Theratechnologies Inc T.TH

Alternate Symbol(s): THTX

Healthcare Biotechnology

Theratechnologies Inc. is a Canada-based clinical-stage biopharmaceutical company. The Company is focused on the development and commercialization of therapies addressing unmet medical needs. It markets prescription products for people with human immunodeficiency viruses (HIV) in the United States. The Company's research pipeline focuses on specialized therapies addressing unmet medical needs in HIV, nonalcoholic steatohepatitis (NASH) and oncology. Its medicines include Trogarzo and EGRIFTA SV (tesamorelin for injection). Trogarzo (ibalizumab-uiyk) injection is a long-acting monoclonal antibody which binds to domain 2 of the CD4 T cell receptors. EGRIFTA SV (tesamorelin for injection) is approved in the United States for the reduction of excess abdominal fat in people with HIV who have lipodystrophy. Its portfolio includes Phase I clinical trial of sudocetaxel zendusortide (TH1902), a novel peptide-drug conjugate (PDC), in patients with advanced ovarian cancer.

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Comment by jfm1330on Aug 13, 2021 1:22pm

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Post# 33701356

RE:RE:RE:RE:RE:RE:Whats this?

It seems to be the case, unless I totally missed something, but I don't think so. The thing is that it is likely to be much easier to link docetaxel to TH19P01 with succinic anhydride than to link it with dimethyl glutaric anhydride or with protected glutaric acid. So early on maybe they did it with succinic because it was easier and they did not need the selective cleavage attribute, and placed the wrong protocol in the article. I know it looks like chinese to a non chemist, but the succinic road is easy, while the dimethyl glutaric road is likely harder. Look at the two molecules, you will see similarities, but also the differences.

https://www.sigmaaldrich.com/CA/en/product/aldrich/239690

https://www.sigmaaldrich.com/CA/en/product/aldrich/d159808

SPCEO1 wrote: So, what is the implication of what you are saying - that the peer review process failed and there is something wrong with the article?

jfm1330 wrote: I started to read the article, but just at the chemistry section I was baffled. First they finally give the amino acids sequence of TH19P01 which is:

Acetyl-Gly-Val-Arg-Ala-Lys-Ala-Gly-Val-Arg-Asn-(Nle)-Phe-Lys-Ser-Glu-Ser-Tyr

So they have two lysines (Lys) strategically situated on both side of the peptide, with a nice gap in the middle. It's on these two lysines that the linker + docetaxel will be achored to the peptide. They have an acetyl group on the N-terminus of the peptide to give it more stability against enzymatic cleavage, they also have a norleucine (Nle) in the middle, which is probably a more stable (non sulfur) replacement for methionine.

That being said what I don't understand in the chemistry part is the linker. They use succinic anhydride to attach docetaxel to the lysines on the peptide, leaving a linker structure that is not what I saw in one of their previous presentation where they were claiming to use dimethyl glutaryl linker. And in the article, after descrbing the chemical reactions they end up with a molecule called TH19P01(SuDoce)2 or TH1902. So they claim there that the PDC with the succinyl linker is TH1902. It does not make sense because the succinyl linker is not cleavable under physilogic conditions. It is categorized as a non cleavable linker for ADCs. So I really don't understand why they claim that TH1902 has a succinyl linker, while before, they claimed it was dimethyl glutaryl.

https://www.selleckchem.com/products/succinic-anhydride.html