RE:RE:RE:RE:A few reminders from the KOL event a while backI realize the mice/human difference. That is his quote from the KOL event. I don't know the science enough around what he was talking about, but perhaps it's that the docetaxol is attached and that it's all encompassed by a polymer. The slide up when he referred to it was one showing a chart from the AACR 2020 Abstract with plasma concentration v. time. Perhaps what he was trying to suggest was that whatever does not migrate to a target stays in your bloodstream and is ultimately dispersed or finds its way out after 2 hours, meaning that most found a target in the mouse, some went off target (the ratio they showed of amount measured in tumor v. healthy was 8000/300) and some degraged or was expelled, but whatever it was, there was minimal docetaxal floating around in the bloodstream after 1 hour and next to none in 2 hours.
jfm1330 wrote: All that tells us nothing about what is going on in humans. This study gives in vitro results with progranulin as the sortilin ligand, but progranulin is not TH1902, it's affinity to sortilin is not the same. Also where is this "all PDC is out of the body after two hours". We know nothing about that in humans, and TH1902 and docetaxel related to injected TH1902 are two different things. If I remember well, Marsolais was claiming that TH1902 had a half life in the bloodstream of mice of about one hour. Half life of TH1902 is not half life of docetaxel related to TH1902. And again, this was on xenografts nude mice. We have nothing about that in humans.
Wino115 wrote: It's not from their mice studies. It's from a paper they reference done by another team in a lab who were trying to find out how long sortilin took to internalize what it "scavenged" from the surface area of the cell. So, in other words, sort1 will grab the PDC and bring it into the cell in a very short time frame (but don't hold me to that interpretation as I really don't know the full extent of this lab experiment). And since the PDC is all out the body after 2 hours, the whole treatment is internalized quite rapidly, unlike an ADC that hangs around for 6-10 hours, spreading around and getting some in the tumor and some not. It's from the following slide on the KOL presentation, entitled
"SORT1 Rapidly Internalizes Ligands (progranulin) Increasing Half-Life". Here's from the paper and the reference is below. You may recognize the chart at 6E as that's what THTX used in their KOL presentation.
"Over the ensuing 10 minutes, nearly all Progranulin is removed from the cell surface of Sortilin-expressing cells. By 18 min, no diffuse plasma membrane Progranulin signal is visible, and limited signal remaining near the cell surface is concentrated in mobile puncta consistent with endosomes. The half-life for Progranulin bound to Sortilin at the cell surface is 4 min (
Fig. 6E)"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990962/
LouisW wrote: YOu mentioned "half life of TH1902 is 1 hour. " Is this in mouse? I would say that 1 hr is too shout for patients.