Theralase Technologies Inc. V.TLT

RE:RE:You ain't seen nuthin' yet - TLD1433 on Steroids in 2025

[CancerSlayer]

enriquesuave wrote:

That is why I have suggested that they eventually do a trial for patients who don't respond to Ruvidar to get treated with IV Rutherin or Rutherin/ Ruvidar combo.  Just IMHO.  I think we would get close to 100% CR overall, and any recurring cancer would be retreated also with close to 100% CR potentially.  I think they should point that possibility out to the FDA.  Time will tell.

Eoganacht wrote: The current trial is experiencing outstanding results - at least as good as, or better than, any currently approved or prospective treatment for high grade BCG-unresponsive NMIBC.

Ruvidar PDT could well could become a new standard of care treatment for bladder cancer.

Nonetheless, not all patients treated experienced a complete response. The reason for this was unobtrusively explained in a 2020 paper by Dr. Lilge and colleagues.

"This study does not address possible caveats for the clinical translation of TLD-1433 mediated PDT for NMIBC. For example, the urothelial layer over the tumor must be compromised for the photosensitizer to gain access to the malignant cells. Therefore, a tumor growing under an intact urothelial layer may not be sensitized by instillation alone. Also, NMIBC can be present upstream of the bladder, which is not targeted by PDT limited to intravesical illumination and bladder cancer cells as cancer cells may shed upstream and reseed on the bladder wall denuded of the urothelium, suggesting that for clinical use, repeat treatments may be advisable."

Evaluation of a Ruthenium coordination complex as photosensitizer for PDT of bladder cancer: Cellular response, tissue selectivity and in vivo response

So, most likely, some bladder cancer cells are escaping the onslaught of TLD1433 instillation, and some patients who experience a complete response are having their bladders reseeded with cancer cells  from upstream of the bladder.

The current TLD1433 trial is an intravesical procedure because Theralase could not afford to get their first trial wrong. The deeper muscle layer of the bladder had to be protected at all costs, as the earlier intravenously delivered photofrin trial had demonstrated how

 

Good point...utilizing both an intravesicular (Ruvidar) & IV (Rutherrin) approach would not only help overcome Ruvidar's delivery limitations, but could potentially allow treatment/delivery to the upper urinary tract as well (systemically & via kidney clearance), which could help decrease the risk for any cancer recurrence or spread.  

It would also be interesting to compare IV Rutherrin monotherapy vs the combo of Ruvidar/Rutherrin....with the ultimate goal of using IV Rutherrin as a stand-alone, which would certainly simplify the procedure (non-invasive approach) & decrease pain & infection risk.  This advantage could also lead to greater compliance & quality of life.

Lastly, as Rutherrin is a more selective compound (primarily targets cancer cells), there would potentially be less risk of bladder complications (i.e. contraction/impact on muscle layer) that was seen with IV Photofrin & made its clinical application limited.  Rutherrin/Ruvidar also does not carry the side effect of skin light sensitivity.

If we are approved, there's the realistic chance we replace Photofrin & become the new standard for the PDT market (& likely other markets in time).  The PDT market alone represents a > $1 billion market that is expected to triple in the next 10 years. 

I'm liking our chances.  Good luck...