Hi
Indeed a strange and unwanted behaviour.
Please tell us about your system and software versions:
Windows or macOS,
RME interface model,
RME driver and firmware versions,
Studio One version …

Hopefully some Windows and UFX III experts will chime in. I can’t help, I’m on Mac and don’t use Studio One (except sometimes the free version).

Ah yes, sorry. That should work using the loopback feature in TotalMix.
How exactly is the 'Pipeline' working? I guess just like an insert on a mixing desk?
If so, I would select an unused output (stereo pair) of your interface and the corresponding input. Let’s take ADAT 1/2 for example.
Also please note I have Totalmix set to submix view.
When you select this output in the plugin, the audio signal should reach ADAT 1/2 software playback channels in the Totalmix window. On this channel, set the EQ as you wish. Now click on hardware output ADAT 1/2 (bottom row) to select it (it should change to a brighter background colour). Now close all faders on the hardware input (top) row as well as on software playback (middle) row. Only raise up (double click) the fader of software playback ADAT 1/2. Also the fader of hardware out ADAT 1/2 has to be open of course. Open the tools of hardware out ADAT 1/2. Click on the 'loopback' button (it becomes orange highlighted). The signal - including the eq modification - now is sent internally to ADAT 1/2 hardware input (so no cables needed). And from there it should reach the 'Pipeline' plugin with the added eq.
You can select any output / input channels to do this. The signal stays within the UFX, there is no DA/AD conversion involved, even when you select 'analog' channels! And there is almost no latency, a few milliseconds maybe…