At some point shorts will start to increase as the sp moves up,...

At some point shorts will start to increase as the sp moves up, in particular if the company has one approved drug. If the volume traded in the stock rises significantly post FDA approval that will be advantageous for the sp as the shorts will have less control over it, but for me it is almost a certainty that shorting will tame the sp over the coming years. The commercial potential of the drug is such that this could offset the effect of heavy shorting, but I would expect the market capitalisation to be slightly below what it should be on paper. That said, I still expect the market cap post FDA approval first year revenues to be anywhere between $1.2 billion and $2 billion.