Drawing upon the GSK no regrets article previously mentioned, we could ask the question why doesn't GSK have no regrets on swapping out cell therapy for an oligo strategy. One extremely likely possibility is that, according to the article and comments from the Head of Research for GSK, genetically validated targets have at least a twofold higher chance of approval.
So, GSK likes the twofold increased odds!!! Say if you could increase the odds six-fold. Referencing slide 13 from the PYC Investor Update, it is possible using genetic validation of targets to yield success rates six-fold greater than the industry average. Are we comparing apples with apples or are they pineapples? I suspect its apples with apples but to go from twofold to six-fold, I'm guessing one has to add in a couple of extra steps which we will now call powerful forces.
- Facilitate the delivery of RNA drugs to their target cell
- Apply RNA drugs in the context of increasing gene expression
- Select monogenic genetically validated targets
- Use patient-derived models to validate drug candidates before progressing into the clinic.
Lets summarise. If you want to go from twofold to six-fold increased odds then, apart from using the principle of genetically validated targets, you need an efficient delivery system to get RNA safely into the cell; focus on disease indications that responds to increasing gene expression e.g. haploinsufficiency diseases; select genetically validated targets that are monogenic i.e. controlled by a single gene; and finally use better predictive models such as patient-organoids that mimic the biological characteristics found within the disease setting.
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