Theralase Technologies Inc. V.TLT

Science discussion - for TLT geeks only

[DJDawg]

I was reading up on the whole issue of partial response (PR) and had a few thoughts.

The company and a few posters are hopeful that patients who have positive cytology but normal appearing cystoscopy may in fact get to be labelled as CR if they find that the cancer is in fact upper tract (ureter and higher). The way do do that is a CT scan.

It is confusing to me but from what I can see, most bladder cancer doesn't have upper tract cancer at the same time. Depends on smoker status but range is something like 2-20%. That means that for all the PR's in the TLT research, not that many are likely to switch to CR due to upper tract foci.

The thing I have found interesting is that CT scans are cheap and easy to order. Doesn't take long to get one at all. I can say that as I i have worked in parts of healthcare where CT requisitions were placed. MRI's were a totally different thing. It seems odd to me that there are patients that have been PR for so long as if it was in fact an upper source for the cytology, the CT would have been done by now.

My hunch is that many have had CT and no upper source was found. BUT, that they have been kept rolling in the study and are still PR because if you find the positive cell cytology in the urine that means that, at best, they are PR. If you cannot see the cancer on the scope and you cannot see any recurrence on the ureteric CT imaging, then you can't quite say that they are full NR either as a full Non-response would be cells found and some kind of visualization of cancer recurrence together.

So what does that mean? My hunch is that they are dealing with a new issue of sorts which is due to how TLD-1433 works. If cancer growths are a collection of cells that are not entirely uniform then I think that the rapid growing ones are the ones that are likely most drug avid. The treatment protocol would lead to the fast multiplying and expanding cells being ablated. Leaving the slow growing and slow multiplying residual cells still present for some patients. Those cells may still shed a few here and there so that they are on the cytology but if they are not rapid growing and dividing, they may stay at low size so that you don't get the ability to see the leftover cancer focus. Means in a way that you are in PR limbo for a while.

But I think that this is still a good thing. Research into a variety of cancers have shown that transferrin receptors are more highly expressed in the rapid growing and dviding cancer cells. Which makes sense as they may need iron to grow and spread. So the TLT drug approach is most effective at attacking rapid, aggressive cell lines with high transferrin receptor expression. If cancer clumps or collections have a mix of cells, then the ones that are not rapid expanders are perhaps not going to to killed off as well by the drug. Which is not the worst thing as those slow growing and slow multiplying cell lines are not as likely to invade, spread, metastasize.

All in all, I wonder if it is going to play out that TLD-1433 works to kills of all cancer in some patients but in others, only kills off the aggressive cell lines, leaving some cancer still present. That would count as a non-progression in my view. Non progression still means no need to remove bladder. Non-progression for brain and lung cancer could still mean that the patient does well, with the cancer being restrained into being a slow, stable cell line leftover. Not ideal but still a good thing. The area that I used to work in dealt with thyroid cancer. Many patients had surgery and a type of ablation. Then still had some cancer cells left. However, they would just have imaging for years and year and nothing would change. The few small clumps of definite leftover cancer would stay the same. Which is funny if the initial cancer had growth and spread all over the neck. With thyroid cancer, when you ablate the left over cancer cells, the treatment also is selected more towards fast growning and fast mutiplying cells. So even if you are not cured in the end, you can live decades plus with a residual clump of cells.

When I've read up on immunotherapy with BCG or the like, it strikes me that the methodology works against NMBIC cells without any distinction for aggressive cells or slower cells. As such, it seems like it is whack a mole therapy. Cells grow and divide, BCG tries to attach and trigger immune response to the cancer cells. If cells divide faster, cancer spreads and wins. If BCG/immune response is faster, cancer is treated.

So in summary
- I'm bored (obviously)
- CT's are easy and quick to get, even if you factor in pandemic.
- upper tract cancers is not too too common (at same time as bladder cancer)
- Suspect many PR's have had CT scans and that they are still labelled PR because CT didn't find anything, but neither did the cystoscope - I call this limbo PR
- suspect many PR's are in limbo because the left over (after TLD-1433) cancer cells have been selected to be slow going.
- TLD-1433 working against agressive (high transferrin receptor expressing) cancer cells is a good thing and may make some patient's long lived but not necessarily cured. That is still a valuable drug.

Comment away. I'm no expert  :)

[Longholder99]

Suspect you like to bury a little bit of doubt in the science of this process in almost every one of your 'Im pro TLT ....BUT' posts. Suspect your motives. Thats what I suspect.

