SPCEO1 wrote: The following are comments on Egrifta in NASH from a US analyst. I would be interested to see if any among our medically competent group here would like to comment on his thoughts:
"I have seen their NAFLD data – the data is from a small trial in HIV patients with NAFLD – the MRI data is OK. True placebo in non HIV patients with NASH (not NAFLD) is like 15% which diminishes the effect there which makes me skeptical.
Also the question is what is the translatability of data from HIV patients with NAFLD to actual NASH patients? I don’t think we definitively know that and I am not sure they have data there.
Seems high risk to go straight into Ph3 NASH trial.
I have seen companies with better drugs and better data fail in NASH. It is a very tough space."
I think this is an overly harsh view of TH's data but it is nevertheless the standard view and the reason why the stock is not getting any respect for its NASH efforts. A few thoughts from a non-medical guy:
1.) MRI data - they had biopsy data so why is he focused on MRI data?
I think you need to accept that the biopsy data is seriously lacking in Grinspoon's trial. Maybe his other data can step in to some extent but that data is largely missing.Biopsy data may be lacking but it is not non-existent. There is a reason why the FDA approved of THTX pursuing a phase III trial and why a well-known NASH consultant like Loomba endorses it as well.
2.) I get the impression he may ahve only looked at one of Grinspoon's trials
In a sense this is the point I've been trying to make, why I think it's natural for the market to be in a wait-and-see mode. I think you go to the data you think tells you most about the program, look at that, and when it doesn't match your expectations then that's where you stop. I think that's partly what's wrong with Grinspoon's trial, because it wasn't exactly focused on what a company needs it looks lacking. I agree with you that if he took a deeper dive into all the evidence he'd probably see more strength but I think the majority are taking the first step, see it's lacking and stopping there. This is where THTX has to step up and make sure the analysts are looking at all the data the FDA and Loomba were looking at to reach their favorable conclusions about its NASH phase III trial.
3.) There were some NASH patients in the last Grinspoon trial if I recall cirrecctly, so it was not all NAFLD
Again limited enough data to think it's not enough to support a move into Ph3 Dr. Grinspoon’s subsequent work on the genomic aspect of their data compensates to some degree for this limited initial data. The analysts above apparently did not pay any attention to that and may not even know that it exists.
4.) I thinnk AKRO had no placebo effect in their trial but their stock is still highly valued by Wall Street.
I agree the placebo is the placebo, in a sense you just have to accept it, and from the MRI data the drug effect is strong enough to make the variability in placebo in NASH maybe less important. Again though I think the fact that Grinspoon's trial is not focused in the way a company Ph2b trial would be focused gives people the wiggle room to be less certain and raise these sorts of worries. It's possible to come up with a long list of weaknesses, it seems people are constructing those lists and never getting to the strengths. As exciting as Grinspoon's data is it's just not what people expect from a NASH company, the things they expect and are missing are all they are focusing on. It doesn't pay to be odd. What I hear from this guy is a 2b just so he has the thing he's comfortable analyzing. JFM1330 made a very good point that with 18 months of data in THTX’s phase III trial, the placebo effect will be minimized as people who are overweight due to bad habits are unlikely to maintain good habits (better diet and exercise) over a longer time period. So this placebo effect issue, which has hurt other NASH trials, may not be a factor in THTX’s NASH trial, or at least a smaller factor.
5.) While we don't know exactly how the data will translate from hiv to non-HIV patients, it seems fair to expect it to translate pretty well. I have to believe the tenedncy would be for Egrifta's impact to be better rather than worse on less difficult livers.
I agree hiv to non-hiv may not be a big issue but I don't think the problem is exactly with the science. It's really with the ability of folks that look at this program to raise doubts. I can see thru 2020 the company going to investors and this guy being the typical sort of response, lot's of doubts arising from the poorly focused ttrial (that's not a criticism of Grinspoon or even the company trying to make the most from Grinspoon's work but just a fact in relation to how people expect 2b data to look). It may be written in all the various molecular studies that Grinspoon has done from this trial that the drug works but people want to see that in a non-HIV, F2/F3 NASH cohort. In general I think what investors really want from a 2b is a mini version of the Ph3 that empirically points them to where that trial will land, overall Grinspoon's trial doesn't provide that, that's it's basic flaw and nobody is going beyond that to look at the positives.
