27 October 2021 – Race Oncology Limited (“Race”) is pleased to announce it has entered into a research collaboration with Dr Dan Dominissini of the Chaim Sheba Medical Center, Israel to analyse clinical patient samples from the ongoing Zantrene® Phase 1b/2 trial in relapsed/refractory Acute Myeloid Leukaemia (R/R AML) for FTO and FTO-related biomarkers (ASX Announcement: 9 August 2021).

The biomarker testing will include FTO gene sequencing, FTO protein levels (intracellular staining and flow cytometry), FTO mRNA levels, and analysis of the m⁶A/A ratio in mRNA from patient tumour samples before, during and after treatment with Zantrene.

Dr Dominissini is a world-renowned expert in RNA methylation and m⁶A RNA methylation and has authored more than 32 publications in high impact peer-reviewed journals including Nature, Science and Cell.

This research collaboration has strategic importance for Race as the data will advance Race’s ‘Three Pillar’ strategy announced at the 2020 AGM (ASX Announcement: 30 November 2020).

“We are delighted to be extending our successful collaboration with the team at Chaim Sheba to generate important data on the effects of Zantrene on FTO and related molecules. These data will give us the first insights into the effect of Zantrene in patients on FTO and m⁶A RNA methylation and continues to advance our Three Pillar Strategy.”

Race CSO Dr Daniel Tillett

“Conceptual and technological breakthroughs since 2011, by our group and others, have introduced the novel notion that internal chemical modifications of mRNA and long non-coding RNA are abundant, dynamic and sometimes reversible events, which constitute essential regulatory elements in RNA metabolism. Dedicated cellular machineries that install (‘writers’), remove (‘erasers’) and recognize (‘readers’) the various RNA modifications have been discovered, revealing essential roles for mRNA and lncRNA modification in various cellular, developmental and disease processes, and providing avenues for therapeutic intervention. N6-methyladenosine (m6A) is the most prevalent internal mRNA modification, removed by the enzyme FTO, with established key roles in carcinogenesis. We are excited to see these basic discoveries translated into the clinic by the Zantrene study of Race Oncology for relapsed or refractory AML. We hope that our scientific collaboration will advance the understanding of the correlation between FTO and m6A status in AML and response to treatment.”

Dr Dominissini from Chaim Sheba

Relapsed or Refractory Acute Myeloid Leukemia

Primary refractory or relapsed acute myeloid leukemia is associated with poor prognosis and remains a major therapeutic challenge. Primary refractory AML is defined by the absence of complete remission (CR), manifested by blast count of ≥5% in bone marrow after one or two cycles of intense induction chemotherapy.

Up to 30% of adults with newly diagnosed AML fail to achieve CR after two courses of intensive chemotherapy.

Even when CR is achieved through intense chemotherapy, approximately half of the younger and 80% of the older patient’s relapse. In both clinical situations, refractory and/or relapsed AML, active disease remains a major therapeutic challenge despite recent advances.

Study Design

Samples will be taken from patients participating in the existing study, “An open-label, Phase 1b/2 study of intravenous FluCloZan (fludarabine, clofarabine, Zantrene (bisantrene dihydrochloride)” in cohorts of adult patients with R/R AML using a Simon’s 2-stage design: a Phase 1b lead-in dose escalation stage to establish the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of FluCloZan and a Phase 2 expansion stage to determine efficacy and confirm safety of the FluCloXan regimen at the RP2D in up to 17 subjects.