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Oct 16, 2014

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Scientist aims to speed drug for vascular health through innovation pipeline

By Alisa Kim

The process of getting a new drug to market is lengthy and exceedingly expensive. But for Dr. Dan Dumont, a senior scientist at Sunnybrook Research Institute, the odds of doing just that are better thanks to a $1.5 million investment from Genome Canada, Vasomune Therapeutics and an industry partner.

The award was made through Genome Canada’s Genomic Applications Partnership Program, which supports the commercialization of genome-based technologies.

The technology is Vasculotide, a drug that was engineered in Dumont’s lab at SRI eight years ago by Dr. Paul Van Slyke, who was then his PhD student. A condition of the award is acquiring matching funds from industry. Dumont has secured $500,000 from each of a medical products company and Vasomune Therapeutics, an SRI startup created in partnership with MaRS Innovation that is commercializing the treatment.

“The money is there to fill that translational gap—to get [Vasculotide] from the bench to the bedside. We’ve been able to raise about $6 million, and it’s all been [for] pretranslational and developmental work. Now we need to get it to the point where we’re in front of Health Canada and the [U.S. Food and Drug Administration] to be able to put it into a patient,” says Dumont, who is also a professor at the University of Toronto and the Canada Research Chair in Angiogenic and Lymphangiogenic Signalling.

Vasculotide mimics the actions of angiopoietin-1 (Ang-1), a protein made by our bodies that binds to and activates Tie-2, a receptor on endothelial cells that line the inside of blood vessels. When Ang-1 and Tie-2 are engaged, the attachments between endothelial cells become tighter, preventing the leakage of blood and other solutes outside the vessel.

In short, says Dumont, “Ang-1 is a gatekeeper of vascular health. Ang-2, a related protein, plays a role in destabilizing or making vascular health worse. In disease you’ve got more Ang-2. With Vasculotide, which is an Ang-1-like molecule, you start doing this,” he says, moving his hands mimicking weights on a scale. “[Vasculotide] brings balance, and that maintains or re-establishes vascular health.”

Vasomune’s initial focus is treatment of acute kidney injury (AKI), a disease marked by rapid loss of kidney function that can be caused by decreased blood flow. There is no treatment for AKI, which strikes up to 20% of patients in intensive care units. Thus, doctors concentrate on managing symptoms.

Studies of Vasculotide have shown it is effective in treating preclinical models of AKI by preventing leakage of blood vessels within the kidney, which can cause swelling. This swelling in turn restricts blood flow. “For many renal diseases, including AKI, there’s almost always interrupted blood flow in the kidney and we aim to restore that,” says Van Slyke.

Having completed the necessary preclinical research, Vasomune is transitioning to pharmacokinetics and toxicology studies. It seeks to understand how long Vasculotide circulates in the body, the length of time it activates the target Tie-2, how much of the drug can be given, and the toxicology profile required for drug development and clinical trials.

“This award, in combination with industry funding, validates the Vasculotide opportunity and gives us required funds to advance the asset toward the clinic,” says Parimal Nathwani, president and CEO of Vasomune.

Dumont notes they have worked on the drug’s chemistry to make it easier to purify. “We know it works; now the goal is to prove we can put this into patients—convincing ourselves, Health Canada and the Food and Drug Administration that it’s a safe molecule [that’s] not going to harm anybody is next on the 'to do' list.”

Dan Dumont