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Theratechnologies Inc T.TH

Alternate Symbol(s):  THTX

Theratechnologies Inc. is a Canada-based clinical-stage biopharmaceutical company. The Company is focused on the development and commercialization of therapies addressing unmet medical needs. It markets prescription products for people with human immunodeficiency viruses (HIV) in the United States. The Company's research pipeline focuses on specialized therapies addressing unmet medical needs in HIV, nonalcoholic steatohepatitis (NASH) and oncology. Its medicines include Trogarzo and EGRIFTA SV (tesamorelin for injection). Trogarzo (ibalizumab-uiyk) injection is a long-acting monoclonal antibody which binds to domain 2 of the CD4 T cell receptors. EGRIFTA SV (tesamorelin for injection) is approved in the United States for the reduction of excess abdominal fat in people with HIV who have lipodystrophy. Its portfolio includes Phase I clinical trial of sudocetaxel zendusortide (TH1902), a novel peptide-drug conjugate (PDC), in patients with advanced ovarian cancer.


TSX:TH - Post by User

Comment by qwerty22on Jul 19, 2021 2:59pm
137 Views
Post# 33570160

RE:RE:RE:RE:RE:RE:Dose escalation

RE:RE:RE:RE:RE:RE:Dose escalation

All strength to your wife!

You are right about multiple different mechanisms of resistance, and certainly some of those mechanisms th1902 just can't overcome. I think people are grounded about cancer drug efficacy. They expect there will be some cohorts that a drug just can't help and some where it will. They just have to focus on maximizing the later.

This is from a paper on breast cancer.

"However, development of docetaxel resistance is major clinical problem in different cancers including breast cancer patients1. Activation of a number of survival signaling pathways has been reported to promote resistant phenotype in cancer cells in response to docetaxel treatment. Other factors are activation of P-glycoprotein, inhibition of apoptotic mechanism, metabolic alteration, changes in microtubule structure and binding efficiency of docetaxel to the microtubules2. P-glycoprotein or multidrug resistant protein 1 (MDR 1) is the major contributing factor for chemotherapeutic insensitivity."

The MDR1 is identified as the major contributor and this is one where th1902 can potentially have a positive outcome

 


juniper88 wrote: There are other mechanisms of resistance.  The 2 I am most concerned about are resistance to apoptosis and resitance to DNA repair, because I don't believe that TH-1902 specifically overcomes those.  

About efficacy, I just wanted to share our experience with Taxol.  My wife has had a total of 11 cycles of Carboplatin/Taxol.  Many cancers have a blood test for a Cancer Antigen.  For ovarian cancer it is CA-125.  This marker often has a doubling rate.  For my my the CA-125 number would double about every 24 days.  After she was infused with Carboplatin/Taxol she was given a CA-125 blood test 21 days later in order to see if there was any response to the chemo.  Obviously, if the chemo was not doing anything the CA-125 would have about doubled from the last blood test.  Instead, it dropped by about 50%.  That told us right away that there was efficacy.

Thera, would have access to these blood tests and get a good hint if there is efficacy in the patients they have dosed so far.  Now, not all patients are sensitive to these blood test but at least most are.  And a CT Scan wil ultimatly have to confirm efficacy.  But my point is that Thera should have a good idea whether or not there is efficacy.
 

palinc2000 wrote: Qwerty I really  appreciate  your measured ,tempered take ,,,Your posts on the science do not sound like pronouncements  like  others ,,,,,,,,,,, I think your posts accurately  reflect the risks involved in the oncology platform,,,and that lack of toxicity is not a guarantee for efficacy,,,Its a necessary pre requisite but not a predictor of final results in humans,,,I dont think the market lack of giving much weight to the platform has anything to do with credibility of management ,,,,it is mostly related to the market not having strong belief in the science ,,,,,The market is not always right and for sure it would be nice if it were proven wrong  in this case ,,,,,It would be nice if an independant KOL or an analyst involved in oncology  issued a positive report on the platform ,,,,,, but this has not yet happened,,,,
qwerty22 wrote:

... or if it's not bypassing resistance so chemo resistant cells are pumping the drug out as fast as Sortilin is moving it in.

.... or if the docetaxel is not efficiently being released from the PDC inside the cell so it doesn't become active.

.... or if the PDC is not able to get to the cells in the first place, that's to say it doesn't efficiently penetrate the tumour.

All the things they highlight about the drug need to work to some extent to get the final effect. Some of these things have been better "derisked" in the preclinical work than others.

 

jfm1330 wrote: The only explaination would be that docetaxel is not efficacious against certain type of cancers, but it is hard to imagine it would not work against every cancers. That's why the scientific logic leads to think that if the MTD is high, efficacy should be there.

 

 

stockman75 wrote:
Jfm thanks for this great information/analysis. From a scientific perspective how would you explain a scenario where they have such large MTD dosage and NOT have very good efficacy (for sortllin expressing cancers)? Thanks

 

 

 




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