Wino115 wrote: Been putting a bit of thought around this as I read so much about certain targets. The immunotherapy one that seems to be high on everyone's list and already has a slew of drugs out there is the PD-1 target, along with it's two "partners" (ligand) PD-L1 and PD-L2. There's numerous trials of drugs around this target and most are ADC drugs. Load's of combo trials too. They jump up and down around some of SeaGens PD-1 programs and many of the others.
So it got me wondering about the phrase we keep hearing from PL that "...sortilin is not a marginal target -it is a very important target in many solid tumors." If analysts are so excited about PD-1 programs, how does Sort1 expression compare if it is, as Paul says, "not marginal"? My own view would be that the more it is compared to something like PD-1 that analysts drool over, the higher the chance we may see analysts and other firms catch on to this.
In their latest published paper, THTX tells us this exact statistic. Here's the quote, and I think they should add this to their page in bold letters. Time to start educating the market around how "non-marginal" this target is compared to all the ones analysts and industry observers love -- the PD-1's, TROP-2, any large ADC target used.
Here's the quote from their paper:
"
Recently, antiPDL1 antibodies have demonstrated some promising clinical efficacy against
diverse tumor types where early findings revealed a durable clinical response in only
a small (10%13%) fraction of metastatic TNBC patients treated with antagonists for
the PD1/PDL1 pathway.72, 73 When compared to PDL1, which was found to be
upregulated in only 19% of this breast cancer subtype,74 SORT1 expression was threefold
higher in TNBC, which provides an additional advantage in exploiting SORT1
receptormediated chemotherapy for this difficulttotreat disease. It's not marginally higher --- It's 3x the expression you see of PD-1/PD-L1 for TNBC! They need to really hammer this point about SORT1 overexpression numbers versus the other ADC targets and PDC targets out there. That is one thing investors and analysts will understand and perhaps see that SORT1 is something they better learn about if it's 3x more important that PD-1 in TNBC.
Lastly, below is an explanation of PD-1 if you care. And it was taken from the website of the largest player -- Merck. The name of the drug....Keytruda -- the drug that sold $14.4bil globally last year. NOW, before you get too excited, Keytruda as an immunotherapy works on a whole slew of cancer types since immunotherapy is a completely different approach than an ADC or PDC. But there is a decent overlap with the sort1 targets like TNBC, lung, ovarian, colorectal and melanoma. But it has a much wider application. Now, could we conjugate the PD-1 on to our peptide for our cancers and make it work a whole lot better since there's a load more SORT1 in these cancers than you find PD-1? YES -- and that's probably what Paul is thinking about when he talks about conjugating an immunotherapy on theirs. I think you might also be able to do a course of TH1902 and then a course of TH19+Immuno or something like that to have that dual effect of both chemo and immunotherapy combo.
I think THTX needs to start putting numbers around this "sortilin is not marginal" and use the well known targets as a comparison. That way any learning about their program can really see this may be a target far more valuable than things like TROP-2, PD-1, etc... The context of how they discuss SORT1 is necessary since it's so new and more or less completely unknown within the analyst community. Please add that in on all the next slides -- compare expression of SORT1 versus other targets on the 4-5 main targets you're going after. That is very, very valuable info.
What's a PD-1, from Keytruda site.
PD-1 protein is found on immune cells called T cells. It normally acts as a type of "off switch" that helps keep the T cells from attacking other cells in the body. PD-1 attaches to PD-L1, a protein found on some normal (and cancer) cells. This interaction basically tells the T cellto leave the other cell alone and not attack it. Some cancer cells have large amounts of PD-L1, which helps them hide from immune attack. Therapies that target either PD-1 or PD-L1 can stop them from attaching and help keep cancer cells from hiding.