Novartis just spent $1.5B for Myrcix Bio, and the prize is the payload. Here's what the ADC payload landscape looks like now and why this is the next battlefield of innovation:

I used Sleuth to aggregate 1,838 active ADC programs and pull the payload for each. Some takeaways: about half don't disclose payloads, almost all of which are preclinical; of those that do, about 86% are Topo-I or Tubulin, so genuinely new mechanisms are rare and early.

But there's a logical reason for this concentration. The premise of ADCs was to improve the therapeutic index: deliver a tumor-lethal payload dose while sparing healthy tissue. But as constructed, they can leak (off-target binding, imperfect linkers, etc.), which is why safety failure is common. Payload class thus became a good predictor of an ADC's toxicity, causing the field to cluster around those with a proven mix of potency and tolerability.

But the limits are now showing: increasing resistance, non-responders, and a tolerability ceiling (ILD) all cap how potent drugs can be or how much they can be combined. In the pursuit of safer, more effective drugs, the industry is starting to look elsewhere.

A few strategies are emerging among next-gen approaches: flex the payload (a differentiated warhead is the moat); flex the chassis via linker, conjugation and DAR (stable, precise delivery is the moat); flex the format with bispecifics and biparatopics (smarter architecture is the moat); flex the combo (dual mechanisms are the moat); and flex the target (reaching new biology is the moat).

Most sponsors are flexing several at once. And because ADCs are so modular, incumbents like Daiichi Sankyo have an advantage from years of co-optimizing each component together. That integration know-how is a moat as well.

Novartis is among the first Pharma to bet that novel payloads will define what the ADC landscape looks like in 2030 and beyond, but it won't be the last. Half of today's programs haven't revealed their payload, and most are still preclinical. As they advance and unmask, this map will look very different within a year. For anyone in BD or licensing, tracking where these novel payloads emerge over the next 6 to 18 months is how you skate to where the puck is going.