Bisantrene is a small molecule anthracene-based chemotherapeutic that was originally developed by American Cyanamid (Lederle Laboratories) in the 1970s & 1980s with the goal of creating a less cardiotoxic/toxic anthracycline-like chemotherapeutic.
The drug was approved in France for relapsed or refractory (R/R) acute myeloid leukemia (AML) in 1990, however it was not commercialised and was lost to the clinical community for over 30 years due to various merger and acquisition transactions.
Bisantrene & cardio-protection
Bisantrene has been evaluated in over 46 clinical trials and 70 peer reviewed publications, with around 1.8k patients treated, demonstrating efficacy and a well characterised safety profile.
Anthracyclines have been the most administered category of chemotherapy agents for decades, however they can cause significant toxicity in the body. Lifetime limits of anthracyclines are enforced due to the risk of potentially fatal, congestive heart failure.
Studies have shown bisantrene reduces risk of cardiotoxicity and has higher tolerability than anthracyclines, while also demonstrating cardio-protection when used in conjunction with anthracyclines.
Race’s clinical program for bisantrene has been designed to build on the strong foundation of existing clinical data in AML, while also focusing on the drug’s anti-cancer and cardio-protective potential in the high unmet need area of breast cancer.
Bisantrene & FTO
Important scientific discoveries made over the last decade have identified dysregulation (loss of control) of RNA epigenetics (methylation) as a key driver in cancer development. One of the major players in this dynamic regulatory system is the Fatso or FaT and Obesity associated protein (FTO).
In 2011, FTO was identified as an m6A RNA demethylase and subsequent research has identified FTO to be a major global regulator of the m6A RNA epigenetic status in cells.
Other investigators have shown that changes in the expression of the FTO protein have a profound impact on both cancer development and metastasis.
Inhibiting FTO activity in cells has been found to kill or slow the growth of a wide range of cancers including leukaemia, breast, lung, ovarian, gastric, brain, melanoma, pancreatic, kidney and many more. Unsurprisingly, RNA epigenetic dysregulation has become one of the hottest areas of cancer research.
Recent studies by the City of Hope, identified bisantrene as the most potent enzymatic inhibitor of FTO (IC50 142nM) from a screen of more than 260,000 chemical compounds contained in the US National Institute of Health’s (NIH) National Cancer Institute’s (NCI) chemical library. The research also demonstrated in both cell and animal models, that bisantrene specifically killed FTO overexpressing cancers when used at concentrations far below that known to be toxic in humans.
Race has a worldwide license agreement with City of Hope that exclusively secures the rights to a City of Hope patent application and associated know-how to collaborate to elucidate the mechanism of action of bisantrene, and the role of FTO to develop a targeted approach with subsequent biomarker development.
History of bisantrene
Bisantrene was originally developed by Lederle Laboratories (a division of American Cyanamid) in the 1970s as an alternative to the commonly used anthracycline chemotherapeutics. Lederle and collaborators trialled bisantrene in the 1980s in more than 50 clinical trials containing over 1500 patients, where it showed activity in wide range of cancers including leukemias, breast cancer and ovarian cancer.
These clinical trials demonstrated that bisantrene was an effective anticancer chemotherapeutic with reduced cardiotoxicity.
In 1988, bisantrene was approved in France for relapsed or refractory (R/R) acute myeloid leukemia (AML) in 1988, however was never brought to market for non-clinical reasons.
What happened to bisantrene is not uncommon in the pharmaceutical industry. The drugs we have today are the lucky survivors of a brutal battle that few candidates survive. Many good drugs were lost along the way and are candidates for rediscovery.
Clinical pipeline
Race is progressing a robust pipeline of clinical activities for bisantrene to maximise commercialisation and partnership opportunities to benefit cancer patients worldwide.
