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Sanofi Message Board

scistats 111 posts  |  Last Activity: Oct 17, 2014 7:30 PM Member since: Apr 5, 2009
  • We have been informed by Dr. Tefferi that he has submitted data from the Myelofibrosis IST as an abstract to be considered for presentation at the American Society of Hematology or ASH annual meeting to be held in San Francisco in December. The abstract contains safety and efficacy data from patients with MF which have been updated since his presentation at ASH 2013.

    Unfortunately, updated data sets from the MDS-RARS and blast phase MF patients were not available to Dr. Tefferi at the time of the ASH abstract deadline and as a consequence he did not submit abstracts to ASH regarding the treatment outcomes in these IST cohorts.

    These data sets were not available because of the extensive data entry and analysis required to update the MF IST cohort data sets in order to support the preparation of this complete response to the FDA partial hold as well as the activities required to prepare for the transfer of the IND and study sponsorship for Mayo Clinic to Geron.

    We look forward to the data from the patients with MDS-RARS and patients with blast phase MF being presented or published by Dr. Tefferi at a future venue.

    This year we have also initiated collaborations with a select group of academic investigators who are looking into the effects of the imetelstat in non-clinical models of MF and other myeloid malignancies such as AML.

    From these studies we may gain insight into the potential mechanisms of action of our drug in these malignances as well as non-clinical data to support broader clinical development of imetelstat. We’re pleased to report that our collaborators have submitted some of these data as abstract for ASH 2014. In keeping with standard ASH embargo policy, I will not be making any further comments on any of the submitted data from the collaborators.

    Sentiment: Strong Buy

  • scistats scistats Sep 13, 2014 2:51 PM Flag

    Alternatively, if stroke trial fails, PPS = 0.

    Sentiment: Strong Buy

  • We will have some competition from Mesoblast and the like, but the key feature of Multistem is ability to expand for cost-effective, off the shelf therapy.

    Taking into account the competition and a conservative market penetration of 20%. Lets cut the market size on the low end by half (see below) to $7 billion. That would be 1.4 billion per year or 350 million per quarter until something better comes along.

    This puts us at 33 PPS as a very conservative estimate relative to PCYC as a reference for a company with similar total shares. The maximum high end would be no more than PCYC at around 100 PPS.

    "As a consequence of an aging population, recent forecasts from the American Heart Association project that the prevalence of stroke will increase by 25% in the next twenty years, and the total estimated annual cost for treating and caring for stroke survivors in the United States will skyrocket from $64 billion in 2010 to $140 billion in 2030, representing a substantial increase in costs to the healthcare system. The company believes that the market for a safe and effective therapy for stroke that could be administered within a clinically reasonable time frame could represent a $15 to 20 billion annual market opportunity."

    Sentiment: Strong Buy

  • Reply to

    Stroke Trial completion date moved up?

    by brody_pierce Aug 13, 2014 11:17 AM
    scistats scistats Sep 1, 2014 4:03 PM Flag

    No, I decided not to waste my time emailing Athersys. Instead I have focused on crunching the numbers for the phase 2 stroke trial that is underway using the method that I outlined in detail above.

    During the next Q&A, an analyst could ask the question: Why are the 5 to 3 Rankin score improvements in the Multistem stroke trial being moved to the secondary outcome measure where these case improvements do not count?

    Patients who do not improve within 24-48 hours are the only ones being enrolled, and while they are less likely to spontaneously improve and inflate the placebo response, these patients are also the most challenging for Multistem and may, at best, only achieve a 5 to 3 Rankin score improvement for many cases. Still, this would hint that a large Multistem trial would identify a sufficient number of cases moving from 4 to 2 which is our definition of success. The problem is, the number of patients needed to statistically prove this in the current Multistem stroke trial are most likely insufficient. Plug in the numbers as I have described above.

    So, will the same excuse be used for the stroke trial failure that was used for the UC trial failure? "We enrolled the most difficult stroke cases, those that did not improve within 24-48 hours, and because of this, one dose of Multistem was simply not enough to meet the primary outcome measure of a Rankin of 2 or less, but we did see some secondary measure improvements that we hope to follow up over time. Thank you for your money. Good day. Sorry for losing all your money. Thanks for the big salary."

    My Long-Term Sentiment Disclosure: A very prudent strong buy with an urgent warning to invest absolutely no more than you and your family can afford to lose. If Multistem has the potential that Gil has stated, even a very small investment will yield well without the risk exposure.

