The Cancer Company That Came Home

It's Thursday, August twentieth. Moderna's stock went up 177 percent yesterday, which is the kind of move that almost never happens to a company this size. The reason is a clinical trial result that the company's own chief development officer called "one of the holy grails" of medicine: the first mRNA cancer vaccine to succeed in a final-stage trial. If you know Moderna at all, you probably know them as the COVID vaccine company, the one that went from obscure biotech to household name during the pandemic and then lost over 90 percent of its stock value as COVID demand faded. But what I didn't know until today is that Moderna was never really a COVID company. It was founded in 2010 as a cancer company developing mRNA therapies, pivoted to COVID when the pandemic hit because the technology was a perfect fit, and has been trying to get back to cancer ever since. Their president said it directly: "People will experience this as the COVID company taking on cancer. But for those of us that live in it, it's the cancer company that pivoted to help with COVID and has now finally come home." To understand why yesterday's announcement matters, you need to understand what cancer treatment has looked like for most of modern medicine, because the approach Moderna is using is fundamentally different from almost everything that came before it.

Traditional chemotherapy, which has been the backbone of cancer treatment since the 1940s, works by exploiting the fact that cancer cells grow and divide faster than normal cells. Chemo drugs target rapidly dividing cells and kill them. The problem is that they can't tell the difference between a cancer cell dividing rapidly and a healthy cell dividing rapidly, which is why chemo patients lose their hair (hair follicles are some of the fastest-dividing cells in the body), experience nausea (the gut lining regenerates constantly), and suffer immune suppression (immune cells divide frequently). One oncologist described the approach as "trying to kill the cancer before the drug kills the patient," which is blunt but not inaccurate. It works often enough that it's saved millions of lives, but the side effects are brutal because the treatment isn't targeted. It's a carpet bomb when what you really want is a sniper.

Immunotherapy, which emerged over the last two decades, was the first major shift away from carpet bombing. Drugs like Merck's Keytruda (kee-TROO-dah) work by removing the "brakes" that cancer cells put on the immune system. Cancer is sneaky because it figures out how to hide from your immune cells by sending signals that say "I'm not a threat, leave me alone." Keytruda blocks those signals, which lets the immune system see the cancer and attack it. It's been a massive breakthrough for certain cancers, but it doesn't work for every patient because some tumors are better at hiding than others, and the immune system still has to figure out what to target on its own. What Moderna announced yesterday is a combination of both approaches, but with an added layer that makes it unlike anything that's been approved before: the vaccine is custom-built for each individual patient.

Here's how it works. After a patient has surgery to remove a melanoma tumor, doctors take a sample of the removed tumor and sequence its DNA. They identify the specific mutations that are unique to that patient's cancer, mutations that don't exist in the patient's healthy cells. Moderna then builds an mRNA vaccine that encodes those exact mutations and injects it into the patient. The mRNA teaches the patient's immune system to recognize cells carrying those specific mutations as threats, essentially giving the immune system a wanted poster with the cancer's unique face on it. Combined with Keytruda to remove the brakes, the immune system can now both see the cancer and know exactly what it's looking for.

The trial involved over 1,100 patients with high-risk melanoma that had been surgically removed, and the combination of the personalized vaccine plus Keytruda significantly reduced the rate of cancer recurrence compared to Keytruda alone. It also met its secondary goal of preventing the cancer from spreading to other parts of the body. The side effect profile was mild compared to traditional chemotherapy because the vaccine isn't poisoning rapidly dividing cells indiscriminately. It's training the immune system to do a specific job.

Every vaccine in the trial was different because every patient's tumor was different. That's what makes this a departure from how medicine has worked for essentially all of modern history: instead of one drug designed to treat millions of people, this is a platform that produces millions of unique drugs designed for one person each. The mRNA technology is the platform. The patient's tumor provides the instructions. And the immune system does the killing. The stock story makes the science story even more interesting. Moderna was founded in 2010 by a group of scientists including Derrick Rossi, who had been experimenting with modified messenger RNA at Harvard, and Robert Langer, one of the most prolific biomedical engineers in history. The name "Moderna" comes from "modified RNA." The company spent a decade developing mRNA technology for cancer and rare diseases, burning through billions in venture capital funding while generating zero revenue. By early 2020, they had never brought a product to market.

Then COVID hit, and mRNA turned out to be uniquely suited for building vaccines quickly because you don't need to grow the actual virus. You just need the genetic sequence, which China published in January 2020. Moderna designed its COVID vaccine in two days. The clinical trials, manufacturing scale-up, and regulatory review took months, but the core design took 48 hours. The vaccine was authorized in December 2020, and Moderna went from a company that had never sold anything to one generating over $18 billion in annual revenue. The stock peaked above $480 in August 2021.

Then demand collapsed. Boosters slowed, governments canceled orders, and the stock fell over 90 percent from its peak to about $63 by yesterday. The narrative shifted from "miracle vaccine company" to "one-hit wonder." And then this morning, the company that most people had written off announced the first successful Phase 3 result for a personalized mRNA cancer vaccine, and the stock nearly tripled in a single day. The trials are ongoing in lung cancer, bladder cancer, and kidney cancer, and if the melanoma results hold up and extend to other tumor types, the platform could eventually be applied to any solid tumor where the mutations can be sequenced. Moderna's cofounder Robert Langer called it "a potential paradigm shift." The company that the market left for dead six months ago might be sitting on the most important cancer treatment technology developed in decades. A company that spent ten years trying to cure cancer, pivoted to COVID, became the most famous biotech in the world, lost 90 percent of its value, and then came back to cancer and produced the first successful mRNA cancer vaccine in history. That's the kind of arc that doesn't happen very often.

Stay informed, stay curious, and we'll see you tomorrow.