Targeting Cancer Vaccines
Cynthia Robbins-Roth, Forbes ASAP, 05.28.01
Genzyme Molecular Oncology (nasdaq: GZMO - news - people ) is betting that its emphasis on biology coupled with snazzy technology will pump out a host of important cancer drugs long before new products emerge from the heavily hyped genomics companies.
Gail Maderis, president of GZMO ("Gizmo" to insiders), says her company lets cancer patients' immune systems point the way to important tumor proteins. These proteins, termed antigens, are the signposts used by the immune system to identify cells to destroy. Once you know which antigens show up on tumors and not on healthy cells, you have a quick path to monoclonal antibody drugs and cancer vaccines. Monoclonal antibodies can trigger selective killing of targeted cells, and vaccines stimulate a patient's immune system to seek out and destroy cells carrying the antigen.
A straight genomics approach looks at all the genes expressed by tumor cells and by healthy cells and tries to figure out which are specific to the tumor cells. Then you have to find out which of those thousand-plus tumor genes could be drug targets.
GZMO puts biology at the front end. Research starts with T cells (immune-system cells that can kill "bad guys") isolated from patient tumors and incubates them with panels of tumor cell lines carrying different antigens. Those tumor cells carrying antigens recognized by the T cells are destroyed. GZMO then uses its genomics tools to look at all the genes turned on in each tumor line. Tumor genes that show up only in those tumor lines being attacked probably encode antigens that target the tumor for destruction.
Says Maderis, "This takes you from thousands of genes down to a handful, and often down to a single gene, very quickly." Each tumor antigen can be used in two ways: as the target for an antibody that will destroy it, or as the basis for a vaccine.
Cancer cells try to hide from the immune system, so naturally occurring antigens often don't generate a response that will protect patients from a cancer recurrence. GZMO scientists use a high-throughput screening process, coupled with a proprietary combinatorial chemistry library, to tinker with the antigens and find versions that kick-start a powerful cancer-killing response.
The best part is that the entire process - from tumor isolation to identifying antigen fragments for vaccine development - takes about two to three months. Tack on another year for animal studies to make sure the vaccine won't cause attack of healthy tissues. In 12 to 18 months GZMO has a vaccine candidate that reacts to tumor antigens ready for clinical testing.
GZMO still must prove that this will generate commercially and clinically successful vaccines. But things are moving in the right direction. Started in 1999, the Tumor Antigen Discovery Program should have its first vaccine candidate in the clinic this year. The company has about 10 target antigens so far.
GZMO's antigen discovery technology is essentially a powerful form of functional genomics : using old-fashioned biology to figure out where the key drug targets are hiding. All the fancy computer algorithms in the world can't replace "wet ware," Maderis notes. "We have married biology and genomics, which makes the genomics more readily translatable into targets. We are cherry-picking the best, most relevant genes right up front."
In October the program attracted its first big partner, Purdue Pharma. Purdue gets to choose up to 20 different tumor antigens to use in its cancer program, and GZMO gets more than $21 million in committed funding and up to $310 million in milestone payments.
GZMO stock has been on a roller coaster since it hit the public market in 1997, but Maderis is optimistic. She has reason to be, with five clinical trials under way, partners clamoring to team up, $30 million in the bank, and access to parent Genzyme General's checkbook. "We can point to real accomplishments now," Maderis says. "We can't control the stock market, but we will keep creating real value and eventually get recognition."
Cynthia Robbins-Roth is the founding partner of BioVenture Consultants and author of From Alchemy to IPO: The Business of Biotechnology.
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