RE:RE:RE:RE:RE:RE:Finally listened to call It's very funny. They were asked about MDR HIV population size.
Paul chimes in with "There is a significant unmet medical need for that. No question. What is the untapped population? Is it 2,000? Is it 3,000 patients? We're not entirely sure."
John Leasure, the commercial guy, says very straightforwardly "Well, we understand the market size, I think fairly well, it’s around 2,000 patients a year."
Paul's not an idiot, he knows very well what their internal figure is for the MDR market size, it's 2000 patients but he can't help pumping it higher by 1000 with a suggestion (see question mark) that it might be 3000. There probably is uncertainty about that number, 3000 is probably possible but unlikely, but dropping the 3000 is there to make things look better more than express that uncertainty. This is his MO. I'm not suggesting that everything he's saying is inflated but around some of these more vague statements we need to remain critical.
SPCEO1 wrote: The "one, a couple or several pieces of data between now and Christmas" is pretty close to what Paul said in mid-August and it was not vague. I have no problem with Paul giving best case scenarios but it would be better for both him and investors if he identified it as such. For example, he could have said at that time, "The phase 1b trial is progressing nicely and we might start seeing developments in the trial which would lead to one or more protocol amendments between now and Christmas, with the probability of seeing such events increasing as we move closer to the end of 2022". I think we all would have understood better then that there was a small chance of early successes being reported but it was much more likely to occur later. Perhaps he could have explained the difficulty in seeing results earlier in the trial just as you did in yesterday's post. Maybe, as Joemare suggests, since they are rookies at cancer trials, they are learning a lot of this on the fly as I am from you. While I am very grateful for the great education you provide me.and the rest of us here I would really like the company to ease your burden and do it instead. That is just good expectations management. But since they may be just learning some of these cancer trial dynamics themselves, they are making some mistakes that cannot be avoided.
In private conversations I have previously been involved in with the management team and as my friends also reported yesterday, Paul leaned heavily on Christian to get enrollment moving. So, it is clear to me the main obstacle to getting trial results is enrollment. If enrollment was going well, they would be happy to talk about actual numbers.
Someone posted earlier about Christian's positive comments during the conference call and these sentiments were apparently reiterated during my friends call with management yesterday. Paul does have the propensity to act like many CEO's by putting the best possible spin on things but Christian has always seemed to me to be giving a more realistic view. Based on his comments, the liklihood of success in the phase 1b remains good but, like most everything in biotech drug development, we need to hurry up and wait some more.
qwerty22 wrote: I can't recall the exact comments if you have them we can discuss. I expect they are sufficiently vague as to have many meanings. I'm still not against them hitting two responders in one cancer before Christmas though. That could still be on the optimistic side. What would we have? 7 patients on-boarded for each cancer. 2 patients at their 3rd scan, 2 more at 2nd, 2 at 1st and one yet to reach 1st scan (assuming no dropouts). You could get confirmed responders from that but still you are at less than half your target patients beyond 2nd scan. I guess odds are increased by the fact you are chasing multiple cancers here.
Paul more often than not gives best case scenarios. He's telling you what's technically possible rather than what's likely. We have to get used to that. I think we all know this then somehow forget it, then relearn it and rinse and repeat.
We should probably prepare ourselves for Christian's timeline to have some chance of being delayed. It could be that timeline assumes everything runs perfect and in the real world of clinical trials not everything runs smooth.
SPCEO1 wrote: Remember, Paul said in mid-August at the Cannaccord conference that they could report one, a couple or maybe several pieces of data between then and Christmas? He gave the impression something might possibly be announced quickly. When you consider that comment, how does it fit into the scenario you laid out. And why would he build expectations for a possible early good report in September or October? What might have been going on in the trial at that point to lead him to say that?
qwerty22 wrote: The other thought that struck me recently which we've ignored given the focus on efficacy is that we are still very early in the process for safety. Only 13 patients in 1a recieved 300/420 mg doses. We really should be considering that the breaks on enrolment aren't off yet from a safety perspective. It's noticeable that they are timelining 10 months for enrolment and there are 10 patients in each cancer. It's possible the fda has set a max enrolment rate, say one patient for each cancer completing a cycle before the next can be enrolled. This would protect greater numbers of patients from being exposed to unknown risks.
