Theratechnologies Inc T.TH

The Sort1+ Platform

[Wino115]

The points from JFM, Sabbo and Juniper are important and they really have to discuss this in reasonable depth once they get revised protocol approved. For them to pause enrollment and not outright stop it there must have been something in the totality of all the data collected and what others may know about PDCs, taxols and other dosign approaches to at least have some belief that they can use some part of the function they've observed to the benefit of efficacy. Maybe it's that half life issue that is advantageous in being able to dose more frequently and not take a 3 week pause in getting the chemo agent in to the tumor. I'm totally speculating, but that is the kind of disclosures they need to make to investors once they relaunch the trial. Give us the full logic --what was seen and why a different approach to get from only seeing 2-3 signs of efficacy to something more robust and how dosing is an element they can play with to try to get there. They need to explain to us the parts of the concept they "think" are valid and functioning enough in humans to theorize there should be efficacy with that type of chemo dosing regimin and why. 

It's also encumbant that if they do think it's the chemo, that what they're seeing in their lab with other agents might lead to something more effective like what Sabbo and JFM are speculating on. If there is, that can be the basis for a partnership with someone who's taken those toxins further down the road and is looking for some way to target cells better. But they need to show that with data if it's there, which no one knows at this point.  They've talked about SN38 and SiRNA so give any insights if there are any.  That may be asking for too much, but the point of trying to validate the concept of the peptide and target would be valuable if there's any ability to actually do that from the data. 

Last point, I think their  trial is not a whole lot different than any other trial where you are trying to help the very late stage, heavily treated and resistant enrollees. All of those would face the same difficulties since it's just what happens at that stage unfortunately. I would assume there is always a mix of types of enrollees at the larger cancer centers in cities - some will try but end up deciding to stay at home with hospice and some will stay in centers doing everything they can to get through a trial. And you get everything in between. The unfortunate truth is there aren't many options left at that point and it would only be through a trial, and this is one of them some may try. I would think one advantage would be the side effects and safety issues have all been reported as still well below SAE3 levels. The issue is the robustness of the toxin doing it's thing on the tumors, not so much any treatment effects causing disenrollments.  Anyway, it's incumbant on them to really explain it all in a reasonable depth so there can be a far better understanding based on that collected data and their reasonable theories on the restarted trial. 

 "If they treat patient with 1x docetaxel of TH1902 once weekly, the toxcity might be weaker and efficacy might be better."

[jfm1330]

Sorry, if lower and more frequent doses bring more TH1902 into cells expressing sortilin over time, it will do it for all cells expressing the receptor, not only cancer cells, so I don't see how you increase efficacy without increasing side effects. Unless side effects are related to free docetaxel. But hey! Only 10% of free docetaxel Thera told us. What is this10%? We still don't know

[juniper88]

If the toxicity to the eyes is because the eyes have high sortilin expression and the docetaxol is entering the eye cells to the extend that it is causing the side effects then why would a more potent payload that destroys the cell and surrounding cells have less side effects? Unfotunately we don't have any information of what is causing the side effects in the eyes and how serious those side

[PinnacleX]

 Did you not read that report this was mainly "mainly" result, this wasn't all of it they didn't tell us everything that went wrong they only told us 2 things, why don't you ask what the others things were  that went wrong, going blind was just one lol

[jfm1330]

I will repeat myself for maybe the tenth time about that, but the ressources to do a Ga68-DOTA-TH19P01 PDC are available near Montreal, in Sherbrooke, at CHUS. That's where I go for my Ga68 imaging scans. They put the Ga68 on Dotatate in house. Ga68 is emitting only positrons, not radiations. It has very low toxicity. The only thing I don't know is if they have a small PET scan machine for

[qwerty22]

Sure just attach some radionucleosides to the peptide and start pumping it into patients. Easy as. I can't see the hospital people at CHUS or CHUM asking if this has gone through the whole R&D and preclinical process. Can't see them needing to develop an SOP, develop the parameters for successful, repeatable conjugation, test it to the hilt before giving it to patients.. Can't see

[jfm1330]

With the actual situation I flushed my ignore list to get as many point of view as possible on the actual situation. I thought maybe some people changed since a placed them there. As I can see this is not your case. If one read my message properly,he will see that I talk about preliminary work and small PET scan machine were you can do a scan on mice. So my message was clear. I was talking

[jfm1330]

I was obviously talking about an hypothetical Ga68-DOTA-TH19P01 imaging PDC, not the approved Ga68 Dotatate for neuroendocrine tumors. Sorry.

[qwerty22]

I guess I just don't see hospital service centres, serving people like you, as places for animal research. Whenever I've looked at biotechs working in this area they have grown out of academic centres where they are already specializing in this type of work. . I struggle to see companies simply deciding that they are now radioligand guys, my instinct is this is not how it goes. Even

[qwerty22]

I think to a large extent being in the dark about many things is the normal state of affairs, and not just for shareholders. When NGM shut down their NASH program it wasn't because they'd discovered something new about the MOA, it was because they didn't see that they were reaching the required efficacy. No need to know the "whys", just need to know if they can get that

[juniper88]

I pretty much agree with everything you wrote.  But exactly how do you screen for sortilin?  You take a biopsy?  Well, we all know that tumors are different within a single person.  There can even be multilple cell lines within the same tumor.   I believe we need to realize that sortilin as a cancer target is stil in the very early stages of cancer research. 

[qwerty22]

But exactly how do you screen for sortilin? Well the trite answer is you measure it the best that you can with the tools at your disposal and you come up with an imperfect answer. I would say that part of the reason they didn't prescreen was to amass as much data as possible in order to understand exactly what your eventual screening method is telling you when you do finally apply it

[jfm1330]

That's why they ideally need a partner. The other day I listened to a webcast by an oncologist about neuroendocrine cancers. And with this type of cancer the rate of cell division (Ki-67) is talked about a lot. Grade 1 tumors have a Ki-67 of 3% or lower, Grade 2 of 3-20% and grade 3 a Ki-67 above 20%. So the doctor said this grading can be misleading and said that he did two biopsies on the