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COVID shots made Moderna biotech’s biggest star, but what now?

The Cambridge company is poised to make strides in mRNA vaccines for diseases ranging from flu to HIV to cancer. But scientific and economic hurdles make success far from guaranteed.

Moderna is headquartered in Cambridge.Adam Glanzman/Bloomberg

What does a breakout company like Moderna do for an encore? More than a decade after its founding, the Cambridge biotech rolled out its first commercial product last year. And what a debut it was: a cutting-edge COVID-19 vaccine that helped to save thousands ― if not millions ― of lives around the world.

It was also a massive moneymaker for Moderna, which up until then had been unprofitable. With more than $38 billion in total COVID-19 vaccine sales expected by the end of this year ― many of the doses paid for by governments ― investors are wondering what the company plans to do with that windfall. Despite Moderna’s spectacular success, the question of what’s next looms large, and the pressure is on to avoid becoming a one-hit wonder.


Moderna, which will turn 12 this fall, was founded on a bold promise: that an injection of messenger RNA ― a biological code used as blueprints by all living things to make proteins ― would give the body’s cells instructions for making therapies or train their immune systems to ward off invading viruses. No one knew whether it would work and the early clinical indications were lackluster.

At the beginning of the pandemic, the company had just over 800 employees and deep annual losses from its research spending. Every dollar raised from an investor tantalized by the potential was matched with rising skepticism.

Those doubts dissipated in 2021 as people began to roll up their sleeves for COVID shots. Moderna became a household name overnight, fueling a meteoric rise of its stock last summer, which has since fallen back to earth. The company has quadrupled its staff to 3,200, owns one of the best-selling biotech products of all time, and is sitting on about $19 billion in cash. Its market value of about $54 billion makes the company one of the biggest in Massachusetts.


CEO Stéphane Bancel, who has led Moderna since 2011, told the Globe that he believes it can repeat the success of its COVID shots. The company will have four vaccines for common viral infections in advanced clinical trials before the end of June, with many more following close behind, he said. “The pace at which we are going to be going will be surprising to people,” Bancel said.

One of those four vaccines is a booster shot tailored to the Omicron strain of the coronavirus that the firm hopes will be available in the fall, and Bancel believes people will likely need booster shots at least once a year, creating a steady market for Moderna products. Yet given the lukewarm uptake of first and second boosters, analysts don’t expect sales to reach anywhere near the heights they did in the first two years of the pandemic.

But Moderna has no shortage of ideas for products beyond iterations of its COVID vaccine. It has 29 mRNA vaccines and therapies already in clinical studies for cancer, genetic diseases, heart conditions, and a bevy of infectious diseases. Vaccines for cytomegalovirus, respiratory syncytial virus — which can pose problems for babies, pregnant women, and older people — and the flu will all be in advanced clinical studies this summer and could become the firm’s first non-COVID products over the next few years.

Even analysts are having a hard time keeping tabs on it all. Karen Andersen, a health care strategist for Morningstar, said the experience and money Moderna reaped from COVID are allowing the firm to start research programs “in every imaginable therapeutic area where mRNA might be useful.” And it is essentially doing that.


“They are just pursuing everything very aggressively,” Andersen said.

That doesn’t mean every new vaccine will be a slam dunk. Only about one in 10 experimental drugs and vaccines makes it to approval. But the company hopes to beat the odds. “All of our vaccines are the same technology,” Bancel said. “If you were safe once, and it works, it will be safe again and work again.”

It’s true that using the same mRNA chemistry and the same lipid nanoparticles to deliver mRNA into the body allows Moderna to design, manufacture, and test new shots quickly. But many scientists — even those devoted to mRNA — are more circumspect about applying the technology to other diseases.

“The mRNA vaccine platform is flexible, adaptable, cost-effective, and potent, but that doesn’t mean it will solve every problem in the world,” said Mohamad-Gabriel Alameh, director of the Engineered mRNA and Targeted Nanomedicine Core at the University of Pennsylvania. “We can’t take mRNA and shove it into another pathogen and expect it to work.”

COVID vaccines were about 95 percent effective at preventing infections early in the pandemic, in part due to a unique situation where the vaccine’s mRNA code matched the circulating virus almost perfectly. That initial success, “far more than any optimist could have even expected,” may have set unrealistic standards for future mRNA vaccines, said Dr. Christian W Mandl, former head of vaccine research at pharma giant Novartis.


