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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 Sep 09, 2021 3:14pm
136 Views
Post# 33834690

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

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

I'm not saying similar toxicities described here will happen with th1902 (if I was forced to guess I'd probably say they won't). But the company making public statements assuming they won't happen makes no sense.

https://www.annalsofoncology.org/article/S0923-7534(19)36547-0/fulltext

(particularly lesson 1)


qwerty22 wrote:

He didn't make any projection about reaching MTD, that is not possible without a time machine, I'd like to see the exact quote. I also don't think Christian works by making the sorts of assumptions JFM makes. He might have made a projection about reaching the last scheduled dose based on the speed at which doses were escalating at the time, that's a different thing. I just don't think the company is in the business of guessing when a patient will hit a dose limiting toxicity, it's just not something you can do. This guy talks utter BS some times.

The number of assumptions you'd have to make to project from a couple of pK measurements of free Docetaxel to predict when a patient will hit a DLT in their first dose is crazy. Christian might be satisfying his own curiosity with back of the envelope thoughts but this sort of thing but there is no way he would put that into a public statement. One thing JFM is ignoring is typically the safety profile of targeted therapeutics like ADCs and PDCs does not just come from the free payload circulating in the blood. The carrier (peptide or antibody) is also a biologically active molecule and it has been shown to produce toxicities that don't occur in the payload and therefore are probably coming from the presence of the carrier molecule. I just don't think Christian can assume th1902 doesn't also have those issues.

 

jfm1330 wrote: Here is my full original post describing how everything is supposed to go assuming one full month per cycle. It is based on one slide they showed in the KOL presentation. The fact is, I think some cycle could have been shorter than a full month, especially at the begining. Remember that Marsolais said in the KOL presentation that they expect to reach the MTD at the end of the summer or the begining of the fall. So it's either this cycle or the next one. Now how can he make such a projection? Because he had pharmacokinetic data of TH1902 in humans back in June. Based on the level of free docetaxel he saw at low doses back then, he was able to extrapolate when the level of free docetaxel would reach toxic level at much higer doses. We are entering in this area now. Again, will it be this dose ( 558.6 mg/m2) or the next one (742 mg/m2), or even one notch higher (987 mg/m2)? Hard to say for sure.

As for the disclosure of the MTD when it will be reached. I don't know how long they will sit on it. They are not forced to disclose it the next day, but I don't think they can sit on the info for a long time. I think they will release it at the same time as the early efficacy data, if there is early efficacy. But remember, Levesque said in the last chat that it was just a matter of time before they would see something very interesting within the clinic, in humans (the quote can be heard at 13:18). In other words, just a matter of time before they see efficacy. He told it right there. Go, listen to it and all what he said before and after that. It's in plain sight.

 

 

jfm1330 wrote: I went back to the KOL presentation to determine at what dose Thera likely is right now in the dose escalation trial. Marsolais said it take three to four weeks for every cycle. It was annouced on March 23 that they injected the first patient of the trial at 30 mg/m2. So taking that date as the starting point it gives this assuming a full four weeks for every cycle, which is likely not the case, especially in the first two or three cycles. Anyways, it gives this

March 23: 30 mg/m2

April 20: 60 mg/m2

May 18: 120 mg/m2

June 15: 200.4  (on June 21, Marsolais said they were close to the MTD of docetaxel of 230 mg/m2. So this is in line with what he said then)

July 13: 300.6 mg/m2

So it gives July 13 for the first dose well above the MTD of free docetaxel. Again, Marsolais said three to four weeks per cycle, so more than three weeks, but in some cases, probably in the first cycles, with one patient, less than four weeks. So this dose of 300 mg/m2 has been likely given somewhere between July 5 and July 15. Likely in the middle of that interval. So it is easy to understand why Marsolais willing to say in the last CC that they will surely have a MTD of TH1902 that is higher than the MTD of free docetaxel. Also, he probably already had the dosing of free docetaxel over time in the blood after the injection of the 300 mg/m2 dose. So he knew the level of free docetaxel this dose was generating. If the number was as low as expected, it confirmed to him that toxicity at that dose was very unlikely.

The next step will be 420 mg/m2 on August 10. This will be close to two times the MTD of free docetaxel.

Then, if they get there, it would be 558.6 mg/m2 on September 7, and 742 mg/m2 on October 5. This would be a bit higherthan three times the MTD of free docetaxel, which is what they saw on rats in the preclinical.

So we are sure to have a significantly higher MTD of docetaxel with TH1902. At this stage the only question to answer is how much higher will it be. The higher it will be, obviously, the better it will bode for efficacy. This helps understanding why they are so confident with TH1902 anf the SORT1 approach in general. Why they hire people to coordonate preclinical and clinical work. It also allows to understand why they were willing to write in their last press release, and say through the CEO in their last CC that they believe that They have developed a targeted peptide-drug conjugate that may potentially transform the way cancer is treated. These are their words, not mine, and this is a very bold statement coming from them. I can't figure how they can be more positive than that without releassing real good results. After such a statement, coming out in a few months with negative results would be an absolute surprise. But again with this company at this time, it is a matter of credibility and they obviously don't have much with the market. So this statement went by like it was never made. Even here, I have been the only one underlining it. So we will have to wait for the real results. It will either be a shocker for many, or a big disapointment for me.

 




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