Does Moderna Therapeutics Have the NEXT Next Big Thing?

Photos by Mark Fleming

For its first two years, Moderna Therapeutics, a biotech startup in Kendall Square, operated in stealth mode. Its website consisted of nothing but a single page, which described in only the vaguest of terms what the company was working on. Scientists applying to work at the company had to sign a confidentiality agreement before being granted an interview, and once hired were forbidden from discussing the nature of their research with anyone, including their spouses. The companies that supplied the lab were forced to sign similar agreements and were given only the bare minimum of information about what the company was up to. Not even the CEO’s friends or business contacts knew what the company really did.

Then, on December 6 of last year, the secrecy—or at least some of it—came to an end. At 12:01 a.m., the company’s PR firm sent a press release to media and investors over the PR Newswire, announcing triumphantly that Moderna was on the verge of “adding an entirely new drug category to the pharmaceutical arsenal in the fight against important diseases.” What the company had been so quietly pioneering was a fundamentally new form of drug delivery—one that would allow for the targeted production of medicine inside the human body.

It was a startling idea. Moderna claimed to have figured out a way of instructing specific cells to manufacture drugs on demand. The company said it had completed extensive preclinical trials, including a successful trial in nonhuman primates. Still to come was the final frontier: clinical trials in humans. If they proved successful, Moderna declared, it would be able to slash the rate of drug discovery from years to mere weeks, and treat dozens of diseases for which currently there were no drugs. The practice of medicine, and the pharmaceutical business, would be changed forever.

The release went on to describe the scientists and entrepreneurs who’d founded the company. It was a lineup guaranteed to attract serious attention even in Cambridge, which rivals the Bay Area as the biotech capital of the world. The company’s founders were a veritable dream team: Robert Langer, a renowned professor of bioengineering at MIT, who is considered a founder of the fields of controlled-release drug delivery and tissue engineering; the venture capitalist and biochemical engineer Noubar Afeyan, who has started 25 companies and runs Flagship Ventures, Moderna’s sole institutional investor; Ken Chien, who holds appointments at both the Karolinska Institute, in Stockholm, and Harvard’s Stem Cell and Regenerative Biology Department; and Derrick Rossi, an assistant professor in the Stem Cell and Regenerative Biology Department at Harvard Medical School, who discovered the technology upon which the company was based. Also of considerable note was the company’s CEO, Stephane Bancel, who’d just abandoned a plum job as the CEO of the French diagnostics giant BioMérieux in order to run the tiny startup. And then there was the advisory board, made up of a number of scientific luminaries from around Boston, among them Harvard’s Jack Szostak, the winner of the 2009 Nobel Prize for Medicine, and Doug Melton, the codirector of the Harvard Stem Cell Institute and a founding member of the International Society for Stem Cell Research.

The day of the release, Bancel spent hours fielding calls from reporters and potential investors. Traffic on the company’s website spiked so dramatically that Bancel worried it would crash. Soon articles began to appear that giddily celebrated the company’s prospects. If its technology proved successful in humans, one tech website declared, “it could be the biggest story since, well, probably the rise of Genentech and the entire [biotech] industry in the late ’70s and early ’80s.”

But the release also drew skepticism. The history of the biotech industry, after all, is littered with the stories of startups that announced themselves as the next big thing only to become the latest entry in the industry’s lengthy anthology of disappointments and failures. Was Moderna really on the verge of finding the holy grail? Upon seeing the glowing early coverage, some critics quietly grumbled that the company had yet to release any data or scientific papers that would allow outsiders to properly assess the grand claims it was making. Moderna’s press release, in other words, seemed to raise as many questions as it answered. Yet despite the concerns, these facts remained: Moderna had attracted the attention and backing of some of the best in the business; its core technology, if workable in humans, had truly revolutionary potential; and the stakes, as a result, were intoxicatingly high. Even Langer, whose career has helped define the biotech age, and who has seen countless startups fail to deliver on their breathless early promises, feels that Moderna represents a breed apart. “It is very, very rare,” he says, “that an idea this big comes along.”

Moderna’s story began in 2007, when Derrick Rossi, only six months into his new job as an assistant professor at Harvard Medical School and running his own lab for the very first time, decided to embark on something of a side project. A young scientist with a soul patch and a penchant for braving Boston by bike, Rossi’s main area of research was blood stem cells. But in 2006 he read about an astonishing discovery made by the Japanese researcher Shinya Yamanaka, and he decided to branch out.

Yamanaka had figured out a way to do vitally important stem cell research without having to use embryonic stem cells, which, because they are harvested from discarded embryos, have been the source of endless ethical and political controversy. Yamanaka had bypassed that altogether, by using DNA-based viruses to reprogram regular adult cells and create what are known as induced pluripotent stem (IPS) cells, which behave like embryonic stem cells. It was a landmark achievement, significant enough to win Yamanaka the Nobel Prize for Medicine or Physiology last year. But translating it into something with a practical application in patients posed serious challenges. One of the biggest was that by using DNA-based viruses to reprogram the cells into stem cells, Yamanaka’s process had the potential to cause unintended mutations in the genome, which risked prompting the development of cancer.

Rossi was curious to see if a tweak to Yamanaka’s method might allow him to overcome this hurdle. Rather than using the viral approach to reprogramming the cells, he would use messenger RNA—the single strand of nucleotides that carries the instructions found within DNA into the cell, where they can be carried out. Unlike DNA-based viruses, mRNA doesn’t integrate into the genome, so in this case it wouldn’t produce a cancer risk.