Assistant Managing Editor

Move over, antibodies. Toxin-based molecules could become the next generation of targeted biologics, at least if Molecular Templates Inc. has its way.

The Georgetown, Texas-based firm, which boasts screening libraries of ETBs, or engineered toxin bodies, will put its technology to the test in its first deal, an oncology discovery and translation research agreement with ImClone Systems, a unit of Eli Lilly and Co. If the firms successfully create ETBs against a target chosen by ImClone, Molecular Templates could earn up-front fees, milestones and royalties.

More importantly, success would be able to show how toxin-based drugs stack up against antibodies.

ImClone, which developed blockbuster cancer drug Erbitux (cetuximab) "clearly understands antibodies very well," said Eric E. Poma, president and CEO of Molecular Templates. "So this will be a good test case to see if toxins can do what we think they can."

The idea of using bacterial toxin scaffolds is not new, Poma said. "The literature goes back 20 or 30 years." Toxins offer potential advantages over both antibodies and small molecules because of their ability to gain cell entry through targets that might not normally internalize into the cells and their ability to enzymatically trigger apoptosis.

But the limited ability to screen for targets meant that most firms working in the biologics arena opted for an antibody approach instead. With the earlier toxin platforms, "you could only go after targets you knew," he told BioWorld Today. "You couldn't do widespread screening."

Molecular Templates set out to build screenable libraries, similar to existing antibody libraries, and now has created "billions and billions" of molecules, each with a different affinity, Poma said. Instead of screening for binding ability, however, the company's screening platform looks at cell-killing ability.

One of the biggest advantages of etiology-based screening is that the company doesn't have to know the target beforehand. Its lead program, MTI-SAM3, which targets an undisclosed receptor present on certain melanoma cells, was found by screening without a target, he added.

The company's technology has been around for about a decade. In fact, the "first iteration" of Molecular Templates was formed in 2000 by researchers at the University of Toronto and the Ontario Cancer Institute, Poma said.

He joined the firm in 2008, and a year later, it underwent a restructuring and relocation after securing $2.5 million in Series A funding from Sante Ventures. The platform uses a modified Shiga-like toxin, a ribosome-inhibiting agent, so its use could go beyond the obvious oncology targets. Poma said the company might also look at viral and autoimmune diseases as well.

The goal now is to look at other possible partnerships. "We'll probably put in place one or two more collaborations," he said, and then focus efforts on building out the company's pipeline. Over the next year or so, Molecular Templates hopes to develop a number of new leads, and then advance to the clinic "in the next two or three years."

Unlike many start-ups, Molecular Templates has opted to forgo the virtual model. The company has a 5,000-square-foot R&D facility and 12 full-time employees, with all research conducted in-house.

No Comments