West Coast Editor

Word that Immtech Pharmaceuticals Inc.'s Phase III lead compound pafuramidine has been placed on clinical hold left shares lighter by half - and left company officials scratching their heads over abnormal liver function found in several subjects in a 100-volunteer South African safety trial.

Immtech's stock (AMEX:IMM) closed Wednesday at $2.88, down $2.97, or 51 percent, after trading as low as $2.50.

"This was a very strange result," said Eric Sorkin, chairman and CEO of the New York-based firm. "It could be human error, or genetics [of] a subgroup, or diet, or pre-existing conditions that didn't show up earlier. We're looking at every single one of these things."

Pafuramidine, an aromatic cationic compound that binds to segments of DNA to block enzymes that enable microbial growth, has reached Phase III trials for the orphan indications African sleeping sickness (trypanosomiasis), and Pneumocystis carinii pneumonia (PCP), the most common opportunistic infection in people with HIV.

The sleeping sickness study has completed enrollment, and Immtech has reported interim results. Sorkin said the company expects to finish 12-month follow-up with all patients at the end of next year's first quarter. Further clinical work is held up by the latest development in the Phase I safety trial, but Sorkin could not say for how long.

"Until we know a lot more, we won't be able to respond to that at all," he said. "If we knew the issue, I could tell you the best time [frame] for working through it."

Participants were given the drug twice daily for 14 days or placebo, and all are undergoing close monitoring for any changes in the status of their liver function, with none so far requiring any treatment or hospitalization. When the subjects with liver abnormalities stabilize or return to baseline status, independent experts will prepare a full report, and Immtech will consult with the FDA on the path forward, Sorkin told BioWorld Today.

"We put a plan together within 24 hours of discovering this, which included liver experts and looking at a lot of things we haven't had to look at in the past," he said. "We've never had a problem with maximum tolerated dosage, and we don't know that we have a problem [with MTD] now."

The safety study testing a 100-mg dose of pafuramidine passed a monitoring board's muster in October, Sorkin noted, and the drug has gained positive results at the 50-mg dose in other trials. "There's plenty of room between [doses], plenty of things we can continue to do" if necessary, he said.

Woodcliff Lake, N.J.-based Par Pharmaceutical Cos. Inc. over the summer entered a deal with Immtech for rights to the compound for PCP in AIDS patients, providing $3 million up front and agreeing to as much as $29 million in milestone payments through approval, plus up to $115 million in sales-based milestone payments and royalties. (See BioWorld Today, June 13, 2007.)

Current options for PCP include trimethoprim-sulfamethoxazole, primaquine plus clindamycin, trimetrexate (with or without dapsone) plus leucovorin, atovaquone and pentamidine, but as much as 57 percent of patients trying those drugs switch to better-tolerated regimens. Pafuramidine is a "very distant relative" of pentamidine, Sorkin said - a relative that Immtech hopes will prove a better alternative.

For malaria treatment and prevention, the compound has reached Phase II trials. Immtech at the start of December granted an exclusive license to Paris-based BioAlliance Pharma SA to commercialize pafuramidine in Europe for PCP in AIDS patients and for sleeping sickness. That agreement, which brings $3 million up front and as much as $13 million in milestone payments, also carries an option to commercialize pafuramidine in Europe for prevention and treatment of malaria in travelers.