Quantum Encoding Strategies for Drug Response Prediction: An Exhaustive Benchmark on a 20-Qubit Superconducting QPU

We present the first systematic, hardware-executed benchmark of twelve distinct quantum data-encoding strategies for drug-response prediction on a real superconducting quantum processing unit (QPU). All experiments were conducted on the IQM Garnet 20-qubit QPU via the IQM Resonance cloud platform, using the Qrisp quantum-software framework (v 0.8.2). Each encoding was evaluated on n = 50 stratified samples drawn from the Genomics of Drug Sensitivity in Cancer dataset (GDSC2, 242 036 drug–cell-line pairs), targeting the natural-log IC ₅₀ response variable. Variational weights were optimised offline with the gradient-free COBYLA algorithm before hardware submission. Every circuit was executed with 1024 shots; the regression signal is the zero-qubit Pauli expectation value ⟨ Z ₀ ⟩. Results show that the QAOA-inspired encoding achieves the best RMSE of 3.314 and is statistically superior ( p < 0.05, Wilcoxon signed-rank test) to six of the remaining eleven encodings. Hardware-efficient entanglement structures—specifically alternating cost and mixer layers—provide a systematic advantage over purely rotational or diagonal encodings under realistic noise conditions. This work constitutes a reproducible baseline for noise-aware quantum machine learning on pharmaceutical data; all code, data, and raw QPU outputs are publicly released.