Download the Report
In AML, selectivity, not target count, is the constraint
The most pursued drug targets in acute myeloid leukemia (AML) are also expressed on healthy blood-forming cells, so selectivity, not target count, is the field’s core constraint. Sleuth’s January 2026 landscape analysis maps 957 AML programs, and the six validated targets that draw the most competition, FLT3, CD33, CD123, CLL-1, CD7 and Bcl-2, account for only about 16% of them. Another 349 targets have just one or two programs each.
The most pursued targets overlap with healthy hematopoiesis
In Sleuth’s January 2026 analysis, the leading AML targets, including FLT3, CD33 and CD123, are shared with normal hematopoietic stem or progenitor cells, which creates built-in on-target toxicity. Myelosuppression and prolonged cytopenias recur across modalities as a result. Selectivity evidence is thin: fewer than half of the 957 programs (47%) report both protein-level and functional validation, and many claims rest on transcript data or inference.
For many AML targets, the therapeutic window is assumed rather than demonstrated, which makes selectivity evidence one of the first things to diligence.
Small molecules lead on volume, and cell therapy is stuck early
Small molecules are the largest AML modality in the January 2026 analysis, with 347 programs, and the only one spread evenly from preclinical to approved. Cell therapy is second, with 287 programs (30%), but 230 of them are preclinical or in Phase 1. Antibodies and bispecifics (118 programs) and ADCs (49) sit mostly in preclinical and early clinical stages. Mitigation strategies diverge by modality: cell therapies rely on lineage-restricted target selection (57%) and post-transplant timing (43%), while small-molecule programs depend on split dosing (51%) and combinations (54%), and 44% of them cite no explicit mitigation strategy.
Volume is not validation. As of September 2026, no cell therapy aimed at an AML target antigen has been approved; Orca Bio’s Tregzi, approved in June 2026, is a cell therapy used in stem cell transplants for blood cancers including AML, not an AML-targeted drug. Sleuth’s look at AML’s cell therapy bet covers the gap.
Mature-restricted targets with low competition are the open ground
Sleuth’s January 2026 analysis names targets with expression restricted to mature cells and little competition, including LILRB4, PRAME, CD25 and Siglec-6, as underexplored. Its opportunity score, HSC selectivity minus a crowding penalty, ranks crowded targets that overlap with stem cells, such as FLT3 and CD123, lowest.
These targets suit discovery approaches that resolve selectivity up front rather than engineering around toxicity downstream.
Counts are rounded. Programs and targets come from Sleuth’s January 2026 AML landscape analysis; approval status checked through September 2026.
Frequently asked questions about the AML landscape
How many AML programs did Sleuth map?
Sleuth mapped 957 AML programs in its January 2026 landscape analysis. Six validated targets account for about 16% of them, and 349 targets have only one or two programs each.
What are the most validated AML targets?
FLT3, CD33, CD123, CLL-1, CD7 and Bcl-2. In Sleuth’s January 2026 analysis they draw the most competition but account for only about 16% of AML programs.
Why is AML hard to target safely?
Most pursued AML targets are also expressed on healthy hematopoietic stem or progenitor cells, so hitting them causes myelosuppression and cytopenias. In Sleuth’s January 2026 analysis, fewer than half of programs (47%) report both protein-level and functional evidence of selectivity.
Which AML targets are underexplored?
Targets with expression restricted to mature cells and little competition, such as LILRB4, PRAME, CD25 and Siglec-6, according to Sleuth’s January 2026 analysis. They suit discovery approaches that build selectivity in from the start.
How current is this analysis?
The program and target counts come from Sleuth’s January 2026 AML landscape analysis. Approval status on this page was checked through September 2026.
