RE:RE:RE:RE:All comersMy understanding is that MTD will be the dose where they see no more than one DLT event out of six patients treated at that dose, and that the dose above that had at least two DLT events. So, let's say they dis three patients at 420 mg/m2 without a DLT event (grade 2 toxicity is not a DLT event). So, after that, they went to 560 mg/m2 and they had two DLT event out of six patients or less. Now they are back at 420 mg/m2 to test it on three more patients in order to have six patients treated with no more than one DLT event and declare 420 mg/m2 the MTD. This is just an hypothesis. We don't know. I don't know from where this one patient treated at 560 mg/m2 comes from, but it's not from Thera. All we know from the company is that they are evaluating the 420 mg/m2 dose at the time of publication of the new corporate presentation.
Also, remember that Levesque, on November 11, during the Credit Suisse presentation, said that at that time, they were testing many or at least several patients above 300 mg/m2, the next dose is 420 mg/m2. So it's as if he said back then that they were testing many or at least several patients at 420 mg/m2. That's three months ago. Several ot many means more than one, at least two, or likely more, back at the beginning of November 2021. So let's say many or at least several is three patients, that means it would have taken three months to test the 420 mg/m2 on three more patients to get to six??? No! It makes no sense.
To me, either what Levesque said during the Credit Suisse presentation was false, or they tested the 560 mg/m2, failed, and are now back at 420 mg/m2 to confirm it as the MTD. Remember, to go to 560 mg/m2, they did not need to enroll many new patients. The one that passed 420 mg/m2 would go to 560 mg/m2, so at least three patients already enrolled went from 420 to 560 mg/m2. So no need to recruit many new patients to go to 560 mg/m2, maybe none. Then, coming back to 420 mg/m2, needed to enroll only three new patients. So this hypothesis is coherent with waiting line for enrollment.
Also, remember that they follow the pharmacokinetic parameters of these patients after every injection of TH1902. So again, they can see toxicity coming out of that data. Also, as I said before, the design of the trial was not great to distinguish between sortilin overexpression levels. So the possibility of delays due to discussions with FDA are there. The more I think about it, the more I think that a trial with two arms would have been the ideal way to do the phase Ia. One arm with no sortilin expression or very low expression, and one arm with high to very high expression.