Theratechnologies Inc T.TH

TH2101

[jfm1330]

On new information in the updated corporate presentation is the identity of a new PDC made out of TH19P01. It was given the codename TH2101, which likely mean it was the first research molecule made by Thera in 2021, jusy my guess. That being said, they also revealed with is the cytotoxic drud that is attached to TH19P01, and it is a molecule called SN38, which is the active metabolite of a drug called Irinotecan. This is a topoisomerase I inhibitor and it is 1000 times more active than irinotecan.

https://en.wikipedia.org/wiki/SN-38

[Wino115]

This is strategically very ballsy!  I haven't been able to read the new deck,  but this is potentially huge.   The reason?  That cytotoxic is what is on the ADC Immunomedics created that was bought by Gilead for $21bil. And we know its name -Trodelvy.  This would be the Trodelvy killer! So the industry and FDA gushed over the Trodelvy science for mTNBC and it was

[Wino115]

This would also really help but parameters around the program and and u Delhi get possible valuation metric.  Certainly narrows that unknown future value that we and the market don't quite have a handle on now.  Putting that comp up there makes it really easy for analysts to justify rather large values.

[jfm1330]

I forgot this was the cytotoxic agent in the Immunomedic ADC, even though I saw it was very potent. Now, as the codename suggests, they have this molecule since January of this year, so they likely already have some animal data with it. Now, if Thera can come with a clear proof of concept with TH1902, the then they come out with spectacular animal data with with TH2101. 1+1=2. It would really

[Wino115]

Absolutely, and I think in this case 1+1=5. The POC would get the interest of other producers with newer toxins or immunotherapy drugs that want a vastly superior delivery mechanism for their drug in advanced cases with high Sortilin.  If there is some additional benefits to interacting with Sortilin as THYX says with VM and mestaticism, then even better.   Trodelvy targets TROP1 or 2.

[qwerty22]

They have this as the 3rd point on slide 31 but for me I think it's too early for partnering with proprietary chemos. It's worth looking at what many companies actually do. So there are a lot of molecules in development built on trastuzumab which is an old, approved HER2 antibody. You would wonder what the commercial interest is in going after a target which already has approved drugs

[jfm1330]

I did a quick search, it seems SN38 is off patent, all I found were patents for ADC using it, like Immunomedic. Anyways, SN38 is not an approved drug because it's not soluble enough in aqueous conditions, also, I think it is too toxic for systemic use. That's why it makes sense to use it in a conjugated system or in liposomes. As for immunotherapy, I don't think their MOA is a good

[jfm1330]

In the new corporate presentation, there is a line about combo therapies with immunotherapy drugs, But it talks about using both drugs in combination, not linking a monoclonal antibody to TH19P01. It reads as follow: Explore rational combinations of SORT1+ TechnologyTM with other treatments, especially immunotherapies

[jfm1330]

In the corporate presentation, in the section: "SORT1+ TechnologyTM: Future Opportunities". They talk about exploring the need for a companion diagnostic tool for SORT1, but they talk about some immunohistological tool to detect the level of sortilin expression in biopsies. Unfortunately, there is still no words about the possibility of using TH19P01 with Gallium 68 as an PETscan imaging

[jfm1330]

Sorry to come again with that, but in the new corporate presentation one item in the section "SORT1+ TechnologyTM: Future Opportunities" is this: Gain better understanding of the exact MOA, impact on surrounding tissue/tumor microenvironment (TME) and fate of conjugate once it enters the cell and is degraded One thing the imaging TH19P01-DOTA-Ga68 would allow to do, is to follow over

[realitycheck4u]

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[jfm1330]

For the stock price, the key will be efficacy results until the end of the year, but for the long term view, the key will be the proof of concept. I say that because proof of concept is linked to the peptide TH19P01, that is the basis of the whole platform, while efficacy of TH1902 could depend on the effectiveness of docetaxel on a given cancer. What I am trying to explain, is the fact that the

[SPCEO1]

Well, I thought they seemed pretty confident, but that pretty much tells me they are very very confident!

[SPCEO1]

I think I can imagine how Paul will start the NASH partnership negotiations with Big Pharma. His first line will be something like this, "If you hope to have any chance of partnering with us on cancer, you had better impress me with your offer on our NASH partnership first." They may have a stronger negotiating position in NASH than we may have first thought!

[jfm1330]

There is still a job offer on their website drom April 15 for a drug discovery scientist. These are the first lines of the offer: Under the supervision of the Manager, Chemistry, the Drug Discovery Scientist is responsible for managing a variety of activities, including the synthesis and purification of new anti-cancer molecules,  So it is pretty clear that they are in the process of

[stockman75]

Certainly appears all is going well with phase 1. Hopefully we are all not victims of confirmation bias.  Though the evidence is certainly pointing to success at this point. I am sure things could reverse course quickly but hard not to be encouraged. 

