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Biotech / Medical : ArQule -- Ignore unavailable to you. Want to Upgrade?

To: Peter Silsbee who wrote (170)	2/4/1998 10:31:00 PM
From: Dr. John M. de Castro	Read Replies (1) \| Respond to of 399

There's a couple of points that I'd like to make regarding ARQL's technology and business model. First, the molecules are proprietary. ARQL does not inform their partners of the exact nature of the molecules supplied. They're the only ones that know exactly what molecule is in well 95 of plate 844. This preserves their proprietary position and disallows cheating. In addition, there are literally infinite numbers of possible molecules. So, the probability of someone else stumbling on the same molecule is actually pretty small. The second point that I'd like to make is that ARQL's procedure is far from mindless. SBD is a rational approach. ARQL's is an empirical approach. They gather a tremendous amount of information regarding what kinds of molecules affect particular targets and which do not. This is their bioinformatics data base. (BTW: I believe that this data base may be the most valuable asset in the company.) These data can then be used to better understand the active "structure" of the target and can then be used to design even more effective molecules. (ARQL's directed arrays). If you truly believe that we are using stone axes and bear skins, then the belief that we really understand the structure of the targets and can rationally design molecules to affect them is not logical. If our knowledge is crude then we shouldn't rely on it to design drugs. Empiricism works much more effectively when understanding is crude. The history of science and technology has shown this to be true repeatedly. In addition, it the empirics has led to better understanding rather than the converse. So, IMO ARQL is on an excellent course. I like the way they are thinking and their scientific approach. The bioinformatic data that they are acquiring is, IMO, of more value than any of our theoretical beliefs about the structure of biological targets. It will allow them to continuously improve and streamline the process of drug discovery. I also like their management and business plan. It is competent and has proven very effective. As a result I consider ARQL to be at or near the top of biotechs in quality and potential. Obviously I am long and plan to hold and enjoy watching the value of this fine company appreciate at well above the market. John de C

To: Peter Silsbee who wrote (170)	2/5/1998 1:42:00 AM
From: ahhaha	Read Replies (1) \| Respond to of 399

What are the criteria of "promising"? That is part of the issue. What is promising is unknown because if you knew that, you wouldn't have to extend the search vector into another dimension. Promising is heuristic and your assertion begs the question. Let's assume perfect rigor is available within the criteria of "promising", .i.e. we're starting on a solid basis on a sub-search. The sub-search necessarily adds combinatorial complexity up to the number of additional components added so that with k more points of complexity we can only be confident in retaining our original chemical predictability by trying (m + k)^n possibilities, where n is number of functionally useful twists in the original molecule, and m is the number of functional components. It's not hard to see that this blows up on you. And this is only a minimum of required trials. I don't see where the SBD group constrains the blowup. Indeed, it enters its own factor, j, into the equation, (j + m + k)^n, or j*(m + k)^n. Please tell me. What do the theoreticians say about practicality?