By Mary Welch
A discovery about scavenger cells led to the formation of Slil Biomedical Corp., which is banking on its breakthrough to develop therapeutic and diagnostic products for diseases caused by excessive cell proliferation.
The San Mateo, Calif.-based company is targeting several cancers (such as AIDS-related lymphoma), cardiovascular disorders, kidney disease, infections and neurological disorders (such as dementia and Alzheimer's disease).
The company, which has raised almost $3 million in private capital, has exclusive licensing rights to six patents on its sequential pathogenesis technology — based on studies of macrophage cells — and on individual chemical entities.
Slil was formed in April by the merger of S'Lil Pharmaceuticals, of Madison, Wis., and Sequential Medical Sciences, of Menlo Park, Calif. Slil (pronounced Saleel) comes from the Hebrew word for helix — as in the double helix — in DNA structure.
Sequential was studying macrophage cells — the immune system's scavenger cells as targets for drugs and needed S'Lil's therapeutic compounds, which were developed at the University of Wisconsin, in Madison.
Nelson Schneider, a former Wall Street biotechnology analyst who founded CalBio (now Scios Inc., of Mountain View, Calif.) and SciClone Pharmaceuticals, of San Mateo, suggested S'Lil and Sequential combine. Schneider put the deal together and now serves as chairman of the board. He also is chairman and CEO of Redem Corp., of San Francisco.
Sequential's major discovery stems from research done at the University of California at San Francisco (UCSF) showing that macrophage cells are linked to diseases caused by excessive, uncontrolled cell proliferation. Acquired genetic changes in those cells, such as an insertion of HIV retroviral DNA, caused these normally dormant cells to increase in number. These dividing macrophages then released cytokines that, in turn, triggered the proliferation of other cell types involved in a range of diseases.
"What was found was that the macrophage cell, rather than functioning in its normal capacity as a scavenger, became an initiator of the disease," said Laurence Marton, Slil's president and CEO. Marton is a former dean of the School of Medicine at the University of Wisconsin and former chairman of the department of laboratory medicine at UCSF.
Sequential Pathogenesis Offers Therapeutic Leads
While looking at the AIDS virus, the UCSF researchers, who were cofounders of Sequential Medical Sciences, realized the HIV virus inserts itself into specific regions of the macrophage DNA and that the insertion always was found in the same region, depending on the disease.
"It wasn't a variable," Marton said. "For instance, in lymphomas, the viral insertion was always in the area of a specific oncogene and for dementia, in the area of a different oncogene. Modification of macrophage DNA in non-AIDS-related diseases also occurs in the same regions. It was really intriguing."
Dubbed sequential pathogenesis, Marton said the discovery suggests points of therapeutic intervention and provides the basis for developing tools to predict disease onset and progression.
"What we want to know is what caused normal cells to turn bad. And can we find a drug that affects the modified macrophage cells but not the normal ones," he stated. S'Lil Pharmaceuticals provided the compounds to address the second issue.
There are two separate components of the new company; but eventually they will both be headquartered in San Mateo. The first division, Biomedical Analysis, in Menlo Park, is working on the sequential pathogenesis discovery and is further developing the link between the macrophage cells and excessive cell proliferation.
The pharmaceutical division, located in Madison, is making compounds for treatment of proliferative diseases. The drug candidates include agents in the chemical classes of polyamines, porphyrins and naphthoquinones. The first two are known to act upon macrophage cells.
Polyamine Analogues Stop Cancer Growth In Vitro
Slil has synthesized analogues of natural polyamines, which have been efficient in stopping cell growth in vitro against a variety of cancer cell lines.
"The polyamines were known for some period of time, but few investigators worked with them," Marton said. "They are fundamental to growth in all mammalian cells. If cells can't accumulate them, they don't grow."
Porphyrins are compounds noted for their use as photosensitizers in photodynamic cancer therapies. They accumulate in tumor tissue, which makes them potentially less toxic than current therapies.
Naphthoquinones act on a "well-known" anticancer target, topoisomerase II, and inhibit cell proliferation.
Slil expects to take at least one of these compounds into human clinical trials this year and has research agreements with Chiron Corp., of Emeryville, Calif., and E.I DuPont & Co., of Wilmington, Del. No money is involved — yet.
Every new company has a unique science, Marton acknowledged. "We have a scientific discovery that provides a new paradigm for disease, which gives us some sex appeal. And lots of companies have brilliant scientists who don't have a pragmatic understanding that you must turn the research into useful products."
Slil, Marton offered, has coalesced those two factors — excellent science and a practical orientation — into a company whose scientists and management are "driven to focus on producing useful outcomes. It's that focus that makes us stand out from many other new companies." *