Synta's Surprise - Pharmaceutical Executive

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Synta's Surprise
A small molecule for autoimmune diseases? No one expected that.


Pharmaceutical Executive


"The problem is that single proteins never work in isolation in the body. They are always in a complex ecosystem in a cell and in different activity states, depending on what disease you have or what type of patient you are," he explains. "What we do is a turbocharged version of the old pharma discovery approach rather than the current genomic-inspired fashion of 'start with the protein.' We believe that we have to look at the whole system, the properties of the cell, rather than individual proteins in isolation. So we start with the chemistry, and when we see compounds that have the desired behavior in the whole cell system, then we really drill down. We go inside the cell to improve our understanding of the biology and then use that understanding to improve the quality of the compound—absorption properties, potency, specificity. It is the rapid feedback loop between the biology and chemistry that is the key to high productivity and high quality of final compound."

Bahcall also believes that it is the ability to innovate that marks the distinction between biotech and pharma, not large versus small molecules. He compares the industry to the way baseball is set up with minor and major leagues, with the minor leagues having the responsibility of looking at "1,000 local high schools to find a few promising, young pitchers." Then the minor leagues, or biotechs, test and develop theearly stage talent, and eventually "feed" the most successful, grown-up talent to the major leagues, or Big Pharma. There is, however, the exciting possibility—if a club can hold on to the talent as it grows up—that the club could graduate from the minor to the major leagues.

Bahcall is clearly aiming for the major leagues. The company is privately owned, and its pipeline is totally proprietary. "We have a strong fortress of intellectual property protection around our discoveries, from composition of matter to method of use, synthesis, and in certain cases, mechanism of action. And these drug candidates are novel, in that they are not me-too drugs, variants of known products, where the competition is more intense. "These are first-in-class mechanisms, so we have the benefit of first-mover advantage and the potential to be not only first in class, but also best in class and dominating the eventual franchise. Retaining these rights is a very attractive value proposition for all of our stakeholders."

Bahcall admits that it is a temptation to keep it that way. But Phase III clinical trials are expensive and a licensing agreement with a partner may become necessary. "Next year it will probably make sense for us to pick up the phone, start the discussions, see if there is an arrangement which works both for us and for a partner," says Bahcall.

Small Molecules for Big Diseases Synta's pipeline of mostly oral drugs targets the big three: cancer, immune disorders, and metabolic diseases.


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