I haven't ridden the highway, but I've driven it… It is quite beautiful and I'm sure it would make an extraordinary bike trip. As far as late September goes - Fall weather can be really wonderful here - but do remember you will be going quite high up in the mountains - the weather can be erratic - It may not be terribly warm in the passes, rain and even snow would not be unheard of, but the pass generally remains open until November and I've driven it in October when it's been lovely (photos - https://flic.kr/s/aHsjKX7FA8 ) The days start to become short for us in the fall - the sun likely comes up later and goes down earlier than you'll be used to down in California, so be sure to have lights and plan for that too.

There's pretty much nothing between Marblemount and Winthrop, which is an 88 mile stretch with several mountain passes, so you'll have to plan accordingly to either have a long hard day or camp. If you are out during the week, traffic should be light, at least once you get out beyond the towns.