GLP Toxicology Results of TLD-1433 on Rat & Dog Models
[News Release September 10, 2015) - Please see the extremely low Toxicity of TLD-1433
Conclusions of the GLP toxicology analysis demonstrate success in both the rat and dog models evaluated. The rat model successfully determined toxicity levels after an intravenous (“IV”) injection, while the dog model successfully determined toxicity levels after an intravesical bladder installation followed by Photo Dynamic Therapy (“PDT”) laser light activation.
In the rat toxicology study, the No Observed Adverse Events Level (“NOAEL”) IV limit was determined to be 1.2 mg/mL (6 mg/kg).
In the dog toxicology study, NOAEL was determined to be 6 mg/ml (30 mg/kg) for dog bladder infusion. Within 24 hours after instillation, the maximum level of TLD-1433 detected in blood was 0.03 ug/mL. This value is 200,000 times less than the instilled dose, indicating an ultra-low level of seepage into the blood stream supporting an extremely high safety margin. 7 days after infusion, the maximum level of TLD-1433 detected in blood was 0.002 ug/mL. This value is 3 million times less than the instilled dose, indicating a barely detectable level of TLD-1433 in the blood stream. This supports the conclusion that an infusion of 6 mg/ml of TLD-1433 (high human dose) into the bladder will be almost completely removed from the blood stream within 7 days. Thus the patient may be light sensitive for up to 7 days, which is significantly less than 30 to 90 days for Photofrin®.
In summary, the maximum detected dose in the blood stream within 24 hours after Beagle bladder infusion is 40,000 times lower than the IV NOAEL and 600,000 lower in 7 days, making bladder infusion an extremely safe route of administration for patients presenting with NMIBC.