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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: derekb.lowe@gmail.com Twitter: Dereklowe

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September 14, 2011

Lilly's Open Screening Program: An Update

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Posted by Derek

I'm still at the RSC/SCI symposium in Cambridge, and a talk yesterday by Marta Pineiro-Nuñez gives me a chance to update this post about Eli Lilly's foray into opening up its screening to outside collaboration. That effort has been working away for the last two or three years, and the company is now revealing some details about how it's been going.

The original plan was to allow people to put compounds into a set of Lilly phenotypic screens. No structures would be revealed, and the company would have "first rights of negotiated access" for any interesting hits. They have a new web gateway for the whole thing, since now they've added several target-based screens to the process. As mentioned in the earlier post, they've come up with a universal Material Transfer Agreement to bring the compounds in, but Pineiro-Nuñez said that this was still a bit of a struggle at first. Small companies were pretty open to the idea, she said, but there were some suspicious responses from academia, with a lot of careful digging through the MTA to make sure that they wouldn't be giving away too much.

But things seem to have gotten going pretty well. According to the presentation, Lilly has 252 affiliations in 27 countries. That breaks down as 174 academic partners and 78 small companies. About 42,000 compounds have been accepted for screening - that's after a firewalled computational screen of the structures to eliminate nasty functional groups and the like. About 40% of the submissions fail the suitability screens, but the single biggest reason is lack of structural novelty - too close to marketed drugs, too close to controlled substances, or too close to things that are already in Lilly's files.

Here's a recent overview of the screening results. In the end, 115 structures were requested for disclosure, and 97 of those ended up being shared with Lilly, who still wanted 13 of them after looking them over. And those have (so far) led to two recent signed collaborations, with one more set to go and two others still in negotiations. The compounds certainly aren't instant clinical candidates, but have been interesting enough to put money on. And so far, the initiative is seen as successful, enough to expand it to more assays.

It'll be interesting to see if more companies try this out. It would seem especially suited for unusual proprietary assays that might be hiding behind industrial walls. Having Lilly demonstrate that a model of this sort can actually work in practice should help - congratulations to them for putting the work in to make it happen.

Comments (10) + TrackBacks (0) | Category: Drug Assays


COMMENTS

1. Jose on September 14, 2011 6:31 AM writes...

I find the "97 of those ended up being shared with Lilly, who still wanted 13 of them after looking them over" triage fascinating. Somewhere around 87% were of no sustained interest. Are the submitters unclear about good medchem properties, or has Lilly become totally rigid with standard medchem dogma?

Submitters- be sure to google "Icos, Inc." before you sign.

Permalink to Comment

2. Anonymous on September 14, 2011 8:29 AM writes...

Hey Jose - I felt momentarily heartened by Derek's post, that is until I googled 'Icos, Inc' and it reminded me what a bunch of crooks Lilly and their ilk actually are. Beware bright people with a good idea - there are some big, nasty sharks in the water

Permalink to Comment

3. johnnyboy on September 14, 2011 9:02 AM writes...

An interesting approach for sure, although... i'm not at all familiar with the kind of success rate you get with screening early compounds, but 13 possibly interesting ones out of 42000 seems pretty low. And these haven't gone into animals models at all yet. So the likelihood that any of these 13 makes it to an IND (let alone an NDA) seems rather low to me. Would also be interesting to tallying up the amount of work and resources that needed to put into this system by Lilly and its 252 collaborating institutions, just to get to this point, to see how 'productive' this collaboration is.
It's enough to make one despair of the future of drug development. Or maybe I just haven't had my coffee yet this morning.

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4. Student on September 14, 2011 12:37 PM writes...

@1 I am curious about this as well...
"97 of those ended up being shared with Lilly, who still wanted 13 of them after looking them over"
What is the difference? Understandably Lilly won't want to disclose any trade-secrets, be it how one of their assays works, or how a group of assays collectively gives the best insight...But it would help them get better candidates if they could provide feedback to the academic community as a whole. If we are missing things it is in everyone's best interest (maybe except for their competitors) to understand what academics/biotechs are missing. Maybe academics are cheap (run fewest assays) and too eager to get their candidates off the ground??? What is the academic to industry gap? I am really curious about this now.

Permalink to Comment

5. Student on September 14, 2011 12:38 PM writes...

@1 I am curious about this as well...
"97 of those ended up being shared with Lilly, who still wanted 13 of them after looking them over"
What is the difference? Understandably Lilly won't want to disclose any trade-secrets, be it how one of their assays works, or how a group of assays collectively gives the best insight...But it would help them get better candidates if they could provide feedback to the academic community as a whole. If we are missing things it is in everyone's best interest (maybe except for their competitors) to understand what academics/biotechs are missing. Maybe academics are cheap (run fewest assays) and too eager to get their candidates off the ground??? What is the academic to industry gap? I am really curious about this now.

Permalink to Comment

6. BiotechTranslated on September 14, 2011 3:30 PM writes...

We actually did this with Merck back when I was in grad school during the late 90's. Any time we made a new compound (verified as novel by a literature search), Merck would pay us $100 to send them 25 mg.

I have no idea if there was any MTA in place or what each party's rights were if the compounds lit up some assay.

Mike

Permalink to Comment

7. Anonymous on September 14, 2011 6:56 PM writes...

I sold a great number of compounds from our group to pharma and related companies. It's not a bad idea, the money can really go far to help academic labs.

Most of the interesting compounds were weird side products, or from some failed side projects. Some were plug and chug compounds from methodology papers.

In terms of IP rights aren't we missing the big picture. There is a really small chance that one will light up the assay. And even then, it's just a hint of where to start.

So people out there. Be grateful for the cash and be happy that your molecule has found some practicals use. You didn't build the assay or research the target. You didn't spend millions in further developing the drug which in all likelihood will not resemble what you submitted.

No one is exploiting anyone. BTW I don't work for lilly, or even pharma any more.

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8. BCP on September 14, 2011 10:40 PM writes...

@johnnyboy/3 actually 13 confirmed hits with (presumably) developable/optimizable structures from a screening of 42,000 structures sounds pretty good when compared to many HTS campaigns I've seen in years gone by.

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9. dvizard on September 15, 2011 4:56 AM writes...

@BCP: But then again, academic labs are probably way more selective in what they send in for testing.

Permalink to Comment

10. You're Pfizered on September 15, 2011 8:28 AM writes...

@BiotechTranlated

We had something similar when I was in graduate school. Don't recall the company, though. May have been Lilly or Merck, and was a one-time deal, looking for chemical matter.

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