I've been doing drug research since 1989 myself, which means that I'm fairly experienced. But Regeneron (REGN) started in this business a year or two before I did, and they're just now getting their first major drug, Eylea (aflibercept) onto the market. To be fair, they did get approval for Araclyst (rilonacept) in 2008, but that one pays the electric bill and not much more - although that might be changing (see below).
As Andrew Pollack at the New York Times points out, the company has run through over two billion dollars over the years. I remember when they were working on nerve growth factors for ALS and other diseases, back in the early 1990s (I worked in the area briefly myself, to no good effect whatsoever). There are not a lot of nerve growth factor drugs on the market, although it seemed like a perfectly plausible mechanism for one back then.
That work shaded into another indication, ciliary neurotrophic factor for obesity. Regeneron spent a lot of time and money developing a modified form of that protein called Axokine, but in 2003 that project ran into the rocks. Some patients did lose weight on the drug (with daily injections), but too many of them developed antibodies to it, which raised the possibility of cross-reactivity with their own CNF, which would surely not have been a good thing. So much for Axokine.
But Eylea, a VEGF-based therapy for macular degeneration (entering the same space as Lucentis and Avastin), has now made it. And the company has another use for Arcalyst in preventative gout therapy coming along, and some interesting cholesterol work targeting PCSK9 in collaboration with Sanofi. So welcome, Regeneron, to the ranks of profitable biotech companies (well, pretty soon) who've developed their own products. It's taken a lot of time, a lot of patience - yours and your investors' - and a lot of cash. But you're still here, and how many other bioctech startups from the late 1980s can say that?