Well firstly, the director of the first four games (Takashi Oda) said that if THoTD5 would be in development, it would be based around The Mystery Man as the game's main antagonist. For this to work, THoTD5 would most likely be set after House of The Dead 3, seeing as we were first introduced to The Mystery Man in one of House of The Dead 3's alternate endings. It may be set a few months to a year after THoTD3 was set, (Halloween 2019) because The Mystery Man is obviously working on something that needed Curien 's antidote? Either that or the bad ending of THoTD5 could involve The Mystery Man escaping. With the antidote, we also learned from THoTD3 that the antidote can cure terminal illnesses but will eventually mutate the person with the antidote inside them into a zombie. (As we saw from THoTD3's bad ending when Daniel Curien mutated into a zombie) This could mean that The Mystery Man is planning a fifth outbreak.