Ann: Race Appoints George Clinical for Phase 1 Trial of RC220, page-134

Yeah, I think you are right. The evidence clearly demonstrates greater dosing within the month is optimal for anti-cancer efficacy. I'm not sure how it might appear to new investors, but if Bisantrene prevents the cardiotoxicity of doxorubicin, even in a phase 1a/b model, it is likely to attract significant investor interest. People invest in an opportunity and accept a certain amount of risk. Proven cardioprotection of Bisantrene with the known anti-cancer effects becomes a very exciting investment.

I think KB has raised some excellent points. The thing that I would say to add is the mechanism(s) of cardioprotection reqiures a higher dose than that of anti-cancer efficacy. This is evidenced by the in vitro studies where Bisantrene provides cardioprotection really from about 1uM (1000 nM), while inhibiting FTO at 0.142 uM (142 nM). What the in vitro work fails to capture is the effects of extracellular targets for the drug a1/a2 adrenoceptors and macrophage polarization/activity. You definitely want an instance where you are finding the maximally tolerated dose for cardioprotection and not synergy.

I think point 2 is accurate, as there are biomarkers that can be used to establish anti-cancer effects alone and in combination. Point 3 is particularly interesting and might explain why RAC has engaged with Asian jurisdictions. The governance of ethics in Australia is likely stricter compared to some Asian counterparts, where the criteria for safety and tolerability might allow for adjustments to the dosing regimen more readily. In truth, I don't know about Aus/Asia, but I would not be surprised if this was the case.