Adding a third antisense cancer drug to its pipeline, OncoGenex Technologies Inc. licensed rights to inhibitors of heat-shock protein 27, which will be included as part of its expanded collaboration with Isis Pharmaceuticals Inc.
The company licensed the Hsp27-related patents from the University of British Columbia; they are based on research conducted at the nearby Prostate Center at Vancouver General Hospital. OncoGenex has identified a lead compound, OGX-427, a second-generation antisense drug to target Hsp27, a protein that is overexpressed in tumors and helps cancer cells resist standard therapies.
Compelling data demonstrating antitumor activity by inhibiting Hsp27, as well as the correlation between protein expression and treatment resistance "across a whole spectrum of tumors," generated OncoGenex's interest in the Hsp27 inhibitors, said Scott Cormack, president and CEO of the Vancouver-based company.
In fact, those data were so promising, even though OGX-427 is the third compound to be identified through the company's agreement with antisense veteran Carlsbad, Calif.-based Isis, it will "leapfrog" the second one and enter clinical trials before it, likely beginning in 2006, he said.
Hsp27 serves as a "molecular chaperone" and protects other proteins, much like Hsp70 and Hsp90. Expressed in tumor cells, Hsp27 can help those cells survive, and there is evidence that the administration of existing cancer treatment can dramatically provoke an increased expression of the protein, Cormack told BioWorld Today.
Preclinical studies of OGX-427 demonstrate its effectiveness to inhibit Hsp27 as a single agent, as well as its ability to enhance the therapeutic response when combined with standard cancer therapies.
When the drug enters clinical trials, OncoGenex would evaluate it in solid tumors, as well as in liquid tumors, such as those associated with multiple myeloma and hematological tumors.
"It will be across a pretty broad platform," Cormack said, "much like we did with OGX-011," the compound identified through OncoGenex's initial collaboration with Isis signed in November 2001.
The first second-generation antisense chemosensitizer in the company's pipeline, OGX-011 has completed Phase I studies and is scheduled to be evaluated in five Phase II trials this year.
All candidates in OncoGenex's pipeline are antisense compounds, an approach, Cormack said, that has proved effective so far.
"Most of the drug targets we've identified are not traditionally druggable or even approachable with monoclonal" compounds, he said. "We're going to apply whatever therapeutic strategy makes the most sense for the biology."
He said he has heard his share of concerns regarding antisense, but said the Phase I results presented by OncoGenex at the American Society of Clinical Oncology last year showed that OGX-011 was able to reduce the amount of clusterin in patients by 90 percent. In a study of prostate cancer patients, the drug was administered once weekly with a two-hour intravenous infusion. After six weeks, results also indicated 98 percent suppression in lymph nodes. The product also was found to be safe and well tolerated.
"That background shows that this drug, with second-generation chemistry, is doing what it's supposed to be doing," Cormack said. "I have huge faith in that data set and in this field."
After identifying OGX-011, OncoGenex and Isis agreed to expand their collaboration a year ago to develop OGX-225, a preclinical antisense compound that targets the productions of both insulin-like growth factor binding protein-2 and insulin-like growth factor binding protein-5.
OGX-427 is the first candidate selected after the companies agreed to another collaboration expansion last month, and a second compound falls under that agreement.
The partnership combines OncoGenex's position in developing inhibitors to validated drug targets with Isis' proprietary second-generation antisense chemistry. Terms of the expanded partnership call for OncoGenex to handle the preclinical and clinical development, with Isis receiving an up-front fee, milestone payments and royalties on product sales. OncoGenex retains the rights to nominate the second target candidate.