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New Yale-Novogen Venture to Develop Powerful Treatment for Ovarian Cancer

November 19, 2013
by Brita Belli

A new joint venture, CanTx, Inc., has a simple mission: cure ovarian cancer. The venture—announced on Nov. 6—brings together the research advances of Gil Mor, Professor of Obstetrics, Gynecology, and Reproductive Sciences at Yale University, the first researcher to isolate and clone ovarian cancer stem cells, with Novogen, an Australian-US biotech company that has developed compounds that target these cancer cells. What makes the Novogen compounds unique is that they are active against the full range of cells within a tumor, including both cancer stem cells and their daughter cancer cells. They also can be used alone or in combinations in order to be modified for individual patient treatment.

The venture has an office in New Haven although its early drug development will happen at Mor's lab under the company's Sponsored Research Agreement with the university. Within 12 months, however, CanTx expects to be looking for independent lab and office space and currently is considering both Yale West Campus and Science Park in New Haven as possible locations.

The arrangement was facilitated by the Yale Office of Cooperative Research, which helps to maturate basic science concepts into real-world solutions. This partnership, Mor says, will speed the discovery of new treatments for ovarian cancer from the lab to the patient. "This is the future," he says "academia and industry working together for the benefit of the patient."

Mor notes that there have been no new therapies for ovarian cancer in the past 30 years and research has failed to improve the survival of patients by more than a few years. Unfortunately, the physical symptoms of ovarian cancer are difficult to identify (they include abdominal pain, bloating and feeling full quickly), which means that most ovarian cancer cases are not identified until the disease has spread and survival rates are poor. If the cancer has spread to areas outside the pelvis, the five-year survival rate for ovarian cancer is about 30%. Many patients will respond to the first round of chemotherapy, but around 70% of patients diagnosed with ovarian cancer will have a recurrence with very high mortality, according to the Ovarian Cancer National Alliance.

This ovarian cancer recurrence is the result of cancer stem cells, which don’t respond to chemotherapy and have a high capacity for self-repair following treatment. This is the focus of the CanTx strategy: target the cancer stem cells.

Isolating Ovarian Cancer Stem Cells

Over 10 years ago, Mor isolated ovarian cancer cells in his lab at Yale and provided the cells as a resource to pharmaceutical companies to develop better drugs. Companies would submit their compounds for testing, and Mor would test their ability to kill the cells. Novogen was one of the companies who submitted their drugs for testing by the Mor lab. "The Novogen drug, phenoxodiol, was the only drug that killed these cells," Mor says, which led to Yale and Novogen taking that drug into the clinic in women with late-stage ovarian cancer.

Dr. Graham Kelly, Novogen CEO, said, "Phenoxodiol ultimately failed, but the underlying family of drugs still was doing something that no other anti-cancer drugs were capable of, so we went back to square one and looked at what it would take to make these drugs more active in the clinic."

"We made the required breakthrough and now have a new generation of drugs that are thousands of times more powerful than the original drugs. But more importantly, we found that the changes we made now led to them killing cancer stem cells as well as the more prevalent somatic cancer cells," Kelly added.

At the same time that Novogen’s technology advanced, so did Mor's. His ability to identify, isolate and culture ovarian cancer stem cells is a major advance making it possible to test drugs before they go into the clinic to see if they are able to kill the full range of cells within a cancer.

"Chemotherapy is like cutting the grass," says Mor. "It doesn't kill the roots—the tumor-initiating cells. With this technology we can for the first time have a high degree of confidence in whether a drug is likely to be able to wipe out the full range of cancer cells within an ovarian cancer. And that is what we need to do in order to put patients into long-term if not permanent remission."

Creating a Personal Oncology Treatment

The idea behind CanTx (shorthand for "cancer therapy," the capital "CT" references Connecticut) is to launch an all-out attack on ovarian cancer using a number of different strategies.

The first and immediate strategy is to develop a product that can be injected into the peritoneal cavity (the space where the intestines, stomach and liver are held) to attack the cancer directly. "Usually, only 3-4% of cancer drugs that are injected intravenously or taken orally get into the tumor," says Mor, a complication that requires heavy dosing of drugs and results in massive side-effects. "My idea was to develop nanoparticles coated with a peptide that seek out the tumor and then pack those particles with one of Novogen's drugs. In that way, we can ensure that almost all the drug we put into the patient gets to the cancer."

Yale and Novogen have identified a compound that is killing both ovarian cancer stem cells and their daughter cells, and CanTx currently is moving as quickly as it can to bring the intra-peritoneal product into the clinic. While the company's focus is on ovarian cancer, Mor adds that they anticipate the same concept being used for other cancers of the peritoneal cavity including endometrial, colo-rectal and pancreatic cancers.

The second (and longer-term) strategy is to match an individual cancer with the appropriate drug. Mor said, "we know that there is an enormous variation between patients in the responsiveness of their ovarian cancers to different drug therapies, and we think this reflects different mutations. For this reason we think that we will need to develop different Novogen drugs that will work across a range of different genotypes."

That is where the ability Mor's laboratory to isolate the cancer stem cells from individual ovarian tumors will be so critical. "Our goal is personalized chemotherapy," Mor said. "We foresee a panel of Novogen drugs, each a slight variation of each other, that will target individual tumor genotypes, with the right match being determined on the basis of markers of sensitivity," Mor added.

In addition to developing markers to identify the best candidates for specific drugs, CanTx plans to develop markers to track how a patient responds to treatment, so that treatment can be modified or changed as needed. Markers will be identified either from taking a biopsy of a tumor, or from a blood sample.

Any drugs they develop will not only kill the "root" of cancer cells as no treatment has done before, but any promising treatment will be moved quickly to clinical trial and patient treatment in months instead of years.

Submitted by Liz Pantani on November 19, 2013