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Speedy Discovery

Kalypsys hopes to accelerate the flow of high-quality drug candidates into the clinic

by Lisa M. Jarvis
August 28, 2006 | A version of this story appeared in Volume 84, Issue 35

Credit: Kalypsys
Engineer Benjamin Baumann operates Kalypsys' uHTS system.
Credit: Kalypsys
Engineer Benjamin Baumann operates Kalypsys' uHTS system.

Entering the screening laboratories at the San Diego-based drug discovery company Kalypsys is like stepping into a science fiction novel: A bright yellow robotic arm whizzes around a shiny metal platform, transporting plates containing hundreds of tiny wells filled with compounds that could, one day, become treatments for any number of diseases.

Those robots are part of Kalypsys' effort to solve one of the pharmaceutical industry's biggest quandaries: how to get drugs into the clinic faster and at a lower cost, while also improving the odds that they will prove to be safe and effective in patients.

Kalypsys, a privately held, 125-person firm, was founded in 2001 as one of three spin-offs from the Genomics Institute of the Novartis Research Foundation. The company inherited from Novartis a suite of drug discovery technologies, including its futuristic-looking ultra-high-throughput screening (uHTS) system, which can run a million samples per day, and a library of 2.2 million chemical compounds.

Screening at a big pharma company is typically a four- to six-month process, from idea to decision-making, says Stewart Noble, Kalypsys' vice president of discovery chemistry. At Kalypsys, the uHTS system allows a campaign to be collapsed into 24 hours, a time frame that challenges most drug companies' traditional views of drug discovery. Even Noble, whose previous stints include senior director of chemistry at Pharmacia and discovery posts at Searle and Glaxo, admits that it took him a while to come to terms with the approach. "It's been enlightening for me to have our technology completely change my mind-set," he adds.

Though the uHTS technology enables the company to zip through a million samples each day, executives at Kalypsys stress that speed does not automatically translate into success in the drug discovery business. "Michael Jordan didn't just have a good jump shot," says John McKearn, the firm's president and chief executive officer.

Noble believes Kalypsys differentiates itself by the quality of the questions being asked in each campaign and by its ability to handle the heavy flow of data that emerges from its system. "You can go fast, but if you don't improve the odds ratio, then essentially you're spinning your wheels," he adds.

One critical factor, Noble says, is the company's starting materials. Traditional drug discovery efforts force researchers to choose either a biochemical or a cell-based assay, but Kalypsys' system enables its entire collection of compounds to be run against both types of assays in a single day, saving time and avoiding the variability of separate campaigns.

And rather than interrogating a random assortment of interesting compounds, Kalypsys' internal chemical library contains about 900,000 compounds that have been cherry-picked on the basis of their adherence to Christopher A. Lipinski's "Rule of Five," a rule of thumb that helps researchers predict whether a small molecule will be orally bioavailable.

Furthermore, the company maintains that it never takes a cookie-cutter approach by performing screens without regard to the target. Instead, Kalypsys builds a chemical profile that incorporates all the known information about a target into each drug-seeking mission. The process is iterative, so that the first batch of drug candidates to come out of a screening campaign can be winnowed down based on issues like safety, drug-drug interactions, and selectivity for the target.

The last piece of the equation is data management. Generating more than a million data points per day could easily leave a company reeling from information overload. Kalypsys has developed data processing, storage, and analysis tools that enable the company to make quick and informed decisions about drug candidates.

Armed with this collection of tools, Kalypsys has set lofty goals for its drug discovery operations. The company believes it can shrink the time it takes to move from concepts and theories to the filing of an Investigational New Drug (IND) application with the Food & Drug Administration. On average, it takes companies five to seven years to go from idea to IND, McKearn says. The company is on track to complete its first IND application in less than three years, he notes. "And I think we can do better than 34 months." With that pace, Kalypsys intends to file one to two IND applications each year.

In addition to time, the company is also confident it can significantly cut costs. Kalypsys believes that it will spend $12 million to bring a drug from idea to IND, about one-fifth of the $70 million industry average. Part of its ability to trim costs is its technology's miniature scale, which enables the company to stretch its compound supplies.

Those time and investment targets remain to be proven: Though Kalypsys has an internal pipeline of drug leads and preclinical compounds focused on cardiovascular and metabolic diseases, inflammation, and oncology, the company has yet to file its first IND application.

Meanwhile, Kalypsys is allowing other firms to tap into its technology as a means of both generating revenue and adding to its pipeline. Early relationships were generally focused on a single target, such as a 2003 deal with CV Therapeutics to develop high-throughput screens for a cardiovascular target.

More recently, the strategy has shifted to signing multiyear R&D collaborations across a therapeutic area, cluster of targets, or disease pathway, McKearn says. The first such deal was established in January, when eye-care company Alcon signed on for a four-year stint to develop and commercialize ophthalmic drug candidates.

Kalypsys intends to establish two more similarly structured partnerships over the next 18 months, McKearn says. Between its internal efforts and its partners, the firm's goal is to retain one or two specialty drugs, develop them, and bring them to market.



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