Benitec Biopharma Ltd (BNTC)

[Blane]

Another great response from Panno...

Author’s reply » All ddRNAi treatments SHOULD target specific cell or tissue types. To not do so could lead to off-target and potentially harmful side effects. This is why biodistribution studies are essential to both pre-clinical and clinical data collection programs. In pre-clinical studies, up to ten percent of TT-034 was found in cells other than hepatocytes but TT-034 targets viral RNA, not host RNA, and so this distribution pattern is not considered harmful.

Clearly, a 100% transfection/transduction rate is desirable, but is not essential for complete reduction of viral load because not all hepatocytes are infected. However, the vector (AAV8) does not know which cells are infected and so a shotgun approach to delivery has to be taken where the aim is to hit all hepatocytes.

In theory, a if a 40% transfection rate was achieved but that 40% included all the infected cells, then a significant reduction in a patient's viral load could be achieved. However, the next patient may see no reduction at all. This is why large scale Plll trials are conducted for all drugs to prove their general applicability. This is why I would caution against reading too much (one way or the other) into the results from the first patient in cohort three of the current trial.