Sarepta Therapeutics, Inc. (SRPT)
2012 Lazard Capital Markets Healthcare Conference
November 11, 2012 4:30 PM ET
Chris Garabedian – President and CEO
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Thanks Bill and thanks to Lazard for the invitation and well done some great research following the company. We appreciate that. I’d like to talk to you about Sarepta Therapeutics. We are an RNA based technology, but we think it’s differentiated from other approaches and we show this in the clinic, most notably with our Duchenne Muscular Dystrophy product and I’d like to talk to you about some recent data we shared. I’m going to be making some forward looking statements so please refer to your SEC documents on Sarepta to understand the risk factors associated with the company.
Our proprietary pipeline is focused on Duchenne Muscular Dystrophy program is the drug Eteplirsen where we just announced 48 week data from our phase two study and I’ll reveal those to you today. We also have a couple of other follow on compounds. This is a genetic based disease. It’s very fragmented and requires many drugs to treat all of the potential patients that would be amenable to our technology. And so we’re focused on bringing other Duchenne products with our safe technology through the clinic.
We also have an infectious disease portfolio, but largely elder funded or is currently funded by the government and department of defense, most specifically and I’ll be talking – I won’t be talking about the infectious disease program today, but I will say that our novel virus program is an active program in development that has shown very good activity on survival in non-human primates and has been shown to be safe in single setting dose. We are preparing for multiple setting dose that will take place next year.
So Duchenne is really a devastating neuromuscular disease. It affects mostly brains (inaudible) connect chromosome disease and it’s a very progressive disease. It starts with diagnosis usually by the age of three to five years of age. It typically leads to a level of progression of loss of ambulation until their pre-teens or early teen years where they’ll require a wheelchair and then they start to lose their basal muscle function, their pulmonary and cardiac function start to see this congestial decline.
They won’t live beyond the age of 30 and so this is largely caused by their lack of the essential protein that’s found in healthy muscle called dystrophin. And so what we’re attempting to do with our product and our technology is to repair the mutations that occur in the dystrophin gene that render them unable to translate and produce the protein. And so what you see on the right here is, on the top cell you see what Duchenne Muscular Dystrophy tissue looks like when say for Dystrophy you hardly see any discernible dystrophin. On the bottom is the healthy muscle tissue, what our muscles would look like with 100% dystrophin part of the fabric.
So Eteplirsen is the molecule that I’m going to be talking about today and this is a RNA antisense oligomer type that has a very different backbone chemistry than other RNA antisense approaches and really different than most of the RNA applications we see out there, whether it’s SRNA or RNAi or microRNA. It does not appear to the (inaudible) chemistry, the nucleic acid type structure negatively charged which typically interacts with other host proteins. It has inflammatory effects. It basically produces these off target effects that limit their ability to get to a dose window that phase.
And so it works in DMD by directing alternative splicing that we call exon skipping and I’ll explain that in a minute. It administers systemically through IV infusions weekly. This is the DMD application I’m referring to. The PMO here, this is the Phosphorodiamidate Morpholino Oligomer that I’m referring to is neutrally charged and the plasma half life has very attractive drug like properties. It has a short plasma half-life, two to six hours but that exposure to in this case the muscle cells get uptick and produces Dystrophin has a very much longer half-life. It can be two to four weeks, the Dystrophin half-life and potentially we might see a longer half life in compartments or inside the cell.
It’s close to the kidney. We’ve seen that it occurred intact in the urine normal tab light. We’ve not seen any antibody or imminent genetic response to the drug and in the current DMD tests we’ve tested this drug up to 15mg/kg weekly in patients that we saw low treatment adverse events, low lab abnormalities, no signals of toxicity through four weeks treatment.
The mechanism of action that I described, the exon skipping or direct alternative splicing is really attending to repair the lesion that occurs in the Dystrophin gene in these patients. Now, lesions along the gene can manifest itself in two ways. It can produce a Duchenne patient that is a much more severe phenotype. It’s degenerative embedded with 100% fatal. Typically the majority of patients lose the ability to walk by age 12 and it’s characterized by an outer frame deletion that renders them unable to reach through and produce the protein.