be the technology the issue, it might be the biology but everybody including us is going to believe it's the technology Instead of taking on cancer Moderna decided to focus on treating things like the flu and genetic diseases We were very worried in the early days kind of paranoid worried of going the wrong way and taking so long to realize we are in the wrong way on the science that we might kill the company The CEO, Stefan Bunsell, was very much the realist in the situation here, right?

7:28Xavier Martinez:And I think that goes for a lot of the executives. They were very much focused on proving out this technology, showing that it worked, you know, for other sort of types of diseases. And then, of course, maybe going into things like oncology later down the line. You know, we were able to sit down with the CEO and some of the executives last week, and they really made a point to say that, no, we were actually kind of afraid of going into oncology too early. because it was going to be so cost-intensive. It cost millions of dollars to enroll patients in clinical trials and things like that. And more importantly, the science just wasn't there at the time, right?

8:01Xavier Martinez:There had been all these attempts to try to use these therapeutic cancer vaccines to try to reshape the immune system, and just none of them really worked. And so, you know, when you're a really small biotech company, you don't have a lot of money, you don't have a lot of runway, you kind of need something that's a little easier to target. Still, some Moderna executives thought a cancer vaccine was possible and didn't want to give up on that dream, including the company's president, Stephen Hogue. Stephen Hogue, who is a scientist, he's a physician, he was a McKinsey consultant. He sort of, maybe you could think of him as a little more of the dreamer and the scientist of the executive group.

8:38Xavier Martinez:I have come to realize that optimism is my greatest privilege. That's Hogue, talking about his impressions of Moderna when he joined the company in 2013. Moderna just kept striking me as odd. It was trying to pursue a phenomenally big idea, like sort of farcically big, that we're going to figure out a way to turn medicine into information or information into medicine. I was not totally daunted as an optimist when people told me that was a crazy thing to do. More than a decade ago, developments with some other drugs made by other companies made Hoag think Moderna should give mRNA cancer treatment a serious look.

9:20Xavier Martinez:In the early and mid-2010s, you see this big wave of immune-focused cancer therapies coming out. You can sort of see and trace out the logic of how, well, if we can maybe target the immune system and use mRNA to tell it to actually do different things, to target different things, well, maybe that might actually be useful in oncology. Hoag showed Boncel scientific studies that mapped out new mRNA concepts in cancer biology. But Boncel told Hoag that Moderna didn't have the money to spend on an oncology program. In those days, Moderna had fewer than 100 employees, and it didn't even have a single product in the market, meaning it wasn't bringing in any revenue.

9:59So, without more funding, Boncel and the realists at Moderna won the argument. Developing a cancer vaccine was just too expensive, and the payoff too uncertain, for a little startup like Moderna to spend its limited resources on. But then, in 2013, one of Moderna's early investors reached out to Bancel. His wife had been diagnosed with stage 4 lung cancer.

10:23Xavier Martinez:He personally talks to Stefan, the CEO, to Bancel, and he kind of says, hey, is there any chance at all that you guys could potentially look into this whole cancer thing and see if your mRNA technology might be useful there? And Bunsel, the CEO, says, sorry, no, it's going to be way too expensive. Even just to hire a couple of researchers, it's going to cost$500 ,000, half a million dollars, right? And so he goes home, he goes back to his office in Cambridge. And a couple of days later, a FedEx envelope shows up on his desk. And it's a check from that hedge fund manager for$500 ,000. With that cash, Moderna hired two cancer researchers and its oncology program got underway.

11:13The hard part about treating cancer, though, is that each person's cancer is different, meaning each mRNA vaccine would have to be tailor-made to each individual patient. And making bespoke vaccines is expensive.

11:27Xavier Martinez:And then Sal says, well, it's going to cost a lot of money, so can you figure out how to maybe keep the cost down on that? And so a couple of Moderna employees at the time locked themselves in a room, They scribble on this whiteboard. Bunsell still has a photo of the whiteboard. It has all these different sort of colors written on it in marker, green and purple and red and pink. And, you know, they actually sort of sketch out how this might work. Once they sort of start sketching it out, once they start using the technologies they have in-house, they realize, well, shoot. We're going to need a whole lot more money if we want to actually test to see if this technology is going to work.

12:05Xavier Martinez:You know, not in a lab, not on the whiteboard, but if it's actually going to work in patients who have cancer. And for that, Moderna needed a partner. What they do is they end up thinking like, okay, there's all these great pharmaceutical companies that, A, they know how to do clinical trials. They know how to work with academic centers. They have relationships with them. They know the process for, you know, making these experimental medications for testing. They know the distribution. Which ones are good at cancer? And so they approach a couple of companies, they're in conversation with a couple of companies, and ultimately to settle on Merck.

12:42Merck, the pharmaceutical giant behind one of the most successful cancer drugs, Keytruda. Unlike chemotherapy treatments, which effectively poison cancer tumors, Keytruda is an immunotherapy drug, meaning it stimulates a person's natural immune system to fight cancer, similar to what Moderna was trying to do with mRNA. So in 2016, Bancel and Hogue visited Merck to pitch the company on a partnership.

