Theralase Technologies Inc. V.TLT

RE:RE:RE:RE:Isolated data on the optimized group

[Eoganacht]

The thing about Theralase's pdt is that it's not just a drug treatment that cancer cells can build up resistance to. It's a two step process. By itself the photosensensitizer is harmless enough and is permitted access to the cancer cell interior. And it remains harmless until acted upon by an external force - the application of radiation of a certain wavength which induces the creation of ROS which blows the affected cell to smithereens. How can the poor cancer cells be expected to defend against that? It's difficult to build up resistance to being hit on the head with a hammer. Somehow the cancer cells would have to figure out it was the TLD1433 that was softening them up for the hammer blow.

Eoganacht wrote: I'm not sure what would make cancer cells "sensitive" or "resistant" to the treatment. According to one of Dr. Kapler's papers:

"Upon administration Ru2+ complexes associate with albumin and transferrin enabling receptor-mediated transport into cells."

https://pubs.rsc.org/en/content/getauthorversionpdf/C5PP00450K    (page4-5)

TLD1433 binds to naturally occuring transferrin in the bladder and then preferentially accumulates in malignant tumors versus normal host tissue by way of the overexpression of transferrin receptors on the surface of cancer cells. The overexpression of transferrin receptors is necessary for malignant cells as they require extra iron in order to proliferate.

The only way I can see that the cancer cells could become less sensitive to the treatment would be if they could cut back on the number of transferrin receptors on their surface so that less photosensitizer could accumulate in their interior. But this would also mean having to cope with a reduced supply of the iron which they need to grow.

CancerSlayer wrote:

I would also add that a sub therapeutic dose followed by a therapeutic dose 6 months later may have contributed to the NR.  Swift & thorough cancer eradication is key in preventing cancer resistance, which highlights the importance of proper dosing, number of treatments & timing of treatments.  The sub-therapeutic dose that had been given may have not only "partially" treated the cancer, but may have potentially encouraged the growth of both treatment sensitive & treatment resistant cancer cells...all imo.  If this were the case, the timing of a subsequent optimized treatment may come more into play.  Just thinking out loud, but perhaps an optimized treatment administered earlier (before 6 months) for this suboptimally treated group (or even two optimized treatments subsequently administered) may have led to a different result.  I think over time & with additional experience/study, the ideal treatment time interval/density of treatments for a given cancer (especially for a resistant or stubborn one) will continue to evolve for the better.  Good luck...

 

Eoganacht wrote: Hi ScienceFirst - I'm nit-picking here, but only 4 of the first 12 patients received an optimized second treatment. I believe one eligible patient of the 5 opted not to remain in the trial. The fact that these 4 patients ultimately ended up NR, despite their single optimized treatment, demonstrates the wisdom of treating each patient twice.
 

 

From the Nov 27, 2020 MD&A

 

"Study II has enrolled and treated 12 patients as of September 30, 2020. Out of the 7 patients that are eligible to receive the second treatment, 5 have been treated and 2 are pending. 2 of the 5 patients treated for the second time have been treated with the optimized Study II treatment, which will also be the case for the 2 patients that are pending their second treatment."

 

ScienceFirst wrote: April 22, 2022, TLT produced a separate chart for the optimized group.  See "Study II Clinical Study Data (Optimized: Post August 1, 2020):"

Assessment (Days)	Complete Response (“CR”) 2	Partial Response (“PR”) 3	Pending 4	CR (Evaluable Patients) 5	Total Responders (CR + PR) 6	Potential Responders (CR + PR + Pending) 7
90	52.2%	17.4%	13.0%	60.0%	69.6%	82.6%
180	22.2%	18.5%	40.7%	40.0%	42.3%	83.0%
270	14.8%	3.7%	59.3%	36.4%	18.5%	77.8%
360	3.7%	7.4%	66.7%	11.1%	11.1%	77.8%
450	3.7%	3.7%	66.7%	11.1%	7.4%	74.1%

Take into consideration this passage below of July 30, 2020, as it seems to confirm that p# 8-9-10-11-12 might be considered belonging to that optimized group and if so, could have prevented us to reach close to 100% as it seems that they ended up being NR @450-days.  So if we would have excluded them, we could certainly have had higher efficacy %.  That's why the data on August 30 on the 11 pending ones is so important to try to see through the data.



July 30, 2020:

Theralase Reports on Phase II Non-Muscle Invasive Bladder Cancer (“NMIBC”) Clinical Study (“Study II”) Progress – Theralase Technologies



... Study II enrolled and treated 12 patients

Study Treatment Optimizations:

Additional optimizations to the clinical study protocol that have been implemented for all future patients to be enrolled and treated in Study II and for the five patients yet (so p#8-9-10-11-12) to receive their second treatment