RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:Any comments on this from Leede's Doug Loe?Sorry Wino, you still base you thinking on preclinical data that we now know is irrelevant. We know that because the only thing we know for sure is that they are testing 300 mg/m2 as the MTD. They decided that 420 mg/m2 was not tolerable, so it cannot be the maximun
tolerable dose.
OK. So follow me. In the preclinical data, Thera stated that for TH1902 they reached an equivalent MTD of three times the MTD of docetaxel alone. So they reached a MTD on mice of 690 mg/m2. We now know that the MTD on humans will be at best 300 mg/m2. So the conclusion is that all the data on animal is inflated by a lot, if it really works. We don't know if it works on humans. It also means that the proof of concept established on xenograft mice cannot be taken for granted on humans because the MTDs are so different. So all the other data can no longer be trusted. The difference in MTDs is so huge. So forget about your graphics of efficacy on xenograft mice. It is now worthless. The whole concept may be invalid. We don't know at this point. They gave no hints that would allow to be optimistic. Nothing about any sign of efficacy and proof of concept. So you are down to a MTD that at best will be 30% higher than the MTD of docetaxel alone, and like it or not, the therapeutic window you can now hope for is much smaller that what was hope for. Listen to Marsolais in the KOL presentation Q&A part. For him at that time, the linker would release only 1% of the docetaxel in the bloodstream. So why is it now toxic at 420 mg/m2?
Again, as I also wrote, maybe phase Ib on selected patients and many more patients will allow to better understand how TH1902 is really behaving on patients that are really highly overexpressing sortilin and that it will lead to a revised higher dose for phase II. I don't want to discard this program at this stage. All I say is that it is not going as planned it is taking much, much, longer than expected by the company and all we have is the disapointing side, with nothing on the positive side. Also, their tone is much less enthusiastic about the whole thing. It is beyond understanding that it will take more than a year to complete this trial. Something went wrong at some point and they don't tell us what was the problem. They did not explain how this trial would really be conducted. We know almost nothing about it. Back in June, during the KOL presentation they were expecting results to be published at the beginning of the fall. Now it will something like seven or eight months later. Such a delay would have warranted a much better explaination from them. So if somebody wants to complain about poor communication, complain about that. For once it would be about important stuff.
Wino115 wrote: Sorry JFM, I believe you are wrong on this. Take a look at this chart in the January IP. This is a 1 for 1 comparison of TH1902 vs. docetaxol. So your argument would be the OPPOSITE -- it will be 30 to 50% BETTER since the RP2D will be higher than what this chart shows, not lower as you state. These charts showing tumor suppresion and progression free survival are equimolar, not at the max dose of TH1902. It would only increase, not decrease. There are some charts where they did use more TH1902 vs. docetaxol, but not these.
Also, the step-down to 300 is the final test for the RP2D given the MTD was 460. That is what I understood from Christian.
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