Staff Writer

Curis Inc. said that partners Roche AG and Genentech Inc., part of the Roche Group, will conduct "further analyses" of a Phase II ovarian cancer study of GDC-0449, a Hedgehog pathway inhibitor.

Based on the analyses – including subset analyses – Roche and Genentech will decide whether, or to what extent, to continue development of the compound GDC-0449 in advanced ovarian cancer.

Genentech initiated the advanced ovarian cancer trial in December 2008 and completed enrollment last year. The Phase II trial was designed to investigate whether GDC-0449 might help to delay and/or attenuate tumor re-growth following clinical remission after second-line chemotherapy treatment in patients with recurrent disease

No obvious new safety signals were observed in patients treated with GDC-0449, Curis said. Data from the Phase II ovarian cancer study will be submitted for presentation at an upcoming medical meeting, the company said.

Cambridge, Mass.-based Curis, an industry pioneer with respect to the Hedgehog pathway, is eligible to receive milestones under a 2003 agreement with collaborators Roche and Genentech in the potential $240 million deal. Its next milestone would be triggered if the GDC-0449 ovarian cancer trial advanced to Phase III, Dan Passeri, Curis president and CEO, said.

Passeri told BioWorld Today that the ovarian cancer study of GDC-0449 is "still active," and he emphasized that "we remain encouraged that there are data that warrant further analysis."

Yet Wall Street remained skeptical, sending shares in Curis (NASDAQ:CRIS) down 22 cents, or 12.6 percent, closing at $1.52.

Joseph Pantginis, a senior analyst with Roth Capital, wrote in a research note, "In our view, this news does not send a positive signal to investors based on such phrases as 'warrants additional investigation' and 'will look at subsets.'" He surmised that "the primary endpoint of the study was not or will not be met."

When asked whether the endpoint was missed, Michael Gray, Curis chief financial officer and chief operating officer, said that has not yet been determined. He contrasted the ovarian cancer data with that in colorectal cancer where GDC-0449 failed to hit the mark in a Phase II study.

In that study, GDC-0449 was studied in combination with Avastin (bevacizumab) and chemotherapy in first-line metastatic colorectal cancer patients.

In the colorectal cancer study, Gray said, it was clear the endpoint was not met. "In this case, the data is a lot less clear," he said of the ovarian cancer study.

The failed colorectal cancer study only added to Pantginis' misgivings about GDC-0449. Coupled with the recent colorectal cancer study miss, "today's additional failure further decreases our confidence in GDC-0449."

But he also noted that studies of the compound in basal cell carcinoma are "still moving full steam ahead."

Roche expects to initiate a Phase II trial in operable basal cell carcinoma patients during the second half of the year. In addition, the compound is being studied in patients with advanced basal cell carcinoma, with results from a pivotal Phase II study expected in 2011. Regulatory submissions could be filed in 2011, assuming positive results from that study.

The National Cancer Institute also is studying GDC-0449 in 10-15 studies in a variety of cancers, including pancreatic, lung and breast cancer.

Curis and its partner are in the lead in terms of development of a drug candidate aimed at the Hedgehog pathway.

Others further back in the field include Infinity Pharmaceuticals Inc., which is studying its IPI-926 Hedgehog pathway inhibitor in Phase I trials in patients with solid tumors and in combination with gemcitabine for metastatic pancreatic cancer.

Exelixis Inc. and Bristol-Myers Squibb Co. also have a Phase I Hedgehog inhibitor aimed at advanced solid tumors.

Curis' platform includes several other cancer drug programs aimed at multiple signaling pathways, including histone deacetylase (HDAC).

Earlier this month, Curis began dosing in a Phase Ib expansion trial of CUDC-101 for patients with head and neck, gastric, breast and liver cancer. That compound is a first-in-class small-molecule drug candidate that has been designed to block HDAC, epidermal growth factor receptor (EGFR) and epidermal growth factor receptor 2 (Her2).

Curis plans to initiate a Phase I/II trial of CUDC-101 in head and neck cancer patients later this year and is currently working to formalize the design of that study.

In preclinical studies, CUDC-101 demonstrated the potential to inhibit all three molecular targets (HDAC, EGFR and Her2), resulting in the potent killing of a wide range of cancer cell lines that are representative of a variety of human cancer types, many of which have demonstrated resistance to various approved targeted agents.

Calling CUDC-101 a "primary value driver, Pantginis said, "We believe that the company's product candidates will continue to attract partners."