Background on Cancer

Cancer is the second-leading cause of death worldwide. According to the International Agency for Cancer Research (“IACR”) there were 14.1 million new cancer cases, 8.2 million cancer deaths and 32.6 million people living with cancer (within 5 years of diagnosis) in 2012 worldwide. The American Cancer Society estimates that in 2016 there was approximately 1.7 million new cases and approximately 595,000 deaths from cancer in the United States.

Cancer is characterized by abnormal cells that grow and proliferate, forming masses called tumors. Under the right circumstances, these proliferating cells can metastasize, or spread, throughout the body and produce deposits of tumor cells called metastases. As the tumors grow, they may cause tissue and organ failure and, ultimately, death.

The most common methods of treating patients with cancer are surgery, radiation and drug therapy. A cancer patient often receives treatment with a combination of these modalities. Physicians generally use systemic drug therapies in situations in which the cancer has metastasized and spread beyond the primary site or cannot otherwise be treated through surgery. Active immunotherapies, such as our ReVax product candidates, are designed to stimulate the immune system, the body’s natural mechanism for fighting disease, to mount a specific response to tumor cells; this approach may target both primary tumor sites as well as metastasis and may overcome some of the limitations of current standard-of-care cancer therapies.

 Tumor Marker Glycolipids and Cancer

It has been known for decades that a unique class of neoantigen carbohydrates, called tumor marker glycolipids ("TMGs"), are highly overexpressed in a large number of widely prevalent tumors, but to date have not been targetable using an active immune response (such as vaccines). For example, the TMG known as GD2 is a clinically-validated target, given there are two approved passive immunotherapies (monoclonal antibodies) against GD2, but these products are expensive, have significant side-effects, require co-administration of other products (GM-CSF, IL-2 etc.) and are not particularly effective.

TMGs have homogeneous expression within the tumor and are expressed at very high levels in each cancer cell (i.e. up to millions of copies per cell) in a high percentage of patients in certain cancer indications (with the precise indications depending on the TMG in question). TMG expression is stable, and according to the scientific literature is not down-regulated in tumors, even after chemotherapy.

TMGs also perform specialized functions in signal transduction, cell-cell and cell-extracellular matrix interactions, and are functionally implicated in transformation and cancer growth.

To our knowledge, Realist is the first company to develop products capable of successfully targeting these TMGs using an active immunity therapeutic paradigm, which we do by activating a robust and selective immune response against cancers, primarily through a T cell-mediated response.