Race Oncology Ltd (ASX:RAC, OTC:RAONF) has presented new preclinical data suggesting its (E,E)-bisantrene can both protect the heart and boost tumour-killing activity when combined with standard-dose doxorubicin, with the findings showcased at the European Society for Medical Oncology (ESMO) Congress in Berlin (October 17-21, 2025).
The poster — Discovery of (E,E)-bisantrene as a dual-cardioprotective and anticancer agent in combination with doxorubicin — summarised results across in vitro and in vivo models:
- Anticancer activity: Adding bisantrene to doxorubicin lowered the IC50 across a panel of 111 human cancer cell lines spanning 22 tissue types, indicating higher potency than doxorubicin alone. In a 4T1 syngeneic breast cancer mouse model, the combination improved survival versus either agent alone.
- Cardioprotection: Bisantrene reduced doxorubicin-induced cytotoxicity in primary human cardiomyocytes and neonatal rat ventricular myocytes and mitigated doxorubicin-driven beat-rate increases in induced pluripotent stem cell–derived cardiomyocytes. In animal studies (mice and dogs), the combo produced significant improvements in left-ventricular ejection fraction over doxorubicin alone.
- Mechanism: Race reports the cardioprotective effect follows a clinically validated pathway — reducing topoisomerase-2β–mediated double-strand DNA breaks in cardiomyocytes — similar to the mechanism of FDA-approved dexrazoxane. Unlike dexrazoxane, bisantrene is also described as stabilising G-quadruplex DNA/RNA structures, leading to down-regulation of the oncogenic regulator MYC, which may add anticancer benefit when paired with doxorubicin.
Race is advancing RC220, a proprietary formulation of (E,E)-bisantrene designed to improve solubility and enable peripheral IV administration. The company says the preclinical data support its ongoing Phase 1 dose-escalation study testing RC220 with standard doxorubicin (60 mg/m²) in advanced solid tumours (NCT06815575).
“It is an honour for me to be able to share Race’s MOA data at such a major international oncology congress. I wish to thank the entire Race preclinical team and all our collaborators for the amazing work they have done and which has enabled us to start treating cancer patients with the potentially practice-changing combination of doxorubicin and RC220,” CEO and managing director Dr Daniel Tillett said.
Doxorubicin remains a backbone therapy across multiple cancers but is limited by dose-dependent cardiotoxicity. Bisantrene, first tested clinically in the 1980s, historically showed broad antitumour activity with comparatively low cardiotoxicity; Race’s formulation aims to overcome prior solubility and injection-site limitations.
What’s next
Race is pursuing combinations with anthracyclines in solid tumours where dual outcomes — cardioprotection plus anticancer activity — could be clinically meaningful, while also exploring lower-intensity applications in acute myeloid leukaemia and other settings.