The new story is about Isaac & Co.'s descendants, not their ancestors/forebears. Those two guys in the image aren't Isaac and Garet, they're Isaac and Garet's great-great-great-great-great grandsons. The only characters who could reasonably still be around are the Lemurians, since, you know, immortality and all that. I assume that it'll pick up some time after the world's started to rebuild itself thanks to the return of alchemy. I'm looking forward to seeing new civilizations and cities and stuff. Plus, I expect the attack will be even more epic. I'm betting the story involves Alex getting free somehow.