Does Moderna Therapeutics Have the NEXT Next Big Thing?

Scenes from inside Moderna’s Cambridge offices.

Viewed from the outside, Moderna’s offices, housed in a four-story brick building on First Street, in Kendall Square, don’t look like a place where cutting-edge science is taking place. Much of the first floor consists of office space and meeting rooms that could belong to any small company. But on one side of that floor, and in half of the basement, are laboratories that Bancel, after his hiring, quickly filled with scientists whose job it would be to start testing and refining the technology. He also began to attract luminaries to his advisory board, which now looks like a who’s who of the Boston-area scientific community.

In late November, Bancel invited me to come visit the Moderna offices and watch his team at work. In one part of the office, a scientist explained to me how he used a computer to design a strand of mRNA that codes for a protein missing in patients with a certain genetic defect. Elsewhere in the building, a researcher in a lab was taking those designs and making actual strands of Moderna’s patented modified mRNA, which he placed in a solution. In yet another lab area, a team was introducing those strands of mRNA into human cells in a dish. All of this was preparation for the main event, when another scientist would drop those cells into a series of tray wells containing a reactive agent that would change colors in the presence of the protein they had coded for—if, of course, they had succeeded in producing it. The day I visited, I stood by as a Moderna scientist dropped the cells into the wells. We waited patiently for a short while, and then the wells turned a gratifying shade of blue. Moderna’s chief scientific officer, Tony de Fougerolles, patted the scientist on the back. “Congratulations,” he told him, “you just got another hit.” Then, turning to me, he added, “In five years, that mRNA you just saw there might treat a disease that is currently not druggable.”

Bancel says Moderna has engineered more than 100 proteins this way. He won’t yet say which they are—but all, he assured me, are proteins the absence of which in a human body can cause disease. The company has been running experiments like this since the first few weeks of its existence. By the summer of 2011, encouraged by a dazzling few weeks of success with in vitro experiments, Moderna decided it was ready for the next step: conducting live experiments. Researchers began by working with mice and rats, some bred to have a single gene mutation that made them unable to produce a particular protein—and, by extension, unhealthy. Moderna scientists engineered their mRNA, coded it for the missing proteins, injected it into the sick animals, and restored them to health. When it comes to small animals, Bancel says, the technology works.

One of the biggest challenges of working with RNA is getting it to the correct therapeutic target in the human body. Indeed, this is one of the problems that has made it impossible for another similar technology, known as RNA interference, to fulfill its promise of being the next biotech game-changer. When I asked Bancel how Moderna gets its modified mRNA to the correct cell or organ system, he didn’t offer any details. All he would say was that it was related to the mRNA coding. The company, he assured me, now has the capability to target the blood system as well as the heart, lungs, liver, kidneys, and muscles, meaning it can potentially address illnesses in all of them. Because of intellectual-property concerns, Bancel said, he couldn’t be any more specific. Moderna does indeed take IP very seriously: So far it has filed 90 patent applications containing more than 4,500 claims.

Moderna’s scientists refined Rossi’s technology, and in less than a year—warp speed in the world of drug development—they were ready for the next step: testing their wares in nonhuman primates. The big moment came last June, when de Fougerolles and several others on the Moderna team traveled to a contract lab in Montreal, where, on June 5, they injected lab monkeys with mRNA that they’d coded for a specific protein. The next day they drew the monkeys’ blood to see if the protein was circulating, and the Moderna scientists began to analyze it.

The scientists got the results on June 7, and de Fougerolles called Bancel right away, reaching him at a Red Sox game. This was the moment of truth. All Bancel says he could hear was de Fougerolle’s voice on the other end of the phone—telling him that the data looked fantastic. They had found a lot of the coded protein circulating in the monkey’s blood, and the immune response to it was very low. The technology worked in primates, in other words, and it was safe. Bancel spent the rest of the game calling board members to share the news. Soon his staff’s cell phones were lighting up with a picture of the wells of the experiment tray, colored blue.

Six months later, Moderna sent out its press release and burst out into the open.

Nobody knows for sure what Moderna can actually do, because the company hasn’t released its data—at least not to anyone who isn’t legally bound to secrecy. I didn’t get to see any data myself. Given how the company has hyped itself since sending out its press release, this kind of secrecy rubs some area scientists the wrong way. “How they came out really ruffled some feathers,” says a Boston scientist who works in the field of RNA drug delivery, and who asked not to be referred to by name. “Everyone here is trying to do something great,” he says, alluding to the many biotech companies and academic labs in the Boston area. “They’re claiming they are doing something great, but without having the papers to show for it.”

Is it all bluster, designed to help Moderna raise money and perhaps even attract licensing from Big Pharma? (Moderna does hope to license its technology for some applications, while keeping rare diseases and oncology to itself.) Or is Moderna on to something genuinely so big that it needs this sort of secrecy to protect its intellectual property? Other biotech startups have certainly played this game the same way, boasting about the potential of their technology well before they choose to publish anything about it. As the pharmaceutical-industry historian Jeremy Greene, of Johns Hopkins University, observes, pharmaceutical startups often have to “tout their scientific relevance even before they are able to demonstrate it.” The revolution might not occur, in other words, if you don’t first declare that it’s under way.

The week after Moderna came out of stealth mode, I sat in on a meeting that Stephane Bancel held with three newly hired scientists at the company’s offices. Wearing a black sweater, black pants, and black-rimmed glasses, he reviewed the company’s organization chart with them, and then started talking excitedly about the science. He got up from the table and began to draw diagrams on a whiteboard wall. He walked the new hires through the history of the company’s research, charting its course from Rossi’s initial discovery to where things stood in the lab that very day. And then he reminded everybody of where they were all headed. “Our goal is not to do cool science,” he said. “It’s to do cool science in man.” The year 2013, he told them, would be Moderna’s make-or-break year, when, in the intoxicating pursuit of scientific discovery and entrepreneurial success, the company would launch its human clinical trials—and would at last learn if it had found the holy grail.

Bancel wrapped up his talk soon after. As he gathered his papers from the table, he welcomed his new hires aboard one more time, and then told them it was time to get busy. They had a lot of work to do.

More scenes from Moderna’s offices.