Hypothetically, failure to commercialise this candidate drug...

Hypothetically, failure to commercialise this candidate drug post phase III trials would spell absolute disaster. I think you're looking at this 'hypothetical' - yet not impossible scenario the wrong way. A 50% loss isn't just a 50% loss. There's also opportunity cost. Fancy having a decent investment in OPT for years only for it to fail? In the meantime, there's the possibility that you might've invested elsewhere in an already profitable company and had a change of fortune. How would you measure that? What would the real loss be?

Also, consider that the people behind this business are extremely well paid individuals. Many of them are probably already worth millions. I've noted this before in another comment whereby I mentioned that at the end of the day, retail investors are left carrying the can. Megan and Co. will still dine out on lobster and chardonnay. Carlyle/Abingworth probably have a very astute team that handle all matters related to legal and taxation implications.

That leaves speculative investors with a great big question mark hanging over their heads. As a shareholder in CSL, for years I took interest in CSL's proposed blockbuster drug - CSL 112. Move forward a decade and a billion dollars later and this "blockbuster" drug was put on the scrap heap as it did not meet efficacy and safety requirements.

I don't get hung up on companies quoting TAM's. I see OPT's presentations as promotional material. Bit like a trailer to a new blockbuster movie. You see and hear snippets of the good bits that last for a minute or two. But when you sit and watch the movie for 2 hours, it's pretty easy to ask yourself - "What the f**k am I doing here?". But in that time, I've paid for the ticket, I've loaded up on popcorn, fizzy drinks and a great big bag of kick arse maltesers and now I'm leaving the theatre disappointed, having to drive home in the rain and asking myself why it was that I didn't stay at home with my girl and just did Netflix and chill?

Investing in Biotechs can more often than not (fact) become a great trailer to a really bad premier screening.

So, to actually answer your initial hypothetical question, here is my answer...It's all or nothing. Or, seeing as I'm using theatre as an analogy, maybe this is a more appropriate response; It's an Academy Award...or a Golden Raspberry.