Shares of Immunovaccine Inc. (TSX:V:IMV) gained 14.4 percent Monday, to close at C$1.11 (US$1.01), after the Halifax, Nova Scotia-based company reported that monkeys dosed with an Ebola vaccine employing its Depovax formulation technology survived exposure to a lethal dose of the virus in a challenge study performed by the National Institute of Allergy and Infectious Diseases (NIAID).

Four cynomolgus macaques received two doses of the Depovax-formulated vaccine, once at the study's start and again on day 56. At day 70, researchers gave all six monkeys in the study a lethal dose of the wild type Zaire strain of the Ebola virus. Seven days later, the two control animals were dead. The vaccinated monkeys, however, survived with no disease symptoms more than two weeks following exposure.

Impressed by the results of the company's ongoing anthrax vaccine program, the NIAID approached the firm about four months ago, asking if it would like to incorporate Depovax into some of the vaccines it was already testing, Immunovaccine CEO Marc Mansour told BioWorld Today.

The results won't change the company's focus on developing cancer and infectious disease vaccines already in its pipeline, said Mansour, but they have sparked preliminary talks with potential partners who could incorporate Depovax into existing Ebola programs. (See BioWorld's Special Report: The Push to Contain the Ebola Virus.)

NIAID will next move the Depovax-formulated vaccine into wider testing with bigger animal groups, testing different timing and other factors. "What that means for us is that with these data we can now talk to various organizations about whether there's a development program we can get involved in for an Ebola vaccine," Mansour said.

CANCER, TOO

While the Ebola trials have piqued investor interest, Immunovaccine has been working on infectious disease vaccines for years. The company's Depovax-formulated respiratory syncytial virus is already slated for a phase I study, expected to begin this year, while it continues to pursue its collaboration with the NIH to develop and test a rapid response anthrax vaccine.

More advanced, however, are Immunovaccine's Depovax-formulated cancer vaccines, DPX-0907 and the survivin-targeted DPX-Survivac, which is expected to enter a phase I/II study in glioblastoma and a phase II study in ovarian cancer later this year.

The ovarian cancer trial will enroll 250 patients and will be sponsored and conducted by Canada's NCIC Clinical Trials Group, while the ovarian cancer study is sponsored by the University of Rome. Furthermore, the company is looking at running additional smaller phase II trials to investigate the clinical activity of DPX-Survivac in ovarian cancer and lymphoma.

The company has also drawn attention from the Dana-Farber Cancer Institute, which recently selected Depovax as the underlying enhancement technology for a new HPV-related cervical and head and neck cancer vaccine. The vaccine will be the focus of a clinical study, expected to start in 2015, that will be funded by a grant from Stand Up To Cancer and the Farrah Fawcett Foundation.

HUNGRY SEALS

Immunovaccine got its start at Halifax's Dalhousie University, thanks to cod-hungry seals. Looking for an alternative to clubbing the animals in order to control their numbers, the Canadian government gave the Dalhousie team $5 million to develop a more humane method of population control. While contraceptive vaccines already existed, getting seals to revisit researchers for an annual booster shot was out of the question. "There's only one time a year that you can get close to a seal," Mansour said, "when it's breeding on Sable Island, a sand strip 200 kilometers off shore."

To solve the problem, researchers came up with a highly adjuvanted vaccine technology. Researchers returned the following year to check in on the animals that had returned for another breeding season. Not one of the vaccinated seals was pregnant or had pups. Ten years later, there were still no babies, all from the single vaccination. "It was a very dramatic result," Mansour said.

As an adjuvanting platform, Depovax provides controlled and prolonged exposure of antigens and adjuvant to the immune system, by encapsulating both antigens and adjuvant in a liposome shell. The vaccine is then stored in a dry format. When it's time for administration, the vaccine is suspended in oil and injected, creating a "depot" to which antigen-presenting cells are attracted.

