failed-so-far

CD47 is the 'don't eat me' signal: it binds SIRP-alpha on macrophages to stop them engulfing the cell, and over 90% of AML blasts and large B-cell lymphoma cells display it. Blocking it should let macrophages eat tumour cells, but red cells carry CD47 too, so anaemia is built in, and the lead antibody magrolimab was dropped after failed trials.

ESSA Pharma developed masofaniten, an AR N-terminal-domain inhibitor whose phase 2 was stopped for futility in 2024-25.

Fianlimab is Regeneron's LAG-3 blocking antibody, paired with the PD-1 blocker cemiplimab. A 60% phase 1 response rate in untreated melanoma prompted phase 3 trials, but the metastatic trial against pembrolizumab missed its progression endpoint in 2026.

A drug designed to block the part of the androgen receptor that resistant variants keep; its phase 2 was stopped for futility and development ended.

TIGIT is an inhibitory receptor on T and natural killer cells that binds PVR (CD155) on tumour cells, so blocking it was expected to amplify PD-1 and PD-L1 inhibitors. Tiragolumab, domvanalimab and others then failed to add benefit in phase 3 lung cancer trials despite encouraging phase 2 signals, and the lack of a TIGIT-specific biomarker remains a weakness.