What I would do:

my $original = 'KLEWREGREG-----REGREGEWD....-EWGREGERABCSHRE..----...X
+FGHWW';
my $copy = $original;
$copy =~ s/[-.]+//g;
if ($copy =~ /(...)XFGHWW/) {
    print "Found it: $1\n";
}
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Of course, if there's no need to preserve the original string, there's no need to make a copy.