Jim,
I appreciate your response and thought it might be helpful to clarify a few issues:
Any combi chem company that hopes to succeed must have systems that allow for the integration of SBDD and CC and bioinformatics. Pharmacopeia has several in house teams dedicated to these efforts. 1) Our rational design team consists of Ph.D. computational chemists who spend all their time attempting either to maximize the diversity of our Discovery Libraries or to work with crystallographic data to better understand the shape, charge etc. of biological targets and binding sites. 2) our solid phase chemists, headed by Jack Baldwin (30 years at Merck) then use this information to design compounds which they believe will either a)maximize diversity, b)agonize/antagonize a known interaction, or c)optimize the potency/selectivity of an existing lead compound. 3) then, our bioinformatics group (Now headed by Peter Gund, the pioneer of rational drug design, previously with Merck, MSI and MDL)uses the abundant structure activity relationship data generated from the screening of our many compounds (something the parallel synthesis companies lack) to design follow-on programs.
I agree that chemistry, in and of itself,is not proprietary. The trick is to get talented chemists and give them tools that enable them to design better compounds, quickly and easily. If you look at our seven big pharma partners, 8 biotechnology partners, 3 milestone payments and 3 partnership renewals, I think you'll agree that our partners value our ability to design the "right" compounds. I'd also caution you to differentiate big pharma deals from the biotechnology deals. They are quite different in scope.
At the risk of boring you, let me provide you with a quote from the head of chemical research at Schering-Plough. He made this comment at an investor conference last May in New York to describe why they choose to do their own parallel synthesis in house but have to outsource their large library requirements to Pharmacopeia:
"Now single compound - they (ArQule) make smaller member libraries. But the technology used, unlike the technology of Pharmacopeia, actually already exists. Potentially there will be improvisation -- I don't want to minimize the importance of that. Just to say that the technology in concept exists."
Finally, I whole heartedly agree with you that numbers alone don't result in more drugs. However, what the large numbers result in, namely 1) more potent compounds right off the bat and 2) more SAR, does. For instance, when we screen large numbers, it is very common for us to find compounds active in the nanomolar range, 1000 times more potent than our competitors who find micromolar hits. I'm sure you can appreciate the months, maybe even years, of optimization time that is saved. Also, by screening large numbers of compounds, we get much more SAR which also helps guide and shorten the optimization process. Also of interest, Pharmacopeia has parallel synthesis capabilities which do in fact become very useful when we simply need to make hundreds or a few thousand analogs for an optimization program.
In attempting to value different combi chem companies, you should also keep in mind what other value added services the company contributes to the overall drug discovery process. For instance, Pharmacopeia, in addition to rational drug design and combi chem, also has a high throughput screening operation, similar to those found in big pharma.
Sue |
