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ALBANY, N.Y.—In a move facilitated by AMRI's 300,000-plus natural products library, Cystic Fibrosis Foundation Therapeutics Inc. (CFFT), the nonprofit affiliate of the Cystic Fibrosis Foundation, has entered into a four-year research collaboration with AMRI worth up to $23.7 million, aimed at identifying novel treatments that address the core defect in cystic fibrosis.
AMRI's Dr. Bruce Sargent, vice president, discovery R&D, notes that natural products comprise about half of all drugs but despite this, pharma lost interest in them 10 or so years ago. "To date, CF has not proven to be hugely responsive to regular small molecules," Sargent notes, "so CFFT thought our natural products were worth a look."
Sargent notes that there are hints of the potential efficacy of natural compounds in two recently published studies, both of which reported use of natural products to improve chloride clearance from cells expressing the cystic fibrosis transmembrane conductance regulator (CFTR).
"The basic defect in CF," points out Robert J. Beall, Ph.D., president and CEO of the Cystic Fibrosis Foundation, "is that chloride and sodium are not transferred across the pulmonary epithelium—chloride can't get out and sodium floods in too rapidly. The resulting dehydration creates thick mucous that harbors bacteria leading to sickness and death. Natural products provide a greater chance that an extract is conducive to supporting life than is true of synthetic molecules." Noting that the vast majority of today's drugs come from natural sources, he adds that, "sometimes the body is a better chemist than a chemist."
AMRI will also conduct an integrated drug discovery program—including chemistry and in vitro biology, on promising compounds that may emerge from the screening program. Should any compounds identified under the agreement progress into preclinical or clinical testing, AMRI has the option to provide chemical development and GMP manufacturing services to CFFT on those compounds.
Cystic fibrosis is a life-threatening genetic disease that affects approximately 30,000 children and adults in the United States and 70,000 worldwide. As is true of other "small market" diseases such as Huntington's disease, Parkinson's disease and others, what Dr. Sargent refers to as "venture philanthropy" plays an important role in drug discovery for these conditions. AMRI won't be involved in commercialization of any CF therapeutic it may develop but will pursue additional, broader indications if the opportunity presents itself.
It is encouraging, he adds, that natural products have been making something of a comeback over the past two to three years. The collaboration with CFFT marks AMRI's fourth natural products-based research agreement in the last 10 months, including two others that have previously been announced. Typically, such projects are particularly attractive because they result in the company collecting downstream fees in addition to their fee for services arrangement as a CRO.
Through its collaborating partners, CFF has a number of potential new drugs in its pipeline, including VX-770 (Vertex Pharmaceuticals) , a new compound called a "potentiator" that may act upon the CFTR protein and help to open the chloride channel in CF cells. Phase Idosing has been completed in patients. Researchers are evaluating results and Phase II has begun. The foundation has invested about $72 million in VX-770 to date, Dr. Beall notes. He expects the foundation's collaboration with AMRI to identify an effective natural compound in three to four years.