So Takeda has opened up its roomy wallet once again, and signed on with Alnylam for a nonexclusive partnership in oncology and metabolics. The InVivoBlog has all the details, but the main point is that Takeda had to put $100 million down at the beginning, with all the milestones, options, and extras coming after that. And Alnylam’s CEO seems to be saying that he’s not going to bother with any offers down in the mere double-digit millions, so don’t waste the man’s time. Roche didn’t – they signed a non-exclusive deal of their own with the company last year.

There are several interesting things about this. One is that Takeda is really in a deal-making mode, apparently, which (historically) has been unusual for a Japanese company. But no Japanese drug company has ever quite been in the position that they find themselves in – a big international player with patent expirations coming – so I guess we should expect something new. More remarkable, though, is the nonexclusive nature of all these deals that Alnylam is making. Other things being equal, of course, larger drug companies much prefer exclusive deals, or a complete buyout. That's what Merck did with Sirna in this same area, in what was no cheap deal, and one that led to Alnylam terminating their own Merck agreement. In this case, though, the amount of money for such terms has apparently been too much for anyone to handle, or Alnylam has perhaps just refused to go exclusive. It’s worth thinking about the position they feel they must be in, to make that stick.

The last time I can remember a situation like this was when the genomics frenzy was on. And I think the RNAi business is turning into something very similar, for very similar reasons: fear and greed, the two flywheels of the financial world. We'll take the greed as stipulated, since the whole purpose of modern capitalism is to harness its mighty and potentially destructive force. But the fear, in both cases, was the very real fear of being left behind when a rare landscape-altering technology is potentially coming on. If there really had been dozens of good ready-for-prime-time targets lurking out there in the genomic data, well, the companies that sewed them up would do very well, and the ones that didn’t would eat dirt. So better to spend the money, right? And so it is with RNA interference: if it really does work therapeutically, there are going to be a lot of previously-undruggable targets within reach, as well as a lot of new shots at the ones we already know. So. . .better to spend the money again?

I suppose there’s no way around it, even though I’m not convinced that RNAi is going to deliver any time soon (or at all?) After all, its difficulties seem (to me) very much like those of antisense DNA, subject of yet another train’s-leaving-the-station investing frenzy in the late 1980s and early 1990s. For one thing, delivering these oligonucleotides in a living human is definitely nontrivial, to use a word that scientists and engineers use to mean anything from “pretty damn hard” to “impossible at the present level of human civilization”. I don’t think that RNA therapy is in the second category, but I do think that it’s in the first category good and hard.

And there’s the whole question of off-target effects, which I’ve spoken about here before. These may not be show-stoppers, true, but the problem is that we don’t know if they are or not. At the very least, it’s a complicating factor, and a big one – and the fact that it’s out there makes you wonder what other interesting complications are yet to be discovered as we go into humans.

So no, RNAi is not going to remake the landscape later this year or anything. It’s going to be a long business, with (I feel sure of it) plenty of expensive head-slapping and hand-wringing along the way. But all that said, can a company like Takeda (or Roche, or Merck, or. . .) afford to ignore it? After all, by the time the kinks are worked out of the technology, it’s presumably going to be too late to buy into it. (Or if you can, it’s going to make the 2008 prices look like the discount rack). Perhaps it’s better to just decide that that’s what the money’s for, to buy into things that could pay off big, with the realization that most of those purchases are going to look idiotic in ten years. . .