[CAinPlap]

Suspect you are being a little harsh on the Dawg. Perhaps my ignorance is showing but I took the post as positive. It's too late for us as we are likely already "married to the stock". Maintaining a little doubt is likely a good thing to prevent a bad relationship. lol For better or worse for the sake of our kids and future grandkids. :)  I think we have a few who fall in this

[DJDawg]

Sigh. I've never been anything but a big supporter of this stock. I was just bored and thinking about some of the patients in the PR category who have stayed PR for quite a long time given that CT scans are not hard to get (something I know about). If you read me as as being down on the stock then that is unfortunate.

[Longholder99]

Or accurate. BTD on the horizon. Nice volume today.

[socksnblonds642]

All good thoughts I think. I read your post as a positive outlook on long term correct dose PR's. It's not a stretch to consider that CT's have been performed. From what I understand you are speculating that a good PR is better than a NR. It's also healthy to pump the brakes once in a while, so easy to get caught up in the positive results. We are all waiting to see what happens to

[enriquesuave]

From the press releases it sounds like PR patients have not yet had CT scans? Are they waiting till end of trial?  Would be good to find out.    

[skier59]

Ya this one could blow the roofs off. That whole gang whom were undertreated, got their second 6 month treatment with the optimized corrected procedure. Those results will be extremely interesting, along with what we suspect from all proceeding procedures. Not sure about all you longs as me, but I'm feeling really good :)

[DJDawg]

Thank you! Great to have conversation. I like some of the ideas put out there. My only outstanding point is that CT's don't take 6m to do and when read, the radiologist can give a report in less than a day. For that reason, I suspect that some of the PR's have likely had a CT for which nothing was found. Then nothing on the cystoscope....so all you have is a healthier looking urinary

[Oilminerdeluxe]

Any thoughts on when GBM can realistically start? Just for speculation. Would not mind at all if they announce they have applied for BTD. Perhaps such things are not announced, but one can at least hope. A j/v, a grant, a virus update. there could be sop many things happening in Q1. Have a blessed New Year all.

[menoalittle]

>> "married to the stock" common law marriage, eh? (think that's 7 years most places... lol.) maybe a few others (like me) simply proposed after the first date. (either way, probably feels much the same after a few years...)  

[Eoganacht]

Hi Dawg - I was not aware that there are less aggressive bladder cancer cells which have fewer transferrin receptors. That could possibly explain how some bladder cancer cells can escape from the onslaught of Theralase's ACT.  Another possible explanation of how some cancer cells might escape was offered by Dr. Lilge in a 2020 paper. "This study does not address possible caveats for

[enriquesuave]

A few points which I will address Dawg but overall good analysis.   1)  Remaining Low Grade cancer is considered CR if I remember as risk of progression is low and Turbt can be performed  I will recheck FDA guidelines  2)TLD-1433 destroyed 98-100% of tumors in preclinical NMIBC and 100-% for MIBC 3) Most probably the activity of the transferin receptors is increased even if

[enriquesuave]

From FDA document   "For the purposes of determining the duration of a complete response, the FDA defines a recurrence as findings on follow-up that no longer meet the above definition for a complete response. The protocol should provide a plan for the evaluation of patients with suspicious urine cytology. Suspicious cytology does not include the presence of atypical cells. This plan

[Oilminerdeluxe]

Theralase is 33% of my portolio's value. The young me would probably have increased it to 75%, he he.  But suspect it is better for my health if it rises on its own to that level. On the other hand, beginning a shopping shopping spree would make the days more interesting. Sweat, greed, anxiety, frustration, despair, anger. I mean, what's not to like ? :-)

[CAinPlap]

Your not suggesting TLT being 75% or more of one's portfolio a bad thing are ya? ;)

[CancerSlayer]

  Boy, back from the Holiday vacation & it seems I missed a lot.  Good points DJDawg.   It is my understanding that a PR can also represent a positive cytoscopy with a negative urine cytology.  In such an instance, a patient would require a bladder biopsy which could delay the reporting of response results.  Such a patient would be considered a "CR" if he

[DJDawg]

Great points. Thanks for engaging in this as I do feel it is a small head scratcher in the whole process. I'm not doing a very good job of articulating when I say slow growing. I guess what I'm thinking about his how some research into GBM, for example. found that the cancer was more heterogenous than just one mutated cell line. For some GBM there are a whole variety of EGFR mutations in