    Sentiment: Strong Buy

  • Reply to

    Stroke Trial completion date moved up?

    by brody_pierce Aug 13, 2014 11:17 AM
    scistats scistats Sep 1, 2014 2:30 PM Flag

    Show us the numbers Ohmtaxi.
    You are sounding like a long short.

    Sentiment: Strong Buy

  • Reply to

    Stroke Trial completion date moved up?

    by brody_pierce Aug 13, 2014 11:17 AM
    scistats scistats Sep 1, 2014 12:39 AM Flag

    "Give it up shortie?"
    Nice, thought provoking response Ohmtaxi.
    Anyway, try the calculator and see what you come up with.
    Maybe I will agree with you, but try to at least back up what you are saying.
    "Give it up shortie" does not cut it. Nor does "real deal" with exclamantion marks.

    Sentiment: Strong Buy

  • Reply to

    Stroke Trial completion date moved up?

    by brody_pierce Aug 13, 2014 11:17 AM
    scistats scistats Sep 1, 2014 12:33 AM Flag

    There may be others, but sealdenvelope has a sample size calculator that everyone can use. Tell us how you get your numbers and plug them into this calculator. Provide some dicussion relative to the following reference Stroke 2004 May 351216-24. In terms of the success of this trial you have to look at the normal recovery and reduce it a bit to account for the 24-48 hour observation period to select those patients who do not improve during this time frame and consider that these patients may never make it back to 2 or below. But, go ahead and give you your numbers a shot, and we can all cuss and discuss what you find.

    We are sampling the stroke population for a binary response to Multistem or placebo. The binary outcome is either 2 or less (success) or, alternatively, more than 2 (failure) on the Rankin scale.

    The more patients we evaluate, the more likely we are to reveal a differene, if one exists. Whether you call it larage number or more patients, the bottom line is the same. The more numbers we have the more power we have to reveal the true average response in the population. The fewer patients we have, the more likely we are to be unable to prove the benefit of Multistem, even if it does exist, because of error and other factors.

    When I get time, I will try my hand at running some number through the calculator too.

    Sentiment: Strong Buy

  • Reply to

    Stroke Trial completion date moved up?

    by brody_pierce Aug 13, 2014 11:17 AM
    scistats scistats Aug 30, 2014 4:48 PM Flag

    We need MORE patients enrolled to prove significance, not FEWER.

    Multistem has to have more recoveries (2 or less on the Rankin scale).

    To prove Multistem successful, we have to beat standard of care 'natural recoveries' which occurs at a high rate, as much as 40% but perhaps 30% in our case because they are enrolling only cases showing no improvement at 24-48 hours.

    However, enrolling these difficult cases is risky!

    Multistem has to really work well because some of these risky cases are Rankin score 5 have underlying health conditions, and improvement from a score of 5 down to a much less severe score of 3 DOES NOT COUNT. 5 to 3 conversion is a secondary outcome measure which means nothing if we cannot meet the primary outcome measure of reducing severity to 2.

    If placebo and standard of care achieve 30% of recoveries from say 3 to 2, we have to have large numbers to prove statistical significance for Multistem. It is going to be touch and go as Gil has put in the secondary outcome measure what should be in the primary outcome measure.

    Gil has set the highest bar possible and demands success with an absolute minimum number of patients enrolled. If I wanted a phase 2 to fail, I would design it just like this, push reason down into the secondary outcome measure and put out a one liner of did not meet primary outcome on judgement day.

    GO FIGURE!

    Sentiment: Strong Buy

  • scistats scistats Aug 28, 2014 8:43 PM Flag

    Thanks, I will take a look!

    Sentiment: Strong Buy

  • scistats scistats Aug 28, 2014 4:48 PM Flag

    8 people received Multistem.
    Do the math. Gil knows the results.

    Furthermore, if a safety committee knows the results, a lot more people know.
    Unless you still believe in the tooth fairy.

    Third, the study is now a balanced design between placebo and Multistem.
    Moderate to severe stroke is scored 3-5 on the Rankin scale.
    We already know the outcome for standard of care in terms of the proportion to expect converting to less than or equal to 2, which is the primary outcome measure. So, once again, if you do the math with knowledge of the collective patient outcomes after 90 days, its not too difficult to determine if Multistem is working as the study progresses.

    As the trial moves toward completion of enrollment and more patients complete their 90 day period, the writing will be on the wall for those in the know.

    Sentiment: Strong Buy

  • Athersys recruited 10 stroke patients (Cohort 1 and 2) to evaluate the safety to of high dose Multistem before enrolling the remaining 120 for Cohort 3. More than likely 4 patients received low dose, 4 high dose, and 2 placebo.

