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
I've heard that Pfizer is doing something unusual with its proprietary compound collection: they're offering to let other people screen it.
Now, that's quite a step. Most companies guard their compounds pretty closely, considering them to be key assets. But I'm told that Pfizer has been meeting with several other (mostly smaller) companies, offering their (entire?) compound library as a screening resource. As I understand it, you need to come to them with a reasonably formatted HTS assay, and there's a fee in the high hundreds of thousands to run the screen.
That doesn't seem like much of a moneymaker, to be honest. The whole thing appears to me to be a way for Pfizer to strike deals with a number of other companies, since the compounds that come out of the screen will (likely as not) be covered by Pfizer's own patents. I haven't heard of how the IP issues are to be worked out in these deals, but that's the first thing that occurs to me. Anyone have more details?
Harkin's back to the glory (or gory?) days of combinatorial chemistry with a twist that instead of small companies creating libraries of compounds to sell to those with HTS assays (i.e Pfizer and other big Pharma mostly) this situation is run in reverse. I do not think intent would be to make money, except perhaps to pay for some overhead required to run. Might be of value for spawning some innovation because of the constant bridging required to get (bio)assays and compounds together to produce leads but correct on IP as sure would like to see the contract in terms of ownership and other rights. Bioinformatics and Price barriers would have to be dealt with as many small companies who might have a viable assay may not be able to handle from both data and costs view although Pfizer may be selecting potential "collaborators" according to those factors. Wonder if could be a graduated system where payouts are tied to milestones (hits, candidates, tox clearance, clinical initiation etc...) as that would be a reversal of how biotech-pharma deals have been conducted.
2. You're Pfizered on May 19, 2009 3:38 PM writes...
It's brilliant, actually. You make others pay you to find new indications for your compounds.
I'd be interested to see what the contract stipulates about ownership of compounds and the data that is generated by the screens. Does Pfizer get a look-see and right of first refusal on anything that looks promising? Very interesting.
There are a some other (IP/confidentiality)issues with this:
1. It is hard to believe the whole of Pfizer's compound file will be screened each time owing to costs - so who does the selection of a target-focused library? Hard to imagine Pf letting its compound database out for analysis by external comp chemists .....?
2. Presumably, Pf would only release the structures of hits leaving the smaller company in the dark about negative SAR. Or does it become a 20 questions game? (did the compound library contain a pyridoquinazoline etc etc?).
6. partial agonist on May 19, 2009 9:35 PM writes...
Milkshake may be on to something- you bring Pfizer a good screen, they give you a subset of their library to screen at your place, maybe with shared rights, then...
THEY set up your screen on your target with the rest (and the best?) of their compounds IN THEIR SHOP, not sharing ANYTHING!
I met a Pfizer person at a conference a few months ago & they did mentioned that they were thinking of doing this! They also said that they were considering offering follow-up med chem 'support' (consultancy ?).........for a fee of course!
Nano-dispensing technology makes that the compounds can be screened, but there isnt enough material to determine the structure, so the biotech has to go back to PFE with the screening results.
Presumably other pharmas is working on similar ideas
My expectation would be they make a standard diverse subset available (designed by Pfizer comp chemists), maybe structure-blinded until confirmed hits are identified, and retain IP rights of the compounds themselves and anything developed via optimization, with the understanding of co-development. I suspect in certain cases, they may license compounds that hit in collaborator assays, but restrict it to specific therapeutic approaches, thereby leaving the IP field open for Pfizer for other indications. I doubt very much that they'd expect payment for the compounds, and expect that they would do internal med chem with an external collaborator if there was mutual interest in the indication. It's a brilliant idea, really - it opens the field to new approaches but makes it more likely that the chemical matter identified by these external people would be attractive for pursuit for Pfizer. It will also be a powerful enabler for the small company to (1) access a proprietary and drug-like screening set so they're not screening their target against commercial, non-proprietary libraries and (2) make inroads into a company that might provide a higher liklihood of success (read: getting to the clinic) than going it alone. I think it might also be an indication of Pfizer's realization that they don't have all the answers for fruitful drug discovery, and that more can be achieved by reaching out to others rather than playing everything so close to the vest.
