Since the early 1990s, some employees of Sunol Molecular Corp. have been working in the area of tissue factor, even before the company was incorporated in 1995. Now, that long-term interest is becoming more focused with the start of Phase I trials.
Tissue factor, as described by Sunol, is "an integral membrane protein expressed on the surface of the subendothelial cells." In healthy people, tissue factor contributes to hemostasis, infection prevention and wound healing, Sunol said. But the Miramar, Fla.-based company's lead product is looking at its pathophysiological role in thrombosis, inflammation (including sepsis, acute respiratory distress syndrome and rheumatoid arthritis) and cancer.
"The more they've looked at it, the more interesting it's become," said Newell Bascomb, vice president of business development at Sunol. Sunol bought Bascomb's company, Xios Biosciences Inc., in 2002, and Bascomb joined Sunol.
"Originally, it was just thought of as an activator of a protease," Bascomb said. "Now, they see it is much more involved in signaling and cytokines."
Sunol's lead product is the tissue factor antagonist Sunol-cH36, a chimeric recombinant antibody in development for the treatment of coronary artery disease. The difference between that product and current antithrombotic agents is that existing ones inhibit coagulation downstream in the cascade after thrombogenesis already has been initiated, Sunol CEO Hing Wong said. Bleeding, Wong said, is a common side effect of those agents.
"By employing a novel mechanism of action to inhibit the binding of Factor X or Factor IX to the TF-factor VIIa complex, the TF antagonist blocks initiation of the coagulation cascade, thereby minimizing consequential bleeding complications," the company said.
Specifically, the Phase I trial involves 24 people and is part of the thrombolysis in myocardial infarction study group at the Brigham & Women's Hospital in Boston, the University of Miami's Jackson Memorial Hospital and the University of Minnesota. Sunol expects to initiate a Phase II trial for unstable angina in the second half of 2003.
The company also is looking at trials for Sunol-cH35 in inflammatory disorders such as sepsis and acute respiratory distress syndrome.
The company also is developing antibodies that neutralize the Shiga toxins Stx1 and Stx2. Another antibody with potential against the Escherichia coli infection that causes hemolytic uremic syndrome is already in a Phase I trial through Sunol's partnership with the Uniformed Services University of Health Services, also known as the medical school for the U.S. armed forces.
Another area of interest for Sunol-cH36 is cancer, for which Sunol is developing a fully humanized version of the antibody.
"We have so much data [indicating] this thing works against so much cancer," Wong said, noting that Sunol has studied tissue factor in melanoma, prostate and breast cancer, as well as others in animal models.
Wong said "this is a great opportunity for us," adding that he is positioning the company for a cancer trial to begin next year.
Sunol has been the breeding ground for another company. In 1999, Sunol spun off Biosynexus Inc., based in Rockville, Md. Biosynexus was created to develop drugs to prevent and treat hospital-acquired infections, many of which have become resistant to existing antibiotics. Wong said Sunol still owns a "substantial amount" of Biosynexus and gets a royalty stream on every product that comes out of the company. (See BioWorld Today, March 14, 2002.)
At the moment, Sunol, which has raised funding in the low $30 million range since its inception, is in the process of raising its Series E of $15 million, funding it expects to close in late June or early July, said Wong.
"If we're active in clinical development it will be good for two years," said Bascomb.
The company's long-term strategy is to partner once it has positive Phase II data in the areas of cardiovascular, inflammatory disease and cancer.
"We would only partner once we have efficacy data," Wong said.