One issue is the mix of passengers. SQ decided make their SIN - EWR/LAX flights business class only presumably because J passengers are time sensitive and value non stop services and are willing to pay a premium. Long distance is a lot more bearable in premium and a full fuel load can be carried with only 100 pax + crew in a 345. Even so the economics don't appear to be working and SQ are dropping the two routes.
I've just been checking the International Passenger Survey. Whilst the UK - Oz market is around 3m one-way trips annually only about 250,000 are travelling on business. I'm not sure what proportion are LON - SYD, lets say 100,000 p.a. If you could capture half of this market you could probably fill a 777LR in all F/J config (maybe even a little W not all business pax travel in premium). A 777LR neo with next generation engines & other enhancements could probably fly non stop in both directions and (easier in the eastbound direction). However would manufacturers be able to make a business case to certify an aircraft that would only few a sell models? The 77L is not a large seller, certainly not compared with the 77W.
So yes it could be done but making it work is another matter.