For years, scientists have been trying to find ways to block angiogenesis, the process by which cancerous tumors give off chemical signals to stimulate the formation of new blood vessels that bring them the nutrients and oxygen they need to grow.
Angiogenesis inhibitors are now the standard therapy for many cancers, including of the colon, brain, lung and liver.
Scientists, however, are still seeking more effective medications with fewer side effects. If they succeed in their efforts to better target blood vessels, patients will be able to live with cancer, just as HIV patients now live with the virus.
Enter Israeli company Vascular Biogenics Ltd. (VBL), which believes it has found a way to target these vessels and impede their growth.
“Tumors are smart,” said VBL’s CEO Dror Harats in an interview in Tel Aviv. “They have 20 agents that they can excrete to stimulate the buildup of new blood vessels. For this reason, trying to block one or two of these factors will not be potent enough. We took another approach — when the tumor tries to build these new vessels, we activate a deadly gene, targeting only the angiogenic blood vessels.”
The company, founded in 2000 by Harats, a professor at Tel Aviv University and a doctor at the Sheba Medical Center in Ramat Gan, develops anti-cancer gene therapies. Its flagship drug, VB-111, targets glioblastoma multiforme, an aggressive and difficult to treat type of brain tumor.
“This kind of brain tumor is deadly, and there is no treatment for it,” said Harats. “At VBL, we have found a genetic engine that can direct destructive genes to blood vessels, and halt their development.”
All mammalian DNA, explained Harats, has controlling elements — the expression of every protein created by DNA is regulated by a “genetic engine,” called a promoter, which dictates where and when the protein will be made. VBL researchers found that in mice there is a unique part of this engine that can be attached to any other gene, and this engine can dictate expression of this gene only in the angiogenic blood vessels.
“I can put the most toxic gene behind this special engine, and the engine will make it work only in the angiogenic blood vessels,” Harats said, explaining that in adults blood vessels are fully developed, so any angiogenic vessels the genetic engine destroys are new ones, aimed to feed the cancer cells. Not only that — because the VB-111 product was created by taking a common cold virus and manipulating it to hold the promoter and the deadly gene – the immune system appears to recognize the virus within the tumor setting, and fights it.
“So we are not just killing the blood vessels,” said Harats. “We are actually also exposing the tumor to the immune system — because the immune system recognizes the tumor with the virus and sets out to fight both the virus and the tumor. With our drug, we are killing the blood vessels, but we are also bringing the immune system to the tumor itself.”
Results of a Phase II study on the efficacy of VB-111 published a year ago showed that patients treated with the drug, in combination with another medication, Avastin, attained an overall survival rate of 59 weeks, compared with the 32 weeks attained by patients who had limited exposure to VB-111 and those who received just Avastin, also an angiogenesis inhibitor. The study also showed that VB-111 also induces an immune response in patients. The company is now recruiting patients for its much awaited and pivotal Phase III clinical trial, called the GLOBE trial, for the brain tumor. The interim results of the trial are expected in mid -2017.
“Compared to marketed anti-angiogenesis drugs, VBL’s gene therapy has the advantages of better tissue specific activity, lower toxicity, simple dosing regimen and is also able to incite a potent immune response against cancer,” said investment bank H.C. Wainwright & Co. analysts in a report on VBL in June, when it initiated coverage of the company with a “buy” recommendation and a 12-month price target of $11 for its share price, more than three times the $3.95 share price on June 28, when the report was released. The share closed at $5.65 on Nov.29 on the Nasdaq exchange, bringing the company’s market share to $152 million.
H.C. Wainwright & Co. analysts Swayampakula Ramakanth and Sean Lee wrote in their report that if successfully developed, VBL’s gene therapy platform “could revolutionize the multi-billion-dollar angiogenesis inhibitor market.” They added that they expect VB-111 to reach market in 2019 and achieve risk adjusted annual sales of $326 million by 2026.
In August, Roth Capital Partners reiterated its “buy” recommendation for VBL’s share, with a 12-month target price of $17 per share.
VBL is also developing VB-111 for additional tumor types, including ovarian and thyroid cancers, and has a number of follow on drugs in the pipeline. On Tuesday, the company said top line results from its exploratory Phase 2 study for VB-111 for thyroid patients met its primary endpoint, demonstrating stabilization of the disease and safety of the drug. The share on the Nasdaq rose 13 percent on Tuesday when the news was released.
The company has also said it plans to set up a new manufacturing facility in Israel’s Modiin, which will bring the company closer to the potential commercialization of the VB-111 drug.
“I believe that this unique therapeutic approach could really make a difference and affect the life expectancy of patients with various types of solid tumors,” said Harats in the interview. The company will keep on with its work “to make this drug candidate available to those who need it so much,” he said.