Wino115 wrote: We'll likely learn more, but the paradox is the trade-off you have to make with extremely ill patients who really can't deal with much in the way of side-effects. One of the issues is what we've discussed --the requirements to enter are you've exhausted ALL standard treatments. In other words, nothing is currently working on your cancer --you are succumbing and we can test to see if this drug will make you a bit more comfortable and shrink your tumors, stop the spread, and allow you to live another 6-12-20 months with lower side effects. That's the market they're testing for and it's darn hard.
Treatment SAEs can tip them over or make them withdraw from the trial as we know from first hand evidence here. So it's safety first, efficacy second. And as their pre-clinical showed and likely what 1a showed, for most of these drugs to show any effect, you have to have the patient on it for more than a few cycles and hope whatever side effects they can tolerate and won't drop out for one reason or another. Chemo's invariably a nasty undertaking, especially for weak bodies.
If the dose they gave was just causing what they mentioned (dry eye, nerve issues), it may have been enough on top of their situation to just stop the trial and not continue on to the point of seeing much with efficacy. Hence, their statement -the efficacy wasn't consistently enough to not go back and figure out what to do to lower the safety issues which likely was thwarting patient treatment.
We saw a few of those short cycle ones in 1A where one had great results in 3 cycles and one was just stable with something like 5. Both dropped out. Who knows what would have happened had they both been able to go 30 weeks like that one lady. So if all that 1b was putting up was a lot of 2-3-4 cycle patients with stable or single-digit tumor shrinkage but not enough time under the treatment to see substantial RECIST effects, but the side effects caused enough issues for them to give up or force a withdrawal, then they weren't getting anywhere with that design. Rethink it.
Their initial approach was to go for a max dose since it appears very safe. But while neutropenia wasn't an issue, even small things like neuropathy and dry eye are enough to make a patient stop treatments. Now the tradeoff is to lower the dose so you essentially eliminate or lower the safety issues thus extending your treatment window, and then up the frequency so the toxin is getting in there at lower levels but more consistently and accumulating. If that's the trick for getting hard-to-treat patients on a path for getting 10-15 doses over a 3-4 month period so you can see if the docetaxol you're getting in there does it's thing, then that's what you try next. Try to eliminate safety issues (or at least lower them a lot), but still get where the measurable toxin should effect the tumor primarily and not the other safety issues. Some tumors may respond to that, some likely won't. They don't need 100%, just enough to get this darn thing to work like the clinical. I'd still like to know the types of cancers they got to test this on and what the numbers showed, although we likely won't get all that. There's a lot they should discuss with investors to illuminate what the science taught them about the drug so we can understand at least a few more aspects around this trial change.
LouisW wrote: Will you and your friends call them for further discussion to know the rationale behind the decision?
I still believe in the TH1902. CMO said the adverse events mainly in of neuropathy and eye toxicity. Both eye cells and neuronal cells express relatively high SORT1, meaning TH1902 can find the cells which have SORT1 expression. We have two positive cases in prostate cancer and cancer experts like soleus and MorganStanley are buying.
Regarding the news, i do frustrated since CMO said the enrollment going well. But now he said the data is not convinsing enough to pursuing enrolling patients.........this is totally paradoxical.
SPCEO1 wrote: I will need to hear more before drawing any conclusions but I think we all knew any early stage cancer trial has meaningful risk associated with it. I noted that the risk increased when we did not hear any good results by mid-October. While we can certainly blame management for quite a few issues, in this case I am not sure we can. A result like this is hardly uncommon in the world of cancer research. TH certainly had some unusually promising pre-clinical results, an unusually early FDA Fast Track designation, a sizable investment from a very knowledgeable investor (who kept adding to their position), a cancer focused report just this week (hard to believe they could not find a way to put the brakes on that) and the recent re-posting of the oncology regulatory relations job - all encouraging indicators. But cancer is a nasty beast and isn't going down easily. So, while the track record of TH is dubious, I am not yet ready to blame they for making what by all appearances was a fairly solid effort in a very difficult field. And it may yet work. Unfortunately, it looks like TH-1902 is maybe already following too closely the very winding path Trodelvy took to FDA approval!
SABBOBCAT wrote: I hear the optimism from some folks that this is merely a pivot on the learning path, but what I don't think is resonating with me until now is the repeated failures of this organization. They are becoming too many and too loud to ignore.
- Commercialization of Egrifta: This is an old old story some may or may not know
- Re-commercialization of Egrifta: This is the more recent story we have seen slowly play out with lackluster results
- Commercialization of Trogarzo: Never achieved a significant fraction of the projected market share, with delayed launch of IVPush/IM formula, and the abandonment of the european market.
- Phase 2/3 NASH: the "position of strength" appears to be balled up in the corner doing SFA. No material progression in years.
- TH1902: P1A delayed as they didnt want to admit to a lower dose so they scraped into 1B and realized that they now need to reconfigure again. so another 6-8 months of delays on top of the initial 6-8 months.
Absent of a favorable partnership announcement in NASH or oncology, I don't see any near term upside that would prevent another OO. Yet management deemed a 6:30PM press release sufficient to communicate to investors how screwed they are with no planned call for further clarity? How disrespectful and out of touch are these folks?
The only thing I can think of is their hand was forced somehow in communicating this. Was it the Cantor report that eluded to it that made them realize they inadvertently let it slip? or is there some other deal that is pending that requires the disclosure? Time will tell.
SPCEO, I can only imagine the conversations you now have to have with your clients and I would not be surprised if this was the straw (or hay bale) that broke the camel's back, but if you do stay, I think you finally agree that something needs to be done about the culture and direction.
Absense of big news or big change, I may need to finally say enough is enough and move on. It is going to be a tough puill to swallow as I broke every rule on this one and will take a long time to come back from this, but I cant ignore the greener pastures any longer.