Moderna’s Vaccine Is A Startup Triumph, Too

With the first doses of Moderna’s vaccine rolling out to frontline workers across the country, it’s easy to forget that the company behind this crucial tool toward ending the pandemic is itself little more than a startup.

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To deliver a vaccine for mass inoculation with 94.5 percent efficacy in clinical trials in under 11 months is obviously in itself an astonishing achievement.

But what makes Moderna’s accomplishment all the more remarkable is that the company behind the effort got its start less than a decade ago and went public only two years ago. Its founding principle—the notion that the human body could be harnessed to make its own medicine—was considered outlandishly futuristic at the time.

In the words of co-founder and early backer Noubar Afeyan, it’s “a powerful reminder of what is possible when we journey forth, armed with propositions that may—in just a decade—go from outrageous, to obvious, to lifesaving.”

In an effort to shed some light on Moderna’s history-making startup journey, Crunchbase News sat down with Afeyan, a venture capitalist and serial entrepreneur who’s been building startups for more than three decades. In addition to his role as co-founder and chairman of Moderna, Afeyan is also founder and CEO of Flagship Pioneering, the Cambridge, Massachusetts, biotech venture firm that launched and funded the company in its early days.

A Beirut-born, MIT-educated biochemical engineer, Afeyan is a well-known figure in biotech startup circles. Soft-spoken demeanor aside, he’s a leading power player in the space, with a key role in the launch, funding and scaling of a long list of prominent public and private companies, including sustainable agriculture unicorn Indigo, microbiome-focused drug developer Seres Therapeutics, and, of course, Moderna.

Below are key takeaways from a conversation this week around Moderna’s early days, its startup DNA, immigrant leadership, and why the recent focus on a COVID-19 vaccine should not be called a pivot.

As a 10-year-old venture firm-founded company, Moderna is not far removed from its startup roots. And some things startups are known for is their willingness to work grueling hours, do things that have never been done before, move fast, and pursue long-term, longshot goals. I’m curious to what extent Moderna’s startup orientation was helpful in the task at hand of developing an effective vaccine in an extraordinarily short time span.

“It’s definitely a startup mentality,” Afeyan said, observing that: “Moderna’s culture has been to be unafraid of trying things that have never been tried.” The governing philosophy is to “be rigorous to a massive extent,” and to act urgently, but also “to recognize that it takes time to get things done.”

If there’s a cultural element, Afeyan said, it’s that which he calls pioneering. It’s a term he sees as different from innovating–another favored startup verb–in that pioneering involves “going to a place that’s never been inhabited before and making it habitable.” It’s also a term with a long history at Afeyan’s venture firm, which in 2016 changed its name from Flagship Ventures to Flagship Pioneering. At the time, Afeyan described the name change as part of a strategy to “purposely distance ourselves from current products and advances that represent only a short leap in innovation beyond them.”

Although Moderna is now a company with roughly 1,300 employees, the culture is still one of startup-like fearlessness around trying something new, Afeyan said. Specialization also benefited the company in tackling COVID-19, since unlike older, more established big pharma companies, Moderna remained focused since inception on a single area: messenger RNA (mRNA) therapeutics and vaccines.

So, the period when Moderna was founded, from 2010 to 2011, was a tough time for biotech. Investment was scarce and the economy was just beginning to recover from the financial crisis. To what extent did you face extra-normal challenges launching such an ambitious startup?

While the general investment climate was not the best a decade ago, Afeyan said its effect on Moderna was minimal as the startup was an in-house effort.

“The way we operate is that we launch our own explorations through which we discover things that will create a lot of value, come up with hypotheses, and go test them,” he recalled. “Moderna was the product of that … it was an exploration of: Could we make a drug inside a patient that could be effective?”

Founders initially envisioned applications in therapeutics, Afeyan said, but also, to a lesser extent, vaccines. After identifying a mission in the summer of 2010, Flagship launched an effort to look for ways to technologically accomplish its goal. The team was acquainted with a body of emerging research around messenger RNA focused on applying it to transform cells. “We thought: What if you could use it in animals or in humans,” Afeyan said. “That is essentially how Moderna got its start.”

By 2011, Flagship had assembled some intellectual property around its latest venture, initially named LS18. The plan was to incubate and grow the company in-house, its typical practice, using capital from its most recent venture fund. It was more at the later stages, Afeyan said, that founders envisioned bringing in outside investors.

“The company’s adversity was rather more in attracting people and large sums of capital in that what we were doing was both unheard of and unbelievable,” Afeyan said.

