Theratechnologies Inc T.TH

To better understand the complexity of ADCs

[jfm1330]

Really great article. ADCs are a much more complex matter than I thought and more complexity means more possibilities for something to go wrong. It is quite technical, some understanding of biochemistry is necessary to understand the essence of what is explained in there. After reading that I am more convinced that a good peptide drug conjugate can be better than ADC, but it need to be good, good peptide, good linker and good target. That being said, ADCs and PDCs faced some shared challenges an that make this read interesting to identify and understand some of the potential problems that could be encountered by Thera's PDC. It is not a slam dunk at all.

https://ascopubs.org/doi/10.1200/EDBK_281103

[jfm1330]

Back to serious stuff. I am now reading a good article on PDCs. I have not yet finished to read it, but this part is interesting, since again, they compare PDCs to ADCs: Although these conjugates reached the market and proved the feasibility of this approach, antibodies have serious limitations. Most mAbs do not penetrate into tumors. With a molecular weight of about 150 kDa, they are too big

[jfm1330]

Now the advantages of peptides as drug carriers. Most of these drawbacks can be eliminated by using smaller biomolecules like peptides. In fact, peptide-drug conjugates (PDC) comprise several advantages as carrier molecules. Peptides with up to 50 amino acids can be easily synthesized in large scale to a reasonable price and modifications as non-natural amino acids can be directly introduced in

[jfm1330]

Now a critical aspect that I pointed to many times here and maybe the greatest weakness in Thera's approach as far as I know. This is critical to have a chance to acieve success. That is why I talk so often about the imaging possibility with radioisotopes like Ga68. Peptide Receptors as Targets in Cancer Therapy A major challenge in the development of novel and highly effective anti

[jfm1330]

From the same article again. On the importance for Thera to developp asap their peptide coupled with Ga68. It is a common thing in this field an easy to do. Look. More than 200 reports were published focusing on the investigation of various Bn-like peptides conjugated primarily with radionuclides, including 9mTc, 111In, 67Ga, 68Ga, 64Cu, 177Lu, 90Y or 

[jfm1330]

So here is the link to the full article about PDCs. The only approved one is Lutathera, which was the source of my enthusiasm for this approach used by Thera in SORT1+. That being said, Lutathera is a peptide linked to a radioisotope. The linker is stable and no cleavage within the cell is needed for cytotoxic activity. No PDCs carrying chemotherapy drugs have been approved yet, only ADCs were

[Wino115]

A good day of research for us JFM! Thanks.  By the way, I've dug into a UK company called Bicycle Therapeutics and one of the things they do is use peptides for deliveries.  They're just a tad ahead of THTX with some of their stuff.  Completely different cancers and targets, but interesting nonetheless.  In looking in their publications area I came across his, which

[palinc2000]

Excuse my ignorance but it seems to me that since TH has already committed to and received a may proceed letter from Fda that the rehashing of ADC vs PDC and most of the other scientific stuff adds nothing to the investment thesis ,Unfortunately or fortunately the decision to go ahead with the peptide has been vetted by the scientific team ,consuktants and the CMO at TH.I dont see how all this

[Wino115]

You can skip them. It all came about from the Barclays Capital model on Trodelvy. Since it's selling into a similar market as TH1902 would if successful in trials, we can think of that as an attainable revenue stream for THTX. Knowing what they got in their Phase 2 and 3 trial, we can understand what would be needed for Accelerated Approval.  Given there the drug was effective, but still

[palinc2000]

I get everything you say in paragraph 3 ..We have known that for quite a while ,,,We are all hoping it works on human given that the dose can be multiplkied by x factor with low toxivcity ,,,,But what is the purpose of talking about the molecuklar structure or whatever,,,,Thus is not a scientific forum where PHD s argue and argue over such things This is how I feel and am guessing the silent

[qwerty22]

What was the point of talking about the CEO's skill set when he delivered us such an ugly deal? What was the point of find comparable when the company was prepared to accept their R&D was worthless? What's the point of forward looking financial statements like 25% YoY growth when it's based on a bunch of assumptions and can evaporate in an instant.. What's the point of any

[palinc2000]

    I think talking about the CEO and growth etc is more concrete and more useful and accessible to investors than long discussions in scientific terms that nobody really understands and are mostly just opinions....There are many many studies on Sortiln ....... are the details useful for investors ....maybe ....But as investor I need to decide if I sell or buy the stock or increase

[palinc2000]

Oups wrong link!!! I will try to find it

[scarlet1967]

The CEO is great at marketing, I enjoyed listening to him every single time when he presented company's prospects, he was the guy who said "Tesamorelin can be the first drug to be approved for NASH" he was the guy who said they are many catalyst in new future "dosing first patient, early readouts" he was the guy who claimed they have two promising drugs from the very

[palinc2000]

The CEO did not hand picked the BOD members,,,Still has to deal with 2 of the former CEO s friends and I would be surprised if he had any input in the nomination of Molson ,,,whom I see as someone who brings very little ,,, The CEO is the leader and may need to pound the table  with the BOD and also by now he should be in a position to evaluate the rest of the team    and act

[Wino115]

I also see that the venture cap arm of Gothenburg Univ invested in their startup, called Sortina Pharm.  If you just google Sortina Pharma it will pop up along with some other stuff.  Seems they are only at the process of screening through all sorts of possibilities, although they talk about their "lead prospect".  Can't see what it is.  Sortina Pharma AB today

[qwerty22]

Well I guess scrap any idea of collaborating with them as academics but no loss I now release thtx have the same skills in-house anyway at UQAM. Some of their IP (claims 40-45) https://patents.google.com/patent/WO2015144860A1/en and a little more of their science. https://www.humangeneticsjournal.com/articles/commentary-sortilin-inhibition-limits-secretioninduced-progranulindependent

[SPCEO1]

The work done here by JFM and others has been very helpful to me as I try to understand how high a chance of success we may have in that phase I trial. I am very grateful for it.

