Hi Chris,
note that the Librem 5 is at a very early stage. Hopefully the first real backer will receive one in the coming weeks. Obviously, it is not very polished yet.
You could try to get some idea with the virtual machine image (Link to VM Documentation).
Do you happen to know if Orca supports Wayland? Or rather, if Wayland has a screenreader API? As you might know, Wayland wants to be more secure than X11 by not exposing window contents to other processes. So, that might be the main problem, but either it’s already solved or it has to be solved anyway as X11 gets replaced by Wayland more and more.
The harder part would most likely be navigation and Orca activation without a physical keyboard. But of course, all the sensors (touch, microphone, gyroscope) open up interesting possibilities.
I personally would assume the most promising way to bring the necessary changes about would be to hire a couple of developers who help to incorporate them into Gnome and PureOS. And for that, you’d probably need a group of hundreds of people willing to invest in that.
Out of curiosity, is your screen reader butchering Librem? Because you spell it as M5, and it should be Libre plus M as one word 