[qwerty22]

 I would caution a little realism. Anybody have an older version of the investor presentation, say 12 or more months old? Th1904 has been on the pipeline graphic for a long time now, it's milestones now are toxicity and scale-up. Has that changed at all from earlier presentations? I don't have an earlier version but I doubt it has changed much. I think they can do early research and

[palinc2000]

Qwerty you are such a downer!!!!You seem to be a scientist fixated on facts rather than  fantasy,,,LOL BUT I value your opinion A LOT

[juniper88]

Initially Th1902 was for TNBC and Th1904 for Ovarian cancer.  But then they started doing more test and as you know Th1902 worked on other cancers too.  And Th1902 actually worked better on Ovarian cancer than Th1904. I believe that first Thera should concentrate on Th1902, there is a lot to be learned.  And if the peptide works some serious research should be done to see what

[jfm1330]

It is clear right now that preclinical research is already undeway with other PDCs, and that they plan to further the preclinical work. You don't look to hire a preclinical project manager if this not your plan, and you don't hire a drug discovery scientist if your plan is not to make new PDCs out of TH19P01. Look at the new corporate presentation, they are all in on oncology. A switch

[SPCEO1]

Oh, they could express it more strongly. I am 100% certain that if the CEO of CYDY had seen whatever it is that THTX management is seeing in the phase I cnacer trial, he would have had 8 confernce calls about it by now and twice as many press releases. I am not suggesting that is the extent that THTX should go to but just saying they are in a pretty normal spot versus the average copany with

[scarlet1967]

Couldn't agree more, yes they are very optimistic but who is paying attention? CYDY announced their results for phase1 cancer trial in two days their valuation jumped from already elevated levels by over 30% which is more than THTX's market cap. It's not only supporting a better current depressed valuation but also about future potential positive reaction to their announcements if and

[qwerty22]

And the announcement is again horrible. It's another piece of unscientific filth. I'm with JFM this is not any sort of comparison to make.

[scarlet1967]

The comparison isn't between THTX and CYDY but many other companies who are far more proactive in messaging. They have the Cantor meeting behind closed doors. It's about the time to have meetings with doors open. This is a public company ran so far like a private company. So far this year they have not attended many/any conferences I think they had a couple abstracts during the AACR

[qwerty22]

Read this Twitter thread if you want to know how bad it is. https://twitter.com/IamBreastCancer/status/1417563369175801856 And stop wishing thtx be like them.

[scarlet1967]

Who wish them to be like CYDY, we are talking about two extremes both scenarios are bad

[SPCEO1]

JFM and Qwerty are either willfully mistating my point re:CYDY or just have an understandable bad emotional overreaction when that company is mentioned. To be clear, and to say again what I have said in the past, I don't think CYDY is borderline criminal, it is totally criminal. I don't  want THTX to become CYDY but I would like them learn that there are different places on the

[scarlet1967]

The problem is they don't have a measured retail strategy, they had one chat this year and LSA. The chat was with new company with not many followers and the LSA has limited retail investors. The retail segment of the market is more relevant than ever now, general public have access to information thanks to fast electronic communication. Many of them don't invest based on institutional

[canadapiet]

You all are doing great work here, heads off!!  And thx for the great info/opinions, it is of great help to make educated decisions!  For me, the company does not have to communicate that much, if there is not much of important developments happening! And that's exactly what mrs. Gibson told me. But they can do 1 (ONE) thing and it would give the market of retail investors a

[jfm1330]

The best argument you have is again this comparison with a borderline fraudulent company? A company the FDA came out to correct the false statements? Anyways, my point was not in form but in substance. Also, some will likely regret not paying attention right now. If they come out will really good results, you will see that, suddenly, many will pay attention. . The reality is that many that are

[qwerty22]

I think if you have a handful (6 is a number I have in my head) of research scientist on a couple of benches in beliveau's labs then that's never going to be enough to keep a clinical program going so hirings are inevitable. And diversification in skill sets is great in my book. It doesn't mean that any of these things will move into the clinic any time soon. TH2101 peaked my

[SPCEO1]

The company could share more info with investors if they wanted us to not extrpolate things we should not, but they likely, with good reason, want to have much greater control over the message. If they were completely open with every twist and turn in the trial, the market would likely not be able to handle that sensibly, unfortunately. So, they keep a tight rein on info, tell us only what they

[qwerty22]

Yep, I'm English I don't have the N.American can-do attitude, maybe I can state this point a little more positively. I think the lead drug is great. I think it's totally fit for purpose. The fact it's profile is so well understood I think adds a lot to the drug development process, it makes some things simpler, it might allow them to draw stronger conclusions earlier in the

[juniper88]

From what I understand of Sortilin is that it is a receptor highly associated with Cancer Stem Cells (CSC).  These cells are harder to kill and the theory is that cancer often recurs because these CSC were not killed off by the chemo drug during first line treatment.   qwerty, I would like to hear your thoughts how Th-1902 could kill of these CSC, when taxol was not able to during

[qwerty22]

  Here's a review on how CSC affect therapy. https://www.cancernetwork.com/view/cancer-stem-cells-implications-cancer-therapy Here's a paper linking Sortilin to breast CSC https://bmccancer.biomedcentral.com/articles/10.1186/s12885-021-07854-0 Your question is way above my pay grade. It sounds like CSCs are a tricky problem and expecting one treatment to solve it is

