Last year, OncoMyx Therapeutics unveiled preclinical data showing its engineered rabbit pox virus therapy could slow tumor growth in mouse models of melanoma and bone cancer. Now, it's unveiling more preclinical evidence, this time in non-small cell lung cancer (NSCLC).
To make its therapy, OncoMyx armed the rabbit pox virus, called myxoma virus, with genes encoding for the cytokine interleukin-12 and the sugared protein decorin. In a mouse model of NSCLC, the drug successfully slowed tumor growth, according to results unveiled at the American Association for Cancer Research (AACR) virtual annual meeting.
OncoMyx believes the data build on a growing body of evidence that supports the development of its oncolytic virus, which its scientsts are engineering to carry therapeutic proteins that directly eliminate cancer cells while simultaneously stimulating an anti-tumor immune response.
The virus at the core of OncoMyx’s therapy doesn’t cause disease in humans but can infect cancer cells, allowing it to be systemically administered via intravenous infusion. As a DNA virus, it's quite large, making it amenable to an engineering process that allows it to express other genes.
For the therapy described at AACR, OncoMyx picked IL-12 and decorin to pair with the virus because they are known for their immune-modulating mechanisms. The theory was that IL-12 and decorin would create a hostile immune environment that would make it difficult for cancer cells to survive. In lab dishes, the engineered virus was able to neutralize a broad range of cancer cell lines, including those from lung, skin and gastrointestinal cancers.
The drug also boosts interferon-alpha, interferon-gamma and IL-12 signaling pathways, which are associated with anti-tumor immune responses, according to OncoMyx. Previously, the company had shown that its multi-armed myxoma-based oncolytic therapy could modulate immune cell populations entering tumor cells, increasing the ratio of anti-tumor immune cells to immune-suppressing cells.
But systemic exposure to a virus and inflammatory molecules could potentially pose a safety threat, causing an overstimulated immune system to hurt healthy tissues. OncoMyx used a computer model to determine that at the planned doses, “the upper range of predicted systemic cytokine exposure in humans is still expected to fall within known safety margin,” the company said in a poster presentation.
OncoMyx tested the drug in immunodeficient mice bearing human NSCLC cells. The multi-armed viral therapy slowed tumor growth better than control or unedited myxoma virus did, the company found. The therapy also extended the lives of rodent models of breast cancer, melanoma and osteosarcoma.
“We are steadfastly building a substantial amount of data supporting the safety and efficacy of our multi-armed myxoma virotherapy as an important oncolytic immunotherapy for the treatment of cancer,” OncoMyx’s chief scientific officer, Leslie Sharp, Ph.D., said in a statement. “These data presented over the last five months show myxoma virus can be constructed to stimulate anti-tumor immunity and produce anti-tumor efficacy in a wide range of models following IV or IT administration.”