RE:RE:RE:RE:RE:RE:RE:10% drop for whatIn the press release about phase I results, Marsolais is quoted saying this:
"The early efficacy data for our lead peptide-drug conjugate, sudocetaxel zendusortide, confirm that it rapidly internalizes and hyper-targets delivery of cytotoxic payload directly into cancer cells," said Christian Marsolais, PhD, senior vice-president and chief medical officer at Theratechnologies. llll
Sorry, they have no direct proof of internalization, because following this logic, when there is no efficacy in patients, it would mean it is not internalized. The efficacy signs they saw are mild and can be seen in control arms in other trial design. Again, look at this phase III study of Lutathera. They got 12% of partial responses with Lutathera + Octreotide, and 4% of partial responses with Octreotide alone in the control arm. Luthathera also had 1% of complete response. So Lutathera is clearly effective, but with Octreotide alone you also have what is called efficacy.
All that to say that when you inject TH1902, you are injecting docetaxel a cytotoxic drug, so even without internalization you cannot exclude some efficacy. Also, cancer can sometime regress without clear reasons. Marsolais should refrain himself from making such statements without a direct scientific proof or an overwhelming indirect proof like really high efficacy and correlation with sortilin overexpression.
https://www.hcp.novartis.com/products/lutathera/gep-nets/efficacy/#:~:text=79%25%20reduction%20in%20the%20risk,arm%20vs%20active%2Dcontrol%20arm&text=At%20time%20of%20analysis%20detailed%20in%20Prescribing%20Information%20for%20LUTATHERA.&text=Based%20on%20the%20PFS%20results,LUTATHERA%20for%20second%2Dline%20treatment.
SPCEO1 wrote: On the poster it indicates that moderate to strong Sort1 expression (H score >100) was found in around 60% of the available patient biopsies. but ""data is insuffecient at this time to correlate efficacy with Sort1 expression".
So, they did do an undetermined amount of biopsies. I find the 60% number to be lower than I would have thought. I imagine the FDA is going to want to see enough data to correlate it before allowing things to move forward. I also imagine THTX is going to figure out how to get that info but there was nothing in the PR about biopsies. Nor was there any info in any of the communications prior to phase 1a & 1b as best I can recall. So, it is clear as mud at this point whether biopsies are normally done or when they are done. Should be a good question for the investor call.
jfm1330 wrote: Yeah, but it would be so useful to have this data to be able to corelate any efficacy with real sortilin expression. That's the big freakin hole in all of this story. I still don't understand how you can develop a targeted drug without precisely assessing the level of target expression and location. If this strategy is valid, efficacy is supposed to be dependant on the "quality" of sortilin expression. Other factors can play a role to hamper efficacy, like taxanes resistance, but without proper sortilin expression, failure is assured.
SPCEO1 wrote: "Patient selection has also been refined to focus on those who are less heavily pretreated, with no more than one taxane failure and a maximum of eight prior cancer treatment regimens."
Not what you were hoping for but I imagine they think sortilin is overexpressed enough in ovarian cancer that there is limited utility in a screening for it before treatment? jfm1330 wrote: Nothing on protocol for patient selection, have I missed something?