Theratechnologies Inc T.TH

FDA Clears Peptide-Drug Conjugate for RRMM

[scarlet1967]

 FDA yesterday approved first PDC for relapsed/refractory multiple myeloma which is great news for company’s TH19.. series, this is a milestone for PDC in any cancer therapeutic program.

Good recognition for the technology.
"The FDA Friday approved the first anticancer peptide-drug conjugate, melphalan flufenamide, or melflufen, for use in combination with dexamethasone in adult patients with relapsed/refractory multiple myeloma (RRMM), who have received at least 4 prior lines of therapy and whose disease is refractory to at least 1 proteasome inhibitor, 1 immunomodulatory agent, and 1 CD38-directed monoclonal antibody."
https://www.ajmc.com/view/fda-clears-peptide-drug-conjugate-for-rrmm

[jfm1330]

To call this drug a PDC is a strech in my opinion. The drug itself, melphalan is like an unnatural amino acid and it is linked through a peptide bond to another unnatural amino acid para-fluoro phenyalanine. So the peptide is the smallest peptide possible, a di peptide (2 AA) and there is no linker, only a peptide bond. As a reminder, peptides are polymer of amino acids linked together through

[scarlet1967]

We can say the same for Lutathera as the drug is a radiopeptide. Lutathera’s MOA is also a bit different than TH19... series, Lutathera cancer therapy is really a PRRT (Peptide Receptor Radionuclide Therapy) a radioactive targeted therapy. “Lutathera is a radiolabeled somatostatin analog (a cell-targeting protein called octreotide combined with a radionuclide called Lutetium)." Lutetium is

[jfm1330]

Sorry, you are wrong on that. Lutathera is a real PDC with a real peptide, a real linker and a real cytotoxic agent. The only difference is the fact that the linker is not cleavable since the isotope does not need to be free to emit radiations.

[scarlet1967]

My point is as the other drug was an amino acid as per yourself rather than a peptide  therefore it wouldn't classify as a PDC but a radiopeptide would classify?!

[jfm1330]

Again, isotope or chemo drug, the principle is the same. Apeptide with affinity to an overexpressed receptor is able to bind with it while carrying a cytotoxic agent. The only difference, the chemo drug needs to be released free inside the cancer cell, so the linker needs to be seltively cleavable inside the cell. In the other case, it was not that. The drug is part of the peptide, a dipeptide

[scarlet1967]

I won't look into it again take your word for it.

[qwerty22]

Apart from the structure it's got a very odd mechanism of action. Looks like it relies on the first 10mins after injection for the PDC to enter all cells but be preferentially be toxic to cancer cells, after that time the PDC is all cleaved in the blood and can enter every cell as parent chemo where it is toxic to every cell, that must be why they have the neutropenia. Once they do head-to

[scarlet1967]

Thank you for looking it up.