From the new prospectus ...
The key inclusion criteria for the ACT-NMIBC Study will be patients with cystoscopically confirmed NMIBC Carcinoma In-Situ (“CIS”) with resected papillary disease (Ta, T1) (high grade) via Trans-Urethral Resection of the Bladder Tumour (“TURBT”) that are considered BCG-Unresponsive. The ACT-NMIBC Study will focus on the treatment of approximately 100 BCG-unresponsive NMIBC CIS patients in approximately 20 clinical study sites located in Canada, the US and internationally, with a primary endpoint of efficacy, evaluated by Complete Response (“CR”) at 90 days and duration of CR at 360 days post treatment and a secondary endpoint of safety, as measured by Adverse Events (“AEs”) Grade 4 or higher that do not resolve within 360 days post treatment.
Study sites will be launched first in Canada, followed by the US, subject to Food and Drug Administration approval, and then internationally, subject to international regulatory approval. It was noted in the Corporation’s MD&A for the year ended December 31, 2018 that during the Phase Ib NMIBC clinical study, patient 4 was found to have developed metastatic urothelial carcinoma and was subsequently released from the study. The release of such patient from the Phase Ib NMIBC clinical study is not expected to have any implications for the ACT-NMIBC Study as the metastatic disease was determined to be non-study related by the principal investigator. The Phase Ib NMIBC clinical study demonstrated a 66% CR with one therapeutic dose (0.70 mg/cm2 ) at 360 days post treatment (2 out of 3 patients).
ACT-NMIBC Study Drug(4) – TLD-1433 Mechanism of Action(1)
TLD-1433 is a Ruthenium based PDC, which is able to bind to a glycoprotein known as transferrin to form Rutherrin®. Transferrin transports molecular iron to cells in the body. Ruthenium is a transitional metal having similar properties to iron. Cancer cells have a larger number of transferrin receptors versus healthy cells(2),(3) . Rutherrin® is preferentially attracted to a wide variety of cancer cells, allowing TLD-1433 to cross the cancer cell membrane and, when light activated, produce powerful cytotoxins in the form of Reactive Oxygen Species and singlet oxygen.
The Phase Ib demonstrated that TLD-1433 has a strong safety profile with 95% of AEs completely resolved within 180 days. The 5% of AEs not completely resolved were not related to study drug.
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ACT-NMIBC Study Treatment Procedure The proposed Photo Dynamic Therapy (“PDT”) treatment procedure is as follows:
1. Study Drug (TLD-1433) reconstituted in pharmacy up to 24 hours prior to treatment procedure.
2. Catheter inserted through urethra and Study Drug instilled intravesically into bladder for approximately 60 minutes.
3. Patient taken to operating room, where bladder is voided and patient undergoes general anesthetic
4. Cystoscope inserted through urethra into bladder.
5. Bladder rinsed with sterile water via cystoscope to remove excess PDC.
6. Bladder distended using instillation of sterile water to prevent folds that prevent uniform light illumination.
7. Emitter and Detector inserted through working channel of flexible cystoscope and positioned in bladder with the aid of diagnostic ultrasound.
8. Bladder illuminated with green laser light to ensure placement and then full power initiated.
9. TLC-3200 measures light delivery in real time, allowing for treatment interruptions (i.e.: bladder irrigations, fiber positioning) while helping to ensure that the laser light energy density delivered to the bladder wall is approximately 90 J/cm2 . (1)