West Coast Editor

The Cystic Fibrosis Foundation entered research and development deals with two companies - Predix Pharmaceuticals Inc., which is getting up to $12.5 million in milestone-driven funds, and Alnylam Pharmaceuticals Inc., in line for $1.5 million.

"Predix is the broader one and it's based more on discovery," said Suzanne Pattee, vice president of public policy and patient affairs at the foundation, noting that Alnylam, though it has a smaller deal, could come back for additional funds if the company gets results.

"We've had a history of doing this for the last five or so years," Pattee told BioWorld Today. "It depends on the technology and what we think looks promising."

Woburn, Mass.-based Predix is getting the money through Predix Pharmaceuticals Holdings Inc. from Cystic Fibrosis Foundation Therapeutics Inc. over a three-year period that will include work on two programs.

The first is focused on the defective cystic fibrosis transmembrane conductance regulator protein, and the mutated gene that produces it is one of the key factors that leads to symptoms, complications and premature mortality. Predix will use its PREDICT technology to model the structure of the ion channel and then identify sites in the channel for therapeutic intervention to discover a drug that restores function.

"The whole idea with lung function is that you need to clear the mucus layer all the time," said Oren Becker, chief scientific officer of Predix and co-founder of the company. "It has to be wet but not overly, so you have the balance of salt, which is maintained by this [defective] transporter. The goal is how do we correct this - that's the Holy Grail. No one knows if that is possible, but the first step is to get that 3-dimensional structure of the protein."

Meanwhile, he said, "most of the approaches are to up-regulate something else to help regain the balance. The second program is one of these bypassing regulator mechanisms."

The program will use the same technology featuring 3-dimensional G protein-coupled receptor modeling and optimization, to come up with a small-molecule agonist to P2Y(2) to treat the disease. P2Y(2) receptor agonists help expel chloride from cells using a channel that bypasses the CFTR defect, and getting the chloride out would go a long way toward restoring proper salt and water balance in the cells.

"We've already done quite a few of these GPCR programs," Becker told BioWorld Today, noting that Predix has two products from such work in the clinic and another set to enter the clinic this quarter. Predix retains the right to develop and commercialize any compounds discovered through the second research program.

Cambridge, Mass.-based Alnylam, the RNA interference company, will apply its RNAi approach to find short interfering RNAs to restore protein function in cystic fibrosis patients.

Nagesh Mahanthappa, senior director of business development and strategy for Alnylam, called his firm's deal with the Bethesda, Md.-based Cystic Fibrosis Foundation "the first phase of an otherwise relatively open-ended relationship. In the first phase the major focus will be identifying the best targets for intervention."

But there's hope for more.

"If you look historically at the way the foundation has worked with a variety of companies, they start with sort of a taste spoon," Mahanthappa told BioWorld Today. "When they see good progress, they quite eagerly put more into the program."

A recent example of that is Vertex Pharmaceuticals Inc., of Cambridge, which last spring got $21 million as part of an expanded partnership for cystic fibrosis research. (See BioWorld Today, May 25, 2004.)

"Certainly within approximately a 12-month period," Alnylam likely is to have a product ready for clinical testing, Mahanthappa said.

Alnylam's stock (NASDAQ:ALNY) closed Wednesday at $6.98, unchanged. Predix, which is January raised $43 million in its third financing round, is privately held. (See BioWorld Today, Jan. 26, 2004.)