Semafore Pharmaceuticals Inc. is looking to make a name for itself in the fight against cancer, taking a new identity central to its oncology-focused direction.

"Semafore is discovering and developing the next generation of novel cancer therapeutics to enhance and extend people's lives in a very meaningful way," Joseph Garlich, its president and chief scientific officer, told BioWorld Today.

The company recently changed its name from ComChem Technologies Inc., the moniker under which it opened its doors as a contract combinatorial chemistry firm with a bit of drug discovery work on the side, to better reflect its revised business strategy. Garlich founded ComChem in 2000 with Barry Dreikorn, the company's executive vice president, along with Jim Kneisley, who provided financial advice.

But the company wanted to move beyond being a service organization. Its amended plan is centered on the regulation of cell signaling pathways to combat cancer, a concentration that came into focus through research sponsored by the National Cancer Institute in Bethesda, Md.

Through that program, Garlich came in contact with Donald Durden, a professor at Indiana University's medical school. In search of someone with vascular biology knowledge to advise on the NCI research, Garlich brought Durden on board as a consultant. A practicing physician, Durden also works as a researcher in the area of pathways and their roles in processes such as cancer metastasis and angiogenesis.

Thus the opportunity presented itself to transform the company based on those pathways, with Durden a scientific adviser to the process. Specifically, Semafore's therapeutic programs are based on the P13K/PTEN pathway, the primary controlling mechanism for cell survival, programmed cell death, angiogenesis, cell migration and cell proliferation.

"Our new strategic focus is to leverage our knowledge of this critical, non-redundant cell-signaling pathway," Garlich said. "We want to turn that into new drugs, get them into the clinic, and show that we can enhance and extend people's lives."

To date, Semafore has developed two preclinical programs related to P13K/PTEN.

Its Interceptors are inhibitors of P13K, designed to shut down angiogenesis and induce apoptosis. Garlich called the P13K pathway common to growth factor receptors to which various new cancer drugs interfere, products such as Erbitux, Iressa, Tarceva and Avastin.

"Rather than go after one receptor, in which case a cell has redundant ways to get around that," he said, "we're going after the jugular of the cell - the P13 kinase pathway."

The Interceptor program's initial focus is on brain and lung cancers. In nude mice models of glioma and non-small-cell lung cancer, Semafore's small-molecule Interceptor compound demonstrated statistically significant reductions (p=0.0009, p=0.0057) in tumor mass, compared to a control group, and was very well tolerated in both groups. Garlich said the company aims to move the program into clinical trials next year, expecting to conduct the first human studies of that class of drugs.

Beyond oncology, the anti-angiogenesis effects of P13K inhibitors have applications in other indications, such as macular degeneration, coronary artery disease and inflammatory diseases.

Semafore's MarrowShield products are small-molecule inhibitors of PTEN designed to protect healthy cells during chemotherapy or radiation. The program is in in vitro testing, with animal studies scheduled to begin within a couple of months.

"We believe that if we can deliver PTEN inhibitors to marrow, and protect those cells during chemotherapy and radiation therapy, that it could have a major impact on how oncologists will aggressively be able to treat cancer," Garlich said. He added that the products might find military applications as well, in terms of protecting personnel from fall-out effects.

Semafore plans to advance the Interceptor and MarrowShield programs through Phase II before seeking development partners. But Garlich added that the company would explore fully developing and eventually registering its Interceptor products in hematological indications.

Resources are a matter of somewhat near-term need. Funded since its founding with about $4 million in private capital, angel investors and private individual backers, Garlich said Semafore would go out in about eight months to seek financing that would support a move into clinical development.

In the meantime, the 20-employee company will continue its in-house research activities, while also making use of relationships with university labs to further its programs. Recent personnel additions, such as board member John Crowley and scientific adviser Larry Hertel, are expected to impact the business's revised focus as well.

"There is a lot of activity now going on in this area," Garlich said, "but we think we're the first. We were in early and we believe we have a lead on the rest of the world."