Moderna, $40M in Tow, Hopes to Reinvent Biotech with “Make Your Own Drug”

12/6/12Follow @gthuang

Noubar Afeyan, Bob Langer, Tim Springer, and a host of other Boston biotech luminaries have been sitting on a big secret. Today we’re going to out them.

Moderna Therapeutics, a stealthy startup in Cambridge, MA, is the subject of their considerable brainpower and experiments. The company is finally emerging from stealth, having raised $40 million to date from Flagship Ventures and private investors.

Here’s the idea: Instead of producing protein drugs using genetically engineered bacteria in dedicated manufacturing plants—the dominant biotech model of the past 30 years—why not enable the human body to produce its own protein drugs, on demand?

Much easier said than done, of course. The key is developing a technique that triggers cells to produce the drug proteins, without also making the body’s immune system go haywire. To that end, Moderna (pronounced “mode-UR-nuh”) starts by making a specially modified version of messenger RNA. Inject that messenger RNA into the body—so far the company has done tests in mice, rats, and monkeys—and the cells produce the drug proteins right in the body. (More on this below, but the gist is that mRNA, an important intermediary in the process that cells use to make proteins, can be produced using relatively cheap chemistry, whereas proteins themselves cannot.)

If the process works safely in human patients—always a huge “if” in biotech—it could be the biggest story since, well, probably the rise of Genentech and the entire industry in the late ‘70s and early ‘80s. But there’s a lot to be done before the company gets to that point.

“If we’re safe in man, this is crazy,” says Stéphane Bancel, the CEO of Moderna. “It will change the industry in several ways. One is how fast we’ll be able to bring new protein-based drugs to market, with a manufacturing process that’s much cheaper. Our technology can make any human protein.”

The back-story here is pretty interesting. Moderna’s technology was born in the lab of researcher Derrick Rossi at the Harvard Stem Cell Institute and Harvard Medical School. In 2010, Rossi’s team developed a method for modifying messenger RNA and injecting it into human cells as a way to produce cells that mimic embryonic stem cells, in that they can become any other kind of cell. The key advance: the method did not run the risk of triggering an immune-system response if the cells were used to treat patients. (The original technique for producing such stem cells used viruses, posing a risk of an immune response. It also earned its inventor, Shinya Yamanaka, a share of the Nobel Prize in physiology/medicine this year. Yamanaka’s Nobel lecture is this Friday.)

To commercialize his method, Rossi met with Tim Springer, an immune-disease expert also from Harvard Medical School; Springer is known for founding LeukoSite, which was bought by Millennium in 1999. They then hooked up with Bob Langer, the prolific MIT scientist and entrepreneur, and Ken Chien, a cardiology expert from Massachusetts General Hospital and Harvard Medical School. Together they had an idea to start a stem-cell company. Their first stop: venture capitalist Noubar Afeyan, the managing partner and CEO of Flagship Ventures.

Afeyan (pictured at left) knows his biochemical engineering and proteins, among other things, and he saw something very different in what they were showing him. For one thing, he didn’t want to invest in a stem-cell company—there would be too much biology risk. Instead, Afeyan asked the researchers if they could inject some of their messenger RNA, coded for a human protein (say, EPO, a hormone that regulates production of red blood cells), into a mouse and see if they find the human protein in the mouse’s blood.

Rossi went back to his lab and did the experiment—and it worked. Afeyan and the team recognized the significance of the result and filed their first patent shortly thereafter. And so Moderna was born, with Rossi, Afeyan, Chien, and Langer as its co-founders. (Springer is on the board of directors.)

Afeyan is cautiously optimistic about the startup’s chances. “It definitely could enable a resurgence of a new type of biotech industry and company,” he told me earlier this year. “It certainly has a disruptive potential. And it builds on lots of things that have been tried before.”

Rewrite the Book of Biotech

Since the Genentech days, the biotech industry has made protein drugs by taking cells that grow well in culture—typically bacteria, yeast, or mammalian cell lines—and inserting a human gene that codes for a particular therapeutic protein. Grown in big vats, the cells produce the desired protein (insulin, say), and a company can purify it into a form that can be put in a syringe and injected into patients. That’s the idea behind protein drugs from Amgen, Baxter, Genzyme (now part of Sanofi), and all the other big-name biotechs.

Yet, after all this time, the entire biotech industry has yielded only about 100 approved drugs on the market. Everyone in the industry knows the immense amount of time and resources it takes to formulate and fine-tune the production of a new protein drug. By contrast, Moderna has already looked at dozens of proteins—some secreted in the blood and some intracellular (expressed inside cells). As Bancel puts it, “We can make any therapeutic protein in a matter of weeks.”

That’s because, if it really works, Moderna’s technology will let the body’s cells produce the proteins themselves—in response to the right messenger RNA. The company’s process for making mRNA is fast and compact, Bancel says. It buys nucleotides altered by a special chemical process—that’s the trick—and uses a catalytic process to create many copies of the messenger RNA, so that a tank of material will fit in a coffee cup, he says.

At a high level, this sounds a bit like what researchers were trying to do in the early ‘90s, in experiments that eventually led to the discovery of RNA interference. They were trying to make flowers more purple (and other colors) by adding an mRNA for a “purple” gene, but they wound up making them whiter instead—meaning the gene expression was inhibited instead of boosted. Bancel emphasizes that his company’s technology, if it’s related at all, does the opposite of RNAi. But exactly what makes Moderna’s mRNA work so differently is under wraps.

Bancel (left) joined the company as employee number two last year, after stepping down as CEO of bioMérieux, the French diagnostics company. He says it took a lot to get him to leave his previous job. “I wanted to start a company from scratch,” he says. “I turned down many, many projects because the potential was not big enough.”

