Eoganacht wrote: I agree that the addition of up to 9 new sites may be a positive signal about financing. The original plan was for 20 clinical sites and we currently have 11. But in 2022 Theralase starting talking about 15 potential study sites rather than 20 potential study sites (4 more rather than 9 more). I took this to be another economy measure, like the others we saw in 2022 - the employee cutbacks and the reduction of the MSAB to just 2 members. So if the CSS reduction was an economy measure it is heartening that Theralase no longer thinks it's necessary.
I'm not clear about how bladder cancer cells could build up resistance to TLD1433 pdt. Once TLD1433 has gained access to the interior of a cancer cell, activation by light creates "highly volatile singlet oxygen and Reactive Oxygen Species (“ROS”)" which destroys the cancer cell.
Unless cancer cells can reduce the transferrin receptors expressed on their surface, to reduce the amount of TLD1433 that gains access or find a way to differentiate between transferrin bound to TLD1433 and transferrin bound to Fe3+ molecules, and allow access only to the iron variety, how could cancer cells build up resistance?
If cancer cells could find a way to propogate with less iron maybe they could reduce the amount of TLD1433 they absorbed by reducing TfR receptors. Is this possible? Is it possible that cancer cells could detect TLD1433 present in transferrin and restrict access to that kind of transferrin? In both cases cancer cells would be reducing the total amount of iron available to them.
Are there other resistance methods available to cancer cells that would work against pdt? ( I'm way out of my depth )
SF wrote:
"These "up to 9 new sites" could also be because the FDA wants 125 patients, instead of only 100, considering the 12 undertreated patients, in order to have a better picture. But even there, even with these 12 undertreated patients, we already have excellent numbers (28% CR and 38% TR), despite them representing 41% of our 29 evaluable patients (12 NR out of 29 evaluable patients)."
CancerSlayer wrote:
I believe the FDA would want a more representative sample of patients treated (i.e. a total of 125) especially considering 10% of this total will have been undertreated.
When looking at the durable response numbers in those Ph 2 patients who received "two optimized" treatments (patient 13 & on), the 450 day CR is 35%. If you add in the two Ph 1 patients who received a single optimized treatment, the 450d CR rises to 47%.
The above suggests that optimization helps, but hypothetically, more treatments may not always translate into better outcomes across the board. Imo, the key for any successful treatment is to pack a big punch at the beginning, which our ACT attempts to do at the molecular level & is thus far doing relatively well...multiple weaker/ineffective punches (or too many of the same punches) could not only potentially lead to more side effects, but also more treatment resistance (I.e. a weaker punch(es) can unintentionally encourage the growth of more resistant cancer cells). You can see this resistance happening repeatedly in oncology wherein a highly-focused treatment attacks a single target/checkpoint. When such a highly-targeted treatment is performed over & over & over again, such a serial approach may actually promote a more aggressive cancer & metastasis.
The big reason I invested in this tech is because TLT is approaching cancer treatment from a more universal (a one mechanism fits all) perspective. And in those cases where more is needed, you can combine the better/best option with the lesser one...all imo.
I am still thinking the 9 new sites in "2023" has some connection with a friendly partner/funding...& possibly grant help. There is "a lot" of pressure at both federal & state levels for the FDA to perform its obligation in providing the public not only safe & effective treatment options in a timely manner, but also optioms that are both patient & pocket book friendly. This is only a matter of time in my analysis...