I think it might be possible to get through with Shrink only, if you are masochistic enough to try it.

With all the shield/regen/hp upgrades you can ignore Red, and occasional Purple hit will be quickly recovered. So once you unlock Break The Box you can get to the ending with no abilities at all as long as you dodge all the Blue Arrows.

The hardest parts are
being shoved around by shrinking the box but once you know when and how it happens, then with a bit of luck you should be able to reach final stage with no skill usage at all.
And afterwards being stuck in shrunk box where the only way to dodge is with Shrink.

Slow Time would help greatly, and if anyone manages to fully upgrade Shockwave before finishing game it might be useful as well.
But because in final stage you have no room to dodge either Shrink or Shield will be needed as I doubt anyone has enough luck to survive last 10 seconds without them.

I made a single test run, with full health and all upgrades you need 20%-30% extra HP to survive with no Skills. With some masochistic grind in Fragile challenge it might be possible to do no-skill run.

I am at 3:05 for my best in Fragile Challenge, that does take a bit of grind though. With that it is definitely possible with that to win with any two skills.

So far my best with Slow time only is 4:59. Near the end you have to start manipulating the invuln to get past the last little bit (not too bad with slow time, but does require luck), it should be possible I think?