“How about conjugating LL with a checkpoint inhi
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Posted On: 08/26/2024 2:29:01 PM
“How about conjugating LL with a checkpoint inhibitor? As I understand it, those MOAs are different. Not beating a dead horse, just interested in the conjugation route, as far as I know that hasn't been discussed much.”
Drug conjugation has a specific definition in my mind and with regards to MAB’s present challenges that reasonably cause you to need to re-assess efficacy, that’s why I suspect it will be unlikely with Leronlimab. Conjugation is leveraged to good purpose in oncology:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC...f%20cancer.
“the three key components that form an ADC (a monoclonal antibody bound to a cytotoxic drug via a chemical linker moiety) achieve remarkable improvement in terms of targeted killing of cancer cells and, while sparing healthy tissues, a reduction in systemic side effects caused by off-tumor toxicity.”
If Leronlimab is technically conjugated to another drug there is no guarantee that the conformation of the molecule (how it is folded in three dimensional space) that allows for the adept interaction with the CCR5 receptor, will remain intact without further testing. Far easier and more likely is that the drugs will simply be administered separately as part of a treatment protocol. This is VERY common for oncology regimens. I see a lot of room for Leronlimab being combined in a protocol with other drugs and that is probably the easiest route to FDA approval until such time as funds and clinical data make clear monotherapy is equally efficacious and with fewer side effects for a select indication. Hints of this may well come from the MASH murine study results in the Leronlimab only study arm.
Conjugation is of course very different than reformulation of a drug for combination, for example Lortab (Hydrocodone and acetaminophen combine into one tablet). For reasons outlined above I don’t see Leronlimab in the same vial as other drugs, it may change the chemical/organic properties.
Drug conjugation has a specific definition in my mind and with regards to MAB’s present challenges that reasonably cause you to need to re-assess efficacy, that’s why I suspect it will be unlikely with Leronlimab. Conjugation is leveraged to good purpose in oncology:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC...f%20cancer.
“the three key components that form an ADC (a monoclonal antibody bound to a cytotoxic drug via a chemical linker moiety) achieve remarkable improvement in terms of targeted killing of cancer cells and, while sparing healthy tissues, a reduction in systemic side effects caused by off-tumor toxicity.”
If Leronlimab is technically conjugated to another drug there is no guarantee that the conformation of the molecule (how it is folded in three dimensional space) that allows for the adept interaction with the CCR5 receptor, will remain intact without further testing. Far easier and more likely is that the drugs will simply be administered separately as part of a treatment protocol. This is VERY common for oncology regimens. I see a lot of room for Leronlimab being combined in a protocol with other drugs and that is probably the easiest route to FDA approval until such time as funds and clinical data make clear monotherapy is equally efficacious and with fewer side effects for a select indication. Hints of this may well come from the MASH murine study results in the Leronlimab only study arm.
Conjugation is of course very different than reformulation of a drug for combination, for example Lortab (Hydrocodone and acetaminophen combine into one tablet). For reasons outlined above I don’t see Leronlimab in the same vial as other drugs, it may change the chemical/organic properties.
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