RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:Credit Suisse event now availableI listened to the presentation. Nothing really new on the fundamentals.
To me it is clear that they are on the right path and there are no red flags at this point.
It is also clear that the strategy is to say the minimum about what is going on in the trial. A simple example of that is the answer to the question about the level of free docetaxel in the bloodstream after injection of TH1902. Levesque specefied, because he was asked, that they see a similar profile in humans that the preclinical data he showed in the presentation. As I said many times here before, the pharmacodynamic data is the first thing they got in that trial. They know since June the the profile is similar in humans to what it is in mice, but they did not say a word about that until being asked in this presentation. But after being asked, Levesque went further by pointing out the obvious, if free docetaxel in the bloodstream is low after injection of TH1902 in humans, it is in line with lower toxicity, that's why they are now at twice the MTD of docetaxel injected alone. But if you push this logic to its limit, it means TH1902 is moatly out of the bloodstream and goes inside cells with sortilin receptors. So it the next logic step is efficacy if doceraxel is selectively cleaved from TH19P01 inside cells. So all that to say that Thera could have released the info back in June, at the oncology KOL presentation. They had it back then and did not release it. So if the had efficacy signals up to now in the trial, be sure that they will not say a word about that. To me, it is clear that they want to come out with the clearest picture possible and be as sure as possible about the data they will release.
As I wrote before here, given they are now at twice the MTD of unconjugated docetaxel, the only question is about the selective cleavage of docetaxel in the cells expressing sortilin. So it comes down to the linker. I spent a lot of time trying to learn more about the linkers they are using, and it was for a good reason. It seems that the only thing preventing good efficacy based on what we know would be a linker that would be hard to cleave from docetaxel.
So to me, Thera is Thera in all of that, even though they have a new CEO and Tanguay is no longer there. Levesque comes from Pfizer, a very big pharma, and these big pharma are not releasing clinical data easily. The realease some data when it is advantageous for them, or when they drop a program as a way to justify it. So I think Levesque is likely to act in a similar way.
One positive bit Levesque said is when he talked about how it goes in strategic meetings about the future of SORT1 plaform. The fact that there are so many ideas. You don't have so many ideas for possible uses of TH19P01 when you phase Ia trial is giving negative signals.
One new option of conjugation to TH19P01 that Levesque talked about was to conjugate siRNA to the peptide. On paper it's a good idea. I am still waiting to hear him talk about the posiblity of using radioisotopes for imaging and treatment.
He confirmed again that results of phase Ia could be published only at the beginning of 2022. It means the door is still open to a MTD that would be higher than two times unconjugated docetaxel.
If they come with very good results in January, including clear efficacy data, nobody will complain because they kept it all for them until that time. The best impact will be with a big release of full results at the end of part A.
The company and Levesque are not behaving like a company that are aware that they run a trial in oncolgy that will fail. To the contrary, oncolgy is now the main program of the company and all signs point to a positive outcome of phase Ia. That being said, they make it clear that the trial aiming at showing efficacy is phase Ib. I think it's true, but also a way to lower the expectations for phase Ia. Personnally, I think they will have efficacy signals in phase Ia, but not to the full extent because the few patients recieving the highest doses will have only one or two cycles of treatment before the end of the year and they won't be selected for sortilin overexpression.