13:06Xavier Martinez:And so they go to Merck's offices, they pitch this idea, and they say, you know, we have this idea. We actually want to make a vaccine for cancer. And the Merck executives have tons of questions. And at the end, you know, these Merck executives are still doubtful. They, frankly, don't necessarily think it's going to work. And I should also say, Moderna's not confident that it will work. They're, for years and years and years, and even through this process, saying, well, we don't want to hype this up too much. You know, we just want to see if this will yield anything. Because if it does, it would be very promising, right?

13:42Xavier Martinez:And so Merck expresses some doubt, but ultimately they say, let's do it. Merck agreed to pay Moderna$200 million to fund research into how its mRNA vaccine might work in combination with Keytruda. In 2019, Moderna and Merck started a phase two study and administered the vaccine to a small number of cancer patients. At long last, Moderna would be able to see if its cancer vaccine actually worked. A lot of people didn't even think they would get this far with the cancer vaccine, let alone with the mRNA technology. But then, something got in the way. The coronavirus outbreak has been declared a pandemic.

14:23How COVID-19 nearly derailed the cancer shot is next.

14:51kids end up better off. Anthropic asked over 100 ,000 people their thoughts on AI and is tracking in public what it does about them and where they might not have the answer just yet. There's hope in hard questions. Ask yours at claude.ai slash the journal.

15:16Six months after Moderna started the phase two study of its cancer vaccine, the COVID-19 pandemic hit. The world is scrambling to stop the spread of COVID-19. More and more cases are popping up in countries far from the epicenter of the outbreak. And Moderna pivoted quickly to develop a vaccine.

15:36Xavier Martinez:Moderna is one of the first companies to develop a vaccine. They do it from when they start development of that vaccine to when they actually get it approved by the FDA on this sort of expedited pathway as part of Operation Warp Speed at the end of the first Trump administration, it's less than a year, right? And when you compare that to other drug development timelines, that's extraordinarily quickly. So I think, you know, puts them on the map, both to the public, but also to investors and to the scientific community saying, oh, wow, this biotech can actually, they can play ball, right? They can put a drug on the market.

16:10Xavier Martinez:They can use this mRNA technology to actually address a pressing need that we have here in society. And they can do it very quickly. But as Moderna's priorities shifted to COVID, its cancer program suffered. It is actually very bad for the program. They're using the same equipment that they use for the cancer vaccine. So they literally have to pick, OK, are we going to, we know we have patients in this clinical trial that have cancer who might die from that cancer. Are we going to treat them? Are we going to make their individualized cancer vaccines? Or are we going to, you know, make six million doses for the global public?

16:44Xavier Martinez:And of course, they chose the latter, right? But talking to the executives, that was not an easy decision. It certainly was not a fun decision to have to make. But that decision led to a huge windfall.

16:59Moderna won more than a billion dollars from the Trump administration to speed up its development of its COVID shot, which was authorized for emergency use that December. And in the first two years the vaccine was on the market, it generated$36 billion in sales. Moderna used that money to expand and grow other programs, including oncology. But as the pandemic subsided, Moderna's business got hit with a hangover.

17:24Xavier Martinez:Oh, I mean, a hangover doesn't even begin to describe it. As COVID starts to wind down, as they're losing money, they have to cut programs eventually. They have to cut some of their developmental programs that they're kind of bringing into the clinic to prioritize the ones that they're most excited about. Moderna cut jobs and ended research programs into things like a pediatric RSV vaccine and other cancer therapies. The stock fell, and some investors even made bets that it would keep falling. Earlier this year, the short interest in Moderna hit 20%. But Moderna's research into a cancer vaccine survived all those cuts.

18:00So despite all of the doubts about the viability of a cancer vaccine, why did that research continue? Among all the things that they cut, Why didn't they cut that?

18:09Xavier Martinez:Well, I think a very important inflection point happens in 2022, which is when they get the results from that phase two study. Phase two, a critical stage of clinical trials where researchers find out if their cancer vaccine works on actual melanoma patients. The hope was that the vaccine would prevent cancer from returning or spreading in patients diagnosed with melanoma. Phase two studies are really, really important. And for a lot of people in the industry, they sort of represent the make or break moment, right? Like, you're not going to push something beyond a phase two if you don't really think it's going to read out well.

18:47Xavier Martinez:It's going to have some really strong results. And so Moderna and Merck get sort of interim looks at the data in 2022. And the results are really promising for them. Around this time, Merck committed to a full partnership with Moderna to make and sell the cancer vaccine together. Then, the study moved to phase 3, basically a much bigger version of the phase 2 study. In both studies, every patient took Merck's existing cancer treatment, Keytruda, but only some also took a dose of Moderna's vaccine. This was a very big trial. It was over 1 ,000 patients, which, if you think about the logistics of it, meant that it was 1 ,000 people with high-risk melanoma getting their melanoma removed, sending that and a blood sample to Moderna and Merck, having them actually sequence those mutations, formatting cancer vaccine, and then dosing them for about a year.

19:45Xavier Martinez:So throughout the year, Moderna had been signaling that in the second half of this year, in the second half of 2026, they were going to get the results from that phase three, that late stage study of the cancer vaccine in these melanoma patients. And it comes a lot sooner than anyone thinks. The company says the vaccine worked. It was helping real melanoma patients fight cancer. The company announced the high-level results last week. Now, according to Merck and Moderna, a combination of the vaccine and medication appeared to stop the cancer from returning or spreading in high-risk patients. Moderna still hasn't shared the specific details about how well the treatment worked and in what percentage of patients.