[palinc2000]

So what are the odds now? compared to the  odds a week ago based on what has been posted ,,,,We all know about FDA s designation 

[scarlet1967]

There have been many discussions re what they don't have "holes in their programs" thus low SP, well how is that those holes didn't stop comparable companies get credit for their progress yet THTX hasn't been ascribed any value for their progress, zero. Why not discussing what they do have and how to increase market awareness re their progress so far?

[palinc2000]

I dont care if they want to show that they are fluent in scientific terms but I just think its a waste of time,,,,,I like your post and mostly those of Wino but ,,,,,

[Greenviolino]

No, the silent majority does not feel the same. Thanks for the insight on the science.   

[scarlet1967]

Well the silent majority are investors who would like to have ROI and this is an investment board right?

[scarlet1967]

I agree with you the science needs to be understood by investors so they can put a valuation on it. The IP is too scientific for retail investors as not all of them have scientific background yet many buy biotech stocks when they understand the $$ behind their R&D programs. To approach the retail investors company needs to make many changes to their marketing strategies which I will try to

[palinc2000]

Of course but a go /no go on clinicaltrials is based on managements decision and mostly based on their evaluation of the odds of success ,,,,,,Far from being a guarantee of sucess but if those with a scientific background dont think so then selling remains an option AS you know financial engineering is much easier to evaluate and much easier to react to bad decisions and faster 

[scarlet1967]

Yes I agree I think folks here need to be reminded their science is backed by many world famous KOLs  so by all means if anyone think their findings are substantial send it to the company but very likely they are already aware of what's happening in terms of new research studies. For instance I with limited knowledge put 2 and 2 together and posted  the effect of Tesamorelin on covid

[scarlet1967]

This is not unusual question asked many times on Stocktwits??? https://stocktwits.com/manny1/message/284913302

[scarlet1967]

Then he goes to the amateurish designed website looking for investor presentation which he can't understand cause the long term value driver for this company which is the R&D programs is written so only people with science background understand! Now please tell me how the mom and dad investors would even consider this company as an investment when they can't understand the protocols!

[realitycheck4u]

This post has been removed in accordance with Community Policy

[qwerty22]

Ur right. Just musing. When it matters we'll know until then let us just have the conversation.  

[Wino115]

Another thing about Bicycle Therap. They have 2 cancer peptide conjugates going in to Phase 1 or 2 and 4 or so more partnerships on other kinds of drugs (not cancer).  One recently reported 4 case studies from their dosage escalation that all showed tumor shrinkage and the stock shot up 50%.  The Phase 2 for their other PDC looked to have pretty average response rates in Phase 1 to me. &

[SPCEO1]

And it is worth noting that BCYC has a market cap of $645 million.

[jfm1330]

This is exactly what I want them to do. Put the DOTA chelating linker on their peptide, add Ga68 tho the linker, purify the peptide and inject it to an animal model with a cancer xenograft overexpressing Sortilin receptor and do a PET scan. That is easy to do. The science is developed to do that, so just do it. And they would not need to go very far to fing missing expertise and hardware to do it.

[qwerty22]

The empirical evidence is more biotech choose the ADC route over PDC, more ADCs have been approved than PDCs. There are potential pros and cons to both approaches but there are really no fixed rule. Each approach, each molecule tested, needs to be supported by it's own empirical evidence. There is only so much you can learn from these generalized statements. Docetaxel failed in pancreatic

[Wino115]

I never took Chemistry! Quite complex, but another take on it is that they have advanced the science on each part at an amazing clip. Given time, they seem to find novel ways to overcome problems.  It is complex and I guess that's why those Trodelvy improvement numbers, despite being fairly small, are really a big deal in the science.  Let's hope the UMontreal guys understand

[jfm1330]

It is Beliveau, Richard Beliveau and he is not at Universite de Montreal (UdeM), but at Universite du Quebec a Montreal (UQAM). Sorry, Stockhouse does not accept french accents.

[scarlet1967]

I believe the science of the protocols which have been discussed here is much better understood by the scientific advisers of the company but if anyone think there is a new finding that they despite all odds are not aware of send it to CMO or even Leah. Posting then here to inform a handful investors is ok but if you really want to contribute to their protocols please send it to them too. Although

[SPCEO1]

I did forward to the CMO one of JFM's early posts on this subject. I imagine he was already well aware of it but it never hurts to make sure.

[Bucknelly21]

For a company who doesn't have much bad news we sure do lose a lot of market cap for no reason and do gain any for good reasons 

[scarlet1967]

I have lined up a list of questions/suggestions addressing your and I believe many others concerns to discuss with Leah. I hope she doesn't only listen but hear our concerns, believe me I know how to talk the talk so it will be interesting to see if they start the walk the walk.

[SPCEO1]

And Beliveau is listed as a paid consultant at THTX. I met him at one of the annual meetings - nice guy. As a cell expert he told me we should all eat blueberries and drink green tea to hvae good cell health. I took his advice on the former but have not yet developed a taste for green tea. If all I ever get from TH is some good health advice, I suppose that will not be the worst possible outcome