Pfizer’s recent release of Zeldox, an antischizophrenic drug, would not have been possible without Captisol®, a product developed by CyDex, Inc., an Overland Park, Kansas-based HBC spin-off company founded in 1993. Recently launched onto the commercial market in Sweden, Zeldox is the first Captisol®-containing formulation sold. Though Zeldox was the breakthrough drug using Captisol®, the compound has also been licensed for use in prescription eye drops, an antifungal compound and several other drugs in development. CyDex also plans to develop Captisol® formulations for drugs either already off patent or soon to be open for competition.

Pfizer approached Captisol® inventors, the Higuchi Bioscience Center’s Valentino Stella and Roger Rajewski, years ago, offering to license it before the Captisol® drug delivery technology was fully developed. Now, Pfizer is not the only company interested in Captisol®, which allows the delivery of drugs that are poorly soluble in water. It is now licensed by Allergan, Bristol-Myers Squibb, Daiichi Pharmaceutical and Peptichemio.

Carrier module
Captisol® is a derivative of one of the naturally occurring cyclodextrins, which are themselves byproducts of bacterial fermentation of sugars and starch. Cyclodextrins are made up of sugar molecules which form a doughnut-shaped carbohydrate molecule with a hydrophilic or water-loving outer surface, which makes them water-soluble, and a lipophilic internal cavity. It is in this lipophilic internal cavity that allows cyclodextrins to join with certain water soluble drug compounds to produce a drug/cyclodextrin complex that is more easily formulated and administered to patients.

"You could compare Captisol® to an inner tube," said Karl Strohmeier, Vice-President of Corporate Development at CyDex. "The drug is carried in the interior of the Captisol® molecule."

Captisol® generated plenty of industry interest because many drugs, such as Pfizer’s Zeldox, are hydrophobic and need just such a carrier mechanism to get the drug into the patient’s body. Once the drug complex is administered to the patient, the drug leaves the Captisol® carrier molecule to do its pharmacological activity.

Marketing Technology
Founded primarily to develop and market Captisol®, CyDex, Inc. models how a company can take technology developed in a university setting and put it out in the commercial arena. In 1993, Peter Higuchi, son of late HBC founder Takeru Higuchi, presented a proposal to the University of Kansas and HBC for commercializing Captisol®, and CyDex, Inc. was born. Strohmeier said, "The company is also a good example of how developing a compound such as Captisol® can be financially advantageous for both the company and the university organizations that invented it."

Over the years, CyDex has outgrown its creators’ original vision. At first, CyDex was to be a virtual company where HBC could funnel outsource activities for Captisol®. CyDex would then pass revenues earned from Captisol® through this corporate structure to private shareholders and the university, which still retains ownership of nearly 40 percent of the company. However, as CyDex evolved, its creators realized that they would have the opportunity to do more that just a couple of licenses for Captisol®. They knew they needed more than just a virtual company. "To flesh out the full potential of Captisol®, CyDex needed to become a real company," Strohmeier said. "Now we’re evolving into a complete drug delivery company." In fact, CyDex is currently developing Captisol® formulations that they themselves can bring to the pharmaceutical industry.

Financial Boost
The recent financial commitment of four venture capital firms has made way for an exciting new growth spurt at CyDex. Together the firms–TVM Techno Venture Management, an affiliate of TVM IV GmbH & Co. KG; VBTC Management Ltd.; Clariden Investment Guernsey; and RiverVest–have contributed a total of $12.5 million.

Though Captisol® was originally designed to be uniquely safe for parenteral administration, CyDex now plans to develop its utility for oral or pulmonary administration. "With this financing, we can develop a safety data package for these other uses for Captisol®," said Strohmeier.

The financing has also made way for construction of a new laboratory in Overland Park, Kansas. Among the primary activities to go on at this new facility is the creation of Captisol® formulations for smaller drug companies. Though Captisol® is easily transferred to large companies such as Pfizer to formulate drugs in their own labs, smaller companies that outsource the research and development phase of the process needs CyDex to formulate drugs for them. With the addition of the laboratory, CyDex has expanded to a staff of 15 and expects to add even more people in the coming year.

CyDex continues to maintain its strong connection to HBC and the University of Kansas. In addition to KU alumni Peter Higuchi, CyDex’s Senior Vice-President of Research and Development, Diane Thompson, once worked in HBC’s Center for Drug Delivery Research, overseeing research into cyclodextrin technology. Additional research into Captisol® applications still occurs at HBC, continuing evidence of a practical and mutually beneficial relationship.