RE:RE:RE:The phase 1a trial has already been de-riskedBarring any clear sign of efficacy, I would take data around the proof of concept -- the SORT1 target is valid, the peptide affinity is valid, SORT1 is internalizing it, it is not being repeled, it appears the linker works, it appears metasticizing was stopped, etc... From what I've learned here, some of that may be implied by the data and some of that "internal cellular" science would be very hard at this stage. But anything along the lines of validating SORT1 as a very important target and the peptide as doing what it did in preclinical is a win for me.
jfm1330 wrote: We all know that phase Ia is not designed to produce the maximum efficacy results. At the same time, the FDA forced Thera to take all comers in the trial in order to show if efficacy is related to sortilin expression. So it seems that FDA thinks that even though this trial is designed to understand safety parameters, that it will likely also show be able to show efficacy. Obviously, this is not 100% sure. TH1902 could be plainly efficacious in any patient, sortilin expression or not. But they requested to enrol all comers, so efficacy data is clearly a possibility for them.
Also, Marsolais and Levesque pointed out many times the fact that in animal model, TH1902 allowed efficacy at equivalent doses where docetaxel alone had no effect. They claim that TH1902 is able to concentrate docetaxel in sortilin expressing cells and that the higher that expression is, the more docetaxel can be concentrated. In preclinical they found that for equivalent doses of TH1902 and docetaxel alone, TH1902 could concentrate docetaxel uo to six times higher. So if the concept is good, and TH1902 really works as expected, efficacy is likely, even in phase Ia, especially if they selected patient with cancer types that are very likely to overexpress sortilin, and if they are lucky enough to get one or two patient with very high overexpression, then results could be great, even with only two or three cycles of treatment.
We will see. It is speculative at this point, but many indirect signs are pointing in the right direction. My guess is that they will see some efficacy, and that in the results, they will correlate it with the level of sortilin expression. Also, at the time of the press release on the MTD, they will likely say that some patients are still under treatment and that an update wil follow later on about these patients to see the full effect of the drug on these patients.