Technology

What is Pelareorep

Pelareorep is a proprietary isolate of a naturally occurring, non-pathogenic double-stranded RNA (dsRNA) virus commonly found in environmental waters, known as reovirus. It is being developed as a first-in-class intravenously delivered immunotherapeutic agent for the treatment of solid tumors and hematological malignancies. It activates the innate and adaptive immune systems and weakens tumor defense mechanisms. This improves the ability of the immune system to fight cancer, making tumors more susceptible to a broad range of oncology treatments.

Pelareorep activates the innate and adaptive immune systems and weakens tumor defense mechanisms. This improves the ability of the immune system to fight cancer, making tumors more susceptible to a broad range of oncology treatments. Pelareorep has demonstrated synergies with immune checkpoint inhibitors and may also be synergistic with other approved oncology treatments, including CAR T therapies, bispecific antibodies, and CDK4/6 and PARP inhibitors. We are currently conducting and planning clinical trials evaluating pelareorep in combination with checkpoint inhibitors and targeted therapies in solid and hematological malignancies as it advances towards a registration study in metastatic breast cancer.

Mechanism of Action

How Pelareorep Works

Clinical trials have provided us with a multitude of observations and conclusions thus far regarding the effectiveness of pelareorep in normal cells versus cancerous cells.

Normal Cells/Cancer Cells

In normal cells
In non-cancer cells, pelareorep enters the cells but is unable to replicate and the virus is actively cleared.

In cancer cells
pelareorep selectively replicates in permissive cancer cells. Upon virus replication, cancer cells lyse/die releasing additional virus particles to infect nearby cancer cells.

Direct Cell Lysis

Pelareorep is able to selectively replicate in cancer cells, but not in normal cells due to a number of factors that are unique to cancer cells, including:

  • Defective cell signaling pathways
  • A high level of genomic mutations (or mutations in key tumor suppressor genes and oncogenes)
  • Cellular stress from chemo and radiation therapy

Pelareorep enhances the body's natural anti-cancer immune response by activating both the innate and adaptive immune systems, converting immune unresponsive 'cold tumors' into immune responsive 'hot tumors'.

Pelareorep Innate Immune Response

Cancer cells infected with pelareorep release inflammatory cytokines. This inflammatory milieu activates natural killer (NK) cells and promotes the migration of NK cells, dendritic cells, and T-cells, to the tumor microenvironment which aids in immune cell mediated cancer cell death.

Pelareorep Adaptive Immune Response

Following pelareorep mediated cancer cell death, the release of the tumor and viral associated antigens are taken up by antigen presenting cells (APCs). APCs then process and present antigens to T-cells. This trains the adaptive immune system to recognize and kill cancer cells. An adaptive immune response allows for: existing cancer cells to be eliminated, constant cancer cell surveillance, relapse prevention, and increased overall survival.