But Bancel’s background was a good fit for Moderna because he was a biochemical engineer by training, had experience manufacturing drugs at Eli Lilly, and had run a large, publicly traded company in bioMérieux. And he was still hungry to change the world. “He’s every bit an entrepreneurial startup guy in character, mindset, and approach,” Afeyan says.

Indeed, Bancel adds, “We’re going to rewrite the book of biotech on this company. Everything’s going to be different. We’ll do nothing by the playbook.”

Make Your Own Drug

With any such bluster, skeptics are sure to abound—as well as some confusion. The mere presence of any kind of “RNA” in the company’s approach might make some observers think of RNAi and other techniques for controlling gene activity. These methods have proven difficult to commercialize and sustain in some cases, and a lot of basic science is still being worked out.

In any case, most of the biotech community will be hearing the truth about what Moderna is doing for the first time today. Since its founding, the company has been in “total stealth mode,” Bancel says. “Because if anybody in pharma got hold of that idea, they’d put 50 people and $50 million on it, and they would kill us.” (To keep things on the down-low, the company also hasn’t corrected the misperception that it was working on stem cells, until now.)

The startup says it is protected by its patent filings—80 of them, according to Bancel, covering everything from the chemistry to manufacturing techniques to specific gene sequences for individual protein drugs. “We went crazy on the IP so that when we come out of stealth mode, we’ve locked our position and we secure the company in a very broad and aggressive way,” he says.

Indeed, Moderna spent a good chunk of its early funding on securing intellectual property, Bancel says. Now it is looking to expand its operations and get down to the business of developing drugs and running clinical trials. The company is recruiting staff and says it currently has more than 25 employees. It will also try to form a few high-quality partnerships with pharma and large biotech companies when the time is right, Bancel says.

Moderna says it plans to develop drugs for rare diseases by itself, while working with big companies that have the resources to develop, test, and sell drugs for larger disease markets such as cancer and cardiology. “A company could partner with us and get five drug candidates,” Bancel says. “They can be in five Phase 1 [clinical trials] in a year from now.”

As the company’s chairman and lead investor, Afeyan isn’t counting his chickens just yet. He points out that the biotech industry has seen many cases of “a lot of excitement followed by disappointment.” He emphasizes that Moderna must show how broadly applicable its technology is, and that it is safe in humans. Still, he says, “It’s quite intriguing.”

Bancel concurs with Afeyan’s cautionary tone. “With biology, until you’re in man, you’re not in man,” he says. “I’m not saying it will [definitely] work. But what if?” He adds, “Here there’s no biology risk. We just make what the body makes.” And if all goes well in clinical trials—yes, still a big “if”—the team should know exactly what its drugs will do, because they will, by design, produce human proteins with the right shape, configuration, and so forth.

“It’s the perfect personalized medicine,” Bancel says. “You make your own drug.”

Gregory T. Huang is Xconomy's Deputy Editor, National IT Editor, and the Editor of Xconomy Boston. You can e-mail him at gthuang@xconomy.com or call him at 617-252-7323. Follow @gthuang

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  • Beth

    This is outrageous!

    • Beth

      I am looking forward to getting my hands on the data. Great stuff!

      • Bill

        Several labs claimed that Rossi publication could not be reproduced.

      • Beth

        Lucky you! The data already exists by researchers at the University of Pennsylvania who discovered this about 6 years ago! K. Kariko

    • Dan

      Don’t believe the hype.

  • http://www.engag.io/Abdallah Abdallah Al-Hakim

    it does sound very intriguing and has a bit of thinking out of the box.

  • Jaclyn

    Isn’t this the same technology another company started with in 2009? I thought researchers at the University of Pennsylvania had this idea.

    Here’s the link to a government small business grant.
    http://www.sbir.gov/sbirsearch/detail/294079

    • Daavd

      That is shameful. Looks like they have been “make your own drug” for years!

  • Dan

    It’s rather easy to deliver things to the blood, say EPO, but what about delivery to other organ systems? If we can’t get a stabilized siRNA to the tissue of interest, how are going to get an mRNA?

    • Daavid
      • Don

        Didn’t Tekmira sue Alnylam for using those LNPs that Tekmira owns? It looks like Alnylam had to pay $65M and $10M milestone payments. http://www.reuters.com/article/2012/11/13/idUS126737+13-Nov-2012+HUG20121113

        I wonder if Moderna will have to pay the University of Pennsylvania that much for infringing on any patents from the University of Pennsylvania.

      • Dan

        Right. I’m aware of that technology. Unfortunately, it doesn’t work so well either.

    • Evan

      Other companies have used lipid nanoparticles to deliver a range of drugs into people—from chemo-therapeutics like tamoxifen to even some nucleic acid molecules. Usually these lipids formulations come with some pretty serious side effects…and in the case of a nucleic acid things like gout and possible kidney problems from excess uric acid. I guess it depends on how often they have to dose it. But since it’s an mRNA and not stable, probably more than once.

      • Dan

        True, but they don’t work especially well. There’s also a secondary issue of targeting the cells of interest.

  • yeahright

    Show some results.

  • Sidv220

    Nice review though. You can get a real picture of Moderna from its present and former employees at http://www.glassdoor.com/Reviews/ModeRNA-Therapeutics-Reviews-E453959.htm. I would assume its management is over claiming and making claims which could be questionable. My assumption is based upon company review/comments from its employee and former employee. Moderna can never be Genentec but definitely qualify for a company which would disappear from the radar after 2-5 years.