Partners target ovarian cancer

TORONTO—Targeted toward developing a more personalized—andmore effective —therapy for cancer patients, Canadian company Axela and Irvine,Calif.-based OvaGene Oncology have agreed to a molecular diagnosticspartnership aimed at developing and marketing a test to discover the bestweapon to kill ovarian cancer, one of the deadliest forms of cancer.

Axela's Ziplex platform is optimized to perform complex geneand protein expression assays in a distributed testing environment, and isdesigned for customized applications in RNA and protein research, according toa company press release.

By partnering with OvaGene for proprietary content, Axelacreates an opportunity to make such tests available on a global basis.

In the United States alone, 182,000 women are currentlyliving with a confirmed diagnosis of ovarian cancer, OvaGene reports.Approximately 145,000 of those patients will receive chemotherapy and couldpotentially benefit from the diagnostics test. The U.S. National Institute ofHealth (NIH) reports that 1 million American women have a confirmed diagnosisof a gynecologic cancer, 587,000 have endometrial cancer and 250,000 havecervical cancer.

OvaGene, with its particular expertise within the field ofgynecologic cancers and through its CLIA Laboratory, is focused on developingand commercializing proprietary gene-based signatures and assays to personalizethe treatment of ovarian, uterine and cervical cancers.

The first of OvaGene's proprietary gene signatures wasimplemented on Axela's Ziplex platform beginning on Aug. 21. The signature willbe made available to physicians to assist in personalizing the selection ofdrugs commonly used to treat recurrent ovarian cancer.

Michael Treble, executive chairman of Axela, says thepartnership "is another important addition to Axela's pipeline of diagnosticcontent. OvaGene's unique signature directly complements our other developmentprograms, including the breast cancer risk-of-recurrence assay."

"The relationship with Axela has the potential to rapidlyyield significant benefits to patients and their physicians. In the U.S., over20 drugs may be used to treat recurrent ovarian cancer, each showing a low 12-to 15-percent response rate," Frank J. Kiesner, founder and CEO of OvaGene,stated in a press release. "When available, OvaGene's proprietary genesignature will provide physicians an opportunity to improve these responserates by personalizing drug selection. Through this partnership with Axela andwith access to their unique platform, we can rapidly offer the highest qualitygene signature-based testing to gynecologic oncologists."

In utilizing the Flow-Thru Chip's versatility to performboth gene and protein analysis, Axela is well positioned to address the needfor automated multiplex testing in a wide range of laboratory environments, headds.

"The combination of OvaGene's validation expertise, Axela'sdistributed platform and complementary signature content led to creation of thepartnership," says Paul Smith, chief operating officer of Axela.

The personalized selection of drugs is achieved through twocomponents, Smith says. First, a gene signature is validated to accuratelyidentify the pathways that are activated in a particular tumor sample in orderto match those to the mechanism of specific drug therapies. The Ziplex platformthen enables these tests to be carried out.

Dr. Jay Coonan, founder, director and executive vicepresident of OvaGene's strategy and business development, tells ddn, "the area of gynecologic cancers, including ovariancancer, represents a huge unmet need in diagnostic tools to help the physiciancare for oncology patients. The addition of the OvaGene content (the initialassay to predict response to chemotherapy for ovarian cancer) to the Axelaplatform in this partnership will accelerate the distribution both locally and,with continued clinical validation, globally in a cost-efficient manner."

The statistics for ovarian cancer "are grim," Coonan says."There are about 23,000 new cases per year, but about 15,000 deaths yearly. Thevast majority of patients are diagnosed at an advanced stage (III/IV) due tothe vagueness of the presenting symptoms, often causing missed or delayeddiagnosis."

Plus, the diagnostic tools have been "woefully inadequate,"Coonan says.

"There have been no dramatic therapeutic breakthroughs asyet, either," he notes. "Thus, about 75 percent of ovarian cancer patients diewithin five years of initial diagnosis. Unfortunately, 25 percent of thoseinitially treated have either no response or an early recurrence within sixmonths and are called 'platinum-resistant.' Those patients having a recurrenceof cancer at 12 months or later after chemotherapy are classified as'platinum-sensitive' and are generally retreated with a platinum drug. Sadly,eventually all patients become 'platinum-resistant.'"

Ovarian cancer, like all cancers, arises by mutations in thegenes and DNA of the cells, he said. The Cancer Genome Atlas analysis ofovarian cancer showed 85 genes associated with improved survival and 108 genesassociated with poor survival. The problem remains of how to apply thisenormous amount of new information realistically in the clinic.

"It is a huge challenge in the condition of 'platinumresistance' to find another drug or drug combination to which the tumor mightrespond," Coonan says. "Currently, the selection of drug is based on thephysician's experience, specific drug toxicities or randomly chosen from thosedrugs traditionally tried for the disease. That selection numbers almost 25different drugs. Unfortunately, each drug generally has only a 10- to15-percent response rate in this resistant/recurrence setting. The new hope of'targeted therapies' (bevacizumab, Avastin) has led to some renewed optimism.However, even these drugs so far have generally poor response rates.

"The challenge going forward is to correlate these multiplegenetic/DNA changes in the form of gene signatures, such as OvaGene and Axelaare developing, with specific drugs to identify which tumors have a trulybetter chance of responding to a particular therapy," Coonan continues. "Tumorsare 'smart' and mutate frequently to bypass the genetic pathway that a specificdrug blocks, thus rendering the cancer again 'resistant.' Going forward, itbecomes vital in drug selection for each individual patient to know whatgenetic pathways are active to match the therapy with a similar activity, thusgiving the best chance of a good result."

OvaGene has a strong pipeline of proprietary moleculardiagnostics that, with proper validation and appropriate approval on amultiplexing platform, could have a global effect on improving the care ofwomen suffering from gynecologic cancers, Coonan says.

"Many of OvaGene's assays have the potential applicabilityto other tumor types as well. Together with Axela, this represents anextraordinary opportunity for both companies," he says.