Double-checked the firewall settings (working from a home network) & ADE is allowed access (also turned off the firewall & still got the e_io_cannot_open error; I posted here as this error isn't as widely reported as others and was curious if there were known issues/troubleshooting steps specific to that error).
I'm able to access the page listed in step 5 on this page in my browser http://helpx.adobe.com/digital-editions/kb/error-drm-error-activate-access.html
Are there other pages I can test via browser to know I'm connecting with Adobe Content servers?