Model-based reinforcement learning (MBRL) is sample-efficient but struggles in sparse reward settings. A critical bottleneck arises from the lack of informative gradients in sparse settings, where standard reward models often yield flat landscapes that struggle to guide planning. To address this challenge, we propose Shaping Landscapes with Optimistic Potential Estimates (SLOPE), a novel framework that shifts reward modeling from predicting sparse scalars to constructing informative potential landscapes. SLOPE employs optimistic distributional regression to estimate high-confidence upper bounds, which amplifies rare success signals and ensures sufficient exploration gradients. Evaluations on 30+ tasks across 5 benchmarks and real-world robotic deployments, demonstrate that SLOPE consistently outperforms leading baselines in fully sparse, semi-sparse, and dense rewards. The project code is available at https://github.com/Arya87/SLOPE.
Macrocyclic peptides are an emerging modality that combines biologics-like affinity with small-molecule-like developability, yet their vast combinatorial space and multi-parameter objectives make lead optimization slow and challenging. Prior generative approaches for peptide lead optimization (e.g., PepINVENT) require chemists to pre-specify mutable positions for optimization, choices that are not always known a priori, and rely on static pretraining and optimization algorithms that limit the model's ability to generalize and effectively optimize peptide sequences. We introduce PepEVOLVE, a position-aware, dynamic framework that learns both where to edit and how to dynamically optimize peptides for multi-parameter improvement. PepEVOLVE (i) augments pretraining with dynamic masking and CHUCKLES shifting to improve generalization, (ii) uses a context-free multi-armed-bandit router that discovers high-reward residues, and (iii) couples a novel evolving optimization algorithm with group-relative advantage to stabilize reinforcement updates. During in silico evaluations, the router policy reliably learns and concentrates probability on chemically tractable sites that influence the desired peptide's properties. On a therapeutically motivated Rev-binding macrocycle benchmark, PepEVOLVE outperformed PepINVENT by reaching higher averaged permeability-weighted optimization scores of approximately 0.8 vs. 0.6, achieving best candidates with score of 0.97 (vs. 0.89), and converging in fewer steps under the task of optimizing permeability and lipophilicity with structure constraints. Overall, PepEVOLVE offers a practical, reproducible path to linear and macrocyclic peptide lead optimization when optimal edit sites are unknown, enabling more efficient chemical space exploration and improving design quality across multiple objectives to accelerate the design cycles.