Nice essay Ankit!
I think there are two more factors worth touching on that make things difficult in drug discovery:
1. It feels like you're differentiating a bit but I always hear of the APIs being leaky. The selection of a target in the target discovery phase may drive which modalities are even available to try to engineer an intervention (e.g., intracellular vs extracellular targets can be addressed with different types of drugs). Clinical factors can also determine whether a particular modality is appropriate (e.g., keeping drugs refrigerated).
2. Costs create constraints that need to be applied at all the stages of the pipeline. Does gathering evidence during target discovery require a unique assay or access to very rare patient samples? What is the size of the addressable market? If you can only target a narrow patient population, it may not end up justifying the costs involved in running the clinical trials. If your chosen drug modality costs $500k to synthesize one dose, how will it be paid for?