Benitec Biopharma Ltd (BNTC)

[Wildbilly]

BENITEC PROVIDES UPDATE ON TT-034 TRIAL

• shRNA detected in liver biopsies at levels in line with expectations

• no treatment-related adverse events reported

Sydney, Australia: Benitec Biopharma is pleased to advise that laboratory results from liver biopsies
in the company’s ‘first in man’, Phase I/IIa clinical trial of TT-034 for hepatitis C confirmed that the
trial is proceeding according to expectations.
TT-034 works by producing (in the liver) three silencing short hairpin RNAs (shRNAs), each
responsible for targeting a different part of the hepatitis C virus’ genome. The expression of the three
shRNAs in patients’ liver cells is thus an essential requirement for TT-034 to exert a clinical reduction
of hepatitis C viral load. The most recent assay of the biopsies confirmed this expression occurred in
all three patients dosed to date. These results were obtained from the biopsies of the first two
patients in cohort 1 and the first patient in cohort 2. The second patient in cohort 2 has not yet been
biopsied, and the third patient in cohort 2 is yet to be dosed due to a personal issue.
In cohorts 1 and 2, the dose of TT-034 is sub-therapeutic and, therefore, the amount of shRNA
produced will not result in reduction of hepatitis C viral load.
Furthermore, to date there have been no treatment-related serious adverse effects (SAEs) in any of
the four patients dosed.

Ends
More detail on the TT-034 trial
TT-034 is a ddRNAi-based therapeutic, designed to treat and potentially cure hepatitis C (HCV) with a
single administration. TT-034 targets the hepatitis C viral RNA at three separate, highly conserved
sites. As such it acts as a “triple therapy” even though it is a monotherapy, and minimises the ability
of the virus to mutate and escape the therapy. Once it reaches the liver cells it enters the nucleus and
produces three separate short hairpin RNAs continuously for the life time of the cell. Thus it has the
potential to not only treat the existing HCV infection but to guard against reinfection for months to
years without the need to re-treat. It has been extensively tested in pre-clinical in vivo studies and no
adverse effects were seen at any therapeutic dose. However, as it is regulated as a gene therapy, the
trial design is to primarily ensure that treatment with TT-034 is safe, hence the gradual dose
escalation.

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