About the GDC-0449 Ovarian Cancer Phase II Clinical Trial

Genentech  initiated the advanced ovarian cancer trial in December 2008 and Roche  informed Curis in August 2010 that preliminary findings from the primary  analysis of the study warrant additional investigation to clarify and  interpret potential clinical activity of GDC-0449 observed in this  trial.  Accordingly, Roche and Genentech have indicated that they plan to further analyze the data, including subset analyses in the coming months.  Following these analyses, they expect to make a portfolio decision regarding whether, or to what extent, they will continue development of GDC-0449 in advanced ovarian cancer.  Roche further noted that no obvious new safety signals were observed in patients treated with GDC-0449 in this study. 

Genentech  designed this Phase II clinical trial to investigate whether GDC-0449  might help to delay and/or attenuate tumor re-growth in a maintenance  setting following clinical remission of cancer after second-line  chemotherapy treatment for recurrent disease.  GDC-0449 was evaluated in this study as  a single agent maintenance therapy tested in 104 patients with ovarian  cancer in second or third complete remission in a randomized,  placebo-controlled, double-blind, multi-center, Phase II clinical trial.  Patients were randomized in a 1:1 ratio to receive either a 150 mg daily dose of GDC-0449 or placebo and were stratified based on whether their cancer was in a second or third complete remission.  The  primary endpoint of the trial was progression-free survival. Secondary  outcome measures included overall survival, measurement of Hedgehog  ligand expression in archival tissue, and number and attribution of  adverse events. 

Additional details for this clinical trial are available at www.clinicaltrials.gov. 

About the Genentech Collaboration

Under  the ongoing collaboration agreement between Genentech, a member of the  Roche Group, and Curis, GDC-0449 was discovered by Genentech and was  jointly validated through a series of preclinical studies.  Through  this collaboration, Genentech and Roche are responsible for clinical  development, and Genentech (U.S.), Roche (Ex-U.S. excluding Japan) and Chugai Pharmaceuticals (Japan) are responsible for commercialization of GDC-0449.  Curis  is eligible to receive cash payments assuming successful achievement of  specified clinical development and regulatory approval milestones, and  is also eligible to receive royalties assuming successful  commercialization of GDC-0449 by Genentech and its sublicensees, which  include Roche and Chugai.

In  addition to the ovarian cancer study, GDC-0449 is currently being  developed by Genentech and Roche in a pivotal trial in advanced basal  cell carcinoma, and Genentech and Roche have indicated that they also  plan to initiate a Phase II clinical trial in operable basal cell  carcinoma during the second half of 2010.  Through  a collaborative relationship with the National Cancer Institute (NCI),  the molecule is also being tested in several additional NCI-sponsored  trials.  Details for all GDC-0449 clinical trials are available at ClinicalTrials.gov.

About the Hedgehog Signaling Pathway

The  Hedgehog pathway is normally active during embryonic development and  plays a central role in cell differentiation and proliferation.  Inappropriate  activation or dysregulation of the Hedgehog pathway is believed to play  a critical role in the proliferation and survival of certain cancer  cells, including in basal cell carcinoma and medulloblastoma as well as  in colorectal, ovarian, pancreatic, small cell lung and breast cancers,  among others. The Hedgehog pathway is also thought to be a potential  regulator of cancer stem cells, which are discrete tumor cell  populations that display self-renewal and tumorigenic properties.

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