jrrt1, Credit Suisse and Morgan Stanley is a big step up from the Rodman and Renshaw days. It will be virtually impossible , if one has an account with either one of theses houses, to receive any of these shares. Supply and DEMAND.
jrrt1, Agree with your assessment. There are 2 sides to this deal. The brokerages want in now to realize much of the pending increases in share price and Kaye agreed. Once eteplirsen is approved and the other exons start to be priced into the market cap 3 million shares is minuscule.
JRRT, There was a 1 year study on the MDX mouse model utilizing the naked PMO and they discovered that dystrophin was produced in the heart [single digits] muscles of mice and cardiac function [output] was stabilized. STUDY: One-year Treatment of Morpholino Antisense Oligomer Improves Skeletal and Cardiac Muscle Functions in Dystrophic mdx Mice
I can't recall another new drug application that was accepted by the FDA based on Phase II data when the subsequent Phase III trial failed. The failed Phase III dataset is included in the NDA so how does the FDA rationalize an AA approval when there is no proof that Drisa effects dystrophin production? A 6MWT that tracks with the historical placebo cohort and little reported about how this drug effects pulmonary Fx. or cardiac output. If I scratch my head any longer I'll have no hair left.
Sentiment: Strong Buy
According to Ed Kaye Sarepta has corresponded with the FDA over 70 times since the NDA was filed in late June. This demonstrates that the FDA is not only well briefed on the data but is aggressively assisting SRPT in it seeking full FDA approval of eteplirsen. Even the Cowan biotech analyst, who was bearish on eteplirsen's FDA chances, was caught off guard by today's presentation and stated that these results are better then he anticipated. Are there any "shorts" left??
I always thought that a percentage of ADCOM members would have a problem with the small treated population until today. This dataset is compelling and the ADCOM will recommend conditional AA approval this Q.
by 4 independent pathologists equals 14% [+] fibers dystrophin @ 36 weeks. In context of 192 week dystrophin data confirms that the longer boys are on eteplirsen the more dystrophin produced. This suggests that many of the hypothesis' are correct including length of therapy, myogenesis etc.
Besides proving the mechanism of action of an exon skipping oligo the last biopsy will disprove that the small population treated was due to variance inherent in the muscular dystrophy population. A stabilization or increase in dystrophin over the baseline three years out would prove the underlying MOA but shatter that the correlation to improved 6MWT scores Vs. historical data is due to increased or stabile dystrophin production. Dystrophin is the key to AA approval.
Sentiment: Strong Buy
The initial biopsies were not "garbage" and the FDA did not "trash" them but reaffirmed the use of IMF for localization and quantification. What the FDA wanted was additional pathological review and WB/ELISA counts included. The "trash" as you state was a result of Biomarin crying that Drisapersen created no new dystrophin so Sarepta's PMO-induced dystrophin quantification methods must be suspect.
I have never bought into the "leaky membrane" hypothesis for one obvious reason. Once the cell membrane's integrity has been compromised the cell is no longer viable as in cell death. Who cares if the oligos enter via these membrane disruptions if they are passing the cell's organelles on their way out of the cell? There are numerous papers that address leaky membranes. There is a chemistry blog that i read called "Woodward's Whiskey". he lists his thought on this topic and lists the scientific papers to support his conclusions.
Sentiment: Strong Buy
tred, I use to believe what you believe but decades of experience paints a different story. Analysts use code words like adding "color" to an issue, "background" ,"granularity". It is very possible that management conveyed specific knowledge without unequivocally stated said information. No one can convince me that CG didn't have specific knowledge of the initial 36 week Phase II data before conducting their reverse split. Did he officially have knowledge of data, probably not. 3 days later data was released [officially] and the rest is history.
jrrt1, The mouse model is the more sensitive toxicological system for testing oligos, not the rat. Without looking up the exact target sequence used for the rat PMO it is very likely that it is target specific. Relating to the target sequence it is most likely that the patching over the target exonic sequence causes the toxicity itself or the binding of this rat sequence resulted in mismatch patching causing toxicity. This is only demonstrative at super high doses in the less then optimal model that tests for oligo toxicity. My previous comment regarding granulation is so unlikely even at the doses reported in the rat study that I shouldn't have mentioned it. Granulation has been reported in animal models with dosing over the gram/'kg dosing in the rat study and over long durations. It is no secret that oligos in general can accumulate in organs over time. This fact is well documented and not relevant in these studies.
Very interesting and revealing comment by Baird analyst. He reports that after spending time with SRPT management they provided "granularity" to upcoming new data points prior to adcom and risk is greatly mitigated hence upgrade to $47 pps. It sounds like dystrophin data and 6MWT scores were revealed in these meetings.
"The problem is that the Mercuri decline is 1/2 driven by the rare, but extreme, declines to non amb. Sarepta just had to get a little bit lucky (est 30% to 50% chance) in picking their 6 patients to avoid getting any declines-to-non-amb-in-3-years"…That is one explanation but I have a better one that is supported by a proven mechanism of action and quantifiable and qualifiable drug induced Dystrophin production correlating with 6MWT scores. What happens to the "30% to 50% chance" when the trial reaches 4 years and there are no additional wheelchair bound boys?
The exon 53 rat data did not experience toxicity until 1 gram/kg. This is an enormous dose. DMD animal models use different sequences to patch over sequence to ameliorate dystrophin functionality compared to human DMD patch sequence. there are only two possibilities for the PMO toxicity at such a large dose. First it is sequence specific which is very likely or organ granulation which has been reported in animal models at multiple gram'/kg weights over prolonged periods of time. The later finding does not appear in the literature but has been relayed to me in unpublished experiments
Ifxxx, Remember all the comments post 168 week 6MWT scores from analysts that they expected increased decline in these scores? At the time I thought it was more likely to stabilize then decrease significantly. This is all unchartered territory.