Theratechnologies Inc T.TH

Combo tests with anti PD-L1 chekpoint inhibitors

[jfm1330]

I finally read this article about pre-clinical work. When it was published, I had other stuff to worry about starting chemo treatment, and I was also fed up with Thera's lack of disclosure about their clinical results, so to read about another pre-clinical study about results on mice was a little too much for me at the time. By the way, I went to see my oncologist today after my Ga68 SPECT scan from Monday, the result was is that my cancer is stable for the last four months. So I will continue on that chemo for at least another four months. My quality of life is degraded, especially for 10-12 days every 28 days, but hey, it's the price to pay to live longer. But I can tell you that to be able to keep a decent quality of life is critical to stay on an anti-cancer treatment. I am still above that line, so I will continue.

So back to this pre-clinical stuff. It's pretty interesting, even though on mice. I was most impressed with the change that allow different types of leukocytes (white blood cells) to penetrate a tumor, even one on mice. As always, the problem is to know how that would translate in real tumors on real human patients, and with other types of cancers. Also, no scientific explaination is given that would justify why TH1902 allows these leukocytes to migrate into the mouse tumor.

Obviously, when you read these results, the first reaction is to want to see them testing it on humans as soon as possible, but they don't identify which anti-PD-L1 checkpoint inhibitors were tested, so it's impossible to identify exactly the company that could be a partner for Thera. A quick search gave me these three monoclonal antibodies as PD-L1 inhibitors: atezolizumab (Tecentriq, Genentech), avelumab (Bavenico, Pfizer) and durvalumab (Imfinzi, MedImmune/Astra Zeneca).

[Mannequin]

Does CM @ Thera read your commentary and think "I know" or "hmmm I had not thought of that".     

[scarlet1967]

Also, no scientific explaination is given that would justify why TH1902 allows these leukocytes to migrate into the mouse tumor." I am just guessing but as we know Sortilin progressively is over expressed in late stage cancers and it seems it has a contributing function in tumor cells evasions from  the immune system so as TH1902 binds to receptor and internalize into cell the

[jfm1330]

Immune cells are not entering cancer cells, they infiltrate tumors by being able to migrate out of the bloodstream in tumors between cancer cells. A cell cannot penetrate another cell, but some white blood cells can migrate out of the bloodstream by migrating between cells forming the blood vessels walls. This process is called diapedesis. https://en.wikipedia.org/wiki/Leukocyte_extravasation

[scarlet1967]

That's correct I should have said infiltration of tumor not cancer cells having said that the sortilin seems to have a major roll stopping that infiltration again I am just speculating about how and why the presence of TH1902 can contribute to immune cells infiltration!

[Wino115]

Interesting thoughts, indeed.  I've also thought that it doesn't necessarily need to be one of the existing PD-L1 therapy companies that woudl be interested --of course, they should be as if it works it would propel your therapy into uncharted cold tumor territory.  But it would be most appealing for someone looking to get into the immuno-oncology field with a more unique and

[Trogarzon]

Usually when something is that good it gets noticed.  For now it's ignored at best from what the market is doing wich is lot of nothing at the moment.

[jfm1330]

I am not sure, but I doubt that you can do a combo trial with two phase I drugs. Phase I is for safety and combining two new drugs could make it too complicated for the FDA. Again, I am not sure what are the rules about that.

[qwerty22]

To me two experimental drugs in a combo trial is not a great way to go. It looks an ugly bet. How do you untangle the contribution of each drug to the toxicity signals? Or efficacy signals? It seems to me to bring far more disadvantages than advantages.  I was drawn to a little comment by FM-B. Towards the end, when talking about the protocol changes, she noted disparagingly that two

[scarlet1967]

Posted earlier: "Under the terms of the agreement, Genentech and Bicycle will collaborate on the discovery and pre-clinical development of novel Bicycle-based immunotherapies against multiple targets. Bicycle will receive a $30 million upfront payment. The upfront payment and potential discovery, development, regulatory and commercial-based milestone payments could total up to $1.7

[jfm1330]

Hey! They go into radio-conjugates. Good for Bicycle but not for Thera. Again, Bicycle thinks in terms of PDCs, not ADCs. They are not the same thing. But Thera does not have the money and seems unable to sign partnerships of any kind. I thought Paul was supposed to be the guy with connexions with big pharmas.

[Trogarzon]

We ain't exactly the chosen people.  Anyway, like they say the proof is the pudding.