TransMolecular Inc. is relying on a toxin from scorpions, called chlorotoxin, to lead its way in fighting glioma, the deadly brain cancer.

The Birmingham, Ala.-based drug discovery and development company last month moved its first drug candidate into the clinic. The candidate, 131I-TM-601, is a radiopharmaceutical containing the chlorotoxin and is in a Phase I/II trial, with one of the endpoints being survival and another being biodistribution.

"The particular peptide we're working with is a neurotoxin, which knows how to enter the central nervous system," said TransMolecular President and CEO Matthew Gonda.

The drug uses toxin sequences from chlorotoxin that have evolved to locate and bind to their receptor, which is expressed on tumor cells but not on normal cells. Gonda said it's like "molecular surgery," with the sequences being used to guide the radioactive payload to the target.

And unlike surgery, which Gonda calls "a sledgehammer approach," the drug has a way of distinguishing between normal and tumor cells. Because it's a targeting drug, it can also concentrate at the tumor site, like a "smart bomb," Gonda said.

Scorpions would use the toxin to kill cockroaches, for example.

"The receptor is shared between insects and man, but in man it's only found in tumor cells," he said.

Gonda said that the chlorotoxin is chemically synthesized with peptide chemistry in order to get "high purity and functionality."

"In preclinical studies we haven't seen any toxic side effects at 100-fold what we would have in people," Gonda said. "That doesn't mean it would not be toxic at 1,000-fold." The company's strategic plan is to treat brain cancer comprehensively.

"What we'd like to be able to do is diagnose the disease, develop the drug, treat it, and then better follow up with an image of how the drug is working," Gonda said. "We're developing a franchise in the area of oncology."

The 131I-TM-601 product is TransMolecular's only candidate in the clinic, but its scientists have found the receptor on a range of other tumor types, Gonda said.

Gonda said 131I-TM-601 is an adjuvant therapy with an enhanced ability to kill tumor cells.

"It not only delivers the drug, it sensitizes the cell to be killed," Gonda said.

TransMolecular also is developing therapeutics to treat neuropathic pain, which, Gonda noted, is associated with cancer, arthritis, stroke, diabetes and back pain.

Relying on research in ion channels, the company has discovered a sodium ion channel addressing pain-signaling neurons. The particular ion channel is a molecular target for pain, he said.

Gonda said TransMolecular is seeking pharmaceutical partners for high-throughput screening of that molecular target. The company is in discussions with potential partners regarding agreements in which TransMolecular would do the up-front research, and the partner would do the screening and development, allowing TransMolecular to participate in later revenues.

TransMolecular raised $9 million in a Series B financing in 2000, and within the next few months will be looking to complete a Series C round of $25 million to $30 million.

"We think it will take us a long way down the road," Gonda said.

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