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Orion 0.99.130.1-beta (WebKit 619.1.11.111.2) under MacOS 12.7.6.
My three extensions are set to Always Allow on Every Website (Orion menu → Preferences → Websites → Extension Settings). Nevertheless, on some sites—YouTube in this example—all three extensions are disabled. Even if I change each one from "Deny" to "Allow", the setting doesn't take. See for yourself:
I know it shouldn't be necessary (and might make problems) to run uBlock Origin on top of Orion's inbuilt blockers; I installed it just now to see if it would block YouTube ads—which Orion by itself does not—and/or if it would also be forcibly disabled despite my "Allow" settings. Answer to question 1 can't be known until question 2 is addressed.
I tried uninstalling uBlock origin and installing some other extensions, one at a time, and they are all forcibly denied on YouTube, whether or not they have anything to do with anything YouTube does (e.g., 1Password).
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0.99.130.1-beta (WebKit 619.1.11.111.2)
Monterey (12)