Curis Inc. said partner Genentech Inc. is moving forward with its lead systemic Hedgehog antagonist and plans to initiate Phase II trials in one or more undisclosed solid tumor indications during the first half of next year.

The news may have lain to rest some investor skepticism due to previous setbacks in Curis' Hedgehog programs. Shares of the Cambridge, Mass.-based company (NASDAQ:CRIS) gained 13 cents, or nearly 14 percent, to close at $1.07 on Wednesday.

Genentech licensed Curis' small molecule and antibody Hedgehog antagonists for cancer back in 2003 in a deal worth up to $240 million. Curis got $8.5 million upfront and about $7 million to cover research spending, but most of the money was tied to development and regulatory milestones. (See BioWorld Today, June 12, 2003.)

The first lead candidate under the deal, a topical drug for basal-cell carcinoma, was discontinued after a Phase I trial failed to show a complete clearance of skin lesions. (See BioWorld Today, Jan. 25, 2006.)

Next in line was an oral, small molecule, systemic Hedgehog antagonist for solid tumors. Curis got a $3 million milestone payment when Genentech filed its investigational new drug application. Good safety and pharmacokinetic data from the Phase I trial prompted Genentech to expand the study and evaluate efficacy, triggering another $3 million milestone payment to Curis.

When Genentech initiates the Phase II trial, Curis will earn yet another milestone, but Curis' Chief Financial Officer Michael Gray declined to specify the amount.

Genentech is not Curis' only partner for its Hedgehog programs, nor was it the only partner to experience a setback. Curis previously had a deal with Procter & Gamble Pharmaceuticals for development of a topically applied Hedgehog agonist for hair growth, but the program was terminated earlier this year due to safety issues.

Meanwhile, preclinical development is moving forward under a collaboration with Wyeth Pharmaceuticals for a small molecule systemic Hedgehog agonist to treat stroke and neurological disorders and a protein systemic Hedgehog agonist for cardiovascular indications. Wyeth licensed the programs in 2004 in a deal worth up to $170 million. (See BioWorld Today, Jan. 14, 2004.)

Other companies working on the Hedgehog signaling pathway, which contributes to the development and healing of tissues and organs and may be over-activated in cancer, include Infinity Pharmaceuticals Inc. and AstraZeneca plc.

Infinity plans to begin clinical trials with its anti-cancer Hedgehog antagonist IPI-926 in 2008. The company regained rights to the program last month, after partner MedImmune Inc. was acquired by AstraZeneca, placing the companies' programs in potential competition. (See BioWorld Today, Nov. 13, 2007.)

Beyond its Hedgehog work, Curis has "spent the last couple of years repositioning ourselves as a small molecule cancer company" and building a pipeline, Gray said. Preclinical studies are underway with CUDC-101, a small molecule triple inhibitor of histone deacetylase (HDAC) as well as EGFR and Her2 kinases. Gray said the company plans to file an IND in the first quarter of 2008 and begin cancer clinical trials in the second quarter.

Curis also plans to select and file an IND for another multi-targeted anti-cancer molecule next year, and research is also ongoing in a Wnt pathway program partnered with Genentech. Gray said Curis is also continuing "ongoing discussions" with potential partners for its bone morphogenetic protein-7 program for kidney disease, which Ortho Biotech Products LP returned the rights on earlier this year. (See BioWorld Today, May 22, 2007.)

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