Moderna Therapeutics, the most highly valued private company in biotech, has run into troubling safety problems with its most ambitious therapy, STAT has learned — and is now banking on a mysterious new technology to keep afloat its brash promise of reinventing modern medicine.
Exactly one year ago, Moderna CEO Stéphane Bancel talked up his company’s “unbelievable” future before a standing-room-only crowd at the annual J.P. Morgan Healthcare Conference here. He promised that Moderna’s treatment for a rare and debilitating disease known as Crigler-Najjar syndrome, developed alongside biotech giant Alexion Pharmaceuticals, would enter human trials in 2016.
It was to be the first therapy using audacious new technology that Bancel promised would yield dozens of drugs in the coming decade.
But the Crigler-Najjar treatment has been indefinitely delayed, an Alexion spokeswoman told STAT. It never proved safe enough to test in humans, according to several former Moderna employees and collaborators who worked closely on the project. Unable to press forward with that technology, Moderna has had to focus instead on developing a handful of vaccines, turning to a less lucrative field that might not justify the company’s nearly $5 billion valuation.
“It’s all vaccines right now, and vaccines are a loss-leader,” said one former Moderna manager. “Moderna right now is a multibillion-dollar vaccines company, and I don’t see how that holds up.”
Bancel made no mention of the Crigler-Najjar drug when he spoke Monday before a similarly packed room at this year’s J.P. Morgan conference.
But mRNA is a tricky technology. Several major pharmaceutical companies have tried and abandoned the idea, struggling to get mRNA into cells without triggering nasty side effects.
Bancel has repeatedly promised that Moderna’s new therapies will change the world, but the company has refused to publish any data on its mRNA vehicles, sparking skepticism from some scientists and a chiding from the editors of Nature.
The indefinite delay on the Crigler-Najjar project signals persistent and troubling safety concerns for any mRNA treatment that needs to be delivered in multiple doses, covering almost everything that isn’t a vaccine, former employees and collaborators said.
The company did disclose a new technology on Monday that it says will more safely deliver mRNA. It’s called V1GL. Last month, Bancel told Forbes about another new technology, N1GL.
But in neither case has the company provided any details. And that lack of specificity has inevitably raised questions.
Three former employees and collaborators close to the process said Moderna was always toiling away on new delivery technologies in hopes of hitting on something safer than what it had. (Even Bancel has acknowledged, in an interview with Forbes, that the delivery method used in Moderna’s first vaccines “was not very good.”)
Patients with Crigler-Najjar are missing a key liver enzyme needed to break down bilirubin, a yellowish substance that crops up in the body as old red blood cells break down. Without that enzyme, bilirubin proliferates in the blood, leading to jaundice, muscle degeneration, and even brain damage.
In Moderna’s eyes, the one-in-million disease looked like an ideal candidate for mRNA therapy. The company crafted a string of mRNA that would encode for the missing enzyme, believing it had hit upon an excellent starting point to prove technology could be used to treat rare diseases.
But things gradually came apart last year.
Every drug has what’s called a therapeutic window, the scientific sweet spot where a treatment is powerful enough to have an effect on a disease but not so strong as to put patients at too much risk. For mRNA, that has proved elusive.
In February 2016, a Nature editorial criticized Moderna for not publishing any peer-reviewed papers on its technology, unlike most other emerging and established biotech companies, and compared its approach to that of the controversially failed Theranos. In September 2018, Thrillist published an article titled, “Why This Secretive Tech Start-Up Could Be The Next Theranos”, criticizing its reputation for secrecy and the absence of scientific validation or independent peer-review of its research, though having the highest valuation of any U.S. private biotech company at more than $5 billion. A former Moderna scientist told Stat: “It’s a case of the emperor’s new clothes. They’re running an investment firm, and then hopefully it also develops a drug that’s successful.”
In May 2020, Moderna board member Dr. Moncef Slaoui resigned from the company to become Chief Scientist for US’s “Operation Warp Speed”, a group designed to accelerate the development of a COVID-19 vaccine. Slaoui continued to hold more than $10 million in stock options in the company in his new role while the federal government invested $483 million in the company to assist in COVID-19 vaccine trials. Senator Elizabeth Warren called the holding a conflict of interest and said Slaoui should have divested his options.