Speculative M&A Transaction Analysis, page-747

You have actually asked a rather interesting question, John.

Every in vivo program that has been published as demonstrated synergy, and almost all in vitro work completed has shown some level of synergy at certain dose levels. The issue is that the in vitro work only captures a fraction of Bisantrenes true anti-cancer effects.

Thanks to the excellent due dilligence of @Boffin99 he showed me this little gem of information from the Melanoma patent.



The decrease in M2b and increase in M1 macrophages is statistically significant. A dose of 5 mg/kg equates to a human dose of roughly 61 mg/m2, which indicates Bisantrene is very potent at this effect. This confirms historic literature that investigated Bisantrene in macrophage activity.



Essentially, Bisantrene is synergistically hitting the breaks (M1 macrophage activation) on cancer whilst also taking off the accelerator (M2b macrophage inhibition), which brings the cancer car to a full stop by reprogramming macrophages into an anti-cancer state. What this means is that testing Bisantrene in vitro does not capture the full therapeutic potential of the drug, as macrophages exist outside of cells, therefore it is impossible to fully understand Bisantrene in combination with anything without an accompanying in vivo program.

The next thing investors need to do is consult this table that highlights the number of different drugs that are resistant to M2b macrophages. You will notice that Bisantrene has shown synergy with many of these drug classes where M2b macrophages resist their effects.



So, it is currently impossible to conclude the synergistic potential of Bisantrene, but I have a feeling we are about to find out. Given the plethora of data supporting M2b resistance, I'd say Bisantrene synergy should improve from in vitro to in vivo and at the very least provide a clearer picture of potential TAM.