Staff Writer

Since its founding last spring, Archer Pharmaceuticals Inc., a company focused on Alzheimer's products, had one financing round, the amount of which was not disclosed. But it was enough to launch the firm.

And while the company believes it can carry its lead Alzheimer's products through an investigational new drug application, Archer Pharma will need $25 million to get from Phase I to the end of Phase II in U.S. patients, Michael Mullan, CEO and chief scientific officer of Archer, told BioWorld Today.

The company has been in partner discussions with big pharmaceutical companies for more than a year, and those talks are "going quite nicely," Mullan said.

Archer sees an opening, despite some major setbacks in the Alzheimer's space - Myriad Genetics' Flurizan, Elan Corp. plc and Wyeth Pharmaceutical's bapineuzumab, and Alzhemed by Neurochem Inc. (renamed Bellus Health).

Some of the antibody approaches specifically target the aggregated (plaque) forms of amyloid, while Archer's compounds are being developed to target the soluble form. Mullan said his firm takes " a more simple approach": by clearing excess amyloid beta in its soluble form, other forms of it are expected to be reduced, he explained.

So far, he said, "We don't see any toxic effect from any of the drugs we've used in preclinical models." Nor have toxic effects been seen in trials of drugs used in some humans, he said.

He also pointed out that Archer's compounds do not appear to be completely switching off amyloid production but instead are modulating the artificial overproduction of the protein. Archer's drug candidates are designed to restore amyloid production to normal levels.

In normal mice that don't overproduce amyloid, he said, no toxic effects or effects on memory impairment have been observed.

The Sarasota, Fla.-based company is a spinout of the Roskamp Institute, where Mullan serves as executive director. He and Fiona Crawford, Roskamp's associate director and associate chief scientific officer at Archer, were part of the team that discovered that amyloid buildup in the brain is a cause of Alzheimer's disease. The discovery was seen as the first genetic cause of Alzheimer's disease.

Mullan and Crawford discovered what's known as the Swedish mutation, a genetic error that leads to the overproduction of amyloid and causes Alzheimer's to develop in people in their 50s. The theory at the time was that any accumulation of amyloid protein always would lead to Alzheimer's disease, Mullan explained.

Although Archer Pharma buys certain services from Roskamp, such as payroll and human services, the company is a separate entity from the institute, which was part of the University of South Florida until 2003.

The company was created based on the institute's research on nilvadipine. Currently, nilvadipine is available only in Japan and Europe, where it is used as an antihypertensive to lower blood pressure.

Mullan was in the UK when he made the discovery of the genetic errors that occur in the early onset of Alzheimer's disease. Additional funding was needed at the time to continue the research, but he said, "There wasn't any funding in Europe."

The University of Florida was an unlikely place to continue his research on Alzheimer's disease; it was "not necessarily one of the top places" for Alzheimer's research, Mullan noted. But he said Roskamp, named after a local developer who funded the institute, was flush with cash.

Looking back, Mullan said he is pleased with how things worked out at Roskamp.

Archer Pharma is now working to take its two lead compounds into the clinic, ARC-29, its version of the approved drug nilvadipine, and ARC-31, which is chemically related to nilvadipine.

The company has not yet disclosed the structure of ARC-31, but believes it may hold some advantages over ARC-29, most importantly that it doesn't have antihypertensive (blood pressure-lowering) effects.

Archer has completed a Phase I trial of ARC-29 in Ireland in Alzheimer's disease patients. The drug candidate didn't lower pressure significantly and didn't lower blood pressure at all overall, Mullan noted.

However, patients potentially could run into problems with lowering blood pressure if the dose of ARC-29 were to be raised.

On the other hand, ARC-31, doesn't relax the blood vessels and may not run into those kinds of problems unless it was given at doses 100 times higher than the current dose, Mullan indicated.

Last year, Archer submitted an application to the FDA for a Phase I trial in the U.S. The application was well received, Mullan said, but the agency has asked for stability data to ensure that the drug doesn't degrade while it's on the shelf. Those data were not included in the company's original investigational new drug application, but they are being resubmitted to the agency at the end of April, he noted.

Echoing a familiar refrain, Mullan indicated that it has been tough trying to raise money in the current economy. But he said, "Ultimately, the science will determine whether we have an attractive enough product or not."

One advantage, he said, is that the basic compound already has been shown in small clinical trials in Japan to have a solid safety profile and efficacy in Alzheimer's disease.

The company also is working on other approaches to Alzheimer's disease, including a gamma secretase inhibitor in preclinical development.