In the end, Moderna skipped outside venture financing in favor of an enormous strategic investment from AstraZeneca. By 2014, the pharma giant had invested $300 million at a peak valuation of $3 billion, an astonishing sum and valuation at the time for such a little-known newcomer. Other big pharma names—Merck, Alexion and Vertex—rounded out Moderna’s strategic investor pipeline. Later financing came from Moderna’s IPO in December 2018.

To what extent did the clinical trials and research that didn’t go as hoped pave the way with insights and research results to enable success with the COVID-19 vaccines?

Although Moderna, like virtually every biotech involved in clinical trials, has seen disappointing results at times, Afeyan pushed back against the come-from-behind narrative that Moderna’s tale is one of serial disappointments followed by a breakthrough success.

“It’s the conventional story line. And it’s not that we didn’t have disappointments … But a lot of this idea that nothing worked and we pivoted and we got a vaccine is provably wrong because we had vaccines in our product concepts in 2010. We worked on vaccines as early as 2013 and 2014, and the very first clinical trials Moderna ever did were for two vaccines—influenza vaccines—in pandemic strains that did not yet enter humans,” Afeyan said.

In its earliest trials, Afeyan continued, Moderna used mRNA to show it could stimulate an immune response in humans. Since then, the company has worked on 10 human vaccines in parallel with 10 non-vaccine products.

Afeyan said the conception that a particular project is either flat-out succeeding or failing isn’t consistent with how things actually work at Moderna. The company describes its process as a platform approach, with researchers commonly applying Moderna’s mRNA technology to more than 20 programs at the same time. It’s less about canceling one project and greenlighting another, and more about shifting resources to and away from particular efforts, presumably based on factors like progress and urgency.

Moderna, like a lot of transformative American companies, is founded and led by immigrants. Reading your bio, you were born in Lebanon to Armenian parents, immigrated to Canada as a teenager, and then got a Ph.D. from MIT before launching Flagship. And Stéphane Bancel, Moderna’s CEO, is a native of France. I’m curious to get your thoughts on the state of immigrant startup entrepreneurship in the U.S.

There’s been quite a lot of attention paid of late to immigrants in the vaccine space, Afeyan observed. It’s reflective of the fact that there are a lot of immigrant scientists in immunology and biotech. However, Afeyan added that he’s acutely aware that many immigrants today face greater hurdles than those, such as himself, who obtained American degrees and founded companies here decades earlier.

Afeyan said he’s encouraged to see that leading research universities continue to attract students from all over the world, and many, if not most, would choose to stay. However, he’s concerned that if the country shuts off more immigration, it will harm our ability to keep building transformative companies. He also makes the case that immigrants are uniquely well-equipped for startup life.

“The immigrant experience and survivalist mindset of having to make do in a new culture; that spirit absolutely ports to entrepreneurship,” he said. Just as your brand doesn’t mean anything when you’re a startup, your family name and home country credentials don’t mean much when you’re an immigrant.

In a letter to staff, you talk about propositions that may—in just a decade—go from outrageous, to obvious, to lifesaving. I’m curious if that arc of progress appears to be accelerating. Ten years, by historical standards, sounds pretty fast, particularly for biotech.

“It’s an interesting question, because you know enough about the industry to know that’s fast,” Afeyan said. It’s especially fast, he added, if you consider that “in those 10 years, the first eight years, you have to explain to people why they have to believe you every day.”

He credits the maturation of the platform approach to biotech company-building, in part, for Moderna’s historically fast evolution from pie-in-the-sky concept company to purveyor of a pandemic-ending vaccine. Urgency also played a role, Afeyan said.

“The pandemic, if it did nothing else, it gave us the ability to prove everything from soup to nuts in a short time frame,” he said.

This has been a big year, of course, for Moderna, but Flagship also has been keeping busy, with several portfolio companies closing new rounds and a few stealth projects probably still in the very early stages. I’m curious about some of the next new things you’re finding most intriguing.

At a big-picture level, for people who work on things that are out there, Afeyan said he’s intrigued by the area they call health security.

“If you look at human health and what we call health care, it’s usually sick care,” Afeyan said. “So to go from sick care to deterring and preventing disease, in a world where securing our health is the focus instead of treating sickness, that would itself be a gigantic market.”

Broadly, health security involves taking all our knowledge and looking at the conditions before a sickness. There is a long period when bodies go through patterns of alterations after which a disease becomes manifest, and a paucity of care around monitoring and prevention.

Afeyan said he compares health security to the way we think about military spending. A lot of funding goes to weapons systems. However, a great deal also goes to monitoring, security, intelligence and other functions that allow us to deter threats so we don’t need to use those weapons. The same should hold true for health spending.

“We think society’s going to have to shift capital and incentives to getting ahead of disease,” he said.

Photos courtesy of Moderna.

Blogroll illustration: Dom Guzman