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India Is Connexios’ Competitive Advantage

By John Russell

March 1, 2008 | All biotech start-ups wrestle with raising capital, proving their science, and navigating unforgiving markets. Suri Venkatachalam, CEO and managing director of Bangalore-based Connexios, believes that being in India is a competitive edge that will enable Connexios to survive where other worthy companies might not, and to become one of the first successful systems biology-based drug companies.

Lower cost is clearly the biggest advantage. He estimates Connexios’ costs are one sixth to one eighth of what they would be in the U.S. Given that his young company has already raised roughly $20 million and that its primary investor is patient, India’s lower cost of operation has allowed Connexios to grow head count to 120, to substantially expand the scope of its activities, and to still enjoy the luxury of a long runway to success.

“Even in the context of Indian costs, this is a very reasonable amount of money. We’ve spent maybe $5 or $6 million to build this up. So, we have a reasonable amount of money to carry a few programs into the clinic, a couple of programs at least,” he says. Add to this financial strength India’s glut of technical talent, its growing life science ecosystem of companies, ready access to clinical trial participants, and a national hunger for equal footing on the world stage, and you understand why Venkatachalam likes his chances for success.

Venkatachalam founded Connexios in 2003. Imagine a sort of amalgam of Ingenuity Systems (pathway analysis and DB) and BioSeek (cell-based assays) supplemented by chemistry and clinical divisions, whose mission is to use network biology to discover and develop drugs and important biomarkers. The science is not revolutionary, though it is impressive.

“Connexios didn’t really start as a drug discovery company,” remembers Venkatachalam. “The idea was to try and build an information-centric platform, pretty much along the lines of Ingenuity (Systems). I quickly realized it didn’t make a lot of sense to be just a back end kind of business model.”

A Pool of Candidates
With funding from Nadathur Holdings and Investments, Venkatachalam formed Connexios. The first step was building a manually-curated database of pathway information as well as analysis tools. As the business model was transformed,z other needs became apparent, such as an experimental assay platform to validate and inform in silico efforts. In fairly rapid succession, Connexios further focused on disease areas, expanded chemistry operations, and most recently began beefing up clinical research capabilities.

As Venkatachalam says , “The business strategy is really to say this whole platform approach is giving us a pool of interesting, well-characterized candidates; molecules, which we are beginning to call early drug candidates as opposed to just optimized leads because we’re able to readout and characterize a lot more of the biology.”

While the goal is to become a full-fledged drug company, Venkatachalam is also eager to pursue collaboration. “You’re continuously looking at this pool [of candidates] that you’re creating and leveraging the Indian ecosystem in terms of development to take it through the animal and then proof of concept to the human. [We can also] actively pursue partnership opportunities. We want to get and sell licensing-joint-development kinds of approaches too.”

Predictably, most of the work is around interpreting differential gene expression analysis. Hypotheses that were developed in silico were then tested using Connexios proprietary assays and a database of signatures and insights around network biology, and disease states were developed. Other kinds of omics data are slowly being incorporated in the platform.

Collaborations have already been important. There was an early project with the Central Drug Research Institute in India around diabetes. CDRI was trying to establish mechanisms of action for complex mixtures of natural products. “We thought it was a good project to try and get our hands dirty.”

Having little gene expression experimental capacity of its own, Connexios first relied on Vanderbilt University’s core microarray facility and was one of its largest users for awhile, says Venkatachalam.

This was a fruitful period. “We started getting a sense of the biological circuits or the cellular circuits. We defined a lot of our tools. We learned a lot about direct biology. We were still being given a very long rope by the investors. So, we were building the kind of understanding that is required in terms of being able to translate these data into sort of insights in terms of biology.

“To cut a long story short, at that point in time many things started to converge and we felt that there is a way to bring in a lot more biology of drug discovery, you know, a lot more of the biology of the therapeutic action or the overall pharmacology of the drug into the early stage of discovery, into the discovery itself,” says Venkatachalam.

Rapid Build
Work with the Joslin Diabetes Center at Harvard extended Connexios’ knowledge and the company has initially focused on metabolic disease. Recently, the company’s clinical group assembled “over 300 subjects” to work with and to obtain blood and urine from for metabolomic analysis. “So, now we’ve invested in sort of a metabolomic set up to do both metabolomics and proteomics,” says Venkatachalam.

Given the rapid build out of disciplines — chemistry, biology, information technology, various omics, and now clinical — loss of focus would seem to be a potential worry. Indeed, Connexios only recently ended a natural products screening initiative, in part because it was diversionary and in part because, “we didn’t seem to add much value because people didn’t clearly care about mechanisms there.”

Nevertheless, Venkatachalam has broad ambitions. “We don’t want to be the metabolic syndrome company,” he insists. “We want to be a network biology-based discovery company. You start looking at the information at the cellular and molecular level there is really no distinction. When we started looking at more fundamental biology, many of these connections (metabolic disease) are connected to other diseases as well.”

Time will tell.


 This article appeared in Bio-IT World Magazine.
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