    Athersys confirmed the high dose was safe and has moved on to Cohort 3, the large part of the phase 2 currently underway. The question is: Since Cohort 1 and 2 were unblinded to know that those receiving Multistem high dose is safe, what were the results of this preliminary safety evaluation which should give us an idea of whether Multistem is working or not. The 8 patients who received Multistem should have shown better than average progress. Was this the case. Gil has the results. So, what happened to these patients after 90 days???

    Experimental: Cohort 1
    Low dose MultiStem vs. Placebo

    Experimental: Cohort 2
    Low dose MultiStem vs. Placebo

    Sentiment: Strong Buy

  • scistats scistats Aug 26, 2014 12:55 AM Flag

    Not at all Dr. Sumitchawla, I am here, just like you, to debate both sides and seek the truth. You seem to think the odds of Multistem success are far from a slam dunk. Are you long or short this stock? Just curious. Stictly look at the odds, you should be short, so if you are, this is ok.

    I am sure you meant 'infusion' rather than 'injection' of Multistem, and Athersys does not have the resources to remotely beging to fund a phase 3.

    Regarding the current tiral desing. What I am saying is, 'hey lets give credit for a 2 point reduction from 5 to 3 on the Rankin scale in the current trial'. Right now, we do not do this, so I am not following your arguement above. If we can show 2 point reductions, one would assume 4 to 2 reduction will put patients back in the game even if this particular metric eludes us in this particual trial. Do you see the weak link here?

    Had we really rather address reimbursement potential now rather than demonstrate Multistem is effective for reducing stroke symptoms, even if we cannot definitively prove the strict defition of success as reduction equal to or less than a Rankin score of 2 or less with so few patients enrolled in this small overly ambitious phase 2 trial.

    I am a Strong prudent Buy. Bet no more than you can afford to gamble on this peculiar experimental design that insists on absolute perfection, ignores 5 to 3 successes, and accepts nothing less with total failure (just like the UC trial) a likely outcome. Cheers.

    Sentiment: Strong Buy

  • scistats scistats Aug 25, 2014 5:34 AM Flag

    I am long in the five digit range.
    I have about as much exposure as I stand.
    If there was a 'Strong Prudent Buy' option, I would select it.

    Sentiment: Strong Buy

  • scistats scistats Aug 25, 2014 5:11 AM Flag

    Sometime you really do have to laugh. I am pointing out literature references and debating sample size calculations and overestimations of Multistem efficacy and how Gil set the highest bar possible for success. You have to allow for some fun and games along the way. Although, the sinking ship video is a very real possiblity. This is a high stakes gamble.

    Sentiment: Strong Buy

  • scistats scistats Aug 25, 2014 5:06 AM Flag

    Did you see bar that Gil and Pfizer set for the UC trial? Impossible to succeed, and now the readily admit it.

    The most difficult patients with a decade of UC to be cured by a single dose of Multistem. Really?

    The front wheels of the bust have already run over us, now we await the back end as the next high bar stroke trial is set to fail because of being "grossly overoptimistic in their expectation of treatment effect" Stroke. 2004 May;35(5):1216-24

    Sentiment: Strong Buy

  • Reply to

    couldnt help answering scistats as he is wrong

    by isaacandromeda Aug 24, 2014 11:27 PM
    scistats scistats Aug 25, 2014 5:01 AM Flag

    Sorry, Yahoo chopped my message the publication is Stroke. 2004 May 35(5)1216-24.

    "Most [Stroke] trials were underpowered, ie, power less than 0.90, used inappropriate assumptions for event rates, and were grossly overoptimistic in their expectation of treatment effect. These deficiencies will together have resulted in trials being far too small and reduced their chance of being able to detect real treatment effects."

    I think Athersys is both overoptimistic and moving forwad with too small a sample size.

    This is why I want Gil to accomodate all the successful mRS reductions due to Multistem and not just those resulting in reductions to less than 2. Now we have to datamine to prove this, and it is not part of our stated outcome measure. So by definition, Gil has set the highest expectation for success with a relatively small sample size.

