Anti-PD-L1 Poster.
Interesting that this also seems to have come out of the UQAM collaboration, with their name on top and funding note at bottom. So that’s good — great research done with the sponsorship grant at UQAM and THTX didn’t pay for it all.
Once again, al the caveats about mice v human and the fact they haven’t demonstrated Th1902 clearly working in human tumors yet. I wanted to focus on what the “delta” is in all this data and charts as they needed something significant enough that the results not only wouldn’t be questioned, but that they would provide some real credence with the data to at least listen, look and see what possibilities there are in pursuing a test run in humans along the lines of the lab work. Very early days, but the delta’s are very significant in my view and I can see why they are interested in highlighting this as potentially important data. To me, it definitely adds some value to the pipeline, but until they get responsive human data, it’s hard to say what it may be worth. There's also a lot of competing ideas, so they need to be clever and hustle out there. Pull in all your industry contacts on this one.
It just takes one firm wanting to get into the massive immuno-oncology market in a novel way to cheaply move this to the clinic, but they’d probably also like to see human data even though it may or may not be applicable to TH1902 enhancing anti PD-L1’s in cold tumors. I suspect we’ll hear more about this as they strategize on next moves. First, getting enrollment back on a small trial, then partnering talks.
The delta’s are definitely statistically significant and not just percentages higher, but MULTIPLES higher which is darn good. The key ones that stick out the most to me are:
- 6x more of the most important types of immune cells in the cold tumor vs. docetaxel alone
- Tumor burden 11x bigger in the anti-PD-L1 vs. the combo with TH1902 at 2 weeks or so.
- Tumor burden 17x bigger in the docetaxel/PD-L1 vc. TH1902+PD-L1 combo at 2 weeks.
- Basically, the tumor didn’t grow with TH1902 while taking the combo drug. It only grew after they stopped administering the drug.
- Survival was 2.3x more with the TH1902 Combo than just the anti PD-L1 drug alone. That’s a huge survival delta.
Those are the big picture numbers. The dosing of TH1902 was also only 1/2 MTD of docetaxel given weekly in these tests. There’s a lot more details, but that’s the big picture therapeutic effect they saw in the lab. Like I said, it’s not just adding tiny amounts, but huge differences in my view — multiples are meaningful. I know we’ve see great lab numbers like this before and look where it got us. One major difference in the combo is that you are showing these highly meaningful improvements in an area where there’s a load of companies desperately trying to get in to the market and take a part of the $30bil and rapidly growing immuno therapy market. That is a totally different economic opportunity set and should help these findings get some level of interest out there. It’s a different economic equation and one where the clinical reward is known and becoming a $50bil market in a few years. I can see en easier route to justify it, but I”m probably being optimistic. Really need to hear their plan and what they actually think and have heard out there once they speak to N. Am companies for the first time.
Differential Expression in Tissue Poster
Most of this is the ongoing development of the Sort1 expression in actual human tissue, so continuing to build-up the human targeting data. This and the similar paper they published with the initial 2000 or so samples is probably part of the roadmap they will use to pick which kind of tumors to test on in a restarted trial.
- They’ll probably use other data around pre-treatments, etc.. and pick from the list of endometial, thyroid, melanoma, urothelial small cell lung. The original study had invasive ductal breast and TNBC, two types of ovarian, pancreatic and adenocarcinoma colorectal. So that’s a nice large list to pick from to increase your chance of response. Knowing the pathological sub-type expressions may help a lot as you can see some subtypes really don’t lend themselves to sort1 over expression like others do. This is part of the learning process that a lot of drug developments go through —the fits and starts to hone in on what is optimal. But that is the likely list —so no prostate despite seeing some response there, no NSCL, no bladder, kidney and maybe no pancreas. As qwerty mentioned, seeing the P11&b data on the 38 patients Marsolais mentioned could either worry us more or provide us some optimism depending on whether their data showed a lot of the enrollees had the wrong sub—types or pretreatments. Seems to make a huge difference in expression at least.
- They once again found that in the “high” expression cancers, stage doesn’t seem to matter much. This backs up the previous study and is not what they originally thought based on other academicians papers on sort1 expression. This is actually quite good — I would guess this may also be what they would show to the FDA to say that we needn’t just have stage 4 or worse enrollees and that we should enroll some stage 2/3 types if they don’t have any options or are just using docetaxel.
- Net/Net — they are honing in at least on the question of “where” it may work better given just the expression levels amongst sub-types.
TNBC/HER+ Poster -
This is definitely the UQAM work as they’re labeled up top.
I don’t know enough about trafficking through lysosomes to understand that aspect, which seems to be one of the new conclusions on the poster. I guess it has something to do with it being a marker that it clearly shows it “…internalized via endoyctosis pathways leading to lysosomes”. Only other possibly new feature is they showed TH1902 worked in a Her2-positive tumor where Herceptin typically doesn’t work, and a combo with Herceptin was also highly effective. Seems a lot of these broad conclusions were basically known, so nothing seriously new and it’s all still mice v. Humans before anyone will take this pre-clinical stuff to the bank again.