RE:RE:RE:RE:Any comments on this from Leede's Doug Loe?Someone I know who has a friend who is a doctor sent this to me and I thought I would share it in case it helped:
TH1902 contains 2 dox molecules per peptide.
It’s weight contribution to 1902 is 43% (2x800/3700x100). Therefore, 300 mg of TH1902 is 129 mg of Dox.
Approved dose of dox is 70-100 mg/m2.
So 1902 delivers about 1.5 fold more dox per cycle.
Does this mean more efficacy?
Abraxane is delivers 100 mg Dox and has 20% neutropenia in phase 3 trials.
I expect that 1902 will be dosed around 250 mg/m2 in chronic treatment. The dose titration is due to toxicity due to drug accumulation and recovery of white cells.
So 250 mg of 1902 means 107 mg of Dox similar to Abraxane.
Sortillin may be over-expressed in cancers but normal cells also have sortillin. So it is the difference of expression.
qwerty22 wrote: Just to clarify. This paper from THTX's scientists
https://onlinelibrary.wiley.com/doi/10.1111/cas.15086
states " Note that 35 mg/kg TH1902 and 15 mg/kg docetaxel contain equimolar amounts of docetaxel. "
When you do the calculations ther is 100mg of docetaxel in 233.33mg of th1902
So 300mg is exactly 1.5x higher than a 100mg dose of docetaxel. So THTX's numbers are correct but it's hard to know what point Loe is making here. All that aside it's a pretty positive note in my view, he's acknowledging the progress they've made but still putting that valuation point in the future. That seems to be a fair assessment to me.
The point I was mostly trying to make yesterday is IF those 420 AEs had not arisen then they probably would have continued to move forward with 420 dosing and we may have been at that valuation point for Loe now. As Paul said this process isn't always linear, they had to take a step back and that has added 3 or so months to the process.
qwerty22 wrote:
It does sound like he's mis-understanding that but given he doesn't state his own multiple it's hard to say. It could just be that he thinks by picking 100mg/mm2 that THTX are at the cautious end of this equivalent estimate. Does it say what he thinks the multiple is anywhere else in the report?
Wino115 wrote: I belive one of our science experts once discussed how to convert what the PDC level attached means in relation to the normal IV administration levels. Revolved around the fact the peptide has two units attached and there's some sort of molecular weight conversion you have to do to make it an apples-to-apples conversion. I think Loe is not doing that so it's not the proper comparison. Sorry, can't get more specific but I think JFM is the molecular chemist that did those comps before.
SPCEO1 wrote: Thera provided an update on its Phase I solid tumor testing with TH-1902, indicating that it has likely identified a maximum (barely) tolerable dose that is at or above 420 mg per square meter of body surface area, and this observation motivated the decision to shift all future patient dosing to a lower level of 300 mg/m2. Thera indicated that this represents a 1.5x elevated dosing level over that commonly used for docetaxel itself in solid tumor chemotherapy, but in our review of the literature, it is far higher than that (docetaxel as a monotherapy tends to be administered initially in most tumor types at 75-to-100 mg/m2). Accordingly, we believe that dosing at or above 300 mg/m2 still reflects favorably on the tumor targeting pharmacology that conjugation to sortilin receptor-binding peptides confers in TH-1902. As stated above, the concept of incorporating sortilin biochemistry into TH-1902 for targeted chemotherapy still seems reasonable to us and we are optimistic that justification for us to ascribe formal market value to this program will be forthcoming.