Theratechnologies Inc T.TH

New PDC article mentionning TH1902 and TH1904

[jfm1330]

4.2. PDCs in clinical trials

Although the structures of PDCs are similar to antibody-drug-conjugates (ADCs), these functional peptide conjugates offer several advantages over ADCs, including selectivity, deeper tumor penetration, rapid extravasation, and slower renal clearance. The PDC drug Lu-dotatate177 has been approved by the US Food and Drug Administration (FDA) for the treatment of gastrointestinal pancreatic neuroendocrine tumors [231]. However, there are more PDCs in the development stage, such as TH1902, a PDC with a docetaxel cargo for the treatment of triple-negative breast and ovarian cancer. TH1904, a PDC loaded with DOX, can be used to treat ovarian cancer. Both PDCs target the overexpression of sortilin 1 (SORT1) receptors in cancers, including triple-negative breast, ovarian, lung, colorectal, skin, and pancreatic [232]. Another PDC drug based on a composition called a bicycle peptide is also very popular. Bicycle peptides are usually 9–20 amino acids in length and have three cysteine residues in their sequence. These cysteine residues react with small molecule linkers to constrain the peptide into a rigid conformation. Bicycle toxin conjugate can be used as a transporter for drug molecules. The drug is attached to the bicycle peptides to ensure an unhindered conformation [233]. Several types of bicycle therapeutics have entered clinical trials for specific tumors [234] Table 5. summarizes the reported clinical research progress involving PDCs published on the US FDA website (https://www.fda.gov/).


https://www.sciencedirect.com/science/article/pii/S2666138122000160

[jfm1330]

We did not learn anything new about TH1902 out of this scientific article, but it shows that the scientific community is well aware of the existence of this program. A meaningful development about it will quickly make its way through the scientific and medical community. That's why I think that most of the promotion will be made through real good results. The better these results would be, the

[Wino115]

Yes, as we've been saying, frankly any continuing good news around either ADC or PDC technology and efficacy for targeted cancer treatment is at least positive news. There's still only a few on the market. THTX can show a highly unique and helpful aspect to it's SORT1+ platform in a few different ways. We have multiple shots to get that PR you talk about.  It can be any of 1

[Wino115]

Sorry, here's the second part of that message, it was corrupted or something. I saw a new paper written about a different topic (hypertension) and sortilin. The most interesting fact I learned is this --in normal tissue only around 1/10th of the amount of sotrilin in a cell makes it to the surface. I guess that is what helps it become overexpressed in the advanced cancers --there's 9x more

[jeffm34]

You can find articles on Sortilin and its involvement in lipid metabolism as well. There are potentially other applications for Theras peptide outside of oncology. The company said in their last call they are not interested in looking into other applications. Why are they not getting other companies or universities to do that for them ? 

[jfm1330]

So far, TH19P01, the peptide involved in TH1902, which is a ligand of sortilin has shown no biological activity by itself, no anticancer effect without docetaxel. Also, bloodstream half lije of TH19P01 alone, not linked to two docetaxel molecules, is probably much shorter than the half life of TH1902. All that to say that having a peptide that is a ligand to sortilin and can act as drug carrier at

[jeffm34]

https://www.liebertpub.com/doi/10.1089/dna.2017.3853 Sortilin facilitates hepatic cholesterol accumulation by inhibiting hepatic cholesterol catabolism, which promotes the development of nonalcoholic fatty liver disease (NAFLD). Sortilin plays an important role in lipid metabolism and represents a promising therapeutic target for lipid disorder diseases.

[jfm1330]

Again, to have a peptide ligand to sortilin does not mean you can alter the diffrent roles it can have in the metabolism. Again, naked peptide like TH19P01 have half lives that are very short. The do not remain intact in the bloodstream long enough to have any meaningful biological impact. It's like GRF (1-44), the natural peptide on which Egrifta (tesamorelin) is based. Tesamorelin is a

[jeffm34]

The way the peptide works is that you can attach different drug molecules to it, not just docetaxal or other cytotoxic agents. It can deliver other therapeutic drugs as well. Why would you just administer the peptide on its own ?  That's not how a PDC works 

[jfm1330]

Sortilin is expressed at different levels in many organs and tissues, maybe every organs, I am not sure abot that, But anyway, it's pointless to talk about it as a target, unless it is significantly overexpressed, and the only cells where we know it is highly overexpressed is in some types of cancer, especially advanced ones.

[Wino115]

That's the issue Jeff -- while sortilin exists in every cell (I think) and very little gets to the surface (one tenth) in a cell acting normally, it's the fact that in a tumor environment sortilin goes crazy and explodes in it's intensity and amount on the cell surface looking to "scavenge" that makes TH1902 work.  The additional fact that it increases in relation to the

[jfm1330]

My basic point is that to have a targeted approach, you need a target. In certain types of cancer, it seems sortilin, because of its overexpression becomes a target, otherwise, if there is no overexpression, there is no target since it is more or less everywhere within a rather narrow range of expression levels. So again, what's make TH1902, in theory, a targetted drug, is the clear

[qwerty22]

They haven't even hinted at using it in other diseases. That's where the story starts and ends for me.