Ann: Race Appoints George Clinical for Phase 1 Trial of RC220, page-60

Hey mate.

This is what I have put together so far. It's probably not going to be accurate, but this is what I would do based on the information I have. @RaceOncology give us the in vivo Bis+Dox data!

D3Q3W = Dosing once per day for three days repeated every three weeks
D1Q3W = Dosing once repeated every three weeks

I think they will give Bisantrene before Doxorubicin because of what I believe the cardioprotection mechanism to be. I don't know how many days of Bisantrene will be given, but the research I have completed to date clearly demonstrates more frequent dosing of Bisantrene in the month drives better efficacy. The lead-in dose with 3-day course provides a clinically meaningful amount of Bisantrene in the first month. The 3-day Bis and 1-day Dox is repeated every three weeks until response, tumor progression, or the maximum cumulative dose of doxorubicin recommended for patients.



There will be many ways RAC will evaluate the cardioprotective effect of Bisantrene in combination with Doxorubicin. The most sensitive measure is VO2peak, which is extremely sensitive and can demonstrate significant cardiac damage while traditional markers may show no significant difference. This provides RAC with short-term cardioprotection data for Bisantrene. Traditional markers of cardiotoxicity will still be measured.

There are known cohorts receiving cardiotoxic chemotherapy with VO2peak data, comparable Doxorubicin and Dexrazoxane cohorts, as well as single-agent Doxorubicin cohorts without cardioprotective agents to refer to for cardioprotection. To be considered an effective cardioprotective agent, Bisantrene needs to demonstrate a 30% decrease in cardiac events.

Patients included into the trial will be anthracycline naive as well as probably void of any known metabolic risk factors associated with CVD likely to confound the data.

It's an excellent question on dose. I suspect the P1b will not be able to extend the dose of Doxorubicin, but this may be explored in future clinical trials. The real strength of Bisantrene is to increase the cumulative dose ceiling of Doxorubicin in patients.

There have been breakthrough therapy designations on P1 data, and the Bis+Dox CPACS trial has all the hallmarks of a BTD approval. If Bisantrene can indeed decrease cardiac events while improving response rates and PFS, we are on!