Dave, Diabetes also runs in my family and I have actively followed the Biotech sector, especially LGND (I formed its parent company, Progenx). As you know, there is no such thing as a slam dunk in the Biotech sector, although LGND is the closest that I can find (and its stock price has certainly been a roller coster although it has avoided bad news). LGND has many programs, but the one that would be of most interest to readers of this board (assuming they are interested in diabetes) is LGND's rexinoid program.
The rexinoids have many applications, but recently (just under a year ago) they presented animal data indicating that two of their Rexinoids had potent activity in two mouse models (db/db for diabetes and ob/ob for obesity). Rexinoid treatment produced dramatic reductions in glucose, insulin, and triglyceride lvels. The reductions were similar to those obtained by a second generation TZD. Moreover, the combination of the rexinoid with the TZD produced additive results in all three parameters (larger decreases). The animal data supported earlier (1992) molecular data which showed that the receptor for the rexinoids (RXRs) formed a heteroduplex (complex) with the target of the TZD (PPAR). It was the complex of the two activated receptors (RXR/PPAR) that changed the gene expression that overcame the underlying cause of type II diabetes, insulin resistance.
Of course animal data does not always translate into human data. However, both rexinoids worked in both mouse strains (as did the TZD) and both synergized with the TZD. To prove that the rexinoids would also work in humans, LGND initiated phase II trials (in March) in Europe on type II diabetics. These results have not been released, but it was an open label trial and LGND has been negotiating with big pharmas (including WLA - whose Parke-Davis division makes Rezulin). I assume they also have talked to Sankyo, the discoverer of Rezulin and an alliance partner of LGND (on inflammation). LGND also has a TZD program (in part with another Alliance partner, GLX, and they may also have discussed the diabetes deal with them).
Although I don't know what the human data is, LGND's future partner does. I just talked to LGND investor relations and they say that the announcement of the deal is on schedule (which has always been sometime around the end of 3Q and beginning of 4Q). The deal is supposed to be far larger than any prior deal (and LGND has 7 Alliance partners) so I assume that the human data is on a par with the animal data. I also assume that the new partner has seen more of the Targretin data on cancer treatment and they know how realistic a 1998 NDA is.
Rezulin has produced some dramatic effects and WLA has more or less designed the road map for approval (since Targretin is supposed to work like Rezulin - by activating a hormone recpetor that subsequently combines with another activated receptor), I expect the trials to go fairly smoothly (although they will take awhile and be expensive). |
