GRN-1201

GRN-1201 is a novel cancer peptide vaccine targeting four novel tumor-associated antigens common to major cancer types. The peptides of GRN-1201 are restricted to HLA-A2, which comprises approximately 50% of the populations in the US and Europe, as well as 40% of the population in Japan.

An open-label Phase I clinical trial for melanoma and a Phase II clinical study in combination with an immune checkpoint inhibitor for non-small cell lung cancer are ongoing in the US.

The development of GRN-1201 is focused on combination therapies with other immune checkpoint inhibitors, such as anti-PD-1-blocking antibodies.

The immune system distinguishes between normal cells (self) and those it sees as "foreign" cells, which trigger the immune system to attack the foreign cells only. The trigger depends on "checkpoints" - molecules on certain immune cells that need to be activated (or inactivated) to initiate an immune response. Cancer cells sometimes utilize "brake" type checkpoints, which normally function to prevent the immune system from attacking normal cells in the body, to evade immune attack. Immune checkpoint inhibitors block the "brake," that is, the binding of checkpoint molecules on immune cancer cells, and unleash the immune response to kill the cancer cells. With their remarkable clinical outcomes, immune checkpoint blockades have been remodeling the cancer-treatment landscape.

However, the response rate to these immune checkpoint inhibitors as monotherapy is reported to be 10-40%, depending on the cancer types and stages, which means that a sufficient therapeutic effect is not achieved in 60-90% of patients. One reason for this low effective rate is an inadequate capacity to induce the immune system to eliminate cancer due to an insufficient supply of high-immunogenicity cancer antigens. In order for an immune checkpoint inhibitor to work effectively in the strongly immunosuppressive tumor microenvironment, it is crucial to infiltrate the tumor site with abundant cytotoxic T cells.

The functions of a cancer vaccine are to boost the immune response to TAAs and increase the activation of tumor-specific T cells, which infiltrate the tumor site and eliminate cancer cells. Therefore, cancer vaccines and immune checkpoint inhibitors are complementary, and the combination has the potential for synergistic effects. Further improvement of the efficacy of cancer immunotherapy can be expected by using our product in combination with immune checkpoint inhibitors.

To evaluate this potential, a Phase II clinical trial combining GRN-1201 with a checkpoint inhibitor for non-small cell lung cancer is ongoing.