Theratechnologies Inc T.TH

A few reminders from the KOL event a while back

[Wino115]

1. Ovary tumor total accumulation in healthy vs. tumor cells (Rubicin v. TH1904)
For TH1904 the tumor cells accumulated 8000 ng/g of tissue
For TH1904 the healthy cells accumulated 300 ng/g of tissue

For plain Rubicin, tumor cells accumulated 1000ng/g of tissue
For plain Rubicin, healthy cells accumulated 1200ng/g of tissue.

Which means sort1 as a target pulled in a lot of the dose and very little appeared in healthy tissue. Both went in the right direction --more in tumor, less in healthy - especially compared to control of IV rubicin.


2. Half life of sort1 is 4 minutes, half life of TH1902 is 1 hour.  So in 2 hours, it's all out.
For an ADC, it takes 6 to 10 hours to get it all out.


3. Off target accumulation. Marsolais pointed out that the control is an IV of a chemo that goes into essentially every cell in your body with no targeting at all; hence, the safety issues.  Sort1 is the only protein they know of that increases a lot with the severity of the cancer progression, so for the patients they are targeting, it will be by definition very high.  His quote on the off target is that sort1 normally is not very highly expressed (as seen in the healthy tissue stain samples), and given this, the half life, and the PDC approach the concentration in other cells expressing sort1 would be "...very, very low".  Obviously, this is all in vivo he's talking about. Did mention it will not cross the blood brain barrier. When you listen back on it, you are reminded that the important factor is not necessarily a massive dose of chemo, but the ability to be far safer and quickly concentrate it in as many sort1 expressed cells quickly, thus reducing side effects and allowing patient to get another dose quickly and keep going. Did mention that for any of the cancers that are typically not detected early (lung, ovary), targeting sort1 may be best option.

[LouisW]

YOu mentioned "half life of TH1902 is 1 hour. " Is this in mouse? I would say that 1 hr is too shout for patients.

[LouisW]

Typo in last comment, sorry......i mean 1 hr is too short for patients.

[Wino115]

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'

[Wino115]

Sorry LouisW - this is the data for the half life of sortilin internalization.  The TH1902 half life is, I believe, from their plasma studies done in mice. Remember the chart measuring the amount of docetaxal and TH1902 in the blood stream over time.  I believe that's where they got that from.

[jfm1330]

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

[Wino115]

I 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

[SPCEO1]

To sum up what I think Wino was saying here, if you are making your decisions because of your emotional reaction to a falling share price rather than based on the science, you are doing it wrong. Stock prices rise and fall based on a myriad of factors which impact the supply and demand for the shares in the short term. Those factors often have nothing to do with the fundamental position of the