Tacere Therapeutics Inc. teamed up with Pfizer Inc. to develop and commercialize TT-033, a preclinical hepatitis C drug consisting of three short-hairpin RNAs (shRNAs) delivered within an adeno-associated virus (AAV) protein coat.

Mike Catelani, chairman, president and chief financial officer of San Jose, Calif.-based Tacere, said his company will receive an undisclosed up-front payment as well as up to $145 million in milestone payments from Pfizer. Those milestones are weighted "more to the development side than the commercialization side," Catelani said.

Pfizer will also fund all future work with the drug and pay Tacere royalties that have the potential to escalate from high single digits to low double digits, Catelani added.

The research funding will support Tacere's ongoing preclinical work, which will culminate in an investigational new drug application filing within the next 15 to 18 months. After that, a joint steering committee will split up the responsibilities for managing clinical development, which Catelani said will "most likely" be assigned to Pfizer, although "nothing is set in stone at this point."

The deal provides Pfizer with exclusive rights to TT-033 outside of Asia, where Tacere previously had granted an option to the drug to Tokyo-based Oncolys BioPharma Inc. in exchange for an undisclosed equity investment. Oncolys has until the end of Phase I trials to exercise its option, but Catelani said he expects discussions to move forward quickly because Pfizer also is interested in rounding out its deal by picking up Asian rights.

HCV drugs commanded significant big pharma interest in 2006. HCV deals worth more than half a billion dollars were signed between Idenix Pharmaceuticals Inc. and Novartis AG; Vertex Pharmaceuticals Inc. and Janssen Pharmaceutica NV; and InterMune Inc. and F. Hoffmann-La Roche Ltd. (See BioWorld Today, March 30, 2006, July 5, 2006, and Oct. 18, 2006.)

But 2007 was fraught with HCV data setbacks and clinical holds, which affected Idenix's nucleoside polymerase inhibitor valopicitabine, ViroPharma Inc.'s non-nucleoside polymerase inhibitor HCV-796, Maxygen Inc.'s PEGylated interferon-alpha MAXY-alpha and XTL Biopharmaceuticals Ltd.'s non-nucleoside polymerase inhibitor XTL-2125. (See BioWorld Today, July 16, 2007, Aug. 13, 2007, and Sept. 24, 2007.)

Other drugs continue to move forward in 2008, including Vertex's protease inhibitor telaprevir, Intermune's protease inhibitor ITMN-191 (R7227), Pharmasset Inc.'s polymerase inhibitor R7128, and Idenix's second-generation polymerase inhibitors IDX184 and IDX102. (See related story in this issue.)

Pfizer has an HCV drug in Phase II, but overall the company hasn't been as active in the space as some of the other big pharmas. Catelani noted that the deal with Tacere made sense because it also allowed Pfizer to get into RNAi, another area the pharma hasn't targeted aggressively.

Merck & Co. Inc. established itself in the RNAi space through its 2006 acquisition of Sirna Therapeutics Inc. Others to stake out RNAi claims included Roche Holding AG through a nonexclusive deal with Alnylam Pharmaceuticals Inc., AstraZeneca plc through a deal with Silence Therapeutics plc and GlaxoSmithKline plc through a deal with Santaris Pharma A/S. (See BioWorld Today, Nov. 1, 2006, July 9, 2007, July 10, 2007, and Dec. 20, 2007.)

Yet Tacere's approach differs from others in the RNAi field. While most companies pursue "delivered" RNA, which uses a small-molecule type of approach to deliver short-interfering RNA (siRNA), Tacere focuses on "expressed" RNA, which uses viral vectors to deliver shRNA.

The ability to incorporate multiple targeted shRNAs into a single treatment provides an advantage over siRNA, Catelani said. In HCV, TT-033 can target three separate regions of the HCV genome, potentially providing efficacy against all HCV genotypes while preventing resistance. In preclinical studies, a single administration of TT-033 provided more than 60 percent inhibition of the three targeted regions of the HCV genome for two months.

Founded in 2006, Tacere acquired its expressed RNA patent portfolio and TT-033 from Benitec Ltd. (See BioWorld Today, July 24, 2007.)

With its lead candidate funded and likely soon to be under development by a partner, Catelani said Tacere is "looking at a number of different things" to add to its pipeline, with particular interest in other shRNA programs. The company is also evaluating financing options, including a Series A round.

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