Theratechnologies Inc T.TH

RE:RE:RE:Open Label?

[qwerty22]

I think you might be over-optimistic that science will come up with the answer here. Palinc is right they might not move forward but if they do they might still be mostly doing it thru guesswork. Mostly looking at what worked with others. That might be fine purely on the basis that the reward for reactivating the program is so high but it would likely have a high risk of failure. My instinct is that if they are going to solve this with science then that's more likely a months/years project rather than weeks. But who knows maybe the answer is close at hand.

I've been trying to put myself in their shoes. I mostly expect there is a huge sense of disbelief. The preclinical was solid. They went through multiple steps to show the basic MOA was at play here. They did enough expts to show Sortilin was being engaged and the PDC being internalized even in resistant scenarios. As JayJay pointed out earlier the toxicity is another clue that in the patients the PDC is doing it's thing just unfortunately in healthy tissue. The absence of neutropenia (assuming it isn't showing up) would be telling. This is a really fat signal in docetaxel treatment, you'd expect it to show up in even a small number of patients if this was purely docetaxel-like toxicity. If it is absent there is some suggestion the PDC is discriminating between certain tissues. That in my book is a further clue the PDC can work. The scenario being it's finding the Sortilin in eyes and nerves, not hitting white blood cells because they don't have Sortilin. But why not hitting tumours?

I keep coming back in my mind to the tumour micro-environment (TME). We know this is a barrier for many drugs. We know the conditions in the tumour are different to the rest of the body. There's a lot of thought that a mouse Xenograft isn't a great analog to real world human tumours. From the things we know publicly there aren't a lot of clues about how the PDC would handle the TME. The problem could lie there. I identified pH as a possibility largely because I think that is testable in the lab but if they didn't get any quick answers from something like that then I think the complexity of the TME would suggest a long slog to find an answer. I'm speculating here, I'm looking for where there might be holes in the preclinical. There are probably many more, it's was never easy for them  to cover every possibility.

I'm still curious what unconvincing efficacy might mean. Almost no efficacy? If it's something more than that what does the pattern of efficacy signals look like? Could it be that the drug works on the smallest tumours (one's most like mouse tumours, my guess) but fails on the bigger tumours picked to be the RECIST tumours? Maybe they have clues like that.

All guessing in the dark here.

Wino115 wrote: I am not at all making excuses here because I, too, would have liked to see at least a little bit more color and thought-logic to the extent there was some. But there is an inherant problem in a drug trial with a go/no-go point  if you think about it.

You dose, watch, test, see how data is accumulating, assess if time to make a decision. Nowhere in the day to day process are you actually going back to check the theoretical science, you're just looking at post-dose results on those tumors to see if it basically aligns with science. They just hit a decision point in which they could see it would be hard with 40 patients to conclude enough and the observations were not lining up with the expected science.

When they reached the pause, they didn't really have anything other than what they told us -- we are not seeing the consistent potency in activity that we would expect and it's not worth patients dealing with the SAEs unless there's some activity. Let's try a better way to get more toxin in consistently and lower SAEs and see if that improves it enough to hit the hurdles.  We'll be back shortly with that plan after talking with team and FDA.  Stay tuned.

The time they could talk about it is only after they actually have those plans worked out and when they have corporate strategy worked out (cost containment/revenue estimates) to reestablish the underlying growing business. We've seen some of the notes from their analyst calls and they haven't added a whole lot more so the silence is because both the corporate strategy and the next steps in Sort1 are pretty complex and need a lot of examination around them before you can definitively say anything. From those reports, they aren't hiding, they are starting the process now. 

To your all's point though, I don't see anyway in which they won't be able to share a lot more at some later date. That silence would be the travesty, not this one. Because by then, they should have done all the iterative science around the issues and at least have some logical basis for what they plan to do. They certainly should be able to address some of those issues Qwerty and the Leeds guy brought up as they will be asked.  Don't foget, it's not Christians call either --it will be the investigators, FDA, probably some Rothenberg okay, and then them. There will be a whole lot of eyes going in to the next plan and the team will have to be fully listened to. 
 

realitycheck4u wrote: I can honestly say I've never heard silence like this before from a company (in this sector) when a trial halt to a botential blockbuster occurs. This trial had the potential to transform the company. Any company. This is not a multi-billion dollar company where one would typically say little, and move on to other trials. Thera did not just have an on-going Ph1, but a trial that could have transformed the company and revolutionized standard care if the platform was indeed a platform that worked. Is the platform concept in trouble? We are in the dark.

If this hlat request came from left field, then say it. If it was a calculated response to some data or something they have learned over the past year, then say it. If they think reducing the dose will aliviate some of the noted concerns, then say it.

Being silient this long is truly mind boggling and hardly appropriate. Yes, they halted it. Yes, they said they will resubmit. But why does halting it and resubmitting provide any different outcomes from the existing trial. Are they planning on targeting a different population? Do they have information to share, or at least say for compeitive reasons they do not want to share this info. 

Kd5513 wrote:
Wasnt this an open trial?

They can share anything?

Irritating that they have chosen to be silent, leads me to think efficacay was non-existence the longer they say nothing. This will unfortunately continue to bleed for weeks if they continue this stupidity.

share the details!!!!!