Hi nic,
I think we finally know what's going on! It took a lot of digging, but what you're seeing is a bug. Your report and willingness to share your setup with us made it much, much easier to diagnose the problem. Thanks!
It turns out there’s a bug related to the Flip Direction toggle for moments when we transfer loads from generative design to simulation. The issue causes the moment to twist the part in the opposite direction you expect (opposite even than the arrow is pointing). Notice how in the result below our intuition wouldn’t expect the part to twist clockwise when the applied moment appears to be turning it counter-clockwise.

We’ll work on fixing this on our end, but for now you can correct the simulation by editing the Moment load and clicking OK without changing anything. At least on my end, that seems to clean up the bad data and produce the expected simulation result. If you're still seeing issues, try deleting the moment load and re-creating it using the "Vectors" method of input (which bypasses the Flip Direction toggle):

Now I see a more intuitive distortion given your loading conditions:

Let’s compare this new simulation result to the values we expected from generative design.

Displacement is slightly higher in the simulation environment (3.28 mm vs. 3.12 mm, or +5%), but factor of safety is still low (though not nearly as bad as it was before) at 0.6 vs the expected 2.0. However, as noted in the article you linked to in your original post, we may see some stress concentrations near the interface with the preserves. If we look at the regions of the model with safety factor less than 2.0, we see a few red specs near the preserve transitions, and a region of yellow where the T-Spline body got cut by the obstacles. Even these yellow regions are all above a safety factor of 1.5, which is consistent with the level of accuracy I expect given the shape changes in the T-Spline conversion and simulator differences between generative design and the simulation environment.

We've got the bug report filed with the correct team to handle the problem. I can't guarantee it will be fixed in the next release, but at least we have a workaround that gets you back to a sensible solution.
Thanks again, and my apologies that the simulation tool simulated the wrong loads!
Ben
Ben Weiss
Senior Research Engineer