INxin™ Platform

Protox uses genetic engineering to transform naturally occurring proteins into novel targeted therapeutics for cancer and other proliferative diseases.

Protox’s lead INxin™ drug, PRX321, is a novel protein comprised of interleukin-4 (IL-4), a protein that stimulates the immune system, in combination with Pseudomonas exotoxin. The IL-4 portion of PRX321 has been designed so that the molecule can bind with a very high level of specificity to IL-4 receptors on the surface of cancer cells. The IL-4 receptor is an attractive target since studies have shown it to be highly expressed in a large number of different types of cancer cells. The Pseudomonas exotoxin portion of PRX321 has been designed to minimize undesirable side effects by reducing its ability to bind non-specifically to cells containing the Pseudomonas exotoxin receptor. Once internalized into the target cell, the toxin component of PRX321 causes cell death by arresting protein synthesis and inducing apoptosis or cell death. The combined features of PRX321 allow for specific targeting to IL-4 receptors on the surface of cancer cells while retaining the high potency of the toxin component.

Advantages of INxin™ Technology Platform

POTENCY – The engineered version of Pseudomonas exotoxin is a highly potent toxin derived from a well established bacterial toxin. A single targeted toxin molecule can react enzymatically in the cytosol to cause cell death. This engineered toxin has been combined with a variety of different targeting agents and is currently in clinical development for a number of cancer indications.

REDUCED TOXICITY – Native Pseudomonas exotoxin is not suitable for drug development since it destroys both healthy and cancer cells. The toxin has been engineered to reduce its non-specific toxicity while maintaining its ability to kill cancer cells. Combining our engineered toxin with a ligand that targets IL-4 receptors on cancer cells provides an additional level of specificity. Hence, INxin™ drugs are expected to have a relatively large therapeutic index compared to other chemotherapeutic drugs. Pre-clinical and clinical studies conducted to date have demonstrated that PRX321 can be a safe and effective treatment for a variety of solid tumors.

UNIQUE MODE OF ACTION – INxin™ drugs are internalized into the target cell via a mechanism that is independent of p-glycoprotein, a membrane associated protein that is commonly used to transport chemotherapeutic drugs. Mutations in p-glycoprotein often lead to cancer cells becoming resistant to traditional chemotherapeutic drugs, a problem not expected with INxin™ drugs since they do not rely on p-glycoprotein for entry into the cell. Another key advantage of INxin™ drugs is that they are effective against hypoxic cells. Hypoxic cells are cells within the tumor that are starved of oxygen and are more difficult to destroy since they can become resistant to radiation therapy and chemotherapeutic drugs. INxin™ drugs therefore have the potential to overcome many of the problems associated with resistance of cancer cells to treatment by traditional chemotherapies.  

MANUFACTURING – INxin™ drug candidates are manufactured by a simple and efficient fermentation-based process using a well established bacterial expression system. INxin™ production is therefore not affected by the inherent difficulties and high cost typically associated with the manufacture of antibody-based therapies.

BROAD PLATFORM – INxin™ drug candidates can be developed to treat any cancer in which IL-4 receptor is overexpressed.  Besides primary brain cancer, renal cell carcinoma and non-small cell lung cancer, Protox plans to develop PRX321 for a range of other peripheral solid and hematological tumors.