The cells pick up the vaccine, process and display the antigens through the MHC pathway. Killer T cells recognize the antigens, are activated and multiply, going on to search out tumor cells that display the antigens, then dispersing cytotoxic molecules that disrupt cell membranes or kill the cancer cell by signaling apoptosis.

SEEING GREATER POTENTIAL

Since then, the company has changed and grown, delivering positive results from a phase I/Ib study of its lead cancer vaccine candidate at the American Society of Clinical Oncology last year and showing early evidence of clinical activity in ovarian cancer patients.

Immunovaccine's original business model focused on out-licensing: finding companies with vaccines that need improvement and out-licensing its technology to do that. But "immunocontraception is very difficult commercially," Mansour said. So, in 2004, the company started a collaboration with CSL Ltd., which later became Pfizer Inc.'s animal health, then Zoetis Inc. CSL was interested in single-dose veterinary vaccines to address the compliance problems in the industry. "Ours was one of the few single-dose vaccine technologies they believed in," Mansour said.

In 2008, with studies proving the technology a success, Pfizer exclusively in-licensed the platform for cattle applications, a deal that brought Immunovaccine $1.8 million plus the promise of future milestone payments and royalties.

While that helped finance the company to a degree, the company was was realizing that it really wanted to focus on the human health care market, not the veterinary market.

The challenge its executives faced was that although the technology looked great in animal studies, to move it into human application, the company needed to work out the manufacturing. So, starting in 2005, it began developing a manufacturing process that's implementable in a GMP environment, that's fully scalable and can demonstrate the commercial potential.

"It might work great, but if you can't manufacture and produce it for human use, what's the point?" At the same time the company was investing in process development, it started changing its business model from a pure out-licensing model to a combination model, still out-licensing but also developing its own products.

The company liked the idea of cancer vaccines but wasn't sure the technology would be good for that application. Around 2006 or 2007, the firm tested it in animal models and saw "some pretty dramatic results compared to what was out there and being published," Mansour said. "That's when we realized we had something that had a shot at enabling cancer vaccines."

It was then Immunovaccine began seeking targets, antigens and even other companies that it could bring in-house. By 2008, it had found a set of cancer antigens that fit the criteria: seven antigens discovered by Doylestown, Pa.-based Immunotope Inc., which was discovering cancer antigens using the same technology as Germany's Immatics Biotechnologies GmbH (a company that recently signed a deal with Roche AG for its discovery platform). Based on the confidence in the discovery and validation process behind those antigens, Immunovaccine exclusively in-licensed them. (See BioWorld Today, Nov. 14, 2013.)

Immunovaccine quickly put the antigens in Depovax to create its first cancer vaccine, DPX-0907. In about a year the company conducted a phase I in about 23 prostate cancer patients. While the firm were running the trial, execs started to connect with Merck KGaA, which had a cancer vaccines focus on the target survivin. Merck was losing interest in the program, which was making an unimpressive showing in a phase I, Mansour said. "They had good antigens, but they weren't formulated the right way. They didn't have an adjuvanted delivery platform for it."

Immunovaccine ended up in-licensing the antigens on an exclusive worldwide basis to create its second vaccine, DPX-Survivac. It quickly took the program into a phase I trial focused on ovarian cancer. "That's when our thinking around immune therapies began to evolve and mature," Mansour said.

Now the company is focused not just on having the right targets and adjuvanting them properly, but also "really thinking about the therapeutic area we're going into and how a cancer vaccine fits."

THROUGH THE RANKS

Since its founding in 2002, when a three-person team spun the company out from Halifax's Dalhousie University, Immunovaccine has grown to a team of 20 employees today. When Mansour talks about it, he speaks easily, fueled by an intimate knowledge of the company's ascent since he first joined as a staff scientist more than 12 years ago. Since then, he's served as the company's chief operating officer, chief scientific officer. Finally in June, he took the next logical step to become CEO.