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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 SPCEO1on Jul 01, 2021 1:41pm
115 Views
Post# 33479564

RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:Fitting

RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:Fittingi suppose if we see any preliminary efficacy in phase 1a, it will have the best chance of occurring if the trial goes a full 28 weeks without having to stop because of toxiicity issues arising. Or, even when such issues arise, the trial continues using the previous dose. If so, the question then becomes one of whether those doses were given to patients with sortilin expressing tumors and how many doses where such patients able to get before the trial ended. So, there are certainly a number of important variables that will immpact the preliminary efficacy reading. Good preliminary efficacy will obviosuly be a hopeful sign but  preliminary efficacy numbers that are not clearly good may not be indicative that the drug does not work since these other factors may be in play.  

jfm1330 wrote: Marsolais said during the presentation that if there is efficacy in part I of the trial, they will wait to see the full effect through multiple cycles of treatment, but at the same time he said that since they have fast track status, they would quickly meet with the FDA to decide what to do next. To me this is a very volatile situation at this point. I say volatile in the sense that nothing is sure, and it could evolve very quickly. Again, all will depend on efficacy, and if TH1902 is efficacious, we already know that this will come with lesse toxicity at the same docetaxel dose, and with a wider therapeutic window. I would not worry that much about timelines at this point. The key is proof of concept, then, efficacy, and if efficacious, how much efficacious? To me, toxicity is not an issue. The peptide and the linker are not toxic, so the driver of toxicity will be free docetaxel in the bloodstream versus time. The toxicity factor here could be critical because FDA normally worry about that first. But if they can quickly be convinced that toxicity will not be a problem, the phase Ib could quickly become a phase IIa.


SPCEO1 wrote: I think we should drill down as best we canon the timelines for TH-1902's pahse I and possible phase II trial. The 3/21 endpoint for the phase I on Clinicaltrials.gov needs to be updated for the info the company gave at the webinar. The last slide if the presentation indicated we will get a safety and preliminary efficacy readout on the phase 1a in Q4, that the dose escalation and MTD determination will happen by the end of 2021 and that the phase 1b will start in early 2022. 

Elsewhere in the presentation, we were told the phase 1a would be 28 weeks in length and the phase 1b would be 24 weeks in length.

If I recall correctly, the first patient in phase 1a was dosed in early March.

So, if phase 1a is really going to be 28 weeks in length and it started in the second week of March, we just are completing the 17th week and it should end the week of 9/13. 

So, why would TH say the phase 1a not officially end until the end of 2021? Are they just giving themselves time to put the data together following the end of the trial in mid-Spetember and determine the MTD from it? Would they really need 3 and a half months to do that? Or has the tril been delayed in some way. Would the death of the first patient caused them to have to restart the trial and it has been delayed?  

TH  gave us a very optimistic view of TH-1902 in the webinar and brought up no concerns that they might be dealing with in the development of the drug. Did they tell us almost nothing about the trial, however, because there were some troubling details that they would have had to share if they said anything about it at all? Does this seemingly longer trial timeline tell us there have been some issues in the phase 1a? Or does it simply reflect the normal time a drug commpany takes to compile and analyze the data? 

Scarlett suggested that the AACR meeting in early October might be a good time to have the preliminary phase 1a data presented, and that makes sense to me although it might be a bit optimistic depending on what they would choose to present.

As for a phase II start, that would depend in part on when the phase 1b ends. If the phase 1a data looks very good, I am going to guess they get it started in the middle of February 2022. 24 weeks after that is the third week of July for its completion. Do you think that leaves enough time to get the phase II started in September 2022?

How long should we expect the phase II to last? 

Sorry for all the questions but it is good for us to have some sort of reasonable expectations about the likely timing of all this.  

jfm1330 wrote: For a very effective cancer drug, the path to approval can be pretty quick. A phase I followed by a phase II on 100-200 patients. Look at Blenrep, an ADC approved in August 2020 in relapsed refractory multiple myelomas. They did a phase I on 73 patients with differents doses. Than, a phase II testing two doses on 218 patients. The primary endpoint goal was 15% overall reponse rate (ORR). They were finally approved for the lower of the two doses with a ORR of 31%. That was well over the primary endpoint goal, but still, only 31%, which shows that the bar in cancer is relatively low. It does not need to be close to 100% efficacy. ORR is defined as partial reponse rate or better. So it is based on tumor shrinkage, not on survival time. The phase II started in June 2018, and they got approval before the end of the trial in August 2020.

So on clinicaltrials.gov, TH1902 phase I is expected to end in March 2021. Let's say they would start a phase II in September 2022. It would mean a possible approval somewhere at the end of 2023. But if Thera goes in phase II with a single dose, less patients would be needed, so a shorter trial. Also, the level of efficacy, if any, they will see in phase I will be critical. The better it is, the faster the FDA will allow things to go forward. All that to say that cancer drugs showing early signs of very good efficacy can be approved very quickly.

 https://aetion.com/evidence-hub/fda-decision-alerts/cder-approved-nda-for-blenrep-belantamab-mafodotin-blmf/




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