PORxin™ Platform

Protox’s lead drug developed from its PORxin platform, PRX302, is an engineered version of proaerolysin, a protein secreted by the bacteria Aeromonas hydrophilia. Proaerolysin contains two important regions that allow it to exert its effect. The first is a binding site that allows the molecule to attach to the surface of a cell and the second is an “activation tail” that must be removed before it is able to form a pore. Protox has engineered the tail on PRX302 so it can be cut off and activated by prostate specific antigen (PSA), an enzyme that is produced at high levels in the prostates of patients with prostate cancer and BPH. Once bound and activated, PRX302 combines with other activated PRX302 molecules to form a mushroom shaped structure that is able to perforate the cell membrane. The cell contents leak out through the resulting pore and the cell dies. PRX302 is injected locally into the prostate to treat prostate cancer and BPH using “molecular surgery” which is much less invasive and potentially safer than traditional surgery. In the case of prostate cancer, the goal is to reduce the size of the tumor or eliminate the tumor altogether. In the case of BPH, lower amounts of PRX302 are used to reduce the size of the prostate, thereby restoring normal urinary function. Protox is also developing second generation PORxin drug candidates with altered binding sites. Altering the binding site may further increase the drug’s specificity, providing greater flexibility to administer and treat an even wider range of diseases. These molecules are currently at the discovery stage.

Advantages of PORxin™ Technology Platform

The PORxin™ technology has the potential to produce effective and potent therapeutics with minimal side effects via a unique mode of action.

POTENCY – Protox has engineered compounds that are not only selective but are extremely potent in the presence of certain proteases (a type of enzyme) produced by target cells. An amount of PRX302 as small as a grain of salt is enough to destroy a tumor the size of a golf ball.

REDUCED TOXICITY – It is expected that drug candidates generated through the PORxin™ technology platform will have fewer side effects than traditional or current treatments. Because PORxin™ candidates can be engineered to contain specific binding and/or activation sites which make them selective to target cells, there is a reduction in the likelihood of toxicity to neighboring healthy cells.

UNIQUE MODE OF ACTION – The ability of Protox’s therapeutics to form a pore in the cell membrane is not only a unique mechanism of action but advantageous as well. Exerting its action outside the cell eliminates the need and sometimes difficulty of getting a drug inside a cell. In addition, many cancer therapies rely on the fact that cancer cells are rapidly dividing—in the case of PORxin™, there is no requirement for cells to be growing so quickly. This is beneficial in particular for prostate cancer which is inherently a slower growing cancer.

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

BROAD PLATFORM – By modifying the binding and activation regions, toxins such as proaerolysin can be engineered to form a variety of unique drug candidates that act on different types of cancers and other diseases. In the future, Protox plans to combine its own drug candidates with other targeted molecules such as antibodies or ligands in order to further increase the drug’s specificity. Such dual targeting may lead to even greater efficacy and safety than either approach alone.