My understanding is Zantrene is a phase 3 asset, although I think it is still in phase 1 for an FTO-directed pathway. Everything you have said is correct about historic dosing being safe and tolerable at levels that far exceed those theorised for FTO inhibition, which can provide a lot of confidence about the drug moving forward into phase 1 clinical trials. I have explained this table in one of my videos, but it provides a very interesting glimpse of the relatively small impact low dose Zantrene over 5 days can have on hematological toxicity. Doses above and including the yellow line are those theorised for FTO inhibition.
The main reason that I think we are still in phase 1 is because of your questions to
@RaceOncology. I am yet to see a piece of research that demonstrates the appropriate amount of time or dose a patient requires of Zantrene for the best effect. As such, I suspect it to be elucidated in the phase 1 dose escalation (P1DE) trial. Of course, I don't have the knowledge of the board do, so I may be wrong about this. I don't think dose and duration is dependent on the size/stage of the cancer, moreso how sensitive the cancer is to an FTO inhibitor. The table below highlights the importance of screening participants using a companion diagnostic or sensitivity assay and then including those patients into clinical trials. An example to look at is patient 37, who was very sensitive to Zantrene in vitro (graph on the left), achieved a complete response after a single 5-day course @ 240 mg/m2.
I can't really comment on cumulative doses until we know the dose and regimen to be used, but I don't an FTO-directed cycle will achieve greater cumulative doses than what has been achieved in the past. I have attached a reconstructed table below from a phase 2 clinical trial of Zantrene in refractory lymphoma patients, which shows some patients achieved cumulative doses between 4500 and 7080 mg/m2. The phase III BC trial is another example where 25 patients had greater than 7 courses of Zantrene, with an average number of courses at 17 (or 5440 mg/m2 cumulative dose). If you dosed Zantrene at 50 mg/m2 3x per week, you would need to dose for 36 weeks (or 9 months) to reach 5440 mg/m2 cumulative dose. Based on this, I agree with you that cumulative dose should not be a concern.
A further point about the P1DE is that it will be an opportunity to showcase a process. By this I mean receiving a patient, taking a biopsy and testing it with a sensitivity assay to determine sensitivity to Zantrene, and then dosing the patient. If RAC can show a process to BP that can identify appropriate patients, treat them, and get great objective clinical responses, then RAC shareholder will probably be part of the largest ever Australian biotechnology buyout. In my opinion, when the P1DE starts, the clock starts ticking.
(20min delay)