About the addition of up to 9 CSS ...It's not sure, but it's more and more plausible that this objective could be linked to a conditional Accelerated Approval, to act as a confirmatory trial. Especially that we have a holy grail oncology treatment.
We know that the FDA requires that such confirmatory trial be already active, but is not dogmatic for smaller biotechs as per a recent article on the subject, considering the burden of such request. So maybe they are being comprenhensible and flexible enough about when could these CSS be added and if these CSS could qualify as a confirmatory trial.
With our actual 12 CSS, we're treating on avg. 1 patient/month, globally. COVID-19 clearly didn't help.(as it prevented us to enroll for 18 months). A Breakthrough Therapy designation could certainly create more demand for our 12 CSS. So having a higher avg/month (lets assume 2/month) would allow us finish our current trial faster..
Being at least at 51 patients (lets assume 54 as of today now) so far, 50% into a pivotal Ph. 2, and already having claimed that, late 2025/mid-2026, TLT could receive full FDA approval, I don't think these "up to 9 new sites" would make much of a difference in reaching that "2026" commercial rights as you have to remove almost 18-20 months to that "mid-2026" full approval (450 days since the last treated patient + 6 months of FDA evaluation/decision). So assume that our 100th patient would be treated late 2024. With 12 CSS that would treat 2 patients/months, for 18 months (April 2023 to Dec. 2024), we could already add 36 new patients (12 CSS x 2/months x 1.5 years). 36 + 54 = 90. So without adding any new CSS, we could already be close to 100 patients by end of 2024.
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).
So that leaves us with another potential purpose for such "up to 9 new sites" and that could be because of an obligation that comes from the Accelerated Approval program that requires a confirmatory approval trial, considering that we will have higher CR and DR the more we add optimized patients and that we would really qualifiy even more for Accelerated Approval program.
We also clearly fit the spirit of the FrontRunner program (bringing late-stage treatment to early stage patients). That would instantly jeopardize the BCG dominance.
We'll soon find out. And it all depends on what the FDA has in mind regarding our trial (12 undertreated patients) and treatment (only up to 2 treatments, durable response, no serious adverse events (SAE) related to the treatment itself, higher efficacy than competition and higher reliability than BCG, no dependence with BCG).
We really have the holy grail key attributes of an oncology treatment:
- low number of treatments (1-2)
- high CR%
- high DR%
- high safety profile (no SAE)
- high efficacy
- standalone treatment
- no BCG dependent
- no patient discrimination (unlike immunotheapy treatments)
- no patient limitations (unlike gene therapy)
- low cost therapy, given low number of treatments, no combo and no SAE (Keytruda costs 455K$ for 2y)
Feb. 23, 2023:
Arkady Mandel MD, Ph.D., D.Sc., Interim Chief Executive Officer and Chief Scientific Officer, Theralase® stated, “The high complete response rates and duration of this complete response without serious adverse events, directly related to the study drug or study device, indicates that intravesical Ruvidar™ is a promising alternative to existing therapies and compares favorably to other approved therapies; including: valrubicin, pembrolizumab and Adstiladrin®.Ruvidar™, as an intravesical monotherapy, has the potential to be introduced into mainstream medical practice, subject to regulatory approval, based on its one to two treatment methodology, high efficacy and high safety profile. One day we hope that Ruvidar™ will become the organ-sparing solution that is a game-changer for both patients and physicians.”
From the ASCO-GU poster:
There have been eight Serious Adverse Events (“SAEs”) identified (2 Grade II (tachycardia, hematuria), 3 Grade III (acute kidney injury, cellulitis), 2 Grade IV (urosepsis, depression/anxiety) and 1 Grade V). None of the SAEs were deemed to be directly related to the Study Drug or Study Device according to the Data Safety Monitoring Board.
Source: https://theralase.com/wp-content/uploads/2023/02/2023-GU-ASCO-Poster-Presentation-02-01-2023.pdf