If there is a safety component to the enrolment rate (which I imagine there should be at this very early stage) then probably enrolment is neither fast or slow but proceeding steadily as they indicated yesterday. It would mean that no one individual cancer type could race ahead and get across the finishing line faster. It might explain why for now they are comfortable with just 6 centres enrolling. My original thought, which would be wrong if this is true, was that if they could aggressively recruit one particular cancer type that could get us to a go/no-go signal earlier but if we are still looking at very controlled enrolment for safety reasons then that's not possible. A good reason why they still aren't reporting efficacy yet. It's possible some efficacy signals are popping up in different cancer but nothing has got across the finishing line. That might put them at about 5 enrolled patients in each cancer type atm. Remember five enrolled steadily in each cancer would break down as say 2 with 2 scans, 2 with 1 scan and 1 yet to be scanned. You wouldnt expect that to get you across the line for a go signal.
It's possible they do cross the line from an efficacy point of view before the end of Q1/23. If the drug is good it probably should happen in the next 90 days as you say. Whether from a safety perspective they are still tied to a steady enrolment rate due to safety after that IDK, it would make sense that they are.
I'm imagining those centres waiting in the wings in the US, Europe and Canada are for when the breaks are eased a little more on enrolment. It would be useful if anybody has some solid info on how fda safety concerns is likely to be controlling enrolment rates at this point. That might be the elephant in the room we haven't considered. BTW I'm not saying there is a particular safety issue with th1902 but this is how the fda always proceeds.
Inthink if enrolment is steady and controlled and across the range of cancer types then basically we are just too early for any one cancer to have reached the go signal for expansion. And if that's what they are waiting for for public announcements then we were all too aggressive in our expectations for this Q. The go signal is not so high that we will be waiting forever (although it might seem like that) but now is just too early.
PWIB123 wrote: You and Scarlett picked up on the ssame thing I did after I listened to the call myself. It was around the 35 min mark where the lady filling in for Ed Nash started asking questions about the basket trial and when we could expect information on data to be shared. I thought Christian's comments were extremely positive and provided insight into what his true thoughts were and the best and worse case timelines. He said he believes we will see signs of eficacy in some (plural) of those tumor types. He reiterated they are looking for 2 responses or more in at least 1 tumor type. He said they expect to be able to announce signs of efficacy by end of quarter, and then he backed up and said at least by end of first quarter next year, wihtin next 90 days. Christian was as direct and confident as anyone could expect. I thought this was hugely positive!
I also picked up on Paul making a statement that they were seeing a shift in the industry toward administration of Trogarzo in pharmacies rather than clinics and that the IMF push would benefit there.
I thought the team expressed additional confidence in Egrifta being a viable solution in spite of not being an easy to administer pill.
All in all, while not overly energetic, I thought the call was mostly postured with positive overtones. I still wanted more, and Paul and the board have got to accept the fact that they have to communicate differently in the future, but I didn't walk away thinking TH-1902 was a dud and the program would be scrapped. It's just a long-time in the making of what will be an overnight success story. Hopefully they build on it.
qwerty22 wrote: I was going on people reaction here before.
I thought the call was fine apart from no ongoing trial update.
There was one nugget when Christian seems to suggest that all the main cancers in the trial had over 85% Sortilin expression. He seemed to suggest that was what the up and coming microarray poster would say. If that's true then that is great, in fact fantastic. The worry that they are enrolling significant SORT- patients is really off the table now. It also makes screening for Sortilin less of a priority for now. That's great news.
The other good point for me is Christian clear said the protocol going forward is see two responders from upto 10 patients, expand to 25 and then move forward to the next phase if they have the data to support that.
They obviously made a prior decision not to discuss the ongoing trial. My take is it is hitting that 2 responders from 10 that triggers the next update especially if that triggers a quick expansion to 25. So this is what we should be expecting. Should that have happened by now? I don't think so necessarily. If no one cancer type has aggressively enrolled then they could have a mish mash of results where none of those quite reach that go signal benchmark. I guess we have to accept they aren't going to dribble out results on every responder leading up to that point.
I can sort of even understand why they don't want to talk about enrolment rates. If you say it's slow, then that's a negative. If you say it's fast and aren't releasing details on responders then it looks like the drug is a dud.
I think the one conclusion we can say is the probably haven't hit the go signal yet. I'm not too bothered (yet) about the trial being a dud. I'm putting this down to our expectations being too high about was is possible yet. You sort of have to admire their discipline is saying nothing about the ongoing trial. It sucks but they clearly decided to say nothing and they did it well.
On other things. I thought they contextualized the NASH situation the way I understand it. I also thought they inspired a bit more hope that the Trogarzo management plan could yield some potential benefits (eventually).