• In >40 clinical trials, Bisantrene has been shown to have low cardiotoxicity
• This study will assess the molecular mechanisms of Bisantrene heart safety using
  current molecular biology techniques
• Led by an established chemotherapeutic cardiology experienced team at the University of Newcastle

Race Oncology Limited (“Race”) is pleased to announce that it has entered into a collaborative preclinical research program with The University of Newcastle to investigate the heart safety Bisantrene offers over current anthracycline therapeutics. Eminent cardiotoxicity researchers, Associate Professors Aaron Sverdlov and Doan Ngo of the University of Newcastle, will lead the project.

While Bisantrene’s heart safety has been demonstrated in more than 40 clinical trials, exactly how it avoids causing cardiotoxicity is unknown. Advances in molecular biology since the 1980s now allow the underlying mechanism of action to be determined. The aim of this project is to explore Bisantrene’s low cardiotoxicity at the molecular level. Bisantrene has recently been identified as a targeted inhibitor of the Fatso/Fat mass and obesity-associated protein (FTO)¹. The possible role of FTO inhibition in Bisantrene’s lack of cardiotoxicity will be a primary focus of this research project.

Pillar 2 of Race’s Three Pillar strategy (ASX Announcement: 30 Nov 2020) is focused on the potential for Bisantrene to act as an anthracycline replacement, which are commonly used in the treatment of breast cancer. Anthracyclines are a class of chemotherapeutics known to be effective, but also cardiotoxic. The results of this study will support Phase IIb human trials of a Bisantrene in anthracycline naïve breast cancer patients. These trials are currently being explored for feasibility in Europe, with a potential for initiation in 2022.

“This is an exciting development for Race and we are looking forward to collaborating with Assistant Professors Sverdlov and Ngo on this important project. Understanding how Bisantrene works at a molecular level to avoid damage to the heart will aid all our clinical plans.”

Chief Scientific Officer, Dr Daniel Tillett

This preclinical study is to start immediately with result to be reported over the coming 12 months.

About Associate Professors Aaron Sverdlov and Doan Ngo

Associate Professors Sverdlov and Ngo lead the dedicated Australian-first, bench-to- bedside “Cancer and the Heart” clinical and research program at University of Newcastle, Hunter Medical Research Institute, Hunter New England Local Health District and Calvary Mater Newcastle Hospitals. This program incorporates basic mechanistic discovery studies looking at mechanisms of cardiotoxicity, drug discovery studies, translational human research, clinical research and clinical inpatient and outpatient service delivery.

In recognition of this important initiative, A/Prof Aaron Sverdlov was awarded the 2018 Ministerial Award for Rising Stars in Cardiovascular Research. A/Prof Doan Ngo, a co- lead of the program was awarded NSW Health EMC Fellowship in Cardio-Oncology (2018-2021) and the highly prestigious National Heart Foundation Future Leader Fellowship (2021-2025) for the cardio-oncology program of work.

Both A/Profs Aaron Sverdlov and Doan Ngo have been invited to establish and co-chair the National Cardio-Oncology Working Group under the auspices of the Australian Cardiovascular Alliance (ACvA). The aim of the group is to coordinate clinical and research activities in the field of Cardio-Oncology in Australia and act as a scientific and advocacy body to improve the quality of cardiovascular care for our cancer patients.

Associate Professor Sverdlov has over 50 peer-reviewed publications and 4 book chapters (including chapters on Oxidative Stress in Heart Failure in the textbook “Heart Failure: A Companion to Braunwald’s Heart Disease”) with over 1100 citations and has had more than 80 presentations at international and national meetings. He received over 30 competitive grants, with >20 in the last 5 years (total >$2.5M AUD).

Associate Professor Ngo is an academic pharmacist and a successful basic and translational scientist with multiple important contributions in the cardiovascular and metabolic field. She has more than 55 publications, of which more than 40 were published in the last 5 years.

1. Su, R., Dong, L., Li, Y., Gao, M., Han, L., Wunderlich, M., et al. (2020). Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion. Cancer Cell, 38(1), 79–96.e11.