CPACS: Research, Results, Market Comparisons, and Valuations, page-184

Just a quick one from me.

Dexrazoxane (DEX) is FDA approved for providing cardioprotection against Doxorubicin (DOX), and, as such, is a benchmark that we can refer to.

Here is a preclinical model demonstrating changes in fractional shortening (FS%) and brain natriuretic peptide (BNP). Fractional shortening measures the percentage change in the diameter of the left ventricle between the contracted (systole) and relaxed (diastole) states. It is an indicator of the contractile function of the heart. BNP levels in the blood increase in response to ventricular volume expansion and pressure overload, such as in heart failure. Elevated BNP levels are used to diagnose and assess the severity of heart failure.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10298964/pdf/ijms-24-10202.pdf

Briefly, there is a non-significant improvement in FS% when DEX is used in combination with DOX, indicating an improvement in contractile function of the heart. There is also a significant decrease in BNP production when DEX is used in combination with DOX at the 11-week mark, but not the 21-week. This indicates that DEX decreases markers associated with the severity of heart damage during exposure to DOX, but this may not persist long term.

In preclinical models, Bisantrene significantly improves FS% and decreases BNP production in combination with DOX, indicating that it can also improve contractile function and decrease markers associated with the severity of heart damage.



The key difference is clearly not in the responses observed, but instead in the amount of Doxorubicin given in each model. The graph below captures the dosing of DOX in the DEX and BIS in vivo models. There was over 3x as much DOX per kg given in the Bisantrene preclinical model than DEX. The DEX preclinical model ran for 10-weeks of dosing, but the cumulative dose of DOX was still significantly higher in the Bisantrene preclinical model.



Bisantrene is demonstrating comparable preclinical cardioprotection to DEX in this model despite 3x more DOX/kg being used and significantly greater cumulative doses. Bisantrenes mechanism of cardioprotection appears to be of particular significance. I wonder what the cardioprotective effects of DEX in comparison to Bisantrene might be if equal amounts of DOX are used.

A world first in oncology - a strong anti-cancer agent that provides cardioprotection.