I love what Benitec (ASX : BLT) is doing and I want to thank their shareholders for the profound contribution to science that they are personally bankrolling.
Whaaaaaaat, you may ask? Has Long Tail had one glass of vino tinto too many on a blustery Melbourne Sunday evening? Well, yes – probably. But let me explain.
Gene therapy is kind of a big deal. Gene therapy is going to be one of those technologies that in 50 years we will look back on and wonder what all the fuss was about. Gene therapy is one of those things that will remove lifetime breast cancer risk (think correcting BRCA mutations at birth), slash Alzheimer’s disease (rub out that e4 variant of the APOE gene) and make a missed cystic fibrosis screen a mere “glitch” in the otherwise healthy life trajectory of a young child. The great tragedy for gene therapy is that we didn’t get to it 20 years ago when we could have, and that academic hubris and scientific ego got in the way of learning to master this amazing technology in a manner that didn’t undermine its incredible potential. By the way if we had got onto it a couple of decades ago when we should have, BLT would have undoubtedly been (at some stage) a multi-$Bn company.
For for many BLT shareholders, this weeks stock “bump” on the back of the news that an AASLD abstract was published that indicates that TT-034 reaches the liver and does its biz, was a brief moment of adulation. The ASX disclosure was fairly perfunctory but had a nice glow to it.
However, the information also has some challenges. The transduction is behaving exactly as you would expect for this type of vector – it’s fairly heterogeneous. Also, although the dose escalation is showing the right sort of profile, it also isn’t indicating the “one shot” profile that TT-034 needs in order to be successful. In short, the data is scientifically extremely interesting (and I hope that BLT will publish it in an appropriate clinical journal in due course) but it’s not, so far, delivering on the company’s hype.
In my view, the company is right on track. Right on track to show a great scientific outcome in a system and product strategy that will, ultimately, have no impact on human health. But the knowledge gleaned is invaluable and for that we should be thankful to BLT’s shareholders for their generosity.
Addendum : 26/10/15
Since a number of HotCopper punters have posted and emailed me about this post, a clarification is warranted. There are three very simple things that I believe are important to understand :
- Plenty of things that “work”, fail. I know this might be incredible to understand, but it’s absolutely the case in drug development. Unless something works REALLY well, it doesn’t make it to the end. In the case of the HCV program (TT-034) there are two red flags. The first is that we would know by now, even at very low doses, if there was any change in HCV RNA profile. It’s actually pretty sensitive to perturbation and very accurate to measure. The company has had plenty of time to determine whether there is any impact on HCV RNA expression (without worrying about a “macro” measurement like viral loading) and the fact that it isn’t jumping from the rooftop with news is worrisome – in fact, one can take the argument that BLT simply just reporting the “wrong” information to shareholders because it sounds better. Secondly, the transduction profile (the information BLT is sharing) is quite heterogeneous and this means that it could take very VERY (i.e. impossibly) high doses of TT-034 to achieve the “one shot” differentiation that BLT needs to have in order to have a crack at being successful.
- If TT-034 doesn’t deliver the “one shot” performance it needs, it will fail commercially. We have too many other successful (and available!) HCV drugs with astonishing cure rates in most patient populations.
- I am genuine when I say that this is wonderful science, and the information we are learning about this kind of gene therapy in the clinical setting is an enormous contribution to human knowledge. But it’s also pretty much unfolding the way one would expect it to unfold – imperfectly. If TT-034 fails in HCV, there is, alas, also no magic bullet for “Hepbarna” (noting already that a drug that is branded before it is even in living systems is – by fate – doomed to fail).
Hope this clarifies.