Every TROP2 ADC on the market or in the clinic uses the same basic idea.
Stick a cytotoxic chemo warhead on an antibody, point it at TROP2, and hope the cancer cells die faster than the healthy cells.
Daiichi Sankyo and AstraZeneca‘s Trodelvy uses a topoisomerase inhibitor.
Gilead‘s datopotamab deruxtecan uses one too.
Merck‘s TROP2 ADC. Same idea.
The problem is that everyone’s warhead is a cousin of everyone else’s. So, cells that get resistant to one tend to get resistant to the rest. Toxicity profiles look similar. And if you’ve read our recent piece on ABION, the whole field is starting to bump up against the ceiling of what tubulin and topoisomerase payloads can do.
Akari Therapeutics is trying something different.
Their lead asset, AKTX-101, is a TROP2 ADC.
Same target, same general idea. But the warhead is PH1, a Thailanstatin analog that modulates the spliceosome.
It kills cancer cells by breaking RNA splicing instead of damaging DNA or microtubules.
ADC payload classes
Kadcyla, Adcetris
Trodelvy, Enhertu
Akari AKTX-101
PH1 is a distinct mechanism. Cells resistant to chemo-class payloads may still respond.
The Biotech Voyager
Early-stage biotech signals, personalized.
The signals that matter to you, contextualized and written directly to you, so you cut through the noise and immediately understand why it matters.
Akari presented preclinical data at AACR this week.
AKTX-101 showed sub-nanomolar potency in bladder, lung, and breast cancer cell models, with superior potency versus existing TROP2 ADCs in head-to-head testing. PH1 also stays potent against cells that pump out standard ADC payloads through efflux pumps, a known resistance mechanism for the chemo-class warheads.
There’s a second thing happening.
When the spliceosome gets modulated, cancer cells produce mis-spliced proteins. Those show up on the cell surface as neoantigens and potentially activate the immune system.
In preclinical work, Akari saw 74% complete tumor regressions when their HER2-PH1 ADC was combined with anti-PD1, versus 42% for Kadcyla plus anti-PD1.
This is still preclinical. AKTX-101 is in IND-enabling studies with a first-in-human planned for late 2026 or early 2027. The company merged with Peak Bio in late 2024 and has been pretty cash-thin since, raising $2.5M in a registered direct in October 2025 and $6.6M in a March 2025 placement.
If the immune-activation angle holds up in the clinic, Akari has a real case for being more than just another TROP2 ADC.
If it doesn’t, they’re fighting Gilead and AstraZeneca with less capital.
