On March 17, 2022 Race Oncology Ltd (ASX:RAC) reported that it has received interim results from an extramedullary acute myeloid leukaemia (AML) preclinical program that suggest that its asset, Zantrene, in combination with decitabine, can kill AML tumours in a mouse model of extramedullary AML (Press release, Race Oncology, MAR 17, 2022, View Source [SID1234610228]).
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The research, led by eminent cancer researcher Associate Professor Nikki Verrills of The University of Newcastle and Hunter Medical Research Institute, found that low dose Zantrene in combination with decitabine can kill AML tumours in a mouse model.
Difficult-to-treat disease
Extramedullary AML occurs when the leukaemia spreads from the bone marrow and forms solid tumours in tissues such as the skin, breast, kidney, brain or other organs. A 2020 prospective positron imaging trial identified that up to 22% of AML patients have the extramedullary form.
Patients with extramedullary AML have no clinically approved treatments and only limited experimental treatment options. Many clinical trials exclude patients with this difficult-to-treat form of AML.
Combination of Zantrene and decitabine
In a 2020 Phase 2 clinical trial conducted at Chaim Sheba Medical Centre, Tel Aviv, in relapsed and refractory AML patients, Zantrene was observed to have clear efficacy in patients with extramedullary AML.
On the basis that Zantrene is a potent FTO inhibitor, it was hypothesised that Zantrene and decitabine would synergise to better kill AML cells.
This hypothesis was tested both in vitro in AML cell cultures and in vivo in a mouse model of extramedullary AML.
These findings build on the results of earlier AML clinical trials and reveal that:
Zantrene in combination with decitabine was found to target extramedullary tumours as well as in the bone marrow and spleen using an AML mouse model;
Zantrene alone found to kill a genetically diverse range of AML cells at low drug concentrations and slow the growth of AML tumours in mice; and
Zantrene in combination with decitabine showed significantly greater cell killing across a diverse panel of AML cell lines than either drug on its own (true synergy).
RAC chief executive officer Phillip Lynch said, "These results provide support for our well advanced extramedullary AML clinical trial and provides important guidance for the study’s design and treatment protocol."
Next steps
Race Oncology is rapidly advancing Zantrene into the clinic as a possible new treatment option for patients with extramedullary AML.
The company will conduct further mouse studies to explore optimal dosing schedules to report in the second quarter of 2022 and is pursuing publication of results in a high impact, peer-reviewed journal.
Race is now initiating clinical studies using low dose Zantrene and decitabine in combination to treat patients with extramedullary AML or MDS who cannot tolerate, or who are unwilling to tolerate, high-intensity chemotherapy.
This trial is expected to begin patient recruitment in the next quarter.
"The results from Professor Verrills’ laboratory are highly supportive of our upcoming extramedullary AML Phase 1/2 trial for Zantrene," RAC chief scientific officer Dr Daniel Tillett said.
"This work further builds on the 2020 Phase 2 trial of Prof Arnon Nagler, who identified Zantrene as showing encouraging efficacy in extramedullary AML.
"The optimised drug combination and schedule identified in this preclinical mouse study will be rapidly translated to the clinic via our extramedullary AML trial."
RAC shares have been as much as 5.8% higher this morning to A$2.75.