Existing flu shots are only about 40 to 60 percent effective, and sometimes much lower. Mandl doubts that mRNA flu shots will reach 95 percent protection. But since mRNA vaccines can be designed and manufactured more quickly than traditional shots, Moderna may achieve higher protection by better matching the flu strains circulating each season.

“Theoretically, that should help a lot,” said Anna Blakney, an mRNA scientist at the University of British Columbia. Moderna could also easily add to its inoculation more than the four strains currently used in annual shots. But that might mean higher doses of mRNA, which increases the likelihood of side effects like fevers and aches, she added.

Bancel said the company is considering adding more strains to future COVID boosters. The version planned for the fall contains two kinds of mRNA: one from the original shot and one for Omicron. “In 2023, you might have three or four mRNAs” in a single booster, to build broader immunity, he added.

Some academic scientists and small companies are taking a more sweeping approach, trying to develop universal coronavirus vaccines that protect against many forms of the virus. But Moderna believes such an uber vaccine “is not ready for prime time,” Bancel said. “If the science is ready one day, trust me, we will run into it.”


Among Moderna’s most widely discussed research programs are those involving potential vaccines for HIV. Many scientists doubt that Moderna will succeed where so many others have failed, at least initially. MRNA isn’t a magic bullet, and the record-breaking development of the COVID shot was in part because scientists had already figured out how to design synthetic coronavirus spike proteins.

That’s not the case with HIV. Researchers haven’t nailed down the design for synthetic HIV proteins that will trigger antibodies to neutralize the ever-evolving virus in humans. Moderna recently began testing two designs of an HIV vaccine in the clinic. Bancel acknowledges that the chances of success are lower than for COVID vaccines.

The same thing is true for the firm’s personalized cancer vaccines, he said. Those shots — designed to treat cancer, not prevent it — are custom-made based on unique mutations in a patient’s tumor, with the goal of spurring the immune system to attack and destroy the disease. Data from an intermediate clinical study of those shots are expected before the end of the year. “Could it fail? Yes. But it could also work,” Bancel said. “We will know for sure.”

If the cancer vaccines succeed, they could easily become multibillion-dollar products. Moderna’s other experimental therapies for cancer and rare diseases also could become big moneymakers.

But making mRNA therapies poses unique challenges. One is that the mRNA typically only stays in the body a day or two after injection, long enough for an immunization but “just too short” to be convenient for chronic conditions, including genetic diseases, said Jacob Becraft, cofounder of the Cambridge mRNA startup Strand Therapeutics.

Even if Moderna solves that problem, it needs to prove that giving people mRNA therapies on a regular basis is safe. “We just haven’t seen that data yet,” said Myles Minter, a biotech research analyst for the investment firm William Blair.

In the past year, Moderna finally began testing mRNA therapies in people with two rare genetic diseases that leave them without crucial enzymes for metabolism. Moderna hopes to treat those conditions by supplying them with mRNA every two to four weeks, allowing their livers to make the missing enzymes.

“If we get positive data in those two rare disease programs, then you will see a tsunami of rare disease drugs moving from the labs into the clinic,” Bancel said.

Expanding the scope of what mRNA can do may require bringing new technology into the company. Geoff Meacham, a biotech and pharma analyst at Bank of America, said Moderna is well positioned, given its sudden vast wealth, to acquire early-stage companies working on cell therapy, gene editing, protein engineering, or other technologies that could be paired with mRNA. “Moderna could be very opportunistic,” he said.

Bancel said the company’s growing business development team “is very busy looking at a lot of things.” Moderna recently announced partnerships with the cell therapy startup Carisma Therapeutics and the gene editing startup Metagenomi.

Experts say Moderna can parlay the success of its COVID shots into a launch pad for expanding its business. But producing something with sales as staggeringly high as its COVID vaccine is not likely, at least not anytime soon.

“I see a big future for mRNA, but we haven’t solved everything,” said Mandl, the former Novartis head, who founded Cambridge mRNA startup Tiba Biotech in 2018. “There will be many failures that go with the initial wins.”

But there is no doubt that mRNA has cemented its status as the vaccine technology of choice during pandemics, he said. “So if there is another pandemic, I am very sure that mRNA vaccines will play an important role.”

And expect Moderna to once again be in the thick of it, this time perhaps with fewer skeptics weighing in from the sidelines.

“These mRNA vaccines are such a breakthrough and such a gift to humanity,” said Dr. H. Cody Meissner, chief of pediatric infectious diseases at Tufts Children’s Hospital. “We are living through a revolution in vaccinology.”

Ryan Cross can be reached at Follow him on Twitter @RLCscienceboss.