Ann: First Patient Dosed in Phase 1b/2 AML Trial, page-246

Looking forward to the interim results of Phase II R/R AML trial, a.k.a. Sheba 2.0 in H2.

Historical Trials

Historical trials for Bisantrene (Link: the-rediscovery-of-bisantrene-a-review-of-the-literature-ijcrt-17-015.pdf (raceoncology.com))

Modern Trial

Sheba 1.0 results in Phase II study completed in June 2020 40% clinical response as a mono-theraphy. (Link:RACE ONCOLOGY LTD (ASX:RAC) - Ann: Impressive 40% response in Phase II Bisantrene AML Trial, page-1 - HotCopper | ASX Share Prices, Stock Market & Share Trading Forum )

R/R AML Patients Cured

Two Paedeatric patients cured from R/R AML in France, for Bisantrene that was previously approved. Link: PBC-060818-Bisantrene-Combo-Poster.pdf (raceoncology.com)



Current Trial

Current trial Phase 1B dose escalation - although this is just to establish safety tolerance and max dosage resulted in 75% Response and 50% bridged to stem cell transplant (3 of 6). The number of lines of treatment ranged from 3 to 8 lines (which is extreme - but Bisantrene still triggered a response).



Independent Studies

Independent studies from MD Anderson Cancer Studies in the US Full article: Enhanced cytotoxicity of bisantrene when combined with venetoclax, panobinostat, decitabine and olaparib in acute myeloid leukemia cells (tandfonline.com)
Source: 0e15acc3fd1b966eae2967af5dc2e522 (sharelinktechnologies.com)

ChatGPT:
The combination of fludarabine, clofarabine, and Bisantrene may potentially be beneficial in treating certain hematological malignancies. These drugs have different mechanisms of action that target cancer cells through DNA synthesis and repair inhibition, intercalation with DNA, and topoisomerase II inhibition. By combining their effects, there is a possibility of enhanced efficacy against cancer cells.

Why it works (FTO Inhibitor)?

Bisantrene is the worlds best known inhibitor of the FTO protein, which is been observed to be relevant in the progression of 30+ cancers. AML has advanced FTO expression compared to other cancers see below.

Source: Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion - ScienceDirect

Source: 15f1a31caa3b9bda90cb1e1fdb955f38 (sharelinktechnologies.com)

Also, as cancer progresses in stages it has been proven than FTO expression increases. Therefore reducing FTO overexpression in AML and late stage cancers such as R/R AML ought to have a double benefit. There is often synergy with Bisantrene in combo with other drugs providing triple benefits in some instances.


Source: FTO is upregulated in human melanoma. a Immunofluorescence staining of... | Download Scientific Diagram (researchgate.net)

Final Thoughts

Looking forward to the Sheba 2.0 results. Could we see an overall response ~70% and 50%+ bridged to stem cells for R/R AML which would make this an amazing drug in the clinic, with a clinical response of 10% being seen as clinically relevant in some instances. We are four patients recruited and once we reach 9 interim results will be provided, so we are on the count down and hopefully see the interim results in H2 CY2023.