Potential of Anisina to Become Major New Chemotherapy Confirmed by Coda Study
SYDNEY, March 19, 2015 /PRNewswire/ — Novogen announced on 18th March, 2015 that one of its oncology pipeline drug candidates, Anisina (ATM-3507), has achieved a major milestone in its development, confirming the concept that comprehensive destruction of a cancer cell’s cytoskeleton can deliver a powerful anti-cancer effect.
Dr Kelly was interviewed by Channel 7 health reporter, Dr Andrew Rochford about Anisina’s potential. To view the interview click here… or visit the Novogen website.
The cytoskeleton (cell skeletal structure) is a common and validated target for anti-cancer therapy. The most commonly used drugs in chemotherapy target the cytoskeleton by destabilising one of its two key components, the microtubules. These drugs are known as ‘anti-mitotics’ and include the taxanes (paclitaxel, docetaxel) and the vinca alkaloids (vincristine, vinblastine). Collectively, these anti-mitotics have dominated chemotherapy for the past 30 years and look set to do so for many years to come.
The rationale behind the development of Anisina was that the anti-mitotic drugs only do half the job, because they leave the other major component of the cytoskeleton, the microfilaments, intact. It was reasoned that this half-complete destruction of the cytoskeleton by the anti-mitotic drugs accounted for their low rate of patient response for many tumor types and for the generally short-term response to therapy. Anisina was developed specifically to destroy the microfilaments and to work in combination with the anti-mitotic drugs to deliver comprehensive destruction of the cancer cell’s architecture.
Anisina targets a specific protein known as tropomyosin Tpm3.1 (previously known as Tm5NM1). Tpm3.1 is a protein that provides structural integrity to the microfilaments of a cell. It is present in both normal cells and cancer cells, the difference being that cancer cells have an increased reliance on this form of tropomyosin to survive.
It has been announced previously that anti-tropomyosin drugs in combination with anti-mitotic drugs boost the cancer-killing ability of a drug such as vincristine 20-fold in vitro against neuroblastoma cancer cells.
The next crucial step was to confirm that this powerful combined anti-cancer effect was transferable to animals. The study reported today confirms this.
This proof of concept study was done as part of the Children’s Oncology Drug Alliance (CODA) involving Australian charity, The Kids’ Cancer Project (Sydney), The University of New South Wales (Sydney), The Nationwide Children’s Hospital (Columbus, Ohio), and Novogen. The studies were conducted using cancer cells derived from children who had developed neuroblastoma.
The full details of these studies will be presented at the Eighth Annual Cancer Molecular Therapeutics Research Association (CMTRA) meeting in the USA in July of this year.
Justine Stehn PhD, Novogen Anti-Tropomyosin Program Director, said, "This was the crucial step we needed to bring Anisina into the clinic. We now are proceeding to bring Anisina into the clinic in 2016 into both adults and children. In adults we will be looking to use Anisina to potentiate the anti-cancer effect of anti-mitotics in cancers such as prostate, ovarian, lung, breast, colorectal and haematological cancers, as well as in cancers such as melanoma where anti-mitotics currently show little benefit."
"But what particularly excites us from a CODA perspective is the promise that this technology holds in being able to achieve a potent anti-cancer effect in children where anti-mitotics currently are widely used, but being able to use lower dosages of anti-mitotics that hopefully will lower the risk of leaving children with side-effects with life-long consequences."
Graham Kelly PhD, Novogen CEO and Executive Chairman said, "From the outset, the anti-tropomyosin technology platform has held the promise of delivering a major new chemotherapy, one that we saw becoming a standard companion drug to the most commonly-used drugs in chemotherapy. Today’s announcement just serves to reinforce that promise."
"The promise of Anisina is that it is not a drug limited to working in a proportion of patients with a particular form of cancer, or one that is reliant on the over-expression of certain functions such as immune checkpoints or pro-survival mechanisms. Its promise lies in its ability to make the most widely-used chemotherapy drugs work better and safer in more forms of cancer and in more patients. Our objective is to see Anisina become one of the most widely used drugs in chemotherapy."
