Drug Development, RNAi

Benitec’s abandoned one-dose hep C “cure” actually had two big problems

Back in February execs at the Sydney-based microcap biotech Benitec Biopharma $BNTC told their investors that they were going to drop their hepatitis C therapy because they felt that the market opportunities had dried up after a series of game-changing therapies were introduced. Now they’re also conceding another little problem with the treatment: It didn’t actually work.


Benitec CEO Greg West

The main goal for their Phase I/IIa study, the lead effort in its pipeline, was determining the safety of the therapy, which they say investigators clearly hit. However, it also didn’t have any kind of appreciable effect on viral load.

Last spring, the company — pursuing its own twist on RNAi gene silencing in search of a one-dose “cure” — said that it had decided to drop its plans to pursue a hep C therapy because of all the astounding new combos around that were attracting a considerable amount of attention. The focus had shifted so hard to Gilead and its rivals that they were having a difficult time recruiting patients for their small study. And Big Pharma had become so uninterested in hep C deals now, the best way forward was to shift to hepatitis B, where they felt the experimental hep C drug, TT-034, had helped show them the way.

“Simply put,” said CEO Greg West in a call with analysts, “the TT-034 program has not attracted meaningful interest from Big Pharma in spite of many meetings and negotiations.”

Those potential partners would have been even less interested in TT-034 if they had known the early-stage study would fail at reducing the viral burden of patients.


David Suhy, CSO of Bentitec

Dr. David Suhy, chief scientific officer for Benitec, said:

“We are obviously disappointed that we did not see a reduction in viral burden as a result of TT-034 administration. Although we will complete a more detailed assessment of the data, it is likely that TT-034 produced insufficient levels of the anti-HCV shRNA. Several years ago, we published a paper in which we made genetic changes into the TT-034 construct to down-regulate expression levels of shRNA in order to avoid toxicity at exceptionally high doses in animal models. While it is possible that the reduction in shRNA levels was further exacerbated when TT-034 was administered to human subjects, it is important to note that we have already used these learnings from this clinical study to make design modifications to other programs. In particular we have made a series of changes to generate more potent triggers of RNAi as well as modify the constructs to significantly enhance shRNA expression levels. As one example, the design of BB-103 for the HBV program, used several new approaches to significantly enhance the level of shRNA expression while still maintaining a safe profile.”

Benitec’s market cap sits at $10.7 million.

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