How do you manufacture a medicine that keeps changing?

**Akshara** (0:04)
In today's episode, we'll break down one interesting story in depth, followed by a shorter story. First, we'll talk about how you manufacture a medicine that keeps changing, and then we'll talk about whether Meghalaya can actually stop uranium mining.
Welcome back to The Daily Brief by Xero Da, where we cut through the noise to help you understand what's actually happening in the most important stories from business and markets. I'm your host Akshara. Today is Monday, 31st August. Before we begin, in the latest episode of Subtext, Abid, Bhuvan and Akanksha dissect the structural conflicts of interest in mutual fund distribution, the red flags hidden inside your CAS statement, and why keeping your portfolio simple will always make you more money than chasing cute thematic funds. You can watch the full episode on YouTube or follow the link to read more. Coming to the first story.
On August 19th, Moderna and Merck announced positive results from the phase 3 trial of their personalized cancer treatment. And Moderna's stock jumped 177% that day, and Merck rose 12.6%.
Now, a one-day stock move tells us very little about what the treatment will ultimately be worth. But the market clearly thought something important had changed. So the trial was for melanoma, which is a skin cancer that becomes dangerous once it starts to spread. And every patient in the trial had already had their tumour surgically removed. That sounds like the cancer should be gone, but often it isn't quite that simple. So surgery can remove everything doctors can see, but microscopic cancer cells may already be left behind elsewhere in the body, too small to detect. Months or years later, those cells can grow again and cause a recurrence. So after surgery, doctors sometimes use additional treatment to reduce the odds that the cancer comes back. For melanoma, one of those treatments is Keytruda. We have covered Keytruda on The Daily Brief before. But in short, cancer cells are abnormal cells that keep growing when they shouldn't, and normally, immune cells called T cells can recognize and attack them. But some cancer cells use certain signals to switch those T cells off. Keytruda jams that switch. It keeps the immune system awake and able to attack. But that only solves half the problem. You can wake the immune system up, but how do you tell it exactly which cells to go after?
That is the part Moderna is trying to add. Its approach starts with the tumor removed during surgery, then doctors study the mutations inside it, the specific quirks that make this person's cancer different from someone else's, and then they use those quirks to design a vaccine tailored to that one patient. So the cancer itself ends up supplying the recipe for the medicine meant to destroy it.
At the expense of over-simplifying, the two treatments split the work. Keytruda keeps the immune system switched on, and Moderna's vaccine shows it a photograph of the enemy, and that makes this treatment unusual in another way. So Keytruda can be manufactured years in advance and in bulk. But that doesn't make it easy to manufacture. Biologic drugs like Keytruda are notoriously difficult to make consistently, but once you crack the process, the goal is to make the same drug again and again. But Moderna's vaccine is different. The final medicine itself changes with every patient, and it does not exist until doctors have studied that person's tumor. Now, most of modern pharma was built around one idea. Find a medicine that works, then make millions of identical copies of it.
This treatment asks whether the industry can do the opposite. Run the same manufacturing process again and again, but produce a different medicine for every patient. It all starts with the tumour that was removed. Doctors read its genetic code and compare it with healthy DNA from the same patient, and they look for mutations that appeared in the cancer cells but are missing from the patient's healthy cells. Because some of those mutations change the proteins a cancer cell makes, and that can leave tiny abnormal markers on the cancer cell's surface. These markers are called neoantigens, which these cells can recognize. So those markers are useful targets. But a tumor can carry hundreds or even thousands of mutations, and most will not make good targets. The challenge is figuring out which ones the immune system can actually see and track. And that answer differs from person to person. So our cells have their own machinery for picking up pieces of proteins and showing them to T cells. But that machinery varies widely between people. So the same cancer mutation might give the immune system a clear target in one patient, and be practically invisible in another. So Moderna has to narrow the list down. Its system predicts which mutations in that particular patient's tumor are most likely to produce useful targets, and the treatment can encode up to 34 of them.