So I'm curious to know how the acquisition of Wyeth plays into this novel concept. Wyeth has a decent pipeline and a decent screening facility...does PF layoff the entire Wyeth site or do they keep portions of it??
I would suspect that it would not take much compound to determine the ~ structure. But agree that acquistion would happen with anything that pfizer thinks is really good.
With Wyeth, I expect the med. chem. to go, the vaccines to stay, and the veternary health being up for a "decision". Of course, the Feds may force disposal of the latter overlap.
14. ex-Pfizerite on May 20, 2009 9:25 PM writes...
You need to remember that Pfizer has abandoned the patent rights to a large number of compounds that either washed out of the clinic or never made it into the clinic. Additionally, a screening hit is just the first step in finding an active, drug able compound for the clinic.
Presumably the structures will be blind, or covered by layers of previous patents. PFE gets nuggets of interesting biology and assays, and only has to give away the structure of a garbage wholly un-optimizable "lead" and then will be free to screen real compounds from related focused libraries. All for the dangling carrot of the riches in PFEs library and hopes of becoming a takeover target if the biology is novel enough. Many cash strapped biotech would sell their souls for that opportunity. Slick.
There have been two mentionings on conferences - SBS 2009 in Lille (25.th April) and Compound Management & Integrity in London (20.th May). The bits below are in the public domain.
"Pfizer currently works on a pilot project to allow external customers access to our file for screening their targets"
Here's how structure disclosure works- you do get to screen the whole deck (~3M) if you can afford it. You only get to see the structures of hit compounds, and that assumes a reasonable hit rate- no saying, "hey, my hit rate is 99%, show me the whole deck." However, if one of those structures is part of an active development series on another Pfizer project, it stays hidden.
1. CMCguy on May 19, 2009 2:47 PM writes...
Harkin's back to the glory (or gory?) days of combinatorial chemistry with a twist that instead of small companies creating libraries of compounds to sell to those with HTS assays (i.e Pfizer and other big Pharma mostly) this situation is run in reverse. I do not think intent would be to make money, except perhaps to pay for some overhead required to run. Might be of value for spawning some innovation because of the constant bridging required to get (bio)assays and compounds together to produce leads but correct on IP as sure would like to see the contract in terms of ownership and other rights. Bioinformatics and Price barriers would have to be dealt with as many small companies who might have a viable assay may not be able to handle from both data and costs view although Pfizer may be selecting potential "collaborators" according to those factors. Wonder if could be a graduated system where payouts are tied to milestones (hits, candidates, tox clearance, clinical initiation etc...) as that would be a reversal of how biotech-pharma deals have been conducted.
Permalink to Comment2. You're Pfizered on May 19, 2009 3:38 PM writes...
It's brilliant, actually. You make others pay you to find new indications for your compounds.
I'd be interested to see what the contract stipulates about ownership of compounds and the data that is generated by the screens. Does Pfizer get a look-see and right of first refusal on anything that looks promising? Very interesting.
Permalink to Comment3. JC on May 19, 2009 3:49 PM writes...
Who knows maybe some of that purified garbage from the DPI collaboration will eventually find a use.
Permalink to Comment4. eurochemist on May 19, 2009 4:27 PM writes...
There are a some other (IP/confidentiality)issues with this:
1. It is hard to believe the whole of Pfizer's compound file will be screened each time owing to costs - so who does the selection of a target-focused library? Hard to imagine Pf letting its compound database out for analysis by external comp chemists .....?
2. Presumably, Pf would only release the structures of hits leaving the smaller company in the dark about negative SAR. Or does it become a 20 questions game? (did the compound library contain a pyridoquinazoline etc etc?).
It will be interesting to see how this runs.
Permalink to Comment5. milkshake on May 19, 2009 6:11 PM writes...
I think Pfizer is primarily interested in new targets and assays. And takeovers.
Permalink to Comment6. partial agonist on May 19, 2009 9:35 PM writes...
Milkshake may be on to something- you bring Pfizer a good screen, they give you a subset of their library to screen at your place, maybe with shared rights, then...
THEY set up your screen on your target with the rest (and the best?) of their compounds IN THEIR SHOP, not sharing ANYTHING!
