RE:RE:RE:RE:RE:RE:RE:RE:RE:TH2101
Here's a review on how CSC affect therapy.
https://www.cancernetwork.com/view/cancer-stem-cells-implications-cancer-therapy
Here's a paper linking Sortilin to breast CSC
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-021-07854-0
Your question is way above my pay grade. It sounds like CSCs are a tricky problem and expecting one treatment to solve it is probably hoping for too much. They are inherently adaptable so whether they can adapt to whatever is thrown at them is a big question.
Most of the papers I've read about Sortilin in cancer seem to give it a role in these adaptability powers and have it contribute to aggressiveness and plasticity which are the hallmarks of CSC. It may be that CSCs use Sortilin for some of these purposes and so you may target CSC with an anti-Sortilin drug. It may be that CSC use multiple pathways to achieve these outcome and simply adapt away from Sortilin under pressure from drug treatment.
I keep thinking the VM results are about the ability of Sortilin to affect plasticity. Producing VM structures in a tumour are about changes in the physical structure of cells and how they interact with each other, that's plasticity. It seems th1902 is stopping that at concentrations way below the level where it might be explained by the toxicity of docetaxel so it might be doing something else like interrupting Sortilin role in plasticity. I don't have enough actual knowledge of the subject so I could just be seeing patterns I want to see.
It would be great if somebody nailed down the role Sortilin plays in cancer, somebody might then be able to answer your question. But Sortilin seems to be linked to aggressiveness and plasticity which potentially gives it a link to CSCs.
juniper88 wrote: From what I understand of Sortilin is that it is a receptor highly associated with Cancer Stem Cells (CSC). These cells are harder to kill and the theory is that cancer often recurs because these CSC were not killed off by the chemo drug during first line treatment.
qwerty, I would like to hear your thoughts how Th-1902 could kill of these CSC, when taxol was not able to during first line treatment.
qwerty22 wrote: Yep, I'm English I don't have the N.American can-do attitude, maybe I can state this point a little more positively.
I think the lead drug is great. I think it's totally fit for purpose. The fact it's profile is so well understood I think adds a lot to the drug development process, it makes some things simpler, it might allow them to draw stronger conclusions earlier in the process than would be the case with a newer drug. And as a chemo drug it looks totally solid. So when people are talking about newer more powerful drugs I get a sense they think docetaxel might be a make-do drug and I think it's much more than that.
I also like biotech as a goal driven process and the main goal is to get the lead asset across the finishing line. I understand proving the versatility of the tech is important but I don't want that to be a distraction.
This is where I go negative. I'm super sceptical about pipelines, not thtx specifically but biotech in general. I've been an insider, I've seen companies prove the bare minimum that gets a drug on the pipeline then do nothing for a decade. I see inactive pipelines in the companies I'm invested in now. I have to have a real sense they are actually doing something with an asset for me to value it. They employ research scientists so something is always happening in the research lab, that might get them posters at ASCO, but that doesn't guarantee it will move to clinical.
Jfm said something yesterday that sparked my interest though. He pointed out docetaxel might not be the best chemo for some indications, it could be the weakest link in some situations. So that got me reading. I came up with small cell lung cancer and colorectal cancer. Both seem to show weak responses to docetaxel. Both show better responses to sn-38 or irhinotecan, it's precursor. And both are on the graphic in the investor presentation as Sortilin expressors. Maybe there is a plan with th2101 but it's super, super early.
I still think the lead asset matters most but oncology at this point looks like the best thing they have so maybe Paul/Christain want to hit it hard.
palinc2000 wrote: Qwerty you are such a downer!!!!You seem to be a scientist fixated on facts rather than fantasy,,,LOL BUT I value your opinion A LOT
qwerty22 wrote: I would caution a little realism.
Anybody have an older version of the investor presentation, say 12 or more months old?
Th1904 has been on the pipeline graphic for a long time now, it's milestones now are toxicity and scale-up. Has that changed at all from earlier presentations? I don't have an earlier version but I doubt it has changed much. I think they can do early research and mouse work on numerous molecules but having them move beyond that takes resources away from th1902.
It seems the most likely scenario is th1902 remains the only cancer molecule in the clinic unless something dramatic happens. Proving out th1902 is a big enough job.
jfm1330 wrote: There is still a job offer on their website drom April 15 for a drug discovery scientist. These are the first lines of the offer:<br /> <br /> <span style="color: rgb(51, 51, 51); font-family: Barlow, sans-serif; font-size: 16px; background-color: rgb(240, 244, 249);">Under the supervision of the Manager, Chemistry, the Drug Discovery Scientist is responsible for managing a variety of activities, including the synthesis and purification of new anti-cancer molecules, </span><br /> <br /> <br /> So it is pretty clear that they are in the process of developping the SORT1 platform. Also, the recent job offer for a preclinical project manager is in line with the drud discovery scientistt job offer. After synthesizing a new PDC, you need people qualified to test it in vitro, then in vivo (in animal models). So they are clearly working on that at every levels of the chain. As I said before, it is likely that TH2101 has already been tested in vitro and probably some in vivo testing as well. The fact that they put this new information in their new presentation is a hint about things to come. Remember how, in previous versions of the corporate presentation, oncology was gaining ground. Disclosing the TH2101 info follows the same logic. First a hint, then, a few months later, they come with the "piece de resistance".
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