Completely rewriting this question since I've discovered the tru source of the problem.
I have the following text file:
strUpdateSql.Append(" this is a string ,")
strUpdateSql.Append(" that has multiple lines ,")
strUpdateSql.Append(" which need replacing,")
strUpdateSql.Append(" with regex. ,")
strUpdateSql.Append(" I need multiline support. ,")
In .NET, I can use ^*.strUpdateSql.Append\(" regex multiline mode to remove all of the unwanted characters at the beginning of each line. Notepad2, by default, doesn't recognize multiple lines, so it ends up removing almost the entire text. I could craft my own harrowing regex string to look for newline characters, but I am looking for a simpler approach. Newline mode would fit the bill.