Could you operate a SST with a fuel burn about 20-25% higher than a sub-sonic?
If you are talking a 1.8M aircraft, I seriously doubt you can. Remember, we might have made many advances to make a supersonic jet much more efficient than the Concorde, but, at the same time, we have made other advances that make subsonic jets more efficient, too. So, the delta will always be about the same.
Could you shift 150 or so airframes to cover development costs?
You're not going to cover the development costs with 150 planes. Just take a look at the L-1011, of which 250 were built. Even the DC-10 didn't make money for McDonnell Douglas, and more than 400 of them were built.
(Or alternatively, tap into an appropriately targeted NASA program, as US mfrs tend to).
And you don't think Airbus leverages research by European agencies like DERA, ONERA, DLR, NLR, etc.?
Is there a market? Suppose you designed one hull, with several fuel and fitting options. One could carry 240 economy pax for 3-4 hours, at a premium of (say) 30% - Say W. Europe - E.USA. Bear in mind that there is already a market for an upgraded economy product, with more legroom. What about halving journey time? No need to travel W-E overnight!
Can you tell me how many subsonic trans-Atlantic flights there are each day, and how many supersonic flights there are? How can you say there is already a market for supersonic travel? Anyway, all your hypothetic scenarios are all unrealistic.