Pipeline: CS-6 “The Stealth Bomber” program

Novogen designed its first library of super-benzopyrans to target the most common form and the most aggressive type of primary brain cancer; glioblastoma multiforme (GBM).

GBM has a very poor prognosis and is invariably fatal for three main reasons:

Glioma cells are very poorly sensitive to conventional therapies of radiation and drugs.
The brain is very susceptible to damage from conventional therapy, limiting dosages to sub- therapeutic levels.
The blood–brain barrier effectively blocks most anti-cancer drugs from reaching the cancer.

To meet this challenge, the design criteria for the first Novogen drug discovery library stipulated new test molecules meet the following 5 criteria:

Have broad activity against all human cancer types at micromolar or nanomolar potency.
Have significant activity against a range of glioma cell lines.
Have excellent pharmaceutical properties, specifically pharmacokinetic profile.
Have molecular design properties that meet the known structural criteria for ability to cross the blood-brain barrier.
Have the capability of being manufactured efficiently.

The first library of super-benzopyrans afforded several hit molecules that met our stringent internal criteria to be considered for further development. The graph below indicates the relative activity of a series of compounds from the initial library. In this data a compound that has excellent cancer activity has the lowest sized bars: a low bar indicating very little compound is required to kill cancer cells. This data clearly indicates that while a series of molecules met our design criteria, CS-5 and CS-6 were clear standouts. Deeper analysis of the data indicated that CS-6 met even the most stringent of our internal design criteria as a potential drug for the treatment of GBM. This identified CS-6 as progressing from a hit to a lead compound.

Critically CS-6 demonstrated another fundamentally important benefit … an ability to avoid the action of drug-elimination enzymes that are present in some cancer cells and which effectively reduce the ability of anti-cancer activity of drugs such as benzopyrans. This effect is related to one of the sub-units in CS-6 having subtle remote effects on other parts of the CS-6 molecule. These remote effects manifest themselves as modulation of the electric field density at critical parts of the molecule that interact with these drug-elimination enzymes. The results to date have demonstrated that CS-6 is active against specific cancer cell lines that have high levels of these enzymes; indicating CS-6 has higher access to cancer cells and remains intact as it enters and kills the cell. Our analogy is that CS-6 can act like a stealth bomber – successfully avoiding the cancer cells natural defenses. This stealth technology is an important component of the Company’s overall technology platform.

CS-6 is now progressing through the next advanced phase of pre-clinical screening. Details of the progress of CS-6 will be updated in the LATEST NEWS part of this site.

CS-6XX Program

The treatment of many cancers now involves the use of cocktails of drugs, in place of a single agent. A pertinent example is the cocktail of drugs used to treat triple positive breast cancer; a form of the disease whereby the cancer cells express hormone and HER-2 receptors on the cell surface. These cancers are treated with not just cancer killing drugs, such as docetaxel but also the HER-2 therapeutic agent Herceptin. In effect these drugs act synergistically whereby the effect of both drugs in combination is far greater then the benefit of using each drug in isolation. The CS-6XX program is generating libraries of molecules that will be developed as potential dual therapy super-benzopyrans. The dual therapy development strategy comprises testing the new super-benzopyrans concert with standard of care chemotherapeutic agents. The aim is to develop comprehensive cancer treatments using the new class of super-benzopyrans synergistically with existing chemotherapy.