This 5 billion dollars startup made its first Cancer vaccine - for just one person

By Caroline Chen

For Moderna Therapeutics, the road to a cancer breakthrough begins on the back of a FedEx truck.

Six weeks ago, a 1-millimeter cube of cancer tissue collected by doctors from the right lung of 67-year-old retiree Glenda Cleaver was packed in a box at the Sarah Cannon Research Institute in Nashville, Tennessee. It was the beginning of a journey Moderna hopes will lead to a long-sought goal: a vaccine that trains the body to attack tumors.

Novel cancer drugs often come with six-figure price tags, so success could be lucrative. Numerous companies are chasing a cancer vaccine. Others have been ruined by the pursuit.

"It'd be a tremendous technological achievement to open up the cancer vaccine space, given the history of nothing but failures," says Wedbush biotech analyst David Nierengarten.

Swathed in cooling gel packs to keep it at 5 degrees Celsius, Cleaver's tissue was sent with a second box containing a four-inch vial of Cleaver's frozen blood to Kentucky, where it was entered into a tracking system. From there, the samples were shipped to a facility on the West Coast where machines scanned the tumor's genetic code and compared it to the blood, hunting for the malevolent changes that spawned Cleaver's cancer.

On Monday, Cleaver, the first person to be enrolled in Moderna's study of its personalized cancer vaccine, returned to Sarah Cannon, where another FedEx box waited. It contained a vial no larger than Cleaver's palm. It took about 100 people to make and will work for only one person—her.

Valued at about $5 billion, closely held Moderna, headquartered in Cambridge, Massachusetts, is one of the biggest biotechnology startups in the U.S. Since its 2010 founding it has attracted $1.9 billion from investors, partnered with drug giants, and taken fire from skeptics.

Moderna claims it can upend how drugs are made. Traditional protein-based biotechnology medicines are grown in vats and harvested from living organisms, a tedious and expensive process. The company wants to make it possible for a patient's body to make its own medicine using strands of genetic instructions called messenger RNA, or mRNA.

Chief Executive Officer Stephane Bancel likens mRNA to computer code. With the right combination of letters, Moderna says it can hijack a cell's protein-making mechanisms to create a drug within the body. If it works, mRNA could have many applications: The company also has programs for infectious diseases, cardiovascular disorders, and rare diseases.

But the technology is unproven. It is difficult to deliver mRNA to the right cells without the immune system destroying it. Critics of the company said it has a one-size-fits-all approach.

"At Moderna, it's like the answer is mRNA," says Andrew Allen, CEO of rival Gritstone Oncology, which is planning to start a trial of a competing cancer vaccine next year. "What's the question?"

A decade ago, tailoring a vaccine to a single patient's cancer would have been impractical, and other companies failed in their search. Formerly high-flying Dendreon Corp. got its prostate-cancer vaccine Provenge approved in 2010, only to file for bankruptcy in 2014 after the $93,000 treatment—seen to have minimal benefit and cumbersome logistics—fizzled commercially.

Today, "personalized medicine" is biotech's biggest buzzword. The cost of sequencing a whole genome has fallen to about $2,000, from millions in the early 2000s, unlocking new insights on how diseases work. Cancer drugs now routinely come with and are given only to patients with the right genetic features.

For Cleaver, Moderna's software produced a list of 20 protein targets specific to her cancer. Then its scientists assembled DNA building blocks to create the recipe for her treatment. Those DNA templates were sent to Catalent Biologics in Madison, Wisconsin, where they were transcribed into mRNA and packed as a string of instructions into a little glass vial.

Scientists believe that some cancers spread because the immune system doesn't recognize malignant cells as foreign. Moderna's vaccine would teach the body how to recognize protein targets that appear only on the cancer cells.

Rivals want to beat Moderna to market. BioNTech, a German company partnered with Roche Holding AG's Genentech, has finished an early-stage trial in melanoma, the most aggressive form of skin cancer. Neon Therapeutics, whose offices are less than a mile from Moderna's in Cambridge, expects results from its first study, in melanoma, non-small cell lung cancer, and bladder cancer, in early 2018.

There are many ways Moderna could fail. Only about one in 10 biotech drugs make it from the first human trials to the market. Moderna's software could select the wrong tumor targets, or not identify enough of them. The mRNA may not last long enough in the body to induce a strong immune response. Plus, cancer is an elusive foe.

"The tumor has all kinds of tricks to fight back," said Greg Lizee, an associate professor at M.D. Anderson Cancer Center who specializes in melanoma. "Cancers can reduce targets on the surface or secrete nasty stuff that's toxic to the immune system."

For that reason, most makers of personalized cancer vaccines are combining their drugs with other therapies. Moderna partnered with Merck & Co., adding its vaccine to Merck's Keytruda, which works by lowering barriers erected by cancer that stymie the immune system. Merck, the third biggest drugmaker in the U.S. by revenue, is funding the trial with $200 million.

"We don't like doing it alone when the biology risk is high," said Bancel, Moderna's CEO. "With Merck, if it goes to zero we won't lose capital. If it works we'll take 50 percent of the upside."

Bancel said that when he first proposed a personalized cancer vaccine to his board, "They said, go find a partner, someone already in immuno-oncology who will tell you if it's good. See what the market tells us."

"The market loved it," he said.

Eric Rubin, Merck's vice president of global clinical oncology, said the science has advanced enough "that this was the time when it was worth making a reasonably large investment."

Merck has much to gain if the trials are successful. Keytruda, its blockbuster cancer drug, only works for about a third of patients. If combining Keytruda with a vaccine is viable, Merck could vastly expand its market.

For now, Moderna is testing its therapy in patients whose tumors have been cut out—Cleaver's lung tumor was successfully removed in April. Still, about 30 percent of patients with her form of cancer see the disease return, so the hope is that her vaccine will prevent recurrence. If the vaccine proves safe for Cleaver and the first cohort of patients, Moderna will test it in patients with active cancer. The company will try to cut its turnaround time to under four weeks, since those patients may not be able to wait long.

Moderna expects initial results by the end of 2018. It's too early for the company to say what price it will seek for its labor-intensive product. Merck's Keytruda has a list price of $150,000 a year.

"The more personalization is involved, the more cost and logistical challenges—so the result has to justify the extra effort and expense to do it," says Ronald Levy, a professor of medicine at Stanford University.

Moderna and others are anxious to streamline the process in hopes of eventually producing individualized treatments at scale, but that's a work in progress. On Nov. 7, there was a single vial to be taken off a Wisconsin production line, put into a FedEx box, and shipped to Nashville, where Cleaver was waiting, filled with hope and anxiety.

"I have a thing about needles," she said before receiving the vaccine. "But I've reached that age where I'm looking back at my life and thinking, what have you done for humanity, buddy?"

So she'll swallow her fear and hold out her arm, she says. "Somebody's got to do it."