Ann: Race Initiates Heart Safety Preclinical Study for Bisantrene, page-74

One of our lovely shareholders found me an old study that was investigating bisantrene in refractory lymphoma. Now, the PDF was quite blurry, but it had some raw data relating to dose and cardiac function, so I decided to remake it. I added onto the table the difference column and the average at the bottom. The patients included in this table had received greater than 5 courses of bisantrene and their prior doxorubicin dosing was indicated on the left. The most striking observation in this table is the patient with no prior doxorubicin treatment that received 7080 mg/m2 bisantrene and their cardiac ejection fraction increased 12%.



There are major limitations with interpreting the data like this, including and not limited to such a small dataset and inconsistencies with measuring cardiac ejection fraction. However, I thought it was interesting to see this data when you graphed it.

Briefly;
- As the dose of prior doxorubicin treatment increased, cardiac ejection fraction difference got worse and after bisantrene cardiac ejection fraction declined (seen by blue trendlines going down on the two graphs to the left)
- As the dose of bisantrene treatment increased, cardiac ejection fraction difference got better and after bisantrene cardiac ejection fraction improved (seen by blue trendlines going up on the two graphs to the right)



Clearly, due to the limitations I mentioned and the low R2 values, you cannot draw strong inferences from this data. It would be interesting to see a stronger measure of cardiac function with 100 or 200 patients. Despite the limitations, I think seeing the differences like this is quite valuable and interesting. The table below summarises the genes influenced by doxorubicin treatment and FTO inhibition, which really helps me to make sense of the observations above.



Based on this data, I suspect that the preclinical heart safety study will demonstrate that Bisantrene inhibits FTO altering the expression of autophagy related genes and ultimately upregulating autophagy, the cells natural cleaning process.