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Race announced anti-cancer drug combo synergisms

Previous approval in France, 1500+ patientsdosed, 40+ clinical trials. New improved RC220 formulation ready nextmonth.

Groundbreaking Cardio Protection andAnti-Cancer Synergy (CPACS) trial H2 2024.

Summary of Bisantrene super-powers below,enjoy!

Ovarian Cancer (23 February 2021)

Bisantrene is more cytotoxicthan doxorubicin and epirubicin in ovarian cancer cells.

Bisantrene can kill ovarian cancer cell linesresistant to cisplatin, 5-fluorouracil and chlorambucil

Melanoma (30 September 2021)

Bisantrene® is highly effective in killingmelanoma cells at sub-chemotherapeutic levels, sub 100nm and as low as 40nm.

Sensitivity to Bisantrene® is independent ofBRAF and NRAS mutational status.

Bisantrene® at low concentrations kills highFTO producing melanoma cancer cells

Sensitivity to Bisantrene® correlates with FTOlevels, where high FTO producing cells show up to 60x greater sensitivity thanlow FTO producing cells

Anti PD-1 Resistant Melanoma (22 June 2022)

Inhibition of FTO can overcome PD-1 immunecheckpoint resistance in the B16-F10 (known to over-produce FTO) mouse melanomamodel.

Bisantrene used in combination with ananti-PD-1 antibody can induce an effective immunotherapy response in the highlyaggressive B16-F10 mouse model of immunotherapy treatment resistant (“cold”)melanoma.

Bisantrene when used at low,non-chemotherapeutic doses can activate immune cells to aid in the creation ofan anti-tumour immune response.

Bisantrene displays a dose effect on anti-PD-1immunotherapy where low doses of Bisantrene are more efficacious than highchemotherapeutic-level doses.

Bisantrene reduces the expression of genesinvolved in immune evasion by human melanoma cells.

Melanoma (28 June 2022)

Bisantrene in combination with BRAF inhibitorvemurafenib or MEK inhibitors binimetinib and cobimetinib improves the killingof human melanoma cells.

Bisantrene synergizes with vemurafenib tobetter kill melanoma organoid tumours.

Kidney CCRCC (10 March 2022)

Bisantrene improves the killing of ccRCC cellswhen used in combination with other kidney cancer drugs VEGFR kinase inhibitorslenvatinib, cabozantinib and pazopanib.

Bisantrene found to kill a range of kidneycancer cells both on its own and in combination with existing cancer treatments

Breast Cancer (24 December 2020)

Bisantrene as a single drug shows similarefficacy to doxorubicin and epirubicin in a range of different breast cancertypes.

Bisantrene can kill some breast cancer cellsresistant to doxorubicin and epirubicin.

Bisantrene shows additive cell death effectswhen combined with cyclophosphamide that are very similar to that seen whencyclophosphamide is used in combination with doxorubicin or epirubicin.

FTO expression level correlates with breastcancer sensitivity to Bisantrene

Bisantrene was able to kill some breastcancers cells resistant to the doxorubicin and epirubicin, confirming thehistorical clinical data from past Bisantrene Phase II/III clinical trials.

Breast Cancer (9 March 2021)

Bisantrene killed breast cancer cellsresistant to the current standard of care breast cancer drugs etoposide,palbocicclib, fulvestrant, tamoxifen, doxorubicin, epirubicin andcyclophosphamide.

Bisantrene was found to kill breast cancercells from all common breast cancer subtypes including triple negative, ER+,and Her2+.

Bisantrene was less toxic to non-tumorousbreast cancer cells than either doxorubicin or epirubicin, suggesting a moreprecisely targeted mechanism of action.

AML (23 February 2022)

Bisantrene shows synergy when used incombination with the AML drugs venetoclax, panobinostat, decitabine andolaparib, known BCL2 inhibitors.

These combinations were found to enhance DNAdamage, cleavage of Caspase 3 and PARP1, DNA fragmentation, increased ROS, andpotent apoptosis activation in AML cells.

EMD AML (23 March 2023)

Bisantrene in combination with decitabine wasfound to target extramedullary tumours as well as in the bone marrow and spleenusing an AML mouse model.

Bisantrene alone found to kill a geneticallydiverse range of AML cells at low drug concentrations and slow the growth ofAML tumours in mice.

The in vitro cell line data shows that Bisantreneis able to kill AML cells at low concentrations as a single agent irrespectiveof the cancer driver mutations that are common causes of AML in patients withthe possible exception of KIT.

Pancreatic (21 June 2022)

Two abstracts published in Cancer Research byresearch collaborators of Race’s Scientific Advisory Board Member, Prof Chenhave further highlighted Bisantrene’s use as a targeted inhibitor of FTO andanti-cancer agent.

The first abstract demonstrates Bisantrene’sability to target FTO in the suppression of pancreatic cancer.

The second abstract explores the use of Bisantreneas an adjunctive treatment able to overcome colorectal cancer resistant to 5-FUbased chemotherapy via inhibition of FTO in both cell and mouse models.Resistance to 5-FU is a significant clinical issue as this drug remains abackbone of colorectal cancer treatment.

Type 2 Diabetes (22 January 2022)

In this new work, theUniversity of Lille team has identified that FTO plays a critical role in Type2 Diabetes and that inhibition of FTO by Bisantrene at a concentration (100 nM)– below the level observed from prior studies to cause toxicity – is able toincrease the production of insulin by diabetic pancreatic tissue more than20-fold.

Breast Cancer (8 December 2021)

Thesynergy of Bisantrene with carfilzomib in breast cancer cells may open thepossibility of using carfilzomib in solid tumours, extending its potential tocancers beyond multiple myeloma.

Sheba 1.0 (16 June 2020)

Analysis of Phase II trial of Bisantrene forrelapsed or refractory Acute Myeloid Leukaemia showed an objective clinicalresponse in 40% of patients.

Bisantrene had marked activity in 4 out of 4patients with the difficult to treat extramedullary (outside of the bonemarrow) form of AML

Bisantrene was well tolerated with nounexpected serious toxicities

Sheba 2.0 (6 November 2023)

Bisantrene in combination with fludarabine andclofarabine administered over four days induced a clinical response in 6 of 15evaluable patients (40%) with advanced relapsed or refractory Acute MyeloidLeukaemia, with five patients receiving a potentially curative stem celltransplant.

The bisantrene combination was found to besafe and well tolerated without clinically relevant cardiotoxicity or tumourlysis syndrome.

FTO Inhibitor (6 July 2020)

Inhibiting FTO activity in cells has beenfound to kill or slow the growth of a wide range of cancers includingleukaemia, breast, lung, ovarian, gastric, brain, melanoma, pancreatic, kidneyand many more (29+ cancers)

Recent studies by the City of Hope, identifiedbisantrene as the most potent enzymatic inhibitor of FTO (IC50 142nM) from ascreen of more than 260,000 chemical compounds contained in the US NationalInstitute of Health’s (NIH) National Cancer Institute’s (NCI) chemical library.The research also demonstrated in both cell and animal models, that bisantrenespecifically killed FTO overexpressing cancers when used at concentrations farbelow that known to be toxic in humans.

Source: https://pubmed.ncbi.nlm.nih.gov/32531268/

FTO Inhibitor (15 April 2021)

Bisantrene shown by the University of Chicagoto target the Fat Mass and Obesity associated protein (FTO).