[jfm1330]

Some will say again that I am obssessed with PRRT (peptide receptor radionuclide therapy) but I have high hopes about the use of actinium-225 in PDCs. This radioisotope is emitting alpha radiations that are strong enough to break both strands of DNA. This is, in my view, quite a defenitive way to kill a cell, stem cell or not, because it is not acting on a molecular interaction basis to block some

[Wino115]

If we get POC, the hard part will be ranking which approach to do next, and then next, and then next! On the CSC and Sortilin question, I recall that the Univ of Gothenburg team and their spinoff venture (Sortina Pharma) is studying the Sortilin/stem cell nexus for their mTNBC drug they hope to figure out.  Their website or Univ research may have more on it.    

[jfm1330]

I am unable to find a website for Sortina Pharma. That being said searching with some key words I found some interesting scientific articles. I found the following about the role of sortilin in breast cancer: Interestingly, sortilin has been associated with metastatic potential in breast cancer [17] and is highly expressed in breast cancer cell lines compared to non-tumorigenic breast epithelial

[jfm1330]

The sortilin receptor is a prerequisite for progranulin-induced CSC-like propagation In order to identify how progranulin induced cancer stem cell propagation we investigated the role for the receptor sortilin, previously identified as one of the main receptors for progranulin [24, 25]. Silencing of sortilin using siRNA-inhibited progranulin induced increase in mammosphere formation of both

[jfm1330]

So here I think I have the Sortina approach. Using a small molecule called MPEP (1-[2-(2-tert-butyl-5-methylphenoxy)-ethyl]-3-methylpiperidine, which they describe as a sortilin affecting compound. So clearly the idea is to deregulate the sortilin-progranulin axis. Again, TH1902 is doing that as a secondary effect. The primary goal of TH1902 is not to deregulate the sortilin-progranulin axis, it

[jfm1330]

Sorry for the nerdy stuff, but finally, MPEP (1-[2-(2-tert-butyl-5-methylphenoxy)-ethyl]-3-methylpiperidine is not interacting with sortilin, but it works to prevent the cell from expressing sortilin in the first place. So it prevent the cell from making sortilin, the result is that it not there on the membrane to bind progranulin and internalize it. So it increases the level of extracellular

[realitycheck4u]

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[jfm1330]

I am not a cancer expert at all, but I know enough about biochemistry to understand some stuff, to a certain extent, when I do searches about topics of interest and when I read relevant scientific articles. Biochemistry is like a language, when you master enough of that language, it allows you to learn more of that language. That's what I try to do here, use my relatively basic knowledge in

[SPCEO1]

You might have a second career as a cancer expert if you want it! Thanks for all the great work and info you are providing all of us.

[Wino115]

Thank you for digging in.  I do recall in the new presentation their new diagram specifically shows that the Sortilin is recycled and spit out the cell again to attach to the membrane.  That was the first time I saw that.  No doubt they understand the amount and timing of recycle are important factors to  learn in trials.   Very helpful and I think you found the

[SPCEO1]

I don't know if this info might be helpful or not but I pass it along just in case. My wife has a health condition that requires her to take the drug Actemra. This drug deals with IL6 and was recently given EUA for use in late stage covid patients. So, it suppresses the cytokine storm in some manner through how it interacts with IL6. I am not an expert enough to know more than that and it may

[juniper88]

I am sorry to hear that,  I know you had told me that she had an autoimmune problem, but I did not know she had to take a bioligic for it.  My best wishes and prayers for her and your family. As you know my wife also has SLE, which is why I had been especially interested in TH1902, because the sortilin/prograngulin/IL-6 connection.  The oncologist did extensive gene testing on her

[jfm1330]

IL6 is interleukin-6, a protein in the family of what is called cytokines. Progranulin is also classified as a cytokine. We heard about cytokines related to the covid-19 infections. Covid is provoking in some patients what is called a cytokines storm, which is an inflamatory overreaction of the immune system because cytokines are involved in inflamatory processes. But it seems that many cytokines

[Wino115]

It seems the UG labs found that relationship to certain late stage cancer expression of Sort1, specifically mTNBC, but probably also found that the UQAM labs had already built a peptide that latches on and were way, way ahead on that approach and went with the alternative -assuming Sort1 is necessary for tumor cell growth so trying to suppress it.  It does sound a lot more challenging and

[jfm1330]

One thing we are not talking about right now, because it is way too early, even though I mentioned it before, is the possibility of combo therapies with different PDCs that SORT1+ is theoretically allowing for. Again, I know it is way too early, but still, on paper the possibility is there. To attack cancer cells with two or three PDCs at the same time, with different mechanism of actions. If the

[qwerty22]

"I do recall in the new presentation their new diagram specifically shows that the Sortilin is recycled and spit out the cell again to attach to the membrane.  That was the first time I saw that.  No doubt they understand the amount and timing of recycle are important factors to  learn in trials." That would be a big presumption to make. It would take a lot of science