Science

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 leukaemias, 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), however the drug was never brought to market due to the challenges around its solubility and not being able to deliver it to patients peripherally.

Bisantrene & AML

Bisantrene has a long history of efficacy in AML having been approved for use in France in 1988 although never marketed.

Historical studies

  • 146 patients treated across 10 monotherapy R/R AML studies demonstrated an average complete response rate of 46%.

Recent studies

  • Positive single agent Phase 2 R/R AML data from Investigator Sponsored Trial (IST) in Israel with a 40% overall response rate (July 2020).
  • Positive triple agent Phase 1/2 R/R AML data from a follow-on IST in Israel in a very heavily pre-treated AML patients with 40% response rate (November 2023).

Bisantrene & breast cancer

Bisantrene was studied in seven Phase 2 and Phase 3 breast cancer trials in the 1980s. A large Phase 3 trial demonstrated that bisantrene outperformed mitoxantrone and provided a similar overall survival of doxorubicin (current standard of care chemotherapeutic), but with significantly lower rates of serious damage to the heart (4% bisantrene, 12% mitoxantrone, 23% doxorubicin).

In preclinical breast cancer studies conducted by Race Oncology, bisantrene demonstrated strong anticancer efficacy and strong cardioprotective capabilities.

  • In vitro studies in triple negative metastatic breast cancer cells have demonstrated that bisantrene in combination with doxorubicin improved anticancer efficacy, when compared to doxorubicin alone.
  • In vitro studies in human primary cardiomyocytes (heart muscle cells) and in vivo studies in an established mouse model of anthracycline cardiotoxicity bisantrene was able to protect the heart from anthracycline damage.

Bisantrene & m6A RNA

Race is investigating the effect of bisantrene on the m6A RNA pathway, following independent research published by the City of Hope identifying bisantrene as a potent inhibitor of FTO (Fat mass and obesity- associated protein). Dysregulation of the m6A RNA pathway has been described in numerous peer reviewed studies as a driver of a diverse range of cancers.

As part of its clinical trial, Race will investigate the effects of bisantrene on the m6A RNA system to better understand the opportunities in this area.

Bisantrene & AML

Bisantrene has a long history of efficacy in AML having been approved for use in France in 1988 although never marketed.

Historical studies

  • 146 patients treated across 10 monotherapy R/R AML studies demonstrated an average complete response rate of 46%.

Recent studies

  • Positive single agent Phase 2 R/R AML data from Investigator Sponsored Trial (IST) in Israel with a 40% overall response rate (July 2020).
  • Positive triple agent Phase 1/2 R/R AML data from a follow-on IST in Israel in a very heavily pre-treated AML patients with 40% response rate (November 2023).

Bisantrene & breast cancer

Bisantrene was studied in seven Phase 2 and Phase 3 breast cancer trials in the 1980s. A large Phase 3 trial demonstrated that bisantrene outperformed mitoxantrone and provided had a similar overall survival of doxorubicin (current standard of care chemotherapeutic), but with significantly lower rates of serious damage to the heart (4% bisantrene, 12% mitoxantrone, 23% doxorubicin).

In preclinical breast cancer studies conducted by Race Oncology, bisantrene demonstrated strong anticancer efficacy and strong cardioprotective capabilities.

  • In vitro studies in triple negative metastatic breast cancer cells have demonstrated that bisantrene in combination with doxorubicin improved anticancer efficacy, when compared to doxorubicin alone.
  • In vitro studies in human primary cardiomyocytes (heart muscle cells) and in vivo studies in an established mouse model of anthracycline cardiotoxicity bisantrene was able to protect the heart from anthracycline damage.

Bisantrene & m6A RNA

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 regulator of the m6A RNA levels in cells.

Other investigators have shown that changes in the expression or activity of the FTO protein have a profound impact on both cancer development and metastasis. Inhibiting FTO activity 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. Inhibition of FTO activity has been found to overcome anticancer drug resistance and to synergise with a range of anticancer treatments to improve the anticancer response.

Recent studies by the City of Hope, identified bisantrene as the most potent inhibitor of FTO 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.

Race has entered a worldwide license agreement with City of Hope that exclusively secures the rights to a City of Hope patent application and associated know-how identifying that bisantrene may be the most potent inhibitor of the FTO pathway.

As part of its clinical trial, Race will investigate the effects of bisantrene on the m6A RNA system to better understand the opportunities in this area.