“We’re not a screening or tools company; we’re a drug discovery company.” Such is the adamant mantra of Kalypsys’ president and CEO John McKearn.
However, the screening technology and tools used by the San Diego-based company for its own drug discovery are apparently viewed as a valuable commodity. In June, the National Institutes of Health’s newly established Chemical Genomics Center selected Kalypsys to provide it with a suite of ultra-high throughput screening technologies in a deal that could be worth $30 million over the next four years.
Under the terms of the agreement, which was officially announced on June 9, Kalypsys will deliver instrumentation, materials, and service, including an automated robotic system, to the NIH center.
The screening platform is being tailor-made for the center and is based on Kalypsys’ core system, which uses robotics and liquid-handling technologies that dispense reagents onto 1,536-well microplates to assess the effects of hundreds of chemical compounds in parallel. According to Pratik Shah, the company’s chief business officer, the platform allows users to screen “well over a million compounds a day.” It can also be scaled down to run 364-well plates.
Shah told Inside Bioassays last week that a significant portion of the Kalypsys system is proprietary, and that it is a completely integrated system covered by “a large number of patents and patent applications.” Still, he said, the platform remains flexible for researchers to tinker with, particularly when it comes to choosing which scanner to use to record assay results. “We’ve found that scientists like to have the flexibility to use whatever type of reader they want,” Shah said.
According to the company, the platform can run a wide variety of assays, including cell-based, biochemical, yeast, and small, whole organisms such as zebrafish. In fact, Shah said the system was borne out of a need to increase throughput and quality in cell-based assays.
“The system is designed to generate high-quality data with cell-based assays, and to be able to do it cost-effectively and in a very facile and rapid way,” Shah said. “One aspect of that was to be able to move away from batch-mode screening, and to try to get to a paradigm where we could run an entire screen in one batch in one day.
“So we didn’t go to throughput for the sake of throughput,” he added. “People realized that if it takes you six weeks to run a screen, then you know that cells change. So we thought that the optimal way to run a relevant cell-based assay would be to do it in one batch.”
Shah noted that Kalypsys has also developed a variety of dispensing technologies that, among other benefits, are designed to eliminate evaporation — a major problem in all assays using small amounts of reagents, but particularly in cell-based assays.
Screening at the NIH
Inside Bioassays’ sister publication, Pharmacogenomics Reporter, first reported on the NIH’s Chemical Genomics Center initiative last month (see PGx Reporter, 6/17/2004). At the time, the center said it wasn’t created as a drug discovery center, per se. Rather, its main goal is to leverage findings from the Human Genome Project and screen huge amounts of compounds — up to 600,000 in its first three years of operation — in an attempt to find promising small molecules that might be further developed into viable drug candidates, and to elucidate potential drug targets. Kalypsys’ screening technology will be at the center of this effort.
The CGC is headed by Chris Austin, whom the NIH hired away from Merck in January 2003. Two months after the NIH hired Austin, Merck signed on as Kalypsys’ first major customer, inking a deal in which Kalypsys provides a high-throughput lead discovery system. In addition, the companies agreed to collaborate to “extend the capabilities of the system,” according to a Kalypsys news release.
“I am not aware of any connection between the two deals,” Shah told Inside Bioassays last week. “As far as I know the choices were independent.” Austin was unavailable for comment for this story.
More Than Screening
Despite the high-profile NIH and Merck agreements, McKearn maintains that Kalypsys is much more than just a “tools and instrumentation” company, stressing that its major focuses are on providing complete drug-discovery services to customers, as well as cultivating its own drug candidates.
“Kalypsys on the whole is really a drug-discovery company,” Shah said. “Our focus is to take things from ‘twinkle in the eye’ all the way to the clinic … but to do this in a way that tackles some of the key bottlenecks in how drug research is done, and to apply our technologies in a way that enhances the efficiency and effectiveness of how drugs are discovered — that is all part of our mission.”
According to Shah, to accomplish its mission, the company not only leverages expertise in screening and lead discovery automation, but also in “chemistry automation” and “gene functionation.”
Kalypsys has publicly disclosed one other partnership that underscores these ambitions: a November 2003 collaboration with CV Therapeutics to “discover, develop, and commercialize novel treatments for cardiovascular disease,” according to a Kalypsys news release. In this deal, CV will develop assays and lead compounds, and hand off the compounds to Kalypsys for optimization. CV will subsequently carry out the pharmacological studies, pre-clinical development, and human trials, if appropriate. Kalypsys is also developing its own leads from its chemical compound library.
In addition, Kalypsys has generated a pre-clinical pipeline of potential drug therapies in oncology, inflammatory disease, and metabolic disease. According to the company’s website, it has four candidates in the advanced lead stage: One each for inflammatory diseases and oncology, and two for metabolic disease. It also has several potential therapies in each category at the target and lead stage. Shah said the company anticipates filing its first investigational new drug application next year.
As far as competition goes, Shah told Inside Bioassays that Kalypsys sees it only in selected areas of the drug discovery process.
“It’s always a tough question, because there is not what I would call ‘in class’ competition,” Shah said. “There are a lot of companies that are doing small-molecule drug discovery, but they tend to be in a different stage in their life cycle than us.
“On the technology side, there are a number of providers of automation and instrumentation,” he said. “But again, I would say that [they are] not in the same class with the same level of capability.”