but out price, page-76

The very first Phase I trial of Bisantrene (which I first looked at in 2019) applied Bisantrene at low dose (range from 2.5 mg / sq m / day to 90 mg / sq m / day ) in 1981. It was a dose-escalation trial - at doses significantly lower than used for AML in the historic Phase I and II studies and the Israel trial completed in 2020. AML if you look at the studies is dosed at 250 mg / sq m / day.

This Phase I trial had responses as a single agent at low dose for ccRCC aka Renal Cancer aka Kidney Cancer aka hypernephroma.

Now go and have a look at RACE's strategy for Pillar 1 ...





Now back to the historic Phase I trial.

The first patient with Kidney Cancer that responded had 4 courses of treatment ( 4 days ).​

• Dosing ranged between 60 and 80 mg / sq m / day​

The second patient with Kidney Cancer that responded had 8 courses of treatment ( 8 days ).​

• Dosing ranged between 45 and 90 mg / sq m / day​

Was this the optimal dosing for schedule for Kidney Cancer?

Who knows ... the trial investigators wouldn't have because it was the first Phase I trial but we do know Bisantrene worked at low dose.

Bisantrene's usage for inhibiting FTO will be at low dose ...

and we know from this 1981 trial that patients responded at low dose (see extract below). These two patients responded quite well and I guess would have responded better with additional follow-up treatments.

We can assume they would have responded better with a greater duration of treatment ( I think this could be done by increasing the number of consecutive daily doses or by retreating patients with another round of daily doses weeks later ).




Patients are treated with PD-1 inhibitors on a 6-week schedule for up to 24 months.

https://reference.medscape.com/drug/keytruda-pembrolizumab-999962​

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Bisantrene was used at low dose for 5 to 8 days in the historic Phase 1 trial.

The patients responded and we don't even know if this was optimal dosing.

Will patients respond better with the same amount of treatment. I think so.

Another great thing about this trial is it gives RACE some great insights for the dosing levels to use in the FTO dose-escalation study. Because safety of Bisantrene is well known from over 40 Phase II and III trials ( and from the above Phase 1 dose escalation trial ) I think RACE will be able to focus on dose level and schedule to evaluate optimal dosing levels to achieve efficacy.