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Moderna chairman Noubar Afeyan exuded star power earlier this month as he commanded the spotlight at BIO 2023, the industry’s largest convention.
Basking in the accolades heaped on Moderna’s celebrated COVID-19 vaccine, Afeyan regaled the Boston audience with the company’s origin story and greeted fans who lined up to snap selfies with him. Stuart Cable, a partner in the law firm Goodwin who’s represented Moderna and joined Afeyan on stage, called Moderna “arguably the most successful story in the history of biotechnology.”
But the Cambridge-based company can’t afford to rest on its laurels. Two and a half years after its vaccine liberated tens of millions from pandemic lockdowns ― ringing up more than $36 billion in sales so far ― Moderna faces a changing business and regulatory environment. Demand for COVID shots is waning, a backlash over drug prices is gaining traction, and questions about its next act loom.
Declining rates of COVID infection are “good news for the world, but it leads to uncertainty about Moderna’s future sales,” said biotech analyst Michael Yee, managing director at the Jefferies investment bank. Yee said he’s waiting for three to four late-stage research programs to bring new Moderna treatments to the market in the next several years.
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The company’s stock, which soared during the pandemic, has fallen over 30 percent this year, reflecting Wall Street’s impatience for new “growth drivers.” First-quarter revenue dropped by more than 60 percent from a year earlier to $1.8 billion. The federal government, which gave Moderna billions in funding to fast-track and purchase the vaccine, has stopped buying doses, forcing a shift to commercial sales. And critics are balking at Moderna’s new $130-per-dose vaccine price tag.
Yet the toughest challenge for the 13-year-old biotech may be proving that it’s not a one-drug wonder — that its secret sauce, called messenger RNA, can yield a bumper crop of medicines that will not only save and extend lives but return Moderna to expansion mode.
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To admirers who see Afeyan as biotech’s leading impresario, hatching scores of drug discovery companies through his Flagship Pioneering startup generator, Moderna is his master production. It embodies Afeyan’s “platform strategy” of building businesses around novel technologies, like mRNA, with potential to spawn multiple drugs.
Moderna scientists are using mRNA, a single-stranded molecule encoded with genetic instructions, to turn human cells into medicine factories, producing their own disease-fighting proteins.
“The aspiration was nothing short of inventing a way to make the human body make drugs for itself,” Afeyan said at the BIO gathering in the Boston Convention and Exhibition Center.
Afterward, he described the coronavirus as only Moderna’s first target. “The more organs we get into,” Afeyan said, “the more it will expand the applicability” of mRNA technology.
That task falls to Moderna chief executive Stéphane Bancel, a hard-driving operations specialist who, like Afeyan, was catapulted into the billionaire ranks on the success of the company’s breakthrough vaccine.
Bancel and his leadership team have been guarded with the press throughout the pandemic, working to control their narrative amid heightened scrutiny. But they’ve been building a global sales force and a biomanufacturing network stretching from Canada to Kenya to Australia, along with a flagship plant in Norwood — 20 miles from the company’s Kendall Square headquarters — and a new Marlborough site.
At the same time, scientists in Moderna’s labs are advancing a pipeline of nearly 50 experimental drugs, from personalized cancer vaccines to rare disease therapies. The company has projected it will roll out new mRNA vaccines for flu and respiratory syncytial virus, known as RSV, as early as next year, and be ready to dispense combination vaccines that fend off those viruses and COVID in a single dose by 2025.
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Not far behind are its custom-tailored cancer vaccines, which seek to prevent malignancies from spreading and recurring. Presenting promising clinical data at the American Society of Clinical Oncology meeting in Chicago this month, Moderna and its partner, drug giant Merck, said combining an mRNA vaccine with Merck’s approved drug Keytruda reduced the recurrence of disease symptoms and the risk of death in melanoma patients by 65 percent compared with taking Keytruda alone.
Bancel, in an interview, said he believes those clinical results “will replicate in other cancer types,” demonstrating the versatility of the mRNA technology. Moderna has begun testing other vaccines targeting breast, head and neck, and non-small cell lung cancer.
“We are not a one-trick pony, as most biotech companies are,” he said, each word garnished with the accent of his native France.
The pipeline of cancer vaccines, along with drug candidates for cardiovascular disease and rare genetic disorders such as cystic fibrosis, are one reason Bancel believes the company’s stock is undervalued. It’s why Moderna has been buying its own shares during their dip.
Looking ahead, Bancel posed — and answered — a rhetorical question. “If you think about a five- to 10-year time frame, could Moderna be one of the five top pharmaceutical [makers] in the world?” he asked. “It’s something I believe has a high probability of happening.”
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But the company has a steep climb ahead. In an April ranking posted by Fierce Pharma, a trade publication, Moderna was listed as the 18th-largest global pharma company based on 2022 revenue. It generated $19.2 billion in sales last year. By contrast, the top drug maker, Pfizer, which co-developed a rival coronavirus vaccine, generated sales of $100.3 billion. Number five, AbbVie, weighed in with $58 billion.
