Thats a surprise.
When you connect an ISP programmer, the NSS to the LoRa device will be floating, meaning it can be selected, and thus MISO on the LoRa device goes active, directly interferring with the ISP programmer. I have always needed the pull up on my boards, if I want to use the ISP programmer.
Oh, and before you get the PCB you absolutly do need to test the circuit on a breadboard very odd things can happen to sleep current and some components might not work as expected, for instance I doubt the way you have the DS3231 connected it will work as intended …