RE:RE:RE:RE:RE:RE:New Press Release - Theratechnologies' Sudocetaxel Zendusortide ASCO 2024 Presentation Demonstrates Signs of Long-Term Efficacy and Manageable Safety Profile in Patients with Solid Tumors So my initial thoughts revolve around the MOA too. Both positive and negative or should I say still full of questions.
You are right about the multi MOA coming from the preclinical work but I don't think you can quite say they are now seeing those actions in the clinical data. What I'd say they are doing is laying the clinical data next to the preclinical finding and "encouraging" people to join the dots the way you have. I don't think you can directly conclude the MOA from the clinical data. It's a neat PR trick by them.
So if we think about the main touted MOA before the trial began it was simply to actively deliver chemo to the cancer cells via SORT. My expectations were, if it worked, to get rapid tumour reductions. That is the general expectation for chemo drugs. Chemo, when they work, rapidly kill cells and shrink tumours. That suggests to me that the original touted MOA is not at play here and we are looking at these other mechanisms listed as having an affect in this cohort. For example it could be selective impact on the most aggressive (stem-like cells) that is stopping advancement. It's noticeable that they don't talk about simple delivery of chemo to the cell in this PR. It's also worth considering just how heavily pretreated the part1/2 were, things could be different in a less heavily treated cohort. It could be the tumours in these patients carry multiple mechanisms of resistance to chemo, not just the ability to pump the chemo back out of the cell but mechanisms that bypass it's activity when in the cell too. So maybe you can conclude the delivery system worked (which is good news as that's where the patents lie) but the bomb didn't really go off. It's been said before the payload might have let them down, I always thought DOC had some practical advantages maybe those that thought it wasn't quite up to the job where right.
This result from part 1/2 might also explain why they didn't include any efficacy info on the first six patients from part 3 in their recent update, waiting for long term.
There are lots of questions this raises but as Juniper says there is something that would appear meaningful for some patients. It doesn't scream fast path to blockbuster drug but maybe with the right cohort/dose combo they could have something meaningful.
I'm mostly speculating here, but I'm not sure a simple explanation is out there at this moment in time.
Overall feeling : The drug ain't dead (yet) but I'm not jumping (yet). Maybe the delivery system works but this was the wrong payload for this cohort to get blockbuster results. IDK
scarlet1967 wrote: Apart from the clinical efficacy they are talking about and lower concentration of free doxetaxel one thing which they are "suggesting" and I found it interesting is the "multimodal" aspects of the drug. Note all those MOS's listed in the PR were preclinical findings and now they are considered to be responsible for those clinical results!!
In a sense they are claiming due to various MOAs the drug has wider therapeutic potentials(range) in humans. Maybe I am missing something but that is quite a significant "suggestion"!!
"The results suggest a unique, multimodal mechanism of action distinct from other cancer therapeutics, including induction of immune cell infiltration even in “cold” tumor models, inhibition of vasculogenic mimicry, targeting of chemotherapy-resistant cancer stem cells, and activation of the cGAS/STING immune pathway, among other actions."