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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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November 2, 2006

Hope, Springing Eternal And All That

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Posted by Derek

I haven't mentioned Merck's mighty acquisition of Sirna yet - 1.1 billion dollars, eh? If anyone didn't think that RNA interference was hot, that kind of money should change their mind.

But still. . .antisense DNA was hot at one time, too, and then it cooled off considerably. It's come back in recent years, admittedly, as painful progress has been made. In fact, one of the big deals that showed that antisense was taken seriously again was made by. . .Merck, come to think of it. They had a big collaboration with ISIS for diabetes and (I believe) some other indications, but it didn't work out well. That press release has ISIS putting a brave face on having their clinical candidate thrown back over the fence, with talk of taking it on into clinical trials themselves. Four years later, it's still listed as Phase II on the company's website, which isn't a good sign, I think.

The rest of that 2002 press release is also instructive. The Phase III PKC-alpha compound they mention working on with Lilly bit the dust the next year, for one thing. And the ICAM-1 inhibitor met a similar fate in 2004. The 2002 story mentions the company having six products in Phase II, and now, according to their chart, they have five. None of those six candidate have progressed, and no doubt there's been some turnover along the way.

I'm not trying to be hard on ISIS. It's just that antisense DNA therapies have been extraordinarily hard to develop, and I see no reason why RNA interference will not have exactly the same sorts of problems. Small nucleic-acid based compounds are going to be hard, no matter what. It's interesting to note that Merck didn't just up and buy ISIS back then. But they're more desperate to fill their pipeline than they were back in the late 1990s, so out comes the checkbook. Good luck to all concerned.

Comments (4) + TrackBacks (0) | Category: Business and Markets | Drug Development


1. SIRNA millionaire on November 2, 2006 9:58 PM writes...

Hmm.....perhaps the many fold potency advantage of RNAi (due to its catalytic activity) and much improved specificity make RNAi look nothing like antisense (that never really worked well in anyones hands I knew).

What do I know. I just quadrupled my cash in Sirna.

1. Gene splicing
2. Monoclonals
3. RNAi therapeutics

RNAi therapeutics will be bigger than both 1. and 2. combined. Scalable drug discovery of a kind we have never seen.


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2. Chrispy on November 2, 2006 10:42 PM writes...

I hope you're right, Millionaire.

But of course, if you're such a believer you won't sell now. More power to ya -- you might become a zillionalre! And the implications for medicine would make it worth every penny.

But I have to admit that I'm with Derek on this one: these are not going to be easy drugs. We've tried the easy stuff and it hasn't worked.

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3. Athabascan Ranger on November 3, 2006 9:39 AM writes...

From someone who has conducted numerous siRNA screens in a Big-Pharma setting, I'm with Derek on this, too. It's hard to sort through the numerous off-target effects with siRNA. I haven't found that many unique sequences for most genes that produce even a modest knockdown. Power to the people who keep the faith, but, I gave mine up long ago. There's nothing like bench work to throw cold water on the optimism of vendors and prognosticators.

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4. wait-and-see on November 3, 2006 1:13 PM writes...

In real estate, the mantra is location, location, location.

In nucleic acid-based therapeutics, the mantra is delivery, delivery, delivery.

siRNA is an extremely powerful research tool but looks like an iffy route toward drug development.

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