Theratechnologies Inc T.TH

Trial with unique way to deliver Docetaxel

[jeffm34]

https://www.sciencedirect.com/science/article/pii/S0168365920303540

This was a phase I dose escalation trial as well. I assume Thera will be monitoring tumour size in each patient after every treatment cycle as well. Which means they should be seeing efficacy data all the way along the trial. 

"The total tumour burden measured in this patient decreased from 129 mm at screening to 109 mm in cycle 2, 90 mm in cycle 4, 86 mm in cycle 6 and 85 mm at EOT." 

[SPCEO1]

My guess is there could be some interesting aspects to this paper for us and am looking forward to any comments JFM1330 and Qwerty might have about it. I could make some uneducated comments but that would likely be wasting everybody's time.

[qwerty22]

Micelles are like small spheres that have structures similar to cell membranes that allow them to fuse with the membrane and deposit their content (docetaxel) into the cell. So better delivery of chemo to cell but the problem is it does this to all cells. Just looking at the abstract the results fit that. They can dose lower to get efficacy but seems like some DLTs also appear. It doesn't look

[SPCEO1]

If THTX's therapeutic window is larger as seems likely, can you explain what that means for the success of TH-1902 from a commercial perspective? I think we can guess but I would rather get a clearer read on that from someone with your background. Is there anything in the PK or PD info in that article that has any relevance for TH-1902? Hopefully, JFM1330 will weigh in on that as he clearly

[jfm1330]

The therapeutic window, or therapeutic index is the interval between the lowest dose that will provide some efficacy and the maximum tolerable dose. In the cas of free docetaxel, this window, or interval is quite narrow, ranging from 60 mg/m2 to the MTD of 100 mg/m2. So the have some efficacy, you need to go close to the MTD, which is not good for the patient and limits the duration of the

[Wino115]

Glad you clarified this as I had confused therapeutic window with duration in all my posts. I thought it meant the likely time (months, years) you can keep treating patients with your dose and still keep the tumor at bay or shrinking.  I was wrong as the window is the dose range possible with your treatment. Thanks for enlightening me and if anyone reads an old post of mine, I meant duration!

[jfm1330]

I read the article. Some interesting points. First, they use a linker to attach docetaxel to the micelles and this linker binds docetaxel through an ester bond. The ester bond is the same chemical bond that is used to link docetaxel to TH19P01, to make TH1902, and this is the chemical bond that needs to be selctively cleaved once TH1902 is inside cancer cells by an enzyme called esterase

[jfm1330]

On the website of the company it is stated that the linker is not cleaved enzymatically, so this comparison with TH1902 is finally not valid. All ester bonds are not equal, some are stronger and other weaker depending on the rest of the molecule on both side of the bond. The strange thing is that they specify that the cleavage is not enzymatic, but they don't explain how it works. Is it just

[jfm1330]

Here is the link to the website of the company behind this micelle approach. It seems that their micelles are also penetrating skin cells at a higher rate leading to toxicity. Let's hope there is not an unforseen side-effect of that kind with TH1902. https://cristaltherapeutics.com/programs/oncology-programs/