    Sentiment: Strong Buy

  • scistats scistats Aug 25, 2014 4:54 AM Flag

    No, Dr. Sumitchawla, this is not what I said at all. Also, your are wrong about spontaneous recoveries. The Athersys trial is waiting 24-48 hours to remove the spontaneous recoveries (the 40% you mention), so we are dealing with the more difficult cases of people mostly over 65 years of age. I am NOT saying a mRS of 2 or less is impossible to achieve, I am saying the number will be few in this difficult group. I am saying we cannot ignore the 5 to 3 mRS reduction successes which Gil threw out with his bogus primary outcome measure. These 5 to 3 reductions may in fact highlight the benefit of Multistem that cannot be revealed by the small patient numbers we have in this small phase 2 study. This trial is, "grossly overoptimistic in its expectation of treatment effect" Stroke. 2004 May 35 1216 24 Furthermore, your eagerness to move on to reimbursement based on phase 2 data is folly. What we need is first, proof of efficacy. Then let the phase 3 prove a 2 or less Rankin for possible reimburesment. You are getting way ahead of yourself when what we want here is a successful phase 2 that survives to even have the chance of moving on to a phase 3.

    Sentiment: Strong Buy

  • Reply to

    couldnt help answering scistats as he is wrong

    by isaacandromeda Aug 24, 2014 11:27 PM
    scistats scistats Aug 25, 2014 4:40 AM Flag

    isaacandromeda, Google the 'Edison Athersys multipotent stem cells report' which is a pdf. It details what dr.sumitchawla is explaining. We have lost some n value to low dose infusions to confirm high dose safety.

    We are on to Cohort 3 which is using the highest safe dose in a 1:1 randomisation to placebo or MultiStem as single IV infusion 24-48 hrs (ideally 24-36 hrs) following ischaemic stroke.

    The primary endpoint is the % of subjects with a modified Rankin Scale (mRS) score of 0-2 after 90 days.

    dr.sumitchawla spoke of sample size. Lets refer to a publication:
    "Inadequate trial design, especially low sample size, may partly explain failure." "Most [stroke] trials were underpowered, ie, power

    Sentiment: Strong Buy

  • scistats scistats Aug 24, 2014 10:03 PM Flag

    Ok, I will contact Athersys and ask them if Multistem achieving any level of statistically significant reduction in Rankin score relative to placebo, is considered a success? Everyone else is welcome to do the same.

    Or, is Multistem achieving a statistically significant reduction in Rankin score relative to placebo considered a success only if that statistically significant reduction relative to placebo results in a score between 0 and 2?

    We know the study will be Multistem (low dose/high dose) vs. Placebo

    I am afraid that the "Measure Title" will be "Number of Patients With a Modified Rankin Scale (mRS) Score of 0-2 at 3 Months." I think this phase 2 study can afford to be broader at this point in terms of defining success because of the small number of patients being evaluated.

    What we need is a breakdown to the following groups and liberty to define success as simply a reduction in mRS relative to placebo, assuming that in the greater population, some patients will reduce to 2 or below, even if this small trial with a split low and high dose treatment cannot demonstrate this subgroup.

    In other words, this study may be too small to prove the primary outcome measure as it is defined, but in reality, some percentage of people will achieve the desired reduction, perhaps 20%? Multistem is more affordable than others because of cell amplification, so benefiting a smaller % is feasible from a insurance reimbursement/cost standpoint.

    This is where I feel Gil is dropping the ball. He is hanging us out to dry with a strictly defined primary outcome measure. I want him to change this and explain why the study was designed in such s threatening way.

    90 day mRS score of 0 overall
    90 day mRS score of 1 overall
    90 day mRS score of 2 overall
    90 day mRS score of 3 overall
    90 day mRS score of 4 overall
    90 day mRS score of 5 overall
    90 day mRS score of 6 overall

    Sentiment: Strong Buy

  • scistats scistats Aug 24, 2014 5:37 PM Flag

    Ohmtaxi, it depends on your definition of success. Lets say Multistem on average reduces Rankin by 1 point. For some patients, going from 4 to 3 would not meet the outcome measure (although still a success in reduction), but for others going from 3 to 2 would meet the trial's definition of success.

    Now, lets say that the Rankin 3 to 2 scenario happens for 25% of those receiving Multistem. For 75% of people, they did not reach the primary outcome measure , but for 25% it is a miracle therapy.

    Ok then, is the trial itself, as a whole, a success? Keep in mind we have 70 patients receiving treatment and split this because we have two doses, high and low.

    Because of all of this, demanding a Rankin score of less than or equal to 2 is the wrong approach and stacks the odds against us when this was not necessary for a phase 2.

    So Ohmtaxi, define what you consider success, compare it to Gil's definition, and hope that he genuinely has our best interest at heart.

    Sentiment: Strong Buy

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