Modern state-of-the-art planners operate by generating a grounded transition system prior to performing search for a solution to a given planning task. Some tasks involve a significant number of objects or entail managing predicates and action schemas with a significant number of arguments. Hence, this instantiation procedure can exhaust all available memory and therefore prevent a planner from performing search to find a solution. This thesis explores this limitation by presenting a benchmark set of problems based on Organic Chemistry Synthesis that was submitted to the latest International Planning Competition (IPC-2018). This benchmark was constructed to gauge the performance of the competing planners given that instantiation is an issue. Furthermore, a novel algorithm, the Regression-Based Heuristic Planner (RBHP), is developed with the aim of averting this issue. RBHP was inspired by the retro-synthetic approach commonly used to solve organic synthesis problems efficiently. RBHP solves planning tasks by applying domain independent heuristics, computed by regression, and performing best-first search. In contrast to most modern planners, RBHP computes heuristics backwards by applying the goal-directed regression operator. However, the best-first search proceeds forward similar to other planners. The proposed planner is evaluated on a set of planning tasks included in previous International Planning Competitions (IPC) against a subset of the top scoring state-of-the-art planners submitted to the IPC-2018.