附近上门

With the first doses of Moderna鈥檚 vaccine rolling out to frontline workers across the country, it鈥檚 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 聽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鈥攖he notion that the human body could be harnessed to make its own medicine鈥攚as considered outlandishly futuristic at the time.

In the words of co-founder and early backer , it鈥檚 鈥渁 powerful reminder of what is possible when we journey forth, armed with propositions that may鈥攊n just a decade鈥攇o from outrageous, to obvious, to lifesaving.鈥�

In an effort to shed some light on Moderna鈥檚 history-making startup journey, 附近上门 News sat down with Afeyan, a venture capitalist and serial entrepreneur who鈥檚 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 , the Cambridge, Massachusetts, biotech venture firm that launched and funded the company in its early days.

A Beirut-born, -educated biochemical engineer, Afeyan is a well-known figure in biotech startup circles. Soft-spoken demeanor aside, he鈥檚 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 , microbiome-focused drug developer , and, of course, Moderna.

Below are key takeaways from a conversation this week around Moderna鈥檚 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鈥檓 curious to what extent Moderna鈥檚 startup orientation was helpful in the task at hand of developing an effective vaccine in an extraordinarily short time span.

鈥淚t鈥檚 definitely a startup mentality,鈥� Afeyan said, observing that: 鈥淢oderna鈥檚 culture has been to be unafraid of trying things that have never been tried.鈥� The governing philosophy is to 鈥渂e rigorous to a massive extent,鈥� and to act urgently, but also 鈥渢o recognize that it takes time to get things done.鈥�

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

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.

鈥淭he 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,鈥� he recalled. 鈥淢oderna was the product of that 鈥� it was an exploration of: Could we make a drug inside a patient that could be effective?鈥�

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. 鈥淲e thought: What if you could use it in animals or in humans,鈥� Afeyan said. 鈥淭hat is essentially how Moderna got its start.鈥�

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.

鈥淭he company鈥檚 adversity was rather more in attracting people and large sums of capital in that what we were doing was both unheard of and unbelievable,鈥� Afeyan said.

In the end, Moderna skipped outside venture financing in favor of an enormous strategic investment from . 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鈥�, and 鈥攔ounded out Moderna鈥檚 strategic investor pipeline. Later financing came from Moderna鈥檚 IPO in December 2018.

To what extent did the clinical trials and research that didn鈥檛 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鈥檚 tale is one of serial disappointments followed by a breakthrough success.

鈥淚t鈥檚 the conventional story line. And it鈥檚 not that we didn鈥檛 have disappointments 鈥� 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鈥攊nfluenza vaccines鈥攊n pandemic strains that did not yet enter humans,鈥� 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鈥檛 consistent with how things actually work at Moderna. The company describes its process as a platform approach, with researchers commonly applying Moderna鈥檚 mRNA technology to more than 20 programs at the same time. It鈥檚 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 , Moderna鈥檚 CEO, is a native of France. I鈥檓 curious to get your thoughts on the state of immigrant startup entrepreneurship in the U.S.

There鈥檚 been quite a lot of attention paid of late to immigrants in the vaccine space, Afeyan observed. It鈥檚 reflective of the fact that there are a lot of immigrant scientists in immunology and biotech. However, Afeyan added that he鈥檚 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鈥檚 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鈥檚 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,鈥� he said. Just as your brand doesn鈥檛 mean anything when you’re a startup, your family name and home country credentials don鈥檛 mean much when you鈥檙e an immigrant.

In a letter to staff, you talk about propositions that may鈥攊n just a decade鈥攇o from outrageous, to obvious, to lifesaving. I鈥檓 curious if that arc of progress appears to be accelerating. Ten years, by historical standards, sounds pretty fast, particularly for biotech.

鈥淚t鈥檚 an interesting question, because you know enough about the industry to know that鈥檚 fast,鈥� Afeyan said. It鈥檚 especially fast, he added, if you consider that 鈥渋n those 10 years, the first eight years, you have to explain to people why they have to believe you every day.鈥�

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

鈥淭he pandemic, if it did nothing else, it gave us the ability to prove everything from soup to nuts in a short time frame,鈥� 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鈥檓 curious about some of the next new things you鈥檙e finding most intriguing.

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

鈥淚f you look at human health and what we call health care, it鈥檚 usually sick care,鈥� Afeyan said. 鈥淪o 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.鈥�

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鈥檛 need to use those weapons. The same should hold true for health spending.

鈥淲e think society鈥檚 going to have to shift capital and incentives to getting ahead of disease,鈥� he said.

Photos courtesy of Moderna.

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