To crack the top five, Moderna will have to transition from a research-focused business to a multidrug commercial company without losing its science edge, said Andrew Lo, health care finance professor at MIT’s Sloan School of Management. Only a handful of biotechs have successfully executed that maneuver, he said, citing the risk of setbacks in the lab and supply chains — all under the gaze of profit-minded investors.
“In the parlance of Wall Street, it’s always, ‘What have you done for me now?’” Lo said. “They’ve got a really large pipeline of interesting therapeutics. So the world is waiting to see what’s next.”
Kyle Holen, head of oncology and therapeutics development at Moderna, said it’s too soon to predict when cancer or rare disease therapies will reach the commercial market. “We’re going to be as aggressive as possible in trying to get them to patients,” he said.
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The personalized cancer vaccines, delivered by intramuscular injections, will require intricate diagnosis and production procedures. “It’s a huge endeavor, unlike anything that’s ever been done before,” Holen said.
Doctors who treat melanoma patients, for example, will send biopsies of their tumors to Moderna. The company will use a process called “whole exome sequencing” to analyze cell mutations, and build a computer algorithm to find proteins that generate the best immune response.
“We create a vaccine directed toward those specific proteins that are the result of the mutations,” Holen said. “It’s an individualized therapy that can not be administered in any other person. We manufacture that [therapy], and we sent it back to the patient who had that biopsy.”
While personalized vaccines will pose unique production challenges, Yee, at Jefferies, said Moderna can apply to new products some of the innovation and distribution lessons it learned from rolling out its COVID vaccine. Vaccine sales also left the company with more than $16 billion in cash and investments to underwrite drug development.
It is hard to exaggerate the warp speed at which Moderna has already grown. At the time when a frightening new virus began sweeping across the world in early 2020, the company had not brought a single product to market. “This is a totally different company from a capital standpoint than before the pandemic,” Yee said. Most biotechs, he said, are burning through investors’ money rather than sitting on their own stockpile.
Still, there are obstacles ahead. The company, like its biopharma peers, will have to deal with questions over how much drug makers can charge for their products. The biotech business model of fielding high-priced drugs to reward risky investments with outsized profits has come under increased pressure from consumers, health insurers, and politicians in both major political parties.
“The prices of drugs are too high in the US, and we have to come to grips with it,” FDA Commissioner Robert Califf said at the BIO convention.
Moderna, especially, has found itself in the crosshairs of outspoken lawmakers such as Senator Bernie Sanders, the Vermont independent who chairs the Senate health committee. Sanders summoned company executives before his panel in March as federal officials wound down their pandemic response. Critics were rankled by Moderna’s plan to price its vaccine at as much as $130 a dose on the private market, more than four times what the US government paid.
The vaccine’s deployment would have been impossible without the government funding research, helping to rapidly scale up production, and purchasing doses, said Peter Maybarduk, access to medicines director for consumer advocacy group Public Citizen.
“Government was a partner, soup to nuts, on this vaccine,” he said. “Now Moderna’s turning basic health protection into a luxury good.”
At the Senate hearing, Sanders took pains to note that the taxpayer-subsidized COVID vaccine made some company leaders extremely wealthy. In addition to Bancel and Afeyan, cofounder Robert Langer and Timothy Springer, an early Moderna investor, appeared on Forbes magazine’s most recent list of the richest people in America.
Sanders ripped Moderna executives for what he said was “an unprecedented level of corporate greed.” Bancel was unapologetic. Moderna lost money for a decade before shipping its COVID vaccine, which effectively “ended the pandemic,” he told senators, saying, “The price is linked to the value of the product.”
With its pandemic boost, Moderna’s workforce has grown rapidly. The company had about 4,350 employees at the end of March, up more than 1,100 from a year earlier. It plans to hire about 2,000 workers in 2023, the majority in Massachusetts, where it is investing $322 million to open a plant on a site it purchased in Marlborough off Route 495.
Moderna has always been known as a demanding workplace. It was one of the first biotechs to call most of its business employees back to the office when the pandemic subsided. “We are an in-office culture,” said Tracey Franklin, the company’s chief human resources officer.
The company saw a high rate of employee turnover in earlier years, especially in its executive ranks. The most recent high-level departure came just this month, when chief medical officer Paul Burton joined California-based Amgen. Franklin, however, said turnover at Moderna is now running below the industry average, though she didn’t cite specific data.
At a time when many biotechs are struggling to hire in the state’s tight labor market, Franklin said Moderna has little trouble finding workers. Among other recruitment tools, it shares a list of desired “mindsets” with job candidates to set expectations, and runs an in-house “Moderna University,” complete with business case studies, to train employees.
“People are very attracted to the culture of innovation,” she said.
Robert Weisman can be reached at robert.weisman@globe.com.