SLIL Biomedical Corp.

SLIL Biomedical uses macrophage-based technology, combining sequential pathogenesis and synthetic chemistry, to develop therapeutics and diagnostics for diseases characterized by excessive cell proliferation. It was formed as the result of a merger between Sequential Medical Corp. and S'LIL Pharmaceuticals.

• Business: Macrophage-based technology to treat proliferative disorders

• Contact(s): Laurence J. Marton, MD, President & CEO; Nelson Schneider, Chairman

• Address: 411 Borel Ave., Ste. 510

• San Mateo, CA 94402

• Phone: [phone]

• Fax: [phone]

• Founded: April 1998

Historically known as the "good guys," macrophages normally function as cells that engulf foreign materials, telling the immune system to turn on and make antibodies. SLIL Biomedical Corp. co-founder and scientific consultant Michael McGrath—an MD, PhD trained at Stanford University , and now professor of laboratory medicine and director of the AIDS Immunobiology Research Laboratory at the University of California, San Francisco —discovered that macrophages can also be the "bad guys," or initiators of disease. When activated or modified by acquired genetic changes, such as HIV insertion, the normally passive macrophages expand, releasing growth factors that trigger excessive cell proliferation, which can lead to a variety of diseases.

Through AIDS research, McGrath discovered that macrophages, when integrated with HIV, were capable of dividing—proof, he claims, that these cells were turned on in some way that was stimulating the formation of disease processes. He found that HIV actually inserts itself into the DNA of the macrophage in very specific sites, near one of several oncogenes, causing that specific oncogene to become abnormally activated. He found this to be true with retroviruses other than HIV as well—the location at which the retrovirus is integrated into the macrophage, directly correlates with the disease a person will develop. This is the basis for SLIL Biomedical's sequential pathogenesis technology, inherited from predecessor Sequential Medical Corp. which merged with S'LIL Pharmaceuticals [See Deal]. The new company formed holds two patents to this technology, which was originally licensed from UCSF.

A second technology involves the crafting of small molecules in three specific classes (polyamines, porphyrins, and naphthoquinones) to develop therapeutics that kill only activated macrophages, but have no effect on normal macrophages. There are three patents related to this technology from the former S'LIL Pharmaceuticals side—two through the Wisconsin Alumni Research Foundation —the licensing arm of the University of Wisconsin, Madison (UWM); one from the National Institutes of Health .

Polyamines are compounds essential for cell proliferation. Polyamine analog compounds, however, act as antagonists of normal polyamine function, and have been shown in vivoto stop cell growth. Although a number of companies and universities are using these compounds; SLIL has synthesized unique polyamine analogs using a technique called conformational restriction, creating a molecule that assumes only certain shapes, but not others—to selectively modify its activity for use in developing therapeutics for cancer and infectious diseases.

Compounds known as porphyrins are concentrated in tumor cells. When activated, synthetic porphyrins are known to generate reactions within the cell that kill it, thus inhibiting cell proliferation. Many therapeutic approaches involve the activation of porphyrins by a light source. SLIL, however, has developed a variety of unique synthetic porphyrins that work without the need for light activation. It also has a series of porphyrins that can be activated using other energy forms that more readily penetrate the human body.

Naphthoquinones are compounds that have traditionally been extracted from plants. Benjamin Frydman, PhD, a founder of the company, along with Dr. Leroy Liu of the Robert Wood Johnson Medical School, discovered naphthoquinone's ability to modify the activity of the topoisomerase II enzyme—an enzyme responsible for DNA replication within a cell. Synthetic naphthoquinones can therefore prevent DNA from functioning normally, thus killing the cell. The concept of modifying topoisomerase II is not new, but SLIL claims its compounds are unique because they're easily synthesized. Furthermore, topoisomerase II-related drugs tend to induce multi-drug resistance, but according to SLIL, its compounds won't.

These two complementary technology platforms offer a variety of diagnostic, prognostic, and therapeutic applications. SLIL will use the sequential pathogenesis technology initially as an assay, and ultimately prognostically and diagnostically for the identification of individuals with a variety of diseases caused by excessive cell proliferation, such as prostate disease, dementia, Alzheimer's disease, cancer, and infectious diseases. Through its synthetic chemistry technology, it hopes to develop therapeutics to treat these diseases.

SLIL is currently negotiating about six partnerships, and anticipates revealing two or three by year end—including a research agreement to develop a therapeutic with Chiron Corp. SLIL also hopes to develop its own pharmaceuticals, establish relationships with other companies developing new therapeutics for diseases in which proliferating macrophages are implicated, and ultimately use its technology as a diagnostic when those drugs are on the market.

SLIL is headed by Laurence J. Marton, its president and CEO, formerly dean of the School of Medicine at UWM, and its vice president, Benjamin Frydman, previously visiting professor at the UWM's Schools of Pharmacy and Medicine.

To date SLIL has $3mm in financing provided by individual investors to each of the two original companies. It is in advanced discussions with various venture capital firms for a Series A preferred round in the next couple of months.—MR