iNKT platform

PORT-2 is a small molecule iNKT engager (IMM60) packaged in a liposome, which optimally activates multiple components of the immune response and inhibits negative signals in the tumor microenvironment. As a result, cancer cells increase the expression of PD-L1 as an immunotherapy target, enabling the body to better recognize and fight the tumor.

Preclinical data shows that PORT-2 as a monotherapy leads to a heightened immune response seen in PD-1-resistant and PD-1-sensitive animal models. When used in combination with PD-1 checkpoint inhibitors, PORT-2 shows an even greater increase in PD-L1 expression, indicating a higher sensitivity to treatment.

Through a clinical trial sponsorship agreement with Oxford University, Portage was conducting a Phase 1/2 safety trial for PORT-2 alone and in combination with PD-1 checkpoint inhibitors in patients with non-small cell lung cancer (NSCLC) and melanoma, the trial is now paused.

Portage’s iNKT engager, IMM60, can also be co-delivered with antigen-specific vaccines to target tumors that express a specific antigen, such as NY-ESO-1. Preclinical data suggests that when packaged into a single treatment, co-formulations are up to five times more potent than when treatments are given individually. The proximity of treatment increases the potency by allowing each treatment to reach the target cell at the same time and work simultaneously. PORT-3 is a nanoparticle co-formulation of the iNKT engager IMM60 and NY-ESO-1 peptide antigens.

Preclinical data for PORT-3 was published in the journal Frontiers in Immunology in February 2021 and demonstrated good tolerability and a strong cancer-specific B and T-cell response. Portage initiated a Phase 1 trial for PORT-3 in NY-ESO-1 positive tumors in 2020 and dosed its first patient in Europe in April 2021. If the initial proof-of-concept trial is successful, Portage intends to design additional co-formulations with other tumor-specific antigens, potentially offering a new treatment paradigm for patients with limited other options.