Activating the innate and adaptive immune system to recognize and attack tumors

A large number of cancers will respond to PD-1/PD-L1 checkpoint inhibitors; however, for patients with tumors that do not already express PD-L1, response to approved agents is often limited or minimal. PORT-2 and PORT-3 may be able to activate the immune response in these patients to effectively identify and target the tumor.

Portage Biotech’s invariant natural killer T-cell (iNKT) agonists, PORT-2 and PORT-3, lead to a broad reprogramming of the innate and adaptive immune system, enabling the body to recognize and attack tumors that contain few immune cells and usually go undetected. Both may be used alone or in combination with checkpoint inhibitors, potentially helping more patients respond to treatment.

To learn more about Portage’s iNKT agonists, download our fact sheet.

PORT-2

PORT-2 is an iNKT agonist (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 is 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.

PORT-3

Portage’s iNKT agonist, 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 agonist 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.

Pipeline

PLATFORM
TECHNOLOGY
ASSET
INDICATION
STAGE
TECHNOLOGY
iNKT Agonists
Liposomal Formulations
ASSET
IMM60
INDICATION
Melanoma
STAGE
Phase I/II
TECHNOLOGY
iNKT Agonists
Liposomal Formulations
ASSET
IMM60 + Keytruda
INDICATION
Melanoma
STAGE
Phase I/II
TECHNOLOGY
iNKT Agonists
Liposomal Formulations
ASSET
IMM60 + Keytruda
INDICATION
NSCLC
STAGE
Phase I/II
TECHNOLOGY
iNKT Agonists
Liposomal Formulations
ASSET
IMM60 + Cell Therapy
INDICATION
Solid Tumors
STAGE
Preclinical
TECHNOLOGY
iNKT Agonists
Nanoparticle co-formulations
ASSET
(IMM60 / NY-ESO-1) + Keytruda
INDICATION
NY-ESO-1 Positive Tumors
STAGE
Phase I/II
TECHNOLOGY
iNKT Agonists
Nanoparticle co-formulations
ASSET
(IMM60 / NY-ESO-1) + Keytruda
INDICATION
NY-ESO-1 Bladder & Ovarian
STAGE
Phase I/II