RE:RE:RE:RE:RE:RE:RE:RE:Friday or 4pm NR is better The issue of all-comers and efficacy rolls over to 1b and even Ph2. There may be one or two responders in the first dozen or two dozen patients. Nobody (except JFM) expects anything, not least the relationship between SORT expression and efficacy, to be resolved in the first couple dozen patients. The FDA statement roles into the expansion groups and beyond. The company is right to say efficacy is not central to he dose escalation phase. None of these statements lack clarity or accuracy it's just you are interpreting them wrong.
jfm1330 wrote: I don't know what is going on. But just to examplify the lack of clarity of this whole phase Ia thing. Remember that they told us that the FDA requested that patients enrolled in the trial to be all comers because FDA wanted to see if possible efficacy was related to sortilin expression or expression level. But at the same time the company told us that efficacy was not the goal of phase Ia. So why bother with all comers? On top of it, accepting all comers is forgetting it could impact the toxicity of TH1902 for a given dose. So this whole thing is far from clear and they are clearly off their own timeline if they are testing 420 mg/m2 right now. Back on June 21, Marsolais said they were very close to a dose that is equivalent to the MTD of docetaxel alone, so 200 mg/m2. It means that from July to now they tested 200 mg/m2, 300 mg/m2 and 420 mg/m2. So it is two months per new dose level and 420 mg/m2 is not finished yet. Also in the KOL presentation (June 21) Marsolais said that they were expecting to reach toxic doses at the end of the summer or begining of the fall. So they are more than three months behind their own expectations. Again, I have no clue why they are so behind schedule. Did they have to stop at some point to discuss with the FDA because these all comers were messing things up? I don't know. Maybe it was the case and they did not want to discuss it publicly because it is something you don't want to do with the FDA? Again, I don't jnow. One thing is sure, they are way behind their own schedule, and it is not because they are at three times the MTD. They are at two, and we don't know if it will be the MTD. Go back to listen to the part of the KOL where they talk about that.
SPCEO1 wrote: Also, it does not seem like it would be that hard or disruptive to what TH is doing to just tell us what is actually going on with the trial. What might prevent them from doing that?
jfm1330 wrote: They misled us by not correcting their previous statements. Marsolais clearly said that a cycle was one month, three weeks of treatment plus time to make sure everything is fine. They are way behind their own timeline. Back in June theyr were expecting results somewhere in Q4. Then it was, maybe begining of February, and now we have no clues, Also, back on November 11, Levesque said this:
But the strange thing in the Credit Suisse presentation, is that Levesque says that they had "many patients", or "at least several patients" that have been dosed over 300 mg/m2 (300 mg/m2 is step 5 of the escalation process). So over 300 mg/m2 is 420 mg/m2. So back in November he said that they had "many, or at least several patients" that have been dosed above 300 mg/m2, so at 420 mg/m2. So probably, back then, the three added patients at step 6, which, again, is 420 mg/m2, were already injected. This presentation was held on November 11. So by now, the 420 mg/m2 should have been completed and cleared. Without any news at this point, it is likely that they are now at step 7, which is 560 mg/m2 or 2.43 times the MTD of docetaxel alone. Now, a full two months later, they put in the corporate presentation that they are testing at 420 mg/m2, So two months ago they had "many patients' or "at least several patients" dosed above 300 mg/m2, so at 420 mg/m2. And two months later they are at the same point. What does that mean? To me either what Levesque said on November 11 was false, or they are awfully slow, or they tested a higher dose and are now back to 420 mg/m2 to confirm it as the MTD.
But again, this "all comers" thing is problematic to determine the MTD. The MTD will not be the same on patients without tumors overexpressing sortilin or with a very small tumor, and a patient with a large tumor burden overexpressing sortilin. So maybe it led to problems in the trial that they had to fix with the FDA.
jfm1330 wrote: Open label refers only to the fact that both patient and doctor knows that the drug is given. This has no impact on confidentiality related issues. Those with access to results data knowing to what drug it relates are under confidentiality agreements. For all we can be frustrated about with Thera, they are not a leaky company. The slide in the SP is not related to selling by people aware of the results. It's related to the speculative nature of the stock and to the long waiting time. Last year they published Q4 results on February 11. So in theory we are three weeks away from some update.
SPCEO1 wrote: I remember some time back, probably two years or so, Dubuc telling me that cancer trials were open label and therefore they would be able to share results as they see them.
The question for us now is what did they see in October that made them switch to a "no more info on the trial until MTD is reached".
If you are an optimist, you convince yourself they saw some tumor regression and decided to husband the good info for release at a time TH considers optimal (likely just before a fundraising).
If you are a pessimist, you conclude TH already knows TH-1902 has issues and is not sharing anything about it now hoping they can come up with some offsetting good info in the meantime.
Then you need to take into account other info. Dr. Rothenberg joining up. Options granted early and heavily. SN-38 being looked into. I don't think Rothenberg joins up unless they had seen something positive. The options situation still hints at something going on. SN-38 might mean there is an issue with TH-1902 and they believe SN-38 will solve it or that TH-1902 is going great with a safer option for a phase 1 and things could go even betterr with a drug like SN-38.
Wino115 wrote: Question for the board on what the term "open label" means for this Phase 1. If I recall, this has been described as open label. I'm very unclear about what that means. Google just says it means the patient and doctor know what they are getting, so seems more apt for a placebo controlled study.
The reason I bring this up is that if open label means all the data is collected and viewable by other clinicians, CMO, CEO, etc... they would then run the risk of someone "inside" seeing things like scans or responses and trading on that info. Someone on the other board mentioned this situation and felt the declining stock price suggested no efficacy or response seen yet.
Anyone understand the actual intracacies of what open lable means for this trial? If it's as he suggests, then a company absolutely should inform the market of anything material.
SPCEO1 wrote: The first meeting is a breakfast on Monday. So, if TH wants to talk about somethnig other than is in the presentation, they would need to do a press release today or Monday morning before the open. I would be shocked if either happened, so for the moment at least, what is in the presentation is all that we are going to get from the company after a long period of silence. The people meeting with the executive team (CMO, CFO and CEO will be in attendance) will be able to read body language, ,attitudes, etc. and come away with a perception of where things are at but they will not have any hard facts to chew on. The main reason for that is the phase 1a trial is not completed and, for reasons that have yet to be explained, TH has chosen to not share trial info until the MTD is found.
Since I do not think the CMO, CFO and CMO have been on vacation the last few months, we can be sure a lot has happened behind the scenes. The average TH investor, an incredibly patient person, is more than ready to hear what is really going on and it seems like we will have to wait even longer to get the info that is needed to accurately determine the propsects for this investment. The weight of evidence we have at the moment suggests something good is the most likely outcome but we don't know how good and we don't have a firm grasp of the odds of some degree of success. Hopefully, it will not take too much longer for TH to de-risk this situation.
realitycheck4u wrote: As I had stated before. If some news is coming out then it shoulod be released at 4pm as this gives time for news to circulate in advance of a call for the next morning. It ensures good news is digested.