Theratechnologies Inc T.TH

Tarveda Therapeutics

[jeffm34]

A company with similar technology for cancer. They even did work on a NTSR1 targeting conjugate for cancer.   TH19P01 targets NTSR3(sortilin)

https://www.tarvedatx.com/09-16-2021-tarveda-therapeutics-and-sciclone-pharmaceuticals-expand-partnership-by-entering-into-a-license-agreement-for-hsp90-pi3k-miniature-drug-conjugates-in-greater-china

[jfm1330]

We spoke about this company here before. Their first candidate PEN-866 with SN38 went through a dose escalation phase I. It is interesting to read the results. They claim to be able to determine tumor accumulation of the drug through tissue pharmacokinetic (I am not sure exactly what it means and how they can do that). On the efficacy front, out of 26 evaluable patients, 11 had stable disease at 8

[jeffm34]

What's more relevant is the work they've done targeting the NT receptor NTSR1.  Sortilin(NTSR3) and NTSR1 are both overexpressed in some types of cancer cells.  "There have been broad disclosures from Tarveda Therapeutics involving conjugates comprising of a neurotensin analog and an active agent through a linker. For active agents, different payloads like bortezomib

[jeffm34]

More info on targeting NT receptors.  NTSR3 (sortilin) may be the better NT receptor to target because it can deliver the cytotoxic agent into the cancer cell through endocytosis.  NT has been utilized as a platform for the development of NTSR1-targeted agents for the detection and treatment of receptor positive cancers. Tetrabranched/multimeric peptides containing the sequence of human

[jfm1330]

Even though they share similar names and a common ligand (neurotensin), NTSR1 and NTSR3 are very different. NTSR1 is a G protein with seven transmembrane segments, while NTSR3 (sortilin) is a single transmenbrane segment (domain) and is not a specific receptor of neurotensin. So little comparisons to be made.

[jeffm34]

Actually there are significant comparisons and implications for TH1902.  Both receptors are over expressed in some cancer cells and both are present in other non cancer tissues as well.  In the studies targeting NTSR1 they found  "Nontumoral uptake was high in several organs"   This was always going to be the ibiggest ssue to overcome with TH`902.  This is

[SPCEO1]

My understanding is that the sortilin receptors that are contained within the cells are not going to attract TH-1902, only those that are expressed on the cell surface. Is that correct? It also has sounded to me based on earlier discussions here that most sortilin receptors are contained within the cell and that more are expressed in late stage cancer cells. If there are sortilin receptors in

[qwerty22]

You're understanding seems to be about how I understand it too. As I said I generally consider the study deregulated Sortilin expression in cancer as fairly shallow. There's a handful of good papers that have generally taken the first step(s) in describing what is going on in a number of different cancer. Sortilin seems to have been most studied in the brain. From what I've read

[jeffm34]

The amount of off target accumulation of TH1902 will likely be higher than those therapeutics that targeted NTSR1.  You can see the expression of sortilin(NTSR3) is higher in the cancer cells but also much higher in non cancer cells.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464404/  The proportion of cancer tissue which stained positively for NTSR1 (H-score > 0) was

[SPCEO1]

Jeff - am I right in saying that what matters is the amount of sortilin receptors on the cell surface and not the amount of sortilin within a cell? And that late stage cancer cells have shown to have more sortilin receptors at the surface of the cell? If this is correct, do the results you noted below matter much? If it is more about sortilin expression on the cell's surface than about the

[Wino115]

Thanks for all this.  It's clearly an important issue and one that they've likely understood from the beginning.  We'll only really know once the program moves further along and releases data that can aid in understanding it.  Once again, treatment "relative" to the normal standard of doxetaxol is what will be important --if they can get more drug in, safely. &

[qwerty22]

I'm just not sure there's any value in trying to understand what might be the difference between NTSR1 and NTSR3, as you say that's not the measure of success here. For technical reasons I don't think what Jeff is saying is exactly valid but it's not going to be a fruitful discussion to go too deep into that. What matters in all this is th1902's therapeutic window and if

[SPCEO1]

I think we can say confidently that TH1902 is moving forward in the clinical trial progress and that suggests that nothing yet has been discovered by TH that might keep them from pressing forward. They must see a wide enough therapeutic window as a good possibility or they would not commit the money to continue. So, while we do not know much about TH-1902 in humans yet, we do know TH knows a lot

[Wino115]

Qwerties and your point are both good. A flexible window along both dosage and administering would be worth a whole lot of experiments at a latter date.  But if you can prove you do get a lot of chemo in (say it is that 4-7x more), who's to say that you might see a better result in some tumors with lower doses given much more frequently?  It would be interesting to see if they can

[jfm1330]

Non tumoral uptake occurs with any PDC or ADC that works. THe only approved real PDC, Lutathera, has non tumoral uptake. That's why patients are selected based on receptor overexpression. Again NTSR1 and NTSR3 only share a similar name and a common ligand. All the rest is different.