Race Oncology Ltd (ASX:RAC) has received positive interim results from a preclinical heart safety research program 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.
The research program found that Zantrene – RAC’s patented targeted oncology treatment – is capable of protecting heart muscle cells from a new class of anti-cancer chemotherapy drug, carfilzomib, which induces heart cell death, while also improving the ability of carfilzomib to kill cancer cells.
Carfilzomib (trademark Kyprolis®) is a highly effective anti-cancer drug used in the treatment of multiple myeloma (a dangerous blood cancer), but it can cause serious and permanent damage to the heart in many patients.
The risk of cardiac damage is so great that its use in older patients with pre-existing heart disease is often contraindicated.
“Results are genuinely remarkable”
University of Newcastle associate professor Doan Ngo said: “Carfilzomib is a highly effective anti-cancer drug, but its use is limited due to cardiotoxicity.
“Our laboratory has tested numerous drug candidates over the years, we observe that Zantrene has: 1. potent anti-cancer effects; 2. synergistic anticancer effects with both carfilzomib and doxorubicin; and 3. cardioprotective effects against both carfilzomib and doxorubicin-induced cardiotoxicity.
“Zantrene was shown to salvage over 30% of carfilzomib-induced human heart cell from death. These results are genuinely remarkable, as with other clinically used cardioprotective drugs, we only observe a 10-15% protection from heart cell damage.
“Zantrene is the first anti-cancer agent that we have found to exhibit a cardioprotective profile while being synergistically effective as an anti-cancer treatment.
“These results give hope to the millions of patients living with cancer that once they survive cancer, they may not have to live with heart disease.”
Zantrene’s ability to improve heart safety compared to anthracyclines (a different class of broad-spectrum chemotherapy drugs) has been demonstrated in more than 50 human clinical trials. The treatment has also been shown – in preclinical studies – to protect heart muscle cells from anthracycline-induced death.
This is the first study to assess whether Zantrene could help prevent cardiac damage caused by other classes of heart-damaging cancer drugs, with very encouraging results.
In the company's words
Proactive interviewed Race Oncology's CEO, Phillip Lynch who provided a roadmap for the company's $29.7 million share purchase plan, designed to open the door on research opportunities for Race's Zantrene® anti-cancer agent.
“New clinical development pathways”
Race Oncology chief scientific officer Dr Daniel Tillett said: “The expansion of Zantrene’s cardio-protection and anti-cancer synergy beyond the anthracyclines into the completely new drug class of proteasome inhibitors is unexpected.
“This discovery opens new clinical development pathways and partnering opportunities for Zantrene beyond those already identified by Race.”
In this preclinical study, Zantrene was shown to protect heart muscle cells from damage by carfilzomib while synergising to better kill breast cancer cells.
This additional discovery suggests that Zantrene may be able to protect the heart of patients from a range of unrelated cardiac-damaging drugs.
The synergy of Zantrene with carfilzomib in breast cancer cells may open the possibility of using carfilzomib in solid tumours, extending its potential to cancers beyond multiple myeloma.
RAC has submitted a patent application addressing the combination of Zantrene with carfilzomib for the protection of the heart of cancer patients. This patent (if granted) would provide protection of the drug combination and its clinical use through 2041.
“Patient utility and commercial applicability”
Race Oncology CEO Phillip Lynch said, “This additional result further underscores the potential patient utility and commercial applicability for Zantrene. We will be allocating additional resources to ensure this discovery can be comprehensively addressed.”
RAC believes this new heart protection discovery can be rapidly progressed to the clinic. The extensive clinical history of Zantrene allows this combination to be quickly advanced clinically in multiple myeloma, opening new collaboration potential and licensing opportunities for Zantrene.
Next steps
- Animal studies to be conducted in Q1-Q2 CY2022.
- Additional preclinical studies to investigate if Zantrene can protect the heart from damage by other chemotherapeutic drugs that are also known to cause cardio-damage.
- Further studies to determine the molecular mechanism of Zantrene’s cardioprotective 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.
About Race Oncology
Race Oncology is an ASX-listed precision oncology company with a Phase 2/3 cancer drug called Zantrene®.
Zantrene is a potent inhibitor of the Fatso/Fat mass and obesity-associated (FTO) protein. Overexpression of FTO has been shown to be the genetic driver of a diverse range of cancers.
RAC is exploring the use of Zantrene as a new therapy for melanoma and clear cell renal cell carcinoma, which are both frequent FTO over-expressing cancers.
In breakthrough preclinical research, RAC has also discovered that Zantrene protects from anthracycline-induced heart damage, while in tandem acting with anthracyclines and proteasome inhibitors to improve their ability to target breast cancer. The company is evaluating this discovery.
The company also has compelling clinical data for Zantrene as a chemotherapeutic agent and is in clinical trial in Acute Myeloid Leukaemia (AML).
Race Oncology is pursuing outsized commercial returns for shareholders via its ‘Three Pillar’ strategy for the clinical development of Zantrene.