About Anti-mitotic drugs
Anti-mitotic drugs are drugs that block cell division (mitosis). This a shorthand term to describe a family of drugs that embraces mainly the taxanes (paclitaxel, docetaxel, Abraxane) and vinca alkaloids (vincristine, vinblastine, Vineralbine) and which work by blocking the ability of cells to divide (mitosis). These remain among the most widely prescribed anti-cancer drugs after 35 years of use. Anti-mitotic drugs are standard of care for breast, prostate, lung, ovarian, colo-rectal, gastric and head and neck cancer, and many forms of leukaemia.
About the cytoskeleton
The cytoskeleton provides the architecture of a cell. It is a protein structure that gives a cell its shape, ability to move and to divide and to store and move internal structures. It has two main components: the microtubules and the microfilaments. The key component of microtubules is the protein, tubulin, which is the target of the anti-mitotic drugs, and whose destabilisation leads to prevention of cell division (mitosis). The key components of the microfilaments are the proteins, actin and tropomyosin.
Tpm3.1 is a tropomyosin protein. Tropomyosins provide a rigid external scaffold to microfilaments that have a central actin core. Without this rigidity, the microfilaments are inactive. There are over 40 different forms (isoforms) of tropomyosin of which Tpm3.1 is one. Tpm3.1 is present in all cells; normal cells are able to survive and function without Tpm3.1; cancer cells are highly dependent on the presence of Tpm3.1 for their survival and function.
Anisina is a small molecule specifically designed to block the ability of Tpm3.1 to dimerize. By fitting into the C-terminus of the proximal Tpm3.1, it prevents dimerization of the N-terminus of the distal tropomyosin protein. Interruption of dimerization leads to the inability of the microfilaments in cancer cells to remain stable, resulting in their collapse.
CODA’s mission is to accelerate development of innovative new therapeutic approaches to the treatment of chlldhood cancers and to take account of the fact that childhood cancers are different to adult cancers and that the lifelong consequences of cancer drug side-effects can be far more devastating in a child than in an adult.
CODA unites the research and resources of five organisations in Australia and the US.
The Australian members are:
- The charity, The Kids’ Cancer Project
- The originator of the anti-tropomyosin technology, the University of New South Wales and its commercial arm, NewSouth Innovations
- Biotechnology company, Novogen Limited
The US member is:
- Nationwide Children’s Hospital, Columbus, Ohio
Novogen is providing access to both its anti-tropomyosin and super-benzopyran drug technologies. Anisina is being evaluated for its ability to complement the action of standard chemotherapies in childhood cancers. TRXE-009 is being evaluated for its ability to treat brain cancers in children.
Further information on CODA is available at www.childrensoncologydrugalliance.org
About Novogen Limited
Novogen is a public, drug-development company whose shares trade on both the Australian Securities Exchange (‘NRT’) and NASDAQ (‘NVGN’). The Novogen Group includes a New Haven CT – based joint venture company, CanTx Inc., with Yale University.
Novogen has two main drug technology platforms: super-benzopyrans (SBPs) and anti-tropomyosins (ATMs). SBP compounds have been created to kill the full range of cells within a tumor, but particularly the cancer stem cells. The ATM compounds target the microfilament component of the cancer cell and when used in conjunction with standard anti-microtubule drugs, result in comprehensive and fatal destruction of the cancer cell’s cytoskeleton. Ovarian cancer, colorectal cancer, malignant ascites, prostate cancer, neural cancers (glioblastoma, neuroblastoma in children) and melanoma are the key clinical indications being pursued, with the ultimate objective of employing both technologies as a unified approach to first-line therapy.
Further information is available on our websites www.novogen.com
For more information please contact:
Dr. Graham Kelly
Executive Chairman & CEO
+61 (0) 2 9472 4100
Chief Operating Officer
+61 (0) 2 9472 4111
Forward Looking Statement
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