Once upon a time, page-4

The before mentioned article identifies the outstanding challenges for the feasibility of antisense oligomer mediated splice intervention to treat genetic eye diseases. We don't necessarily have to wait to hunker down in Seminar Room 612a. We can make some preliminary observations. For a start - outperformance.

Outperformance is not the be all and end all but its pretty close to it in the competitive biotech world. True, the outperformance is against the current CPP benchmark and we need to consider competing technologies for intracellular delivery so lets get to the other measure which hasn't in fact been measured. SoT raised it in an earlier post in regards to the question what does success look like!

The measure of success is that we can achieve 30-60 times increase in cargo delivery (relative to the naked drug cargo). This measure takes on all comers in the competing delivery stakes albeit toxicity and off target effects are additional constraining factors. Its true we don't yet have a measure because the initial benchmark used was RXR4 - the reference peptide for clinical development. It will come but at this point in time I understand confidence is derived from the current peptide outperformance. We do, however, need to make some mathematical qualification in case anyone is already running numbers on 60 times increase of a naked drug cargo achieving 5% exon skipping. My understanding is that the conceptual comparison refers to in vitro outperformance but in vivo it will switch to disease modification or a cure of sorts.

Things to note include the fact that the CPP is stabilised but not yet optimised. If its good now it can only get better. Also, there are a score of other CPPs under examination. If you think why not be like Sarepta and go with the one they're got - Sarepta only had one. Phylogica have a platform.

One of the big issues is that outperformance floats all boats. Could this be an explanation for why the dual approach was again highlighted in the most recent announcement - in licensing and out licencing i.e. the delivery of third party cargoes through licensing arrangements. The focus upon the delivery of PMOs could well be the master pivot.