6.) While it is clearly high risk to go straight to phase III without the phase II data on non-HIV patients, can TH get a little respect for giving it a try or are we to conclude that Paul and his team are a bunch of kooks for doing so?
This is an odd aspect (of many odd aspects) of their NASH program. The market should give value to any registrational NASH trial. But right now I think the market would give THTX's NASH program more value if it was planning a 2b then it does for the plan to go to Ph3, it seems to be what people want. In an unreal world where time and money didn't matter then 2b feels like the right thing to do. I applaud them for going for Ph3 but if they can't bring the market along with them then maybe it's not the right choice. I've said before it seems to me easier to convince a pharma partner to understand this data set than the market. Maybe our best hope is for a pharma to partner and tell the market what this is worth. The other oddball idea I have to to convince the market they are investing in a registrational Ph2b. Add an interim data readout to a Ph3 that tries to answer the outstanding question and allows the trial to shut down if the answers come back negative, and focus on that as the investable opportunity. I don't know such a trial is possible but it allows the program to get onto the same path other NASH programs are on, I think that's all the THTX NASH program needs. To be seen alongside the other companies in direct comparisons, it's hard to do that right now. Going back and doing a proper phase IIb trial would cost THTX too much money and too much time. So, while the medically oriented who want to see data in the proper way will argue for this, those who are more investment-minded agree it is worth the risk to go straight to phase III.
7.) Everyone has seen companies with better NASH data fail because, technically, TH does not have much, if any (depending on how you want to look at their data) on non-HIV NASH patients. And every drug has failed so far. So, I am not sure his last statement is worht much. I would have preferred he tell us a little more about why he thinks Egrifta is an inferior drug.
There is a lack of rationality to that final statement but it sums up where NASH is at the moment. It is dominated by the fear of failure. I think if you can't rely on the strong frontrunners to get it over the line then I don't think you spend much time looking at the left field contenders. I keep saying it but NASH companies (andTHTX) need a winner to come thru more than they need to see their competitors fail.
In the end, we can protest all we like but this does seem to be the prevailing view in the marketplace and is why TH is not given any value for its NASH program. Paul and his team need to understand this and provide analysts with a well-reasoned rebuttal.
I think that's right. We haven't seen many views of what the market thinks but they are all lining up in a similar way. I think different analysts might find different features to complain about (and we might be able to knock all those arguments down) but in the end they all seem to come to similar conclusions. Doubts. Doubts that I think would be addressed by a Ph2b. I have to believe Paul already knows this from their interactions over the past year or two. I can believe they are getting one message from KOLs, another from regulators and a third from investors, each pulling them in different directions. Is it necessary to bring the market along for this program to be a success? I think Paul has forcefully tried to sell the market a straight THTX-led Ph3 and it's mostly been reluctant. Will the final plan be something other than that or will nailing down the Ph3 protocol force it into sharper focus? They've made fantastic progress but the puzzle is incomplete for me which seems very odd given how close to the end we are.
I'm not sure this can necessarily be won with better arguments, I think they'll need to give something substantially different than what they are offering now. A pharma partner would be a dream, a different sort of trial to invest in or maybe just couple it with a successful cancer program as a complete investable package There is still inherent value in many routes they could take the NASH program down, maybe you back away from what you think is the most valuable just to unlock some of the value. I really like the idea of getting a partnership with a larger pharma company in NASH for a variety of reasons. Like the FDA and Dr. Loomba, a pharma company may be much more willing than NASH analysts to accept what data THTX has in NASH and do a deal with them for the phase III. Such a partnership would instantly bring a much higher level of credibility to THTX’s NASH efforts. Unfortunately, we cannot really know if such a partnership is likely. I also suspect THTX’s board would want to know more about their cancer prospects, which they likely will know by this Fall, before proceeding with a NASH partnership.