Dear Chris Garabedian,

I am writing to you today to introduce myself as a potential candidate for the CSO position at Sarepta.  Based on media reports last week (see here for the Wall Street Journal version), it seems that this position has become vacant after you had a little spat with Art Krieg.  If the anonymous sources close to Sarepta cited so abundantly in those reports were to be believed, at least some of the disagreement related to Art’s failure to push and expand the morpholino-based product pipeline the way you would have liked.  Art maybe be an icon in the oligo industry, but I believe that I am the right man for you as I know where the gold mine for morpholino oligonucleotides lies.

First, however, a few words about myself.  You may have read or at least heard about my critical writings of your company’s pursuit of getting eteplirsen, your exon-skipping drug candidate for Duchenne Muscular Dystrophy, on the market.  In case that there was some truth to speculations that some of the disagreement related to the accelerated approval strategy for eteplirsen, rest assured that I will ignore all my concerns about the conduct of the rather small trial and biochemical assays used, and tow the party line anyway.  Even better, I would be prepared to cede any involvement in the experimental conduct and interpretation of data generated in preparation of filing for accelerated approval although these activities would naturally call for my involvement as the CSO of the company.

Coming back to my prior criticisms of the company….to be frank it was Janet Yellen and the adverse impact her comments have had on biotech stocks that now forces me to apply for employment.  Nothing personal, no hard feelings, we will all be able to get along and laugh about it later.  I am running out of options as I have burned down bridges with virtually all other RNA Therapeutics companies in the field as I have freely criticized them before when I still had money.  As you know from reading the message boards carefully, I have been desperately applying for jobs there only to be rejected and attack them even more venomously.  Given my track record and financial situation, regardless of the fates of both Krieg and Linsley before that, please forgive my youthful follies and I fully expect you to be a difficult and demanding boss and I will put up with it.

I know that you have long made up your mind to not hire me and the only reason for humoring me and reading on is the thing about the gold mine.  I genuinely believe there is one and- you are right- it’s got to do with splice modulation and by extension the modulation of RNA processing by masking sites for RNA binding proteins.  In particular, I find morpholinos highly attractive for splice modulation in pharmacologically contained compartments such as the CNS where the risk- and please excuse my language here- that the expensive oligo is pissed out immediately is limited.  There is a reason why morpholino has become such a popular tool to study developmental biology in zebrafish embryos and the like: they cannot pee!!!  So with the ability of maintaining high tissue concentrations and the amazingly safe morpholino chemistry, you may be able to generate invaluable medicines for awful diseases such as spinal muscular atrophy (maybe even better/safer than what ISIS is generating currently) and Huntington’s disease.

Kind regards,

Dirk.