Copernicus Gene Systems Inc., a Cleveland company that has set out to become the UPS of gene therapy packaging and delivery, has lined up its first corporate partner.
In a research collaboration with Inex Pharmaceutical Corp., the two companies will combine Copernicus' DNA compaction method with Inex's encapsulating delivery system, dubbed the Transmembrane Carrier System.
Financial terms and disease target(s) were not disclosed.
"This collaboration underscores the potential value of our technology to enhance the performance of a variety of gene delivery systems," said Robert Butz, president and CEO of Copernicus.
The DNA compaction method, capable of producing a unimolecular sphere of DNA an order of magnitude smaller than other leading methods, was developed at Case Western Reserve University, also in Cleveland.
Upon its formation as a limited liability company in 1994, Copernicus licensed that technology and other Case Western discoveries related to gene delivery and expression. The company's founders were university scientists who got the business started with the help of the university's Office of Technology Management and a state incubator program.
Since then, the company has adopted a more traditional corporate structure, and with the hiring of Butz last fall, began aggressively seeking financing and collaborations. The 10-employee company is headquartered in a 3,000-square-foot office facility adjacent to Case Western, and in August will acquire laboratory space of more than 3,000 square feet.
The challenge of launching and running a company is a familiar one to Butz, who in the 1980s helped found contract research organization Quintiles Transnational Corp., of Research Triangle Park, N.C. In 1996, that company reported revenues of $538 million.
Right now, Copernicus has less than $1 million, but Butz said he expects to announce this summer a $4 million venture capital infusion, which would carry the company through the middle of 1998.
Besides Inex, Copernicus' only other collaborative agreement is with Case Western. The company is providing research funding totaling $1.5 million in exchange for first crack at any resulting commercial applications.
The company's initial disease targets are familial hypercholesterolemia, hemophilia B and solid tumors. Already, in the Case Western labs, tests on animals with hypercholesterolemia and hemophilia B have produced encouraging results.
Copernicus' key technologies are: DNA compaction, through which synthetic cationic polypeptides are attached to the DNA to protect it from enzymatic and hydrodynamic destruction in the bloodstream; and a safety-modified episomal expression system for cancer gene therapy, which uses a safety-modified viral vector to allow therapeutic DNA to replicate inside cancer cells.
The expression system, the company's first technology to receive a patent, was developed by Mark Cooper, an associate professor of medicine at Case Western's medical school's division of hematology and oncology.
"Being a physician and someone who actively treats cancer all the time, I was acutely aware of the limitations of treatments available now," said Cooper, who combines research and clinical duties at the university, in addition to positions at Copernicus as chairman of the Scientific Advisory Board, vice president of medical affairs, and member of the board of directors.
Cooper's research provided the payload; the compacted delivery system was provided by the concurrent work of fellow Case Western scientists and Copernicus co-founders Richard Hanson, chairman of Case Western's biochemistry department and a member of the company's scientific advisory board; Thomas Ferkol, who specializes in pediatric pulmonology and is also a member of the scientific advisory board; and Jose Carlos Perales, now director of research at Copernicus.
Although the scientists were all working on related technologies, it took James Kovach, of the university's Office of Technology Management, to see the commercial connections and bring the researchers together to form a new company, in which the scientists and the university would have a stake.
Although Copernicus is about two years away from a clinical trial, published animal studies have demonstrated that a single intravenous injection of compacted DNA can insert large amounts of compressed DNA into target cells. Butz said researchers using the company's technology have achieved 18 percent transfection rates into tissue, versus 0.1 percent to 3 percent with other methods.
Similar results from Cooper's in vitro studies with human cancer cells will be published later this month.
The preclinical results are impressive, but the company's human drug discovery program will be a cautious one.
"We want to go after those indications that we can develop quickly for less than $10 million each," Butz said, noting that the company is focusing on small-demographic indications like familial hypercholesterolemia in order to prove its platform technology, which could be used to deliver a wide array of treatments to cells.
"The whole trick is to prove your stuff works," he said, "rather than try to hit a home run with something like diabetes or arthritis."
Under an "open architecture" strategy, the company will make its technology available on a fee-for-service basis, much like a contract research organization, to other biotechnology and pharmaceutical firms.
"Say company X has a DNA payload they're trying to develop," said Butz. "They can work with us at a very low cost."
The arrangement is, in effect, "gene therapy contract services," he said.
"We have developed systems in which we're able to regulate the dose intensity and duration of gene expression," Cooper said. "We have proof of the principle of using nucleic acids as drugs." *