Summit Therapeutics (SMMT) has had the highest return between 2022 and 2025 by a large-cap US stock, returning 849.8%.

ASSET	YEARS	% RETURN
Summit Therapeutics (SMMT)	2022-2025	849.83%
YPF Sociedad Anonima (YPF)	2022-2025	759.22%
Super Micro Computer (SMCI)	2022-2025	606.23%
MicroStrategy (MSTR)	2022-2025	476.09%
Constellation Energy (CEG)	2022-2025	460.41%
Vistra Energy (VST)	2022-2025	442.65%
Sprouts Farmers Market LLC (SFM)	2022-2025	439.59%
Palantir Technologies Inc Class A Common Stock (PLTR)	2022-2025	410.78%
Harmony Gold Mining (HMY)	2022-2025	354.73%
Fair Isaac (FICO)	2022-2025	336.62%
TechnipFMC (FTI)	2022-2025	324.8%
Alamos Gold (AGI)	2022-2025	300.63%
Howmet Aerospace (HWM)	2022-2025	289.12%
Flex (FLEX)	2022-2025	276.7%
MakeMyTrip (MMYT)	2022-2025	268.93%
Targa Resources (TRGP)	2022-2025	259.02%
Axon Enterprise (AXON)	2022-2025	257.3%
Comfort Systems USA (FIX)	2022-2025	255.32%
NVIDIA (NVDA)	2022-2025	240.97%
Unum (UNM)	2022-2025	239.6%
Texas Pacific Land Trust (TPL)	2022-2025	230.91%
TKO (TKO)	2022-2025	216.06%
Eli Lilly and (LLY)	2022-2025	215.89%
GE Aerospace (GE)	2022-2025	211.3%
Duolingo (DUOL)	2022-2025	206.86%

Large-cap stocks are treated as having a market cap of $10B+.