23 February 2022 – Race Oncology Limited (“Race”) is pleased to announce a researcher
team, led by Professor Borje Andersson and Associate Professor Ben Valdez of the MD
Anderson Cancer Center (Texas, USA), have identified a number of additional clinically
translatable drug combinations that showed synergy with Zantrene® when tested in Acute
Myeloid Leukaemia (AML) cells.

This study¹, sponsored by Race Oncology, has been published in the Journal Leukemia & Lymphoma
and is entitled “Enhanced cytotoxicity of bisantrene when combined with venetoclax,
panobinostat, decitabine and olaparib in acute myeloid leukemia cells.”

The MD Anderson team identified synergism of Zantrene and venetoclax in combination
with panobinostat, decitabine, or olaparib, known inhibitors of BCL2, histone deacetylase,
DNA methyltransferase, and poly (ADP-ribose) polymerase, respectively, in AML cells.

These combinations were found to enhance DNA damage, cleavage of Caspase 3 and
PARP1, DNA fragmentation, increased ROS, and potent apoptosis activation in AML cells.
Similar results were observed using mononuclear cells isolated from leukaemia patients,
but not from healthy donors. The SAPK/JNK signalling pathway was strongly activated by
the combination treatments, whereas the PI3K/mTOR and Wnt/b-catenin pro-survival
pathways were inhibited.

Chief Scientific Officer, Dr Daniel Tillett said: “This work provides further preclinical data
to support our upcoming Phase 1b/2 extramedullary AML trial in Australian and Europe, where
patients will be treated with Zantrene in combination with decitabine or cytarabine. We are
extremely excited about being able to quickly translate this work from the lab into the clinic,
where it has the potential to help AML patients in need.”

1. Valdez, B. C. et al. Enhanced cytotoxicity of bisantrene when combined with venetoclax, panobinostat,decitabine and olaparib in acute myeloid leukemia cells. Leukemia Lymphoma 1–11 (2022) doi:10.1080/10428194.2022.2042689.