I’m going to take a different tack with this post. If I am honest with you, the last couple of posts left me feeling vacant and dissatisfied. Plus I received about 50 abusive notes from MediBio shareholders suggesting that I had missed the whole point (quite possible) and that I should focus on writing children’s fantasy instead. It’s not a bad suggestion, there is probably more money in it.
I don’t care much for PharmAust (ASX : PAA) and its affiliated subsidiaries. I haven’t yet done enough research on it to decide if it is a truly awful company or just merely mediocre. But let’s park that for now.
My gripe for the day stems from their use of the ASX disclosure rules to announce that (and I quote) “First Dog Shows Suppression of Cancer Marker.” That’s right, folks. On the 1st of May (not the 1st of April), PAA announced that its first dosing of a canine subject in a pre-clinical study showed a biomarker- based response. Wow.
I’m lost for words.
Previously I had (perhaps somewhat unkindly) lambasted Benitec for doing a drip-feed clinical update to shareholders in what I consider to be the lowest form of clinical and scientific behavior. We deliberately prospectively design clinical trials (especially randomised, properly powered studies) to have the data package statistically completed at the end of the study and we are not supposed to make inferences from individual patient data points. To do so is not only inappropriate but carries real risk of creating decision-making bias and projecting unsubstantiated inferences. When this kind of information is passed on to shareholders, without a complete data analysis and peer-review, it is just simply unethical and misleading.
In the case of PharmAust, it’s not only unethical, its tedious. Are we going to get a mutt-by-mutt breakdown of the study? Is that the gameplan? Are we going to get a sequence of sensationalised press releases that have almost no scientific content or merit? I don’t know of any translational scientist that would take p70S6k suppression (a kinase downstream of mTOR, a very important cancer target) as a sole pharmacodynamic biomarker of efficacy. We know a lot about the PI3 kinase pathway and to use a single kinase as a marker of response doesn’t make sense – it’s a lot more complicated than this.
On the topic of pre-clincal models, I am a big fan of using native cancer models (i.e vet animals) to study potential drug candidates. But it also needs to be recognised that to do so, is a non-trivial task in terms of study design, inclusion criteria and treatment response assessment. We very seldom use such models to make decisions for the purpose of human translation because there is so much variability in the model. Therefore the implication that somehow the efficacy (observed in an N=1 outcome) translates to a potential validation of a therapeutic for human use – or “companion animal use” is absurd.
I should also note that many molecules have an impact on p70S6k, some of which are known to be therapeutically effective and some that are not particularly great. Pretty much any anti-proliferative / cytostatic drug should suppress p70S6k because the target substrate is the S6 ribosomal protein (basically fundamental to cell growth). Even more importantly, if an mTOR modulating drug is to be evaluated in pre-clinical models, suitable controls (i.e. Rapamycin) should be used. Again, the challenge of using a vet model is that such comparative controls are extremely difficult to implement.
I note that poisoning or shooting the dog would have also suppressed p70S6k. I realise that this is crass, but it’s true. I also note that a change in biomarker is not the end-game, survival is the end-game. So really, who cares?
Anyhow, now I have seen everything. I always knew that first-in-human studies were a big deal, but I have never seen a company make a hoo-hah about a first-in-dog study. Remarkable. Of course this company sadly drip-feeds human data as well but when we start to get delightfully doggy updates, we know this is just about primping the stock price. Show some class, show some scientific integrity, and please don’t do it.
Awesome Photo Credit: Ryan McGuire. http://www.gratisography.com/