ReMedI: Inference-Time Refinement and Self-Distillation for Controllable Molecular Optimization

arXiv:2610.32103v1 Announce Type: new Abstract: In drug development, lead optimization must improve competing properties, such as increasing permeability and reducing toxicity, while limiting scaffold changes that could compromise the lead's potency. RL-based post-training, such as C-MORAL, addresses this problem by fine-tuning molecular language models to directly optimize molecular leads for objectives of interest, which relies on expensive task-specific datasets and faces challenges in achieving multi-objective optimization (MOO). We argue a pre-trained model may already contain useful molecular edits that zero-shot generation cannot efficiently reach. Motivated by the limited search capabilities of zero-shot generation, we develop an efficient Metropolis-Hastings search strategy to bet