Breakthrough Chemotherapy Heart Protection Discovery for Australian Biotech

• Race Oncology's drug Zantrene shown to protect human heart muscle cells from anthracycline-induced chemotherapy death. Anthracycline's are the most used and effective anti-cancer drugs, yet they can cause serious heart damage.
• The preclinical research also demonstrated Zantrene's ability to synergise with existing anthracyclines to better kill breast cancer cells.
• Due to significance of the discovery, Zantrene will be fast-tracked to the clinic with a Phase 2b trial planned for 2022 in breast cancer patients at high risk of anthracycline-caused heart damage.
• Offers the potential of outsized clinical and commercial returns from new Zantrene/anthracycline formulations and combinations.

SYDNEY, Nov. 22, 2021 /PRNewswire/ -- Australian biotech and precision oncology company, Race Oncology, has announced breakthrough preclinical research that has found its drug Zantrene^® is able to protect heart muscle cells from death while improving the killing of breast cancer cells when used in combination with the anthracycline, doxorubicin.

This is the first time a drug has demonstrated the ability to both target the cancer and protect the heart from anthracycline damage. This discovery offers new hope to the millions of cancer patients worldwide who undergo chemotherapy with anthracyclines and are at risk of serious and permanent damage to their hearts.

Anthracyclines are widely recognised as the most effective anti-cancer treatments ever developed and are used in more types of cancer than any other class of anti-cancer agent^[1], including leukemias, lymphomas, neuroblastoma, kidney, liver, stomach, uterine, thyroid, ovarian, sarcomas, bladder, lung and breast cancers. However, fears over the damaging side effects of anthracyclines to the heart have led to many oncologists to limit their use of these extremely effective drugs. Race's discovery has the potential to revolutionise the use of anthracyclines by allowing oncologists to use these powerful drugs to their full anti-cancer potential without fear of permanent damage to the heart.

The Zantrene^® heart safety research program is being led by eminent cardiotoxicity researchers, Associate Professors Aaron Sverdlov and Doan Ngo, in collaboration with cancer scientist Associate Professor Nikki Verrills, at The University of Newcastle.

Associate Professor Aaron Sverdlov said: "To date, the concept of potential cancer therapies that are not only non-cardiotoxic but, in fact, cardio-protective has not been evaluated or even entertained, largely due to 'disease-specific' approaches in healthcare. Our results suggest that Zantrene, an effective anti-cancer medication, can concomitantly provide protection against toxic effects on the heart from one of the most commonly used chemotherapy agents, doxorubicin. This is the first evidence of its kind to demonstrate that there is a therapy that both targets the cancer and protects the heart! This has the potential to improve health outcomes for countless cancer patients and survivors by both improving their cancer treatment while preventing development of cardiovascular disease."

While this is an exciting new discovery, Zantrene^® (bisantrene dihydrochloride) has a long clinical history, having been developed in the 1970s as a heartsafer alternative to the anthracyclines^[2] before approval in France in the 1990's. While Zantrene's improved heart safety was proven in more than 50 clinical trials^[3], , the question of whether Zantrene could help prevent the heart damage caused by anthracyclines was never addressed.

Commenting on the new research results, Race's Chief Scientific Officer, Dr Daniel Tillett said: "To find that Zantrene can protect the heart from chemotherapy while also killing cancers better is an extraordinary 'best of both worlds' outcome. Given anthracyclines are used in millions of cancer patients every year, it is hard to overstate the clinical and commercial potential of this breakthrough!"

Conclusions

• In this preclinical model, Zantrene protects the heart muscle cells from damage by doxorubicin while synergising with the anthracyclines to better kill breast cancer cells.
• Race has submitted a patent application addressing the combination of Zantrene with an anthracycline for the protection of the heart of patients. This patent (if granted) would provide protection of the drug combination and its clinical use through 2041.
• This new heart protection discovery will be rapidly progressed to the clinic. The extensive clinical history of Zantrene allows this combination to be quickly advanced clinically.
• Advanced discussions are underway with clinicians in Australia to run a Phase 2b clinical trial in breast cancer patients at serious risk of anthracycline-induced heart damage.
• This discovery opens new market opportunities for Zantrene of similar clinical and commercial potential to the earlier discovery that Zantrene is a potent FTO inhibitor.

Next Steps

• Animal studies to be run in Q4 CY2021/ Q1CY2022.
• Additional preclinical studies to investigate if Zantrene can protect the heart from damage by other chemotherapeutic drugs which are also known to cause cardio-damage.
• Further studies to determine the molecular mechanism of Zantrene's cardio-protective activity. This may allow identification of additional protective functions of Zantrene.
• Development of new and optimised drug combination formulations with improved clinical and commercial value.
• Initiation of a Phase 2b breast cancer clinical trial in 2022.

References

1. Weiss RB. The anthracyclines: will we ever find a better doxorubicin? Semin Oncol. (1992) 9(6):670-86.
2. Citarella, R. V. et al. Activity of a novel anthracenyl bishydrazone, 9,10-anthracenedicarboxyaldehydeBis[(4,5-dihydro-1H-imidazol-2-yl)hydrazone] dihydrochloride, against experimental tumors in mice. (1982) Cancer Res 42, 440–4.
3. Rothman, J. The Rediscovery of Bisantrene: A Review of the Literature. (2017) Int J Cancer Res Ther 2, 1–10.