Permalink to Comment7. viledonkey on May 20, 2009 1:18 AM writes...
I met a Pfizer person at a conference a few months ago & they did mentioned that they were thinking of doing this! They also said that they were considering offering follow-up med chem 'support' (consultancy ?).........for a fee of course!
Permalink to Comment8. Anonymous on May 20, 2009 1:49 AM writes...
Nano-dispensing technology makes that the compounds can be screened, but there isnt enough material to determine the structure, so the biotech has to go back to PFE with the screening results.
Permalink to CommentPresumably other pharmas is working on similar ideas
9. MikeyMedChem on May 20, 2009 6:20 AM writes...
My expectation would be they make a standard diverse subset available (designed by Pfizer comp chemists), maybe structure-blinded until confirmed hits are identified, and retain IP rights of the compounds themselves and anything developed via optimization, with the understanding of co-development. I suspect in certain cases, they may license compounds that hit in collaborator assays, but restrict it to specific therapeutic approaches, thereby leaving the IP field open for Pfizer for other indications. I doubt very much that they'd expect payment for the compounds, and expect that they would do internal med chem with an external collaborator if there was mutual interest in the indication. It's a brilliant idea, really - it opens the field to new approaches but makes it more likely that the chemical matter identified by these external people would be attractive for pursuit for Pfizer. It will also be a powerful enabler for the small company to (1) access a proprietary and drug-like screening set so they're not screening their target against commercial, non-proprietary libraries and (2) make inroads into a company that might provide a higher liklihood of success (read: getting to the clinic) than going it alone. I think it might also be an indication of Pfizer's realization that they don't have all the answers for fruitful drug discovery, and that more can be achieved by reaching out to others rather than playing everything so close to the vest.
Permalink to Comment10. Anonymous on May 20, 2009 6:45 AM writes...
Mikey - I completely agree. Shame they didn't do it a few years back
Permalink to Comment11. Anonymous on May 20, 2009 7:52 AM writes...
So I'm curious to know how the acquisition of Wyeth plays into this novel concept. Wyeth has a decent pipeline and a decent screening facility...does PF layoff the entire Wyeth site or do they keep portions of it??
Permalink to Comment12. Don B. on May 20, 2009 8:42 AM writes...
I would suspect that it would not take much compound to determine the ~ structure. But agree that acquistion would happen with anything that pfizer thinks is really good.
Permalink to CommentWith Wyeth, I expect the med. chem. to go, the vaccines to stay, and the veternary health being up for a "decision". Of course, the Feds may force disposal of the latter overlap.
13. Joerg Kurt Wegner on May 20, 2009 3:38 PM writes...
I am curious to see any announcements on this. For now I share the IP concerns.
Permalink to Comment14. ex-Pfizerite on May 20, 2009 9:25 PM writes...
You need to remember that Pfizer has abandoned the patent rights to a large number of compounds that either washed out of the clinic or never made it into the clinic. Additionally, a screening hit is just the first step in finding an active, drug able compound for the clinic.
Permalink to Comment15. Jose on May 20, 2009 11:46 PM writes...
Presumably the structures will be blind, or covered by layers of previous patents. PFE gets nuggets of interesting biology and assays, and only has to give away the structure of a garbage wholly un-optimizable "lead" and then will be free to screen real compounds from related focused libraries. All for the dangling carrot of the riches in PFEs library and hopes of becoming a takeover target if the biology is novel enough. Many cash strapped biotech would sell their souls for that opportunity. Slick.
Permalink to Comment16. JJL on May 21, 2009 3:44 AM writes...
Viledonkey
There have been two mentionings on conferences - SBS 2009 in Lille (25.th April) and Compound Management & Integrity in London (20.th May). The bits below are in the public domain.
"Pfizer currently works on a pilot project to allow external customers access to our file for screening their targets"
Permalink to Comment17. SP on May 24, 2009 9:01 AM writes...
Here's how structure disclosure works- you do get to screen the whole deck (~3M) if you can afford it. You only get to see the structures of hit compounds, and that assumes a reasonable hit rate- no saying, "hey, my hit rate is 99%, show me the whole deck." However, if one of those structures is part of an active development series on another Pfizer project, it stays hidden.
Permalink to Comment