This is where it gets interesting. If we draw upon the following...

This is where it gets interesting. If we draw upon the following observation from the aforementioned article;

• there appears to be a dose threshold for toxicity. Below the threshold, toxicity is not observed but above it, toxicity is dose-dependent.

Phylogica have stated the cargo of interest - an ASO cargo, but not the disease indication. DMD may not necessarily be the first choice although presumably it will be another neuromuscular disease. The DMD space is well serviced by Sarepta and its PPMO technology will open up more therapies for people suffering from DMD. But are there limitations in the use of PPMO therapies in other neuromuscular diseases? We have already indicated that Sarepta could be sailing close to the threshold where toxicity emerges. What if other neuromuscular diseases require even higher dosages to produce a therapeutic benefit?

Think of a baseball game. The baseball is the disease indication: the arc between first and third base represents the safe and efficacious dose threshold and the batter is peptide delivery. The objective is to score a home run - clinical success, as opposed to dribbling the ball into the outfield or hitting a foul.

This is what I imagine is happening. Sarepta can hit the DMD ball with its PPMO into fair territory even though they might get close to the foul line. Doesn't matter that Phylogica can hit the ball straighter. Its all a home run within the arc of safety.

However, take another ball e.g. Spinal Muscular Atrophy. In this instance we have to redraw the baseball field. Maybe we have to halve the distance between first and third base. Now the arc is smaller, perhaps much smaller. Sarepta is at the plate and the pitch comes in. PPMO hits the ball in the same place as before but the bases have moved - now its a foul. Phylogica comes to the plate and also hits the ball as before and with its more elegant straight play hits a home run.

The key is getting the equivalent response - or better - at a lower dosage in order to keep below the threshold where toxicity comes into play.