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leapfrog ahead of IGN523 in lung cancer. The company started building an antibody-drug conjugate research unit about three years ago, when then-CEO Mike Rothe hired some chemists from Genentech who had worked on ado-trastuzumab emtansine.
However, Igenica decided to invent its own technology to link targeted antibodies to payloads of toxic drug molecules, rather than striking a deal as Genentech did to license “linker” compounds from another company. Genentech has made a series of deals Immunogen (NASDAQ: IMGN) and Seattle Genetics (NASDAQ: SGEN), both pioneers of linker development and antibody-drug conjugates. Seattle Genetics marketed the first successful conjugate, brentuximab vedotin (Adcetris), which was approved in 2011 to treat two types of lymphoma, Hodgkin’s disease and anaplastic large-cell lymphoma.
Haak-Frendscho, who was appointed Igenica’s CEO in September of 2012, says the company wanted a full suite of technology platforms so it wouldn’t have to work around the intellectual property rights of other companies when designing products and setting strategies. The company’s proprietary linker compounds are part of its antibody-drug conjugate platform called SNAP, which can make use of antibodies developed with Igenica’s sTAg and iTAb discovery systems.
“Now we have this kind of trifecta of enablement,” Haak-Frendscho says.
The key goal for many developers of next-generation antibody-drug conjugates is to make a more uniform product than the initial drugs in this class. In the earlier drugs, it was hard to control the number of toxins connected to each antibody.
“Some have none, and some have, quite frankly, too many,” Haak-Frendscho says. This can reduce the effectiveness of the drug.
An antibody crowded with too many toxins may be unable to fit into the binding site on the cancer cell. An antibody with no connected toxins takes up a binding site on the cancer cell, edging out other antibodies that could have delivered the toxic payload.
Drug developers have tried a range of new methods to insure pinpoint placement of a set number of toxins on antibodies. Igenica’s fellow Bay area company, South San Francisco-based Sutro Biopharma, has re-engineered its antibodies to contain specific spots where toxins can be linked. These spots are created by incorporating non-natural amino acids into the antibodies.
Igenica has created its antibody-drug linkages through chemistry rather than genetic engineering, Haak-Frendscho says. The company has developed a bifunctional linker like a two-pronged fork. Each prong forms a bond with a specific amino acid on the antibody, creating a chemical bridge to which a toxin can be attached.
Igenica has raised $70 million since its inception. Its latest fundraising round was a $14 million extension in January of a $33 million Series C round initiated in 2012. That round was led by new investor Third Rock Ventures with participation by prior investors 5AM Ventures, OrbiMed, and The Column Group. The new money raised in January will help support Igenica’s operations through early next year, Haak-Frendscho says.
Most of Igenica’s 42 employees are research scientists. The company also works with contractors and “a constellation of consultants,” Haak-Frendscho says. Before considering any moves to go public, Igenica will try to put a number of drug candidates in play, she says.
The company is actively looking for partners to license its technology or to form a broad R&D collaboration to discover new drug targets and develop antibodies and antibody-drug conjugates for specific disease areas, says Igenica’s chief business officer John Celebi.