In the latest deal involving the development of protease inhibitors against hepatitis C virus, Enanta Pharmaceuticals Inc. partnered a preclinical program with Abbott Laboratories Inc. for a potential $307 million.

That includes an up-front payment of $57 million, giving Abbott access to Enanta's HCV NS3 and NS3/4A protease inhibitors, which have demonstrated efficacy with good pharmacokinetic profiles in preclinical studies.

The majority of the up-front fee will be paid in cash, with "less than a quarter" of that paid in equity, said Jay Luly, president and CEO of Watertown, Mass.-based Enanta.

"It's quite a sum of cash" for an early stage program, he said, attributing the amount to the growing interest in protease inhibitors against HCV and the "scarcity of programs out there."

F. Hoffmann-La Roche Ltd., of Basel, Switzerland, signed a deal in October with Brisbane, Calif.-based InterMune Inc. for a program led by ITMN-191, which is expected to begin Phase I soon. That agreement called for $60 million up front and up to $470 million in milestones. (See BioWorld Today, Oct. 18, 2006.)

In July, Janssen Pharmaceutica NV, a unit of New Brunswick, N.J.-based Johnson & Johnson, partnered with Vertex Pharmaceuticals Inc. on VX-950, a HCV protease inhibitor in Phase II. In exchange for exclusive rights in Europe, South America, the Middle East and Australia, Janssen agreed to pay Cambridge, Mass.-based Vertex $165 million up front, and up to $380 million in milestones. (See BioWorld Today, July 5, 2006.)

In the case of Enanta, Luly said, Abbott Park, Ill.-based Abbott "recognized the strength of our platform," and has a "long-standing traditions in antivirals."

In addition to the up-front payment, Enanta is entitled to clinical and regulatory milestones that could total $250 million for one candidate, with further payments due upon development of additional molecules. At commercialization, Enanta would receive double-digit royalties and retains a "very valuable" option to fund 40 percent of U.S. development in return for 40 percent of U.S. profits, Luly told BioWorld Today.

HCV affects more than 170 million people worldwide. The global market for HCV drugs is about $3 billion, though that figure could to grow to as much as $12 billion over the next several years as the drugs in development reach commercialization.

Despite the lack of late-stage data - the most advanced are Vertex's VX-950 and Kenilworth, N.J.-based Schering-Plough Corp.'s SCH 503034, both of which are in Phase II - protease inhibitors are being viewed as "one of the cornerstones of what will be combination therapy" for HCV, Luly said.

HCV protease inhibitors are designed to block HCV protease, the enzyme needed for the virus to replicate. Protease inhibitors have been successful against HIV, and Luly said he expects the HCV drug development to follow a similar path.

"It was very noisy in the beginning, with a number of molecules in development" before subsequent generation molecules took the lead, he said.

Enanta and Abbott have not yet disclosed a timeline for moving the HCV protease inhibitor program into the clinic.

Besides HCV, Enanta's infectious disease pipeline includes EDP-420, a Bicyclolide (macrolide super family) antibiotic in Phase II studies in community-acquired pneumonia. The company partnered East Asian rights to an oral formulation of the compound to Osaka, Japan-based Shionogi & Co. Ltd. in 2004, and retains rights for the rest of the world for all administrations. (See BioWorld Today, July 28, 2004.)

In earlier-stage development, Enanta has a program aimed at methicillin-resistant Staphylococcus aureus (MRSA) infections, which are a growing problem in hospitals as well as in the community, Luly said, adding that the company is developing a re-engineered macrolide to go after both indications.

All Enanta's programs "are billion-dollar market opportunities," he said. "Our goal is to partner with pharma and yet retain attractive rights for ourselves."