The Ballad of TIGIT

A very nicely written article (and I don’t say that often!)

And the overall premise is spot on: while it’s a shame that the drugs failed, it’s okay, because we want companies to be taking bets on targets that might result in the next big drug to save or prolong lives.

> In 2026, a BMJ Oncology analysis would give a clinical name to what had happened: “herding.” The authors estimated that nearly 49,000 patients had been enrolled in anti-TIGIT trials by pharmaceutical companies, at a cost of more than $3 billion, all because their fellow pharmaceutical companies were doing the same thing

This is also spot on. I’ve been in the room when people have been infected by this peculiar competitive mania. Rational science takes a backseat to FOMO. But it’s also somewhat understandable: the model we have relies on companies making money to continue to exist and invest in further research and drug development. So of course, they all wanted a slice of the pie, no matter how wrong this was in retrospect. It’s just how the current system works, and it’s the least bad (?) system we’ve yet evolved for such sharing out of resources.

At the same time we see TIGIT targeted drugs failing, we are seeing the success of drugs against another white whale of cancer drug targets: KRAS.

It's the most frequently mutated cancer activating gene out there, but has been declared "undruggable" for the 15-20 years I've been close enough to drug developers to have heard about it.

Yet we're seeing clinical successes in recent trials with Revolution Medicine's daraxonrasib, and now there's blood in the water, with tons of new approaches going after it.

The progress in biotech in the past few decades has been unbelievable, and lots of things that were considered impossible a few decades ago are now happening left and right. Whenever I hear that somebody thinks that technological progress has stopped, I just think that they've stopped looking in the right places for the huge advances that are going on.

Anti-amyloid drugs work at reducing amyloid plaques. Only problem is that the idea that those plaques are the root cause for Alzheimer's was academic fraud.