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Solution found!
Not sure where this post* found this text in the documentation, but it worked:
You can use presigned URLs with the Spaces CDN. To do so,configure your SDK or S3 tool to use the non-CDN endpoint, generate a presigned URL for a GetObject request, then modify the hostname in the URL to be the CDN hostname (<space-name>.<region>.cdn.digitaloceanspaces.com, unless the Space uses a custom hostname).
I assume that the reasoning for this is that DO uses some magic links, i.e. adds the region in the original endpoint. A bit hacky, but happy to have found a solution
In code, this means:
// To use DO CDN, you need to generate a signed url with the original endpoint
// and then swap out the domain
const modifiedUrl = process.env.DO_SPACES_CDN + presSignedUrl.split('.com')[1];]