Not all viruses are equal.
Myxoma viruses are ideal for multi-armed, targeted, systemic virotherapies.
To target multiple points in the cancer immunity cycle, 2-5 genes can be engineered into the myxoma virus.
Our myxoma virotherapy can be administered via intravenous (IV) delivery or our proprietary ex vivo virotherapy (EV2).
A nonhuman virus provides improved safety and efficacy profile, with longer dosing window and easier handling.
Myxoma virus selectively kills a wide variety of human cancer cells but not normal cells.
A subset of viruses, called oncolytic viruses, can naturally target and kill cancer cells. This activity was discovered by chance more than a century ago, as a beneficial side effect of influenza infections in leukemia patients. Since then other human viral pathogens, including viruses that cause polio, herpes, and respiratory diseases, have been genetically engineered to reduce pathogenicity and increase oncolytic activity. In addition to safety, these viruses must also overcome pre-existing immunity, established through natural human infections or vaccinations. Myxoma virus is nonpathogenic and naturally immunostimulatory in humans but inherently and selectively propagates and kills a wide variety of human cancer cells, providing an improved safety and efficacy profile.
Multi-armed myxoma virotherapies target multiple points of the cancer immunity cycle.
Cancer cells evolve ways to escape the various search-and-destroy components of the immune system, which has been described as a cancer immunity cycle. The goal of cancer immunotherapy is to reactivate all the steps of the cycle against cancer to durably or completely eradicate cancer, without harming normal cells. To do this most effectively, therapies must either be combined or able to hit multiple targets. In the field of oncolytic viruses, myxoma’s large dsDNA genome (~162 kbp) allows for insertion of multiple genes to “arm” the virus and target multiple steps of the cancer immunity cycle. Myxoma also has a natural capacity to be immunostimulatory in human dendritic cells. With multi-armings, myxoma can deliver immune activators, modulate the tumor microenvironment, enhance other therapies, and target common cancer drivers.
An expanded precision mechanism approach is possible with myxoma virotherapy.
Targeted therapies have traditionally been small molecule kinases that target less than 2% of cancers driven by a specific genetic mutation. While this gives very high response rates for approval, it is difficult to cost-effectively identify these patients. For immunotherapies, conversely, they have been only a few minor targeting approaches, including microsatellite instability and tumor mutation burden. Leveraging both the unique tropism of myxoma and our ability to multi-arm the virus, we can uniquely pursue a precision mechanism approach with oncolytic viruses to target mechanisms that are enriched across a wide range of cancers. By precisely targeting the mechanisms that drive cancers rather than mutations, we can expand the number of patients who can benefit from immunotherapy.
Myxoma can be delivered intravenously or via ex vivo virotherapy.
We are advancing proprietary delivery systems for intravenous delivery and ex vivo virotherapy. Our primary goal is direct intravenous delivery. In addition, ex vivo virotherapy of myxoma virus has shown potential in treatment of hematological cancers. Systemic delivery of oncolytic viruses enables the treatment of both solid tumors and metastatic cancer. Our proprietary systemic delivery approach shields the virotherapy with a protective carrier that is designed to enhance delivery to cancer sites and maximize anti-tumor activity. Furthermore, because myxoma is not pathogenic to humans, it may be able to be safely delivered systemically at higher doses and over a longer dosing period than other oncolytic viruses.
Our scientific cofounder Dr. Grant McFadden and his collaborators have published more than 30 peer-reviewed research papers evaluating the myxoma virus (MYXV) as an oncolytic agent in a variety of tumor models. Here is a selection of publications for reference.
Oncolytic virotherapy for small-cell lung cancer induces immune infiltration and prolongs survival
Ex Vivo Oncolytic Virotherapy with Myxoma Virus Arms Multiple Allogeneic Bone Marrow Transplant Leukocytes to Enhance Graft versus Tumor